Amyotrophic Lateral Sclerosis

Diseases, , ,

Synonyms:

Lou Gehrig disease

Clinical features:

  • Features of upper motor neuron (UMN) disease (including increased reflexes in wasted limb) & lower motor neuron (LMN) disease
  • +/-pseudobular palsy
  • +/-cramps
  • Weakness, fasciculations
  • No sensory disturbance, no bowel or bladder dysfunction

Diagnostic criteria:

  • El Escorial criteria, also known as, World Federation of Neurology criteria (used more for research)
  • In general:
    • Features of upper motor neuron disease, by clinical testing or electrophysiology or neuropathology
    • Plus features of lower motor neuron disease, by clinical testing or electrophysiology or neuropathology
    • Progression over time within the region or to other regions
    • Exclusion of other conditions by electrophysiology and imaging

Findings on Investigations:

Nerve Conduction Studies/Electromyography NCS/EMG:
  • Use to rule out competing diagnosis in the differential diagnosis

Nerve conduction study, NCS:

  • SNAP: normal, normal amplitude, velocity & latency
  • CMAP: normal or mildly reduced velocity & latency, reduced amplitude

Electromyography, EMG:

  • Denervation (fibrillation potentials, positive sharp waves PSW) in 3 limbs or 2 limbs +bulbar muscles. Fasciculation potentials & complex repetitive discharges CRDs may occur.
  • MUAP (reinnervation): polyphasic, large amplitude, increased duration,
  • Decreased recruitment
Other tests:

MRI:

  • T2, FLAIR: symmetric hyperintensity of the corticospinal tracts in the brain (centrum semiovale, internal capsule), brainstem (cerebral peduncles) & spinal cord (lateral columns)

Pathology, Muscle biopsy:

Denervation pattern in clinically unaffected muscle see below
Gross:

  • Atrophy of cervical & lumbosacral parts of the spinal cord. Atrophy of motor nerve roots, sparing of the sensory nerve roots. Atrophy of precentral gyrus.

Microscopically:

  • Loss of anterior horn cells in the spinal cord. Loss of Betz cells in the primary motor cortex. Degeneration (anterograde) of anterior & lateral corticospinal axons/tracts. Myelin loss, astrocytic gliosis & macrophage accumulation. Bunina bodies= small eosinophilic bodies, cytoplasmic, in anterior horn cells. Skeletal muscle; features of denervation

Immunohistochemsitry:

  • Bunina bodies are cystatin C positive & ubiquitin negative. Ubiquitin: positive spherical cytoplasmic inclusions in anterior horn cells. Neurofilament: dystrophic axons
  • TDP-43 (TAR DNA binding protein 43): positive inclusions

Genetic forms:

  • ALS1: Autosomal dominant, Protein= Cu/Zn Superoxide dismutase, SOD1 gene chr. 21,
  • ALS2: autosomal recessive, chr. 2q33, protein= is a GTPase regulator

Related conditions:

  • Frontotemporal lobar degeneration with motor neuron disease FTLD-MND: see FTD
To rule out other disease consider:
  • Hexosaminidase levels: hexosaminidase deficiency
  • MRI: to rule out cervical spondylosis
  • Anti-GM1: MMN, also positive in ALS
  • Parathyroid hormone level: hypoparathyroidism can cause fasciculations & weakness

Treatment

General measures:

Consider Respiratory evaluation:

  • PFTs, Overnight pulse oximetry, SNIP
  • Early morning ABG: hypercapnea i.e. hypoventilation
  • Respiratory support:
    • Consider NIPPV at night time

Speech & language therapy evaluation
Discuss palliation & end of life decisions early & continue
Immobility: consider braces or a walker
Physiotherapy esp. to prevent contractures
Dysphagia, consider:

  • Semiliquid diet
  • Nasogastric tube feeding
  • Percutaneous endoscopic gastroscopy PEG
Pharmacological:
  • Riluzole P.O. to slow progression in ALS

If drooling consider anticholinergics:

  • Glycopyrrolate, trihexyphenidyl, amitriptyline, transdermal hyoscine

Related articles:

References:

  1. Haggiag, S., et al., Seroconversion of anti-GM1 antibodies in patients with amyotrophic lateral sclerosis. Neurology, 2004. 63(4): p. 755-6.