La Grenade-Finch 1
Randolph College
The Efficacy of Herbal and Traditional Medicine In Relation to Parkinson’s Disease
Ariana La Grenade-Finch Biology Senior Seminar- Biology 495 Dr. Bliss 12.11.15
La Grenade-Finch 2 Abstract: Medicine is used by many to relieve the symptoms of many problems such as allergies, illnesses and diseases. If there is any hesitation to take medications, it is usually due to its adverse effects. This study will explore the efficacy of herbal treatments and traditional medicine in relation to the world’s second most common age-related neurodegenerative disease, Parkinson’s Disease. Parkinson’s Disease (PD) is a result of a dopamine deficiency and oxidative damage. A comparison was made between herbal treatments and traditional medicine while being used to treat patients with Parkinson’s disease and Parkinson’s disease models. Their efficacies as well as adverse effects were discussed. It was noted that Levodopa had the most adverse effects inducing dyskinesia (impairment of voluntary movement), but when paired with dopamine agonists the dyskinesia was reduced. Subthalamic deep brain stimulation was discussed and seen to have major improvement in PD patients, but this improvement seemed to be only temporary. Anticholinergics were sometimes used with Subthalamic deep brain stimulation, but this too is also temporary. Given all the drawbacks of these traditional treatments explored, many have turned to herbal treatments. Those discussed in this paper are Banxia Houpo Tang which is a combination of various plants which prevents choking that occurs in many PD patients, by improving the swallowing reflex. Acanthopanax senticosus harms, Hibiscus asper, and Gingko biloba all expressed high neuroprotective and antioxidant properties which aid in the improved symptoms of Parkinson ’s disease. The conclusion made from this research is that CAM (Complementary medical therapies) such as acupuncture, massage therapy, etc. in conjunction with herbal treatments or traditional western medicine has the greatest benefit for Parkinson’s disease patients.
La Grenade-Finch 3 Introduction: Parkinson’s disease (PD) is a chronic neurodegenerative disorder. Neurodegenerative disorder is a term that describes the progressive loss of structure or function of neurons, including death of neurons. In Parkinson’s disease the dopaminergic neurons progressively degenerate causing a consequent reduction of dopamine (DA) levels in the brain. This results in the normal proportions of acetylcholinergic neurons and dopaminergic neurons becoming imbalanced, leading to PD (Li, et. Al., 2013). It is the second most common age-related neurodegenerative disease after Alzheimer’s disease. (Simm, Huertner, & Kortagere, 2015). Many times PD has been associated with age, genetic and epigenetic factors such as environmental triggers and it has been estimated that in the United States alone, about one million people live with PD. That number climbs to more than ten million worldwide. Neurologic diseases such as PD are usually incurable. The true cause for Parkinson’s disease is still unknown, but research has suggested multi-factorial causes for the disease in humans, including a genetic predisposition or susceptibility and environmental exposures (Hritcu, et. Al., 2011), which include: immense oxidative stress, free radical formation, and programmed cell death (Hritcu, et. Al., 2011). Neurodegeneration due to dietary habits such as a deficiency of antioxidant components including folic acid, vitamins A,C,E, and selenium (Hritcu, et. Al., 2011), and neuropathology (Hritcu, et. Al., 2011) have also been linked to causing PD. Parkinson’s disease, like several other neurodegenerative disorders displays many symptoms. It is often initially diagnosed not by the early more subtle signs such as masked or frowning facial expression, but by the more obvious medical signs or physically distressing symptoms that occur later in the onset of the disease in affected individuals. The most common and noticeable symptoms of Parkinson’s disease include: tremors of the extremities, torticolis (twisted neck), bradykinesia, rigidity, stooped posture, shuffling gait, impaired swallowing
La Grenade-Finch 4 reflex and difficulty with verb production (Simms, Huertner, & Kortagere, 2015). Symptoms tend to appear and progress at different rates during the course of the disease. Some may progressively worsen over time, and others may progress then flat-line for a period of years. The disease is incurable thus the symptoms are also incurable. Even though, there are no known cures for this disease, there are many medications which allow the individual with PD to find some relief. This raises the question of which medicine is most beneficial for the patient, capable of ensuring long term relief of the most debilitating symptoms with minimal side effects. There has been a debate among many scholars for several years, on which of traditional western medicine or herbal/alternative medicine is more beneficial to the majority of patients. In this regard, herbal (alternative) medicine has been shown to have fewer adverse effects in comparison to traditional western medicine, when used to treat symptoms of Parkinson’s Disease (PD). This will be examined through a comparison of Levodopa and Dopamine agonists, two common treatments for PD, with various alternative herbal medicines which have been derived from plants such as Acanthopanox senticosus, Gingko biloba, hibiscus asper, pinellia tuber, poria cocos, perilla frutescens, Magnolia bark and Ginger.
Effects of Levodopa on Verb Production Levodopa, according to most traditional western physicians, is the key drug for the treatment of PD. It is recognized as the best available physiological treatment in their field. Studies have been done to test the effect of Levodopa on different symptoms of Parkinson’s disease, such as a recent study which tested this drug's effect on both verbal and motor representation of action in PD patients (Peran, et. Al., 2013). Many cognitive deficits can be observed in PD patients, and these deficits can lead to defective visuospatial processing, working
La Grenade-Finch 5 memory, decision-making, long-term memory, and executive functions. (Peran, et. Al., 2013). This particular study observed how this influenced language production and in particular, verbprocessing. Cerebral changes were investigated after motor improvement occurred as a result of Levodopa treatment. Functional magnetic resonance imaging (fMRI) was used before and after Levodopa treatment, to explore brain activity while performing three distinct tasks. The tasks included: object naming, generation of action verbs, and mental simulation of action. 'Object naming' was self explanatorily naming of an object, 'generation of action verbs' had patients being asked to say an action associated with a picture he or she was shown and 'mental simulation of action' consisted of asking subjects to mentally simulate an action related to a depicted object. All responses were recorded and the results showed, that Levodopa enhances activity in the motor, putaminal cortical loops circuit during lexical search. Researchers found in Figure 1 that premotor cortex regions were more activated in “ON” stage than in the “OFF” stage in PD patients, meaning that the dopaminergic modulation that the drug Levodopa provides, increases the overall verb production. The opposite was also found to be true, that patients in “OFF” dopaminergic treatment state (DTS) exhibited an increase of motor deficit compared to “ON” DTS, meaning that lack of dopaminergic modulation decreases verb production (Peran, et. Al., 2013).
La Grenade-Finch 6 Figure 1: Direct comparisons ON>OFF DTS for (GenA vs OBjN) and (MSoA vs OBjN)
Effect of Levodopa Therapy on Stooped Posture Along with verb production being an issue in those diagnosed with PD, many posture abnormalities represent one group of the main disabling features of Parkinson’s disease. Posture problems seen with this disease include: anterior flexion of the thoracolumbar spine (stooped posture), extreme forward flexion of the trunk (camptocormia), severe lateral flexion (Pisa syndrome), and dropped head (Benninger, et. Al., 2015). These spinal problems often interfere with activities of daily living (bathing/showering, eating, walking, sitting) and cause joint pain with significant discomfort. The effects of Levodopa on stooped posture in those with Parkinson’s disease were studied. The study quantitatively evaluated the effect of Levodopa on spinal posture in patients with PD. Given that most studies rely on subjective estimation, and judgments based on video recordings, it is important that an objective tool of quantitative measure, the SpinalMouse has been used to address the question of the role of dopamine on stooped posture in particular. The SpinalMouse is a computer assisted mechanical hand-held device designed to noninvasively assess the curvature of the vertebral column and the mobility in the sagittal and frontal planes, and in flexion and extension (Benninger, et. Al., 2015). Patients with early Parkinson’s disease were studied before and after Levodopa treatment, as well as those with the advanced disease, and their response fluctuations were measured and recorded during the “on” and “off” treatment states. Forty-eight patients with Parkinson’s were used in the study, twenty-two of whom had never been treated with Levodopa prior to the study (dopa-naive). The other twenty-six
La Grenade-Finch 7 were long-term Levodopa users with motor fluctuations. The SpinalMouse was used to examine spinal mobility, posture, and range of motion. The patients were then examined before and 3 months after stable treatment with Levodopa. Patients with motor fluctuations were examined in the “off” state first—“off” being the state before intake of the first morning dose, and again during the “on” state—45 minutes after taking their regular Levodopa dose. Each patient was then tested for three different positions: standing upright (comfortable, erect standing without outside help), maximal flexion, and maximal extension. The SpinalMouse was used to measure parameters in each position. In dopa-naïve patients (See Figure 3), dopamine replacement therapy led to an improvement in the upright posture with no change in the degree of flexion and extension from treatment (Benninger, et. Al., 2015). Patients with response fluctuations (See Figure 2) due to long term Levodopa administration had an improvement in both upright posture and range of motion in flexion and extension in the “on” period.
Figure 2: Posture in patients with response fluctiations.
La Grenade-Finch 8
Figure 3: Effect of Levodopa on posture in dopa-naïve patients. These results objectively demonstrated that in early disease the thoracic lumbar spine responds favorably to Levodopa, whereas in advanced stages the beneficial effect is more evident in the sacral hip joints. Thus, this study objectively showed that posture abnormalities are related to dopamine deficiency and that Levodopa has some degree of beneficial effect on the posture of those with Parkinson’s disease, regardless of how long they had the disease or even how long they had been on Levodopa treatment. Other earlier studies yielded conflicting results in their attempts to study spinal axial changes in PD. For example in one such study (Wright et al 2010) which investigated the effects of Levodopa on torsion rather than the most commonly seen deficits of flexion/ extension, a negative effect of Levodopa on kinesthetic sensitivity was seen. The recent study (Benninger et. al, 2015) which employed the use of the SpinalMouse to investigate effects of Levodopa on flexion, extension of stooped posture in Parkinson's disease has demonstrated a more appropriate standardized method, which proves that Levodopa can improve stooped posture to some degree in most PD patients.
La Grenade-Finch 9 Effect of Dopamine Agonists on Controlling PD Symptoms Previous research has suggested that Levodopa is a very suitable option for treatment of Parkinson’s disease, but there are various adverse side effects associated with the use of Levodopa as a long term treatment of Parkinson’s disease. Such side effects are often just as disabling as the symptoms of the Parkinson's disease itself and they include: nausea, gastrointestinal bleeding, disturbed respiration, disorientation, anxiety and hallucinations. Long term therapy can even cause an individual to develop abnormal involuntary movements called Ldopa induced dyskinesias (LID). In order to minimize the adverse effects associated with this drug, it was discovered that Levodopa used in conjunction with dopamine agonists has lessened the number and degree of treatment-induced side effects. Research using dopamine agonists, has also been done which proves their direct usefulness in treating PD symptoms of tremor at rest, rigidity, bradykinesia, and postural instability (Simms, Huertner, & Kortagere, 2015). Parkinson's disease has been attributed to the loss of dopaminergic and noradrenergic neurons due the generation of reactive oxygen species. These involve a cascade of physiological and neurological events that eventually leads to the inhibition of the motor thalamus which leads to loss of control of motor movements. In a 2015 study, researchers used a recently developed dopamine agonist SK609 to test its effect on forepaw stepping of rodents. A stepping apparatus made of wood was used to test these rodents, and five consecutive trials were done using the affected and unaffected forelimbs. Researchers found that there was improvement in the affected paws, with no significant difference in response to therapy , and no significant side effects, when dose of SK609 was increased from 4 mg/kg to 100 mg/kg, suggesting that low to moderate doses of SK609 help in treatment of PD. Dose of 300 mg/kg of SK609 led to worsened symptoms of PD, and included seizures and fatalities, suggesting that high doses of SK609 should not be used
La Grenade-Finch 10 in the treatment of PD. Untreated animals with PD showed progressively increased impairment in their affected paw, suggesting that forepaw movement in the affected paw worsened in animals when not treated with SK609. Researchers also found that rodents had improved performance of affected paw along with normalized bilateral asymmetry, suggesting that forepaw movement in PD affected animals improved when treated with SK609 (Simms, Huertner, & Kortagere, 2015). All this suggests that dopamine agonists effectively control the symptoms of PD during the early stages of the disease. Not only were the dopamine agonists found to be effective in improving motor movement, but none of the doses SK609 produced any significant abnormal involuntary movements (AIMs). In conjunction with the L-dopa therapy, it was found that SK609 reduces the AIMs induced by L-dopa in a dose dependent matter (See Figure 4). It was also found that increased doses of L-dopa above 0.5mg/kg in combination with SK609 resulted in higher values of AIMs which suggests that the maximum dose of L-dopa that could be combined with SK609 was 0.5 mg/kg (Simms, Huertner, & Kortagere, 2015).
Figure 4: Adjuvant dose dependent effects of SK09 in combination 6 mg/kg of L-dopa in improving AIMs were evaluated. Effect of Anticholinergics on axial symptoms
La Grenade-Finch 11 In traditional western medicine, other treatments have been used for Parkinson’s disease, such as deep brain stimulation of the subthalamic nucleus (STN-DBS). This is used many times to treat the motor symptoms in patients with PD. STN-DBS when used following low doses of Levodopa has been shown to ameliorate motor fluctuations and dyskinesia that can sometimes be caused by dopaminergic agents. Although STN-DBS has had positive effects in this regard, it comes with some adverse side effects. Axial symptoms such as akinesia (loss or impairment of the power of voluntary movement), speech disturbance, and postural instability and gait difficulties have shown a tendency to worsen over time (Baba, et. Al., 2012). In a recent study it was found that high frequency brain stimulation lead to the accumulation of adenosine in the thalamus. Adenosine enhances neurotransmissions of acetylcholine that affects postural muscle tone and locomotion via certain receptors, meaning that activation of these particular receptors by STN-DBS arouses deterioration of axial symptoms. This study recruited 20 patients with clinically diagnosed PD who had been treated with STN-DBS. After this an anti-cholinergic agent was administered to all patients at a daily dose ranging from 2 to 6 mg. Patients were evaluated one week before surgery, six months after surgery, baseline, and prospectively 1 month after treatment with the anti-cholinergic. The results showed that bilateral STN-DBS led to significant improvement of parkinsonian motor symptoms in the “on” medication state six months after surgery, but was later accompanied by a deterioration in axial symptoms (Baba, et. Al., 2012). The anticholinergic ultimately was initially helpful in ameliorating the deterioration of axial motor symptoms, but this positive effect gradually decreased over time. Anticholinergics block the action of acetylcholine in the brain and peripheral nerves by binding to/blocking the muscarinic receptors in places such as the skeletal muscles, gastrointestinal tract, the urinary
La Grenade-Finch 12 bladder, the lungs and salivary glands, decreasing mucous production and glandular secretions, as well as disrupting contractions/peristalsis throughout organs such as the gastrointestinal tract, and urinary bladder. Thus it is also important to note, that although these anticholinergics were somewhat helpful in the initial post treatment phase of STN-DBS, their unpleasant antimuscarinic side effects such as extreme thirst, nausea, constipation, urinary retention and tachycardia were seen in eighty-five percent of patients.
Effect of Banxia Houpo Tang on Swallowing Reflex in PD Herbal medicines have been being used for years in other parts of the world. China in particular has been accustomed to alternative treatments for many common diseases. A Chinese medicine, Banxia Houpo Tang (BHT), in particular has been used in China to treat Parkinson’s disease. Banxia Houpo Tang consists of various plants: Pinellia ternata, Poria cocos, Magnolia obovate (bark), Perilla frutescens, and Zingiber officinale (Ginger) and in one study was used to test its efficacy in improving the swallowing reflex of PD patients. The swallowing reflex disorder is very common in patients with Parkinson’s disease. Medications such as Levodopa do not generally help with this problem, due to this not being a problem related to central dopaminergic stimulation. In this study, 28 PD patients had been evaluated for swallowing reflex and the concentration of substance –P in their saliva before and after 4 weeks of BHT treatment (Iwasaki, et. Al., 2000). These individuals were compared with five healthy controls of comparative age. They were divided into two different groups. One group of 22 individuals with PD and all healthy controls were given 1.5g of BHT and 6 PD patients were given 1.5 g of lactate. This was taken orally a half hour before each meal three times a day for four weeks. The swallowing
La Grenade-Finch 13 reflex was observed before and after, and evaluated by the latency period at three intervals each five minutes apart. The abnormally long delay of the swallowing reflex before treatment in both PD groups had a positive correlation to Hoehn and Yahr (H-Y) scores which were used to evaluate the reflex, and there was no significant difference in the H-Y scores of the two PD groups at that time. After four weeks of treatment with BHT, there was improvement with a reduced reflex time in the BHT treated group of PD patients, while the abnormally long reflex time remained unchanged/ unimproved in the PD patients who had taken lactate for four weeks. As expected, the controls had a normal reflex time before BHT treatment, and this remained unchanged after treatment (Iwasaki, et. Al., 2000). Therefore, BHT was shown to have a positive effect on the swallowing disorder associated with Parkinson’s disease.
Neuroprotective effect of methanolic extract of Hibiscus asper Although the exact causes of Parkinson’s disease are unknown, there are suggestions that indicate that brain aging, genetic predisposition, mitochondrial dysfunction, free radical production and environmental toxins all contribute to oxidative imbalance that occurs in individuals with Parkinson’s disease (Hritcu, et. Al., 2011). Neurodegeneration has also been linked to dietary habits as well. A lack of antioxidants and other supplements such as various vitamins and folic acid can all aid in neurodegeneration. Without antioxidants, the level of reactive oxygen species (ROS) increases to the point where it causes oxidative damage. In this study, the neuroprotective effects of methanolic extract of hibiscus leaves was being tested in rats with Parkinson’s disease. In particular the antioxidant and antiapoptotic actions of the methanolic extract of hibiscus asper leaves and its neuroprotective properties in the rat models used. Rats were divided into four groups: A. Control group (not lesioned) who
La Grenade-Finch 14 received saline B. 6-OHDA- lesioned group (negative control) which received saline treatment, C. 6-OHDA-lesioned group received 50/mg/kg of the methanolic extract of hibiscus asper leaves treatment, and D. 6-OHDA-lesioned group received 100 mg/kg of the methanolic extract of Hisbiscus asper leaves treatment. After neurological surgery (lesioning), the treatment was administered by injection for 7 consecutive days. Assays for Glutathione (GSH) were performed. Researchers found that leaves improved spatial memory deficits in the 6-OHDAlesioned model rodents. 6-OHDA leads to the production of both hydrogen peroxide and superoxide radicals which both lead to cell damage. Methanolic extract of Hibiscus asper leaves restored the activity of antioxidant enzymes (See Figure 5), GSH levels and decreased lipid peroxidation in the temporal lobe (Hritcu, et. Al., 2011). Overall, Hibiscus asper leaves improved symptoms of PD. Low dose and high dose of methanolic extract of hibiscus asper were found to improve PD symptoms.
Figure 5: Effects of the methanolic extract of Hibiscus asper leaves (50 and 100 mg/kg) on SOD (A), GPX (B), and CAT (C) specific activities in rat temporal lobe homogenates. Neuroprotective Effects of Acanthopanax senticosus Harms
La Grenade-Finch 15 The neuroprotective effects of plants other than Hibiscus asper have also been tested. In traditional Chinese medicine, Acanthopanax senticosus Harms is a widely used herb and in modern pharmacological experiments, it has been extracted and found to have some neuroprotective features, stress-protective and adaptogenic activities (Li, et. Al, 2013). Studies have been done to investigate the metabolic profiles and potential biomarkers in a mice model of methyl phenyl tetrahydropyridine (MPTP)-induced PD after treatment of Extract of Acanthopanax senticosus Harms (EAS) to try and understand the pathological changes of PD and anti-PD mechanisms of EAS. In this study, EAS was prepared with Acanthopanax senticosus Harms. Thirty mice were obtained and randomly divided into; the control group, MPTP model group, and EAS treated group with MPTP. The metabolites were then measured and it was found that EAS protects dopaminergic neurons in PD mice against apoptosis, induced by caspase. It was observed that metabolic abnormalities induced by MPTP were reversed after treatment with EAS. Several different biomarkers were also found to potentially be involved in the pathogenesis of PD, and that many of these biomarkers can be regulated by the EAS treatment. It was found that the therapeutic effects of EAS on PD may involve regulating the tyrosine metabolism, mitochondrial beta-oxidation of long chain saturated fatty acids, fatty acid metabolism, methionine metabolism, and sphingolipid metabolism (Li, et. Al, 2013). The overall conclusion is that the improvement seen with EAS treatment can be linked to the regulation and prevention of conversion of metabolic byproducts of the brain, into toxic isomers which are responsible for apoptosis (cell death) of dopaminergic neurons in Parkinson's disease.
Effect of Gingko Biloba on 6-hydroxydopamine-induced Parkinsonism
La Grenade-Finch 16 Other extracts of plants have been useful in the treatment of Parkinson ’s disease symptoms. Gingko biloba (EGb) is a potent antioxidant, capable of scavenging various reactive oxygen species that has been evaluated for anti-parkinsonian effects in 6-hydroxydopamine (6OHDA) rat model of the disease. Since, past evidence has suggested that immense oxidative stress, free radical formation, genetic susceptibility, and programmed cell death all have a role in the development of Parkinson’s, the potential antioxidant effects of Gingko biloba are important in treating PD (Ahmad, et.Al., 2005). During the following investigation of the effect of Gingko Biloba Extract (EGb), rats were treated with EGb 50, 100, and 150 mg/kg for three weeks after receiving 6-hydroxydopamine (6-OHDA) injections to simulate PD, along with similar EGb treatment in control rats. Three more weeks later, they were all tested for rotational behavior, locomotor activity, and muscular coordination, to confirm PD in the 6-OHDA rats. When the 6 weeks were up, the rats were killed and dopamine (DA) oxidative by-products of lipid peroxidation in the brain were measured. It was found that: 1. EGb treatment in rats with simulated PD decreased induced rotation and restored striatal dopamine (DA) and dopamine metabolites 2. EGb treatment increases the content of reduced glutathione (GSH) which removes excess free radicals in the brain and 3. EGb decreased the extent of lipid peroxidation, the cause of dopaminergic cell death/apoptosis(Ahmad, et.Al., 2005). All three of these effects of EGb therefore diminishes the level of oxidative stress in the brains of those with Parkinson’s disease while increasing the level of dopamine. This therefore makes for a very effective antioxidant treatment for Parkinson’s disease, despite the noted antiplatelet effects in the study.
Use of Complementary and Alternative medicine
La Grenade-Finch 17 As mentioned before, there is no real neuroprotective treatment in western or traditional medicine, that has been found to be therapeutic for symptoms of Parkinson’s disease, and although Levodopa is generally used as the treatment for PD, there are many motor complications that are associated with the progression of the disease. Problems such as freezing/rigidity, falling, speech disturbance, autonomic dysfunction, depression, and dementia all impair the quality of life and the functional status of PD patients. Because of this, many of these patients have turned to complementary or alternative forms of medicine (CAM), some of which have been discussed throughout this paper, to alleviate the symptoms of this disease. CAM refers to a group of diverse medical and health care systems, practices, and products that are not presently considered to be part of conventional medicine, including; oriental medicine, non-prescribed drugs, traditional food, traditional therapies, massage and behavioral therapies (Kim, et. Al., 2009). Asian countries such as Korea tend to use CAM, more than western countries. A study was recently conducted to evaluate the frequency of use, delineate the spectrum of use, and to identify factors influencing CAM utilization in Korean PD patients. 123 patients (42 men and 81 women) ranging in age from 34-83 years, were studied for five months. They were interviewed and filled out questionnaires. In the interview, patients were asked about current and past use of CAM for the management of PD. The associated costs, sources of information about the treatment, subjective effects and adverse effects associated with CAM were also discussed. They found that the mean age at onset of PD was 55.2 years and that the mean disease duration was eight years. The mean cost of prescribed medication was approximately seventy-three US Dollars per month. Sixty of these patients were using at least one form of CAM at the time of the interview with a mean cost of 67 USD per month. Seventy-
La Grenade-Finch 18 six percent used oriental medicines, forty-four percent used traditional foods, thirty-two percent used non-prescribed drugs, seven percent used traditional therapies, seven percent used massage and seven percent used behavioral therapy. 76.6 % of the 123 participants used oriental medicine which included herbs, acupuncture, buwhang, moxa and Koryo, and the second most common was traditional food used by 44.7% of 123 participants. 41.9% of participants had used CAM continuously since the onset of the PD symptoms. 32.2% of patients surveyed reported using CAM from the onset of PD symptoms to the time of diagnosis. 25.9% of patients had started CAM since the diagnosis of PD was made. CAM was used to treat a variety of their symptoms, including fatigue, pain, constipation,. However most (57.6%) reported using CAM primarily for management of the motor symptoms of Parkinson's disease. Only one patient reported using CAM to treat hallucinations and confusion related to the traditional anti-PD medications. 41.6% of patients reported improvement in the PD symptoms with CAM use, especially when acupuncture and massage therapy was used to alleviate pain and muscle stiffness. Only ten percent experienced adverse effects from CAM which included nausea and vomiting, limited movement, dyskinesia, and severe myalgia. 57.4% planned to continue their use of CAM after the interview , but only 16% of all patients had recommended CAM to other PD patients (Kim, et. Al., 2009). These results show that most who used CAM obtained some relief of their pain and stiffness , thus for these symptoms CAM may be a good alternate and/or adjunct to traditional medicines for Parkinson's disease.
Conclusion
La Grenade-Finch 19 According to current published works, it has not been possible to pinpoint one exact cause of Parkinson's disease. Rather, there is strong evidence linking several causal factors with several varying pathways to injury and eventual apoptosis (cell death) of dopamine-producing neurons within the brain. The end result is a deficit in dopamine production, causing a constellation of various symptoms and functional deficits, with varying times of onset centrally within the brain (cognitive/memory/conversational) and in organs distal to the brain (facial, postural, axial, musculoskeletal). Often, it is found that different causal factors may be involved in the pathogenesis of the disease within the same patient, making it impossible to find a single treatment that will take care of all of each patient's symptoms, or be medicinally palliative for everyone with Parkinson's disease. There is currently no cure, thus treatment is symptom-based and therefore must be individualized, so patients must rely on a combination of treatment methods to alleviate their individual symptoms as they arise. New traditional western medicines are on the horizon for the Parkinson's patient, however this paper has examined those most commonly used alone or in combination with other western methods of treatment. •
The most viable option today is Levodopa, treatment with which is meant to replace the deficient dopamine production within the brain. Its greatest benefit is improvement of sitting, standing, walking posture and general skeletal function in the Parkinson's disease patient, reducing the risk of stumbles and falls. Drawbacks occur when the drug is used alone on a long term basis however, since patients begin to experience significant side effects such as nausea, vomiting, gastrointestinal bleeding, difficulty breathing, anxiety, hallucinations, and drug-induced abnormal involuntary movements of the extremities, torso and neck, which can be just as or even more disabling than the symptoms of
La Grenade-Finch 20 Parkinson's disease itself. Another negative, is that treatment with Levodopa also does not improve the difficulty many Parkinson's disease patients eventually experience with delayed swallowing reflex and choking. •
Dopamine agonists when used in combination with levodopa have been shown to alleviate the side effects of abnormal involuntary movements caused by the latter drug. One such drug SK-609 when used in low to moderate doses has the benefit of also decreasing tremors at rest, decreasing skeletal rigidity, improving bradykinesia (slow movements) and reversing postural instability and risk of falls. The major drawback with this western medication is that extreme caution must be exercised in calculating individual patient dose, since when administered in higher doses it causes major seizures, and fatalities.
•
Another treatment method of western medicine, employs the use of subthalamic deep brain stimulation (STN-DBS), which has produced initial dramatic improvement in some Parkinson's disease patients, with complete reversal of tremors, postural imbalances and dyskinesia. The major drawback is that this appears to be only temporary, and as patients have been studied over longer periods of time, they have developed more severe irreversible post-procedure disabilities of speech disturbance, akinesia (loss of voluntary movement) and other postural and much worsened gait difficulties.
•
Anticholinergics, when used with deep brain stimulation temporarily abate the above post-procedure side effects of STN-DBS, but this is only temporary, and there is gradual deterioration in patients' postural and axial abilities over time .
La Grenade-Finch 21 Given the fact that most western treatment modalities improve some, but not all of the symptoms of Parkinson's disease, and over the long term can result in the development of significant side effects in patients, there is a place for the use of herbal (alternative) methods in the palliative treatment of symptoms of Parkinson's disease. •
Research has demonstrated that the Chinese herbal mix Banxia HoupoTang (BHT) consisting of various plants: Pinellia ternata, Poria cocos, Magnolia obovate (bark), and Zingiber officinale (Ginger), prevents choking by improving the swallow reflex in Parkinson's disease.
•
Studies using the herb Hibiscus asper, have demonstrated that in both high and low doses it exerts a biochemical neuroprotective effect which restores antioxidant enzymes and glutathione, while decreasing lipid peroxidation in the temporal lobe which houses the cognitive/memory center of the brain. The net effect is improved cognition in the Parkinson's patient.
•
The herb Acanthopanax senticosus Harms is also neuroprotective, via a different biochemical pathway. It regulates and balances the metabolism of tyrosine, methionine, and sphingolipid within the brain, thus preventing apoptosis of dopaminergic neurons. The net effect would be to halt or delay progression of the dopamine dependant (axial, postural, and kinesic) symptoms of Parkinson's disease.
•
Other studies have demonstrated that Gingko biloba is a powerful antioxidant which increases dopamine production and removes damaging excess free radicals from the brain. In doing so, it decreases the extent of lipid peroxidation which is a cause of dopaminergic neuronal cell injury and apoptosis (cell death). Gingko biloba must be
La Grenade-Finch 22 used with caution since it is known to exert an anti-platelet effect, and therefore can cause thinning of the blood with spontaneous bruising/internal bleeding in humans. A notable drawback to the use of the above herbal medicines is that although they have been used for centuries in non-western cultures quite effectively, there are not many published studies in English, and adverse side effects (or the lack of side effects) on human subjects have not been well described/delineated in the available English language literature. Finally, the combined use of Herbal medicines with complementary medical therapies (CAM) such as acupuncture, massage and behavior modification, was studied in a survey of patients with Parkinson's disease who had used this method. The results revealed that many patients who used CAM had gained some relief from their pain and stiffness, contributing to a greater sense of well-being. The conclusion therefore is that CAM, whether used in combination with Herbs or with western medicine can be of added benefit to the patient with Parkinson's disease, since only one out of ten reported any adverse side effects.
La Grenade-Finch 23
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