Motor Neuron Disease

Question 1

Classification of Neuromuscular disorders:

Answer 1

Myopathy (pure weakness with no sensory involvement or autonomic involvement, usually symmetrical with proximal greater than distal weakness).
- Acquired: Inflammatory, toxic, systemic, endocrine
- Inherited: Muscular dystrophy, mitochondrial, metabolic, congenital myopathy.

Neuromuscular Junction Disorder (fluctuating weakness, absence of sensory or autonomic, symmetrical)
- MG, LE

Peripheral Neuropathy (axonal, demyelinating, mononeuropathy)

Plexopathy (multiple motor and sensory deficits in multiple contiguous nerves, usually painful with diabetic and autoimmune types)

Radiculopathy

Ganglionopathy

Motor Neuron Disease (anterior horn cell) - both UMN and LMN involvement.

Myelopathy

Question 2

Epidemiology of MND

Answer 2

Men > Women
Peak age of onset 60 years
Only 10-15% is familial with mendelian inheritance
Genetics: SOD1, TARDBP, FUS, ANG, OPTN
C9orf72

Question 3

Path of MND

Answer 3

Unclear pathophysiology.
Disease of the ANTERIOR HORN CELL (at the synapse of the UMN and LMN in the spinal cord)

Question 4

MND Phenotypes

Answer 4

Key feature is presence of both upper and lower motor neuron signs, with NO sensory involvement.

Limb onset (75%)
Bulbar onset (25%)
- Bulbar involvement is usually PSEUDO-BULBAR (UMN)
Respiratory muscle involvement

Dementia
- TDP-43-positive cytoplasmic inclusions
- Overlaps with FTD
- Mainly executive function and verbal fluency loss (frontal lobe)

Question 5

Diagnosis of MND

Answer 5

NCS:
- Decreased CMAP
- Normal SNAP (normal sensory function)
- Rule out other potential causes.

EMG:
- Fasciculations, fibrillation potentials, positive sharp waves, chronic neurogenic changes

MRI:
- Corticospinal tract hyper-intensity
- Rule out a myelopathy (could present as mixed UMN/LMN)

Question 6

Treatment of MND:

Answer 6

Riluzole - inhibitor of glutamate release, disease modifying as extends survival by 3-6 months.

Edaravone:
- Free radical scavenger
- Only beneficial in subgroup - disease duration <24 months, FVC >80%, mild disease

Symptomatic control:
- PEG if bulbar dysfunction (CN IX, X, XII)
- Respiratory support with BiPAP