Makindo Medical Notes

Related Subjects: |Neurological History taking |Motor Neuron Disease (MND-ALS) |Miller-Fisher syndrome |Guillain Barre Syndrome |Multifocal Motor Neuropathy with Conduction block | Multiple Sclerosis (MS) Demyelination | Inclusion Body Myositis |Cervical spondylosis |Anterior Spinal Cord syndrome |Central Spinal Cord syndrome |Brown-Sequard Spinal Cord syndrome |Spinal Cord Compression |Spinal Cord Haematoma |Spinal Cord Infarction

Generalized and bulbar weakness with muscle wasting, brisk reflexes, and no sensory loss, with eye and bladder function spared. There is no definitive diagnostic test for MND, and the diagnosis relies on clinical signs affecting both the brain and spinal cord.

About

• Also known as Amyotrophic Lateral Sclerosis (ALS), Charcot's disease, and Lou Gehrig's disease.
• Diagnosis is often delayed, sometimes taking more than 16 months from symptom onset.
• Initial symptoms are often non-specific, such as general fatigue.

How Common Is It?

• Incidence: 1.8 to 2.2 per 100,000 population.
• Prevalence: 4.0 to 4.7 per 100,000 population in the UK.
• At any given time, about 2,000 individuals in England and Wales are affected.

Pathology : a degeneration of

• Motor giant pyramidal Betz cells in layer V neurons of the primary motor cortex (Brodmann area 4).
• Anterior horn cells of the spinal cord.
• Cranial motor nuclei in the brainstem.

Aetiology/Genetics

• A variant form of MND is seen in Guam, associated with dementia and Parkinson's disease, affecting the Chamorro people.
• Superoxide dismutase 1 (SOD1) mutations are implicated in some familial cases.
• Mutations affecting RNA processing and axonal cytoskeleton/transport are also involved.
• Familial ALS: 10% of cases are inherited, usually in an autosomal dominant pattern.

Forms of MND

• Progressive Muscular Atrophy: Primarily lower motor neuron (LMN) involvement. Survival: 5-10 years.
• Progressive Bulbar Palsy: Affects both LMN and upper motor neurons (UMN), presenting with tongue wasting, fasciculations, increased jaw jerk, and spastic palate. Survival: 2-3 years.
• Primary Lateral Sclerosis: Predominantly UMN involvement, often symmetrical. Good prognosis.
• Amyotrophic Lateral Sclerosis (ALS): Predominantly UMN signs. Survival: 3-4 years.
• MND-Dementia: Associated with frontotemporal dementia (FTD).

Clinical Features: Mixed UMN + LMN with Normal Sensory Function

• Subtle weakness, fatigue, and low energy at first.
• Wasting and fasciculation of hand muscles and other muscle groups.
• Painful nocturnal muscle cramps, especially in the thighs.
• Weakness with brisk reflexes and extensor plantar responses.
• No sensory loss, although mild symptoms may be present.
• Spared eye movements and sphincters.
• Bulbar involvement with wasted, fibrillating tongue, dysarthria, and dysphagia.
• Weight loss due to muscle wasting and swallowing difficulties.
• Dropped head and wasted hand appearance.

El Escorial Criteria for MND

• Clinically Definite ALS: Upper and lower motor neuron signs in three or more regions (bulbar, cervical, thoracic, or lumbar).
• Clinically Probable ALS: Upper and lower motor neuron signs in two regions, or upper motor neuron findings above lower motor neuron signs (e.g., increased reflexes in the arms with leg wasting).
• Clinically Possible ALS: Upper and lower motor neuron findings in one region or lower motor neuron findings above upper motor neuron findings.

Differential Diagnosis

• Multifocal motor neuropathy with conduction block (MMN) — Check serum GM-1 antibodies.
• Cervical spondylotic myelopathy with polyradiculopathy.
• Lesions at the foramen magnum or high cervical region with bulbar and long tract signs — MRI needed.
• Chronic inflammatory demyelinating polyneuropathy (CIDP).
• Inclusion body myositis — EMG and muscle biopsy for diagnosis.
• Myasthenia gravis — Tensilon test, antibodies, and single-fiber EMG.
• Kennedy’s syndrome (X-linked bulbospinal neuronopathy).
• Benign fasciculation syndromes and hereditary spastic paraparesis.
• B12 deficiency — Check serum B12 levels.
• Lyme disease — Lyme titers.
• Malignancy — CT chest, abdomen, and pelvis.

Investigations

• FBC, U&E, TFT, CK (can be mildly elevated), and syphilis serology.
• CSF examination may show mildly raised protein levels.
• Autoantibody tests (e.g., anti-acetylcholine receptor antibodies, anti-GM1 antibodies) to rule out other causes.
• MRI of the brain and cervical cord to exclude other causes such as nerve root compression, syringomyelia, or cerebrovascular disease. T2-weighted MRI may show high signal intensity in the corticospinal tracts due to Wallerian degeneration.
• Electromyography (EMG) — Shows fasciculations and fibrillation potentials indicating lower motor neuron involvement.
• Nerve conduction studies — Usually normal until late in the disease.
• Muscle biopsy — Consider if myopathy is suspected.

Management

• General Support: There is no cure for MND; management is primarily supportive. Early involvement of a multidisciplinary team (physiotherapy, occupational therapy, speech and language therapy, etc.) is crucial. Counseling and end-of-life support may be needed.
• Anticholinergics: Used to manage drooling.
• Baclofen or Diazepam: Used for spasticity control.
• Feeding Support: NG or PEG feeding should be discussed with the patient and family as swallowing issues worsen. Radiologically inserted gastrostomy (RIG) may be considered.
• Riluzole (50 mg bd): A glutamate antagonist that can modestly extend survival by 2-3 months in some patients.
• Non-Invasive Ventilation (NIV): Can improve survival by up to 6 months, particularly in patients without severe bulbar involvement. It helps reduce fatigue and improves sleep quality.
• Percutaneous Gastrostomy: To assist feeding as swallowing deteriorates. Tracheostomy and ventilatory support may be considered in advanced cases.
• Speech Synthesizers: Helpful when speech becomes impaired.
• Quinine Sulphate (300 mg): Used for muscle cramps. Alternatives include Carbamazepine or Gabapentin.
• Antidepressants: Citalopram or similar agents may help with depression and emotional lability.

Prognosis

• Median survival is 2-3 years from diagnosis. Approximately 25% of patients survive for 5 years or more.

References

• NICE Guidance on Riluzole