CloudNeuro

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons, leading to muscle weakness, atrophy, and eventually paralysis.

What is involved?

Motor Neurons (Upper and Lower Motor Neurons)

Location

Motor cortex (upper motor neurons)
Brainstem motor nuclei (lower motor neurons)
Anterior horn cells of the spinal cord (lower motor neurons)

Common symptoms

Progressive weakness typically starting asymmetrically
Muscle wasting (atrophy)
Fasciculations (muscle twitching)
Muscle cramps and stiffness
Difficulty with fine motor tasks (buttoning, writing)
Foot drop or hand weakness
Speech difficulties (dysarthria)
Swallowing problems (dysphagia)
Respiratory insufficiency in later stages
Sensation is preserved - this is a key diagnostic feature

Onset

Insidious onset over weeks to months
Most commonly between ages 55-75
Mean survival 3-5 years from symptom onset
Bulbar onset has shorter survival than limb onset

Risk factors

Age over 40
Male gender (slightly higher risk)
Family history of ALS (5-10% familial)
Genetic factors (C9orf72, SOD1 mutations)
Smoking
Military service
Possible environmental factors (heavy metals, pesticides)

Exam

Must demonstrate both Upper Motor Neuron (UMN) and Lower Motor Neuron (LMN) signs:

Lower Motor Neuron Signs

Weakness
Atrophy
Fasciculations
Decreased or absent reflexes in atrophied muscles

Upper Motor Neuron Signs

Spasticity
Hyperreflexia (brisk reflexes in non-atrophied regions)
Babinski sign (upgoing toes)
Hoffman sign
Clonus
Jaw jerk (in bulbar involvement)

Distribution

Signs must be present in multiple body regions (bulbar, cervical, thoracic, lumbosacral)
Split hand sign (thenar > hypothenar weakness) is characteristic

EMG

EMG is the most important diagnostic test for ALS.

Diagnostic Criteria (Awaji-Shima)

Active denervation in at least 3 of 4 body regions:

Bulbar
Cervical
Thoracic
Lumbosacral

Findings

Fibrillation potentials and positive sharp waves (active denervation) in multiple muscles
Fasciculation potentials - count as evidence of denervation per Awaji criteria
Large, polyphasic motor unit potentials (chronic reinnervation)
Reduced recruitment with rapid firing rates
Normal sensory nerve conductions - essential for diagnosis
Motor amplitudes may be reduced but conduction velocities near normal
No conduction block - if present, consider multifocal motor neuropathy
Sample muscles from different nerve/root territories in each region

Important Points

Must sample at least 3 regions
Include thoracic paraspinals (T6-T12) if possible
Tongue EMG helpful for bulbar involvement
Follow-up EMG may be needed if initial study inconclusive

Recommendations

Early referral to ALS multidisciplinary clinic
FDA-approved medications:
- Riluzole (modest survival benefit)
- Edaravone (may slow decline in selected patients)
- Sodium phenylbutyrate/taurursodiol (Relyvrio)
Respiratory monitoring (FVC every 3 months)
Non-invasive ventilation (BiPAP) when FVC drops below 50%
Nutritional support and PEG tube when swallowing unsafe
Physical and occupational therapy
Speech therapy and augmentative communication devices
Psychological support
Advance care planning
Clinical trial consideration

What else could it be?

Treatable mimics must be excluded:

Multifocal Motor Neuropathy - conduction block on EMG, responds to IVIG
Cervical myelopathy with radiculopathy - MRI shows cord compression
Kennedy’s Disease (SBMA) - X-linked, sensory involvement, gynecomastia, slow progression
Inclusion Body Myositis - finger flexor and quadriceps weakness, elevated CK
Myasthenia Gravis - fatigable weakness, responds to treatment
Primary Lateral Sclerosis - pure UMN, slower progression
Progressive Muscular Atrophy - pure LMN, better prognosis
Benign Fasciculation Syndrome - fasciculations without weakness or EMG abnormalities
Hirayama Disease - young males, cervical flexion myelopathy
Post-polio syndrome - history of polio