What are the early symptoms of Amyotrophic Lateral Sclerosis (ALS) and how is it diagnosed and managed?

Early Symptoms of Amyotrophic Lateral Sclerosis (ALS)

ALS typically presents with painless, progressive muscle weakness that manifests in two distinct patterns: limb-onset (spinal) disease showing asymmetric weakness in extremities, or bulbar-onset disease presenting with speech and swallowing difficulties, with the latter carrying a worse prognosis. 1, 2, 3

Initial Clinical Presentations

Limb-Onset (Spinal) ALS

The majority of patients initially develop:

• Asymmetric weakness in one limb - typically starting with difficulty climbing stairs, foot drop causing limping, or hand weakness affecting fine motor tasks like buttoning shirts 3, 4
• Muscle atrophy in the affected limb, often noticed before weakness becomes functionally limiting 3, 5
• Hyperreflexia - abnormally brisk reflexes that seem paradoxical given the muscle weakness 3
• Fasciculations (muscle twitching) that patients may notice, though these are not specific to ALS 5

Bulbar-Onset ALS

Approximately 20-30% of patients present with bulbar symptoms: 2

• Dysarthria - slurred speech or difficulty articulating words clearly 2, 3
• Dysphagia - difficulty swallowing that manifests as prolonged meal times, fatigue during eating, and difficulty with certain food textures 6
• Nasal regurgitation due to reduced soft-palate closure 6
• Sialorrhea (drooling) from inability to manage saliva due to impaired swallowing and poor lip seal 6

Bulbar-onset disease carries a significantly shorter life expectancy compared to limb-onset, making early recognition critical. 1

Key Diagnostic Features

Upper and Lower Motor Neuron Signs

ALS is distinguished by simultaneous presence of both upper and lower motor neuron dysfunction: 2, 7

• Lower motor neuron signs: muscle weakness, atrophy, fasciculations, and hyporeflexia in affected muscles 3
• Upper motor neuron signs: spasticity, hyperreflexia, and pathological reflexes (Babinski sign) 3, 7

Critical Diagnostic Timeline

The average time from symptom onset to diagnosis is approximately 12 months, which represents a significant delay that negatively impacts outcomes. 8 This delay occurs because:

• Initial symptoms are often subtle and attributed to other conditions 3
• No single diagnostic test confirms ALS 3, 7
• The broad differential diagnosis includes many treatable conditions 3

Diagnostic Workup

Clinical Evaluation

When ALS is suspected, focus on: 7

• History of painless, progressive weakness - pain is NOT a typical feature of early ALS 7
• Pattern of weakness progression - documenting which body regions are affected and the timeline 5
• Absence of sensory symptoms - sensory loss should prompt consideration of alternative diagnoses 7

Confirmatory Testing

Electromyography (EMG) is the most important diagnostic test, showing denervation and reinnervation patterns in multiple body regions. 7 Additional supportive tests include:

• Neurofilament light chain (NF-L) levels in CSF or serum - elevated levels support the diagnosis with Class II evidence 8
• Genetic testing for familial ALS genes (C9orf72, SOD1, FUS, TARDBP) - indicated even without family history as genetic factors may be underestimated 5, 7
• MRI of brain and spine - primarily to exclude mimics like cervical myelopathy or structural lesions 1

Gold Coast Criteria

New simplified diagnostic criteria (Gold Coast Criteria) have been introduced to facilitate earlier diagnosis, replacing older, more complex classification systems. 8

Early Management Priorities

Immediate Interventions Upon Diagnosis

A palliative care approach should be adopted from the time of diagnosis, not reserved for end-stage disease. 9, 1 This includes:

• Early referral to palliative services to establish relationships before communication becomes impaired 9
• Multidisciplinary team involvement including neurology, pulmonology, nutrition, speech therapy, and physical therapy 5, 7

Disease-Modifying Therapy

Initiate riluzole immediately upon diagnosis - this glutamate receptor antagonist provides modest survival benefit and is most effective when started early 8, 7

Consider edaravone (free radical scavenger) - FDA-approved in 2017 with evidence of slowing functional decline 8, 7

Nutritional Assessment

Begin regular nutritional monitoring every 3 months from diagnosis, assessing BMI and weight loss to detect early malnutrition 1, 6

For patients with bulbar symptoms:

• Videofluoroscopy should be performed at diagnosis to detect early dysphagia, even in asymptomatic patients 9, 1
• Adapt food textures and implement postural maneuvers (chin-tuck) to prevent aspiration 1, 6

Respiratory Monitoring

Establish baseline pulmonary function with: 5

• Slow vital capacity (SVC) measurements 5
• Peak cough flow (PCF) to assess airway clearance ability 5
• Serial monitoring every 3-6 months to guide timing of non-invasive ventilation 6

Common Pitfalls to Avoid

Do not delay diagnosis waiting for symptoms to spread to multiple body regions - early intervention improves outcomes and reduces psychological distress 8

Do not dismiss bulbar symptoms as "just stress" or attribute them to aging - bulbar-onset ALS progresses rapidly and requires immediate multidisciplinary intervention 1, 2

Do not wait for severe respiratory compromise before discussing ventilatory support - these conversations are easier when patients can still communicate effectively 9

Recognize that approximately 20% of motor neuron loss has already occurred by the time symptoms appear - the neurodegenerative process is active in the presymptomatic stage, emphasizing the importance of rapid diagnosis and treatment initiation 8