Investigation for Amyotrophic Lateral Sclerosis (ALS)

Introduction to Diagnostic Approach

The American Academy of Neurology recommends that the investigation of ALS requires electromyography (EMG) and nerve conduction studies as the cornerstone diagnostic tests, combined with MRI brain imaging to exclude mimics, and a comprehensive panel of laboratory tests to rule out treatable conditions that can present similarly 1, 2

EMG and nerve conduction velocity (NCV) studies are mandatory for diagnosing ALS as they detect lower motor neuron degeneration and distinguish ALS from other conditions 1, 2, 3
MRI brain without IV contrast is the initial imaging study of choice to exclude structural lesions, inflammatory conditions, and other diseases that mimic ALS 1, 2, 3

Abnormal T2/FLAIR signal in corticospinal tracts, particularly in the posterior limb of internal capsule and cerebral peduncles, is a common MRI finding in ALS (supportive but not diagnostic) 1, 3
Abnormal hypointensity in precentral gyrus on T2*-weighted or susceptibility-weighted imaging (highly sensitive and specific) is a common MRI finding in ALS (supportive but not diagnostic) 1

A comprehensive metabolic and immunologic workup is essential to exclude conditions that can be treated and present with similar symptoms 1, 2
Complete blood count (CBC) to evaluate for infectious or inflammatory conditions is recommended 1, 2
Blood chemistry profile including glucose, electrolytes, kidney function, and liver enzymes is recommended 1, 2
Thyroid function tests to rule out thyroid disorders causing weakness are recommended 1, 2
Vitamin B12, folate, and vitamin E levels to exclude nutritional deficiencies are recommended 1, 2
Serum protein electrophoresis to rule out paraproteinemic neuropathies is recommended 1, 2
Anti-ganglioside antibodies (GM1, GD1a, GD1b) to exclude immune-mediated motor neuropathies are recommended 1, 2
Paraneoplastic antibody panel to exclude paraneoplastic syndromes is recommended 1, 2
Anti-acetylcholine receptor and anti-MuSK antibodies to rule out myasthenia gravis are recommended 1, 2

CSF examination should include cell count, protein, glucose, IgG index, oligoclonal bands, and cytology to exclude infectious, inflammatory, or neoplastic causes 1, 2
Marked pleocytosis (>50 cells/μL) suggests an alternative diagnosis and should prompt reconsideration of ALS 1

Screening for dysphagia should be performed at diagnosis and every 3 months during follow-up as part of comprehensive neurological evaluation, even in patients without bulbar symptoms 4, 5
Structured questionnaires (EAT-10) have 86% sensitivity and 76% specificity for identifying unsafe swallowing 5, 2
Volume-Viscosity Swallow Test (V-VST) has 92% sensitivity and 80% specificity for detecting dysphagia 5, 6, 2
Videofluoroscopy should be performed at diagnosis to detect early signs of dysphagia and silent aspirations 7, 6, 2

The diagnosis requires evidence of both upper and lower motor neuron degeneration with progressive spread of symptoms 2
Upper motor neuron signs: Hypertonicity, hyperreflexia, spasticity 3
Lower motor neuron signs: Muscle fasciculations, weakness, atrophy 3
Progressive spread through different body regions over time 2