What are the diagnostic findings and treatment options for a patient with suspected Amyotrophic Lateral Sclerosis (ALS)?

Amyotrophic Lateral Sclerosis: Diagnostic Findings and Treatment

Diagnostic Findings

ALS diagnosis requires demonstrating both upper motor neuron signs (spasticity, hyperreflexia, Babinski sign) and lower motor neuron signs (fasciculations, muscle atrophy, weakness) with progressive spread of symptoms, while systematically excluding treatable mimics through electrophysiological studies and comprehensive laboratory evaluation. 1, 2

Clinical Presentation

• Mixed motor neuron involvement: Patients present with progressive weakness, muscle atrophy, fasciculations, and spasticity in a non-myotomal distribution 3, 4
• Bulbar-onset disease: Approximately 80% of bulbar-onset patients develop dysarthria and dysphagia as presenting symptoms 1
• Focal onset with spread: Disease typically begins focally in one body region (limb, bulbar, or respiratory) and progressively spreads to other regions 5
• Prognosis: Mean survival is 3-5 years after symptom onset, with only 5-10% of patients surviving beyond 10 years 1
• Respiratory failure: The most common cause of death is respiratory muscle weakness leading to respiratory failure 1

Mandatory Electrophysiological Studies

EMG and nerve conduction velocity studies are cornerstone mandatory tests that detect lower motor neuron degeneration and distinguish ALS from treatable motor neuropathies. 2, 6

• Nerve conduction studies: Perform at least four sensory and four motor nerves in both arm and leg, stimulating at least three sites in three different nerves to identify conduction blocks that would indicate motor neuropathy rather than ALS 3
• Needle EMG findings: Widespread non-myotomal denervation with both acute (fibrillations) and chronic changes (fasciculations), demonstrating involvement beyond clinically weak muscles 3
• Extensive sampling required: Examine at least two limbs (arm and leg with at least five muscles each), thoracic paraspinal muscles, and bulbar muscles 3

Neuroimaging

Brain MRI without IV contrast is the primary imaging modality to exclude structural lesions, tumors, and inflammatory conditions that mimic ALS. 2, 6

• Corticospinal tract changes: Look for abnormal T2/FLAIR hyperintensity in the corticospinal tracts, particularly in the posterior limb of the internal capsule and cerebral peduncles 2, 6
• Precentral gyrus findings: T2*-weighted or susceptibility-weighted imaging may show abnormal hypointensity in the precentral gyrus, which can be highly sensitive and specific for ALS 2, 6
• Spine MRI: May be appropriate in certain cases to exclude structural, infectious, or neoplastic etiologies; may show "snake eyes" appearance (abnormal T2/STIR signal in anterior horns), though this is not specific and appears late 6

Comprehensive Laboratory Evaluation to Exclude Mimics

A complete laboratory panel is mandatory because up to 10% of patients initially diagnosed with ALS have a treatable mimic disorder. 2

• Complete blood count: Evaluate for infectious or inflammatory conditions 2, 6
• Comprehensive metabolic panel: Include glucose, electrolytes, kidney function, and liver enzymes 2, 6
• Thyroid function tests: TSH and free T4 to exclude thyroid disorders causing weakness 2, 6
• Vitamin levels: Test B12, folate, and vitamin E to identify deficiencies causing neurological symptoms 2, 6
• Serum protein electrophoresis: Rule out paraproteinemic neuropathies 2, 6
• Anti-ganglioside antibodies: Test GM1, GD1a, GD1b to exclude immune-mediated motor neuropathies like multifocal motor neuropathy 2, 6
• Paraneoplastic antibody panel: Exclude paraneoplastic syndromes 2, 6
• Myasthenia gravis antibodies: Test anti-acetylcholine receptor and anti-MuSK antibodies 2, 6

Cerebrospinal Fluid Analysis

• CSF examination: Perform cell count, protein, glucose, IgG index, oligoclonal bands, and cytology to exclude infectious, inflammatory, or neoplastic causes 2, 6
• CSF protein interpretation: May be normal or mildly elevated in ALS, but marked pleocytosis (>50 cells/μL) suggests alternative diagnoses 6

Genetic Testing

Genetic testing for ALS-associated genes should be performed, particularly when there is family history of ALS or frontotemporal dementia, as approximately 10% of ALS is familial. 2, 6

• Key genes to test: C9orf72 (most common, responsible for 30-50% of familial ALS and 7% of sporadic ALS), SOD1, FUS, and TARDBP 2, 6, 5
• Genetic counseling: Important for family members given autosomal dominant inheritance pattern in familial cases 2, 5

Dysphagia Assessment

Dysphagia screening should be performed at diagnosis and every 3 months thereafter, as swallowing abnormalities can occur even without bulbar symptoms, and early detection prevents aspiration pneumonia. 2

• EAT-10 questionnaire: Has 86% sensitivity and 76% specificity for identifying unsafe swallowing 1, 2
• Volume-Viscosity Swallow Test (V-VST): Demonstrates 92% sensitivity and 80% specificity for detecting dysphagia 1, 2
• Videofluoroscopy: Recommended in the clinical evaluation of dysphagia at diagnosis to detect early signs including oral stasis, piecemeal swallowing, incomplete upper esophageal sphincter relaxation, and silent aspirations 7, 1, 2
• FEES (Fiberoptic endoscopic evaluation): Can identify impaired chewing, tongue muscle deficit, velopharyngeal closure competence, and pharyngeal residues 7

Critical Diagnostic Pitfalls to Avoid

• Do not rely solely on clinical examination: Up to 10% of patients initially diagnosed with ALS have a mimic disorder 2
• Do not skip the comprehensive laboratory panel: Several treatable conditions present identically to ALS 2
• Do not delay genetic testing in familial cases: Genetic counseling is important for family members 2
• Do not overlook early dysphagia: Swallowing abnormalities can occur even without bulbar symptoms 2

Treatment Approach

FDA-Approved Pharmacological Treatment

Riluzole 50 mg twice daily is FDA-approved for ALS treatment and extends survival by approximately 60-90 days. 8

• Mechanism and efficacy: Riluzole demonstrated increased time to tracheostomy or death in two randomized, double-blind, placebo-controlled trials, with median survival differences of approximately 90 days (Study 1) and 60 days (Study 2) 8
• Important limitation: Although riluzole improved survival, measures of muscle strength and neurological function did not show benefit 8
• Dosing: 50 mg twice daily is the recommended dose; lower doses (50 mg per day) could not be statistically distinguished from placebo 8

Multidisciplinary Supportive Care

Nutritional support, respiratory management, and early palliative care referral are essential for improving quality of life and prolonging survival. 1

• Nutritional support: Essential for patients with dysphagia and weight loss 1
• Regular swallowing evaluations: Recommended every 3 months to monitor dysphagia progression 1
• Early palliative care referral: Recommended to establish relationships with staff and address end-of-life issues before communication becomes limited 1
• Respiratory support: Critical given that respiratory failure is the most common cause of death 1
• Caregiver support: Crucial, as caregivers often experience significant burden 1