What is the definition of Motor Neuron Disease (MND)?

Definition of Motor Neuron Disease (MND)

Motor neuron diseases (MND) are a group of neurodegenerative disorders characterized by the degeneration of upper motor neurons, lower motor neurons, or both, with amyotrophic lateral sclerosis (ALS) being the most common type, representing approximately 85% of all cases. 1

Classification of Motor Neuron Diseases

• Amyotrophic Lateral Sclerosis (ALS): Characterized by degeneration of both upper and lower motor neurons in the brain and spinal cord along the corticospinal tracts, with an annual incidence of 1-2/100,000 and median survival of 3-4 years after symptom onset 2, 1
• Progressive Muscular Atrophy (PMA): Involves degeneration of only the lower motor neurons, leading to progressive muscle weakness and atrophy without upper motor neuron signs 1
• Progressive Bulbar Palsy (PBP): A variant that primarily affects the bulbar muscles first, causing difficulties with speech, swallowing, and other functions controlled by lower cranial nerves 1
• Pseudobulbar Palsy: Characterized by upper motor neuron dysfunction affecting the bulbar region, causing symptoms like emotional lability, dysarthria, and dysphagia 1
• Atypical variants: Include flail-leg syndrome, flail-arm syndrome, facial-onset sensory and motor neuronopathy (FOSMN), and other rare presentations 3

Clinical Presentation

• Upper motor neuron signs: Hypertonicity and hyperreflexia 2, 1
• Lower motor neuron signs: Muscle fasciculations, weakness, and atrophy 2, 1
• Mixed presentation: Most common in ALS, with both upper and lower motor neuron involvement 2
• Disease progression: Typically leads to progressive muscle weakness, respiratory compromise, and eventually death, usually from respiratory failure 4
• Sporadic vs. Familial: 85-90% of cases are sporadic, while 10-15% have clear genetic inheritance 2, 1

Diagnostic Features

Key Diagnostic Tests

• Electromyography (EMG) and nerve conduction velocity (NCV): Cornerstone tests for diagnosing MND, particularly ALS, as they can detect lower motor neuron degeneration 2, 1
• MRI of the brain without IV contrast: Optimal initial imaging modality, primarily to exclude other conditions with similar clinical presentations rather than to confirm the diagnosis 2, 1
• Spine MRI: May show abnormal T2/STIR signal in the anterior horns ("snake eyes" appearance), though this finding is not specific for ALS and may only appear later in the disease course 2, 5

Distinguishing Features from Other Conditions

• Peripheral neuropathies: Unlike MND, these typically present with both sensory and motor symptoms, often in a length-dependent pattern 5
• Anterior horn cell disorders: Affect the cell bodies of lower motor neurons in the spinal cord, showing characteristic EMG findings of denervation with fibrillation potentials, positive sharp waves, and fasciculations 5

Genetic Factors

• Familial ALS: Has clear genetic inheritance in a minority of patients 1
• Genetic testing: Should be considered for ALS-associated genes (e.g., C9orf72, SOD1, FUS, TARDBP), especially in cases with family history 1, 6

Management Considerations

• Disease-modifying therapy: Riluzole remains the primary medication, prolonging life by 3-4 months 7, 6
• Tofersen: Should be offered to treat SOD1-MND 6
• Supportive care: Multidisciplinary approach including respiratory support (non-invasive positive pressure ventilation), nutritional support (enteral feeding), and palliative care 7, 6

Emerging Developments

• Biomarkers: Neurofilaments are emerging as important biomarkers for MND 6
• Novel therapies: Platform trials and development of new treatments provide optimism for more effective neuroprotective therapies 6
• Research focus: Current research emphasizes environmental causes, gene-environment interactions, and advanced cellular models of disease 6