What are the typical symptoms and management strategies for the onset of Amyotrophic Lateral Sclerosis (ALS)?

Onset of Amyotrophic Lateral Sclerosis (ALS)

Clinical Presentation at Onset

ALS typically presents in one of two distinct patterns: spinal/limb onset (approximately 67% of cases) with focal muscle weakness and wasting in the extremities, or bulbar onset (approximately 33% of cases) with dysarthria and dysphagia, with bulbar onset carrying a significantly worse prognosis (median survival 25-28 months versus 44 months for spinal onset). 1, 2

Spinal/Limb Onset Features

• Progressive focal muscle weakness that may begin either distally or proximally in upper or lower limbs 3
• Muscle atrophy and fasciculations (visible muscle twitching) reflecting lower motor neuron degeneration 4, 1
• Spasticity and hyperreflexia developing gradually in weakened limbs, affecting manual dexterity and gait, reflecting upper motor neuron involvement 4, 3
• Symptoms typically remain asymmetric initially but progress to involve multiple body regions 5

Bulbar Onset Features

• Dysarthria (speech difficulty) and dysphagia (swallowing difficulty) as initial symptoms, occurring in approximately 80% of bulbar-onset patients 1
• Limb symptoms develop almost simultaneously or within 1-2 years of bulbar symptom onset 3
• Sialorrhea (excessive drooling) due to impaired swallowing of saliva 4
• Nasal regurgitation from soft palate weakness 4

Key Examination Findings

• Mixed upper and lower motor neuron signs are the diagnostic hallmark: hypertonicity and hyperreflexia (upper motor neuron) combined with muscle fasciculations, weakness, and atrophy (lower motor neuron) 4, 1
• Absence of sensory deficits (pain sensation remains intact) 5
• Preserved extraocular movements and sphincter function in early stages 3

Immediate Diagnostic Workup

Electromyography (EMG) is the single most important diagnostic test, demonstrating denervation and reinnervation patterns in multiple body regions to confirm motor neuron involvement. 6

Essential Diagnostic Steps

• EMG and nerve conduction studies to demonstrate widespread motor neuron involvement and exclude ALS mimics like multifocal motor neuropathy 3, 5
• MRI brain and spine without contrast to exclude structural lesions (cervical spondylotic myelopathy, spinal cord tumors) that can mimic ALS 4, 1
  • Look for abnormal T2/FLAIR signal in corticospinal tracts (brain) and "snake eyes" appearance in anterior horns (spine), though these findings may only appear later in disease 4, 1
• Genetic testing for SOD1, C9orf72, FUS, and TARDBP mutations, particularly if family history present or age <50 years 3, 7

Critical ALS Mimics to Exclude

• Cervical spondylotic myelopathy (MRI spine) 3
• Multifocal motor neuropathy (nerve conduction studies showing conduction block) 3
• Kennedy's disease/spinal bulbar muscular atrophy (genetic testing, elevated CK) 3

Initial Management Framework

Adopt a palliative care approach from the time of diagnosis with immediate referral to palliative services, as speech and communication become severely limited in later stages, making advance care planning impossible if delayed. 6, 1, 2

Pharmacologic Disease-Modifying Therapy

• Initiate riluzole 50 mg twice daily immediately upon diagnosis in patients with disease duration <5 years and FVC ≥60% of predicted 8
  • Extends median survival by 60-90 days in clinical trials 8
  • Does not improve muscle strength or neurological function, only prolongs survival 8
  • Monitor liver function tests before and during treatment 8

Multidisciplinary Team Assembly

Establish care with a multidisciplinary ALS team immediately, as this approach improves both survival and quality of life. 1, 2 The team must include:

• Neurology (care coordinator in diagnostic phase) 1
• Pulmonology (respiratory management) 2
• Gastroenterology/nutrition (dysphagia and feeding tube placement) 2
• Speech-language pathology (swallowing assessment and communication devices) 2
• Physical and occupational therapy (mobility aids and adaptive equipment) 2
• Social work and palliative care 2

Baseline Assessments at Diagnosis

Perform comprehensive baseline measurements to guide timing of interventions:

• Nutritional status: BMI and weight, with repeat assessment every 3 months 4, 6
  • Target weight gain if BMI <25 kg/m², weight stabilization if BMI 25-35 kg/m² 4
• Respiratory function: Slow vital capacity (SVC) and peak cough flow (PCF) 6
  • Establish baseline for monitoring decline and timing NIV initiation 6
• Swallowing function: Videofluoroscopy (VFS) at diagnosis for all patients with bulbar symptoms, even if asymptomatic 6, 2
  • Detects silent aspiration and guides dietary modifications 2
• Cognitive screening: Assess for frontotemporal dysfunction, as up to 40% have cognitive impairment affecting treatment decisions 1

Early Symptom Management

Dysphagia Management (if present at onset)

• Modify food texture immediately: use thicker liquids and semisolid foods with high water content instead of thin liquids 6, 1
• Implement chin-tuck posture during swallowing to protect airways and prevent aspiration 1
• Recommend multiple small meals throughout the day rather than three large meals to reduce fatigue 1
• Dietary counseling for meal enrichment with high-calorie foods to prevent weight loss 1

Sialorrhea Management (if present)

• First-line: oral anticholinergic medication (glycopyrrolate or amitriptyline) 2
• Second-line: botulinum toxin injections to salivary glands if anticholinergics ineffective 2

Critical Early Interventions and Timing

Advance Care Planning

Initiate advance directive discussions at diagnosis, before communication becomes impaired, covering:

• Preferences regarding non-invasive ventilation (NIV) 1
• Preferences regarding invasive mechanical ventilation (only 4-9% choose this option) 1
• Preferences regarding feeding tube placement 1
• End-of-life care preferences 1

Gastrostomy Timing Discussion

Begin discussing PEG placement early, as optimal timing is before FVC falls below 50% of predicted, and placement should be refused if FVC <30%. 2

• Mean feeding duration after placement is 11-18 months 1
• Placement becomes high-risk once respiratory function significantly deteriorates 2

Respiratory Monitoring Plan

Establish plan for NIV initiation when FVC <80% with symptoms, FVC <50% predicted, or evidence of sleep-disordered breathing. 2

• Use bilevel positive airway pressure (BPAP) with backup respiratory rate for better patient-ventilator synchrony in bulbar impairment 2

Common Pitfalls to Avoid

• Delaying palliative care referral is the most harmful error, negatively impacting quality of life for patients and caregivers 1
• Treating equipment and service requests as routine rather than urgent can result in catastrophic safety risks; all ALS-related requests require expedited handling 2
• Failing to screen for cognitive impairment, which reduces NIV compliance and affects treatment decision-making capacity 1
• Missing silent aspiration by relying only on patient-reported symptoms rather than objective swallowing studies 1, 2
• Delaying gastrostomy discussion until respiratory function is too compromised for safe placement 2