Neurology Presentation by Christopher Taylor

05/05/2011

Outline • • • • •

Neuroanatomy Thought Senses Movement Neurological disorders and pathology

Neuroscience Created by Daniyal Daud, Christopher Taylor, Edward Tam & Lorna Caulfield ©

What we won’t cover • • • • •

Nerve physiology Detailed anatomy (especially head/neck) Psychiatry – affect/psychosis Detailed musculoskeletal anatomy/physiology Endocrinology – thyroid/parathyroid

NEUROANATOMY

Anatomy – quick overview

Cortex Longitudinal fissure

Pre-central gyrus Post-central gyrus Central sulcus

Left cerebral hemisphere

Right cerebral hemisphere

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Cortex Optic Chiasm

Histology of the cortex I: dendron-axon interactions II: Intracortical connections III: give rise to commissural/ association fibers IV: receive thalamic afferents V: project to subcortical structures VI: project to cortical/ subcortical areas

Olfactory bulb Olfactory tract

Mammillary bodies

Pituitary gland & infundibular stalk

Uncus Parahippocampal gyrus

Cerebral peduncles Pons

Medullary olives Medulla (pyramids)

Left cerebellar hemisphere

â&#x20AC;&#x153;Brainstemâ&#x20AC;?

Spinal cord

Subcortical structures

Subcortical structures - brainstem

Cerebellum

Amygdala

Mammillary body

Crus Cerebri

Sup. cerebellar peduncle Sup. colliculus Midbrain

Thalamus

Inf. colliculus

Pons Middle cerebellar peduncle Pyramids Olives

CN IV Pons

Medullary olive Pyramid

Cerebellar peduncles

Primary Horizontal fissure fissure

Cerebellar hemisphere

Floor of 4th ventricle Flocculonodular Flocculus lobe Nodulus

Vermis Inferior view

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Brainstem and cerebellum

Cranial nerves

• Cortex attaches to brainstem at crus cerebri (cerebral peduncles) • Brainstem has

1 – Olfactory (bulb and tract) 2 - Optic

– nerve fibers (tracts) going to and from cerebrum/cerebellum – Cell bodies (nuclei) of ten cranial nerves: CN 3 – 12 – Reticular formation and respiratory center

• Cerebellum attaches to brainstem via three peduncles • Basal ganglia buried in the cortex, have connections

3 - Oculomotor 4 – Trochlear (dorsal) 7 - Facial

5 - Trigeminal

8 – Vestibulocochlear 6 - Abducens

9 - Glossopharyngeal

10 - Vagus 12 - Hypoglossal

11 - Accessory

C1 spinal nerve

Foramina of skull

What passes through • • • • • • • • • •

Superior orbital fissure

Jugular Foramen Hypoglossal canal

Blood supply • Two systems

ACA

– Vertebro-basilar (~posterior) Circle of Willis MCA – lateral and deep ACA/PCA – medial and deep Strokes are territorial

MCA

PCA

Optic chiasm Posterior comm. artery MCA

CN III Superior Cerebellar Artery

– Carotid (~anterior)

Optic nerve CN 3, 4, 5a, 6 Maxillary branch of 5 Mandibular branch of 5 Middle Meningeal Artery Internal Carotid Artery CN 7 and 8 Jugular vein, CN 9, 10, 11 CN 12 Spinal cord

Blood supply – circle of Willis

Lenticulo -striate Internal Carotid

• • • •

Optic canal Superior Orbital Fissure Foramen rotundum Foramen ovale Foramen spinosum Foramen lacerum Internal acoustic meatus Jugular foramen Hypoglossal canal Foramen Magnum

Communication between ‘anterior’ and ‘posterior’ systems • Ensures backup if one fails • Aneurysms can occur – Proximity to cranial nerves - implications?

Basilar Artery Vertebral artery Posterior Cerebral Artery

Anterior Inferior Cerebellar Artery

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Spinal cord

Peripheral nervous system

Dorsal horn Dorsal roots

Central canal Lateral horn

Anterior fissure Ventral horn Ventral roots Pia mater Arachnoid mater Dura mater

Chemical Neurotransmission

THOUGHT

Noradrenergic pathways • Cell bodies of noradrenergic neurons: – Locus ceruleus (“blue spot”) – Lateral tegmental area

• Projections to – Cortex – Spinal cord – Hippocampus – Hypothalamus

• One way that neurons communicate (other: electrical synapse with gap junctions) • Precursors • Synthesis by enzymes • Stored in vesicles • Electrical signal arrives along membrane  Ca++ channels open • Chemical release • Binds receptor • (Deactivated by enzymes) • Reuptake into presynaptic cell • Degraded by enzymes

Dopaminergic pathways • Cell bodies of dopaminergic neurons: – Substantia nigra compacta (“black stuff”) – Ventral tegmental area – Hypothalamus

• Projections to: – Striatum (nigrostriatal, mesolimbic) – Frontal lobe (mesocortical) – Anterior pituitary (tuberoinfundibular)

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5-HT pathways

Cholinergic pathways

• Cell bodies of serotonergic neurons:

• Cell bodies of cholinergic neurons:

– Raphe (“seam”) nuclei in pons, medulla, midbrain

• Projections to – Cortex – Hippocampus – Hypothalamus – Spinal cord (pain)

Explicit/ declarative Semantic

– Nucleus basalis of Meynert – Pedunculopontine nucleus – Medial septal nuclei

• Projections to – Cortex – Hippocampus – Thalamus

Memory

Memory Implicit

Episodic

Skills/ procedures

Priming

Classical conditioning

• Explicit memory – what you can describe – Episodic – events e.g. Memory of your 18th birthday – Semantic – facts/figures e.g. Capital of Bulgaria? – Hippocampus (“sea horse”) and mammillary bodies important

• Implicit memory – what you can’t describe (easily) – Learnt procedures e.g. Fastening a button – Conditioned responses e.g. Pavlov’s dogs

• Stored throughout cortex • Memory in one sensory modality stored in its association areas (e.g. tune of Lady Gaga’s Paparazzi) • Medial temporal lobe – hippocampus and parahippocampal regions – Crucial in forming new memories – anterograde amnesia (Memento)

• Long-term potentiation (LTP) – one mechanism of learning

Long-term potentiation • Regular coincidental activity at a synapse  more efficient at doing said activity • Requires NMDA receptors (glutamate Ca++ entry) • Ca++ upregulates AMPA receptors – Now post-synaptic cell is stimulated more easily

SENSE Repeated stimulation

• Stimulus-response association formed • See also: long-term depression

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Sensory physiology - basics

• Peripheral receptors

– Concept of receptive field: “territory” of a neuron. A stimulus presented in the field changes the neuron’s firing rate

• Pathway from peripheral to central – – – –

Tracts (fibers) ~ road trip Nuclei (cell bodies) ~ rest stops along the way Convergence As order of neuron increases, receptive field gets larger & more complex

• Central representation: cortical area dedicated to the sense e.g. V1, S1, A1 • Cortical centers can also change what we sense (central  peripheral pathway)

Somatosensation – dorsal columns

Somatosensation • Submodalities – Fine discriminatory touch, vibration, proprioception – Crude touch, pain, temperature

• Peripheral mechano-receptors, nociceptors, stretch receptors • Sensory fibers back to spinal cord – cell bodies in dorsal root ganglion

Somatosensation - spinothalamic

VPL thalamus

• First synapse in Lamina II • Immediate decussation • Go up in the crescent-shaped anterolateral pathway •  VPL thalamus  S1

Somatosensation - head Mesencephalic nucleus

Chief sensory nucleus

•

• • • •

Separate pathway for pain (similar to rest of body) Separate pathways for proprioception and touch (c.f. rest of body) Decussation of 2˚ neurons within brainstem Travel up to ventral-posterior-medial thalamus (lateral for rest of body) NB – tongue somatosensation carried by V3 (lingual nerve) & CN 9

Somatosensation - summary Trunk and limb • Fine touch, proprioception, vibration – Dorsal columns (gracile and cuneate fasciuli) to nuclei – Decussate and then up via medial lemniscus to thalamus

• Crude touch, pain, temperature – 2˚ neurons start in spinal cord gray matter & decussate immediately – Up to thalamus via spinothalamic (or anterolateral) tract

Spinal tract of V nucleus

Head: Trigeminal, Glossopharyngeal, Vagus nerves • Fine touch: Chief sensory nucleus • Pain/temperature: Spinal nucleus of V • Proprioception: Mesencephalic nucleus

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Vision - retina

• Rhodopsin (orange blob) inactive in the dark. Associated Na+ channel open – “dark current” • Cell depolarized – continuous Glu release • Light changes conformation of the retinal in rhodopsin • Na+ channel closes • Cell HYPERPOLARIZES • Glutamate release stops • Therefore phototransduction occurs by hyperpolarization (c.f. normal excitation)

5 layers, 7 types of cells • Vertical connections relay signal Photoreceptor Bipolar cell Retinal ganglion cell

• Horizontal connections (amacrine, horizontal cells) modify signal

Light

Vision – optic nerve

• Nasal fibers from both eyes decussate at optic chiasm, temporal don’t • Lesion of chiasm - ?

Temporal Nasal

cGMP

Photoreceptor cell

Glutamate release

Light

• Optic tract – fibers looking at opposite side of world • Some go to superior colliculus (tectum – “roof”) & pretectum • Most synapse on to lateral geniculate (“knee-like”) nucleus of thalamus • LGN projects to visual cortex via optic radiation • V1 a.k.a ‘striate’ cortex • Topsy-turvy organization

Optic nerve Chiasm Optic tract

LGN Optic radiation Visual cortex V1

Vision - summary

Vision - cortex

• Retina: “phototransduction” – conversion of light signals to electrical impulses

• Visual processing in V1 • Signal passed on to related areas • Two ‘streams’ – Dorsal: perceives spatial aspects e.g. Motion, depth, orientation – occipitoparieto-temporal function – Ventral: perceives descriptive details of object e.g. Color, shape – E.g. driving

trans-retinal 11- cis-retinal

Vision – central pathway

• Each eye looks at both sides of the world – Nasal retina – outer half of world on same side as eye – Temporal – inner half on other side

Na+

Dorsal stream

– Importantly: rods/cones  bipolar cells  ganglion cells – Vertical relay signal, horizontal modify it

• Ganglion cell axons = optic nerve – Axons from nasal half of retina cross over at optic chiasm – After chiasm, the axons ‘looking’ at one side of space are all on the other side of the brain Ventral stream

• Axons synapse on Lateral Geniculate Nucleus (thalamus) • LGN sends fibers to V1 – visual processing • Dorsal & ventral streams for further processing

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Bony Labyrinth

Hearing REISSNER’S MEMBRANE

SCALA MEDIA

SCALA VESTIBULI

Hearing - Frequency analysis 1. Sound enters the cochlea

ORGAN OF CORTI

2. Basilar membrane vibrates SCALA SCALA TYMPANI TYMPANI

TECTORIAL MEMBRANE

BASILAR MEMBRANE

Hearing - Frequency analysis

Organ of Corti

3. Frequency of sound determines position of maximal displacement BASE •High sounds

APEX •Low sounds

4. Displacement excites hair cells

• Bend towards • Bend towards TALLEST stereocilia SHORTEST stereocilia + • Increased K inflow • Decreased K+ Inflow = = DEPOLARISATION HYPERPOLARISATION

Inner hair cells Depolarisation Voltage gated Calcium Channels OPEN

RELEASE OF NEUROTRANSMITTER

Activation of Cochlear Nerve

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Information from Cochlear nerve

Outer Hair Cells • Shorten and lengthen in response to sound stimuli – PRESTIN

Medulla

• AMPLIFY Basilar Membrane movement

Midbrain

• Antibiotics • Aminoglycosides

Thalamus

DORSAL

3. INFERIOR COLLICULUS

4. MEDIAL GENICULATE BODY

Temporal lobe

Auditory pathway Transverse gyri of Heschl (A1)

2. SUPERIOR OLIVARY COMPLEX

4. MEDIAL GENICULATE BODY 5. AUDITORY CORTEX

Midline

• Change length when hairs bend

1. COCHLEAR NUCLEUS

5. AUDITORY CORTEX

Speech and language BROCA’S AREA

WERNICKE’S AREA UNDERSTANDING

PRODUCING LANGUAGE

LANGUAGE Thalamus

Medial geniculate nucleus Inferior colliculus

Midbrain

Pons Pons

Superior olivary nucleus

Cochlear nucleus

RECEPTIVE APHASIA

EXPRESSIVE APHASIA

Medulla

Summary • Cochlea • Frequency analysis: ‘where’ on basilar membrane = identity of frequency • Hair Cells: peripheral receptors of hearing • Auditory Pathway: brainstem, midbrain, thalamus and cortex • Speech: Broca’s & Wernicke’s

Smell • Olfactory receptor cells above superior turbinate in nose • Metabotropic receptors for shapes of chemicals • Signal goes up into olfactory bulb and via olfactory tract to cortex Olfactory receptor cell

Mitral cell (olfactory tract)

Thalamus Piriform cortex Amygdala

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Taste

• Receptor cell bears receptor for one kind of taste • Taste bud = all kinds of receptor cells • Some ionotropic (Na+, H+) some metabotropic • Chorda tympani (CN 7) & CN 9 carry impulses to solitary tract nucleus in brainstem • VPM thalamus • Cortical representation in insula/operculum (“lid”)

Movement What do I need to make a purposeful movement? • Will to move (Prefrontal cortex) • Plan and preparation (Pre-motor areas) • ‘Permission’ to move (Basal ganglia) • Raw command to muscles (Motor cortex) • Coordination & fine tuning (Cerebellum) • Final command to muscles (spinal cord) • Muscles(!) • Sensory feedback (vision, proprioception...)

MOVEMENT

Motor regions of the cortex

• Primary motor cortex (red)

– Represents contralateral half of body

• Premotor cortex & supplementary motor area (bright orange and yellow) – Planning movement, ‘getting into position’ for an action

• Frontal eye fields (brown) – Eye movements: complex & different from other movements

• Posterior parietal motor area (tan) – Sensory feedback: origin of majority of corticospinal fibers

Motor cortex - homunculus • Similar layout to somatosensory homunculus • Greater representation of hands & fingers – For dexterity/fine control

• Lower limbs medial – Not affected by MCA stroke, but ACA stroke would affect them

Corticobulbar tract

• Upper motor neuron fibers from cortex to cranial nerve nuclei • Bilateral innervation except – Lower facial nerve nucleus (only contralateral)

• Decussate BEFORE, not AT the pyramids! • Lesion - ? – Paresis (not total paralysis) of muscles: pseudobulbar palsy

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Lateral Corticospinal Tract

Corticospinal tracts

• Upper motor neuron fibers from cortex to trunk & limb lower motor neurons (LMNs) • Fibers to

Cortex Internal capsule

Sends signals for fine, delicate movements in distal muscles

Crus cerebri

– limb LMNs ≈ Lateral CSTs: dextrous movements – trunk LMNs ≈ Ventral CSTs: postural control

Basal pons Lower medulla

• VCST fibers from one hemisphere go bilaterally • LCST from one hemisphere goes only contralateral: pyramidal decussation

LCST

Descending Pathways

Corticoreticulospinal tract - Muscle tone specific for movement - Breathing

Basal Ganglia VL nucleus of Thalamus

Caudate Putamen

Corpus Striatum – “striped body”

Globus pallidus externa

Subthalamic nucleus

Basal ganglia - loops Direct loop

Direct & Indirect Loops

Premotor & motor Cortex Striatum

Striatum

D1 VPL Thalamus GPi / SNr

Similar structure & function

Indirect loop

Premotor & motor Cortex

SNc

Substantia nigra pars compacta

Globus pallidus interna Substantia nigra pars reticulata

SNc

VPL Thalamus

GPe STN

GPi / SNr

excitatory inhibitory

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Cerebellum

Cerebellum – connections • Superior peduncle:

– Afferent: spinocerebellar – Efferent to basal ganglia & thalamus

• Middle peduncle – Afferent only: olivo/pontocerebellar

Evolution

Anatomy

Afferents

Function

Archicerebellum

Flocculonodular lobe

Vestibulocerebellum

Stability

Paleocerebellum

Vermis & paravermal areas

Spinocerebellum

Muscle tone & posture

Neocerebellum

Cerebellar hemispheres

Cerebro-cerebellum

Motor coordination

• Inferior peduncle – Afferent: vestibulocerebellar – Efferent: Cerebellovesitublar

Cerebellum – basic physiology Mossy fiber

Gray matter

Granule cells Parallel fiber

White matter

Input

Climbing fiber

Purkinje cell

Cerebellar nucleus

Brainstem & thalamus

Cerebellar nuclei

• Mossy:

– Spinocerebellar – Vestibulocerebellar – Pontocerebellar

• Climbing: olivocerebellar • Purkinje cells coordinate input and output • Output to 3 groups of deep nuclei: – Fastigial – Interposed (globose & emboliform) – Dentate

DIAGRAM KEY: PMC = premotor cortex M – I = primary motor cortex VLp = posterior division of ventral lateral nucleus of thalamus CC = cerebrocerebellum SC = spinocerebellum VC = vestibulocerebellum D = dentate nucleus G/E = interposed nuclei (globose and emboliform nuclei) F = fastigial nucleus RetN = reticular nucleus VN = vestibular nucleus

Locomotion

• Multi-step process (pun intended) • Central pattern generators • Stance: lower limb in contact with ground (60%) – Heel strike – Mid-stance – Push off

• Swing: lower limb not in contact with ground (40%)

NEUROLOGICAL DISORDERS & PATHOLOGY

– Acceleration – Deceleration

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Parkinson’s Disease (PD)

Parkinson’s Disease • • • •

100 per 100,000 population affected Male > Female Age - Risk 2nd commonest neuro-degenerative condition – 1st = Alzheimer’s

• Cause(s) unknown! • Possibly: – Genetic – Environmental (pesticides)

Pathophysiology

• Protein misfolding & aggregation in SNc – α-synuclein – Blocks normal function – Build-up of cellular debris (‘rubbish’) – Puts stress on mitochondria – Finally: cell death

• Similar pathophys. in other neurodegenerative conditions

Basal ganglia loops in disease Premotor & motor Cortex Striatum D2 Lewy body in dopaminergic neurons in the nigrostriatal pathway

• Hypokinetic disorder: – Bradykinesia – “slow movement” – Resting tremor – ‘Lead-pipe’ rigidity

• Symptomatic when 80% of dopaminergic neurons lost – Unilateral onset

• Progressive deterioration

VPL Thalamus

SNc GPe

– Alzheimer’s – amyloid-ß – Huntington’s - huntingtin – Fronto-temporal Dementia - tau

Clinical features

STN

GPi / SNr

Other features Motor • Gait disorder: – Short, shuffling steps – ‘Broken’ turn – Loss of arm swing

• Postural instability • Balance • Micrographia – “small handwriting”

Non-Motor • Neuropsychiatric – Depression – Dementia – Visual hallucinations

• Sleep disturbance • Anosmia

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Treatment

Headaches

• Increase dopamine levels in brain – L-DOPA – Dopamine agonists – Stimulation of dopamine production – Stop breakdown of dopamine

• Stop indirect loop overactivity – Deep brain stimulation of subthalamic nucleus

Drowsiness/ coma

‘Thunderclap headache’ Collapse

Alcohol Smoking

Hypertension

CN palsy

Risk Factors

Clinical Features

Hemiplegia

Subarachnoid Haemorrhage

Neck stiffness

CT scan (bleed)

Spontaneous bleeding in subarachnoid space

Migraine

all over

unilateral

Quality

pressure

throbbing

Triggers

yes

usually not

yes

Clinical Features

Photo/phono phobia

Photophobia

usually not

yes

Phonophobia

usually not

yes

no effect

aggravated

Mechanism

Prophylaxis Pizotifen (5-HT anatagonist)

Vomiting

•Bending •Coughing/ sneezing •waking

Subdural haematoma

Causes

Clinical Features

Drowsiness

Cerebral oligaemia from arteriole constriction

Propranolol

Papilloedema Focal neurology

Seizures

Changes in plasma 5-HT

Migraine

unilateral

Headache on:

Movement

Cheese

Triggers Nausea +/vomiting

Irritation of meninges

Tension headache

Nausea

Alcohol

Caffeine

Aura Bleeding Disorders

Location

Aura

Sensory e.g. spreading parasthesia

Mechanism

Investigations Lumbar puncture (bloody or yellow)

Visual e.g. dots+spots/ zig-zag lines

Space Occupying Lesion NOT Lumbar puncture ( herniation through foramen magnum)

Primary or Secondary tumour

CT scan

Investigations

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Petechial rash

N. meningitidis S. pneumoniae

Decreased conscious level

Seizures

•Opthalmic artery obstruction

Cause

Organisms

Clinical Features Photophobia

Age>55

Temporal Artery Inflammation

Hx proximal limb pain (polymyalgia rheumatica)

H. influenzae

Meningitis

Amaurosis fugax

L. monocytogenes

Clinical Features

Jaw claudication

Neck Stiffness

Treatment

Scalp tenderness

Giant Cell Arteritis

Temporal artery biopsy

Investigations Treatment

Broad spectrum antibiotics

Epilepsy

ESR + CRP Steroids

Epilepsy • Tendency to have seizures • Seizure = transient abnormal activity due to synchronous firing of brain neurons • Classification of seizures – Generalized: Entire cerebral cortex involved  loss of consciousness – Partial: Focused in one area – Partial with secondary generalization – Functional

Epilepsy - generalized Grand mal (tonic-clonic) seizure • Aura/prodromal symptoms before • Shaking, frothing at the mouth • Loss of consciousness • Hyper excitable neurons: – Structural lesion – ion channel dysfunction – Infection – Trauma

Epilepsy Petit mal epilepsy (‘typical absence’) • More common in kids • Stop talking mid-sentence and stare into space • Eye twitch, muscle jerk (myoclonus) • Lasts ~ seconds • 3 Hz EEG waves during attack • Dysfunctional thalamic control of cortex • May go on to develop grand mal epilepsy in adulthood

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Epilepsy

Simple partial epilepsy • Restricted to one cortical area e.g. motor cortex • Symptoms reflect function of the affected area – Jacksonian epilepsy: electrical activity spreads across homunculus  contralateral limb jerking – Occipital lobe seizures: lights/colors, visual hallucinations

• Cause: often a structural lesion or abnormal neurodevelopment

Complex partial epilepsy • Usually temporal lobe affected – “Absence attack” – unaware of surroundings – Aura/prodrome of déjà vu – Stereotypical movements e.g. lip smacking

• Cause – structural lesion e.g. arterio-venous malformation – CNS inflammation

• DO NOT CONFUSE WITH ‘typical absences’ i.e. petit mal seizures

Epilepsy - summary • Brain neurons sensitive to agitation – Infection, inflammation, injury, malignancy, scar tissue…

• Classification of epilepsy:

THANKS FOR LISTENING!

Epilepsy Generalized Grand mal

Petit mal

Partial Partial with 2° generalization

Simple partial

Complex partial