What are the main types of Motor Neuron Disease (MND)?

The Four Main Types of Motor Neuron Disease

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

Main Types of Motor Neuron Disease

1. Amyotrophic Lateral Sclerosis (ALS)

   • Characterized by degeneration of both upper and lower motor neurons in the brain and spinal cord along the corticospinal tracts 1
   • Presents with a combination of hypertonicity and hyperreflexia (upper motor neuron signs) and muscle fasciculations, weakness, and atrophy (lower motor neuron signs) 1
   • Has an annual incidence of 1-2/100,000 and median survival of 3-4 years after symptom onset 1
   • Accounts for approximately 85% of all MND cases 1

2. Progressive Muscular Atrophy (PMA)

   • Involves degeneration of only the lower motor neurons 1
   • Leads to progressive muscle weakness and atrophy without upper motor neuron signs 1
   • Primarily affects the anterior horn cells of the spinal cord 2
   • Presents with denervation patterns on EMG including fibrillation potentials, positive sharp waves, and fasciculations 2

3. Progressive Bulbar Palsy (PBP)

   • Primarily affects the bulbar muscles first 1
   • Causes difficulties with speech, swallowing, and other functions controlled by lower cranial nerves 1
   • Involves degeneration of motor neurons in the brainstem that control muscles of the face, mouth, and throat 1
   • Often progresses to more generalized ALS over time 1

4. Pseudobulbar Palsy

   • Characterized by upper motor neuron dysfunction affecting the bulbar region 1
   • Causes symptoms like emotional lability, dysarthria, and dysphagia 1
   • Results from bilateral damage to corticobulbar tracts 1
   • Distinguished from Progressive Bulbar Palsy by the presence of upper rather than lower motor neuron signs 1

Diagnostic Features

• Electromyography (EMG) and nerve conduction velocity (NCV) studies are cornerstone tests for diagnosing motor neuron diseases 1
• MRI of the brain without IV contrast is the optimal initial imaging modality, primarily to exclude other conditions with similar clinical presentations 1
• Common MRI findings in ALS include abnormal T2/FLAIR signal in the corticospinal tracts, particularly in the posterior limb of the internal capsule and cerebral peduncles 1
• Spine MRI may show abnormal T2/STIR signal in the anterior horns ("snake eyes" appearance) 1
• Genetic testing should be considered, especially in cases with family history, for ALS-associated genes (e.g., C9orf72, SOD1, FUS, TARDBP) 1

Clinical Considerations

• Motor neuron diseases must be distinguished from peripheral neuropathies, which typically present with both sensory and motor symptoms 2
• ALS patients have an average life expectancy of 3-5 years, making proper diagnosis, care, and treatment essential 3
• Evidence-based management involves riluzole, multidisciplinary care, provision of noninvasive ventilation and gastrostomy, and symptomatic treatments 4
• Tofersen should be offered to treat SOD1-MND, while edaravone and Relyvrio are approved treatments in the USA 4
• The discovery of neurofilaments as MND biomarkers provides optimism for more powerful neuroprotective therapies 4

Pathophysiology

• Motor neuron degeneration in ALS appears to be a form of apoptotic cell death that may occur by an abnormal programmed cell death mechanism 5
• Recent genetic studies have identified disease-causing mutations in genes in several seemingly disparate functional pathways 6
• Motor neuron degeneration may need to be understood as a common final pathway with a number of upstream causes 6
• The most common mutation, accounting for 10% of all Western hemisphere ALS, is a hexanucleotide repeat expansion in C9orf72 6