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2nd Year - Systems 3 > Neuro 2 - motor control, movement disorders and stroke > Flashcards

Neuro 2 - motor control, movement disorders and stroke Flashcards

1
Q

Cranial nerves

A

Most have both sensory and motor function
All, except I and II, have nuclei in brainstem
In brainstem, arranged in 3 motor and 3 sensory columns
Functionally specific, can have more than one function

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2
Q

Special somatic afferent (SSA) cranial nerves

A

Vision - optic

Auditory and vestibular - vestibulocochlear

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3
Q

Named cranial nerves

A 
Olfactory
Optic
Occulomotor
Trochlear
Trigeminal
Abducens
Facial
Vestibulocochlear
Glossophrayngeal
Vagus
Accessory
Hypoglossal
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4
Q

Special visceral afferent (SVA) cranial nerves

A

Taste - vagus, glossopharyngeal, facial

Olfaction - olfactory

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5
Q

General somatic afferent (GSA) cranial nerves

A

Skin, muscles, joints - vagus, glossopharyngeal, facial, trigeminal

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6
Q

General visceral afferent (GVA) cranial nerves

A

Viscera of head, thorax, abdomen - vagus, glossopharyngeal

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7
Q

General somatic efferent (GSE) cranial nerves

A

Tongue - hypoglossal

Eye muscles - abducens, trochlear, occulomotor

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8
Q

Special visceral efferent (SVE) cranial nerves

A

= Branchial motor (BM), skeletal muscle dervied from branchial arches

Mastication - trigeminal
Facial expression, middle ear - facial
Pharynx, larynx - glossopharyngeal, vagus
Sternocleidomastoid, trapezius - accessory

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9
Q

General visceral efferent (GVE) cranial nerves

A

Parasympathetic neurones for cranial, thoracic and abdominal viscera

Lacrimal and salivary glands (not parotid) - facial
Pupil constrictor, ciliary muscle - occulomotor
Parotid gland - glossopharyngeal
Heart, lungs, digestive tract - vagus

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10
Q

Optic nerve (II)

A

Associated only with special senses

  • axons from ganglion cells in retina
  • vision

If damage optic nerve, earlier, complete blindness in that eye
If damage optic tract (after chiasm), field vision loss - lose medial field in eye opposite, lose lateral field on this side

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11
Q

Vestibulocochlear nerve (VIII)

A

Associated only with special senses

  • axons from spiral ganglion of cochlear and vestibular ganglion in inner ear
  • hearing and position sense

Loss of vestibular inputs - ataxia, loss of balance, nystagmus
Loss of auditory inputs - loss of hearing on side of affected

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12
Q

Olfactory nerve (I)

A

Only special visceral afferent
- axons from olfactory mucosa
- olfaction
Damage -> anosmia

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13
Q

Occulomotor nerve (III)

A

Only motor function (GSE)

  • somatomotor to all eye muscles except LR6SO4
  • visceromotor, parasympathetic to smooth muscles in eye (ciliary and iris)

Damage -> inability to move eye in or up (down and out gaze), lateral strabismus of one eye (crossed eyes), ptosis

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14
Q

Trochlear nerve (IV)

A

Only motor function
GSE- somatomotor to superior oblique eye muscle
GVE - visceromotor to pupillary constrictor

Damage -> vertical diplopia (double vision), head tilt, hypertropia (maladjustment) of right eye when performing left gaze

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15
Q

Abducens nerve (VI)

A

Only motor function (GSE)
- somatomotor to lateral rectus eye muscle

Damage -> can’t look laterally, medial strabismus (crossed eyes)

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16
Q

Hypoglossal nerve (XII)

A

Only motor function (GSE)
- somatomotor to muscles of tongue, extrinsic (except palatoglossus) and intrinsic

Damage -> tongue deviates to side of lesion

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17
Q

Trigeminal nerve (V)

A

Sensory and motor pathways

SENSORY
Opthalmic - V1 - orbit to forehead
Maxillary - V2 - upper jaw to orbit
Mandibular - V3 - lower jaw

MOTOR
V3 only - muscles of mastication

Upper motor neurone lesion -> no deficit in jaw movement
Lower motor neurone lesion -> deviation of mandible to ipsilateral (weak) side

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18
Q

Facial nerve (VII)

A

Sensory and motor pathways

MOTOR (SVE)

  • muscles of facial expression
  • stapedius muscle (dampen sound in ear)
  • part of digastric
VISCERAL SENSORY (SVA)
- taste from anterior 2/3 tongue

GENERAL SOMATIC SENSORY FUNCTION (GSA)
- small region near external auditory meatus

PARASYMPATHETIC (GVE)
- secretory glands in head - lacrimation, nasal secretions, salivary glands

(Two Zebras Bit My Clavicle - temporal, zygomatic, buccal, mandibular, cervical)

Upper motor lesion -> bottom half of face (contralateral) can’t move, forehead sparing
Lower motor lesion -> whole half face (contralateral)

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19
Q

Vagus nerve (X)

A

Sensory and motor pathways

SENSORY
- viscerosensory from organs in thorax and abdomen

MOTOR

  • innervation of some in pharynx and larynx
  • parasympathetic to organs in thorax and abdomen
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20
Q

Accessory nerve (XI)

A

Sensory and motor pathways

Two motor components - cranial root to muscles in larynx and pharynx, spinal root to muscles in neck

Sensory info very small, about pain

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21
Q

Motor neurones in spinal cord

A

Spinal cord enlarged at levels where motor neurones for limbs are located - not uniform
Sensory input to dorsal horn, synapse through ventral horn -> motor
Position in ventral horn depends on type and location of muscle innervated - medial for trunk, lateral for limbs and distal muscles

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22
Q

Alpha motor neurone inputs

A
  • lower motor neurone (as with gamma)

FROM:

  • sensory input from muscles
  • input from upper motor neurones to initiate and control voluntary movement
  • interneurones (excitatory or inhibitory) to form circuits that produce coordinated movements
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23
Q

Types of somatic motor neurone

A

ALPHA

  • large, multipolar neurones
  • cell bodies in ventral horn of spinal cord, originate here
  • terminate at NMJ or end plates
  • innervate extrafusal muscle fibres, skeletal muscle

GAMMA

  • smaller neurones
  • cell bodies in ventral horn of spinal cord, originate here
  • innervate specialised striated muscle fibres (intrafusal)
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24
Q

Motor unit

A

= alpha motor neurone + all innervated muscle fibres

One alpha motor neurone to several muscle fibres, each muscle fibre only one neurone

All alpha motor neurones innervating a muscle = motor neurone pool

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25
Q

Muscle spindles

A

Sensory neurones in muscle spindle encode info on muscle length - moitor extent of stretch and rate of change of length
Intrafusal fibres in parallel
Ia and II afferents

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26
Q

Lower motor neurones innervated by two different mechanisms

A

SUPRASPINAL MOTOR CIRCUITS
- volitional control over movement

SPINAL CORD REFLEX

  • rapid, automatic, stereotyped response
  • couples sensory input to motor output
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27
Q

Types of reflex

A

Monosynaptic - simplest, controls muscle length
Golgi tendon - controls muscle tension
Flexor/withdrawal reflex - rapidly remove limb from painful stimulus
Crossed extensor reflex - maintains body equilibrium

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28
Q

Monosynaptic reflex

A

Sensory receptor, sensory neurone, integrating centre (one synapse in ventral horn), motoneurone, effector muscle or gland

Still need antagonistic muscle pair to relax in response, otherwise muscles would snap - RECIPROCAL INNERVATION

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29
Q

Myotatic reflex

A

= stretch reflex, type of monosynaptic

Weight added to muscle
Transient elongation of muscle
Spindle stretched, neurones fire
Alpha motor neurones fire
Muscle contraction

To maintain tone, prevent muscular damage due to overlengthening
eg patellar tendon reflex
- if weak or absent, lower motor neurone lesion?
- if exaggerated, upper motor neurone lesion?

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30
Q

Gamma motor neurones

A

= fusimotor neurones
To adjust sensitivity of muscle spindles

When muscle contracts, spindle becomes slack, so no sensory info from spindle
Gamma motor neurone activation contracts muscle spindle fibres, so can now respond to eg changes in load weight

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31
Q

Golgi tendon

A

Skeletal muscle tendons contain mechanoreceptors
- golgi tendon organs

Ib sensory neurones in golgi tendon organ encodes info on muscle tension
Inhibit alpha neurones running to muscle of origin

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32
Q

Golgi tendon reflex

A

Muscle tension
Golgi tendon organ activated
Sensory Ib afferemt excoted
Spinal cord activates inhibitory interneurone to same muscle, and activates excitatory interneurone to antagonistic muscle
Motoneurone excited
Effector muscle relaxes, antagonistic muscle contracts

  • protect muscle from producing too much tension and tearing or breaking tendons
  • fine control of tension for grasping fragile objects
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33
Q

Felxor/withdrawal reflex

A

Nociceptor afferents excited
Spinal cord interneurones activate, excite flexor motoneurones
- rapidly withdraw body from painful stimulus
- needs synergy, muscles to work together to remove entire limb

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34
Q

Crossed extensor reflex

A

To maintain balance, eg after withdrawal reflex

- eg strengthen leg standing on, inhibit extensors in leg withdrawing

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35
Q

Central pattern generator

A

Neurones enable oscillations in movement - as one set neurones fire, others stop
To generate rhythmic motor activity

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36
Q

Convergence

A

Termination of several neurones onto one other neurone

  • two nerves activated, subliminal fringes overlap = facilitation zone
  • more motor neurones excited so bigger response, FACILITATION

(Repetitive stimulation of one nerve -> temporal summation)

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37
Q

Types of interneuron

A

INHIBITORY INTERNEURONE
- activated by primary afferent
- inhibit alpha motor neurone
- inhibit contraction of associated muscle
EXCITATORY INTERNEURONE
- activate gamma or alpha motor neurone
- synapse onto intrafusal muscle fibre to increase sensitivity of spindle
RENSHAW CELLS
- inhibitory interneurones
- activated by alpha motor neurones
- inhibits alpha motor neurones, negative feedback
- also inhibit interneurones and gamma motor neurone
- governors, prevent muscle damage from tetanus

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38
Q

Jendrassick manouvre - to condition reflex

A

Exaggerates lower limb tendon reflexes

  • voluntary upper motor neurone innervation of arm overflows, to increase excitability of lower motor neurone pool in lower limbs
  • > increased fusimotor drive
  • > increased amplitude of reflex
  • counteracts some normal descending inhibition from brain
  • modulates interneuron excitability, so removes inhibitory action on late component of stretch reflex
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39
Q

Primary motor cortex - homunculus

A

Region where movement can be evoked with least amount of electrical stimulus
Pre-central gyrus, Brodmann’s area 4
(not 100% true, there are clusters, needed for coordination)

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40
Q

Supplementary motor area

A

= SMA
Medial surface of hemisphere, anterior to primary motor cortex
Medial part of Brodmann’s area 6

SMA PROPER
- contains somatotopic map
- contributes to corticospinal tract
- interconnected to other motor areas
PRE-SMA
- not well connected to other motor areas
- connected to pre-frontal cortex
  • for more complex, purposeful movements, eg vocalisation and complex postural movements
    (transforms kinematic to dynamic info)
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41
Q

Pre-motor area

A

Rostral to primary motor cortex
Two functionally distinct subdivisions - dorsal and ventral
- somatotopically organised
- preparation for movement

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42
Q

Cingulate motor area

A

In cingulate sulcus

  • somatotopically organised
  • preparation and execution of movements
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43
Q

Descending control of motor pathways

A

To innervate alpha, gamma motoneurones, and interneurones
Motor neurones topographically organised in ventral horn - flexors more posterior than extensors
- distal more lateral than proximal

Two major groups:

  • Lateral pathways
  • Medial pathways
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44
Q

Lateral pathways in descending control of motor

A

Controls both proximal and distal muscles
Responsible for most voluntary movements of arms and legs
- Lateral corticospinal tract
- Rubrospinal tract

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45
Q

Medial pathways in descending control of motor

A

Controls axial muscles (core)
Responsible for posture, balance, coarse control of axial and proximal muscles
- Vestibulospinal tracts (lateral and medial)
- Reticulospinal tracts (pontine and medullary)
- Tectospinal tract
- Anterior corticospinal tract

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46
Q

Lateral corticospinal tract

A

Main descending motor pathway
Motor cortex to spinal cord
- fibres form bulge on ventral surface of medulla, = pyramids
- fibres decussate at medulla-spinal cord junction - is the 90%
Innervate motor neurones in ventral horn of spinal cord
Controls muscles of distal limbs
Essential for fine movement of limbs
VOLUNTARY

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47
Q

Anterior corticospinal tract

A

Smaller than lateral pathway
Motor cortex to spinal cord
- is 10% of CST that doesn’t decussate in medulla, instead at spinal cord. Some still don’t decussate so are ipsilateral (minor) -> bilateral innervation for coordination
Controls muscles of trunk

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48
Q

Corticonuclear = corticobulbar tract

A

Motor cortex to brainstem nuclei
Voluntary motor functions of head, neck, face
CRANIAL NERVES
- most nuclei bilateral innervation from cortex except facial and hypoglossal

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49
Q

Rubrospinal tract

A 
Small, role unimportant in humans
Originates in red nucleus
Decussates immediately
(travels alongside lateral CST)
Voluntary movements of upper limbs only
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50
Q

Vestibulospinal tract

A

Head orientation info received by vestibulocochlear nerve
So tract from vestibular nuclei -> motor control of neck, trunk and some leg muscles
Maintain upright posture and head stabilisation
Bilateral innervation of muscles

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51
Q

Tectospinal tract

A

Originates in superior colliculus in midbrain
Info from eyes and visual cortex
Innervate contralateral motor neurones controlling head position

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52
Q

Reticulospinal tract

A

Originates in reticulospinal formation in pons and medulla
Modulates voluntary movements, locomotion and posture, influences muscle tone
Ipsilateral innervation of motor neurones in spinal cord

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53
Q

Damage to descending motor pathways

A
  • > immediate flaccidity of muscles on contralateral side, lose all reflex activity on that side
  • most severe in arms and legs, trunk control usually preserved - as remaining brainstem pathways, bilateral projection of corticospinal pathway
  • initially period of HYPOTONIA (= spinal shock)
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54
Q

Corticospinal tract impairment (lateral system)

A

Weakness of distal muscles (fingers)
Babinski sign (stroke sole of feet, instead of toes flexing they extend. normal in infants)
No spasticity, muscle tone may be decreased

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55
Q

Medial system interruption

A

Initial reduction in tone of postural muscles
Loss of righting reflex
Locomotor impairment, frequent falling

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56
Q

Lower motor neurone injury

A

Damage to alpha motor neurones innervating skeletal muscle
Effects limited to motor unit, so specific deficit

  • muscle atrophy and weakness
  • fasciculations, spontaneous action potentials
  • fibrillation, twitching of individual muscle fibres
  • decreased muscle tone (hypotonia) and reflexes (hyporeflexia)
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57
Q

Upper motor neurone injury

A

-> change in way system works, so planning affected as well as execution
Common, as large amount of cortex occupied by motor areas
If identify specific body regions affected, identify site of injury, as topographical arrangement

  • increased muscle tone (spasticity), hyperactive stretch reflexes
  • weakness, in distal muscles first
  • pathological reflexes, eg Babinski sign
  • reduced superficial reflexes
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58
Q

Lesion dividing spinal cord from CNS

A

Flaccid paralysis, loss of both voluntary and muscle tone

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59
Q

Lesion dividing upper and lower brainstem

A

Decerebrate posture:

Arms adducted and extended, wrists pronated, legs fully extended with plantar flexion of feet

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60
Q

Lesion dividing cerebrum from upper brainstem

A

Decorticate posture:
Arms abducted and flexed, wrists and fingers flexed on chest, legs stiffly extended and internally rotated, plantar flexion of feet

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61
Q

Cerebellum - inc deep nuclei

A

Hindbrain
Neuronal machine
White matter mainly, thin outer layer of densely folded grey matter
Most regular anatomy in brain:
4 deep (intracerebellar) nuclei on each side
- Dentate - don’t
- Emboliform - eat
- Globose - greasy
- Fastigal - food
Info from cerebellar cortex to deep nuclei, then exits cerebellum

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62
Q

Spinal cord inputs into cerebellum

A

Detailed, external proprioceptive information:

  • dorsal spino-cerebellar tract - inferior peduncle - lower limb
  • cuneo-cerebellar tract - inferior peduncle - upper limb

Integrated, internal proprioceptive information:

  • ventral spino-cerebellar tract - superior peduncle - lower limb
  • rostral spino-cerebellar tract - inferior peduncle - upper limb

-> unconscious proprioception, mainly pass ipsilateral to anterior lobe and vermis, straight to cerebellum not higher centres

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63
Q

Non-spinal cord inputs to cerebellum

A

Cerebral cortex -> cerebellar cortex

Vestibular nuclei (ipsilateral) -> floculonodular node

Reticular formation (ipsilateral) -> cerebellar cortex

Inferior olivary nucleus (contralateral) -> cerebellar cortex
- all sources of cerebellar input and all targets of its output go to inferior olivary nucleus

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64
Q

Purkinje cells

A

Large neurones in cortex of cerebellum

  • triangular cell body
  • numerous branching dendrites
  • single long axon

Release GABA to regulate and coordinate motor movements

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65
Q

Cerebellar cortex layer

A

Outer synaptic layer - molecular layer
Immediate discharge layer - purkinje layer
Inner receptive layer - granular layer

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66
Q

Cerebellar inputs

A

Two types of input:
CLIMBING FIBRES - wrap around dendritic tree of purkinje cells
- from inferior olivary nucleus
- end on purkinje cells
- non-movement related
- somatosensory, visual, and cerebral cortical info

MOSSY FIBRES

  • from all other afferents - nuclei in spinal cord and brainstem
  • end on granule cells
  • movement-related behaviour
  • sensory info from periphery, info from cortex
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67
Q

Cerebellar function

A

Balance, posture, muscle tone, limb movements
- skilled voluntary movement planning (ipsilateral)
SUBCONSCIOUS
Relays info between body muscles and areas of cerebral cortex involved in motor control

68
Q

Cerebellar outputs

A

Lateral hemispheric cortex

  • pre-programming movements
  • cerebrocerebellum

Paravermal cortex and Vermis

  • motor excution
  • spinocerebellum

Flocculo-nodular lobe

  • vestibulocerebellum
  • control of posture, balance, eye movement and coordination
69
Q

Cerebellar damage signs

A 
IPSILATERAL (as double crosses)
Danish P:
- dysdiadochokinesis
- ataxia
- nystagmus
- intention tremor
- slurred speech
- hypotonia
- past pointing

eg excessive alcohol abuse -> permanent slurred speech, loss of balance or coordination

70
Q

Basal nuclei

A

= basal ganglia
Subcortical, base of brain, collection of neuronal cell bodies
Includes:
- caudate nucleus
- putamen
- globus pallidus - external and internal segment
- subthalamic nucleus
- substantia nigra - pars compacta and pars reticulata
- nucleus accumbens

71
Q

Components of basal nuclei - striatum

A

= caudate nucleus + putamen
Input region of basal nuclei
Separated by internal capsule

72
Q

Components of basal nuclei - lentiform nucleus

A

= putamen + globus pallidus

73
Q

Components of basal nuclei - internal segment of globus pallidus and pars reticulata of substantia nigra

A

Output region of basal nuclei

Project to thalamus

74
Q

Components of basal nuclei - pars compacta of substantia nigra

A

Dopamine-containing neurones

Project to striatum

75
Q

Components of basal nuclei - nucleus accumbens

A

Forms part of ventral striatum

Involved in motivation and reward

76
Q

Function of basal nuclei

A

Initiation and control of voluntary movements
+ eye movements
+ learning routine behaviour
+ emotional and motivational behavioural responses

77
Q

Basal nuclei motor loop

A

Excitatory connection from cortex to putamen
Cortical activation -> excitation of putamen -> inhibit globus pallidus -> release ventral lateral nucleus from inhibition
-> modulates activity in SMA (supplementary motor area)

78
Q

Direct pathway through basal ganglia

A

Cerebral cortex: excitatory glutamate -> striatum
Tonically active substantia nigra pars compacta: excitatory dopamine -> striatum

Striatum: inhibitory GABA -> INTERNAL globus pallidus

Internal globus pallidus: inhibitory GABA -> thalamus

Thalamus: excitatory glutamate -> motor cortex, and project to all other cortex

OVERALL
- activation of thalamus to activate motor cortex, allowing voluntary movements

79
Q

Indirect pathway through basal ganglia

A

Cerebral cortex: excitatory glutamate -> striatum
Tonically active substantia nigra pars compacta: excitatory dopamine -> striatum

Striatum: inhibitory GABA -> EXTERNAL globus pallidus

External globus pallidus: inhibitory GABA -> subthalamic nucleus

Subthalamic nucleus: excitatory glutamate -> internal globus pallidus

Internal globus pallidus: MORE inhibitory GABA -> thalamus

Thalamus: LESS excitatory glutamate -> motor cortex, and project to all other cortex

Key diff is goes via external globus pallidus and subthalamic nucleus, so inhibition to thalamus
OVERALL
- inhibition of unwanted movement, reduced output to motor cortex

80
Q

Huntingdon’s disease

A

Autosomal dominant neurodegenerative
Loss of striatal neurones, lose inhibitory influence on thalamus
-> loss of cortical neurones

  • hyperkinesia, dyskinesia
  • chorea
  • dementia
  • changes in mood and personality
  • > death
81
Q

Ballism

A

Ballistic movements - violent, flinging movements of extremities
Typically by damage to subthalamic nucleus, may be stroke
(subthalamic nucleus is excitatory to internal globus pallidus, hence suppresses movement)
Often hemiballism, only one side

82
Q

Other basal nuclei loops

A

Occulomotor loop - control gaze
Prefrontal and orbitofrontal loops - cognition
Limbic loop - emotional and visceral functions

83
Q

Aetiology of Parkinson’s disease

A

Genetics - sometimes inheritable, 12 different genes can cause, number of different hits - 10% causes, often when younger onset
Toxins - can be drug induced
Mitochondrial dysfunction - esp in dopamine neurones
Abnormal protein aggregation (Lewy bodies)

-> death of neurones in substantia nigra -> dopamine depletion in striatum
(caffeine and nictotine limit neurodegeneration??)

84
Q

Cardinal features of Parkinson’s disease

A

TREMOR
- 2/3 have
- asymmetric (as 2 nigra-striatal pathways), slow frequency, rhythmic, at rest
- mainly in limbs, not head
RIGIDITY
- hypertonic limbs, uniform increase in tone
- not spasticity
BRADYKINESIA
- decreased frequency and amplitude of movement
- reduced facial expression, gait freezing when environment challenges, micrographia (small writing), fine finger movement hard
POSTURAL INSTABILITY
- reduced postural reflexes, so can’t correct when knocked off balance
- need to attend to gait, can’t walk and talk

OVERALL:
- as is loss of dopamine neurones in substantia nigra pars compacta, damage to indirect pathway so -> can’t prevent unwanted movement, damage to direct pathway so -> can’t initiate voluntary movement

85
Q

Pathology and progression of Parkinson’s

A

Degeneration of dopamine neurones, substantia nigra becomes pale
Also loss in putamen and caudate nucleus, that also use dopamine as neurotransmitter

As substantia nigra reduces, brain compensates until reach threshold for clinical expression, only symptoms at 70% loss of cells (problem for early treatment)
Then rapid degeneration
- live around 25 years post diagnosis, slow degeneration

86
Q

Non-motor complications of Parkinson’s

A

Dementia
Depression - basal ganglia also for cognition and mood, also lose NA neurones and serotonin
Anxiety
Sleep disturbance
Drowsiness
Restlessness
Impulse control problems - basal ganglia also for pleasure and reward

87
Q

Autonomic disturbances in Parkinson’s

A 
Dysphagia
Drooling
Bladder dysfunction
Constipation
Weight loss
Postural hypotension
Pain
88
Q

Treatment options for Parksinson’s

A 
PREVENTATIVE
- none, causal factors unclear
SYMPTOMATIC
- pharmacological
- deep brain stimulation (surgical)
NON-MOTOR MANAGEMENT
- cognitive therapy
- speech therapy
- physiotherapy
- dietician 
- psychologist
RESTORATIVE - experimental
- stem cell transplant
- gene therapy
- neurotrophic factors - to support surviving cells
89
Q

Drug classes to treat Parkinson’s symptoms

A

Dopaminergic agents - Levodopa, dopamine receptor agonists
COMT (catechol-O-methyl transferase) inhibitors
MAO-B (monoamine oxidase) inhibitors
Anticholinergics
Amantadine
Memantine

90
Q

Parkinson’s drugs - Levodopa

A

= L-dopa
Effective to relieve motor symptoms, boost remaining cells function
Requires active transport across gut-blood BB barrier - is partly converted to dopamine in blood, bad as -> GI side effects
Need to give in high doses
Give with decarboxylase inhibitor to limit peripheral conversion to dopamine
Fast onset -> on, but also fast -> off

Side effects -> dyskinesias
- excessive dopaminergic stimulation, at peak dose -> ballistic movement

Initially will increase survival rate, but won’t work forever

91
Q

Parkinson’s drugs - direct dopamine receptor agonists

A

GOOD
- longer half life than L-dopa
- mono or adjunct therapy
- delay/reduce dyskinesias
- neuroprotective???
BAD
- nausea, vomiting - direct action on peripheral dopamine receptors
- dizziness, postural hypotension, headache, drowsiness
- dyskinesias
- confusion, hallucinations, paranoia
- pulmonary and retroperitoneal fibrosis, pleural effusion and thickening

92
Q

Parkinson’s drugs - inhibitors of dopamine metabolism

A

MAO-B (monoamine oxidase) inhibitors
or
COMT (catechol-O-methyl transferase) inhibitors

93
Q

Parkinson’s drugs - MAO-B (monoamine oxidase) inhibitors

A

Selegiline

  • inhibits dopamine metabolism in brain, so dopamine is not broken down in synapse, instead repackaged to vesicles and recycled
  • neuroprotective???
  • given as patch, so constant concentration

Rare side effects, need low tyramine diet, not with antidepressants

94
Q

Parkinson’s drugs - Anticholinergics

A

Works as dopaminergic depletion -> cholinergic overactivity to compensate
Effective for tremor, and ~rigidity
Side effects - dry mouth, sedation, confusion, constipation

eg Trihexyphenidyl, Benztropine, Ethopropazine

95
Q

Parkinson’s drugs - Amantadine

A

Antiviral agent
Effective for tremor, bradykinesia, rigidity, dyskinesias
Exact mechanism unclear
Side effects - autonomic, psychiatric

96
Q

Parkinson’s drugs - Memantine

A

NMDA receptor antagonist

Mechanism unclear

97
Q

Parkinson’s treatment - deep brain stimulation

A

Surgery - electrode implanted to motor output regions, connected to pacemaker in chest
Invasive and risky, only after drugs no longer effective
Very effective to control motor symptoms

98
Q

Parkinson’s treatment - restorative factors?

A

Stem cell transplant?

Gene therapy - neurotrophins?

99
Q

Huntingdon’s disease genetics

A

Autosomal dominant
Polyglutamine expansion repeat on Huntingtin (Htt) gene
- random mutation replicates multiples of GGGGG etc
-> incorrect protein folding
-> oligomers, sticky, as micro-aggregation
-> insoluble so precipitate as solids in cell
-> disrupts cell working, toxic effects on function

More repeats, earlier onset, worse effects

100
Q

Treatment of Huntingdon’s disease

A

Hugely varied symptoms, so need many different treatments

In gene therapy, could inhibit RNA, aggregation, encourage autophagy etc
- but can’t lose Huntingtin, has useful function!

101
Q

Myelination

A

MYELIN
- lipid rich
- spiral wrapping of glial plasma membrane extensions around neurones
NODES OF RANVIER
- periodic gaps in sheath to allow saltatory conduction

  • > faster speed of conduction
  • > cool neurones
  • > structural support for neurones
102
Q

Demyelination vs dysmyelination vs axonal degeneration

A

Demyelination = loss of myelin, with relative preservation of axons. Can be in PNS or CNS.

Dysmyelination = failure to form normal myelin

Axonal degeneration as primary process -> secondary degeneration of myelin. Would get decreased amplitude.

103
Q

Immune-mediated PNS demyelination

A 
ACUTE
Guillain Barre Syndrome - can be post infection
- distal then proximal
- weakness and paraethesia, esp in neck
- early loss of reflexes
-> resp failure, autonomic dysfunction

CHRONIC
Chronic immune demyelinating polyneuropathy

104
Q

Other causes of PNS demyelination

A

Compression

  • often transient and minor
  • carpal tunnel syndrome, radial neuropathy etc

Hereditary
- Charcot Marie Tooth disease

Toxic-metabolic
- lead, leprosy, diptheria

As PNS recovers, -> ‘onion bulb’ formation, layering of myelin formation and destruction

105
Q

Immune-mediated CNS demyelination

A

Multiple sclerosis
Acute disseminated inflammatory demyelination
Acute haemorrhagic leucoencephalitis
Neuromyelitis optica

106
Q

Acute disseminated inflammatory demyelination

A 
= ADEM
Monophasic illness
Post-infection
More children than adults get
-> fever, drowsiness, fits, coma, meningism

Can be fatal, rare so not well understood

107
Q

Neuromyelitis optica

A

Inflammation affecting spinal cord mainly, and optic nerve
NMO-IgG antibody to diagnose
Longitudinally extensive cord lesions, across more than 3 vertebral segments
-> Optic neuritis

Treatment responsive to immunosuppression

108
Q

Central pontine myelinolysis

A

Often after rapid correction of sodium (fast infusion following hyponatraemia)

109
Q

Progressive multifocal leucoencephalopathy

A

JC virus causes - immunocompetent should resist
Can be asymptomatic
Impaired immunity can reactivate
Can’t treat, need immune system to

110
Q

Aetiology of multiple sclerosis

A

UNKNOWN
Genetic susceptibility and environment interplay
- 10x increased risk in 1st degree relatives
- 3x more in women

Environmental triggers:

  • multiple infectious agents - antigens on virus similar to myelin?
  • aberrant response to infection - Epstein-Barr and glandular fever link
  • low sunlight
  • vitamin D deficiency (immune regulator)
  • smoking

-> onset in 20s-30s usually

111
Q

Lesions in multiple sclerosis

A

‘Demyelinating lesions disseminated in time and space’

  • different parts of NS at different times
  • need multiple episodes of neurological dysfunction for 24hours + for diagnosis

Perivenular or periventricular distribution (loss of white matter mainly)

  • > axonal loss (probably secondary)
  • > inflammation
112
Q

Diagnosing MS

A

Presentation:

  • weakness in limb(s)
  • optic neuritis
  • paraesthesiae
  • diplopia
  • urinary symptoms

History:

  • onset over days
  • fatigue
  • family history
  • worse in heat - Uhtoff’s phenomenon
  • shock down spine when bend neck forward - Lhermitte’s phenomenon

Examination:

  • may be no signs
  • or signs of multifocal CNS disease

MRI - white matter lesions
CSF - oligoclonal bands, antibodies, suspicious if not also in blood as implies local process

113
Q

Clinically isolated syndrome - first episode of MS?

A

If normal MRI, very low likelihood of MS

If white matter lesions, 50% MS at 2 years, 80% at 20 years

114
Q

Phases of MS

A

70%
Relapsing-remitting initially, then secondary progressive
- once secondary progressive, neurodegenerative, no treatment

10%
Benign relapsing-remitting
- good treatments, autoimmune

20%
Primary progressive

115
Q

MS presentation - optic neuritis

A

45yrs + usually
Onset 1-2 weeks
Spontaneous improvement, 1/3 recur in 5-10 years
Future MS risk

Peri-ocular pain, worse in heat
Visual field defect
Extent of recovery influenced by severity of visual loss

Steroids improve short term recovery, not long term
Treatment only for - monocular vision, severe bilateral loss, require rapid recovery (occupation)

116
Q

Factors for rapid progression of MS

A
  • male (though more common in females)
  • older age onset
  • primary progressive type MS (PPMS)
  • brainstem/cerebellar presentation
  • change in MRI lesion load
  • more attacks in first year, short gap between first two episodes
117
Q

MS drugs - steroids

A

1st line, corticosteroids

  • only in very severe symptoms - need high doses to penetrate NS so side effects bad
  • no more than 3x per year
  • shorten relapse duration, no effect on extent of functional recovery
118
Q

MS drugs - interferons and glatiramer

A

Reduce relapses by 1/3
No reduction in disability progression - but may delay time to progress to secondary progressive?

Very expensive! So only give if:

  • still ambulant
  • 2 relapses in 2 years
  • 1 disabling relapse
  • MRI evidence of new or enhancing lesions after 1 year

Used less now, not that effective

119
Q

MS drugs - fingolimod

A

Tablet
Sphingosine-1-phosphate receptor inhibitor
- inhibits trafficking of inflammatory cells
BUT risky - CVS, respiratory issues
60% reduction in relapse rate

120
Q

MS drugs - dimethylfumarate

A

Most common, tablet
Transcription factor - anti-inflammatory and lowers oxidative stress
Safe
50% reduction in relapse rate

121
Q

MS drugs - teriflunomide

A 
Tablet
Anti-inflammatory immunosuppressant
30% reduction in relapse rate
Risky - hepatotoxic and teratogenicity
--> rarely used, last line
122
Q

MS drugs - natalizumab

A

Monoclonal antibody therapy
Monthly infusion
2/3 relapse reduction rate at one year
Risky, only for severe relapse-remitting disease

123
Q

MS drugs - alemtuzumab

A

Monoclonal antibody therapy
Reduces relapse by 75%
Decreased disability over three years by 71%

Side effects - increased incidence of other autoimmune diseases

124
Q

MS drugs - neuroprotection

A

No licensed drugs currently

To slow progression

125
Q

Symptoms of MS

A 
Bowel + bladder dysfunction
Spasticity
Mood
Erectile dysfunction
Tremor
Pain
Fatigue
Vision
Cognition
Mobility
Speech + swallow
- drugs available to help relieve these symptoms
126
Q

Cerebral arteries supply

A

Anterior -> motor + sensory cortex of lower limb

Middle -> motor + sensory cortex of upper limb and face, and auditory cortex

Posterior -> visual cortex

Posterior inferior cerebellar artery -> lateral medulla

127
Q

Watershed infarcts

A

Where territories supplied by different vessels overlap

If perfusion pressure is low, terminal branches of major arteries have insufficient supply

128
Q

FAST

A

Face
Arms
Speech
Time

129
Q

Middle cerebral artery syndrome

A

MCA most common site for ischaemic stroke

  • as is main branch of internal carotid, so blood straight from body, bringing clots etc
  • > contralateral hemiparesis, hemisensory loss from face, upper and lower extremities
130
Q

Cerebral aneurysm

A

Weakness in wall of cerebral artery or vein
Dilation/ballooning of vessel
- may cause no symptoms until bursts, -> haemmorhage
- if large, may cause symptoms as press on associated brain structures

Clipping treatment - major surgery - to prevent burst or after to stop bleeding
Coil procedure - less major - wire passed up and coiled into aneurysm to block, preventative

131
Q

Cerebral blood flow

A

50ml/min/100g brain weight
15% cardiac output
Kept constant

CBF = cerebral perfusion pressure / cerebral vascular resistance
(CPP = MAP - ICP, typically 70-90mmHg)
132
Q

Autoregulation of cerebral blood flow

A

Even over large fluctuations in MAP, CBF kept in tight limits

Below limits - CBF lower - ischaemic damage

Above limits - ICP higher - oedema, crushing of brain tissue, shifting of brain structures, restriction of blood flow, herniation

By neural, metabolic, myogenic control - work together to maintain CBF - flow adjusted rapidly at microvascular level

133
Q

Neural control of CBF

A

1 - sympathetic neurones from superior cervical ganglion

  • travel with internal carotid and vertebral arteries into skull
  • release NA -> vasoconstriction

2 - parasympathetic neurones from branches facial nerve
- release ACh -> modest vasodilation

3 - sensory nerve fibres on blood vessels
- release vasodilatory substances

(overall weak control)

134
Q

Metabolic control of CBF

A

Local increase in brain metabolism - lower pO₂, raise pCO₂, lower pH
-> vasodilation of vascular smooth muscle

Increase pCO₂ of arterial blood, CO₂ crosses BBB, lower pH
-> vasodilation of vascular smooth muscle

Hypoxia/seizures increase [K⁺]
-> vasodilation

Reduced O₂ supply, or increased O₂ demand causes rapid adenosine formation
-> potent vasodilator

135
Q

Myogenic control of CBF

A

Stress sensing mechanism
Pressure increases diameter of vessels
-> vasoconstriction

136
Q

Functional MRI scan

A 
fMRI
Fast (5s)
For vascular markers eg gadolinium
Changes in blood flow alter signal
Oxy- and deoxyhameoglobin give different signals
137
Q

Positron emission tomography

A

PET
Radioactive solutions into body
Positron emitting isotopes used as markers of blood flow
Linked to deoxyglucose, and receptor ligands
-> activity maps, not images

138
Q

Stroke definition

A

Acute (rapid onset) focal injury
- of central nervous system
- due to vascular cause
eg cerebral infarction, intracerebral haemorrhage, subarachnoid haemorrhage

Affects brain or (rarely) spinal cord

139
Q

Types of stroke

A

75% - cerebral infarction
20% - intracerebral haemorrhage
5% - subarachnoid haemorrhage

(blood white on CT, darker patches are infarction, white is haemorrhage. Infarct bright on MRI!!)

140
Q

Burden of stroke

A

Second most common cause of death worldwide (after ischaemic heart disease)
Commonest cause of disability
5% NHS resources
- deprived areas more risk, more death
- racial differences, afro-caribbeans and south asians higher risk - higher bp, diabetes, high cholesterol, sickle cell disease

20% strokes fatal
50% -> permanent disability

141
Q

Causes of ischaemic stroke (cerebral infarction)

A

ATHEROSCLEROSIS - form esp in turbulent blood flow, clots group and travel to brain from here

CARDIAC DISEASE - atrial fibrillation mainly, or ventricular aneurysm- blood sits for longer, so clots

  • patent foramen ovale - blood can flow from right heart (maybe DVT in leg) to left heart, clot to brain
  • infective endocarditis or tumours can throw clots

‘SMALL VESSEL DISEASE’ - thickening of small blood vessels in brain, shrink until they block (or become more fragile and bleed, -> haemorrhage)

ARTERIAL DISSECTION - blood gets into wall of vessel
- haemorrhage into vessel -> occlusion, or intimal tear

ABNORMAL BLOOD CLOTTING - anti-phospholipid syndrome (antibodies increase clotting)

  • malignancy, due to systemic inflammation
  • polycythaemia, Hb levels too high, sticky blood

ALSO many other causes - drugs, vasculitis, infection, inherited, metabolic

142
Q

Risk factors for atherosclerosis

A 
Hypertension
Hypercholesterolaemia
Diabetes
Smoking
Excess alcohol
Stress
Male gender
Family history
143
Q

Causes of intracerebral haemorrhage

A

Hypertension
Cerebral amyloid angiopathy - amyloid deposition in vessels, only in age really
Abnormal blood vessels
Dural venous sinus thrombosis
Intracranial neoplasm (tumours, some prone to bleed)
Coagulopathy - clotting problems
Ischaemic stroke -> secondary haemorrhage

144
Q

Clinical features of stroke

A

Sudden onset - not even seconds, instant
‘Negative’ symptoms - lost something not gained, eg lost sensation not started tingling, weakness not twitching

  • explained by single lesion
  • explained by blockage of artery (ischaemic)

All usually, doesn’t always follow rules

145
Q

Vascular territories of brain

A

Cerebral arteries have zones
ACA - medial strips, inside of medial surface
MCA - most of brain, temporal lobe and most of lateral surface
PCA - occipital lobe, stretch to bottom of temporal

Anterior circulation from internal carotid, splits to MCA and ACA
Posterior circulation in vertebro-basilar

-> so different arteries blocked, different functions of the brain, different presentations

146
Q

Stroke syndromes

A 
TACS - total anterior cerebral
PACS - partial anterior cerebral
POCS - posterior cerebral
LACS - lacunar
(ischaemic only)

MANY stroke mimics!

147
Q

Total anterior circulation stroke

A

Need all three of:

  • hemiparesis
  • hemianopia (loss of vision)
  • higher cortical function eg dysphagia, neglect/inattention - unable to attend to opposite side of body
148
Q

Partial anterior circulation stroke

A 
Occlusion of MCA branch or ACA
Need two of:
- hemiparesis - usually face + arm, or leg
- hemianopia (vision loss)
- higher cortical function
OR
- isolated higher cortical function
149
Q

Lacunar stroke

A

Mostly in lenticulostriate arteries, off MCA - no other arteries supply area, these are end arteries

  • > recognised syndromes:
  • pure hemiparesis
  • hemisensory loss
  • dysarthia (clumsy hand)
  • ataxic hemiparesis
150
Q

Posterior circulation stroke

A
  • > recognised syndromes:
  • isolated hemianopia (vision loss)
  • cerebellum
  • brainstem
151
Q

Principles of stroke treatment

A

Hyperacute - protect penumbra (=tissue at risk), need to get clot out to protect and limit cell death (ischaemic core is already irreversibly dead)

Prevention of complications

Secondary prevention (identify cause)

Rehabiliatation and recovery

152
Q

Thrombolysis

A

Tissue plasminogen activator (tPA) given
-> activate plasmin, to digest clots

Needs treatment within 4.5 hours
Will reduce future deficit
MAY reduce mortality if very early
(does increase haemorrhage risk in first 7 days)
- doesn't dissolve big clots well
153
Q

Thrombectomy

A

Insert wire mesh - stent retrievers
Then pull back out, remove clot
Useful for big clots, improves IV access to middle of clot

Can treat slightly later - 6 hours - so time to assess usefulness with brain imaging

154
Q

Immediate care after stroke

A

Only have 24 hour window as long as penumbra persists

Thrombolysis/thrombectomy
Avoid hyperglycaemia
Control temperature in fever
Oxygen
Hydration
Early nutrition
155
Q

Early secondary prevention

A

Anti-thrombotics - balance risk (as may bleed after stroke)

  • anti-platelets - aspirin, clopidogrel
  • anticoagulants
156
Q

Causes of ischaemic stroke

A

50% - arterial atherothromboembolism
25% - intracranial small vessel disease
20% - embolism from heart

Need to know (imaging) for secondary prevention

157
Q

Secondary prevention

A

Lower bp (as long as not hypotensive)
Lipid lowering - no threshold for treatment, need to lower LDL levels, eg statins
Anti-thrombotics - anti-platelets - aspirin, clopidogrel
- anticoagulants - esp if atrial fibrillation
Carotid endarterectomy - need to remove atherosclerotic plaque

Carotid surgery within 48 hours! Sooner the better as long as stable.

158
Q

International classification of Functioning, Disability and health

A

ICF
To ‘mainstream’ experience of disability - everyone will be disabled at some point
Shift focus from cause to impact
Focus on what you can do, not what you can

Stroke is more than a disease, people not patients
More to life than ADL, even if you’re 90!

159
Q

Impairments after stroke

A

Motor function - weakness, incoordination
Sensory function - vision, hearing, numbness, pain
Communication - dysarthia (speech), dysphasia (language), dyslexia, dysgraphia (writing)
Swallowing
Cognitive function - motor planning, attention, memory
Emotional function
Fatigue
Bladder and bowel function
Sexual function
Pain - central or musculoskeletal

  • often ignored, need to consider all aspects if working to ICF
160
Q

Emotional consequences of stroke

A

1/3 have depression
1/4 have anxiety
1/5 have insomnia
1/5 have emotionalism
+ fatigue, lack confidence, fear of second stroke, social isolation
2/3 can’t return to work, decrease in income

+ impact for carers and families

161
Q

Stroke rehabilitation

A

Brain recovery, + bodily maintenance (nutrition, CVS exercise, reconditioning)

  • repetitive practice
  • build up in difficulty
  • targeted activities
  • break activities into components
  • compensation and recovery need to be balanced

Gradual management of expectations, goal setting short and long term
Better in specific stroke rehabilitation units! Coordinate multi-disciplinary team, need stroke specialist team

162
Q

Early supported discharge teams

A

Same kind of high intensity care as in hospital, but in home environment

  • therapists better understand goals and limitations to patient
  • > improved otucomes
163
Q

Determinants of rehab effectiveness

A

Younger age better
Pre-treatment disability
Cognitive impairment

164
Q

Physiotherapy following stroke

A

Return motor function to normal, or find ways to compensate for it
Increase strength
Improve CVS fitness
Prevent deconditioning
Improve spasticity - drugs, passive movement, splinting, botulinum toxin
(exercise also helps with mood, improves neurogenesis)

165
Q

Other therapies following stroke

A

Need to practice:

  • swallowing (modified diet)
  • communication, esp with family/friends
  • arrange for vision/hearing loss help
  • emotional consequences discussed

NEED at least one month off driving, never if visual loss.

2nd Year - Systems 3 (10 decks)

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