Motor Neurone Disease

i.e. the disease behind the ice bucket challenge. Great money raising concept, but I don’t think most people (myself included) actually knew a thing about MND.


Motor Neurone Disease (MND)

Definition: a cluster of major progressive neurodegenerative diseases characterised by selective loss of motor neurones in the motor cortex, cranial nerve nuclei, and anterior horn cells (spinal nerves).

Upper motor neurones (UMN) and lower motor neurones (LMN) are affected but there is no sensory loss or sphincter disturbance (in contrast to MS and polyneuropathies).

MND never affects eye movements (in contrast to myasthenia gravis).

Image result for upper and lower motor neurons

Aetiology/ risk factors:

4 clinical patterns:

  1. ALS/ Amyotrophic Lateral Sclerosis (50%)- loss of motor neurones in motor cortex (UMN) and the anterior horn of the cord (LMN)
  2. Progressive bulbar palsy (10%)- only affects nuclei of cranial nerves IX-XII (glossopharyngeal, vagus, hypoglossal)
  3. Progressive muscular atrophy (10%)- anterior horn cell lesion only (LMN)
  4. Primary lateral sclerosis– loss of Betz cells in motor cortex (UMN)

-Cause unknown. Free radical damage and glutamate excitotoxicity have been implicated.

-Mutations at the ALS-FTD locus on chromosome 9 explain 87% of familial ALS.

-5-10% have family history with autosomal dominant inheritance

Epidemiology: rare

-Prevalence = 6/100,000

-Incidence = 2/100,000/yr

-UK median age of onset = 60 years

-M:F ≈ 3:2

Symptoms & Signs:

⇒ ALS/ Amyotrophic Lateral Sclerosis (UMN + LMN)

-Weakness

-proximal myopathy, weak grip (door handles don’t turn), weak shoulder abduction (hair-washing hard) etc.

Upper motor neurone signs: upgoing plantars, spasticity, brisk reflexes

-stumbling spastic gait

Image result for upgoing plantars

Lower motor neurone signs: muscle wasting, fasciculations (tongue, abdomen, back, thigh)

Split hand sign: excessive wasting around the thumb (thenar), compared to hypothenar wasting )

Image result for split hand sign als

-Fronto-temporal dementia (in ∼25%)

El Escorial diagnostic criteria can be used to help diagnose ALS

Progressive bulbar palsy (CN/LMN)

-LMN signs of tongue and muscles of talking and swallowing

-flaccid, fasciculating tongue (like a sack of worms)

Image result for bulbar palsy tongue

-speech is quiet, hoarse or nasal

-dysarthria, dysphagia

-nasal regurgitation of food, especially fluids (palatal weakness)

-reduced gag reflex

-jaw jerk normal or absent (not sure why this would be tbh, since it’s CNV)

Progressive muscular atrophy (LMN)

-no UMN signs

-affects distal muscle groups before proximal

LMN signs: muscle wasting, fasciculations, flaccid weakness, depressed or absent reflexes

-flail arm or flail foot

Primary lateral sclerosis (UMN)

-Upper motor neurone signs: upgoing plantars, spasticity, brisk reflexes

-Marked spastic leg weakness, stumbling spastic gait

Pseudobulbar palsy– i.e. corticobulbar palsy- UMN lesion of muscles of swallowing and talking due to bilateral lesions above the mid-pons e.g corticobulbar tracts

-slow tongue movements, shrunken immobile tongue (spastic tongue)

-slow, deliberate, montonous speech (scanning/ explosive speech)

-dysphagia

-increased gag reflexes

-increased jaw jerk reflex

Pseudobulbar Affect (PBA)- unprovoked weeping, incongruent giggling (emotional lability)

-No cognitive decline

 

⇒Sensory examination should be normal for MND.

Investigations:

Aim to confirm diagnosis by providing evidence of UMN and LMN loss and excluding other causes.

Blood- Creatine Kinase (slight elevated), ESR, consider anti-GM1 ganglioside antibodies (+ve in multifocal motor neuropathy)

-Electromyography (EMG)- features of acute and chronic denervation with giant motor unit action potentials on more than 1 limb and/ or paraspinals muscles

-Nerve conduction studies- usually normal, help exclude mimicking motor neuropathies

Brain/cord MRI- helps exclude structural causes, cord or root compression and brainstem lesion.

May show high signal in motor tracts on T2 MRI imaging.

Lumbar puncture-helps exclude inflammatory causes

Spirometry- assess respiratory muscle weakness (FVC)

Management: mainstay of treatment is supportive, symptomatic, palliative

MDT approach: neurologist, palliative nurse, hospice care (in final stages), physiotherapy (walking aids), occupational therapy (home adaptations), speech therapy (swallowing assessment, communication aids), dietician, social services, GP, psychological support

Antiglutamatergic drugs: RILUZOLE- prolongs life by ∼3 months but costs a bomb. Need to monitor LFTs.

Drooling- PROPANTHELINE (anti-cholinergic) (15-30mg/8h), AMITRIPTYLINE (tricyclic) (25-50mg/8h)

Dysphagia- blend food, consider nasogastric tube or catheter gastrostomy/ Percutaneous endoscopic gastrostomy (PEG)

Image result for percutaneous endoscopic gastrostomy

Spasticity: BACLOFEN, DIAZEPAM, DANTROLENE, TIZANIDINE, SAVITEX. Botox injection if spasticity is localised.

Joint pains and distress: analgesia- NSAIDs to strong opioids, going up the analgesic ladder

Respiratory failure +/- aspiration pneumonia and sleep apnoea: non-invasive ventilation at home in selected patients

Complications:

-Depression, emotional lability

-Fronto-temporal dementia

-Weight loss and malnutrition (due to dysphagia)

-Immobility related: DVT, aspiration pneumonia

-Respiratory failure because of weakness of ventilatory muscle (usual cause of death)

-Death by choking is rare

Prognosis:

-relentless progression

-often fatal in 2-4 years, mean survival about 3 years

-worse prognosis if bulbar onset and young onset, and if low forced vital capacity (lung capacity)

-progressive muscular atrophy has better prognosis than ALS

References: Cheese & Onion, Rapid Medicine
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