MND Flashcards
definition of MND
progressive neurodegenerative disorder of cortical, brainstem and spinal motor neurons - LMN and UMN
characterized by selective loss of neurons in motor cortex, cranial nerve nuclei, and anterior horn cells.
no sensory loss or sphincter disturbance
never effects eye movement
subtypes of MND
amylotropic lateral sclerosis (ALS) or Lou Gehrig’s disease
progressive muscular atrophy variant
progressive bulbar palsy variant - any lesion affecting CN9-12 at nuclear, nerve or muscle level
pseudobulbar palsy
primary lateral sclerosis variant
amylotrophic lateral sclerosis or Lou Gehrig’s disease
loss iof motor neurons in motor cortex and anterior horn of the cord
combined degeneration of UMN and LMN = signs of both
worse prognosis if bulbar onset, increased age, low FVC
progressive muscular atrophy variant
only LMN - anterior horn cell lesion
eg flail arm, or flail foot syndrome
better prognosis than ALS
distal muscle gps before proximal
progressive bulbar palsy variant
dysarthria and dysphagia
wasted, flaccid fasiculating tongue (LMN)
brisk jaw jerk (UMN) ?absent
nasal speech
nasal regurgitation of food - especially fluids (palatal weakness)
reduced gag reflex
An LMN lesion of the tongue and muscles of talking and swallowing
aetiology: MND, Guillain–Barré, polio, myasthenia gravis, syringobulbia, brainstem tumours, central pontine myelinolysis
psuedobulbar palsy
Any UMN (corticobulbar) lesion to the lower brainstem above the midpons eg corticobulbar tracts (MS, MND, stroke, central pontine myelinolysis),
presenting with monotonous or explosive speech, slow deliberate speech, dysphagia, increased gag reflex, brisk jaw reflex, shrunken immobile tongue, emotional lability, UMN limb spasticity and weakness, increased pharyngeal and palatal reflex
pseudobulbar aff ect (PBA)—weeping unprovoked by sorrow or mood-incongruent giggling
primary lateral sclerosis variant of MND
loss of Betz cells in motor cortex
UMN pattern of weakness
brisk reflex
extensor plantar responses
spastic leg weakness and pseudobulbar palsy - no cognitive decline
w/o LMN signs
aetiology of MND
unknown
free radical damage and glutamate excitotoxicity – mutations in superoxide dismutase (SOD1 gene) affect 20% with familial motor neuron disease and 1-4% of sporadic cases
SOD1 codes for a metalloenzyme for the conversion of free radicals
pathology: progressive motor neuron degeneration and death with gliosis replacing lost neurons. Neurons may exhibit intracellular occlusions (neurofilaments or ubiquinated inclusions) containing the TAR-DNA binding protein 43 (TDP-43)
association – frontotemporal lobar dementia (FTLD) from proganulin mutations
epidemiology of MND
rare
annual incidence 2/100000
55yrs
5-10% have FH with autosomal dominant inheritance
female more
sx of MND
Weakness of limbs – focal/asymmetrical
Speech disturbance – slurring or reduction in volume
Swallowing disturbance – choking on food, nasal regurg
Behavioural changes – disinhibition, emotional liability
signs of MND
Combination of UMN and LMN – affect several regions, asymmetric
LMN – muscle wasting, fasiculations (tongue, back, abdo, thigh), flaccid weakness, depressed/absent reflexes
UMN – spastic weakness, brisk reflex, extensor plantars
Sensoy exam – normal
stumbling spastic gait
foot drop +- prox myopathy
weak grip - door handles dont turn
shoulder abduction (hairwashing hard)
aspiration pneumonia
is speech/swallowing effected - bulbar signs
frontotemporal dementia in 25%
Ix for MND
Confirm diagnosis by providing evidence of UMN and LMN loss and excluding other causes
- Blood
- CK mild increase
- ESR
- Consider anti-GM1 ganglioside Ab – present in multifocal motor neuropathy
- EMG
- Features of acute and chronic denervation with giant motor unit action potentials in >1 limb and/or paraspinals
- Nerve conduction studies – normal
- MRI
- Exclude cord/root compression, brainstem lesion in progressive bulbar palsy
- May show high signal in motor tracts on T2 imaging
- Spirometry
- Assess resp muscle weakness – FVC
- LP
- exclude inflammatory causes
neurophysiology can detect subclinical denervation and help exclude mimicking motor neuropathies
what is multifocal neuropathy
characterised by asymmetrical LMN signs
important to distinguish from MS because it is treatable
motor nerve conduction studies show evidence of conduction block, representing focal demyelination
associated with GM1 autoAb
treatable with IB Ig, steroids or immunosuppression
dx criteria for ALS
Definite = Lower + upper motor neuron signs in 3 regions.
Probable = Lower + upper motor neuron signs in 2 regions.
Probable with lab support = Lower + upper motor neuron signs in 1 region, or upper motor neuron signs in ≥1 region + EMG shows acute denervation in ≥2 limbs.
Possible = Lower + upper motor neuron signs in 1 region.
Suspected = Upper or lower motor neuron signs only—in 1 or more regions
mx of motor neuron disease
riluzole - in ALS, prevents stimulation of glutamate receptors
resp - NIV at night - survival benefit 7 mo
treat sx eg
* drooling -> hyoscyamine
* spacticity -> baclofen
* pseudobulbar effect -> dextromethorphan/quinidine
