Motor Neurone Conditions

Myasthenia Gravis

This is an autoimmune disease caused by autoantibodies against nicotinic acetylcholine receptors (AchR) at the neuromuscular junction (NMJ).

There can be additional antibodies against muscle-specific kinase (MuSK) protein.

It is more common in women and associated with thymus hyperplasia and thymoma.

Symptoms

Use dependent muscle weakness – this worsens with activity and improves with rest

Weakness typically starts with eyes (ptosis, diplopia), and can spread (or generalise) to face, bulbar muscles, neck, trunk, and limbs (proximal > distal muscle weakness)

Symptoms are exacerbated by infections, surgery, and some drugs, e.g., beta-blockers, lithium, certain antibiotics (ciprofloxacin, gentamicin)

Key tests

Blood test shows anti-AChR antibodies, (and anti-MuSK antibodies)

Creatinine kinase is normal, showing the symptoms are not secondary to myositis

EMG shows decreasing response to repetitive nerve stimulation

CT scan imaging can be used to look for a thymoma (tumour of thymus gland)

Management

Anticholinesterases (e.g., pyridostigmine) increase amount of acetylcholine available in the NMJ, therefore improving stimulation of muscles

Immunosuppression e.g., steroids for acute flares

Steroid sparing agents, such as azathioprine, mycophenolate mofetil, rituximab

Thymectomy improves symptoms and may be considered without thymoma in AChRantibody positive disease

Lambert-Eaton Syndrome

A disease caused by antibodies against presynaptic calcium channels (VGCC).

It can either be autoimmune or secondary to a paraneoplastic syndrome e.g., from small cell lung cancer.

This leads to impaired ACh release, causing less activation of the muscle.

Symptoms

Proximal muscle weakness, with pronounced gait problems.

Strength may improve with use

The lower limbs are affected first and eye/respiratory muscles are usually not affected (or affected late)

Autonomic symptoms – dry mouth, urine retention, constipation

Areflexia (compared to normal reflexes in myasthenia gravis)

Key tests

Blood test shows anti-VGCC antibodies

EMG – motor amplitude increases with muscle contraction

CT scan to check for cancer

Management

If due to cancer, treat the cancer to improve symptoms

Steroids or immunosuppression particularly in autoimmune LEMS

3,4 diaminopyridine (amifampridine) – this blocks K+ channels in nerve terminals to depolarise them opening Ca2+ channels open for ACh release

Motor Neurone disease

This is a disease characterised by the loss of motor neurones from the motor cortex (upper motor neurones) and anterior spinal horn cells (lower motor neurones).

MND very rarely affects eye movement; it does not affect sphincter function and it does not give sensory or cerebellar signs.

There are four clinical patterns of MND, but the most commonly tested at medical school is amyotrophic lateral sclerosis (ALS).

Symptoms

Gives a mixture of upper and lower motor neuron symptoms and signs

LMN signs – flaccid paralysis with muscle atrophy, fasciculations, impaired reflexes

UMN signs – spasticity, rigidity, hyperreflexia, clonus, a positive Babinski sign

Wasting of dorsal hand muscles and tibialis anterior

Also affects bulbar and respiratory function, sometimes at presentation

Key tests

It is a clinical diagnosis based on above symptoms and signs

Nerve conduction studies and EMG

Brain and spinal cord MRI to exclude structural cause

Lumbar puncture is used to exclude an inflammatory cause

Management

Managed by a multidisciplinary team as there is no cure available

Riluzole, an NMDA antagonist is used which improves survival by several months

Non-invasive ventilation improves survival