What is the best way to diagnose Amyotrophic Lateral Sclerosis (ALS)?

Diagnosis of Amyotrophic Lateral Sclerosis (ALS)

The best way to diagnose ALS is through a combination of clinical evaluation and electrodiagnostic studies (EMG and nerve conduction studies), followed by instrumental assessment with either videofluoroscopic swallow evaluation (VSE) or fiberoptic endoscopic evaluation of swallowing (FEES) to confirm the diagnosis and assess swallowing function. 1, 2

Clinical Evaluation and Diagnostic Criteria

The diagnosis of ALS is primarily clinical and requires evidence of both:

• Upper motor neuron (UMN) degeneration: spasticity, hyperreflexia, pathological reflexes
• Lower motor neuron (LMN) degeneration: weakness, atrophy, fasciculations

Key diagnostic steps include:

1. Clinical examination to identify progressive weakness in any body segment (bulbar, cervical, thoracic, or lumbosacral) 3

   • Look for combined UMN and LMN signs in the same region
   • Assess for fasciculations, muscle atrophy, and weakness
   • Evaluate bulbar symptoms (speech, swallowing difficulties)

2. Electrodiagnostic studies (essential for diagnosis) 2, 3

   • EMG to detect denervation in multiple body regions
   • Nerve conduction studies to exclude other conditions
   • These tests improve diagnostic sensitivity and help rule out treatable mimics

3. Exclusion of ALS mimics through laboratory and imaging studies 4, 3

   • MRI of brain and spinal cord to rule out structural lesions
   • Laboratory tests to exclude metabolic, infectious, or autoimmune conditions
   • Consider genetic testing for familial ALS cases

Swallowing Assessment in ALS

Even in early stages, swallowing assessment is crucial:

• Screening tools with high sensitivity and specificity 1:

  • EAT-10 questionnaire (sensitivity 86%, specificity 76%)
  • Volume-Viscosity Swallow Test (V-VST) (sensitivity 92%, specificity 80%)

• Instrumental assessment 5, 1:

  • Videofluoroscopy (VFS) is recommended for all ALS patients at diagnosis, even without bulbar symptoms
  • FEES can identify impaired chewing, tongue muscle deficit, and detect pharyngeal residues
  • These tests can detect silent aspirations that may be missed by clinical examination alone

Common Diagnostic Pitfalls

• Delayed diagnosis due to lack of awareness about ALS among physicians 4
• Missing silent aspirations by relying solely on clinical examination without instrumental assessment 1
• Misdiagnosis of ALS variants such as progressive bulbar palsy, progressive muscular atrophy, or primary lateral sclerosis 4
• Overlooking dysphagia in patients with "normal eating habits" 1

Diagnostic Algorithm

1. Suspect ALS in patients with progressive weakness, especially when both UMN and LMN signs are present
2. Perform comprehensive EMG and nerve conduction studies
3. Order MRI of brain and spinal cord to exclude structural lesions
4. Conduct laboratory tests to rule out other conditions
5. Perform swallowing assessment with VFS or FEES, even in patients without obvious bulbar symptoms
6. Consider genetic testing in cases with family history
7. Apply El Escorial diagnostic criteria to confirm the diagnosis

Early and accurate diagnosis is critical as ALS patients have a median survival of only 2-5 years from symptom onset 1, 2, and proper diagnosis enables timely intervention to improve quality of life.