How should autonomic dysfunction be screened and managed in adult patients with amyotrophic lateral sclerosis, including orthostatic hypotension, excessive sweating, bladder dysfunction, and gastrointestinal dysmotility?

Autonomic Dysfunction in ALS: Screening and Management

Recognition and Clinical Significance

Autonomic dysfunction occurs in approximately 68% of ALS patients at diagnosis and progresses over time, representing an intrinsic non-motor feature of the disease that independently predicts faster disease progression and shorter survival. 1

• Autonomic symptoms are mild to moderate in up to 75% of ALS patients and should be systematically assessed at every clinic visit 1, 2
• Higher autonomic symptom burden is an independent marker of faster progression to King's stage 4 (HR 1.05; 95% CI 1.00-1.11) 1
• Urinary complaints specifically predict shorter survival (HR 3.12; 95% CI 1.22-7.97) 1
• Bulbar-onset patients experience more severe autonomic symptoms compared to limb-onset patients 1

Systematic Screening Approach

Gastrointestinal Dysfunction

Constipation increases from 33% pre-diagnosis to 64.7% after ALS diagnosis and should be screened at every visit. 3

• Ask specifically about constipation frequency, bowel urgency (increases from 25.4% to 33.3% over time), and difficulty with evacuation 3
• Screen for dysphagia every 3 months using structured questionnaires (EAT-10 has 86% sensitivity, 76% specificity for unsafe swallowing) 4
• Perform videofluoroscopy at diagnosis to detect silent aspiration, as dysphagia can occur without clinical signs or patient complaints 4, 5

Bladder Dysfunction

Overactive bladder symptoms increase from 3.1% pre-diagnosis to 25% after ALS diagnosis. 3

• Screen for urinary urgency, frequency, nocturia, and incontinence at each visit 3
• Urinary symptoms warrant particular attention given their association with mortality 1
• Assess for urinary retention and incomplete emptying 3

Cardiovascular Autonomic Dysfunction

Heart rate variability testing reveals parasympathetic hypofunction in ALS patients that progressively worsens over time. 1

• Screen for orthostatic lightheadedness (most common cardiovascular symptom) using postural vital signs 3, 6
• Measure blood pressure and heart rate supine and after 3 minutes standing to detect orthostatic hypotension 6
• Consider autonomic reflex screening in patients with symptomatic orthostatic intolerance, though 60% of patients show abnormalities even without symptoms 6

Sudomotor Dysfunction

Sudomotor symptoms occur frequently: stinging eyes (17.2%), oily/greasy skin (14.1%), and skin flaking (29.7%). 3

• Ask about excessive sweating, particularly nocturnal or focal hyperhidrosis 3
• Screen for dry eyes, skin changes, and abnormal sweating patterns 3, 6
• Thermoregulatory sweat testing shows abnormalities in 58% of patients, though this is typically reserved for research settings 6

Management Strategies

Gastrointestinal Management

Constipation responds to docusate, dietary fiber supplementation, increased fluids/exercise, and polyethylene glycol in descending order of frequency. 3

• Initiate dietary fiber supplementation for constipation caused by abdominal muscle weakness 5
• Modify food texture to prevent aspiration and improve nutritional intake once dysphagia is identified 5
• Implement chin-tuck posture as a protective airway mechanism to prevent laryngeal penetration 5
• Consider gastrostomy placement before severe respiratory compromise develops (placement after >10% weight loss increases mortality with RR 4.18) 5

Bladder Management

Urinary symptoms are most commonly treated with intermittent catheterization and oxybutynin. 3

• Initiate anticholinergic therapy (oxybutynin) for overactive bladder symptoms 3
• Implement clean intermittent catheterization for urinary retention 3
• Monitor post-void residual volumes to guide catheterization decisions 3

Orthostatic Hypotension Management

• Increase fluid and salt intake as first-line intervention 6
• Use compression stockings to improve venous return 6
• Elevate head of bed 30 degrees to reduce nocturnal natriuresis 6
• Consider fludrocortisone or midodrine for refractory symptoms, though evidence specific to ALS is limited 6, 2

Excessive Sweating Management

• Trial anticholinergic medications for generalized hyperhidrosis 3
• Consider topical glycopyrrolate for focal sweating 3
• Address environmental triggers and adjust room temperature 3

Critical Pitfalls and Caveats

Autonomic symptoms are often underrecognized because they are not spontaneously reported by patients focused on motor symptoms. 1, 2

• Do not wait for patients to volunteer autonomic complaints—systematically ask about bowel, bladder, cardiovascular, and sudomotor symptoms at every visit 3, 1
• Avoid attributing all autonomic symptoms to immobility or medications; they represent intrinsic disease pathology 1, 2
• Recognize that autonomic dysfunction can lead to circulatory collapse or sudden death in ventilator-dependent patients 2
• Be aware that sympathetic hyperactivity may occur in ALS, potentially contributing to cardiovascular instability 2
• Cognitive impairment (present in 40% of ALS patients) may affect treatment compliance and decision-making regarding autonomic symptom management 4, 5

Prognostic Implications

Document autonomic symptom burden quantitatively, as it provides independent prognostic information beyond motor disability. 1

• Higher baseline autonomic symptom scores predict faster disease progression 1
• Presence of urinary symptoms specifically predicts shorter survival and should trigger more aggressive palliative care planning 1
• Autonomic dysfunction worsens over time independent of motor progression, requiring ongoing reassessment 1, 2