neurodegenerative

Question 1

motor neuron disease

Answer 1

progressive, terminal illness where upper + lower motor neurons stop functioning (resp failure/aspiration)

focal onset + continuous spead -> finallty generalised paresis
has no effect on sensory neurons
cognitive impairment is a feature

more common in men
peaks age 50-75

Question 2

types of motor neuron disease

Answer 2

amyotrophic lateral sclerosis (ALS) = commonest

progressive bulbar palsy

progressive muscular atrophy

primary lateral sclerosis

Question 3

amyotrophic lateral sclerosis (ALS)

Answer 3

commonest MND
typically LMN signs in arms + UMN signs in legs

split hand syndrome = preferential wasting of the thenar group (thumb), hypothenar are spared (pinkie side)

Question 4

progressive bulbar palsy

Answer 4

affect primarily the muscle of tongue, talking + swallowing
women >men (60-80yrs)

always generalised into ALS
Mx - early communicator, nutritional support

Question 5

progressive muscular atrophy

Answer 5

flail arm + leg syndrome - can’t control arms but otherwise well (need help with everythinggg)

affects distal before proximal
mostly LMN signs

Question 6

primary lateral sclerosis

Answer 6

UMN signs only
best prognosis (>5yr)

Question 7

exposure to what increase risk of MND

Answer 7

smoking
heavy metals
certain pesticides

Question 8

lower motor neuron signs

Answer 8

muscle wasting, weakness
reduced tone
fasiculations = twitches in muscles
reduced reflexes

Question 9

upper motor neuron signs

Answer 9

increased tone or spasticity
brisk reflexes
upgoing plantar responses
spastic gait
slowed movements
exaggerated jaw jerk

Question 10

presenting clues of MND

Answer 10

fasiculations
absence of sensory signs/symptoms
mix of LMN + UMN
wasting of thumb muscles but not pinkie

doesnt affect external ocular muscles
no cerebellar signs
abdominal reflexes + sphincter function preserved till late

Question 11

MND presentation

Answer 11

often 1st in upper limbs, spreads
increased fatigue when exercising
complain of clumsiness
slurred speech
wasted tongue, weak neck
dry mouth or excessive saliva
split hand syndrome
cognitive impairment
metabolism increase

eye + sphincter muscles spared until late stage
NO sensory disturbance

Question 12

diagnostic criteria for ALS

Answer 12

El escorial

Question 13

diagnosis of MND

Answer 13

clinical

EMG - muscle denervation + multiple fasiculations, rreduced number of action potential with increased amplitude
nerve conduction studies - normal motor conduction (exclude neuropathy)

MRI to exclude cervical cord compression/myelopathy

Question 14

pharmacological management of MND

Answer 14

Riluzole
- can slow progression + add 3 months but only at end of life (poor uptake, would rather not prolong severe diability)

• prevents stimulation of glutamate receptors

Question 15

supportive management of MND

Answer 15

BiPAP - at night to support breathing
MDT, advance directives
PEG feeding
extra saliva or botox to reduce saliva

muscle cramps - quinine, baclofen

muscle spasms - baclofen, tozanidine, gabapentin

Question 16

prognosis of MND

Answer 16

median survival 3yrs after symptoms onset

(track for first 6 months before telling timeline - see how slow/quick progression is)

Question 17

multiple sclerosis

Answer 17

chronic + progressive involving demyelination of the myelinated neurones in the CNS
-> inflammatory process - immune cells against myelin

more common in women
- **symptoms tend to improve in pregnancy + in post-partum period
- initial presentation in 30s-40s
- more common the more north you go - orkney

Question 18

types of MS

Answer 18

Relapsing remitting MS (85-90%) – progressive spikes

Secondary progressive MS (20-50) – relapsing-remitting at first but now progressive with incomplete remissions, symptoms between relapses, gait + bladder

Primary progressive MS (10-15%) – slow gradual progression, constant slope, old age

Question 19

Multiple sclerosis pathophysio

Answer 19

Myelin covers axons in CNS + allows electrical impulses to move faster along the axon
- MS only affects the CNS -> oligodendrocytes

Inflammation around myelin + infiltration of immune cells that cause damage to the myelin – affecting signals traveling along axons
o Lymphocytic infiltration on histology
o Oligoclonal IgG bands in CSF

In early disease, re-myelination can occur + symptoms can resolve
o In later disease, re-myelination is incomplete + symptoms gradually become more permanent

Lesions vary in their location over time, meaning that different nerves are affected + symptoms change over time
–> Disseminated in time + space

Question 20

where do plaques of demyelination tend to occur in multiple sclerosis?

Answer 20

anywhere in CNS white matter but have a predilection for certain sites -
- optic nerves
- brainstem
- cerebellar connection
- cervical cord (corticospinal tracts + posterior columns)

( MS = T cell mediatied autoimmune disease that causes an inflammatory process mainly within the white mater of the brain + spinal cord)

Question 21

histology of MS plaques

Answer 21

Active plaques
o Perivascular inflammatory cells
o Microglia
o Ongoing demyelination

Inactive plaques
o Gliosis
o Little remaining myelinated axons
o Oligodendrocytes + axons reduced in number
o Classically situated around lateral ventricles

Shadow plaques -> thinned out myelin sheaths at edge of lesions, causing less well defined lesion

Question 22

causes of multiple sclerosis

Answer 22

multiple genes
epstein barr virus
low vit D - more common the further north you go
smoking
obesity

genetic
- 15x risk if 1st degree relative
- 150x risk with affected monozygotic twin
- HLADRB1

Question 23

multiple sclerosis presentation

Answer 23

optic neuritis (often 1st noticed)
- central scotoma - enlarged blind spot
- pain on eye movement
- impaired colour visio
- RAPD - swinging light test

intention tremor
pendular reflexes
dysdiadokinesia - inability to perform rapid alternating movements (flipping hand in palm)

Vi CN palsy - can’t abduct eye/lags
VII palsy - facial weakness

pyramidal dysfuntion - increased tone, spasticity, weakness, extensor of upper, flexors of lower limbs (can’t sense if leg is flexed or extended)
sensory sx - paraesthesia, trigemial neuralgia, loss of proprioception (positive rombergs test)

urinary tract dysfunction
fatigue

Question 24

diagnosis of MS

Answer 24

Diagnosis requires demonstration of lesions disseminated in time and space

multiple distinct CNS lesions on MRI (usually white matter, high signal T2 lesions)

Question 25

MS investigations

Answer 25

MRI –
o High signal (T2) lesions
o Principally a white matter disease
o Exterior normal – cut surface shows plaques
o Periventricular plaques
o Dawson fingers – often seen on FLAIR images – hyperintense lesion penpendicular to the corpus callosum

• Lumbar puncture – oligoclonal bands in CSF
• Evidence of slowed conduction

Question 26

management of acute MS relapse

Answer 26

High-dose steroids (e.g. oral or IV methylprednisolone) for 5 days to shorten the length of an acute relapse
- oral for moderate, IV for bad

–> steroids shorten the duration of a relapse and do not alter the degree of recovery (i.e. whether a patient returns to baseline function)

Question 27

disease modifying therapy for MS

Answer 27

1st line
- Tecfedira, aubagio
- interferon beta, glitiramer acetate

2nd
- monoclonal antibody - tyabri, Ocrevus
- fingolimod, cladribine

3rd
- mitoxantrone
- HSCT - stem cell transplantation

Question 28

symptomatic management of MS

Answer 28

fatigue - amantadine
spasticity - baclofen

antidepressant - amitriptyline
anticonvulsant - gabapentin

increased tone at bladder neck - anticholinergics (oxybutynin), desmopression, catheter