neurodegenerative Flashcards
motor neuron disease
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
types of motor neuron disease
amyotrophic lateral sclerosis (ALS) = commonest
progressive bulbar palsy
progressive muscular atrophy
primary lateral sclerosis
amyotrophic lateral sclerosis (ALS)
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)
progressive bulbar palsy
affect primarily the muscle of tongue, talking + swallowing
women >men (60-80yrs)
always generalised into ALS
Mx - early communicator, nutritional support
progressive muscular atrophy
flail arm + leg syndrome - can’t control arms but otherwise well (need help with everythinggg)
affects distal before proximal
mostly LMN signs
primary lateral sclerosis
UMN signs only
best prognosis (>5yr)
exposure to what increase risk of MND
smoking
heavy metals
certain pesticides
lower motor neuron signs
muscle wasting, weakness
reduced tone
fasiculations = twitches in muscles
reduced reflexes
upper motor neuron signs
increased tone or spasticity
brisk reflexes
upgoing plantar responses
spastic gait
slowed movements
exaggerated jaw jerk
presenting clues of MND
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
MND presentation
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
diagnostic criteria for ALS
El escorial
diagnosis of MND
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
pharmacological management of MND
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
supportive management of MND
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
prognosis of MND
median survival 3yrs after symptoms onset
(track for first 6 months before telling timeline - see how slow/quick progression is)
multiple sclerosis
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
types of MS
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
Multiple sclerosis pathophysio
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
where do plaques of demyelination tend to occur in multiple sclerosis?
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)
histology of MS plaques
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
causes of multiple sclerosis
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
multiple sclerosis presentation
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
diagnosis of MS
Diagnosis requires demonstration of lesions disseminated in time and space
multiple distinct CNS lesions on MRI (usually white matter, high signal T2 lesions)
MS investigations
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
management of acute MS relapse
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)
disease modifying therapy for MS
1st line
- Tecfedira, aubagio
- interferon beta, glitiramer acetate
2nd
- monoclonal antibody - tyabri, Ocrevus
- fingolimod, cladribine
3rd
- mitoxantrone
- HSCT - stem cell transplantation
symptomatic management of MS
fatigue - amantadine
spasticity - baclofen
antidepressant - amitriptyline
anticonvulsant - gabapentin
increased tone at bladder neck - anticholinergics (oxybutynin), desmopression, catheter
