Motor Neurone Disease

Introduction

  • A spectrum of degenerative motor neuron diseases (MND).
  • It is relatively uncommon with an annual incidence of 2 cases per 100,000.
  • The disease onset is usually between 50-70 years of age.
  • The majority of MND cases are sporadic with an unknown cause.
  • Protein aggregation containing RNA processing proteins TDP-43 and FUS in the axon of motor neurons is characteristic of MND.
  • A small percentage of MND cases are familial
  • Mutations are seen free radical scavenging enzyme superoxide dismutase (SOD-1) and other genes including TDP-43 and FUS.
  • A repeat expansion mutation in the C9ORF72 gene on chromosome 9 is associated with a large amount of familial cases of motor neuron disease – frontotemporal dementia overlap.

Classification

The different types of MND include:

  • Amyotrophic lateral sclerosis (ALS) – most common form of MND.
  • Primary lateral sclerosis (PLS).
  • Progressive muscular atrophy.
  • Amyotrophic lateral sclerosis with frontotemporal dementia.

Presentation

Muscle weakness

  • Most commonly assymetric limb weakness
  • Can potentially effect any muscle group

Dyspnoea and orthopnoea
In more advanced disease

  • Frequent aspirations of drinks and eventually food
  • Painful muscle spasms

History

  • Family history of MND?
  • Previous history of smoking?
  • Recent infection?
  • Recent history of falls?
  • Recent outburst of laughter or crying?
  • Excessive drooling?
  • Collateral history need to assess any change in personality/behavioural dysfunction – potential FTD symptoms

Examination

  • The classical presentation of ALS (and some other MNDs) is the presence of both upper and lower motor neurons (UMN and LMN) signs on neurological examination.

Upper extremity weakness – can be due to UMN or LMN weakness
Increased tone and poor coordination – UMN sign
Hyperreflexia – UMN sign
Muscle atrophy – LMN sign
Dysarthria
Strained, slow speech – UMN sign
Slurred, nasal speech – LMN sign
Dysphagia – UMN or LMN sign
Poor posture and lumbar lordosis – LMN sign
Proximal weakness – LMN sign

Laboratory investigations

  • Vitamin B12 levels - normal
  • Creatine kinase – possible elevation
  • Acetylcholine receptor antibodies – negative
  • Voltage-gated calcium-channel antibodies – negative
  • Anti-GM1 antibodies – negative

Radiological investigations

MRI brain and spine – to exclude spinal cord compression

Other investigations

Electromyography (EMG) – evidence of diffuse chronic denervation.
SOD1 mutation testing – may be positive indicative of familial disease.

Management

  • ALS and other MNDs are complex diseases that involve a multidisciplinary team approach to care.
  • Management is mainly symptomatic however oral riluzole 50mg b.d. (prolongs survival).
  • Palliative care should be offered if symptoms are rapidly progressive both ADRT and DNACPR should be considered early.

Muscle problems

  • Spasticity – oral baclofen 5mg t.d.s. (Increase by 5mg/dose every 3 days till effective).
  • Cramps – quinine 200-300mg o.n
  • Physiotherapy and exercise programmes

Gastrointestinal symptoms

  • Dysphagia can lead to mild or significant weight loss.
  • Diet advice/modification.
  • If severe a percutaneous endoscopic gastrostomy (PEG) tube should be used.

Saliva problems

  • Anticholinergic is first line such as: oral hyoscyamine every 4-6 hours
  • If unresponsive use of botulinum toxin may be warranted (specialist use only).

Respiratory problems

  • If forced vital capacity (FVC) is between 30-50% then bilevel positive airway pressure (BiPAP).
  • If FVC is below 30% with hypoxia or hypercapnea then long-term invasive ventilation is needed.

Complications

  • Respiratory failure.
  • Aspiration pneumonia.
  • Hepatatoxicity and neutropenia (riluzole side effects).
  • Nutritional deficiency.
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