ALS Initial Workup
The initial workup for suspected ALS requires EMG/nerve conduction studies as the cornerstone diagnostic test, combined with brain MRI to exclude mimics, and a comprehensive laboratory panel to rule out treatable conditions that present similarly. 1, 2, 3
Clinical Evaluation
The diagnosis requires demonstrating both upper motor neuron (UMN) and lower motor neuron (LMN) degeneration with progressive spread of symptoms. 1, 2
Upper motor neuron signs to identify: 2
- Hypertonicity
- Hyperreflexia
- Spasticity
Lower motor neuron signs to identify: 2
- Muscle fasciculations
- Weakness (strength ≤4 on any muscle strongly suggests ALS rather than primary lateral sclerosis) 4
- Atrophy
Key clinical features at presentation: 4
- Site of onset (limb vs bulbar)
- Lowest strength score of weakest muscle
- Presence of dysphagia or dysarthria (occurs in ~80% of bulbar-onset cases) 1
Mandatory Electrophysiological Testing
EMG and nerve conduction velocity (NCV) studies are non-negotiable as they detect lower motor neuron degeneration and distinguish ALS from mimicking conditions. 1, 2, 3, 5 Look for fibrillation potentials, positive sharp waves, fasciculation potentials at rest, incomplete interference patterns, and abnormal motor unit potentials. 5
Neuroimaging
MRI brain without IV contrast is the required initial imaging study to exclude structural lesions, inflammatory conditions, and other ALS mimics. 1, 2, 3
MRI spine without IV contrast may be appropriate when structural, infectious, or neoplastic spinal etiologies need exclusion. 1, 3
Supportive (but not diagnostic) MRI findings include abnormal T2/FLAIR signal in corticospinal tracts (posterior limb of internal capsule, cerebral peduncles) and abnormal hypointensity in precentral gyrus on T2*/susceptibility-weighted imaging. 2, 3
Comprehensive Laboratory Panel
This panel excludes treatable conditions that mimic ALS: 1, 2, 3
Basic metabolic workup:
- Complete blood count (CBC) 1, 2, 3
- Comprehensive metabolic panel (glucose, electrolytes, kidney function, liver enzymes) 1, 2, 3
Endocrine and nutritional:
Immunologic/autoimmune:
- Serum protein electrophoresis 1, 2, 3
- Anti-ganglioside antibodies (GM1, GD1a, GD1b) 1, 2, 3
- Paraneoplastic antibody panel 1, 2, 3
- Anti-acetylcholine receptor and anti-MuSK antibodies 1, 2, 3
Cerebrospinal Fluid Analysis
CSF examination should include: cell count, protein, glucose, IgG index, oligoclonal bands, and cytology to exclude infectious, inflammatory, or neoplastic causes. 1, 2, 3
Critical caveat: Marked pleocytosis (>50 cells/μL) argues strongly against ALS and should prompt reconsideration of the diagnosis. 2, 3
Genetic Testing
Consider genetic testing for ALS-associated genes (C9orf72, SOD1, FUS, TARDBP), particularly when family history is present. 1, 3 Approximately 10% of ALS cases are familial. 6
Dysphagia Screening
Screen for dysphagia at diagnosis even in patients without bulbar symptoms, as early swallowing alterations occur frequently. 7, 1, 2
Recommended screening tools: 1, 2
- Structured questionnaires (EAT-10): 86% sensitivity, 76% specificity
- Volume-Viscosity Swallow Test (V-VST): 92% sensitivity, 80% specificity
- Videofluoroscopy at diagnosis to detect early dysphagia and silent aspirations
Establish 3-month follow-up intervals for dysphagia monitoring as part of comprehensive neurological evaluation. 7, 1, 2
Common Diagnostic Pitfalls
Average diagnostic delay is 10-16 months due to ALS heterogeneity and the need to exclude mimicking conditions. 6 The absence of a definitive biomarker makes clinical and electrophysiological assessment paramount. 5, 6
Weight loss occurs disproportionately even when controlled for dysphagia and muscle atrophy, making it a useful clinical marker. 4
Patients presenting with only UMN signs require serial monitoring of strength, weight, forced vital capacity, and repeat EMG, as changes signal imminent LMN involvement. 4