Amyotrophic Lateral Sclerosis (ALS) typically presents in adults aged 40-60 years, with progressive weakness, muscle atrophy, and fasciculations due to degeneration of upper and lower motor neurons appearing as increased T2 signal in the corticospinal tract and brainstem.
Description
Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive neurodegenerative disorder affecting motor neurons in the brain and spinal cord. This leads to muscle weakness, atrophy, and spasticity. ALS is predominantly sporadic but can be familial in about 10% of cases, with several genetic mutations identified.
Pathogenesis
ALS is characterised by the progressive loss of both upper and lower motor neurons. While the exact pathogenesis is unknown, it involves a combination of genetic predisposition and environmental factors. Molecular pathways implicated include glutamate excitotoxicity, mitochondrial dysfunction, oxidative stress, and abnormal protein aggregation.
Subtypes
- Sporadic ALS: The most common form, accounting for about 90% of cases.
- Familial ALS: Constitutes about 10%, with mutations in SOD1, C9orf72, and TARDBP genes.
- Guamanian ALS: A distinct variant associated with high incidence in Guam, linked to environmental factors.
Epidemiology, Risk Factors & Associations
- Average onset age: 55 years.
- Slightly more common in males.
- Genetic mutations are risk factors in familial cases.
- Environmental factors: Smoking, military service, and possible exposure to toxins or viruses.
Clinical Features
- Progressive muscle weakness and atrophy.
- Fasciculations and muscle cramps.
- Dysarthria, dysphagia, and respiratory muscle weakness in advanced stages.
- Cognitive changes can occur, particularly in C9orf72 mutation carriers.
Complications
- Respiratory failure is the most common cause of death.
- Malnutrition and aspiration due to bulbar dysfunction.
- Increased risk of pneumonia.
Pathological Features
Histopathology
- Macroscopic: Atrophy of the affected spinal cord regions and motor cortex.
- Microscopic: Loss of motor neurons, presence of Bunina bodies, and TDP-43 inclusions in neurons.
Serology
- Elevated creatine kinase (CK) due to muscle breakdown.
Biochemistry
- Non-specific but may include markers of muscle damage and neurodegeneration.
Radiological Features
General Features
- Bilateral hyperintensities along corticospinal tract extending from corona radiata to brainstem on T2WI/PD/FLAIR
- Atrophy of the precentral gyrus and spinal cord on advanced stages.
CT
- May show cortical atrophy in late stages.
MRI
- T1: Cortical atrophy in advanced disease.
- T2: Hyperintensity in the corticospinal tract.
- FLAIR: Cortical atrophy and hyperintense signal in corticospinal tract.
- T1 Gad+: Not typically used.
- SWI/GRE/T2*: May show iron deposition in motor cortex.
NM
- PET FDG: Can show reduced glucose uptake in motor cortex.
Grading and Staging
No formal grading or staging system for ALS.
Diagnosis
Diagnosis of ALS is primarily clinical, supported by electromyography (EMG) to demonstrate denervation, and exclusion of other conditions. MRI can aid in excluding alternative diagnoses.
Differential Diagnosis
- Multifocal Motor Neuropathy: Characterized by conduction block on nerve conduction studies.
- Spinal Muscular Atrophy: Predominantly lower motor neuron signs.
- Primary Lateral Sclerosis: Slow progression, predominantly upper motor neuron signs.
Management
Management is mainly supportive and symptomatic, involving multidisciplinary care with neurologists, physiotherapists, occupational therapists, and speech therapists. Riluzole and edaravone are medications used to slow disease progression.