How should I evaluate and initially manage a patient suspected of having motor neuron disease (amyotrophic lateral sclerosis)?

Motor Neuron Disease Workup

The workup for suspected motor neuron disease (ALS) requires a systematic approach combining clinical assessment, electrophysiological studies, neuroimaging, and comprehensive laboratory testing to confirm the diagnosis while excluding treatable mimics—a critical step since up to 10% of initially diagnosed ALS cases have reversible conditions. 1

Clinical Diagnostic Criteria

The diagnosis fundamentally requires demonstrating:

• Both upper motor neuron signs (hypertonicity, hyperreflexia, spasticity, Babinski sign) and lower motor neuron signs (fasciculations, muscle weakness, atrophy) 2, 3
• Progressive spread of symptoms within or between body regions 2
• Absence of sensory involvement—if sensory symptoms are present, consider alternative diagnoses 2

The revised El Escorial criteria mandate lower motor neuron signs, upper motor neuron signs, progressive spread, and exclusion of other disease processes through electrophysiological or pathological evidence 2.

Essential Electrophysiological Studies

EMG and nerve conduction velocity studies are mandatory cornerstone tests that detect lower motor neuron degeneration and distinguish ALS from treatable motor neuropathies 3, 1, 4:

• Nerve conduction studies should include at least four sensory and four motor nerves in both arm and leg, with stimulation at three sites in three different nerves to search for conduction blocks that would indicate motor neuropathy rather than ALS 4
• Needle EMG must be extensive, examining at least two limbs (arm and leg with at least five muscles each), thoracic paraspinal muscles, and bulbar muscles 4
• Characteristic findings include widespread non-myotomal denervation (both acute and chronic) with fibrillations and fasciculations 4

Neuroimaging Protocol

MRI brain without IV contrast is the optimal initial imaging modality, primarily to exclude mimics rather than confirm ALS 2, 3:

• Include T2/FLAIR sequences to assess for corticospinal tract hyperintensity in the posterior limb of internal capsule and cerebral peduncles 2
• Include T2*/SWI sequences to detect precentral gyrus hypointensity 2
• MRI cervical and thoracic spine without IV contrast may be appropriate to exclude structural mimics like cervical myelopathy or syrinx, looking for "snake eyes" appearance on T2/STIR images in anterior horns 2, 3

Comprehensive Laboratory Evaluation

A complete laboratory panel is mandatory because up to 10% of patients initially diagnosed with ALS have a treatable mimic disorder 1:

• Complete blood count to evaluate for infectious or inflammatory conditions 3
• Comprehensive metabolic panel including glucose, electrolytes, kidney and liver function 3
• Thyroid function tests to rule out thyroid disorders causing weakness 3
• Vitamin B12, folate, and vitamin E levels to exclude deficiencies 3
• Serum protein electrophoresis to rule out paraproteinemic neuropathies 3
• Anti-ganglioside antibodies to exclude immune-mediated motor neuropathies 3
• Paraneoplastic antibody panel to exclude paraneoplastic syndromes 3
• Anti-acetylcholine receptor and anti-MuSK antibodies to rule out myasthenia gravis 3
• CSF analysis including cell count, protein, glucose, IgG index, oligoclonal bands, and cytology to exclude infectious, inflammatory, or neoplastic causes 3

Genetic Testing

Genetic testing for ALS-associated genes (C9orf72, SOD1, FUS, TARDBP) should be performed, especially in cases with family history of ALS or frontotemporal dementia 2, 3, 1.

Dysphagia Screening at Diagnosis

Dysphagia screening must be performed at diagnosis as part of comprehensive evaluation, even in patients without bulbar symptoms, since swallowing alterations can be present early 5, 3:

• Use structured questionnaires like EAT-10 (sensitivity 86%, specificity 76% for detecting aspiration) 3
• Perform Volume-Viscosity Swallow Test (V-VST) (sensitivity 92%, specificity 80%) 3
• Videofluoroscopy is recommended at diagnosis to detect early signs of dysphagia and silent aspirations 5, 3, 1
• Clinical assessment should evaluate lip closure, saliva pooling, tongue strength and mobility, chewing capacity, palatal movement, cough quality and strength, and phoniatric function 5

Initial Management Framework

Once diagnosis is confirmed, immediate multidisciplinary care referral is essential as it improves both survival and quality of life 2:

• Establish care with neurology, pulmonology, gastroenterology/nutrition, physical therapy, occupational therapy, speech-language pathology, social work, and palliative care 2
• Schedule dysphagia evaluations every 3 months given median survival of 18-28 months and high risk of nutritional compromise 5, 3, 1
• Early palliative care referral is recommended to establish relationships before communication becomes limited 3, 1
• Monitor for respiratory insufficiency, as respiratory failure is the most common cause of death 3, 1

Critical Pitfalls to Avoid

• Do not delay comprehensive laboratory workup—treatable mimics exist in 10% of cases 1
• Do not assume absence of bulbar symptoms means no dysphagia—swallowing alterations occur in 66.7% of patients with "normal eating habits" on clinical scales 5
• Do not rely solely on clinical examination for EMG planning—needle examination must be extensive to demonstrate widespread involvement 4
• Do not skip sensory nerve conduction studies—they are essential to exclude motor neuropathies with conduction blocks 4