Motor Neuron Disease: Diagnosis and Management
Diagnostic Approach
Motor neuron disease (MND) diagnosis requires demonstrating both upper motor neuron (UMN) and lower motor neuron (LMN) signs through clinical examination and electrodiagnostic studies, with MRI brain being the optimal initial imaging to exclude mimics. 1, 2
Clinical Features to Identify
Upper Motor Neuron Signs:
- Spasticity with velocity-dependent increased muscle tone 1, 2
- Hyperreflexia (brisk or exaggerated deep tendon reflexes) 1, 2
- Clonus (rhythmic muscle contractions with sudden stretch) 1, 2
- Extensor plantar response (Babinski sign) 1, 2
Lower Motor Neuron Signs:
- Fasciculations (the most characteristic sign of LMN damage, appearing as spontaneous motor unit discharges) 1, 2
- Flaccid paralysis with decreased muscle tone and weakness 1, 2
- Hyporeflexia or areflexia 1, 2
- Progressive muscle atrophy due to denervation 1, 2
Mandatory Diagnostic Testing
Do not rely on clinical examination alone—electrodiagnostic studies are mandatory for establishing LMN involvement. 1, 2
Electromyography (EMG) findings:
- Fibrillation potentials, positive sharp waves, fasciculations, and complex repetitive discharges indicating denervation 1, 2, 3
Nerve conduction studies:
- Normal or low compound muscle action potential (CMAP) amplitudes with relatively normal conduction velocities 1, 2
Neuroimaging:
- MRI brain without IV contrast is the optimal initial imaging modality 1, 2, 3
- UMN findings: Abnormal T2/FLAIR signal in corticospinal tracts, particularly in the posterior limb of internal capsule and cerebral peduncles 1, 2, 3
- LMN findings: Spine MRI may show abnormal T2/STIR signal in anterior horns ("snake eyes" appearance), though this is not specific and may appear late 1, 2, 3
Laboratory testing:
Critical Diagnostic Pitfalls
If sensory symptoms are present, reconsider the diagnosis of pure motor neuron disease, as sensory pathways are not involved in typical UMN or LMN lesions. 1
Treatable mimics must be excluded before ascribing the diagnosis, including cervical myelopathy, syrinx, and metabolic causes. 3, 4, 5
Treatment and Management
Multidisciplinary care is the cornerstone of MND management and improves both survival and quality of life. 1, 2, 3
Essential Multidisciplinary Team Components
The team should include neurology, pulmonology, nutrition/gastroenterology, physical therapy, occupational therapy, speech-language pathology, social work, and palliative care. 1, 2, 3, 6
Respiratory Management
Non-invasive ventilation (NIV) for respiratory insufficiency improves median survival and quality of life and should be initiated when respiratory function declines. 7, 1, 2, 3, 4
NIV settings for MND patients:
- Low levels of pressure support (PS) are typically required (pressure difference of 8-12 cm H2O) unless significant skeletal deformity is present 7
- NIV should be considered in any breathless/acutely unwell patient with MND before respiratory acidosis develops 7
- In MND, any elevation of pCO2 may herald an impending crisis, unlike COPD where acidosis degree matters more 7
Critical respiratory considerations:
- Patients with bulbar dysfunction may have upper airway obstruction complicating NIV 7
- Diaphragm involvement may precede locomotor disability in some forms (acid maltase deficiency, amyotrophic lateral sclerosis) 7
- Maintain high suspicion for infections, as MND patients are at very high risk for pneumonia and respiratory failure 1, 2
Invasive Mechanical Ventilation Decisions
Senior staff should be involved in decision-making regarding invasive mechanical ventilation (IMV), in conjunction with home mechanical ventilation specialists. 7
The value of IMV in MND should be reconsidered both as an elective policy and at time of crisis, as many patients can survive IMV and be successfully extubated onto NIV, avoiding permanent tracheostomy. 7
Decannulation of tracheostomy is more difficult when bulbar disease is present. 7
Disease-Modifying Pharmacotherapy
Edaravone is FDA-approved for ALS treatment and demonstrated statistically significant slowing of functional decline. 8
Edaravone dosing:
- 60 mg IV infusion over 60 minutes (infusion rate approximately 1 mg per minute) 8
- Initial treatment cycle: daily dosing for 14 days, followed by 14-day drug-free period 8
- Subsequent cycles: daily dosing for 10 days out of 14-day periods, followed by 14-day drug-free periods 8
Edaravone efficacy:
- In a 6-month randomized controlled trial, edaravone reduced decline in ALSFRS-R scores (treatment difference of 2.49 points, p=0.0013) 8
- Study enrolled patients with definite or probable ALS, disease duration ≤2 years, %FVC ≥80%, and retained most activities of daily living 8
Edaravone contraindications and warnings:
- Contraindicated in patients with hypersensitivity to edaravone 8
- Contains sodium bisulfite, which may cause allergic reactions including anaphylaxis, particularly in asthmatic patients 8
- Monitor carefully for hypersensitivity reactions; discontinue immediately if they occur 8
Riluzole prolongs life by only 3-4 months and is available only for the ALS form of MND. 4
Nutritional Support
Malnutrition is a poor prognostic factor, and enteral feeding is recommended in appropriate patients, though survival benefit has not yet been proven. 4
Symptomatic Management
Multiple symptoms can be effectively treated with medications, including pseudobulbar affect, sialorrhea, constipation, spasticity, and cramps. 6
Depression, hopelessness, anxiety, and other mental health issues should be aggressively addressed and treated. 6
Exercise Recommendations
For specific genetic forms of LMN disease, recommend submaximal, functional, and aerobic exercise while avoiding excessive resistive and eccentric exercise. 1, 2
Prognosis and End-of-Life Planning
Most patients with ALS have a median survival of 3-4 years after symptom onset, with death typically from respiratory failure, though a significant minority survives into a second decade. 4, 5, 9
Address spirituality, religion, advance directives, hospice, and the dying process early in the disease course. 6