What are the types of Motor Neuron Disease (MND) and their characteristics?

Types of Motor Neuron Disease and Their Characteristics

Motor neuron diseases (MNDs) 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

Major Types of Motor Neuron Disease

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
• Annual incidence of 1-2/100,000 with median survival of 3-4 years after symptom onset 1
• Clinical features include combination of hypertonicity and hyperreflexia (upper motor neuron signs) along with muscle fasciculations, weakness, and atrophy (lower motor neuron signs) 1
• Most common form, accounting for approximately 85% of all MND cases 1

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
• Characterized by denervation with fibrillation potentials, positive sharp waves, and fasciculations on EMG 2
• Better prognosis than classic ALS 1

Progressive Bulbar Palsy (PBP)

• Variant that primarily affects the bulbar muscles first 1
• Causes difficulties with speech, swallowing, and other functions controlled by lower cranial nerves 1
• Often progresses to involve other motor neurons and may eventually resemble typical ALS 1

Pseudobulbar Palsy

• Characterized by upper motor neuron dysfunction affecting the bulbar region 1
• Symptoms include emotional lability, dysarthria, and dysphagia 1
• Distinguished from PBP by the presence of upper rather than lower motor neuron signs 1

Primary Lateral Sclerosis (PLS)

• Neurodegenerative disorder characterized by a gradually progressive course affecting only the upper motor neurons 3
• Much rarer than ALS 3
• Typically has a slower progression and better prognosis than ALS 3
• Currently no disease-modifying treatment available 3

Diagnostic Features

Clinical Evaluation

• EMG and nerve conduction velocity (NCV) studies are cornerstone tests for diagnosing motor neuron diseases, particularly ALS 1
• Can detect lower motor neuron degeneration and help differentiate from peripheral neuropathies 2
• Needle EMG is essential in the initial evaluation to determine the presence of denervation as evidence of anterior horn cell involvement 2

Neuroimaging

• MRI of the brain without IV contrast is the optimal initial imaging modality for patients with suspected motor neuron disease 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 Factors

• Familial ALS has clear genetic inheritance in a minority of patients 1
• Genetic testing for ALS-associated genes (e.g., C9orf72, SOD1, FUS, TARDBP) should be considered, especially in cases with family history 1
• The most common mutation is a hexanucleotide repeat expansion in C9orf72, accounting for 10% of all Western hemisphere ALS 4

Differential Diagnosis Considerations

• Peripheral neuropathies typically present with both sensory and motor symptoms, often in a length-dependent pattern, unlike MNDs which primarily affect motor function 2
• Cervical spondylotic myelopathy can mimic anterior horn cell disorders but typically has sensory involvement in addition to upper motor neuron signs 2
• When sensory symptoms are present in a patient with suspected motor neuron disease, clinicians should consider alternative diagnoses or comorbid conditions 1

Management Approaches

• Evidence-based management involves riluzole, multidisciplinary care, provision of noninvasive ventilation and gastrostomy, and symptomatic treatments 5
• Tofersen should be offered to treat SOD1-MND 5
• Edaravone and Relyvrio are approved treatments in the USA, but insufficient evidence was found to support approval in the UK and Europe 5
• In the absence of curative or disease-modifying therapy for most forms, management is supportive and requires a multidisciplinary approach 6