Motor neuron disease and MMN - UMN, LMN, mixed. Flashcards
Examination findings and signs of motor neuron disease
Inspection
1. Walking aid or wheelchair
2. Foot drop and shoes scuffing at the front
3. Face - bulbar/pseudobulbar involvement
4. NO oculomotor muscle involvement
5. Limbs
- Wasting and fasciculations
- Early unilateral involvement; late bilateral involvement
- Distal to proximal: difficult in hand movement, foot drop
Weakness - UMNL or LMNL
- Loss of neurons at all levels (cortex to anterior horn cells)
- UMN - hyperreflexia, hypertonia, clonus, Hoffman positive
- LMN - fasciculations, hypotonia, hyporeflexia
- Bulbar/pseudobulbar
- All 4 limbs distal to proximal weakness
- Sensation spared and intact
(Patient may complain of subjective minor sensory symptoms or pain)
Complications
1. Cognitive impairment
2. Respiratory failure
MND caveats and atypical presentation to consider for differential diagnosis
- Limited to either UMN or LMN
- Absence of cranial nerve features
- Involvement of non-motor neurons
- Motor neuronal conduction block on electrophysiological testing
- Consider mimics: lead poisoning, thyrotoxicosis, MMF, poliomyelitis, cervical cord compression
What is fasciculation?
What conditions can cause fasciculations?
Spontaneous firing of large motor units formed by branching fibres of surviving axons that are striving to innervate denervated muscle fibres
Conditions that cause fasciculations
1. Post-exercise
2. Electrolyte deficiency (hypokalaemia, hypomagnesaemia)
3. Thyrotoxic myopathy
4. Cervical spondylosis
5. Syringomyelia
6. HSMN (CMT)
7. Acute poliomyelitis
8. Neuralgic amyotrophy
9. Syphilitic amyotrophy
10. Post-tensilon
11. Benign giant fasciculation
12. SMA
13. Drugs - clofibrate, lithium, salbutamol
What is motor neuron disease?
Examples of MND (4)
Progressive disorder of neuronal loss at all levels of motor system from cortex to brainstem (UMNL) and anterior horn cells of spinal cord (LMNL)
Examples:
1. Amyotrophic lateral sclerosis (ALS): mixed UMM LMN
2. Progressive muscular atrophy/SMA: LMN
3. Primary lateral sclerosis: UMN
4. Progressive bulbar palsy: bulbar involvement
Other similarities:
5. Hereditary spastic paraplegia (HSP): UMN
6. Multifocal motor neuropathy: LMN
Pathophysiology of motor neuron disease?
Death of both upper corticospinal motor neurons and lower motor neurons
- Excitotoxicity
- Glutamate supraphysiological concentration
- Others: AMPA, kainite
- Triggers excessive calcium influx into motor neurons, increased intraneuronal cascade leading to production of excessive free radicals -> cell death
- Eg: riluzole (glutamate release inhibitor) shown some effectiveness as treatment - Free radicals
- Imbalance of anti-oxidants (such as SOD1 gene mutations) leading to excessive free radicals
Genetics of motor neuron disease
Most cases are sporadic (5-10% familial - usually AD)
- SOD1 gene (chromosome 21) - AD
- ALS2 gene (chromosome 2) - AR
- SETX gene (chromosome 9) - AD
- VAPB gene (chromosome 20) - AD
- DCTN1 gene (chromosome 2) - AD
Others:
- Angiogenin (chromosome 14)
- VEGF (chromosome 6)
- Survival motor neuron (chromosome 5)
- Neurofilament protein (chromosome 22)
- Charged multivesicular body protein 2B (chromosome 2)
Clinical course of motor neuron disease
- Onset: 60 years
- Segmental progression - from 1 limb to another
- Mean survival: 3-5 years
- Respiratory failure due to diaphragmatic weakness as main cause of death
What are the features of poor prognosis in MND?
- Older age
- Female
- Bulbar onset
Investigations of motor neuron disease
- MRI brain and spinal cord
- Lumbar puncture - TRO inflammatory cause
- NCS, EMG
- Genetic testing
- Lung function test
- Fiberoptic endoscopic evaluation of swallowing (FEES)
Management of patient with MND
- Multidisciplinary team - Neurology, PT OT ST, Respiratory
- Symptomatic treatment
- Drooling: anticholinergics, hyoscine, glycopyrronium
- Dysphagia: texture and consistency modification, PEG tube
- Speech and language therapy
- Emotional lability: amitriptyline, lithium, levodopa, SSRI
- Fasciculation: phenytoin, CBZ, diazepam
- Spasticity: baclofen
- Limb weakness: PT OT, walking aids
- Respiratory weakness: NIV
- Pain: analgesia, PT OT - Riluzole
- Does not improve symptoms or prognosis
- 3 month increase in survivability only
Amyotrophic lateral sclerosis (ALS)
Mixed UMNL and LMNL
A. Limb weakness
- Asymmetric early -> symmetric later
- Distal -> proximal
- Cramps, volitional movement, spastic resistance
- Fasciculations
- Progressive wasting
- Extensor weakness worse than flexor
- Hyperreflexia (or hyporeflexia)
B. Bulbar/pseudobulbar involvement
- Swallowing difficulty, NGT use
- Facial and tongue fasciculation, atrophy, weakness
- Dysarthria
- Pseudobulbar lability: excessive weep or laughing
C. Complications
- Respiratory failure
- Concurrent frontotemporal dementia
Primary lateral sclerosis (PLS)
Pure UMNL
A. Limb weakness (usually legs)
- Symmetrical involvement
- Spasticity
- Hyperreflexia
- Babinski upgoing
Rarely evolve into ALS
Differential: hereditary spastic paraparesis
Progressive muscular atrophy (PMA)
Pure LMNL
A. Limb weakness
- Asymmetric
- Atrophy
- Fasciculations
- Hyporeflexia
30% may evolve into ALS with UMNL sign
Progressive bulbar palsy
Bulbar UMNL or LMNL
Mostly evolve into ALS with limb involvement
Multifocal motor neuropathy (MMN) is a rare, acquired, immune-mediated disorder of the peripheral nerves
Characterised by:
1. Slowly progressive, asymmetrical LMNL pattern limb weakness.
2. Individual peripheral motor nerves (multifocal pattern).
3. No significant sensory loss
Pathophysiology of multifocal motor neuropathy
Anti-ganglioside GM1 antibodies activates complement and disrupts ion channel function leading to focal motor nerve denervation and conduction block
Examination findings and signs of multifocal motor neuropathy
A. Pure LMNL motor weakness
1. Weakness develops insidiously often over months to years.
2. Asymmetrical, starts in the distal upper limbs
3. Affects muscles supplied by specific nerves
- Wrist drop - radial nerve
- Finger drop - posterior interosseous nerve
- Grip weakness - median/ulnar nerves
- Foot drop (peroneal nerve)
4. Muscle atrophy
5. Fasciculations
B. No UMN signs:
C. No sensory loss
D. Extremely rarely bulbar or respiratory Involvement
Investigations for multifocal motor neuropathy
- Anti-GM1 IgM Antibodies
- Motor NCS - partial motor conduction block
(sensory NCS completely normal) - Needle EMG
- Nerve ultrasound - focal nerve enlargement
- MRI brain and spinal cord - T2 hyperintensity in affected segment
- Lumbar puncture - TRO inflammation/infective cause
Management for multifocal motor neuropathy
- MDT - Neurology, PT, OT
- IVIG - curative
- Refractory - cyclophosphamide or rituximab
Prognosis of multifocal motor neuropathy
No reduced life expectancy
Progressive slowly with cumulative disabilities
Comparison between MMN and MND
Differential diagnoses to consider in:
- Mixed UMN LMN
- Pure UMN
- Pure LMN
Mixed UMN LMN
1. Syringomyelia and syringobulbia - dissociated sensory loss
2. Cervical myelopathy - no bulbar signs, has sensory loss
Pure UMN
1. HIV related myelopathy - has sensory loss
2. Spinal cord tumour - has sensory loss
Pure LMN
1. MMN - asymmetrical
2. CIDP - lumbar puncture
3. SMA - similar to MND
4. Oculopharyngeal muscular dystrophy
5. Kennedy’s syndrome
6. Syphilitic amyotrophy
7. Old poliomyelitis
