What is the treatment for Motor Neuron Disease (MND)?

Treatment for Motor Neuron Disease (MND)

MND treatment requires a multidisciplinary approach combining disease-modifying pharmacotherapy (riluzole and edaravone), respiratory support with non-invasive ventilation (NIV), nutritional management, and symptomatic therapies to maximize survival and quality of life.

Disease-Modifying Pharmacotherapy

Riluzole

• Riluzole is the only globally approved drug that modestly prolongs survival by 2-3 months in MND/ALS patients 1, 2.
• The medication should be initiated early in the disease course, as it has demonstrated survival benefit particularly in limb-onset disease (median survival 3.61 years with riluzole vs 2.62 years without) 3.
• Riluzole works through complex mechanisms including actions on NMDA and kainate receptors and modulation of voltage-gated sodium channels 4.
• Patients receiving both riluzole and NIV simultaneously demonstrate significantly longer survival (16.61 months) compared to supportive treatment alone (10.69 months), indicating these therapies should be combined rather than used in isolation 5.

Edaravone (Intravenous)

• Edaravone injection is administered as 60 mg intravenous infusion over 60 minutes according to a specific schedule: initial treatment cycle with daily dosing for 14 days followed by 14-day drug-free period, then subsequent cycles with daily dosing for 10 days out of 14-day periods 1.
• Each 60 mg dose is given as two consecutive 30 mg infusion bags at approximately 1 mg per minute (3.33 mL per minute) 1.
• Promptly discontinue infusion upon first observation of hypersensitivity reactions (redness, wheals, erythema multiforme) or anaphylaxis (urticaria, decreased blood pressure, dyspnea) 1.
• Edaravone is contraindicated in patients with history of hypersensitivity to edaravone or sulfite allergic reactions, as it contains sodium bisulfite 1.

Respiratory Management

Non-Invasive Ventilation (NIV)

• NIV is the treatment of choice when ventilatory support is needed and significantly improves survival (median 15.41 months with NIV vs 10.88 months without) 6, 5.
• NIV should be considered in any breathless/acutely unwell MND patient before respiratory acidosis develops, as any elevation of pCO2 may herald an impending crisis 6.
• In patients without significant chest wall distortion, low pressure support (IPAP 10-20 cm H2O) is typically sufficient, with I:E ratio of 1:1 recommended 6.
• Bulbar dysfunction makes NIV failure more likely and indicates need for HDU/ICU placement if accompanied by profound hypoxemia or rapid desaturation during NIV breaks 6.
• Following acute recovery, the majority of MND patients will require NIV at home, with overnight continuation until discussion with home ventilation service 6.

Invasive Mechanical Ventilation (IMV)

• IMV outcomes are limited, with median survival of 250 days when initiated emergently and only 17% of patients successfully weaned 6.
• Discussion with specialist centers regarding both IMV delivery and weaning is recommended given the complexity and poor outcomes 6.
• Elective intubation rates vary significantly by country (0.8% in Ireland, 6% in USA, 10.6% in Italy), reflecting different practice patterns 6.

Nutritional Management

Dysphagia Management

• Modified-consistency foods and thickened liquids (semisolid foods with high water content, jellified water) are suggested as alternatives to thin liquids to alleviate aspiration risk 6.
• Chin-tuck posture is the most useful postural maneuver for the majority of MND patients with dysphagia, providing airway protection by opening the valleculae and preventing laryngeal penetration 6.
• Head rotation is indicated for hypertonicity or premature upper esophageal sphincter closure, while hyperextended head posture is indicated only when lingual pump is absent and safe transit is ensured 6.
• Throat clearing every 3-4 swallowing acts can prevent postswallowing inhalation in patients with penetration without aspiration (23% of patients) 6.

Nutritional Supplementation

• Nutritional supplementation is recommended for MND patients who do not cover requirements with enriched diet, though insufficient data exists to affirm oral supplementation improves survival 6.
• Caloric supplementation with carbohydrates appears more beneficial than high-fat supplementation for survival outcomes 6.

Sialorrhea Management

• Anti-muscarinic therapy or botulinum toxin A can be used to manage sialorrhea based on indirect evidence, though no evidence links saliva treatment with dysphagia improvement 6.

Cardiac Management

Arrhythmia and Thrombosis Prevention

• Thrombosis prophylaxis in MND patients with normal systolic function and atrial fibrillation/flutter may be considered, with therapy type determined by individual thrombosis risk 6.
• Anticoagulation or antiplatelet therapy is not recommended for patients without arrhythmia history who have MND types where cardiac involvement commonly manifests as arrhythmia 6.
• Antiarrhythmic drugs (class I, II, or IV) can increase peripheral muscular weakness and should be used cautiously, with treatment tailored to coexisting conduction abnormalities or myocardial dysfunction 6.

Cardioverter-Defibrillator Therapy

• Standard criteria for primary ICD therapy apply: class II or III heart failure with LVEF ≤35% despite medical therapy 6.

Physical Therapy and Exercise

• Submaximal effort strengthening regimens designed to avoid disuse atrophy while preventing exercise-induced muscle injury are probably safe and appropriate 6.
• Walking 15-30 minutes 3-4 days weekly at 50-60% heart rate reserve produces modest but statistically significant decreases in submaximal heart rate and systolic blood pressure 6.
• Strengthening exercises remain controversial in progressive MND due to concern about precipitating muscle breakdown, so intensity must be carefully controlled 6.

Critical Monitoring and Follow-Up

• Specialist neurological opinion should always be sought for diagnosis confirmation, as significant differential diagnoses include treatable conditions 7.
• Recovery from acute respiratory failure takes longer than in COPD, requiring slower NIV weaning with target pCO2 around 6.5 kPa when self-ventilating 6.
• Deterioration may be very sudden due to reduced respiratory reserve, impaired cough, and possibly undiagnosed cardiomyopathy—difficulty achieving adequate oxygenation or rapid desaturation during NIV breaks are critical warning signs 6.

Important Clinical Caveats

• Despite decades of research, there remains no cure for MND, and management remains primarily supportive requiring multidisciplinary coordination 7, 2.
• The diagnosis may initially be difficult to confirm until full clinical features manifest, and some patients present with acute respiratory failure before formal MND diagnosis is established 6.
• Do not deny acute NIV to MND patients presenting with acute hypercapnic respiratory failure—these individuals can survive long-term on home NIV with good quality of life even after severe initial presentation 6.
• Specialized physiotherapy is essential to aid sputum clearance, as bulbar dysfunction renders voluntary cough less effective 6.