What are the essential steps and considerations for diagnosing and managing ALS in an adult patient over 55 years old with progressive muscle weakness, atrophy, or fasciculations?

Diagnosing ALS in Adults Over 55 with Progressive Muscle Weakness

For an adult over 55 presenting with progressive muscle weakness, atrophy, or fasciculations, ALS diagnosis requires demonstrating both upper and lower motor neuron degeneration across multiple body regions through clinical examination and mandatory electrophysiological studies, while systematically excluding treatable mimics through targeted laboratory testing and neuroimaging. 1, 2

Clinical Diagnostic Criteria

The diagnosis of ALS fundamentally depends on recognizing the characteristic pattern of combined upper and lower motor neuron involvement 3:

Upper motor neuron signs:

• Hypertonicity and hyperreflexia 3
• Spasticity in affected limbs 1

Lower motor neuron signs:

• Muscle fasciculations (visible muscle twitching) 3, 4
• Progressive muscle weakness 1
• Muscle atrophy 3, 4

Critical consideration for patients over 55: In this age group with vascular risk factors, you must apply more stringent diagnostic criteria and require a higher number of periventricular lesions on imaging to distinguish ALS from vascular or age-related conditions 5. Approximately 10% of patients initially diagnosed with ALS actually have a mimic disorder, making systematic exclusion of alternatives mandatory 2.

Essential Electrophysiological Studies (Mandatory)

EMG and nerve conduction velocity (NCV) studies are non-negotiable for ALS diagnosis 2, 4:

• Nerve conduction studies: Test at least four sensory and four motor nerves in both an arm and leg 4. Stimulate at least three sites in three different nerves to identify conduction blocks that would indicate treatable motor neuropathy rather than ALS 4.

• Needle EMG findings diagnostic of ALS:

  • Widespread non-myotomal denervation (both acute and chronic) 4
  • Fibrillations and fasciculations 4
  • Must examine at least two limbs (arm and leg; minimum five muscles each), thoracic paraspinal muscles, and bulbar muscles 4

The EMG demonstrates lower motor neuron degeneration in muscles that may not yet be clinically weak, establishing the widespread nature of the disease 4.

Neuroimaging Protocol

Order brain MRI without IV contrast as the primary imaging modality 2:

What to look for on MRI:

• Abnormal T2/FLAIR hyperintensity in the corticospinal tracts, particularly in the posterior limb of the internal capsule and cerebral peduncles 2
• Abnormal T2 signal in the anterior horns with a "snake eyes" appearance, reflecting lower motor neuron disease 2, 3
• T2*-weighted or susceptibility-weighted imaging may show abnormal hypointensity in the precentral gyrus (highly sensitive and specific for ALS) 2

Purpose: Exclude structural lesions, tumors, inflammatory conditions, and vascular disease that mimic ALS 2.

Mandatory Laboratory Testing to Exclude Mimics

Do not skip this comprehensive panel—several treatable conditions present identically to ALS 2:

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

Cerebrospinal Fluid Analysis

Perform CSF examination to exclude inflammatory/infectious mimics 2:

• Cell count, protein, glucose 2
• IgG index and oligoclonal bands 2
• Cytology 2

Genetic Testing Considerations

Order genetic testing when there is a family history of ALS or frontotemporal dementia 2:

• Test for key genes: C9orf72, SOD1, FUS, and TARDBP 2, 6
• Approximately 10% of ALS is familial, making genetic counseling important for family members 2
• Genetic factors may be involved even without obvious family history and may be underestimated 6

Early Dysphagia Assessment (Often Overlooked)

Screen for dysphagia at diagnosis and every 3 months thereafter, even without bulbar symptoms 2:

• EAT-10 questionnaire: 86% sensitivity and 76% specificity for identifying unsafe swallowing 2
• Volume-Viscosity Swallow Test (V-VST): 92% sensitivity and 80% specificity for detecting dysphagia 2
• Videofluoroscopy for instrumental assessment when dysphagia symptoms are present 2

Why this matters: Swallowing abnormalities can occur even without bulbar symptoms, and early detection prevents aspiration pneumonia 2. Approximately 80% of bulbar-onset patients develop dysarthria and dysphagia 1, 3.

Common 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, 7. Diagnostic delays are common due to heterogeneous presentation and overlap with other neurological conditions 1.

Atypical presentations that delay diagnosis 1:

• Asymmetric or predominantly proximal/distal weakness
• Severe diffuse pain preceding weakness
• Symptom onset in less than 24 hours (suggests stroke or other acute process)
• Progression to maximum disability after more than 4 weeks (consider other diagnoses)

Recognize restricted presentations requiring exclusion of alternatives 8:

• Pure bulbar presentation (progressive bulbar palsy)
• Pure lower motor neuron signs (progressive muscular atrophy)
• Pure upper motor neuron signs (primary lateral sclerosis)

Initial Management Considerations

Once ALS is diagnosed, initiate multidisciplinary palliative care immediately—not at end-stage disease 3:

• Mean survival is 3-5 years after symptom onset 1, 3, 9
• Only 5-10% of patients live longer than 10 years 1, 3
• Respiratory failure is the most common cause of death 3

Early interventions that improve survival and quality of life:

• Nutritional support for dysphagia and weight loss 3
• Non-invasive ventilation when respiratory function declines 10
• Riluzole therapy (improves survival but marginal effect on functional deterioration) 10
• Edaravone injection (60 mg IV over 60 minutes, initial 14-day cycle followed by 10 days out of 14-day cycles) slows decline in ALSFRS-R scores 9

Advance care planning must begin at diagnosis, before communication becomes limited 3. Early referral to palliative services establishes relationships with staff and addresses end-of-life issues while the patient can still participate in decision-making 3.