Amyotrophic Lateral Sclerosis: Diagnostic and Treatment Approach
Immediate Diagnostic Strategy
Refer immediately to an experienced neurologist for clinical diagnosis, as ALS is diagnosed primarily through clinical examination showing combined upper and lower motor neuron signs, not through any single confirmatory test. 1
Clinical Examination Findings to Establish Diagnosis
- Upper motor neuron signs: hypertonicity, hyperreflexia, and pathological reflexes 1
- Lower motor neuron signs: muscle fasciculations, progressive weakness, and atrophy 1, 2
- Preserved functions that distinguish ALS: sphincter control remains intact, sensory function is normal, intellectual abilities are preserved (in 60% of patients), and skin integrity is maintained 2
Essential Diagnostic Testing
- MRI brain and spine (without contrast) to exclude structural lesions mimicking ALS and identify characteristic findings: abnormal T2/FLAIR signal in corticospinal tracts and "snake eyes" appearance in anterior horns 1
- Electromyography to support the diagnosis by demonstrating widespread denervation 3
- Genetic testing for C9orf72, SOD1, TARDBP, and FUS mutations, particularly if family history exists (C9orf72 accounts for 40% of familial cases and 10% of sporadic cases) 3
Baseline Assessments Required at Diagnosis
- Videofluoroscopy for all patients at diagnosis to detect early dysphagia and silent aspiration, even without symptoms 1
- Pulmonary function testing: measure forced vital capacity (FVC), slow vital capacity (SVC), and maximum expiratory pressure (MEP) 4
- Nutritional assessment: BMI and weight (malnutrition at diagnosis increases death risk >4-fold) 1
- Cognitive screening: up to 40% have cognitive impairment affecting treatment decisions 1
Immediate Management Framework
Initiate multidisciplinary care immediately upon diagnosis, as this approach prolongs survival and improves quality of life more than any single intervention. 4
Pharmacological Treatment
- Start riluzole immediately as the only medication proven to modestly prolong survival (glutamate receptor antagonist) 5, 3
- Consider edaravone (free radical scavenger) as the second FDA-approved medication with modest survival benefit 3
- Tofersen (antisense oligonucleotide) for SOD1 mutation carriers 1
- Dextromethorphan/quinidine for pseudobulbar affect if present 6
Respiratory Management Algorithm
Initiate noninvasive ventilation (NIV) when ANY of the following criteria are met: 4
- FVC <80% of normal in symptomatic patients
- FVC <50% predicted regardless of symptoms
- Awake PaCO₂ >45 mmHg
- Sleep disturbances indicating respiratory insufficiency
- Use bilevel positive airway pressure (BPAP) with backup respiratory rate for optimal patient-ventilator synchrony 4
- NIV prolongs survival by several months (exceeding riluzole's benefit) and dramatically improves quality of life 4
- Do not withhold NIV trial based solely on bulbar symptoms, though bulbar dysfunction reduces effectiveness 4
- Monitor pulmonary function every 6 months minimum throughout disease course 4
- Implement mechanical insufflation-exsufflation devices when peak cough flow becomes ineffective 4
Nutritional Support Strategy
Target weight gain if BMI <25 kg/m², weight stabilization if BMI 25-35 kg/m² 1
- Each 5% weight loss increases mortality risk by 34%, and each 1-point BMI reduction increases death risk by 24% 1
- Recommend multiple small meals daily with high-calorie food enrichment for patients with fatigue 1
- Modify food texture to prevent aspiration and ease oral/pharyngeal transport 1
- Teach chin-tuck posture to protect airways during swallowing 1
Gastrostomy Timing (Critical Decision Point)
Place gastrostomy (PEG) before FVC drops below 50% and before >10% weight loss occurs. 1, 5
- Performing PEG after >10% weight loss increases mortality risk 4-fold (RR 4.18; 95% CI 2.72-6.42) 1
- Consider radiologically inserted gastrostomy (RIG) as safer alternative when FVC <50% 5
Palliative Care Integration
Integrate palliative care from the time of diagnosis, not as end-of-life care but as comprehensive symptom management throughout the disease course. 1
Advance Care Planning (Initiate at Diagnosis)
- Discuss advance directives at diagnosis, before communication becomes limited 1, 4
- Address preferences regarding: long-term mechanical ventilation via tracheostomy (only 4-9% choose this), feeding tube placement, and end-of-life care 1, 4
- Repeat these discussions as disease progresses, as patient preferences may evolve 4
Caregiver Support
- Implement structured caregiver support from diagnosis: counseling, support groups, and crisis management systems 1
- Behavioral deficits in patients significantly worsen caregiver burden, requiring proactive intervention 1
Monitoring Schedule
- Pulmonary function testing: every 6 months minimum 4
- Nutritional assessment: BMI and weight at every visit 1
- Screen for sleep disturbances: at each clinical visit 4
- Awake CO₂ measurement: at least annually using capnography 4
- Cognitive reassessment: periodically, as cognitive decline affects NIV compliance and treatment decisions 1, 4
Critical Pitfalls to Avoid
- Late referral to palliative services is the most common and harmful error, negatively impacting quality of life for patients and caregivers 1
- Delaying videofluoroscopy leads to undetected silent aspiration, as aspiration occurs without clinical signs 1
- Waiting too long for PEG placement (after severe respiratory compromise or >10% weight loss) markedly increases mortality 1, 5
- Using Harris-Benedict equation for calorie estimation (limits of agreement -677 to +591 kcal/day make it unreliable) 1
- Assuming preserved cognition without screening, as 40% have cognitive impairment affecting treatment adherence 1
Prognosis Communication
- Mean survival is 3-5 years from symptom onset, with only 5-10% living >10 years 1, 2
- Bulbar-onset patients have worse prognosis: median survival 25-28 months versus 44 months for spinal-onset 2
- Respiratory failure is the most common cause of death, followed by aspiration pneumonia (11.4-13% of bulbar cases) 1, 2