Makindo Medical Notes.com

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

Generalised and bulbar weakness with wasting with brisk reflexes and no sensory loss with eyes and bladder spared. There is no diagnostic test for MND. The diagnosis requires the demonstration of clinical signs affecting both the brain and spinal cord.

About

• Also called Amyotrophic lateral sclerosis, Charcot's disease and Lou Gehrig's disease
• Diagnosis is often delayed and can take more than 16 months from the onset
• Initial symptoms are commonly non-specific and include general fatigue.

How common is it

• Incidence of ALS ranges from 1.8 to 2.2 per 100,000 population
• Prevalence ranges from 4.0 to 4.7 per 100,000 population in UK
• At any one time about 2000 affected individuals per year in England and Wales

Pathology: A degenerative disease of

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

Aetiology/Genetics

• There is a form or variant of MND which seems to occur in Guam associated with Dementia and Parkinson's disease. Affects Gomorro people on Island of Guam
• Superoxide dismutase 1 (SOD1) mutations
• Genes mutations affecting RNA processing
• Gene mutation affecting axonal cytoskeleton and transport
• Familial ALS: 10% are inherited as a Autosomal dominant disorder

Forms

• Progressive muscular atrophy - mainly LMN. Survival 5-10 years
• Progressive Bulbar palsy involves both LMN and UMN with a wasted fasciculation of the tongue + increased jaw jerk + spastic palate. Survival 2-3 years
• Primary lateral sclerosis (UMN) - predominately symmetrical UMN. Good prognosis
• Amyotrophic lateral sclerosis UMN (lateral) signs predominantly. Survival 3-4 years
• MND -Dementia - frontotemporal dementia

Clinical: Mixed UMN + LMN and normal sensory

• Subtle weakness and fatigue and low energy at first
• Weakness and Wasting of hand and other muscles
• Painful nocturnal muscle cramps in thigh
• Weakness with wasting and fasciculation
• Weakness with brisk jerks and extensor plantar
• No sensory signs - may be mild symptoms
• Eye movements and sphincters are unaffected
• Wasted fibrillating tongue and impaired swallow
• Dysarthria and dysphagia as bulbar muscles affected
• Retained abdominal reflexes
• Weight loss due to swallowing issues and loss of muscle bulk
• Dropped head, wasted hand

El Escorial criteria for MND

• Clinically Definite ALS: Upper and lower motor neuron signs in three or more regions. Regions are defined as bulbar, cervical, thoracic, or lumbar.
• Clinically Probable ALS: Upper and lower motor neuron findings in two regions or having upper motor neuron findings anatomically rostral (above) lower motor neuron findings. (therefore increased reflexes in the arms with wasting and fasciculations in the legs would qualify, but not the other way around.)
• Clinically Possible ALS: Upper and lower motor neuron findings in one region or lower motor neuron findings above upper motor neuron findings

Differential

• Multifocal motor neuropathy with conduction block (MMN) - Nerve conduction studies and check Serum GM-1 Ab
• Cervical spondylotic myelopathy with polyradiculopathy
• Lesion at foramen magnum or high cervical with bulbar signs and long tract signs. (get MRI)
• Chronic inflammatory demyelinating polyneuropathy
• Inclusion body myositis - distal wasting and weakness in an older person (EMG Muscle biopsy)
• Myasthenia gravis :Tensilon test + Antibodies+ single fibre EMG
• Kennedy's syndrome - X Linked bulbospinal neuronopathy
• Benign fasciculation syndromes, Hereditary spastic paraparesis
• B12 deficiency: measure levels
• Lyme disease: Lyme titres
• Malignancy: CT CAP

Investigations

• FBC, U&E, TFT, CK - can be mildly elevated, PPE, Syphilis serology, CXR
• LP and CSF exam can show a mildly raised protein
• Auto Antibodies: Exclude other causes Anti acetylcholine receptors Ab, Anti GM1,
• MRI of brain and cervical cord may show global atrophy. It is often required to exclude nerve root compression(LMN) or syringomyelia or syringobulbia which along with cerebrovascular disease or other pathologies that could mimic MND. MRI T2 weighted may show high signal intensity within corticospinal tracts due to Wallerian degeneration. The MRI may show significant cervical spondylitis changes but this should not be overinterpreted.
• Electromyogram (EMG) - Fasciculations and fibrillation potentials. The presence of fibrillation and positive waves (together referred to as spontaneous activity) and decreased recruitment in a muscle qualify as lower motor neuron findings, and can be used to upgrade the probability of the diagnosis based on the El Escorial criteria outlined below. Chronic denervation and reinnervation in at least 3 spinal regions (cervical, thoracic, lumbosacral) or 2 spinal regions and bulbar muscles
• Muscle biopsy may be considered if myopathy considered
• Nerve conduction studies: usually normal proximal motor and sensory until late in the disease

Management

• General: There is no current treatment that prevents the underlying disease from progressing. Management is supportive. Counselling, information, End of life support and perhaps hospice care can be introduced as needed. Access to Physiotherapy, OT, SALT and rehab in early disease to optimise and support function and provide equipment and appropriate seating and bed may be useful as patients become weaker. There is little scope for rehabilitation. Fatigue is often significant.
• Anticholinergics may be used for drooling and Baclofen or diazepam for spasticity
• NG and PEG feeding should be discussed with the patient and family and can often provide increased quality of life. A radiologically inserted gastrostomy is an alternative.
• Consider for Riluzole 50 mg bd a glutamate antagonist. The use of riluzole has a modest impact on survival, approximately 2-3 months in selected patients.
• NIV may improve survival up to six months in patients without severe bulbar involvement especially overnight in terms of reducing fatigue and sleepiness and improving the overall quality of life.
• Percutaneous gastrostomy to enable feeding as the ability to swallow decreases and tracheostomy with or without ventilatory support to aid breathing as respiratory muscle weakness increases
• Speech synthesizers may help with communication when normal voice is lost
• Quinine sulphate 300 mg on for cramps. Consider Carbamazepine and Gabapentin too
• Depression - consider Citalopram or similar antidepressant and may also help emotional lability

Prognosis

• Median survival 2-3 years. Only 25% of pts survive for 5 years

References

• NICE Guidance on Riluzole