What are the steps for diagnosing and managing Amyotrophic Lateral Sclerosis (ALS)?

Diagnosing Amyotrophic Lateral Sclerosis (ALS)

The diagnosis of ALS requires demonstrating both upper and lower motor neuron degeneration with progressive spread, confirmed through clinical examination and electromyography, while systematically excluding mimicking conditions through targeted laboratory testing and neuroimaging. 1, 2

Clinical Presentation to Recognize

Look for the combination of:

• Upper motor neuron signs: Hypertonicity, hyperreflexia, spasticity 2
• Lower motor neuron signs: Muscle fasciculations, weakness, atrophy 2
• Progressive spread of symptoms within or between body regions 1, 2
• Painless progressive weakness without sensory involvement 3
• Bulbar-onset features (80% of bulbar-onset cases): Dysarthria and dysphagia 1

When sensory symptoms are present, strongly consider alternative diagnoses rather than ALS 2.

Essential Diagnostic Testing

Electrophysiological Studies (Cornerstone Tests)

• Electromyography (EMG) and nerve conduction velocity (NCV) studies are the most critical diagnostic tests, detecting lower motor neuron degeneration and distinguishing ALS from other conditions 1, 4

Neuroimaging to Exclude Mimics

• MRI brain without IV contrast is the initial imaging study, looking for: 1, 4
  • Abnormal T2/FLAIR signal in corticospinal tracts (posterior limb of internal capsule, cerebral peduncles) 2, 4
  • Abnormal hypointensity in precentral gyrus on T2*/SWI sequences (highly sensitive and specific) 4
• MRI spine without IV contrast may be appropriate to exclude cervical myelopathy, syrinx, or neoplastic causes 1, 4
  • Look for "snake eyes" appearance on T2/STIR in anterior horns (not specific, appears late) 2, 4

Laboratory Tests to Exclude Treatable Mimics

Perform the following blood tests systematically: 1, 4

• Complete blood count (CBC)
• Comprehensive metabolic panel (glucose, electrolytes, kidney and liver function)
• Thyroid function tests
• Vitamin B12, folate, and vitamin E levels
• Serum protein electrophoresis
• Anti-ganglioside antibodies (GM1, GD1a, GD1b)
• Paraneoplastic antibody panel
• Anti-acetylcholine receptor and anti-MuSK antibodies

Cerebrospinal Fluid Analysis

• CSF examination including cell count, protein, glucose, IgG index, oligoclonal bands, and cytology 1, 4
• Marked pleocytosis (>50 cells/μL) suggests an alternative diagnosis 4

Genetic Testing

• Consider testing for ALS-associated genes (C9orf72, SOD1, FUS, TARDBP), particularly with family history 1, 4
• C9orf72 repeat expansions account for approximately 40% of familial cases and 10% of sporadic cases 3

Diagnostic Criteria

The revised El Escorial criteria require: 2

• Lower motor neuron signs
• Upper motor neuron signs
• Progressive spread within or to other regions
• Absence of electrophysiological or pathological evidence of other disease processes

Evaluating Dysphagia in ALS

Since dysphagia affects 80% of bulbar-onset patients and impacts mortality, systematic evaluation is essential: 1

Screening Tools

• EAT-10 questionnaire: Sensitivity 86%, specificity 76% for identifying unsafe airway protection 5, 1
• Volume-Viscosity Swallow Test (V-VST): Sensitivity 92%, specificity 80% for detecting dysphagia 5, 1

Instrumental Evaluation

• Videofluoroscopy should be performed at diagnosis to detect early dysphagia signs, identify silent aspirations, and evaluate compensatory postures 5, 1
• Fiberoptic endoscopic evaluation of swallowing (FEES) can identify chewing deficits, tongue muscle weakness, and pharyngeal residues 5
• Repeat swallowing evaluations every 3 months to monitor progression 1

Management Approach

Disease-Modifying Treatment

• Riluzole 50 mg twice daily is FDA-approved and should be initiated as early as possible 6, 7
  • Take at least 1 hour before or 2 hours after meals 6
  • Extends survival by approximately 60-90 days 6
  • Measure serum aminotransferases before and during treatment 6
  • Discontinue if liver dysfunction develops or baseline transaminases exceed 5 times upper limit of normal 6

Multidisciplinary Care

Establish care with a multidisciplinary team immediately, as this approach improves survival and quality of life: 2, 7

• Neurology
• Pulmonology (for non-invasive ventilation when respiratory insufficiency develops) 2
• Gastroenterology/nutrition (for PEG tube placement before respiratory insufficiency) 7
• Physical therapy, occupational therapy, speech-language pathology
• Social work and palliative care 2

Early Palliative Care

• Refer to palliative services early to establish relationships before communication becomes limited 1
• Discuss advance directives early with patients and caregivers, respecting cultural background 7

Prognostic Information

• Mean survival is 3-5 years after symptom onset 1, 2
• Only 5-10% of patients survive longer than 10 years 1
• Respiratory failure from respiratory muscle weakness is the most common cause of death 1

Critical Pitfalls to Avoid

• Delayed diagnosis: The average time from symptom onset to diagnosis is 12 months, but earlier diagnosis allows earlier riluzole initiation and multidisciplinary care, which improve outcomes 8
• Missing the diagnosis entirely: Many physicians, including neurologists, miss ALS due to lack of familiarity with the disease 9
• Delaying PEG tube placement: Gastrostomy should be placed before respiratory insufficiency develops 7
• Ignoring caregiver burden: Provide support for caregivers throughout the disease course 1