04 Neurology

SECTION 4

Neurology 21.

Practical Approach to a Person Who is Unconscious Nagarajan Venkataraman

107

22.

Influence of Gut Microbiota on the Brain Poorna J Visa, K Venkatraman, AV Srinivasan

112

23.

Clinical Approach to Tremor K Venkatraman, R Lakshminarasimhan, AV Srinivasan

118

24.

Approach to Frequent Falls in Elderly People AR Vijayakumar, VS Prasadh

126

25.

Practical Approach to Peripheral Neuropathy M Rajasekaran

130

26.

An Approach to Headache T Ravikumar, M Gowri Sankar

134

27.

Approach to a Patient with Hemiplegia and Monoplegia Sudhir Kumar, Subhash Kaul

141

28.

Approach to Giddiness Sudha Vidyasagar

147

C H A P T E R

21

Practical Approach to a Person Who is Unconscious Nagarajan Venkataraman

ABSTRACT

Identification and management of acute coma or loss of consciousness is a clinical challenge. Most of the time, the patients are brought by unknown people, or with relatives with little details. Assessing the management, depends on the etiology, which has wide varieties.

Hence it is mandatory that etiology of the coma, has to be determined, before managing the case. Many causes right from head injury, cerebro vascular accidents, infections of CNS, and metabolic causes result in coma. Wide tracking of causes, by repeated patient questioning to the relatives, at the same time, carrying out the emergency measures to recover the patient’s health is imperative. The concept of “Time is Brain” has to be borne in mind, and a work up quick, investigations for the cause of coma, will make a physician’s effort highly successful one.

unconsciousness, caused by varied etiology, for example severe stroke syndromes, brain tumor going in for conning, head injury, encephalitis, other CNS infections, alcohol or toxic drug intoxications, so on so forth. The conscious level is maintained by the ascending reticular activating system in the brain stem.1 And it is maintained by volleys of projections to the cortical system, by it’s lots of inputs from various sensory, motor projections. The cortical alertness is maintained by such projections from ARAS to the cortex. Its functions are compromised either mechanically, or by toxins and toxic metabolites.

SYMPTOMS

LOC or Coma, has fairly definite, constant symptoms 1.

The eyes are closed.

2.

Non responding pupil, some times asymmetric or pin point and nonresponsive as in subarachnoid hemorrhage.

3.

Depressed brain stem reflexes, as evidenced by depressed ocular movements.

4.

No movement in the limbs, and occasionally some reflex movements.

5.

Ataxic breathing, cold clammy skin, and in metabolic coma, special odors like uremic odor or fruit odor of DKA.

6.

Seizures may manifest if the cause is cerebrally oriented, like inflammation or ICH.

INTRODUCTION

A patient brought to your office, in an unconscious state, is a challenge to the Physician, as there are numerous causes for the loss of consciousness, right from common hypoglycemia to a dangerous situation like subarachnoid hemorrhage. The relatives will be highly apprehended, to know the fact regarding recovery, prognosis, even doubts about our capability, approach, and efficiency.

Mostly some will be urging to take the patient to a corporate hospital. We have to face lots of problem, apart from looking into the patient’s welfare, the other issues also. Mostly, they want an answer immediately, about the survival and prognosis of the patient. A calm, quiet, confident, and efficient approach will win all the issues.

Definition

Bed side approach to an unconscious patient

The following points are necessarily to be examined. First

LOC or coma, is a clinical condition of prolonged

Table 1: Evaluation of coma from pseudocoma Method of examination

Functional (Psuedo coma)

Organic

1

Plantar response

Withdrawl or flexor

Extensor

2

Pupil

Normal and reactive

Abnormal, non reactive

3

Tone of muscles and limbs

Variable

Either flaccid or spastic consistently

4

Bladder status

Never incontinent

Mostly incontinent

5.

Blood pressure

Mostly normal

Variable

6

Respiration

Hyperventilation

Ataxic or shallow

7

Neck stiffness, classical

variable

Consistent

8

Forcible eye opening by the examiner

Resistance observed

No Resistance

9

Reflex eye movements

Invariably present

May or may not be present depending on the brain stem integrity

108

will be given. We have to analyze the correct pathway, of identifying the cause, is necessary towards the management of the patient. To achieve that, one should examine the patient in depth, to a possible extent, regarding the etiological discoveries, and apply the same towards eliciting the history. Based on the history elicited, further examination is mandatory. It is highly pertinent to remember, that what ever history is given should correlate with our clinical findings, otherwise we may be dragged to different etiology, missing the proper diagnosis.

Table 2: Common Etiological issues in COMA • Traumatic brain injuries.

Trauma due to road traffic, fall, violence, blasts injuries.

• Stroke. Subarachoid Hemorrhage, intracerebral massive bleed, or major vessel occlusion as in carotid massive occlusion, along with compromised brain stem circulation or due or massive brain oedema and coning.

NEUROLOGY

• Diabetes Mellitus.

Hypoglycemia (acute onset coma) and hyperglycemia. (subacute onset coma) • Uremia – Sub acute onset of loss of consciousness, with obvious history.

2.

In comatose patient’s examination, there will be no resistance for examination but we should not take it to our advantage. A patient with head injury, and coma, may have dislocated cervical injury, and examination for neck stiffness should be extremely careful, as there may not be any resistance. Partial dislocation of spinal discs, will become complete on extreme cervical movements, on examination.

3.

Look for more injuries like abdominal injuries, spleen, liver and any other hollow viscous rupture, even before attending to the patient with head injury and coma, as subsequent examination will be targeted only towards head injury, and death of patient may be due to other concomitant causes. It is always better to examine in a routine way from top to toe. Look for any cause that may be responsible for the coma. This procedure is essential to identify the injuries which may become life or limb threatening. Any negligence to identify the other lesions, may be left untreated till the patient recovers from the coma. The common issues are hip dislocations, spinal fractures, and fractures of metacarpals. It is essential that every joint should be put into full range of movements, to assess the integrity of the long bones. Where ever, suspicion results X ray should be done in that area.

Injuries in the back, and medical conditions like pneumothorax, should not be missed. Palpation of the peripheral pulse is mandatory.

4.

History of injury immediately or in recent past, however trivial it may be, is very important.

A subdural may be “quiet” for some time, and suddenly it may enlarge and cone the brain stem.

Many of the patients who had mild subdural due to trivial head injury, may land in enlargement of the subdural, if they were on medications with antiplatelet drugs for some other ailment. This may cause coning, which will become a practical problem.

5.

Non surgical causes of loss of consciousness are many,which are tabulated (Table 1). Look for evidence for such etiology in case, if you could exclude surgical causes. But never compromise one for other. For example, simple alcoholic coma, may be associated with subdural, and a careful watch for both, is mandatory. Vice versa, a case of head

• Lack of oxygen.

Drowning of post CPR. • Infections.

Encephalitis and meningitis. Toxemia, Septicemia.

• Seizures. Status epilepticus, post ictal coma, • Toxins.

Carbon monoxide, organophosphorous compounds or lead, • Tumors of the brain, Sudden bleeding inside the tumor causing acute swelling, massive brain edema as seen in high malignant tumors, edema and coning of the brain stem.

• Alcohol – Acute alcoholic intoxication results in coma.

• Drugs - Marjuvana, opioids thing to rule out is the functional causes of the so called LOC (Table 1).

Approach To The Etiology (Table 2). One has to do Police Man’s Job, in detecting the etiology.

1.

The following questions may give pathway to examination in a case of coma.

•

Had the LOC started suddenly or gradually?

•

Whether it was accompanied with problems in the vision, such as loss of vision, diplopia, vertigo, fainting spells, or numbness of the limbs etc ?

•

Is the patient a known case of diabetes, or patient on dialysis, seizures or old stroke ?

•

Had the patient severe headache prior to the LOC ?

•

Any mental changes observed, prior to LOC, like confusion, frequent falls etc ?

•

Did the affected person use any medications with or without prescription ?

A very detailed history from the accompanying person, if available, regarding the situation of the patient, is mandatory. Invariably, various histories

109

Table 3: Elements of the scale Glasgow Coma Scale 1 Eye

Does not open eyes

2

3

4

5

6

Opens eyes in response to voice

Opens eyes spontaneously

N/A

N/A

Verbal Makes no sounds

Incomprehensible sounds

Utters inappropriate words

Confused, disoriented

Oriented, converses normally

N/A

Motor

Extension to painful stimuli (decerebrate response)

Abnormal flexion to painful stimuli (decorticate response)

Flexion / Withdrawal to painful stimuli

Localizes painful stimuli

Obeys commands

Makes no movements

Note that a motor response in any limb is acceptable.2 The scale is composed of three tests :eye, verbal and motor responses. The three values separately as well as their sum are considered. The lowest possible GCS (the sum) is 3 (deep coma or death), while the highest is 15 (fully awake person). Interpretation of Glasgow Coma Scale; Individual elements as well as the sum of the score are important. Hence, the score is expressed in the form “GCS 9 = E2 V4 M3 at 07:35 minutes; Generally, brain injury is classified as: Severe, with GCS < 8–9; Moderate, GCS 8 or 9–12 (controversial)4; Minor, GCS ≥ 13. Ref: “The Glasgow Coma Scale: clinical application in Emergency Departments”. Emergency Nurse. 14 (8): 30–5. 2006. doi:10.7748/en2006.12.14.8.30.c4221.

6.

injury may be accompanied with metabolic or alcoholic coma.

5.

Pressing the nasal ridge at the root in between the eyes, and look for wincing.

One of the common causes of LOC is cerebro vascular accident. The coma results mostly in massive intracranial bleed, due to hypertension, aneurysm rupture, leading to acute subarachnoid hemorrhage. Acute intracerebral bleed, if massive, or massive carotid infarcts, do result in LOC.

6.

Eliciting bone pain, by pressursing the shin of tibia and the response of the patient.

EVALUATION OF CMLOTOSE PATIENT

Assessment of level of consciousness is assessed by Glasgow Coma Scale, especially for comatose patients with head injury. GCS can be used for other causes of coma also.

GLASGOW COMA SCALE (TABLE 3)2,3

1.

2.

A practical hint to evaluate the prognosis, and severity of the loss of consciousness. Predominantly applied for head injury and CNS causes, and usually not applied for metabolic causes. But for practical purposes one can apply.

Bed side approach.

All the above methods may give a fair response to the examiner, regarding the level of loss of consciousness, which is very much essential to fix the prognosis.

OBJECTIVE CLINICAL SENSORY RESPONSES

1.

Oculo-cephalic movement reflex. This tests certifies the brain stem integrity. If present give a good prognosis, compared to no response.

2.

Assure that there is no cervical bone injury, when this examination is performed.

3.

Pupillary response, to light, is a mandatory examination. A dilated non responding pupil is a poor prognostic sign.

4.

Cilio spinal reflex can be observed if the papillary response is normal.

5.

Syringing the ear with sterile water, and trying to elicit nystagmus, assessing the integrity of brain stem, connections with the higher brain centers.

6.

Plantar response, is highly dubious, and depends on careful observations of the response, and method of elicitation. Bing’s response is more reliable than Babinski’s. (Bing sign - sharp pressure pain over the dorsum of foot )

7.

Tone of the muscle, is an index of severity or organicity of the LOC. A variable tone is a sign of non organic LOC, where as, a constant tone, as increased or decreased, could be marked as an organic cause of LOC. A continuous flaccid tone is associated with poor prognosis.

Assessing the sensory status and response: 1.

Level of consciousness, is assessed by the sensory stimuli applied to the patient. By calling the patient by his name, either by the examiner or by a close relative of the patient, and seeing the response.

2.

Pinching, the skin of the limbs, clenching the Achilles tendon for deep pressure pain response.

3.

According to some Senior authors, squeezing the nipple is another method, which is not practiced now on ethical issues.

4.

Assessing the corneal reflex, carefully with a sterile cotton wisp and looking for the response.

CHAPTER 21

Opens eyes in response to painful stimuli

110

supplementation of oxygen is mandatory, by all means. It is preferable, over a period of 15 mts, if there are signs of compromised ventilation and oxygenation, detected by PO2 less than 70%, one should immediately switch over to the ventilator drive. It is preferable to have 100% oxygen, to obtain saturation of 98% in the blood. This procedure is highly important to save the neurons, and the remaining dying neurons.

Table 4: Essential Investigations • Blood sugar, blood urea estimation • Basal blood tests, like ESR, CBC, Hb • Parasites in the blood, (malaria) • CT Scan/ Followed by MRI • Electro encephalogram.

• Electrolytes/anion gap, pH determination • Renal function tests, urea, creatinine, GFR

3.

In most of the patients who are comatose, the retina runs to ischemia, and also if it is associated with acute hypotension, and low O2 saturation.

O2 supplementation becomes more mandatory to prevent retinal dysfunction and death of neuronal layer. It is pertinent to observe that hypercapnea is far less likely to render irreparable brain damage than hypoxia. More so the retinal damage is more with hypercapnea, especially in CO2 poisoning, severe macular damage is a usual sequelle.

4.

Apart from this, infective causes also route to LOC. Meningitis, especially pyogenic meningitis, should be treated with appropriate antibiotic.

One of the rare cause of LOC, of nutritional origin is thiamine deficiency, may be associated with situations where the alcoholism is highly prevalent.

In alcoholic coma, even though the LOC is due to toxic causes, an associated thiamine deficiency is invariable associate. Administration of the thiamine is mandatory in such situation.6

5.

Cerebral malaria should be treated with anti parastiticdal drugs, if MP is identified in the peripheral smear. CSF, may be positive for MP, in rare cases apart from the positive peripheral smear.

• X-rays, urine basic tests

NEUROLOGY

• Acetylsalicylic acid/acetaminophen blood level • Ethanol/osmolality • Arterial blood gas/carbon monoxide levels • Lumbar puncture if necessary, and to be avoided as much as possible 8.

Persistent tachy, bradycardia or rather arrhythmias is a sign of organic coma, with poor outcome.

INVESTIGATIONS (TABLE 4)

Investigations have to be performed in a war foot method. Any delay in the investigations will cause more devastating results in the recovery. Mind “Time is Brain”.

THERAPY

The algorithm for management of coma is given in Figure 1. The first and foremost advise to the management of comatose patient, is application of 50% dextrose intravenous infusion as hypoglycemia is one of the most common cause of coma, and the patient’s response is dramatic.4 1.

•

In patients with prolonged hypoglycemia, for more than an hour, or in patients with associated motor seizures, recovery response may be delayed.

It is observed, that patients with ischemic stroke, if IV infusion of 50% dextrose may enhance the anaerobic glycolysis in infarcted area, to induce production of free radicals’, which are harmful to the dying neurons. But it is also observed that most of the ischemic stroke, do not cause comatose state, and coma is uncommon in ischemic stroke, unless it is gross, hemispherical with progressive edema.

Hence application of the dextrose need no worry.5 It is pertinent to observe, that rapid chemstrips may fail to endorse the clinical hypoglycemia in the presence of numerical normoglycemia.5 By giving dextrose to an already hyperglycemic patient is dangerous in a subtle way, than withholding it from a hypoglycemic patient.

If one is afraid a trial dose of 50 ml of 50% dextrose may be infused for elective result, and recovery from coma.6

2.

Prevention of hypercapnea: Neuronal death is rapid in the presence of hypercapnea. A comatose patient has mostly has a compromised ventilator drive, which is deleterious. Immediate

Management of cerebral Malaria

Management is multifocal, right from all parameters of management of coma, cardiac monitoring etc, appropriate drugs are as follows. The drug of choice is quinine and artesunate.

Artesunate has a limited shelf life. The dose is 2.4 mg kg−1 given intravenously, followed by the same dose at 12 and 24 h, then once daily until the patient is able to take artesunate (2 mg/kg per day) by mouth to complete 7 days, then Doxycycline 200 mg or Clindamycin daily by mouth for 7 days There are many complications of artesunate, which has to be balanced between the recovery and side effects of the drug

6.

Metabolic causes like diabetes mellitus with acute hypoglycemia, requires immediate infusion of 50% glucose, 100 ml followed by 5% dextrose saline.

Appropriate correction of acidosis in hyper osmolar ketotic coma, with Ringer solution is mandatory.

7.

In renal failure, care should be taken to reduce the BUN, and patient should be dialyzed, appropriately, with the correction of renal acidosis, electrolyte abnormalities.

MANAGEMENT OF COMA - An ALGORITHM

CONCLUSION

COMA-LOC Clinical Events Organic

Functional

Therapy

Etiologically Managed

Specific

Non-specific & supportive

Assessment

Investigations Final clarified Regime with ref. to Etiology

Assessment of severity towards progress

1.

Kinomura, S.,Larsson, J2., Gulyas, B., & Roland, P.E..

“Activation by attention of the human reticular formation and thalamic intra laminar nuclei. Science 1996; 271:512515. doi: 10.1126/science.271.5248.512PMID8560267

2.

Glasgow coma scale. A Practical hint to evaluate the prognosis, and severity of the loss of consciousness.

Predominantly applied for head injury and CNS causes, and usually not applied foe metabolic causes. But for practical purposes one can apply. Teasdale G, Jennett B. “ Assessment of coma and impaired consciousness. A practical scale. Lancet 1974; 2:81–4. Doi: 10.1016/S01406736(74)91639-0.PMID 4136544.

3.

The Glasgow Coma Scale: clinical application in emergency Department. Emergency Nurse 2006; 14:30-5. Doi:10.7748/ en2006.12.14.8.30.c4221

4.

Hoffman JR, Schriger DL, Votey SL, et al: The empiric use of hypertonic dextrose in patients with altered mental status: Areappraisal. Ann Emerg Med 1992; 21:20-4.

5.

It. Kagansky N, Levy S, Knobler H: The role of hyperglycemia in acute stroke. Arch Neurol 2001;58:1209-12. Schurr A: Energy metabolism, stress hormones and neural recovery from cerebral ischemia /hypoxia. Neruochem Int 2002; 41:18.

6.

Young GB: Nutritional deficiency and imparired consciousness. In: Young GB, Ropper AH, Bolton CF (eds.) Coma and Impaired Consciousness Mc Graw-Hill Companies Inc., New York, NY, 1998 pp.393-8.

7.

Buschanan JF, Brown CR: Designer drugs : A problem in clinical toxicology. Med Toxicol Adverse Drug Exp 1988; 3:117.v

Mortality

Fig. 1: Management of Coma - An Algorithm 8.

Naloxone (0.4 to 2 mg intravenous ) is a tangible remedy in coma due to opoid abuse and intoxication.

Even though this situation is common to some local areas, especially in the high northern side, where in access to the opioids is slightly common.7

The dose of naloxone should be titrated to make the patient breathe without reversing the entire opoid load. This will avoid precipitating the acute opioid with drawl symptoms, more so in absconding cases. It is pertinent to mention the effect of Nalloxone wears off before the opioid, and hence opioid withdrawl symptoms may get precipitated.

COMPLICATIONS

Although many people gradually recover from coma, others enter a vegetative state or even die. Some people who recover from coma may have major or minor disabilities. Complications may develop during coma, including pressure sores, bladder infections, leg vein thrombosis and other problems.

CHAPTER 21

Final Outcome

Persistant Vegetative State

COMA or LOC, is a condition met with by every practioner and consultant, which is a challenge to decide, treat, and to give a good recovery. Early and swift actions of the consultant, practioner, and good co operation of the relatives, accompanying persons, to accept the management, give funds for the tests, is a mandatory issue. Since “Time is Brain”, an earliest intervention will save the patient’s brain and life, to a great extent.

REFERENCES

Fine tuning in the therapy

Recovery

111

C H A P T E R

22

Influence of Gut Microbiota on the Brain

ABSTRACT

The intercommunication between commensal microbiota and its host is necessary for regulation of various aspects of host physiology. These include immune function, nutrient processing, brain development and function.

Gut microbiota influence the stress responses acting through the hypothalamic pituitary adrenal (HPA) axis or the sympathetic adrenal medullary axis resulting in immune function alteration. Alterations in gut microbiota is noted in neuropsychiatric disorders associated with inflammatory state changes such as major depressive disorder, schizophrenia, bipolar disorder as well as in autism and mood disorders. C.jejuni enhances anxiety like behavior by stimulating C- fos protein in selected regions of brain. Central nervous system (CNS) has the capacity to alter gut permeability, motility and secretion by stimulating the HPA axis, autonomic and neuro endocrine pathways which in turn can modulate gut microbial composition. Neuropsychiatric conditions like depression and autism occurs in high degree of concomitance with Gastro intestinal (G.I) disorders. Metabolic products of the microbial community mediates the state of health and illness. A positive the correlation between clostridia species and specific autistic characteristics has been established. Germ free mice are linked with reduced social skills, and this is associated with altered levels of von economo neurons (VEN) neurons. Dysbiosis is the recent concept postulated as a trigger for abnormal protein deposition in neurodegenerative disease like Parkinson disease and as a immunological trigger in RRMS. H.pylori infection increases antral relaxation, acting through the cholinergic nervous system or nonadrenergic â&#x20AC;&#x201C; noncholinergic nervous system. Alteration in the process of colonization, in neonates could predispose to disease in later life. Normal microbiota plays a vital role in the development of the brain systematized by specific time constraints. Gut microbiome takes part in the myelination process involving the region of prefrontal cortex. Therefore alteration of gut microbiome is linked to aberrant myelination and neuropsychiatric symptoms.

INTRODUCTION

In todayâ&#x20AC;&#x2122;s stressful life with the increased incidence of stress related neuropsychiatric illness, advancement in the insight into gut microbiota, would prove indispensable.

Our gut is composed of more bacterial organisms than the number of eukaryotic cells. Colonization with microbes could occur earlier than expected, where bacteria are identified in the placenta, umblical cord and

Poorna J Visa, K Venkatraman, AV Srinivasan

amniotic fluid4. Gut microbiota plays a vital role in the post natal maturation of the immune system, digestion and absorption of macromolecules, protection of gut from pathogens and behavioral development.1,2 There is a relationship between a personâ&#x20AC;&#x2122;s emotional state and gastric acid secretion. This association is regulated by immune, metabolic, neural and endocrine pathway.1-3 These concepts reflect the interplay between gut microbiota and brain.

Experiments to establish relationship between gut function and mood started as early as 18th century, when an army surgeon studied the gastric fluid secretions from a retained stomach orifice of an 18 year old, as part of his experiments, who he had operated on previously for an accidental gunshot wound, perforating the stomach among other injuries5. There is robust data showing coexistence of stress related CNS disease like depression with peripheral diseases like irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD)6. Maternal separation (MS) brings about stress associated G.I and mood disorders6. Disrupted normal microbiota plays a key role in the development of mood disorders and autism7. Bifidobacterium species was particularly susceptible to emotional stress6. There is no exact mechanism known by which gut microbiota influences the brain or whether the changes in the gut flora are the cause or effect of a disesase8. There are however links such as hormones, immune molecules and specialized metabolites found to play a role in the influence of gut microbiome on psychiatric neurological conditions like depression, anxiety, autism, schizophrenia and other neurodegenerative disorders6. The gut microbiota plays an important role in the maturation of the immune system.

It triggers the innate immunity causing the maturation of gut associated lymphoid tissue, and acquired immunity by stimulating the local and systemic immune responses6.

Persistent stimulation of the immune system by gut microbiota leads to low grade physiological inflammation, for defence against pathogens6.

Gut Microbiota and Mood disorders

Role in anxiety: Serotonin is not only produced in the brain but also released largely by the enterochromaffin cells in the gut2, which could be the basis for the concept, that the antidepressant drugs work better along with dietary modifications. Plasma levels of serotonin were 2.8 fold higher in conventional animals than germ free animals2.

Increased plasma serotonin levels are an indirect effect of host microbe interaction2. Karolinska team found out

that in the striatum of germ free mice there was a higher production of important neurochemicals like serotonin8 probably contributing to the lesser anxious behavior in germ free mice than mice colonized with indigenous microbes8. Gut microbiota by modulating neuronal proteins like synaptophysin and PSD – 95 influences anxiety like behavior in adult life. Further administered glucocorticoids reduce synaptophysin expression in the fetal brain, suggesting that stress hormones influenced by the gut microbiota play a role in this9.

Role in depression: Depression is associated with G.I disorders like stress, Crohn’s disease and ulcerative colitis6, 7. It is speculated that this is caused due to an imbalance between the sympathetic and parasympathetic discharge from the central nervous system, which would also contribute to behavioral impairment10. There is a hypothesis linking T cell deficiency to behavioral impairment10. However whether these cells act from the periphery or cross the blood brain barrier is unknown.

Lactose malabsorption albeit does not produce an effect by itself, but along with fructose malabsorption intervenes with L- tryptophan metabolism and therefore low serum tryptophan levels were especially found in the serum of fructose malabsorbers11,12. Reduced L-tryptophan predisposes to depression11. Therefore depression is influenced by changes in metabolic activity and composition of gut microbes2, 6,11,12. It is postulated that toxic bacterial by products reaching the colon causes a disruption of neurotransmitter metabolism and contribute to depression12. Collado et al using the heuristic maternal separation model showed that, maternal separation caused behavioral impairment relating to depression which was accompanied by biochemical changes like reduced noradrenaline in the brain, increased cortisol releasing factor mRNA levels in the amygdaloid cortex, and elevated release of cytokine IL – 6 after immune stimulation in MS rats4.

Probiotic Bifidobacterium has a therapeutic effect on stress related psychiatric diseases affecting the CNS function like depression and anxiety6. Probiotics exert

Gut Microbiota and Stress Response via HPA axis

Neuroendocrine pathways stimulating stress response are the HPA axis acting through glucocorticoid secretion and the sympathetic branch of the autonomic nervous system acting through the release of epinephrine and norepinephrine3. The products of the endocrine system and products of the nervous system bind to receptors on the various immune cells, like monocytes, macrophages, lymphocytes and granulocytes. This causes a change in CD4 T helper cells profile from Th1 cells to Th2 cells resulting in dysregulation of cell mediated immune system (Th1 cells) and activation of antibody production (Th2 cells)13.

Stress exposure alters gut activity by causing stomach and small intestinal hypo motility which causes bacterial overgrowth, along with a decrease of lactobacilli and Bifidobacterium level in the gut, also referred to as dysbiosis.12 Stress increases mucin secretion which acts as a substrate for bacterial overgrowth. Stress also stimulates colonic inflammation and increases innate immunity.

Probably the bacterial cell wall components3,17 stimulate the immune cells of the gut to produce cytokines which by acting on regions of the central nervous system involved in the HPA axis can modify the neuroendocrine activity and behavioral responses3. Administration of exogenous glucocorticoid betamethasone, caused loss of important proteins involved in brain morphogenesis and function, such as microtubule associated protein and synaptophysin9,18. . This substantiates the hypothesis of gut brain communication through the HPA axis in stress.

Stress is also associated with immune system impairment as the immune system is integrated in the bidirectional network with the HPA axis. Further factors that support the concept linking stress, immune activation, and gut microflora changes in association with gut brain axis can be emphasized by studying the effect of probiotic use.

Exposure to early post natal stress results in impairment of the HPA axis causing hyper responsiveness to ensuing stress stimuli, resulting in long term excessive stimulation of glucocorticoids19. Persistent increased stimulation of HPA axis results in increased neonatal corticosterone levels19. This state if continued to exist in female adults will in their later life manifest as adult elevated Adrenocorticotropic hormone (ACTH) levels.

Maternal probiotic inoculation protects against immune dysfunction and disruption of adult gut microflora following exposure to neonatal maternal separation

113

CHAPTER 22

C.jejuni increases anxiety like behaviour13. C.jejuni infection induces c–fos protein expression in the basolateral nucleus of the amygdyla (BLA), paraventricular nucleus of the hypothalamus (PVN), central nucleus of the amygdyla (CEA), and bed nucleus of the stria terminalis (BST) 13.

These regions are involved in processing autonomic, neuroendocrine and behavioural responses to internal challenges like infection, processive and exteroceptive challenges and are responsible for shift in exploratory strategy with preference for safety over foraging.13 Bacterial endotoxin could alleviate anxiety acting through cytokines14. Mice inoculated with C.jejuni, prior to the activation of cytokines, showed C- fos induction at the nucleus tractus solitarius region of the brain, but no c-fos induction in the enteric ganglion cells, indicating role of vagal sensory neurons, activated by immune cells, paneth cells, or by neuroactive bacterial products, in the early period following infection14.

their antidepressive therapeutic influences in rodents by bringing about various changes in neurotransmitters, growth factors and neuromodulators15. Probiotic Bifidobacterium therapy produced normalization of immune response, restoration of noradrenaline levels and reversal of behavioral impairments6. Studies have shown possible therapeutic approaches which are as follows: Keshavarzi, Zakieh, et al showed that plant aloe vera decreased gastric acid output10. This effect could be due to the composition of the plant contributing to increased mucous blood flow and elevated intestinal mucin and bicarbonate secretion.10

NEUROLOGY

114

or adult restraint stress19. This it achieves by increasing plasma IgA levels. IgA takes part in the first and second line defence against the pathogens breaching the mucosal surface19.

Maternal separation affects the normal balance of gut microbiota. This occurs due to increase in aerobic bacteria like enterococci, anaerobic bacteria like clostridia and gram negative bacteria like E.coli while levels of beneficial bacteria like lactobacilli and bifidobacterium is maintained unchanged19. Study shows that although neonatally stressed adults did not show any change in their gut microflora, when these animals were exposed to an acute stressor in adulthood it resulted in decreased fecal counts of anaerobic bacteria and clostridia. This shows that exposure to stress in early life, sensitizes certain gut microbiota to stress exposure to later life19.

Gut Microbiota and Autism

Autism begins in early childhood and is associated with deficits in social, communication and imaginative development. Changes in the metabolic products and composition of the gut microbiome have been connected to the pathophysiology of autism spectrum disorder (ASD) 7,20,21. There is a frequent association of G.I problems in children with autism as compared to the general population7,20. GI problems occur in parallel with behavioral symptoms more in autistic patients than healthy individuals22. Significant colonization with distinct Clostridial species in gastrointestinal flora and evidence of Clostridial species in the fecal sample21 were found in autistic children in comparison to healthy children21,22. It is postulated that serum concentration of lipopolysaccharide is considerably higher in autistic patients in comparison with healthy individuals,7 this was inversely related to socialization scores in a independent manner7. Further studies prove that interventions with antibiotics and probiotics improve symptoms in ASD subjects19,20. These findings support the concept of modulation of gut barrier integrity and the role of microbiota in the origin of ASD7. Bacterial mediated production of indole containing metabolites like indole -3 â&#x20AC;&#x201C; propionic acid is based on the presence of the particular bacterium, Clostridium sporogens of gut microflora.

The accumulated propionic acid induces mitochondrial dysfunction that leads to energy failure affecting the brain and gut of the autistic children.

Treatment with Vancomycin caused substantial improvements in ASD but was transient as following two weeks after treatment cessation, there was regression probably due to the continued existence of spores of clostridia20. This short term supression of autism related symptoms was probably due to the effect of the antibiotic in eliminating the neurotoxin produced by the bacteria20.

This indicates colonization or action of neurotoxin produced by clostridial species to play a role in ASD20.

Symptoms of ASD is strongly correlated to neurocognitive impairment, in preterm children3,20,21. In a study conducted

by L.Desbonnet et al, germ free (GF) mice showed altered sociability including social avoidance, reduced preference

for social novelty and repetitive self-grooming behavior.

This study shows the important role played by microbiota in the presentation of distinct normal social behavior which is impaired in neurodevelopmental disorders like schizophrenia and autism. There was reduced activity in the right anterior insular region in social tasks as opposed to non social tasks of the brain in autistic subjects when compared to the controls8,22,23. This suggests that VEN might play a role in autism8,23. Recent studies also highlight the role Hyperbaric Oxygen Therapy (HBOT) to reduce the mitochondrial dysfunction and have a good outcome in the behavioral improvement and gut functions of the ASD children 29.

Association Between Gut Microbiota, Myelination and Neuropsychiatric Disorders

Study has shown the association of microbiome with cortical myelination. Appropriate presence of functional microbiota is essential for the correct cortical myelination at well suited times of neurodevelopment24. This study revealed hypertrophic neuronal signaling in GF mice leading to hypermyelination in the prefrontal cortex (PFC). These changes in myelination could be reversed on colonization with conventional microbiota following weaning24. Therefore microbiota could serve as therapeutic targets in psychiatric disorders which are linked to dysmyelination process and have been advocated for remyelination in myelination diseases24.

Gut microbiota and Parkinsonism:

The severity of motor impairment is related to gastroparesis which occurs frequently in Parkinsonism disease (PD). Reduced abundance of Prevotellaceae bacteria and increased abundance of Enterobacteria were found to be prevalent in the postural instability with gait difficulty phenotype of Parkinson disease than the tremor dominant type30. Prevotellaceae bacteria is commensal are involved in mucin synthesis in the gut mucosal layer and production of neuroactive short-chain fatty acids (SCFA) through fiber fermentation. Reduced abundance of Prevotellaceae results in decreased mucin synthesis and increased intestinal permeability leading to the greater local and systemic exposure to bacterial antigens and endotoxins, which in turn would trigger or maintain excessive alpha-synuclein expression in the colon or even promote its miscoding. These misfolded alpha-synuclein may spread along the vagal nerve to the brain stem in a caudo-rostal pathway and reach the dorsomotor vagus nuclei, from there spread to the pedunculopontine nuclei and rostrally to the substantia nigra and basal forebrain explaining the gastrointestinal symptoms like gastroparesis, bloating and constipation prior to the motor symptoms in Parkinson disease. PD through its gastroparesis and impaired GI motility may predispose to SIBO (small intestinal bacterial overgrowth). SIBO independently predisposes to worse motor function. It is possible that SIBO contributes to motor dysfunction by disrupting small intestinal integrity leading to immune stimulation and/or alteration in L-dopa absorption30. Also SIBO may cause changes in the gut permeability which

115 Increased intestinal permeability

CHAPTER 22

Enteric nervous system neurons enteric glial cells

Activation of intestinal mucosa immune system

Gut microbiota alterations

Fig. 1: The link establishing the gut dysbiosis, intestinal permeability and neurological dysfunction in Parkinsons disease promotes translocation of bacteria and endotoxins across the intestinal epithelium, inducing the pro-inflammatory response along with accumulation of misfolded alphasynuclein enteric neurons. Lipopolysacharide derived from gram negative enterobacteria may cause delayed and progressive nigral pathology. Neural dysfunction correlated more with inflammatory response than the extent of bacterial colonisation14. Thus a link between gut dysbiosis, intestinal permeability and neurological dysfunction has been well documented in PD (Figure 1).

H. pylori is correlated with detrimental motor function of Parkinson disease 25. H pylori infection, caused increased muscle contractility which may be due to increased polymorphonuclear cells (PMN) infiltration14. Also antral relaxation was higher which was maybe due to incresed neuronal inhibition or decreased neuronal excitation.

H pylori infection caused reduced acetyl choline (ACh) release14. This lower levels of ACh release was due to either disrupted synthesis or storage of ACh.14 Hence abnormal cholinergic nerve function could be the reason for the higher degree of antral muscle relaxation14.

H pylori by increasing levels of vasoactive intestinal polypeptide (VIP), and causing changes in nitric oxide (NO) containing neurons, contribute to increased antral relaxation14.

Influence of Maternal Microbiota on the Fetus and its effect on the Brain Development

Neonates are first brought in contact with microbes from maternal microbiota4. There are three specific types of microbiota called the enterotypes, manifested at a early

stage in the neonates and therefore have a long term effect on health and immunity of the neonate4.

Breast milk is an efficient and sustained source of streptococci, staphylococci, lactic acid bacilli, and bifidobacterium4. This growth of beneficial bacteria is also contributed by oligosaccharides4. Exposure to microbes before birth, during pregnancy and lactation has an impact on the metabolic and immunologic profiles of the pregnant uterus. Commensal microbiota not only plays a role in the development of the immune system but is also necessary for brain development4. However this regulation has definitive time restraint. Gut microbiota can influence the development of the brain and modulates behavior like decreasing physical activity and increasing anxiety4.

Exposure to IL â&#x20AC;&#x201C; 6, in utero could alter brain development resulting in permanent behavioral damage4. Therefore it is important to understand the time period when changes to the immune function could make the brain susceptible for injury and the period most appropriate for restoration of the brain function4.

Gut microbiota and hologenomic theory of evolution

Hologenome and holobiont occur in concord to act as a selection unit in evolution. The diverse microbial population by holding a symbiotic relationship with the host causes changes in the hologenome which makes the holobiont more fit and adaptive to the changing enviornment28. The capacity for these variations in the hologenomes should be thought of, considering the fact that there are 150 times more bacterial genes than human genes in the gut28.

The host and symbiont become totally dependent on

NEUROLOGY

116

each other especially at times of absolute mutualism.

Among other benefits most importantly this symbiotic relationship favour colonisation of commensal microbiota instead of pathogenic microbes thereby protecting against infections28.

Acquisition of new symbionts from the enviornment leads to incorporation of novel genes into the hologenome28.

This concept opens doors to synthesising genetically modified probiotics. This would aim at achieving favourable hologenomic modifications by changing symbionts genome. This in turn would help the host to survive in adverse conditions.

Gut microbiota in the pathogenesis of Multiple Sclerosis

Multiple sclerosis, an autoimmune disorder characterised by immune mediated destruction of the oligodendrocytres of the central nervous system neurons has been characterised by demyelination and axonal damage.

Several hypothetic models have been put forth to explain the autoimmune trigger for this disorder and the latest and convincing model is the altered gut microbiota.

Several organisms including Parabacteroides, Prevotella (Bacteroidetes), Adlercreutzia which are involved in the metabolism of phytoestrogens, plant-derived xenoestrogen and Collinsella (Actinobacteria), and Erysipelotrichaceae (Firmicutes), involved in the bile acid metabolism were found to be decreased in abundance in the relapsing remitting multiple sclerosis (RRMS) patients compared to the healthy controls. Metabolites derived from the metabolism of phytoestrogens (lignan and isoflavone) and bile acids play an important role in maintaining homeostasis at mucosal surfaces through the induction of anti-inflammatory responses. Thus a perturbation of the gut microbiota results in the altered homeostasis and thus leads on to the activation of immune responses that might trigger a autoimmune trigger in RRMS31.

Role of Nervous system in Gut infection

The GI tract acts as a key interface between the body and the pathogen, the lining epithelium, holds the ability to recognise pathogens, followed by stimulating the host defence mechanism and thereby eliminating the pathogen. The epithelium incorporates macrophages, mast cells and dendritic cells which are innervated by nerve fibres belonging to the enteric ganglia, vagus and spinal visceral sensory fibres. It is postulated that the signals generated by these nerve fibres are responded by the immune cells which are located in close proximity to the nerve fibres14. Also peripheral neurons could take part in this by being activated through bacterial products or through bacterially derived neuroactive substance like the GABA or histamine14. Early vigorous host defence is through neural response which is probably followed by immune mediated brain signaling via the cytokines14.

Bacterial stimulation of vagal sensory neurons indicates the possibility of peripheral nerves to direct local immune or inflammatory condition to play a role in signaling the immune activity to brain pathway which in turn could

contribute to important information like the location of infection corresponding to host defence14.

CONCLUSION

Gut microbiota has a tremendous influence on the brain.

This review focuses on the influence of gut microbiota on diseases concerned with the central nervous system such as depression, autism, Parkinsonism, demyelination diseases and other psychiatric diseases associated with sociocognitive deficits. Various pathways involved in the gut brain axis including some details of the immune and inflammatory system pertaining to the aforementioned conditions is mentioned. This review paves way to the idea that administration of aloe vera, or probiotics, or implementation of novel hologenomics and likewise alternative strategies alongside antibiotics could maintain the balance in gut microbiota. This in turn throws light on the speculation of extending the therapeutic benefits of antibiotics from short term to long term treatment of autism spectrum disorder. Therefore this review advocates the need for further research in this area with the perception; that the harmony in the gut microbiota would enable to improve the treatment of neuropsychiatric diseases from bench to the bedside.

ABBREVIATIONS

1.

CNS – Central nervous system

2.

G.I – Gastrointestinal

3.

VEN – Von economo neurons

4.

IBS – Irritable bowel syndrome

5.

IBD – Inflammatory bowel disease

6.

BLA - Basolateral nucleus of the amygdyla

7.

PVN - Paraventricular nucleus of the hypothalamus

8.

CEA - Central nucleus of the amygdyla

9.

BST - Bed nucleus of the stria terminalis

10.

GABA – Gamma amino butyric acid

11.

IL – 6 - Interleukin 6

12.

Th1 and Th2 – T helper cell 1 and T helper cell 2

13.

HPA axis – Hypothalamic pituitary adrenal axis.

14.

ACTH – Adrenocorticotropic hormone.

15.

Ig A - Ig A antibody

16.

GF - Germ free

17.

ASD – Autism spectrum disorder

18.

PFC - Prefrontal cortex

19.

Ach - Acetyl choline

20.

VIP - Vasoactive intestinal polypeptide

21.

NO - Nitric oxide

22.

CGRP - Calcitonin gene related peptide

23.

SP - Substance P

24.

ACC - Anterior cingulate cortex

25.

SIBO- small intestinal bacterial overgrowth

26.

PD- Parkinson disease

27.

RRMS- Relapsing Remitting Multiple Sclerosis

REFERENCES

Ghosh, Amit, et al. “Microbes-Gut-Brain Axis: A Possible Future Therapeutics Target for Gastrointestinal and Behavioral Disorder.” International Journal of Health Sciences and Research 2015; 5.1:321-29.

2.

Wikoff, William R., et al. “Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites.” Proceedings of the National Academy of Sciences 2009; 106.10:3698-3703.

3.

Galley, Jeffrey D., and Michael T. Bailey. “Impact of stressor exposure on the interplay between commensal microbiota and host inflammation.” Gut Microbes 2014; 5.3:390-396.

4.

Collado, Maria Carmen, et al. “Microbial ecology and host-microbiota interactions during early life stages.” Gut Microbes 2012; 3.4:352-365.

5.

Beaumont W. Experiments and Observations on the Gastric Juice and the Physiology of Digestion. Plattsburg: F.P. Allen; (1833).

6.

Desbonnet, L., et al. “Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression.”

Neuroscience 2010; 170.4:1179-1188.

7.

Mangiola, Francesca, et al. “Gut microbiota in autism and mood disorders.” World Journal of Gastroenterology 2016; 22.1:361.

8.

Smith, Peter Andrey. “The tantalizing links between gut microbes and the brain.” Nature 2015; 526:312-314.

9.

Heijtz, Rochellys Diaz, et al. “Normal gut microbiota modulates brain development and behavior.” Proceedings of the National Academy of Sciences 2011; 108.7:3047-3052.

10. Keshavarzi, Zakieh, et al. “The effects of aqueous extract of Aloe vera leaves on the gastric acid secretion and brain and intestinal water content following acetic acid-induced gastric ulcer in male rats.” Avicenna Journal of Phytomedicine 2014; 4.2:137.

11. Ledochowski, M., et al. “Carbohydrate malabsorption syndromes and early signs of mental depression in females.”

Digestive Diseases and Sciences 2000; 45.7:1255-1259.

12. Ledochowski, M., B. Sperner-Unterweger, and D. Fuchs.

“Lactose malabsorption is associated with early signs of mental depression in females (a preliminary report).”

Digestive Diseases and Sciences 1998; 43.11:2513-2517.

13. Goehler, Lisa E., et al. “Campylobacter jejuni infection increases anxiety-like behavior in the holeboard: possible anatomical substrates for viscerosensory modulation of exploratory behavior.” Brain, Behavior, and Immunity 2008; 22.3:354-366 14. Berčík, Přemysl, et al. “Immune-mediated neural dysfunction in a murine model of chronic Helicobacter pylori infection.” Gastroenterology 2002; 123.4:1205-1215.

117

16. Padgett, David A., and Ronald Glaser. “How stress influences the immune response.” Trends in Immunology 2003; 24.8:444-448.

17. Sudo, Nobuyuki, et al. “Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice.” The Journal of Physiology 2004; 558.1:263-275.

18. Antonow‐Schlorke, Iwa, et al. “Glucocorticoid exposure at the dose used clinically alters cytoskeletal proteins and presynaptic terminals in the fetal baboon brain.” The Journal of Physiology 2003; 547.1:117-123.

19. Barouei, Javad, Mahta Moussavi, and Deborah M. Hodgson.

“Effect of maternal probiotic intervention on HPA axis, immunity and gut microbiota in a rat model of irritable bowel syndrome.” PLoS One 2012; 7.10:e46051.

20. Parracho, Helena MRT, et al. “Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children.” Journal of Medical Microbiology 2005; 54.10:987-991 21. Mayer, Emeran A., et al. “Gut microbes and the brain: paradigm shift in neuroscience.” The Journal of Neuroscience 2014; 34.46:15490-15496.

22. Desbonnet, L et al. “Microbiota Is Essential for Social Development in the Mouse.” Molecular Psychiatry 2014; 19.2:146–148.

23. Allman, John M., et al. “The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans.” Brain Structure and Function 2010; 214.56:495-517.

24. Hoban, A. E., et al. “Regulation of prefrontal cortex myelination by the microbiota.” Translational Psychiatry 2016; 6.4:e774.

25. Parmar, Arpit. “Gut–brain axis, psychobiotics, and mental health.” Asian Journal of Psychiatry 2016; 22:84-85.

26. Critchley, Hugo D., Christopher J. Mathias, and Raymond J. Dolan. “Neural activity in the human brain relating to uncertainty and arousal during anticipation.” Neuron 2001; 29.2:537-545.

27. Mayer, Emeran A. “Gut Feelings: The Emerging Biology of Gut–brain Communication.” Nature reviews. Neuroscience 2011; 12.8:10.1038/nrn3071.

28. Singh, Yadvir, et al. “Emerging importance of holobionts in evolution and in probiotics.” Gut Pathogens 2013; 5.1: 1.

29. Daniel.A.Rossignol. Interrelationships among the Gut, Mitochondrial Function, and Neurologica Sequelae. Autism science digest. The journal of autismone : issue 04 :57-65 30. Agata Mulak, Bruno Bonaz.Brain-gut-microbiota axis in Parkinson’s disease. World J Gastroenterol 2015; 21:1060910620 31. Jun Chen, Nicholas Chia. Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls. www. nature.com Scientific Reports | 6:28484 | DOI: 10.1038/ srep28484.

CHAPTER 22

1.

15. Jagmag, Shail Adrian, et al. “Exploring the Relationship between Gut Microbiome and Depression.” Trends Gastroenterol 2016; 1.001.

Clinical Approach to Tremor

C H A P T E R

23

K Venkatraman, R Lakshminarasimhan, AV Srinivasan

INTRODUCTION

Tremor is defined as rhythmic involuntary oscillatory movement of the body part that is brought about by alternating or synchronous contractions of reciprocally innervated antagonist muscles 1. It is classified under the hyperkinetic movement disorders that are rhythmic and predictable. Tremor is also the most common movement disorder that affects mankind. In clinical practice, the diagnosis of tremor is obvious and cannot be missed.

Identification of the type of tremor is the next important

step in further differentiating the tremors for treatment and prognostication. This review will classify the tremors, enumerate the characteristics and differentiating points for individual tremor syndromes, provides an algorithmic approach to the tremors and finally various treatment options.

TREMOR CHARACTERISTICS AND CLASSIFICATION

Description of the tremor is done using a number of characteristics. In clinical practice a complete description

Table 1: Classification of tremors Nature

Location

Frequency

1. Simple- involves single muscle group

1. Head â&#x20AC;&#x201C; entire head, chin, face, tongue, palate

1. Low (<4 Hz)

2. Compound â&#x20AC;&#x201C; several muscle groups

2. Medium (4-7 Hz) 2. Upper extremity- proximal, distal 3. High (>7 Hz) 3. Trunk 4. Lower extremity- proximal, distal

Amplitude

Rhythmicity

Relation to rest and movement

1. Fine

1. Regular

1. Rest tremors

2. Coarse

2. Irregular

2. Action tremors i. Postural ii. Kinetic A. Non visual guided B. Visually guided a. Simple(non-target directed) b. Intentional( target directed) iii. Task specific iv. Isometric

Pathology:

Etiology:

Mode of onset

1. Physiological

1. Cortical tremor

1. Sudden

2. Enhanced physiological

2. Parkinson tremor

2. Insidious

3. Pathological

3. Mesencephalic or holmes tremor 4. Cerebellar tremor 5. Essential tremor 6. Dystonic tremor 7. Wilson tremor 8. Tremors in peripheral neuropathy 9. Drug induced tremor 10. Psychogenic

Figure 1:Syndrome classification of tremors DIAGNOSIS

FREQUENCY

ACTIVATION BY

REST

119

POSTURE GOAL DIRECTED MOVEMENTS

PHYSIOLOGICAL TREMOR

ENHANCED PHYSIOLOGICAL TREMOR ESSENTIAL TREMOR SYNDROMES CLASSICAL ESSENTIAL TREMOR

UNDETERMINED TREMOR SYNDROME

CHAPTER 23

ORTHOSTATIC TREMOR TASK AND POSITION SPECIFIC TREMORS

DYSTONIC TREMOR

PARKINSONIAN TREMOR CEREBELLAR TREMOR HOLMES TREMOR

PALATAL TREMOR

NEUROPATHIC TREMOR

DRUG INDUCED AND TOXIC TREMORS PSYCHOGENIC TREMORS

Common frequencies

0

5

10

Rare frequencies

15

Low Middle

Frequency range

High Required for diagnosis

May be present

Fig. 1: Syndrome classification of tremors

of the tremor using these characteristics is useful to narrow down the differentials.

1.

Nature

2.

Location

3.

Frequency

4.

Amplitude

5.

Rhythmicity

6.

Relation to rest and movement

For Parkinsonian resting tremor only

7.

Pathology

8.

Etiology

9.

Age of onset

Based on the above parameters tremors are classified (Table 1). Classification based on the relation to rest andmovement is used widely, because of its ease to administer and high yield in clinical practice.

Most of the tremors have more than one component.

120

Table 2: Causes of Rest tremors Idiopathic Parkinson Disease Parkinsonian syndromes

Multiple Systems Atrophy Corticobasal Syndrome Progressive Supranuclear Palsy

NEUROLOGY

Diffuse Lewy  Body disease Parkinsonism-DementiaALS complex of Guam Progressive Pallidal Atrophy Heredodegenerative disorders

Huntingtonâ&#x20AC;&#x2122;s disease Neurodegeneration with Brain Iron Accumulation Chorea-acanthocytosis Gerstmann-StrauslerScheinker disease Neuronal CeroidLipofuscinosis.

Secondary parkinsonism

Toxins (CO,MPTP, Manganese, methanol, cyanide) Drugs (Table 5) (neuroleptics, dopamine depleting medications, antiemitics) Infections (CJD, SSPE, fungal)/ post encephalitic (von economos disease) Metabolic (hypothyroidism, chronic acquired hepatocellular degeneration, mitochondrial cytopathies) Miscellaneous (stroke, head trauma, neoplastic/ paraneoplastic conditions)

Severe essential tremor Mesencephalic tremor Psychogenic tremor Predominant component and associated signs are used to diagnose the etiology of the tremor.

REST TREMORS

Rest tremor is defined by tremor that occurs in a body part that is not voluntarily activated and is completely supported against gravity 1.

MANEUVER

Patient is examined in a relaxed posture. Forearms are rested on the arms of the chair or patients own lap in repose position. Patient can be asked to count backward

from 100 with eyes closed or arithmetic stress test can be performed to distract and bring the tremor

ACTION TREMORS

Action tremor encompasses postural, kinetic tremor, task specific and isometric. Both these tremors can be present in the same individual.1 Each of this group has a prototype example that is explained below.

Postural tremor

Postural tremor is present while voluntarily maintaining a position against gravity. It most commonly involves the hand and forearm. Other areas that may be involved are head, voice, chin, legs and trunk.

Maneuver

Patient is asked to outstretch the arms in front. Patient can be asked to count backward from 100 with eyes closed or arithmetic stress test can be performed to distract and bring the tremor.

Kinetic tremor

Kinetic Tremors are present during any voluntary movement. Kinetic tremors can be non visual guided or visually guided. Among the visually guided category the tremors are sub classified into simple tremor (non goal directed) and intentional tremor (goal directed).

Simple kinetic tremor

Simple kinetic tremor occurs during voluntary movements that are not target-directed. They may persist during voluntary,goal-directed movement without an increase in amplitude during the terminal phase of movement.

Maneuver

Patient is asked to perform simple pronation/supination movement or flexion/extension of wrist joints.

Intentional tremor

Classic intention tremor is present when amplitude increases during visually guided movements toward atarget at the termination of the movement and the possibility of a position-specific tremor or a postural tremorproduced at the beginning or end of a movement is excluded.

Maneuver:

Patient is asked to do a finger nose test. Tremor worsening at the end point suggests intentional tremor.

TREMOR SYNDROMES

The above given tremor phenomenology are combined into specific syndromes (Figure 1).

SYNDROMES WITH PREDOMINANT REST TREMORS

Parkinson tremor

Tremor associated with Parkinson disease (PD) is the prototype tremor under this category. It is present in almost 60% of PD cases. It is typically asymmetrical, unilateral to start and slowly progresses to the uninvolved side. Most PD tremors are upper extremity tremors to start with, but tremors that begin with leg, jaw and larynx have also been reported. Average frequency of Parkinson

121

Table 3: Causes of enhanced physiological tremor Stress, anxiety and fatigue (rock climberâ&#x20AC;&#x2122;s tremor/elvis leg)commonest cause

Endocrine disturbances

Drugs and toxin induced(Table 5)

1. Hypoglycemia

Drug withdrawal (eg.alcohol)

2. Thyrotoxicosis 3. Pheochromocytoma 4. Adrenocorticosteroids

Table 4: Characteristics of essential tremor Characteristic features

1. Bilateral, largely symmetric postural or kinetic tremorinvolving hands and forearms that is visible andpersistent.

postural tremor + kinetic Amplitude of postural tremor(amplitude more tremor> than kinetic than postural tremor) tremor

2. Additional or isolated tremor of the head may occurbut in Somatotrophic spreadhead tremor after hand the absence of abnormal posturing. tremor Exclusion criteria 1. Other abnormal neurologic signs, especially dystonia.

2. The presence of known causes of enhanced physiologic tremor, including current or recent exposure to tremorogenic drugs or the presence of a drug withdrawal state.

3. Historic or clinical evidence of psychogenic tremor.

Red flags

Hand tremor after head tremor

Severity markers Tremor at rest Intentional tremor of the head Jaw tremor

4. Convincing evidence of sudden onset or evidence of stepwise deterioration.

5. Primary orthostatic tremor.

6.vIsolated voice tremor.

7. Isolated position-specific or task-specific tremors, including occupational tremors and primary writing tremor.

8. Isolated tongue or chin tremor.

9. Isolated leg tremor tremor is 4-6 Hz 2. The classical pill rolling movement of the PD is a resting tremor due to the alternate contraction of agonist and antagonist, involving the flexors, extensors, abductors and adductors of the finger and thumbs. Other upper extremity tremors in PD include wrist Flexion/ extension and forearm supination/pronation. Some PD patients also have a postural tremor. This postural tremor appears only a few seconds after the new posture is made from the resting position (re-emergence phenomenon).

Head tremor is a uncommon feature of PD. PD is not the only cause of rest tremor. There are other causes that should be considered along with PD when encountered with a rest tremor3 (Table 2).

Syndromes with predominant postural tremors

Postural tremor, commonly seen physiologically in all human beings due to mechanical and neural factors, is of high frequency (10-12 Hz), low amplitude, and symmetrical character and can be just seen with naked eyes in extended fingers. This physiological tremor can be enhanced under certain situations (Table 3), such that it becomes coarse enough to make it clearly visible and is termed as enhanced physiological tremor.

Essential tremor

Essential tremor is the most common cause for pathological postural tremors. Age of onset has a bimodal peak in the second and sixth decade and the prevalence increases with advanced age (>20% in people aged >95 years). Definition, characteristic features, red flags signs to the diagnosis of essential tremor and the severity markers are listed in Table 4.Tremor frequency ranges between 4-12 Hz. Tremors may also involve the head (no-no>yesyes), jaw, tongue and voice along with hand tremors4.

More than 50% have intentional arm tremor and ataxia suggesting an underlying abnormality in cerebellum or cerebellar systems. Leg tremor, isolated head and voice tremors are uncommon features of essential tremor.

Dystonic tremor5

Dystonia, a movement disorder that causes abnormality of posture of any part of the body, is commonly associated with tremor that is predominantly postural. The classical example is the head tremor in patients with cervical dystonia. But sometimes these tremors occur in parts that are not affected by dystonia and so are named as tremor associated with dystonia. Example for the above is postural hand tremors in patients with cervical dystonia.

CHAPTER 23

Inclusion criteria

122

SYNDROMES WITH PREDOMINANT KINETIC TREMORS

NEUROLOGY

Cerebellar tremors

Tremors occurring in cerebellar dysfunction assume a kinetic property with predominant intentional component. These tremors may also persist for posture but never in rest. The kinetic component usually is 3-5 Hz and the postural component 5-10 Hz6. Cerebellar tremor occurs due to wide range of diseases. Acute onset with asymmetry is noted in conditions like stroke, multiple sclerosis and tumor with sudden hemorrhage. Gradual and symmetrical tremors are seen in degenerative neurological conditions like spinocerebellar ataxia.

worsens with the posture with still more worsening on action. Tremor frequency is usually less than 4.5 Hz. Tremor is usually unilateral and occurs after a latency of 4 weeks – 2 years following a midbrain lesion. It is postulated to occur due to the involvement of the substantia nigra and the cerebellar outflow tracts in the midbrain. Common causes are stroke and tumors.

Task specific and position specific tremors

Some forms of tremors appear only in relation to a particular position or task.

1.

Primary writing tremor1: tremors occur only during writing(task specific or type A) or when the hand adopts a writing position(position specific or type B). No observable dystonia present.

2.

Orthostatic tremor7 (shaky legs syndrome): tremors appear only on standing and disappear on movement and sitting. These are the tremors with highest frequency (13-16 Hz). Because of the high frequency tremors are not visible to clinical examination and most often present as difficulty in balance and falls.

Holmes tremor1

Holmes tremor is characterized by combination of intentional tremor and rest tremor. The rest tremor

Table 5: Drugs causing tremor Postural

Intentional

Rest

Alcohol (withdrawal) Alcohol

Metaclopromide

Amiadarone

Neuroleptics

Lithium

Amphetamines

Reserpine

Beat adrenergic agonists.

OTHER TREMOR SYNDROMES

Drug and toxin induced tremors

Drugs and toxins induce tremors in all the positions. Table 5 lists the drugs responsible for tremors.

Caffeine Cyclosporine

Wilson’s tremor

Dopamine

Patients with Wilson’s disease have both postural and kinetic tremor. The characteristic wing beating tremor is a large amplitude tremor demonstrated in patients shoulders abducted to 90 degrees and elbows flexed.

This is one example of a proximal tremor. Other signs like dystonic limb posturing, rigidity and choreiform movements aid the diagnosis.

Steroids Theopylline Thyroid hormones Tricyclic antidepressants Valproic acid

Table 6: History and examination for a tremor case History

Examination (7step approach)

Age at onset

1. Examination with arms at rest

Body part or parts affected

2. Examination with arms stretched in front(posture)

Nature of onset(sudden, insidious)

3. Examination with arms stretched in front with arms abducted, elbows flexed and extended, supination and pronation of forearms to look for position specificity of dystonic tremor

Course of tremor(static, progressive) Exacerbating and relieving factors Associated neurological symptoms Associated systemic symptoms- h/o for thyroid illness, diabetes, etc, Drug exposure Family history Level of day to day functional impairment

4. Examination during movement like finger nose test and look for both simple kinetic and intentional tremor 5. Ask the patient to write and draw a Archimedes spiral to bring about the task specific tremor, quantify the severity of tremor and distinguish various tremors.

6. Examination of neurological system to look for pathological cerebellar signs, extrapyramidal signs of Parkinson and dystonia, long tact signs for holmes tremor, other movement disorders like myoclonus, chorea to rule out infective and degenerative conditions of nervous system and neuropathic signs.

7. Consider systemic signs like thyroid swelling,eye signs of hyperthyroidism, postural hypotension in pheochromocytoma, cushingoid habitus in corticosteroid intake, malar and palatal rash with photosensitivity for SLE, cutaneous and hair signs for toxin exposure if relevant.

123

TREMOR taking medications associated with tremors yes

no relieved on distraction

Drug induced tremor

yes no

Psychogenic tremor

CHAPTER 23

age <40 years

yes

no

Rest or action tremor

Serum ceruloplasmin, 24 hour urine copper excretion

positive

Wilsons disease

negative

Rest

action

rigidity, bradykinesia, postural instability postural

kinetic

irregular, assymetric, sensory tricks, dystonic posturing atypical features

yes

task speciďŹ c yes

Parkinson tremor

Parkinson plus diseases

no

Dystonic tremor

Drug induced parkinsonism

yes

Frequency reduction by mass loading, systemic signs

Enhanced physiological tremor

Intentional tremor

Task speciďŹ c tremor

rest component

no

yes

no

yes

Essential tremor

no

Cerebellar tremor

Holmes tremor

Chart 1: Algorithmic approach to tremor 4.

Variation of tremor frequency during distraction orduring voluntary movements of the contralateralhand.

5.

Coactivation sign of psychogenic tremor (resistance to passive movements in the tremulous limb with disappearance of tremor during these movements)

Sometimes tremors can be a part of psychogenic disorder.

A careful history is the only available to diagnose this entity. The following points are characteristic of psychogenic tremors1

6.

Somatization in the past history.

7.

Appearance of neurologicsigns.

1.

Sudden onset of the condition, remissions, or both.

Practice points for differentiating the tremors

2.

Unusual clinical combinations of rest and postural/ intentional tremors.

3.

Decrease of tremor amplitude during distraction.

Tremors in peripheral neuropathy

Tremors occur in hands of patients with peripheral neuropathy especially demyelinating, connective tissue disorder associated and dysgammaglobulinemic neuropathy.

Psychogenic tremors

additional

and

unrelated

Most of the patients who present with tremors have a combination of tremor syndromes that might pose a challenge to diagnosis. A patient with severe Parkinson tremor (rest and action) can be differentiated from a severe form of Essential tremor by the re-emergence phenomenon

124

Table 7: Laboratory investigations in a tremor case

Table 9: Interventional treatment for tremors

Cerebellar tremor

CT/ MRI

Essential tremor

Enhanced physiological tremor

Serum glucose level, thyroid-stimulating hormone level, liver function testing, patient history to evaluate for anxiety and caffeine use.

NEUROLOGY

Essential tremor

Parkinson tremor

No specific test; complete blood count, thyroidstimulating hormone level, serum chemistry profile may rule out other disease No specific test; positron emission tomography or single-photon emission computed tomography for atypical presentation

Psychogenic

Careful history

Young age <40 years

Slit lamp for KF ring, Serum ceruloplasmin, urine copper excretion, screening for heavy metal poisoning.

Orthostatic tremor

EMG

Table 8: Medications for tremor treatment Essential tremor

Beta blockers(propranolol/ nipradilol Primidone Clonazepam(for kinetic component)

Parkinson tremor

Dystonic tremor

1. Deep brain stimulation

Parkinson tremor

1. deep brain stimulation of sub thalamic nuclei 2. Gamma knife thalamotomy

Cerebellar tremors

1. thalamic DBS surgery 2. thalamotomy

head tremor, dystonic voice (characterised by change in voice tremor during emotional speech and singing), rapid emergence of a postural tremor, normal olfaction, lack of response to dopaminergic medication, relatively stable natural history help to differentiate a dystonic tremor from Parkinson tremor. Absent tremor at rest, fading of tremor on posture and lower frequency of tremor help distinguish a cerebellar tremor from essential and Parkinson tremor.

Cortical tremors or rhythmic myoclonus are intermittent brief muscle jerks that are rhythmic or irregular with a lower frequency and hyperkinesia limited to segmental levels and should be differentiated from a tremor.

Flapping tremor which is actually a negative myoclonus, can be differentiated from tremors by less regular, long duration (>200ms) of lapses of the outstretched hand.

DIAGNOSTIC APPROACH

History and examination

Botox injection Levodopa

LABORATORY INVESTIGATIONS (TABLE 7)

Clonazepam

Dopaminergic agonist Cerebellar tremors

2. ventralisintermedius (Vim) thalamotomy

History and examination in a tremor patient is targeted to identify the type of tremor, the cause for the tremor and the complications. Table 6 enumerates the historical and examination details in a tremor patient8. Chart 1 provides an algorithmic approach to a case of tremor.

Botox injection(for head, voice tremors) Dystonic tremor

1. deep brain stimulation of the thalamic nucleus ventralisintermedius (Vim) and posterior subthalamic area

Treatment

Anticholinergic drugs

Treatment of tremor is based mainly on

Less amenable to drugs

1.

Carbamazepine, topiramate, isoniazid, buspirone tried with varying efficacy.

treatment of underlying condition/ removal of the offending agent.

2.

pharmacological treatment for reduction of tremors (Table 8).

3.

deep brain stimulation.

4.

surgical treatment.

in posture, and from the Holmes tremor by the severity of tremor in relation to position. Positional preference (amplitude increase when hand positioned near nose) and frequency reduction with mass loading to the hands can help in differentiating a physiological tremor from essential tremor. Less regular, asymmetric,myoclonic component, sensory tricks (gesteantagoniste), aggravation for specific posture or null point, muscle hypertrophy and pain are the points which help distinguish a dystonic tremor from postural tremor. Presence of a jerky tremor,

Treatment of systemic conditions like hyperthyroidism, pheochromocytoma and removal of the offending drug that causes tremor is the first step in the treatment of enhanced physiological tremors.

PHARMACOLOGICAL MEASURES (TABLE 8)

Deep brain stimulation and surgical management

When the tremors are refractory to medical management

deep brain stimulation and surgical management are considered (Table 9).

CONCLUSIONS

Tremor is a frequent neurological entity faced by physician in day to day practice. A comprehensive knowledge into the tremor characteristics, etiological agents and an algorithmic approach will help the physician from ordering unwanted investigations and guide into the qualitative management of the patients.

Fahn S, Jankovic J, Hallett M (Eds). Tremors: diagnosis and treatment. In: Principles and Practice of Movement Disorders, 2nd edition. Saunders, New York, 2011;389-414.

4.

Hubble JP, Busenbark KL, Pahwa R, Lyons K, Koller WC. Clinical expression of essential tremor: effects of gender and age. Mov Disord 1997; 12:969-972.

5.

Young Eun Kim and BeomSeokJeon (2012). Dystonia with Tremors: A Clinical Approach, Dystonia - TheMany Facets, Prof. Raymond Rosales (Ed.), ISBN: 978-953-51-0329-5

6.

Seeberger LC, Hauser RA. Cerebellar tremor. In: Handbook of essential tremor and other tremor disorders. Eds: Lyons KE, Pahwa R. Taylor & Francis Group, Boca Raton, 2005:227-241.

7.

Piboolnurak P, Yu QP, Pullman SL. Clinical and neurophysiological spectrum of orthostatic tremor: case series of 26 subjects. Movement Disorder 2005; 20:1455-1461.

8.

Mark J.Edwards,GuentherDeuschl. Tremor Syndromes.

Continuum 2013; 19:1213-1224.

REFERENCES

1.

2.

Gunther Deuschl,PeterBain,MitchellBrin .Consensus Statement of the Movement Disorder Society on Tremor.

Movement Disorder 1998; 13. Supplement 3. 2-23 Lang AE, Zadikoff C. Parkinsonian Tremor. In: Handbook of Essential Tremor and Other Tremor Disorders. Eds: Lyons KE, Pahwa R. Taylor & Francis Group, Boca Raton, 2005:227-41.

125

CHAPTER 23

3.

C H A P T E R

24

Approach to Frequent Falls in Elderly People

INTRODUCTION

Elderly population is about 8 % of total population in India and is increasing every year. The basic marker of old age is “slowing of behaviour” resulting in slowness of reaction and task performance. Ageing leads to decreased strength, vision, hearing, proprioception and reaction time. These changes lead to reduced balance and altered gait leading to falls. Falls may be due to extrinsic factor (external hazards) or intrinsic factors like diseases, medications or combination of both. Falls may have a very serious consequences like fractures, soft tissue injury, head injury and even death. There are many causes for recurrent falls and falls with injury should be evaluated thoroughly to find out the cause and prevent future falls. Prevention of frequent falls is by multicomponent intervention as suggested by AGS (American Geriatrics society) and BGS (British Geriatrics society) 2010 guidelines.

ELDERLY

Elderly or old age means nearing or surpassing the life expectancy of human beings. It denotes the end of human cycle. The various terms used to denote elderly are seniors, senior citizens and the older adults. The basic mark for old age is “slowing of behaviour”. This “slowing down principle” finds a correlation between advancing age, slowness of reaction and task performance.1 In India according to ministry of statistics and programming the size of elderly population over age of 60 years is fast growing and constitutes about 8 % of total population according to 2011 census.2

FALLS IN ELDERLY

As a person gets older a number of age related changes takes place in the body. There is decrease in muscle mass resulting in decreased strength, decreased visual and hearing acuity, decreased proprioception and reaction time. Because of all these changes there is reduced balance and altered gait in an elderly person leading to falls even when performing routine activities.3 A fall is defined as an event that results in the patient or a body part of the patient coming to rest inadvertently on the ground or other surface lower than the body.4 Falls are common in elderly and it can lead to devastating consequences. It can result in fractures, soft tissue injuries, head injuries and even death. Fractures account for 70 % of serious injuries due to falls, with hip fractures being the most common. It leads to significant morbidity and mortality. While most falls do not result in significant injury, the fear of fall could result in serious psychological

AR Vijayakumar, VS Prasadh

impact. This leads to restriction of activities by the individual and quality of life decreases.5

RECURRENT FALLS

Recurrent falls is defined as 2 or more falls within 6 months. In more active persons fall may result in more serious injury than in a less active person. Frail elderly persons tend to fall and injure themselves during course of routine activities. A fall with injury should be evaluated immediately.5 Recurrent falls are due to multiple disorders superimposed on ageing changes. Recurrent falls may have different etiology and if risk factors are high then there is increased chance of recurrent falls.

Majority of elderly people fall at home (70%) and about 20 % requires hospitalisation. Accidental falls due to environmental hazards (tripping, slippery floors, inadequate lighting) are the most common cause of falls among elderly people living independently. Most of these accidental fall occurs during routine activities like walking or changing position like sitting to standing.3 Falls in elderly are usually due to more than one cause, because of intrinsic deficits like disease and medications, activities at time of fall and extrinsic causes (environmental obstacles).6

EPIDEMIOLOGY

A cross sectional study of elderly people with falls over 1year period done from Chandigarh showed the following results •

31 % of the recruited people had 1 or more falls.

•

Risk of fall was higher among females.

•

Majority of falls (68%) happened in home and most (75%) of them occurred while carrying out activities like bathing, toileting, sleeping, walking and change in position.

•

67 % of the patients sustained injuries and among them 8 % had fractures.7

TYPES OF FALLS

Different types of falls in the elderly are 1.

Mechanical falls due to tripping and slipping.

2.

Drop attacks due to orthostatic hypotension, colloid cyst of third ventricle with intermittent obstruction of foramen monro.

3.

Toppling falls and gait freezing due to parkinsonism

Falls due to reeling or staggering gait of cerebellar ataxia and alcohol.

5.

Falls due to high steppage gait in sensory ataxia.

6.

Falls due to neuromuscular diseases producing high stamping gait and waddling gait.

7.

Falls due to drugs.

8.

Psychogenic gait disorder.

9.

Antalgic gait due to osteoarthritis, podiatric disorders and other painful conditions of lower limb.8

CAUSES OF FALLS IN ELDERLY

•

Decline in peripheral vision

•

Bifocal lenses

18.

Decreased hearing

19.

Painful arthritis and unstable joints

20.

Syncope, drop attacks and epilepsy.5

127

EXTRINSIC CAUSES OF FALLS

1.

Poor lighting

2.

Unsafe stairways

3.

Irregular floor surfaces

4.

Slippery bathroom

5.

Too low furniture and commode

6.

Foot wears with high heels

7.

Obstacles on the floor like rugs and Floor mats

CHAPTER 24

4.

1.

Older age especially > 75 years

2.

Females

3.

Home bound state

4.

Living alone

5.

Use of walker

1.

Sedative/hypnotic

6.

Previous falls

2.

Tricyclic antidepressants

7.

Acute illness like

3.

Antihypertensives

•

Acute Myocardial infarction

4.

Cardiac medications

•

Pneumonia

5.

NSAIDS

•

Stroke

6.

Anticholinergic drugs

•

Gastro Intestinal bleed

7.

Hypoglycemic agents

•

Hypoglycemia

8.

Any medication likely to affect balance5

•

Hyperglycemia

•

Hyponatremia

•

Hypokalemia

8.

Chronic diseases like Chronic obstructive pulmonary disease (COPD), Obstructive sleep apnoea (OSA), Osteoporosis

9.

Physical deficits

10.

Accident fall from bed

11.

Gait disturbances

12.

Balance disorders like vertigo

The following points should be looked for in the physical examination

13.

Medications, alcohol

1.

Visual acuity of the patient should be assessed.

14.

Neuromuscular disorders

2.

Hearing should be tested

15.

Confusion and cognitive impairment

3.

Neurological evaluation

16.

Postural hypotension

•

Cognitive evaluation

17.

Visual disorders like

•

Tests of cortical, extrapyramidal function

•

Cataract

•

Cerebellar function and proprioception

•

Disturbances in accomadation

•

Muscle power (especially of lower extremities)

•

Myopia

•

Assessment of gait and balance

•

Presbyopia

•

•

Decreased night vision

Assessment extremities

MEDICATIONS INCREASING RISK OF FALLS

EVALUATION OF FALLS HISTORY (FIGURE 1)

A detailed history is useful in understanding the mechanism and cause of fall but often it can be incomplete and cause may be difficult to ascertain. The points to be focussed in the history includes past history of falls, any person witnessed the fall, presence of any risk factors, circumstances of fall, review of medications taken by the patient with special attention given to intake of any new medications in the past 2 weeks.5

PHYSICAL EXAMINATION

of

peripheral

nerves

of

lower

NEUROLOGY

128

Table 1: Interventions to be done for abnormal results of Timed Up and Go test Observation

Significance

Intervention

Difficulty rising from chair

Proximal muscle weakness

PT referral for lower extremity strengthening

Staggering or reported dizziness upon rising

Possible orthostasis

Check orthostatic vital signs, review medications that may contribute to orthostasis

Pill rolling tremor, stooped posture, festinating gait

Possible parkinsonism

Consider neurology referral

Increased sway, magnetic gait Possible normal pressure hydrocephalus

Ask about memory issues and urinary incontinence, if + consider CT

Path deviation

Peripheral neuropathy, CVA

Neuropathy work up, PT referral for assisted device

Slow, antalgic gait

Pain from osteoarthritis, peripheral neuropathy, podiatric disorders

Pain control, examination of feet

4

Mobility of joints

5.

Cardiovascular evaluation

•

Heart rate and rhythm

•

Blood pressure and postural variation

•

If necessary B.P and pulse variation to carotid sinus stimulation

6.

Examination of feet and footwear9

SCREENING FOR FALLS

The American and British geriatrics societies (AGS and BGS) in the year 2010 gave a summary of recommendations for prevention of falls in elderly. It states that all persons aged 65 and greater should be asked about history of previous falls. If the patient had history of fall or gait/ balance disorders, patient should undergo in office assessment tests like Timed Up and Go tests.10

TIMED UP AND GO TEST

It is a simple office room test where patient’s gait and balance is tested for abnormality. In this test patient is initially asked to sit back in the chair with armrests. Then patient is asked to get up without using hands, walk for 3 meters without touching the wall, turn around, walk back to the chair and sit down. All these events are timed by the examiner. A normal person should be able to complete all these tasks within 10 seconds. If the person takes more than 30 seconds to complete the tasks, the test is considered as abnormal and the person needs assistance for mobility.5,10

PREVENTION

Elderly people with recurrent falls should have telephone or mobile phones at the reachable level or must have mobile phone in person. They should be taught how to get up from the fall. Use of hip protectors in reducing hip fracture is not clear.6 Various single and multicomponent interventions have shown to decrease the risk and rate of falls.

VITAMIN D

Vitamin D supplementation given in doses of 800 IU/day

or more have shown to decrease the incidence of falls in long term care.4

EXERCISE

Various exercise modalities have been studied to reduce falls. According to 2010 AGS and BGS guidelines individual exercise regimen like Tai chi or physiotherapy is recommended for all at risk patients (grade A recommendation).9 Tai chi is a low impact rhythmic stretch cardiorespiratory exercise practised extensively helps in gait and balance disorders. Tai chi is a combination of strength and balance training, with a certain aerobic element.11 A meta - analysis done in 2008 showed that the fall rates were greatly reduced following programs including combination therapy. This included a combination of greater than 50 hours of duration of exercise (during trial period), challenging balance exercises (e.g, standing with feet together or on one leg, minimising the use of hands to assist and practising controlled movements of the centre of mass) and it did not include a walking program.12

MEDICATIONS

Polypharmacy is very common in elderly due to prevalence of many chronic diseases and multiple providers. Many drugs increase the risk of falls in elderly population. So modification of these drugs results in reduction of falls.

However one should be very cautious when weaning of certain medications suddenly which have been used chronically. According to 1 study a statewise policy to reduce benzodiazepine use did not reduce the fracture rates among that population. This emphasizes the fact that each patient should be managed on an individual basis.11

VISION

Visual impairment increases the risk of falls and early intervention is necessary. Cataract surgery should be done at the earliest. Screening for visual impairment and providing glasses should be done. However it has been found that prescription of new glasses resulted in increased rate of falls. This might be due to difficulty in adjusting to new glasses and increased activity. Also it has been found that people who wear multifocal lenses

ALGORITHM FOR THE EVALUATION OF FALLS IN THE ELDERLY5 Did the patient had recent fall or near fall? No → Stop ↓Yes Cognitive impairment suspected ?

Yes → Cognitive status evaluation

↓No Any obvious immediate cause of fall

Yes → Treat

↓No History + physical examination + lab tests when indicated ↓

REFERENCES

Yes → Treat

1. Wikipedia, accessed on 28/07/16.

↓No

2. http://www.censusindia.gov.in/vital report/9chap%202%20-%202011.pdf.

Further diagnostic tests as indicated

Yes → Treat

↓No

4. Luk JK, Chan TY, Chan DK. Falls prevention in the elderly: translating evidence into practice. Hong Kong Med J 2015; 21:165-71. doi: 10.12809/hkmj144469. Epub 2015 Feb 27.

Review. PubMed PMID: 25722468.

Refer the patient to falls prevention program

Fig. 1: Algorithm for the Evaluation of Falls in the Elderly5

are twice more likely to sustain falls. So people who 5.

CONCLUSION were provided single lens distance glasses experienced Falls in elderly especially with recurrent falls should be evaluated by less falls. However those patients with limited outdoor meticulous history, careful clinical examination, Timed Up and Go test to test activities incidence offall falls these glasses. balance and had gait tomore ascertain the cause for and with take necessary steps to Hence in falls patients limited intervention outdoor asactivities prevent future by single with or multicomponent suggested by 11 providing multifocal glasses areforuseful.

6.

AGS and BGS. Screening and assessing fall risk is very important to prevent falls. The patient, family members, health care team and the health care system ENVIRONMENT will be largely benefited if you find out the cause of fall and prevent further Home safety interventions home visits by occupational falls because “prevention is better like than cure”.

therapists are effective in secondary prevention (patients with falls previously). However its role in primary prevention is limited. Assisting devices such as canes and walkers are useful in elderly and they must be trained to use them properly.

MULTICOMPONENT INTERVENTIONS

Multicomponent interventions were useful if they actively provided treatment rather than giving knowledge or referrals alone. Multifactorial interventions were given a grade A recommendation by 2010 AGS and BGS guidelines.11 According to AGS and BGS 2010 guidelines the components most commonly included in various efficacious interventions were •

Modification or adaptation of home environment

•

Recognising and managing postural hypotension

•

Minimization or if possible psychoactive medications

•

Minimization or if possible withdrawl of other medications

withdrawl

•

Management of foot problems and footwear

•

Balance, gait and strength training9

CONCLUSION

statistics/srs

3. Margaret Beliveau, Geriatrics In:Robert D. Ficalora,Paul S.Mueller, Thomas J Beckman and et al Mayo clinic Internal Medicine Board Review, 10 th edition,Oxford university press 2014,p. 2680.

↓ Cause determined ?

129

of

Falls in elderly especially with recurrent falls should

Americal Family Physician (website). Falls in the elderly (2000). George F.Fuller, COL, Mc, USA, White House Medical Clinic, Washington, D.C. Am Fam Physician 2000; 61:2159 – 2168.Available from : http//www.aafp.org/ afp/2000/0401/p2159.html# G. Michael Harper, C.Bree Johnston, C. Seth Landefeld, Geriatric disorders In: Maxine A. Papadakis, Stephen J. mcphee, Michael W. Rabow. Current Medical Diagnosis and treatment 2016. McGraw Hill Education;p. 63

7. Tripathy NK, Jagnoor J, Patro BK, Dhillon MS, Kumar R. Epidemiology of fallsamong older adults: A cross sectional study from Chandigarh, India. Injury. 2015; 46:18015. doi: 10.1016/j.injury.2015.04.037. Epub 2015 May 7.

PubMedPMID: 25986666.

8. Lewis Sudarsky, Gait and balance Disorders In: Kasper DL, Fauci AS, Hauser SL, longo DL, Jameson JL, Loscalzo J. Harrison’s principles of internal medicine. Vol 1. 19th edn, McGraw Hill Education; 2015.p.162 9. American Geriatrics Society [website]. AGS/BGS clinical practice guideline: prevention of falls in older persons (2010). New York, NY: American Geriatrics Society; 2011.

Available from:www.americangeriatrics.org/healthcare_ professionals/clinical_practice/clinical_guidelines_ recommendations/2010/. Accessed 2016 august 28 10. Lee A, Lee KW, Khang P. Preventing falls in the geriatric population. Perm J Fall 2013; 17:37-9. doi: 10.7812/TPP/12119. PubMed PMID: 24361019; PubMed Central PMCID: PMC3854807.

11. Al-Aama T. Falls in the elderly: spectrum and prevention.

Can Fam Physician 2011; 57:771-6. Erratum in: Can Fam Physician. 2014 Mar;60(3):225. PubMed PMID: 21753098; PubMed Central PMCID: PMC3135440 12. Sherrington C, Whitney JC, Lord SR, Herbert RD, Cumming RG, Close JC. Effective exercise for the prevention of falls: a systematic review and meta-analysis. J Am Geriatr Soc 2008; 56:2234-43. doi: 10.1111/j.1532-5415.2008.02014.x. Review.

PubMed PMID: 19093923.

CHAPTER 24

Cause determined ?

be evaluated by meticulous history, careful clinical examination, Timed Up and Go test to test balance and gait to ascertain the cause for fall and take necessary steps to prevent future falls by single or multicomponent intervention as suggested by AGS and BGS. Screening and assessing for fall risk is very important to prevent falls. The patient, family members, health care team and the health care system will be largely benefited if you find out the cause of fall and prevent further falls because “prevention is better than cure”.

C H A P T E R

25

Practical Approach to Peripheral Neuropathy

KEY WORDS

Practical approach, neuropathy, causes, evaluation.

Peripheral neuropathy occurs as a component of several common and many rare diseases. It is heterogeneous in etiology, diverse in pathology, and varied in severity. Peripheral neuropathy is often overlooked, underestimated and not evaluated in day to day practice.

The prevalence of neuropathy is well studied in patients with diabetes mellitus in most of the studies and other causes of neuropathies are not well documented. The overall prevalence of neuropathy in south Indian diabetic population is 19.1%. A practical approach is therefore necessary to identify and manage neuropathies in clinical practice. Though there are lot of algorithmic approaches, this article gives a simple bedside assessment for peripheral neuropathic symptoms.

A discussion of neuropathic disorders encompasses those diseases that affect the neuron’s cell body, neuronopathies, and those affecting the peripheral process, peripheral neuropathies.

Neuronopathies can be further subdivided into those that affect only the anterior horn cells, or motor neuron disease, and those involving only the sensory neurons, also called sensory neuronopathies or ganglionopathies. Peripheral neuropathies can be broadly subdivided into those that primarily affect myelin, or myelinopathies, and those that affect the axon, or axonopathies. Each of these pathologic categories has distinct clinical and electrophysiologic features which allow the clinician to place a patient’s disease into one of these groups. Therefore, the goals in the approach to a neuropathic disorder is to determine : 1.

Where the lesion is? (Table 1)

2.

What is the cause of the lesion? (Table 2).

3.

What is the possible therapy?

The final goal in approaching the patient with a neuropathic disorder is to determine whether or not

Table 1: Pathologic Classification of Neuropathic Disorders 1. Neuronopathies (pure sensory or pure motor) :

Sensory neuronopathies (ganglionopathies)

Motor neuronopathies (motor neuron disease)

2. Peripheral neuropathies (usually sensorimotor):

Myelinopathies

Axonopathies

M Rajasekaran

Table 2: Etiology of Neuropathic Disorders I . ACQUIRED Dysmetabolic states Diabetes mellitus Neuropathy related to renal disease Vitamin deficiency states (ex. Vitamin B12 deficiency) Primary amyloidosis Immune-mediated Guillain-Barre Syndrome Chronic inflammatory demyelinating polyneuropathy (CIDP) Vasculitis Infectious Herpes zoster Leprosy, Lyme, HIV, and Sarcoid related Cancer related Lymphoma, myeloma, carcinoma related Paraneoplastic subacute sensory neuronopathy Drugs or toxins Chemotheraphy induced Other drugs Heavy metals and industrial toxins Mechanical /Compressive Radiculopathy Mononeuropathy Unknown etiology Cryptogenic sensory and sensorimotor neuropathy Amyotrophic lateral sclerosis II. HEREDITARY Hereditary Motor Sensory Neuropathy (Charcot- Marie – Tooth disease) Hereditory neuropathy with predisposition to pressure palsies Familia! Brachial plexopathy Familial amyloidosis Porphyria Other rare peripheral neuropathies (Fabry’s, metachromatic eukodystrophy,adrenolen kodystrophy, Refsum’s disease etc.)

Motor neuron disease Spinal muscular atrophy Familial amyotrophic lateral sclerosis X- linked bulbospinal muscular atrophy

Table 3

Table 5: Peripheral Neuropathies With Autonomic Nervous System Involvement

1. What systems are involved?

-

Diabetes mellitus

Motor, sensory, autonomic, or mixed

Amyloidosis (familial and acquired)

2. What is the distribution of weakness ?

-

Only distal Vs proximal and distal

-

Focal / asymmetric Vs symmetric

Guillain – Barre syndrome Vincristine induced Porphyria

3. What is the nature of the sensory involvement ? pain / burning,or stabbing

-

proprioceptive loss-joint position and vibration sense

HIV – related autonomic neuropathy

Table 6: Neuropathic Disorders that Produce Asymmetric/ Focal Weakness

4. Is there evidence UMN involvement?

-

without sensory loss

-

with sensory loss

Motor Neuron disease Amyotrophic lateral sclerosis Radiculopathy – cervical or lumbosacral

5. What is the temporal evolution ?

Plexopathy – brachial or lumbosacral

-

Acute (days to 4 weeks)

Mononeuropathy multiplex due to:

-

Subacute (4 to 8 weeks)

Vasculitis

-

Chronic (> 8 weeks)

Lyme disease

-

Preceding events, drugs, toxins

Sarcoid

6. Is there evidence for a hereditary neuropathy?

Leprosy

-

Family history of neuropathy

HIV infection

-

Lack of sensory symptoms despite sensory signs

Hereditary neuropathy with liability to pressure palsy

Table 4: Neuropathic Disorders That May Have Only Motors Symptoms At Presentation

Entrapment mononeuropathies Median neuropathy

Motor neuron disease

Ulnar neuropathy

Lead intoxication

Peroneal neuropathy

Acute porphyria Hereditary motor sensory neuropathy*

The first step in this approach is to ask six key questions based on the patients symptoms and signs (Table 3):

CIDP*

1.

What systems are involved?

therapy is possible, and if so, what the course of therapy should be. Even if a specific therapy is not available, a management plan should be developed. These final two steps are often frustrating as it is not always possible to determine the cause or alter the natural history of neuropathic disorders.

It is important to determine if the patients symptoms and signs are pure motor, pure sensory, or both.

If the patients has only weakness without any evidence of sensory loss, a motor neuronopathy, or motor neuron disease, is the most likely diagnosis (Table 4).

In order to accomplish the goal of determining the site and cause of the lesion, and if possible, a therapy, the clinician gathers information from the history, the neurologic examination and various laboratory studies. While gathering this information, six key questions are asked.

From the answer to these six key questions, the patient is placed into 9 different phenotype patterns. Therefore, it is the 3-6-9 step clinical approach to neuropathy:

*Usually has sensory signs on examination

Guillian- Barre Syndrome

3 goals – 6 key questions- 9 phenotypic patterns.

IMPORTANT INFORMATION FROM THE HISTORY AND PHYSICAL EXAMINATION

– Six Key Questions

Some peripheral neuropathies are associated with significant autonomic nervous system dysfunction (Table 5).

Inquire if the patient has fainting spells or orthostatic light headedness, sweating abnormalities or any bowel, bladder, or sexual dysfunction. These features suggest the presence of autonomic involvement.

2.

What is the distribution of weakness?

The distribution of the patient’s weakness is crucial for an accurate diagnosis and In this regard two questions should be asked: (1) Is the weakness distal only or is it both proximal and distal? And

CHAPTER 25

-

131

132

Table 7: Peripheral Neuropathies That Are Often Associated With Pain

Table 8: Causes of Sensory Neuronopathy (Ganglionopathy)

Cryptogenic sensory or sensorimotor neuropathy

Sjogran’s syndrome

Cancer (Paraneoplastic)

Diabetes mellitus

Idiopathic sensory neuronpathy

Vasculitis

Cisplatinum and other analogues

Guillain – Barre syndrome

Vitamin B6 toxicity

Amyloidosis Toxic (arsenic, thallium) HIV related distal symmetrical polyneuropathy

NEUROLOGY

Fabry’s disease (2) is the weakness symmetric or focal, asymmetric.

The finding of weakness in both proximal and distal muscle groups in a symmetric fashion is the hallmark for acquired immune demyelinating polyneuropathies, both the acute (GBS) and the chronic form (CIDP) Asymmetry or focal nature of the weakness is also a feature that can narrow the diagnostic possibilities (Table 6).

Some neuropathic disorder may present with unilateral leg weakness. If sensory symptoms and sign are absent, patient presents with painless foot drop evolving over weeks or months, Motor neuron disease is the leading diagnostic possibility. if a patient present with subacute or acute sensory and motor symptoms of one leg, lumbosacral radiculopathies, plexopathies, vasculitis, and compressive mononeuropathy need to be considered. if the clinical manifestations are pure motor weakness in one arm or hand, motor neuron disease is probably the leading consideration. If sensory symptoms are also present, cervical radiculopathy, brachial plexopathy, or a mononeuropathy are likely. Leprosy often presents with asymmetric sensory or sensorimotor features, and one needs to have a high index of suspicion for this disorder.

The importance of finding symmetric proximal and distal weakness in a patient who presents with both motor and sensory symptoms identifies the patients who may have a treatable acquired demyelinating neuropathic disorder.

If a patient with both symmetric sensory and motor findings has weakness involving only the distal lower and upper extremities, reflects a primary axonal peripheral neuropathy and is much less likely to represent a treatable entity.

3.

What is the nature of the sensory involvement?

It is important to determine if the patient has loss of sensation (numbness), altered sensation (tingling), or pain. Sometimes patient may find it difficult to distinguish between uncomfortable tingling sensations (dysesthesias) and pain. Neuropathic pain be burning, dull and poorly localized (protopathic pain), or sharp and lancinating (epicritic pain). If severe pain is one of the patients symptoms, certain peripheral neuropathies should be considered (Table 7).

HIV – related sensory neuronopathy The cryptogenic sensory polyneuropathy (CSPN) and neuropathy due to diabetes are the most common neuropathies that are associated with severe pain peripheral nerve vasculitis and Guillain- Barre Syndrome (GBS) are important to recognize because these disorders are treatable. The pain in vasculitic neuropathy is generally distal and asymmetric in the most severely involved extremity. Some patients with GBS have severe back pain associated with symmetric numbness and paresthesias in the extremities. Another painful form of diabetic neuropathy is lumbosacral radiculoplexopathy (also known as diabetic amyotrophy), in which patients may present with the abrupt onset of back, hip or thigh pain that may precede weakness by days or weeks.

If the neurologic examination reveals a asymmetric loss of proprioception with significant vibration loss and normal strength consider a sensory neuro-nopathy (i.e.,ganglionopathy). The various causes of sensory neuronopathy are as follows (Table 8): The modalitities of light touch, pain sensation, vibration and proprioception should be assessed in all four limbs in a patient with a peripheral neuropathy.

4.

Is there evidence involvement?

of

upper

motor

neuron

In patients with symptoms of signs suggestive of lower motor neuron pathology without sensory loss, the presence of concomitant upper motor neuron signs is the hallmark of amyotrophic lateral sclerosis.

On the other hand, if the patient presents with symmetric distal sensory symptoms and signs suggestive of a distal sensory neuropathy, but there is additional evidence of symmetric upper motor involvement, the physician should consider a disorder such as combined system degeneration with neuropathy. The most common cause for this pattern is B12 deficiency HIV infection, severe hepatic disease, adrenomyeloneuropathy.

5.

What is the temporal evolution?

Does the disease have an acute (days to 4 weeks), subacute (4 to 8 weeks), or chronic (greater than 8 weeks) course? Is the course monophasic, progressive, or relapsing? Neuropathies with acute and subacute presentations include GBS, vasculitis, and diabetic lumbosacral radiculoplexopathy.

A relapsing course can be present in CIDP and

porphyria. Inquire about preceding or concurrent infections, associated medical conditions, drug use including over-the-counter vitamin preparations (B6), alcohol, and dietary habits.

Table 9: Nine Patterns of Neuropathic Disorders Pattern1: Symmetric proximal and distal weakness with sensory loss inflammatory demyelinating polyneuropathy (GBS and CIDP) Pattern 2: Symmetric distal weakness with sensory loss

Is there evidence for a hereditary neuropathy?

In patients with a chronic, very slowly progressive distal weakness over many years, with very little in the way of sensory symptoms, pay particular attention to the family history and inquire about foot deformities in immediate relatives. episodes of recurrent compressive mononeuropathies may indicate an underlying hereditary predisposition to pressure palsies. One must look carefully at the feet for arch and toe abnormalities (high or flat arches, hammer toes scoliosis

metabolic disorders, Hereditary toxins Drugs, Pattern 3: Asymmetric distal weakness with sensory loss Multiple nerves- vasculitis Single nerves/regions- compressive mononeuropathy and radiculopathy Pattern 4: Asymmetric distal weakness without sensory loss motor neuron disease â&#x20AC;&#x201C; with upper motor neuron findings Multifocal motor neuropathy â&#x20AC;&#x201C; without upper motor neuron findings Pattern 5: Asymmetric proximal and distal weakness with sensory loss Polyradiculopathy or plexopathy due to diabetes mellitus, Meningeal carcinomatosis Pattern 6 : Symmetric sensory loss without weakness Cryptogenic sensory polyneuropathy (CSPN), metabolic (diabetes and others) drugs, toxins Pattern 7: Symmetric sensory loss and distal areflexia with upper motor neuron findings B12deficiency, HIV, hepatic disease Pattern 8: A symmetric proprioceptive sensory loss without weakness sensory neuronopathy (ganglionopathy) Pattern 9: Autonomic Symptoms and Signs neuropathies associated with autonomic dysfunction

PATTERN RECOGNITION APPROACH OF NEUROPATHIC DISORDERS

After answering the six key questions obtained from the history and neurologic examination outlined above, one can classify neuropathic disorders into several patterns based on sensory and motor involvement and distribution of signs (Table 9). A final diagnosis is arrived at by utilizing other clues such as the temporal course, presence of other disease states, and family history and information from lab tests and electrophysiology.

Electrophysiology, an extension of the clinical examination and nerve and muscle biosy, punch biopsy of the skin adds to the information derived from the above mentioned approach and helpful in planning treatment. Even then the etiology eludes in more than 1/3rd of patients presenting with peripheral neuropathy in the best of centers.

REFERENCES

1.

S Ashok, M Ramu, R Deepa, V Mohan. Prevalence of neuropathy in type 2 diabetic patients attending a diabetes center in south India. JAPI 2002; 546-550.

2.

Dyck PJ,Oviatt KF,Lambert EH. Intensive evaluation of referred unclassified neuropathies yield improved diagnosis. Ann Neurol 1981; 10:222-226.

3.

Barohn RJ. Approach to Peripheral Neuropathy and neuronopathy. Seminars in Neurology 1998; 18:7-18.

4.

Wolfe GI, Barohn PJ. Cryptogenic sensory and sesorymotor polyneuropathies. Seminars in Neurology 1998; 18:105-112.

CHAPTER 25

6.

133

An Approach to Headache

C H A P T E R

26

T Ravikumar, M Gowri Sankar

Headache is a common symptom worldwide, it is important for physicians to evaluate patients with headache to determine whether the condition is benign or it is a serious neurological or systematic illness.

Table 2: Disorders causing secondary headache

CLASSIFICATION OF HEADACHE1,2,3

International Headache Society classifies headache as primary or secondary.

Primary headache are recurrent headaches where there is no cause identifiable on examination or investigation and where diagnosis is made by recognizing a pattern eg.

Migraine, tension type headache, cluster headache Table 1.

Secondary headaches are those headache where there is a definite underlying cause identifiable on examination

Table 1: Primary headache disorders characteristics Cause

Clinical features

Migraine

Frequently unilateral, Clinical pulsating/throbbing evaluation type lasting for 4-72 hours, occasionally with aura, phonophobia, photophobia, worse with activity, preference to lie in the dark, resolution with sleep

Diagnostic approach

Frequent or continuous, mild, bilateral, band-like holocranial, occipital or frontal pain the that spreads to entire head, worse at the end of the day.

Clinical evaluation

Cluster headache Unilateral orbitotemporal attacks at the same time of day, deep, severe lasting 30-180 min, often with facial flushing, lacrimation, Hornerâ&#x20AC;&#x2122;s syndrome, restlessness, cannot sit still in a place

Clinical evaluation

Tension â&#x20AC;&#x201C;type headache

or in investigations Table 2. Ninety percent of headache in practice are primary headache, and less than 10% are secondary headaches.

Cause

Examples

Extracranial disorders

Glaucoma Sinusitis Dental disorders Temporomandibular joint dysfunction Carotid or vertebral artery dissection

Intracranial disorders Infections (meningitis, encephalitis, abscess, Subdural empyema) Noninfectious meningitis (carcinomatous, chemical) Brain space occupying lesion Cerebrospinal fluid leak with low-pressure headache Hemorrhage (Intracranial, subdural, subarachnoid) Idiopathic intracranial hypertension Obstructive hydrocephalus Vascular disorders (e.g. vascular malformations, vasculitis, venous sinus thrombosis) Chiari Type 1 malformation Systemic disorders

Viral infections Fever

Primary stabbing / coughing / exertional / sex-related headache

Acute severe hypertension Giant cell arteritis Hypercapnia Drugs and toxins

Analgesics overuse Nitrates Caffeine withdrawal Hormones (estrogen) Carbon monoxide Proton pump inhibitors

Box 1: The Pain Sensitive Cranial Structures are4 Skin, subcutaneous tissue, muscles, extra cranial arteries, and peritoneum of the skull Delicate structures of the eye, ear, nasal cavities, and para nasal sinuses The optic, oculomotor, trigeminal, glossopharyngeal, vagus, and first three cervical nerves Middle meningeal and superficial temporal arteries Intracranial venous sinuses and their large tributaries

Cluster headache – localized to ocular and retro ocular region

•

Migraine tends to involve entire hemi cranium

•

Tension type headache typically bilateral, but can be unilateral, often involving frontal, temporal and occipital region – band like or cap like tightness.

•

Trigeminal neuralgia involves one division of trigeminal nerve.

•

Pain that is occipital or unilateral but becomes holocranial during valsalva maneuver suggests intra cranial abnormalities and probable increased intracranial pressure.

CHARACTER AND SEVERICY OF PAIN

The diagnosis of headache depends on three elements5

•

History Physical Examination Investigations

Vascular headache – throbbing and pulsatile in nature, with intense pain.

•

Cluster headache – deeper boring and burning quality.

The gold standard in diagnosing headache is by history and clinical examination.

•

Trigeminal neuralgia – paroxysmal jab like or shock like pain.

A Suggested framework for the targeted headache history6.

•

Tension type of headache – persistent dull aching pain, band like, occasional exacerbations.

AGE OF ONSET

•

•

Childhood and adolescent-secondary to sinusitis, pharyngitis, otitis and primary headache like migraine is common

Head ache associated with lumbar puncture will worsen when patient assumes the recumbent position.

•

Adult- tension type headache, medication overuse

•

•

Elderly-glaucoma, hypertension, stroke, brain tumor or brain metastasis

In migraine premonitory symptoms precedes 2-48 hours.

•

Tumors involving the occipital lobe may produce symptoms similar to migranous aura.

DURATION AND FREQUENCY OF PAIN

•

Vascular headache and trigeminal neuralgia – episodic pattern

•

Cluster headache – seasonal and it range in minutes

•

Migraine in hours

•

Headaches of organic origin (eg. ocular disease sinusitis, brain tumor) are continuous with acute exacerbate caused by exercise, change in position and valsalva maneuver.

PREMONITORY SYMPTOMT AND AURAE

ASSOCIATED SYMPTOMS

•

In migraine associated symptoms are photophobia, phonophobia, nausea, vomiting, aversion to strong odors and focal neurological changes.

•

Cluster headache associated with complete or partial horner syndrome, including lacrimation, heavy rhinorrhea and blanching of the face on affected side.

•

Tinnitus or hearing loss in trigeminal neuralgia patients indicates an underlying brainstem tumor.

ONSET TO PEAK TIME

•

Rapid onset -to -peak (seconds to minutes) – suspicion of organic disease

•

Tension headache evolve over period of hours to days and then remain constant

•

Cluster headache rapid onset to peak time.

•

Migraine evolve over several hours

LOCATION

•

PRECIPITATING FACTORS

•

Migraine headache triggered by change in diet or sleep habits, tyramine containing foods, monosodium glutamate, nitrates, alcohol, hormones and oral contraceptives, fatique, stress, menstruation, strong odors, and bright sunlight.

•

Tension type headache triggered by underlying environmental or physiological stress, depression, fatigue and occasionally, abnormalities of the cervical spine.

•

Cluster headache triggered by alcohol, high attitude and occasionally, vasodilating substances.

Vascular headache – unilateral, side may change from attack to attack

135

CHAPTER 26

Part of the dura at the base of the brain and the arteries within the dura, particularly the proximal parts of the anterior and middle cerebral arteries and the intracranial segment of the internal carotid artery.

•

136

ENVIRONMENTAL FACTORS

•

Stress and pressure in the workplace, industrial

fumes, carbon monoxide, high attitude implicated as precipitations factors of headache.

FAMILY HISTORY

Migraine is familial disease.

Box 2: Criteria for Low­Risk Headaches Age younger than 30 years Features typical of primary headaches

Box 3: Serious Headaches

History of similar headache No abnormal neurological findings

NEUROLOGY

No concerning change in usual headache pattern No high ­risk comorbid conditions (e.g., human immunodeficiency virus infection) No new concerning historical or physical examination findings

Primary brain tumor

Meningitis

Metastatic brain tumor

Temporal arteritis

Brain abscess

Stroke

Subdural hematoma

Glaucoma

Intra cerebral hemorrhage

Hydrocephalus

Subarachnoid hemorrhage

Table 3: Red flag signs and symptoms in the evaluation of acute headache7 Danger Sign or Symptom

Possible Diagnosis

Tests

First or worst headache of the patient’s life

CNS infection, intracranial hemorrhage

Neuroimaging

Focal neurologic signs (not typical aura)

Intracranial mass lesion, arteriovenous malformation, collagen vascular disease

Blood tests, neuroimaging

Headache triggered by cough or exertion, or while engaged in sexual intercourse

subarachnoid hemorrhage, intracranial mass lesion

Lumbar puncture, neuroimaging

Headache with change in personality, mental status, level of consciousness

CNS infection, intracerebral bleed, mass lesion

Blood tests, lumbar puncture, neuroimaging

Neck stiffness or meningismus

Meningitis

Lumbar puncture

New onset of severe headache in pregnancy or postpartum

Neuroimaging Cortical vein/cranial sinus thrombosis, carotid artery dissection, pituitary apoplexy

Older than 50 years

Temporal arteritis, intracranial mass lesion,

Erythrocyte sedimentation rate, neuroimaging

Papilledema

Meningitis, encephalitis, intracranial mass lesion, pseudotumor cerebri

Lumbar puncture, neuroimaging

Rapid onset with strenuous exercise

Intracranial bleed, carotid artery dissection,

Neuroimaging

Sudden onset (maximal intensity occurs within seconds to minutes, thunderclap headache)

Subarachnoid hemorrhage, bleeding into a mass or arteriovenous malformation, mass lesion (especially in posterior cranial fossa)

Lumbar puncture, neuroimaging

Systemic illness with headache (fever, rash)

Meningitis, encephalitis, arteritis, collagen vascular disease

Blood tests, lumbar puncture, neuroimaging, skin biopsy

Tenderness over temporal artery

Temporal arteritis, polymyalgia rheumatica

Erythrocyte sedimentation rate, temporal artery biopsy

Worsening pattern

History of medication overuse, subdural hematoma, intracranial mass lesion,

Neuroimaging

New headache type in a patient with Metastasis Cancer

Lumbar puncture, neuroimaging

Human immunodeficiency virus infection

Lumbar puncture, neuroimaging

Opportunistic infection, tumor

Table 4: American College of Radiology recommendations for neuroimaging in patients with headache

1.

Ultra Quick Mental Status Examination

•

Orientation

Recommended Imaging Modality

•

Attention and calculation

Headache in immunocompromised

MRI of the head with and without contrast media

•

Memory

•

Speech

Headache in patients older than 60 years with suspected temporal arteritis

MRI of the head with and without contrast media

2.

Cranial nerve examination

3.

Examination of motor, sensory system, reflexes, gait, cerebellar function and pronator drift

Headache with suspected meningitis

CT or MRI of the head without contrast media

4.

Looking for signs of meningitis

Severe headache in pregnancy

CT or MRI of the head without contrast media

•

Neck stiffness, kernig and brudzinski sign

5.

Examination of ear, nose and throat

Severe unilateral headache caused by possible dissection of the carotid or arterial arteries

MRI of the head with and without contrast media, MRA of the head and neck, or CTA of the head and neck

•

Ear and nasal discharge, nasal polyps, pharyngitis, tonsillitis, sinus and mastoid tenderness

6.

Examination of eye

•

Diminished visual acuity suggestive of refractive error, glaucoma, optic neuritis or temporal arteritis.

•

Ophthalmoplegia or visual field defects sign of venous sinus thrombosis, tumor or aneurysm.

•

Afferent pupillary defects can be due to intracranial masses or optic neuritis.

•

Ipsilateral ptosis and miosis (Horners syndrome) with acute headache-Carotid artery dissection.

7.

Fundoscopic examination –absent retinal artery pulsations or papilledema- sign of elevated intracranial pressure.

8.

Examination of mouth and dental portions for caries tooth, root abscess, ulcers and improper denture fittings.

9.

Examination of cervical spine- passive movement and spine tenderness.

10.

Looking for any tenderness over TM joint.

CT of the head without Sudden onset or severe headache; worst headache contrast media; CTA of the head with contrast of the patient’s life media, MRA of the head with or without contrast media, or MRI of the head without contrast media CT = computed tomography; CTA = computed tomographic angiography; MRA = magnetic resonance angiography; MRI = magnetic resonance imaging.

PREGNANCY AND MENSTRUATION

•

Migraine commonly occurs with onset of menses.

•

Pregnancy ameliorates symptoms of migraine after first trimester.

•

Menopause ameliorates symptoms of migraine but may prolong symptoms of headache after hormone replacement therapy.

•

Smoking and oral contraceptives increases the headache in migraine

11.

Examination of scalp and superfical temporal artery tenderness –patient older than 60 years.

•

Some tension type headache patients experience in associated with menses.

12.

Vitals to be checked- Temperature in case of infection

13.

BP measurement.

may

MEDICAL / SURGICAL HISTORY

•

Headache can be a symptom of systemic illness of hypertension, anemia, thyroid disease,depression etc

Table 3 gives an idea about the dangerous types of headaches.

•

Drugs like nitrates, analgesic overuse, disease of eye, ear, nose, throat and cervical spine diseases.

Neuroimaging7 (Table 4)

•

History of head injury, cranial surgery, recent lumbar puncture may reveal important clues

PHYSICAL EXAMINATION12

Should take less than 5 minutes The mandatory elements are:

INVESTIGATIONS

Neuroimaging is indicated for all patients who present with signs or symptoms of dangerous headache, because they are at increased risk of intracranial pathology

LUMBAR PUNCTURE12

Lumbar puncture is indicated to exclude infectious cause of acute headache, particularly in patients with fever or meningeal signs.

CHAPTER 26

Clinical Features

137

138

Table 5: Abortive Therapy for Migraine-Specific Treatment3,8 Drugs

Dose and Route

Ergot Alkaloids

NEUROLOGY

Cafergot (ergotomine tartrate 1mg caffeine 100 mg)

Dihydroergotamine mesylate

One or two tablets taken at the onset of head ache or warning symptoms followed by one tablet every 30 minutes, if necessary 6 tablets /attack and no more than 10 days per month.

0.5- 1mg intravenously (or) 1-2 mg subcutaneously or intramuscularly

5 HT Receptor Agonist Sumitriptan Zolmitriptan

Tonometry for glaucoma CT paranasal sinus- in case of sinusitis, polyps ESR-temporal arteritis, endocarditis Urine analysis-malignant hypertension, preeclampsia

MANAGEMENT OF HEADACHE

Depending on the headache type, one would be prescribed medicines to terminate the headache episode (abortive treatment) or to prevent the occurrence of headache (prophylactic treatment).

TREATMENT OF MIGRAINE8 (TABLE 5)

There are three main aspects of treatment Avoidance of triggers

4-6 mg subcutaneously, may repeat once after 2 hours

•

Treatments of acute attack

•

Migraine prophylaxis

Orally 5 mg/day be repeated after 5 hours

Treatments of acute attack

Nasal spray 5mg in one nostril, one may be repeated once after 2 hours

•

Rest in quiet darkened room until symptoms subside

•

Simple analgesics like aspirin, acetaminophen, ibuprofen or naproxen are most commonly used and provide symptomatic relief.

5-10 mg orally at onset may repeat every 2 hours twice Maximum dose 30 mg/24 hours

Nartriptan

Refractive error testing

•

Maximum dose in both formulation is 10mg in 24 hours Rizatriptan

Other investigations

1-2.5 mg orally at onset may repeat once after 4 hours

PREVENTIVE THERAPY IN MIGRAINE (TABLE 6)

Preventive therapy may be necessary if migraine occurs more frequently than two to three times a month or significant disability in associated with attacks

Treatment of Chronic Tension-Type Headache3 •

Relaxation techniques

•

Abortive treatment - simple analgesic (aspirin, NSAIDs, acetaminophen)

•

Effective prophylactic drug amitriptyline dosage of 50-150 mg per day. Lower dosage may be tried initially.

•

Other drugs are tricyclic antidepressants (TCAs), gabapentin, mirtazapine and topiramate.

Maximum dose 5 mg/24 hours.

Other agents Dopamine antagonist

5-10 mg orally

Prochlorperazine

5-10 mg intravenously or intramuscularly

Treatment of Cluster Headache3 •

Inhalation of 100% oxygen (12-15 L/min)

25 mg rectal suppository

•

Sumatriptan -subcutaneous 6 mg or intranasal 20mg/spray

•

Zolmitriptan- 5 to 10mg nasal spray

•

Dihyroergotamine 0.5-1mg intramuscularly or intravenously

Metoclopramide

10-20 mg intravenously

Cerebrospinal fluid tests should routinely include gram stain, white blood cell count with differential count, red blood cell count, glucose, protein and bacterial culture.

In appropriate patients consider CSF fluid for VDRL (syphilis), cryptococcal antigen (HIV-positive patients) and acid fast bacillus stain and culture (Tuberculous meningitis). Polymerase chain reaction tests for specific infectious pathogens (eg, herpes simplex 2) should also be considered in patients with evidence of central nervous system infection but no identifiable pathogen.

Transitional prophylaxis (short-term use of drugs to vide over the crisis) •

Ergotamine tartrate -Rectal suppositories 0.5-1mg at night or twice daily, by mouth 2mg daily, or by subcutaneous injection 0.25 mg three times daily for 5 days per week (or)

139

Table 6: Preventive Drugs for Headache Dosage

Selected Side Effects

Beta-blocker Propranolol

40-120 mg bid

Tiredness, postural hypotension

Tricyclics: Amitriptyline

10-75 mg at night

Drowsiness, urinary retention

Tricyclics: Nortriptyline

25-75 mg at night

Drowsiness, urinary retention

Anticonvulsants: Topiramate

25-200 mg/day

Paraesthesia, cognitive symptoms, glaucoma, weight loss

Antriconvulsants: Valproate

400-600 mg bid

Tremors, weight gain, drowsiness

Anticonvulsants: Gabapentin

900-3,600 mg/day

Dizziness, sedation

Serotonergic drugs: Methysergide

1-4 mg/day

Drowsiness, leg cramps, hair loss, retroperitoneal fibrosis

Serotonergic drugs: Flunarizine

5-15 mg/day

Drowsiness, parkinsonism, depression

Table 7: Characteristics of headache suffers who may be suited for nonpharmacologic therapies Poor tolerance of drug treatment Medical contraindications for drug treatment Inadequate response to drug treatment Preference for nonpharmacologic intervention Pregnancy or nursing History of frequent or excessive use of analgesics or other acute medications •

Dihydroergotamine 9.25mg intravenously several days or 0.5 mg intramuscularly twice daily (or)

•

Prednisone 50mg daily for 5 days followed by gradual withdrawal

Maintenance prophylaxis (agents throughout the entire expected duration of cluster headache)

Physical relaxation movement or action.

methods

involve

actual

body

In the progressive muscle relaxation method, releasing tension involves purposefully tensing and then relaxing groups of muscles in a definite sequence.

Another method called deep breathing is done by breathing from the bottom of the lungs up, which is characterized by the rise and fall of the stomach, not the chest.

Mental methods

Relaxation therapy can involve mental techniques to decrease body tension.

The focused imagery method involves concentration on relaxed body parts, followed by focus on tense muscles and imagining that the tense areas are being worked on or relaxed.

•

Verapamil 80 mg three times a day to a maximum dose of 720 mg per day; monitor with ECG if total daily dose is more than 480 mg/ day)

The deepening imagery method involves focus on the whole body, instead of its individual parts ie a person imagines the body’s tension as a meter of high to low, and works to reduce tension mentally.

•

Lithium (300 mg three times daily; monitor with lithium levels)

Meditation in a relaxing environment is also suggested to prevent headaches

•

Topiramate (100 -400 mg/day)

•

Sodium valproate 750-1500mg daily

Neurostimulation strategies have been employed in patients who fail on above prophylactic therapies.

Nonpharmacologic Therapies9-11

Nonpharmacologic therapies play an important role in the prevention and treatment of migraine and tension type headache, especially given the number of identified triggers of headache. Nonpharmacologic therapies for headache disorders may be well suited for several types of patients, as outlined in Table 7.

RELAXATION TRAINING

Relaxation training helps to reduce internal tension, allowing a person to control headaches triggered by stress. Relaxation training includes two different types of methods: (1) physical and (2) mental.

Physical methods

BIOFEEDBACK

Biofeedback is often used to evaluate the effectiveness of relaxation training, because it feeds back information to the chronic headache sufferer about the “body’s (biological) current state”. Common bio feedbacks used are electromyography (EMG), electroencephalograph (EEG), thermograph, etc. Biofeedback methods have been proven to work. They allow headache sufferers to identify problems and then seek to reduce them.

BEHAVIORAL THERAPY AND PSYCHOLOGICAL THERAPY

Psychological and behavioral therapies identify stressful situations and teach chronic headache patients to react differently, change their behavior, or adjust attitudes to reduce tension that leads to headaches. Patients are advised to simply avoid stressors when plausible or share their burdens with others. In this way, studies have found that patients with multimodal treatment in a group setting fare better than patients who follow multimodal treatment alone.

CHAPTER 26

Drug

140

ACUPUNTURE

Another nonmedicinal treatment, acupuncture may make the body release chemicals that block pain, such as endorphins. It also may stimulate the brain to give off other chemicals and hormones that send signals between different types of cells, including those of the immune system. Trials show that acupuncture can cause relevant improvements for people with chronic headaches.

NEUROLOGY

CHANGES IN DIET

Many of the chemicals in certain foods can cause chronic headaches, including caffeine, monosodium glutamate (MSG), nitrites, nitrates, tyramine, and alcohols. Some of the foods and beverages that chronic headache sufferers are advised to avoid include caffeinated beverages, chocolate, processed meats, cheese and fermented dairy products, fresh yeast-risen baked goods, nuts, and alcohol as well as certain fruits and vegetables.

To sum up, headache management involves multimodality treatment especially in chronic patients. Every individual patient is a challenge in himself/ herself. The most important component is careful patient listening and reaching a correct diagnosis. Investigations are at best ancillary and should not be the primary focus in reaching a diagnosis

REFERENCES

1.

Headache Classification Subcommittee of the International Headache Society. The International classification of headache disorders-2nd edition, cephalgia 2004; 24 Suppl 1:9-160.

2.

IHS-ICHD-2. International Headache society classification. (online). Available from http://ihs-classification.org/en (Accessed November, 2012).

3.

Current medical diagnosis and treatment-2016;Nervous system disorders;page no:962-966

4.

Adams and victors-Principles of neurology, ninth edition:chapter 10,Headache and other craniofacial pain. page no:163

5.

Daroff RB, Fenichel GM, Jankovic J, et al. Cranial and facial pain. In: Bartleson JD, Black FD, Swancson WJ (Eds). Bradleyâ&#x20AC;&#x2122;s Neurology in Clinical Practice, 6th edition.

Philadelphia, PA:WB Saunders; 2012. Pp.205-11.

6.

Management of acute and chronic headache pain,medical clinics of north America-editor Steven D Waldman :march 2013,Targeted headache history: page no 186-194

7.

Barry L Hainer, Eric M. Matheson. Medical university of south caroline,Am fam physician.2013 may 15:87(10);682-687-Approach to acute headache in adults

8.

Post graduate medicine, advances in clinical medicine including prevention,vol -xxvii-2013, migraine:current trends in diagnosis and management, Aradinda mukherjee, page no:388-389

9.

www.m.webmed.com/ Alternative migraines and headaches

treatments

for

10. Headache: The journal of Head and Face Pain: American headache society, doi 10.11.11, Behavioral and other Nonpharmacologic treatments for headache 11. Nonpharmacologic prevention and treatment of recurrent headache: Donald B Penzien, Mary G, Gabb: Advanced studies in medicine, volume 3b, 2003, page no s168-s173.

12. Current medical diagnosis and treatment-2016; common symptoms; page no:39-40.

Approach to a Patient with Hemiplegia and Monoplegia

C H A P T E R

27

Sudhir Kumar, Subhash Kaul

INTRODUCTION

Monoplegia and hemiplegia are common neurological symptoms in patients presenting to the emergency department as well as outpatient department.

Monoplegia refers to weakness of one limb (either arm or leg) and hemiplegia refers to weakness of one arm and leg on the same side of body (either left or right side).

4.

Injury to multiple cervical nerve roots.

5.

Functional or psychogenic.

Insidious onset, gradually progressive monoplegia affecting lower limb can be caused by the following conditions: 1.

Tumor of the contralateral frontal lobe.

There are a variety of underlying causes for monoplegia and hemiplegia. The causes differ in different age groups.

The causes also differ depending on the onset, progression and duration of weakness. Therefore, one needs to adopt a systematic approach during history taking and examination in order to arrive at the correct diagnosis.

Appropriate investigations after these would confirm the diagnosis.

2.

Tumor of spinal cord at thoracic or lumbar level.

3.

Chronic infection of brain (frontal lobe) or spinal cord (thoracic or lumbar level), such as tuberculous.

4.

Lumbosacral-plexopathy, due to diabetes mellitus.

The aim of this chapter is to systematically look at the differential diagnosis of monoplegia and hemiplegia and outline the approach needed to pinpoint the exact underlying cause.

1.

Tumor of the contralateral parietal lobe.

2.

Compressive lesion (tumor, large disc, etc) in cervical cord region.

3.

Chronic infection of the brain (parietal lobe) or spinal cord (cervical region), such as tuberculous.

4.

Tumor of the brachial plexus.

APPROACH TO THE DIAGNOSIS OF MONOPLEGIA

Causes of Monoplegia

The causes can be classified on the basis of onset- acute or chronic; and involvement of the limb (lower or upper).

Acute onset monoplegia affecting the lower limb can be caused by one of the following conditions: 1.

Stroke- affecting anterior cerebral artery territory.

2.

Cerebral venous sinus superior sagittal sinus.

3.

Trauma-head injury, with contusion in the frontal lobe.

4.

Infection, such as granuloma affecting frontal lobe.

5.

Trauma to the lumbo-sacral plexus, diabetic lumbosacral plexopathy.

6.

Functional or psychogenic.

thrombosis,

Insidious onset, gradually progressive monoplegia, affecting upper limb, can be caused by one of the following conditions:

Causes of hemiplegia

Acute onset hemiplegia can be caused by one of the following conditions: 1.

Ischemic or hemorrhagic stroke, affecting contralateral cerebral hemisphere, internal capsule, brainstem or ipsilateral upper cervical cord.

2.

Cerebral venous sinus thrombosis with venous infarction of contralateral cerebral hemisphere.

3.

Acute central nervous system infection, such as meningitis or encephalitis, brain abscess, granulomatous infections.

4.

Head injury, causing contusion/bleeding in the contralateral cerebral hemisphere, internal capsule, basal ganglia, or brainstem.

5.

Bleeding into a brain tumor on the contralateral side.

6.

Demyelinating illness, such as ADEM (acute disseminated encephalomyelitis) or MS (multiple sclerosis).

7.

Toddâ&#x20AC;&#x2122;s paresis.

affecting

Acute onset monoplegia affecting upper limb can be caused by the following conditions: 1.

Stroke, affecting superior division of contralateral middle cerebral artery territory, affecting parietal lobe, or unpaired anterior cerebral artery.

2.

Head injury, with contusion in the parietal lobe.

3.

Trauma to the brachial plexus.

142

8.

Metabolic derangements, such as hypoglycemia, hyperglycemia or hyponatremia.

9.

Functional or psychogenic.

NEUROLOGY

Insidious onset, gradually progressive hemiplegia can be caused by one of the following conditions: 1.

Brain tumor, affecting cerebral hemisphere, internal capsule, basal ganglia or brainstem.

2.

Tumor of the spinal cord in cervical region.

3.

Chronic infections of the brain, such as tuberculosis, hydatid cysts, etc.

4.

Millâ&#x20AC;&#x2122;s hemiplegic variant of motor neuron disease (MND).

Above, we have seen the list of differential diagnosis for acute onset as well as insidious onset, gradually progressive conditions causing monoplegia and hemiplegia. The list mentions the most common causes encountered in routine clinical practice, and rare conditions have not been listed. Still, there are a lot of conditions/diseases to be considered while evaluating a case. Therefore, it is important to tailor the history and clinical examination to arrive at the correct diagnosis. A thorough history taking and examination would also lead us to order appropriate investigations, in order to clinch the diagnosis.

In the subsequent sections, we would discuss in detail about the approach to monoplegia and hemiplegia. For ease of discussion, we would separately consider the acute onset and chronic conditions.

Acute onset monoplegia affecting lower limb

In this section, we would consider the conditions that cause acute onset weakness of the lower limb, evolving over hours to days. The site of lesion in a patient with lower limb weakness can vary from peripheral to central nervous system.

Lesions in the central nervous system more often cause acute onset monoplegia affecting the lower limb. Among these, the most common are the vascular syndromes. Legpredominant weakness with stroke is due to contralateral anterior cerebral artery (ACA) infarction in only 25% of cases. More often, it is related to lesions in the contralateral corona radiata or internal capsule, in the territory of the anterior choroidal artery or perforators (30%), or in the brainstem (25%) and can occur with lesions in the middle cerebral artery territory or with thalamic hemorrhage.[1] Regarding lesions of the medial aspect of the frontal lobe, those restricted to precentral gyrus of the paracentral lobule cause contralateral leg weakness. In rare cases, lacunar infarction of the corona radiata can cause ipsilateral weakness of the leg.[2] This can happen due to anomalous pyramidal fibers with ipsilateral innervation or due to reorganization of pyramidal fibers due to old stroke. Ipsilateral pure motor monoparesis of the leg can also rarely occur with lateral medullary infarction.

[3] This occurs due to involvement of corticospinal tract fibers innervating the lower limb caudal to pyramidal decussation.

The clue towards a likely vascular cause is the sudden onset of weakness, and the exact time of onset of weakness can be obtained from the history. The exception includes â&#x20AC;&#x153;wake up strokesâ&#x20AC;?, where the patient goes to sleep without any deficits and wakes up with a new onset weakness of the leg.

The diagnosis of stroke can be confirmed by doing a computerized tomography (CT) scan. Hemorrhage or bleeding is easily picked up on the CT scan. Acute infarction may be missed on the CT scan during initial few hours. Therefore, magnetic resonance imaging (MRI) with diffusion-weighted imaging is the modality of choice for diagnosis of acute ischemic stroke causing isolated monoparesis.[4] Acute onset weakness of contralateral leg can also occur with cerebral venous sinus thrombosis (CVST) with venous infarction affecting medial frontal lobe.

Weakness of contralateral leg can also rarely occur due to granulomatous infections affecting the medial frontal lobe and head injury causing contusion/hemorrhage of the precentral gyrus.[5] In peripheral nervous system, involvement of lumbosacral plexus (lumbo-sacral plexopathy) is the commonest cause of acute onset unilateral lower limb weakness. The most characteristic feature of lumbo-sacral plexopathy is the presence of pain along with weakness of the lower limb.

Pain may be severe and poorly localized. It is described as lancinating, aching or burning pain. It may involve thigh, leg and gluteal regions. There is predominant involvement of proximal group of muscles, as compared to the distal group of muscles. In addition, there may be loss of sensations too. Weight loss is noted in most patients.

Clinical examination would confirm the weakness of proximal group of muscles. If patients present after a few weeks, there may be wasting of thigh and leg muscles.

Knee jerk is absent. Ankle jerk may be present, however it may be sluggish or absent, if the patient has associated peripheral neuropathy. The diagnosis of lumbo-sacral plexopathy can be confirmed by nerve conduction studies and needle electromyography. A clinical clue for a plexus lesion (as against multiple peripheral nerves and nerve roots) is the motor and sensory involvement in the distribution of two or more peripheral nerves and two or more nerve root territories in the same limb. The common causes for acute onset lumbo-sacral plexopathy are diabetes mellitus (also called as Bruns Garland syndrome), viral infections, hemorrhage, vasculitis and trauma. In diabetic lumbo-sacral plexopathy, both lower limbs may be affected, however, one side is more affected than the other side.

Acute onset monoplegia affecting upper limb

Lesions in the central as well as peripheral nervous system can cause acute onset monoplegia affecting upper limb.

The most common cause of acute onset isolated arm weakness on one side is stroke. However, it should be noted that it is uncommon for stroke to present with isolated arm weakness without associated face

or leg weakness. Stroke presenting with isolated arm monoparesis may be misdiagnosed as a peripheral nerve disorder, because of absence of pyramidal tract signs or the involvement of the speech, face or lower limbs. Distal arm monoparesis is an unusual form of cortical infarct, which occurs in the parietal lobe or central sulcus region, comprising less than 1% of stroke cases.[6] Again, the acute onset is the key to suspicion of stroke.

The diagnosis can be confirmed by diffusion-weighted imaging on MRI brain.

While evaluating a case of acute onset weakness of leg or arm, we must also consider a diagnosis of psychogenic or functional basis for the same. Psychogenic monoplegia is common in younger people, and is more common in women. Detailed history may reveal stress factors related to personal relationships, job or studies in the affected individual. Psychogenic weakness may be associated with primary gain (deriving attention towards illness) and secondary gain (avoidance of stress factor). Examination of a patient with psychogenic monoplegia may reveal inconsistent findings. Power of the affected limb may change, when repeatedly tested. Also, if a person with psychogenic weakness of leg were made to stand by self, she would avoid injury while falling. Hoover’s sign is very important while examining a person suspected to have psychogenic leg weakness. Palm of the examiner’s hand is placed under the heel of patient’s normal leg; and the patient is asked to raise the weak leg. In a person with true weakness, pressure on the palm would be felt due to downward movement of the normal leg, however, in a person with psychogenic weakness, no such mechanical pressure is felt on the palm.

Slowly progressive monoplegia affecting lower limb

A variety of conditions can cause insidious onset, slowly progressive weakness of one leg. The site of lesion causing such isolated progressive weakness of one leg can extend from brain, spinal cord to nerve roots and plexus. Therefore, a systematic approach is needed while

Tumors of the brain or spinal cord are the common causes of slowly progressive isolated monoparesis of lower limb.

The person presents with weakness of one leg, which often starts distally in the foot, and over a few weeks to months, spreads to involve the proximal group of muscles. This is because the lower limb fibers are located laterally in the spinal cord. Presence of back pain and radicular pain may point towards a spinal cord lesion, most probably a tumor.

Examination, in addition to motor weakness, may reveal loss of sensations in the affected leg. Bladder symptoms are unusual with unilateral leg weakness. Diagnosis is almost always delayed in a case of neoplastic spinal cord compression, when the patient presents with unilateral leg weakness.[8] However, we need to suspect a spinal cord compression even in the absence of sensory level, as 23% of cases may present with unilateral weakness.[9] An MRI of the spine with contrast is valuable in confirming the diagnosis of spinal cord tumor. The common spinal cord tumors include meningioma & schwannoma (benign tumors) and metastases & glioma (malignant tumors).

Tumors of the brain affecting precentral gyrus, medial frontal lobe and paracentral lobule may present with monoparesis of contralateral leg.

Tuberculosis of spine and tuberculous meningitis (TBM) can also present with subacute or chronic weakness of one leg. A case of 37-year old woman is reported where she presented with spastic weakness of right leg of six years duration.[10] The cause was found to be tuberculous syringomyelia, as she had a past history of TBM and had received anti-tuberculous therapy for that.

Among the peripheral nervous system causes, the most common cause for unilateral leg weakness would be lumbo-sacral plexopathy. The clinical features of lumbosacral plexopathy have already been discussed above.

The underlying etiology for slowly progressive lumbosacral plexopathy could be metastases, neurofibroma & nerve sheath tumors, infections and diabetes mellitus.

Slowly progressive monoplegia affecting upper limb

The causes for slowly progressive weakness affecting upper limb would be similar to that of lower limb. This would include spinal cord tumors affecting the cervical cord region, and tumors affecting the parietal lobe of brain. Similarly, infections such as tuberculosis of these areas could also result in unilateral arm weakness.

Among the peripheral nervous system causes, involvement of brachial plexus would present with unilateral arm weakness. Causes of slowly progressive brachial plexopathy include tumors, metastases, infections, etc.

Diabetes could also cause brachial plexopathy, though the involvement of lumbo-sacral plexus is more common with diabetes.[11] In this condition, patients complain of shoulder and arm pain, and there is weakness of hand and forearm muscles.

Another cause to be considered in a patient presenting

143

CHAPTER 27

Acute onset monoplegia of upper limb can also occur due to peripheral nervous system involvement. The most common cause in this category is brachial plexopathy.

Brachial plexus lesions that can result in acute onset weakness include injury/trauma, infections, hemorrhage, etc. The classical features include arm and shoulder pain, weakness and sensory disturbances. Weakness affects proximal group of muscles more than the distal group.

Most patients also have wasting of muscles. Deep tendon reflexes of the affected upper limb may be sluggish or absent. A clinical involvement in the distribution of more than two spinal nerves and more than two peripheral nerves is a strong indicator of brachial plexus lesion.

The diagnosis of brachial plexopathy can be confirmed by doing nerve conduction studies with Erb’s point stimulation and needle EMG. MRI is also valuable in diagnosing brachial plexus lesion. An abnormal hyperintense signal on MRI suggestive of inflammation may be seen in brachial neuritis caused by varicella zoster virus.[7]

evaluating such a case in order to correctly localize and diagnose.

NEUROLOGY

144

with slowly progressive weakness of one limb (upper or lower limb) associated with wasting is monomelic amyotrophy.12 The characteristic clinical features are insidious onset in the second and third decades, male preponderance, sporadic occurrence, wasting and weakness confined to one limb, and absence of involvement of the cranial nerves, cerebrum, brain stem, and sensory system. The electromyographic features, along with histologic features of neurogenic atrophy, are suggestive of an anterior horn cell lesion. The slow progression of illness for two to four years followed by a stationary phase is observed. There is no clinical evidence of involvement of the other three limbs even in patients with long-standing illness of ten to 15 years’ duration.

Monomelic amyotrophy affecting upper limb is also called as Hirayama disease. MRI cervical spine in these cases show asymmetrical lower cervical cord atrophy in about half the cases.[13]

Acute onset hemiplegia

Acute onset hemiplegia is among the commonest presentations in the emergency department. The underlying cause of acute hemiplegia can be varied, however, brain stroke remains the commonest cause.

Also, it is of utmost importance to make a quick diagnosis of acute ischemic stroke, as the only approved therapy for acute stroke (thrombolytic therapy with tissue plasminogen activator) can be given only within the first four and half hours after stroke onset.

The most important consideration in the diagnosis of stroke is the abruptness of onset of symptoms. The typical history of a patient with stroke could be as per the described case here: “Mr KS went for a morning walk as usual and returned in half an hour. He sat down in balcony reading a newspaper and having a cup of tea. All of a sudden, the newspaper fell off his right hand, and he could not hold the cup of tea. He slumped off the chair to the ground. He could not use his right hand or leg. He tried calling for his wife but could not.” This is the typical history of a patient with stroke in left middle cerebral artery (MCA) territory. In fact, the commonest site of arterial occlusion in a patient with hemiplegia is MCA territory. It is also important to enquire about the history of transient ischemic attacks (TIAs), as several patients would have had one or more TIA in previous 30 days.

The risk factors for stroke such as diabetes, hypertension, dyslipidemia, hyperhomocystinemia, cardiac disease and smoking should also be looked into. An enquiry about any accompanying symptoms should also be made. For example, presence of aphasia localizes the site of occlusion to left MCA territory.

When upper and lower limbs are equally affected, it is called as dense hemiplegia, and is typical of infarcts in internal capsule. Motor power is usually grade 0 or 1. On the other hand, unequal involvement of limbs point to a lesion in cerebral cortex. Upper limbs are more affected than the lower limbs in a MCA territory infarction, whereas lower limbs are more affected than the upper limbs in ACA territory infarction.

In the initial period after stroke, upper motor neuron signs are absent. There is hypotonia of affected limbs and deep tendon reflexes are absent. This state is called as cerebral shock. This state should not be confused with a lower motor neuron lesion. Presence of aphasia, visual field defects, cortical sensory loss and extensor plantar response may help in localizing the lesion to cerebral cortex. The typical upper motor neuron signs develop after a few days of stroke onset.

A note should be made of the cranial nerve involvement.

Cranial nerve involvement on the same side of hemiplegia localizes the lesion to the cerebral cortex or internal capsule. Whereas, involvement of cranial nerves on the side opposite to that of hemiplegia (crossed hemiplegia), localizes the lesion to the brainstem.[14] In brainstem, the localization depends on the cranial nerve involvement.

Third cranial nerve involvement along with contralateral hemiplegia localizes the lesion to the midbrain (Weber’s syndrome). Involvement of sixth and seventh cranial nerves along with contralateral hemiplegia localizes the lesion to pons. Ipsilateral hypoglossal palsy and contralateral hemiplegia localizes the lesion to medial medulla.[15] Acute onset hemiplegia may also occur due to spinal cord small infarctions in the upper cervical cord. Hemiplegia in these cases is on the side of lesion. Sensory examination may also reveal ipsilateral loss of joint position and vibratory sensations, and pain and temperature impairment on the contralateral side.[16] The artery affected is usually anterior spinal artery.

In a patient suspected to have stroke, MRI brain or spinal cord (as per the clinical findings) is the imaging modality of choice for confirming the diagnosis. Diffusion weighted sequences are the most preferred and valuable in detecting acute infarcts.

Bleeding into a tumor in brain is another cause of acute hemiplegia. History of headache for a few weeks to months may point towards a neoplastic etiology. The tumor may be located in cerebral cortex, basal ganglia, thalamus or brainstem. CT or MRI scan of brain would confirm the diagnosis.

In addition, we also need to consider demyelinating illnesses and infections as the alternative possible causes for acute onset hemiplegia. Among demyelinating illnesses, acute disseminated encephalomyelitis (ADEM) is more common. ADEM is known to present as acute onset hemiplegia, and may mimic stroke.[17] Patients with ADEM are relatively younger & healthy, and may give a history of fever two weeks prior to the onset of hemiplegia. MRI brain is helpful in differentiating ADEM from MS and brain stroke.

In our country, cerebral venous sinus thrombosis (CVST) is another important diagnostic consideration in patients with acute onset hemiplegia. Almost always, patients complain of headache for a few days preceding the hemiplegia. Most patients are young and the risk factors may be present. These include pregnancy, post-partum

period, use of hormonal pills, nephrotic syndrome, hypercoagulable states, etc. MRI with MR venogram of brain would confirm the diagnosis. Hemiplegia in CVST usually occurs due to hemorrhagic infarctions in the cerebral cortex.

Enquiry should be made about any episode of seizure prior to the onset of hemiplegia. The most common cause of hemiplegia after a seizure could be Todd’s paresis.

Todd’s paresis may occur after a generalized or partial seizure, however, it is more common after a generalized seizure. The weakness usually lasts for a few hours, however, it may last for upto 36 hours in some cases.[19] Weakness may occur after the first seizure or after many years of seizures and does not appear after every seizure.

It should be noted that seizure might also occur in the setting of brain stroke, where it is more common with embolic strokes and venous sinus thrombosis.

Metabolic derangements should also be kept in mind while dealing with acute hemiplegia. Hypoglycemia (low blood glucose) is a well known, but uncommon cause of hemiplegia. Patients with hypoglycemia can present with acute hemiplegia associated with other signs such as aphasia, which can mimic strokes.[20] MRI brain shows infarctions. However, administration of glucose and correction of glucose rapidly reverses the hemiplegia and other neurological deficits. Hemiparesis has also been reported in cases of hyponatremia (low serum sodium) apparently due to central pontine myelinolysis.[21] Functional or psychogenic cause of hemiplegia is also fairly common. The typical scenario is a young woman brought to the hospital with acute onset hemiplegia, with seemingly no risk factors for stroke. History may reveal a stressful mental state. Examination is very important in confirming a psychogenic cause of hemiplegia. When we raise the arm and let it fall, the person typically avoids letting it fall over the face to avoid getting hurt. Similarly, when we make the patient stand and leave, the patient falls “carefully” to avoid getting hurt. While doing these maneuvers, we should be cautious to avoid injury to the patient, if it were not due to a psychogenic cause. Another useful clinical sign is Hoover sign, as described above in the section on monoplegia. Motor-evoked potentials may be done, which are normal.[22] As expected, MRI of brain would also be normal.

In a patient presenting with insidious onset and slowly progressive hemiplegia, brain tumors are the most important consideration. In a series on brain tumors presenting to ER, about 25% of them had hemiparesis.[23] Patients may complain of headache of raised intracranial tension type. Headaches are worse on awakening and are associated with projectile vomiting. There may be visual obscuration at the peak of headaches. CT or MRI brain scan with contrast should be performed in suspected cases to confirm the diagnosis. The commonest brain tumors are metastases and gliomas. Other tumors that can cause hemiparesis are lymphoma, meningioma, neurofibroma, etc. The location of tumor can be in cerebral cortex, basal ganglia, thalamus, and brainstem.

We must also consider infections such as tuberculoma in a patient with slowly progressive hemiplegia. Hemiplegia may also be an initial manifestation of CNS tuberculosis.

[24] It is important to suspect a diagnosis of tuberculosis, if the patient has fever, headache and weight loss as the symptoms. Institution of anti-tuberculous treatment may reverse the hemiparesis. Neurosarcoidosis can also present with various neurological manifestations, including hemiparesis.[25] We should also consider a diagnosis of Mill’s variant of amyotrophic lateral sclerosis in a person presenting with slowly progressive hemiplegia.[26] Pure motor system is affected, with sparing of sensory and autonomic symptoms. Clinical examination would reveal a combination of lower and upper motor neuron signs.

Needle EMG would confirm the diagnosis.

REFERENCES

1.

Schneider R, Gautier JC. Leg weakness due to stroke. Site of lesions, weakness patterns and causes. Brain 1994; 117:34754.

2.

Taniguchi A, Li Y, Kawana Y, Asahi M, Naito Y, Shibata M, et al. Case of ipsilateral monoparesis by lacunar infarction: a consideration of pathological mechanism. Brain Nerve 2011; 63:177-80.

3.

Tsuda H, Tanaka K, Kishida S. Pure motor monoparesis in the leg due to a lateral medullary infarction. Case Rep Med 2012; 2012:758482.

4.

Hiraga A. Pure motor monoparesis due to ischemic stroke.

Neurologist 2011; 17:301-8.

5.

Ando K, Maruya J, Kanemaru Y, Nishimaki K, Minakawa T. Pure motor monoparesis of a lower limb due to head injury: case report. Brain Nerve 2012; 64:1427-30.

6.

Castaldo J, Rodgers J, Rae-Grant A, Barbour P, Jenny D. Diagnosis and neuroimaging of acute stroke producing distal arm monoparesis.

7.

Ayoub T, Raman V, Chowdhury M. Brachial neuritis caused by varicella-zoster diagnosed by changes in brachial plexus on MRI. J Neurol 2010; 257:1-4.

8.

Copeman MC. Presenting symptoms of neoplastic spinal cord compression. J Surg Oncol 1988; 37:24-5.

9.

Dugas AF, Lucas JM, Edlow JA. Diagnosis of spinal cord compression is nontrauma patients in the emergency department. Acad Emerg Med 2011; 18:719-25.

145

CHAPTER 27

Infections such as herpes encephalitis and tuberculous meningitis (TBM) can also rarely cause acute-onset hemiplegia mimicking stroke. In patients with herpes encephalitis, sudden onset stroke-like hemiparesis has been reported.[18] In suspected case of TBM, patient may complain of sudden onset hemiplegia, often due to vasculitis affecting TBM. The commonest artery affected in TBM is MCA. Hemiplegia has also been reported with dengue and falciparum malaria. An infective cause should be suspected when the patient with hemiplegia has a fever. Appropriate investigations should be done to confirm or exclude these infections in a patient presenting with hemiplegia.

Slowly progressive hemiplegia

NEUROLOGY

146

10.

Sundaram SS, Vijeratnam D, Mani R, Ginson D, Chauhan AJ. Tuberculous syringomyelia in an HIV-infected patient: a case report. Int J STD AIDS 2012; 23:140-2.

19. Rolak LA, Rutecki P, Ashizawa T, Harati Y. Clinical features of Toddâ&#x20AC;&#x2122;s post-epileptic paralysis. J Neurol Neurosurg Psychiatry 1992; 55:63-4.

11. Katz JS, Saperstein DS, Wolfe G, Nations SP, Alkhersam H, Amato AA, et al. Cervicobrachial involvement in diabetic radiculoplexopathy. Muscle Nerve 2001; 24:794-8.

20.

12.

Gouri-Devi M, Suresh TG, Shankar SK. Monomelic amyotrophy. Arch Neurol 1984; 41:388-94.

13.

Nalini A, Gouri-Devi M, Thennarasu K, Ramalingaiah AH. Monomelic amyotrophy: Clinical profile and natural history of 279 cases seen over 35 years (1976-2010).

Amyotroph Lateral Scler Frontotemporal Degener. 2014; 22:19.

21. Marra TR. Hemiparesis apparently due to central pontine myelinolysis following hyponatremia. Ann Neurol 1983; 14:687-8.

14.

Silverman IE, Liu GT, Volpe NJ, Galetta SL. The crossed paralyses. The original brain-stem syndromes of MillardGubler, Foville, Weber, and Raymond-Cestan. Arch Neurol 1995; 52:635-8.

15.

Kumral E, Afsar N, Kirbas D, Balkir K, Ozdemirkiran T. Spectrum of medial medullary infarction: clinical and magnetic resonance imaging findings. J Neurol 2002; 249:8593.

16.

Baumgartner RW, Waespe W. Anterior spinal artery syndrome of the cervical hemicord. Eur Arch Psychiatry Clin Neurosci 1992; 241:205-9.

17.

Brinar VV, Poser CM, Basic S, Petelin Z. Sudden onset aphasic hemiplegia: an unusual manifestation of disseminated encephalomyelitis. Clin Neurol Neurosurg 2004; 106:187-96.

18. AbduJabbar M, Gozi I, Haq A, Korner H. Sudden strokelike onset of hemiparesis due to herpetic encephalitis. Can J Neurol Sci 1995; 22:320-1.

Umemura K, Fukuda O, Takaba M, Saito T, Hori E, Kurimoto M, et al. Hypoglycemic hemiplegia: a report of three cases. No To Shinkei 2001; 53:1135-9.

22.

Shahar E, Ravid S, Hafner H, Chisyakov A, Shcif A. Diagnostic value of Hoover sign and motor-evoked potentials in acute somatoform unilateral weakness and sensory impairment mimicking vascular stroke. J Clin Neurosci 2012; 19:980-3.

23.

Snyder H, Robinson K, Shah D, Brennan R, Handrigan M. Signs and symptoms of patients with brain tumors presenting to the emergency department. J Emerg Med 1993; 11:253-8.

24.

Vyravanathan S, Senanayake N. Tuberculosis presenting with hemiplegia. J Trop Med Hyg 1979; 82:38-40.

25.

Titlic M, Bradic-Hammoud M, Miric L, Punda A. Clinical manifestations of Neurosarcoidosis. Bratisl Lek Listy 2009; 110:576-9.

26. Malin JP, Poburski R, Reusche E. Clinical variants of amyotrophic lateral sclerosis: hemiplegic type of ALS and Mills syndrome. A critical review. Fortschr Neurol Psychiatr 1986; 54:101-5.

C H A P T E R

28

KEYWORDS

vertigo, cardiac giddiness, bedside tests for vertigo Giddiness is one of the commonest symptoms encountered by physicians on a day to day basis. As the term suggests, it implies a feeling of imbalance. However, most patients are quite imprecise in their descriptions of giddiness and may variously call it dizziness, spinning, light-headedness, etc. Giddiness can be an innocent symptom of a simple disease or may be a harbinger of a serious condition such as a stroke.1 The challenge in day to day life for physicians is to make a precise diagnosis of such a vague symptom, and to identify and treat the more dangerous diseases that may present with this common symptom.

CAUSES OF GIDDINESS

Broadly classified, the causes of giddiness are due to vestibular dysfunction, brainstem problems, cardiac conditions or psychiatric disorders.

IMPORTANCE OF HISTORY IN GIDDINESS

The first step in trying to find the cause of giddiness is to take a detailed history, because the precise cause of giddiness can be easily identified in several cases by just taking a comprehensive history.

GIDDINESS OR VERTIGO?

The most important task is to differentiate in the history between giddiness and vertigo, as the causes of vertigo are few and easy to identify. The patient should be asked if there is a definite sense of rotation or spinning, which will point to the diagnosis of vertigo. If this is present, it usually means that the vestibular system is involved. This system comprises of the vestibular apparatus in the inner ear, the vestibular nerve and nucleus and the connections of this to the cerebellum.

Benign positional vertigo, vestibular neuritis, Meniereâ&#x20AC;&#x2122;s disease are the peripheral causes connected with the ear, whereas posterior circulation ischemia, infarction or tumors of posterior cranial fossa are called central causes as they involve the brain stem.2 Differentiation of the various causes of vertigo will involve some simple clues from history.

DURATION OF VERTIGO AND ACCOMPANYING SYMPTOMS

If the person has vertigo, the following questions will help to clarify the cause of vertigo. Transient attacks of vertigo generally point to benign paroxysmal positional vertigo (BPPV), where the episode may last even less than a minute. As the name suggests these attacks are episodic,

Approach to Giddiness Sudha Vidyasagar transient,and precipitated by posture.Movements of the head can cause such severe giddiness that some patients are terrified and refuse to move the head even slightly.3 Recurrent spontaneous attacks of vertigo are a feature of Meniereâ&#x20AC;&#x2122;s disease. This is usually associated with auditory symptoms such as hearing loss and pain or fullness in the ear which may occur during the attacks. Vestibular migraine which also lasts few minutes to hours may cause vertigo which is facilitated by visual movements such as while watching movies.

Prolonged periods of severe vertigo of acute onset may be due to vestibular neuritis. These episodes are sudden in onset and may remain even when the head is held still thus differentiating it from BPPV. One of the challenges for the treating doctor is to differentiate this from the vertebrabasilar insufficiency such as due to posterior circulation transient ischemic attacks. These are also episodic and may last only a few minutes with full recovery. This is when we are faced with the challenge of differentiating peripheral causes of vertigo from central causes.

CENTRAL OR PERIPHERAL VERTIGO

Symptoms such as tinnitus, nausea and recurrent vomiting during the episodes are classical of peripheral vertigo due to involvement of the ear. Cerebellar and medullary lesions causing vertigo do not cause tinnitus and much less vomiting. In addition, other symptoms of posterior circulation ischemia such as dysarthria, dysphagia, diplopia quadriparesis and ataxia, may point to a brain stem cause such as vascular events or tumors.4 It is however important to note that patients with peripheral causes of vertigo can also be ataxic during the episode of vertigo, and may manifest a sense of imbalance.

It is the accompanying neurological deficits which will confirm the central cause.

Extension of the neck to look upwards can cause giddiness in patients with cervical spondylosis due to compromise of the vertebral circulation. The classical example of a grandfather pointing out an airplane to a grandson and losing balance every time he attempts this, illustrates this cause. Associated symptoms of cervical spondylosis such as neck pain, restriction of neck movements and weakness in the upper limbs may help to make this diagnosis.5 Chronic persistent vertigo lasting over several months is generally due to psychiatric problems such as somatization, anxiety or depression. These patients are vague in their description of vertigo, and often have several other multiple complaints.

148

GIDDINESS NOT VERTIGO

If the patient has no sense of rotation, but has only giddiness, several other important causes must be considered. The most important of these are cardiac causes.

NEUROLOGY

CARDIAC CAUSES OF GIDDINESS

Orthostatic hypotension is an important cause of giddiness. This is diagnosed as a fall in systolic BP of 20mm of Hg from supine to standing position after 3 minutes of standing. This typically manifests as feeling of faintness or black outs when the patient stands up from supine position. The important causes of orthostatic hypotension are autonomic neuropathy, and other cardiac causes such as arrhythmias and shock.

The causes of autonomic neuropathy are several, the commonest being diabetes mellitus, elderly age and drugs.6 This condition leads to feeling faint on standing up from lying of sitting posture due to lack of appropriate sympathetic response to change of posture due to poor sympathetic tone. Most elderly patients report giddiness as a feeling of blacking out or feeling faint or light headed.

Such pre-syncope can be preceded by pallor which is often observed by bystanders.

Diabetic autonomic neuropathy should be suspected in any long standing diabetic with peripheral neuropathy.

The blood pressure must be checked in the lying and standing position in all diabetics as a routine when they come for follow up.

Orthostatic hypotension can cause postural instability in the elderly and lead to falls. Many old people are unable to report the faintness on standing and describe it vaguely as weakness, which is due to decreased cerebral circulation.7 Some of them may be on anti-hypertensiveâ&#x20AC;&#x2122;s which can cause a significant postural drop such as beta blockers and prazosin. First dose hypotension is a well-known feature of prazosin and all elderly patients are cautioned not to stand up suddenly after initiation of alpha blockers at least in the first few days.

In the emergency setting,any patient complaining of giddiness on standing, must be assessed for volume loss, such as due to vomiting or diarrhea, or occult blood loss, such as bleeding from peptic ulcer into the gut. Loss of more than 10% of blood volume can cause giddiness on standing and orthostatic hypotension with more than 20 mm of BP fall in systolic pressure on standing.8 More than 30% loss of blood volume can cause giddiness even in supine posture, and this should alert the physician to a grave situation.

Further cardiac emergencies such as acute coronary syndrome such as myocardial infarction and pulmonary embolism can also cause severe giddiness and faintness.

Again the accompanying symptom of chest pain or discomfort, and breathlessness may reveal the cardiogenic shock or pulmonary edema.9 Patients with pulmonary embolism feel more giddiness and breathlessness on sitting up, which is the opposite of left ventricular failure, and should alert one to this possibility.

Pre-syncope occurring even in the supine position is probably due to cardiac arrhythmias.10 Both tachyarrhythmias such as supraventricular tachycardias and atrial fibrillation with fast ventricular response and bradyarrhythmias such as complete heart block and sick sinus syndrome can present with giddiness by compromising cerebral blood flow. These can cause giddiness in the lying posture and that is an important clue to the presence of an arrhythmia. A history of palpitations, chest pain or breathlessness preceding the light headedness may give a clue to cardiac nature of the syncope.11

OTHER CAUSES

Sudden rise in blood pressure can cause dizzy spells.

These can be accompanied by headache, and must be thought of in elderly patients, warranting checking of blood pressure. However, chronic hypertension and mild rises of blood pressure hardly cause any giddiness.

Hypoglycaemia can present as giddiness, especially in a diabetic on insulin or sulphonylureas after a missed meal. The setting and the accompanying symptoms of palpitation and sweating may help in clinching this diagnosis.

The last group of non-specific giddiness is due to psychiatric illnesses.12 Patients with panic attacks can have tachycardia, sweating and light headedness, which may be mistaken for a cardiac problem. Hyperventilation due to hysteria can lead to giddiness. However, this cannot last very long as the patient will tire out in a few minutes. The social circumstances and the personality of the patient may help to make the diagnosis of a hysterical conversion reaction.

Post-traumatic giddiness may follow trauma to the head or whiplash injuries. Such episodes can last up to a month following trauma. Post-traumatic stress disorder may also complicate the clinical picture and make differentiation between the two entities difficult.13 A comprehensive drug history regarding the use of antidepressants and anti-cholinergics is important to rule out drug induced causes of dizziness. Several patients introduced to antidepressants or benzodiazepines for the first time, complain of giddiness, and many of them discontinue the drugs due to this symptom. Hence it is important to elicit a complete drug and disease history in all patients with giddiness.

PHYSICAL EXAMINATION IN PATIENTS WITH GIDDINESS

The physical examination must begin with assessment of hemodynamic parameters such as pulse. Tachycardias or arrhythmias such as atrial fibrillation must be ruled out.

Bradyarrythmias such as complete heart block or sick sinus syndrome may present with very low heart rates below 40/minute. Blood pressure must be checked in lying down and standing position to rule out orthostatic hypotension. Hypoxia accompanying giddiness is suggestive of a cardiac emergency.

Nystagmus is an important clue to the presence of a vestibular cause of the giddiness. Nystagmus due to

APPROACH TO GIDDINESS-CAUSES

GIDDINESS

PERIPHERAL:

ORTHOSTATIC HYPOTENSION

BPPV VESTIBULAR NEURONITIS MEINIERE’S DISEASE CENTRAL:

AUTONOMIC NEUROPATHY

MISCELLANIOUS PSYCHIATRIC CAUSES DRUGS

CARDIAC ARRYTHMIAS

POST TRUAMATIC GIDDINESS

CARDAIC ISCHEMIA

ACCELERATED HYPERTENSION

BRAIN STEM PROBLEMS   

MIGRAINE ISCHEMIA TUMOURS

Fig. 1: labyrinthine lesions is usually to the opposite side and increases in frequency and amplitude when the patient is asked to look away from the side of lesion. The type of nystagmus gives an important clue to the site of origin.

A horizontal/torsional nystagmus is due to affection of semicircular canals on one side. It is important to remember that such peripheral nystagmus is never vertical or purely torsional. Further, nystagmus due to peripheral lesion can be suppressed by visual fixation.

BEDSIDE TESTS FOR VERTIGO

Dix-Hallpike’s maneuver

This is a simple bedside test to induce vertiginous attacks and produce nystagmus in a patient with a history of positional vertigo. These tests are designed to diagnose canalithiasis of the posterior semicircular canal, which is an important cause of BPPV.15

Nystagmus due to brainstem lesions can be horizontal, vertical or torsional. Cerebellar nystagmus is gaze dependent and increases in the direction of gaze and is more to the side of lesion. For example, right cerebellar lesion will cause nystagmus to increase on looking to right side. Careful neurological examination must be done in such patients to look for cerebellar signs or lower cranial nerve involvement. Most patients with such lesions are unable to walk and patients may fall to the side of lesion if the cerebellum is involved.14

The patient is made to sit on the bed while the neck is turned to one side and extended. Then he is suddenly changed to supine position with the head hanging over to the side of the bed for 30 seconds. If BPPV is present, nystagmus and vertigo will occur after a latency of a few seconds and last for brief period. Such nystagmus can be torsional in nature. Since this test is fatigable, the duration and intensity of nystagmus may diminish with every repetition. The sensitivity of this maneuver is quite high that is above 85% for the diagnosis of posterior canal BPPV. Thus, it is a very useful test for the confirmation of this simple diagnosis.

An acoustic neuroma is a slow growing intracranial tumor which typically presents with tinnitus, vertigo, deafness and cerebellar involvement. The history may last several years as a tumor grows slowly and does not cause much intracranial tension. Examination typically reveals involvement of seventh and eighth cranial nerves with cerebellar ataxia on the side of lesion.

Several other tests such as head impulse test or head thrust test can also be used. This is done by asking the patient to focus on a distant object and turning the head quickly and unpredictably by about 15 degrees. If the eyes are dragged off the target and followed by a saccade back on to the target after the head turn, this indicates a deficient vestibule-ocular reflex and pointing to a

CHAPTER 28

VERTIGO

149

150

peripheral vestibular lesion. This test may have a higher specificity (80-100%) but poor sensitivity (35-40%).16

NEUROLOGY

LOOKING FOR NEURO DEFICITS

Any cause of vertigo due to a brain stem cause, will be usually accompanied by neurological deficits such as 7th and 8th nerve palsy, ataxia, or quadriparesis. A patient with Wallenberg’s syndrome, due to infarction of lower medulla can complain of vertigo along with ataxia.

Examination in such a patient will show cerebellar signs on side of lesion, lower cranial nerve such as 9th and 10th nerve palsy, in addition to nystagmus, which will help to localize the level of lesion.17

INVESTIGATIONS FOR GIDDINESS

These must be chosen depending upon the clinical diagnosis. For vestibular problems, a caloric test may help in establishing a diagnosis. An audiometry is useful to diagnose conditions such as Meniere’s disease and acoustic neuroma. Audiometry at the time of attack may show decreased hearing and eventually the patient may develop permanent deafness. In acoustic neuroma, audiometry may reveal sensori-neural deafness due to involvement of the cochlear nucleus of the eighth cranial nerve.

An MRI is indicated for imaging of brainstem in patients suspected to have posterior circulation ischemia or infarction. Wallenberg’s syndrome and other medullary or cerebellar infarctions are easily picked up by MRI. MR angiography is very useful in detecting stenosis or thrombosis of the vertebral and basilar arteries with a very high sensitivity and specificity of over 95%. Further, tumors in the posterior cranial fossa such as acoustic neuroma can be diagnosed with MRI of brainstem.18 For cardiac lesions, a basic ECG to diagnose arrhythmias is essential. For patients with paroxysmal giddiness, a transient arrhythmia must be considered. Holter monitoring for 24 hours may be useful in such patients to diagnose conditions such as sick sinus syndrome (bradycardia-tachycardia syndrome), paroxysmal atrial fibrillation, supraventricular tachycardias or a run of ventricular tachycardia.19

3.

Parnes LS, Agrawal SK, Atlas J. Diagnosis and management of benign paroxysmal positional vertigo (BPPV). Canadian Medical Association Journal 2003; 169:681-693.

4.

Karatas M. Central vertigo and dizziness: epidemiology, differential diagnosis, and common causes. The neurologist 2008; 14:355-364.

5.

Toole JF, Tucker SH. Influence of Head Position upon Cerebral Circulation: Studies on Blood Flow in Cadavers. AMA Arch Neurol 1960; 2:616-623.

6.

Rutan GH, Hermanson B, Bild DE, Kittner SJ, LaBaw F, Tell GS. Orthostatic hypotension in older adults. The Cardiovascular Health Study. CHS Collaborative Research Group. Hypertension 1992; 19:508-19.

7.

Gupta V, Lipsitz LA. Orthostatic hypotension in the elderly: diagnosis andtreatment. Am J Med 2007; 120:841-847.

8.

Rothe CF. Shepherd JT, Abboud FM and Geiger SR. Venous System: physiology of the capacitance vessels. In: Handbook of Physiology: The Cardiovascular System Peripheral Circulation. Washington, D.C: American Physiological Society; 1983; 397-452.

9.

Hasdai D, Topol EJ, Califf RM, Berger PB, Holmes DR. Cardiogenic shock complicating acute coronary syndromes.

Lancet 2000; 356:749-56.

10. Barraclough K, Seemungal B. Vertigo and Dizziness in General Medicine. Oxford Textbook of Vertigo and Imbalance. 2013:287-292.

11. Vogler J, Breithardt G, Eckardt L. Bradyarrhythmias and conduction blocks. RevEsp Cardiol (Engl Ed). 2012; 65:65667.

12. Eckhardt-Henn A, Breuer P, Thomalske C, Hoffmann SO, Hopf HC. Anxiety disorders and other psychiatric subgroups in patients complaining of dizziness. Journal of anxiety disorders 2003; 17:369-88.

13. Chen CC, Yeh TL, Yang YK, Chen SJ, Lee IH, Fu LS, Yeh CY, Hsu HC, Tsai WL, Cheng SH, Chen LY. Psychiatric morbidity and post-traumatic symptoms among survivors in the early stage following the 1999 earthquake in Taiwan.

Psychiatry research 2001; 105:13-22.

14. Baloh RW. Differentiating between peripheral and central causes of vertigo. Otolaryngol Head Neck Surg 1998; 119:55.

15. Dix MR, Hallpike CS. The pathology symptomatology and diagnosis of certain common disorders of the vestibular system. Proc R Soc Med 1952; 45:341-54.

Hypoglycaemia can be ruled out by a blood sugar test by glucometer.Hypoxia must be checked in all severely giddy patients with a saturation probe to rule out life threatening cardiac emergencies.

16. Schubert MC, Tusa RJ, Grine LE, Herdman SJ. Optimizing the sensitivity of the head thrust test for identifying vestibular hypofunction. PhysTher 2004; 84:151.

To conclude,the diagnosis of giddiness can thus range from simple conditions such as drug induced problems to very serious life threatening strokes. A careful history, simple bedside tests and judicious use of investigations will help to arrive at correct diagnosis.

18. Brandt T, Steinke W, Thie A, Pessin MS, Caplan LR. Posterior cerebral artery territory infarcts: clinical features, infarct topography, causes and outcome. Multicenter results and a review of the literature.Cerebrovasc Dis 2000; 10:170-82.

REFERENCES

1.

Kerber K, Brown D, Lisabeth L, Smith M, Morgenstern L. Stroke Among Patients With Dizziness, Vertigo, and Imbalance in the Emergency Department: A PopulationBased Study. Stroke 2006; 37:2484-2487.

2.

Hanley K, O’Dowd T, Considine N. A systematic review of vertigo in primary care. Br J Gen Pract 2001; 51:666-671.

17. Savitz SI, Caplan LR. Vertebrobasilar disease. N Engl J Med 2005; 352:2618-26.

19. Crawford MH, Bernstein SJ, Deedwania PC, DiMarco JP, Ferrick KJ, Garson A et al.ACC/AHAguidelines for ambulatory electrocardiography: executive summary andrecommendations. A report of the American College of Cardiology/American HeartAssociation task force on practice guidelines (committee to revise the guidelines for ambulatory electrocardiography). Circulation 1999; 100:88693.