Summary

Motor Neurone Disease (MND), known as Amyotrophic Lateral Sclerosis (ALS) in North America, is a rapidly progressive and invariably fatal neurodegenerative disease affecting upper and lower motor neurones. It causes progressive weakness, wasting, and spasticity while characteristically sparing sensation, eye movements, and sphincter function. Median survival from symptom onset is 3-5 years. Management is multidisciplinary and focuses on maintaining quality of life and function. [1,2]

Key Facts

• Incidence: 2-3 per 100,000 per year; prevalence 5-7 per 100,000. [3]
• Peak Onset: 55-75 years; mean age 65 years.
• Sex Ratio: Male greater than female (1.5:1).
• Genetics: 5-10% familial (C9orf72 most common mutation); 90% sporadic.
• Survival: Median 3-5 years from symptom onset; 10% survive greater than 10 years.
• Hallmark: Combined upper and lower motor neurone signs WITHOUT sensory involvement.
• Disease-Modifying: Riluzole extends survival by approximately 3 months.

Clinical Pearls

The Cardinal Rule: MND = UMN + LMN signs in the SAME limb WITHOUT sensory loss. If sensation is abnormal, consider another diagnosis (cervical myelopathy, B12 deficiency).

Split Hand Sign: Early weakness of thenar muscles (APB, FDI) relative to hypothenar. This pattern is specific to ALS (due to corticomotoneuronal projections to thenar muscles).

Respiratory Failure: The killer. Monitor FVC religiously. Orthopnoea and morning headaches are early warning signs of nocturnal hypoventilation.

Emotional Lability: Pseudobulbar affect (pathological laughing/crying disproportionate to mood) affects 20-50% of patients. It is NOT depression. Treat with low-dose amitriptyline or dextromethorphan/quinidine.

Systematic Approach

Inspection

• Wasting (hands, shoulder girdle, tongue).
• Fasciculations (observe for 60 seconds; also check tongue at rest).
• Posture (foot drop, wrist drop).

Tone

• UMN: Spasticity (velocity-dependent increase in tone).
• LMN: Hypotonia/normal (may be masked by spasticity).

Power

• Test all muscle groups; MRC grading.
• Look for pattern (distal greater than proximal in classic form).
• Note asymmetry (common early).

Reflexes

• Often brisk even in wasted muscles (UMN component).
• Pathologically brisk jaw jerk in bulbar disease.
• Hoffman's sign positive (UMN hands).

Plantars

• Upgoing (Babinski positive) = UMN lesion.

Specific Tests

Bulbar Examination

• Speech quality (spastic = strained, flaccid = nasal).
• Tongue (wasting, fasciculations at rest).
• Palate movement (bilateral LMN = nasal speech).
• Gag reflex (brisk = UMN, absent = LMN).
• Pseudobulbar affect (emotional incontinence).

Respiratory Assessment

• Respiratory rate, accessory muscle use.
• Paradoxical abdominal movement (diaphragm weakness).
• Cough strength.
• Orthopnoea (ask about pillows; lying flat test).

Survival Statistics

• Median Survival: 3-5 years from symptom onset.
• Range: 6 months to greater than 20 years.
• 5-Year Survival: 20-30%.
• 10-Year Survival: 10%.

Prognostic Factors

Worse Prognosis

• Older age at onset.
• Bulbar-onset disease.
• Respiratory-onset disease.
• FTD (cognitive/behavioural impairment).
• Low FVC at diagnosis.
• Rapid rate of decline.
• Weight loss greater than 5%.

Better Prognosis

• Younger age.
• Limb-onset.
• PLS or flail arm phenotype.
• Longer time from symptom onset to diagnosis.
• Use of NIV (adds 7-12 months).
• Riluzole (adds 2-3 months).

Causes of Death

1. Respiratory failure (80%+): Most die peacefully with NIV and palliation.
2. Pneumonia: Aspiration or hypostatic.
3. Suicide/Euthanasia: Significant minority where legal.

Quality of Life

• Variable; not always correlated with physical disability.
• Psychological adaptation occurs.
• Good symptom control improves QoL.
• Carer burden is substantial.

Key Guidelines

Landmark Studies

1. Bensimon et al. Riluzole Trial (1994) [5]

• Question: Does riluzole improve survival?
• N: 155 patients.
• Result: Riluzole extended survival at 12 months (74% vs 58%).
• Impact: Riluzole became first approved treatment.
• PMID: 8302340.

2. EFNS Task Force on NIV (2012) [6]

• Question: Does NIV improve outcomes?
• N: Systematic review.
• Result: NIV improves survival (7-12 months) and quality of life.
• Impact: NIV standard of care.
• PMID: 16796582.

3. C9orf72 Discovery (2011)

• Question: What causes familial ALS-FTD?
• N: Genome-wide studies.
• Result: Hexanucleotide repeat expansion in C9orf72 most common genetic cause.
• Impact: Changed genetic testing landscape.
• PMID: 21944778.

4. PROACT Database Analysis

• Question: What predicts survival?
• N: Pooled trial data (greater than 10,000 patients).
• Result: Predictive models developed for clinical trials.
• Impact: Stratification of patients for future trials.

What is MND?

Motor Neurone Disease (MND), also called ALS, is a condition where the nerve cells (neurones) that control muscles gradually stop working. This leads to progressive weakness and wasting of muscles. It is a serious condition with no cure, but there are treatments that can help manage symptoms and improve quality of life.

What Causes It?

• In most cases (90%), we don't know the cause.
• About 1 in 10 cases run in families (genetic).
• Research is ongoing into what triggers motor neurone death.

What Are the Symptoms?

• Weakness in arms or legs (often starts on one side).
• Difficulty speaking or swallowing.
• Muscle wasting and twitching.
• Stiff or tight muscles.
• Breathlessness.

Importantly, sensation and bladder/bowel control are NOT affected.

How is it Diagnosed?

• There is no single test for MND.
• Diagnosis is based on clinical examination plus nerve tests (EMG).
• Brain and spine scans rule out other conditions.
• Blood tests exclude mimics.

What Treatment is Available?

• Riluzole: A tablet that may slow progression slightly.
• Breathing support (NIV): A mask worn at night (and later daytime) that helps breathing.
• Feeding tube (PEG): If swallowing becomes very difficult.
• Physiotherapy and Occupational Therapy: Maintain function and independence.
• Speech Therapy: Help with communication and swallowing.
• Specialist Team Care: A team of experts works together to provide the best care.

What is the Outlook?

• MND is a progressive condition and average survival is 3-5 years.
• Some people live longer - around 10% survive more than 10 years.
• Treatments and support can significantly improve quality of life.
• Many people with MND continue to do things they enjoy for as long as possible.

Planning Ahead

• Early conversations about future wishes are important.
• Consider things like breathing support, feeding tubes, and end-of-life preferences.
• Legal documents (Power of Attorney, Advance Decisions) should be considered early.

Support Resources

• MND Association (UK): mndassociation.org
• ALS Association (USA): als.org
• Motor Neurone Disease Scotland: mndscotland.org.uk