primary lateral sclerosis

Last edited 11/2023 and last reviewed 11/2023

This is a form of motor neurone disease (MND). It is the most common form of MND and accounts for 65% to 85% of all cases of MND (1).

Amyotrophic lateral sclerosis results from lesions to the corticospinal tract and the anterior horn cells and produces the characteristic feature of tonic atrophy - brisk reflexes and fasciculations.

• a late onset, rapidly progressive and ultimately fatal neurological disorder, caused by the loss of motor neurons in the brain and spinal cord (2)
  • familial aggregation of ALS, with an age-dependent but high penetrance, is a major risk factor for ALS
  • familial ALS (FALS) is clinically and genetically heterogeneous
    • three genes and linkage to four additional gene loci have been identified so far and may either predominantly lead to ALS (ALSI-ALS6) or cause multisystem neurodegeneration with ALS as an occasional symptom (tauopathies, ALS-dementia complex)

This form of the disease includes Progressive Bulbar Palsy (1).

Corticospinal tract degeneration in the absence of significant muscle wasting may be referred to as primary lateral sclerosis (PLS).

• PLS entity is not universally accepted. Debate continues over whether the disease constitutes a distinct clinical and pathological entity or whether it is a part of the spectrum of MNDs that presents an upper motor neuron (UMN) predominant form of MND (3)
  • prospective analysis of a series of PLS case reports was in agreement with data from other studies suggesting that pure PLS cases have a prolonged course of disease with a high level of independence when compared to other MND (3)

Points to consider (5):

• ALS was previously considered rare, but incidence is expected to increase by 30% by 2040
  • MND/ALS is a rare disease with a global prevalence of around 4.5 cases per 100,000, increasing to 12 to 15 per 100,000 in high income settings
    
    
• ALS is a multisystem disease that commonly causes cognitive and behavioural changes; up to one quarter of patients meet the criteria for dementia (5)
  • ALS shares features of frontotemporal dementia, a group of neurodegenerative disorders that causes cognitive, behavioral, and motor dysfunction (6)
    • nearly half of all patients with ALS have varying degrees of cognitive and/or behavioral impairment, with approximately 15% meeting the diagnostic criteria for frontotemporal dementia
    • conversely, about 15% of patients with behavioral variant frontotemporal dementia and 18% of patients with primary progressive aphasia have ALS
      
      
• diagnostic delay may reduce access to treatment and support that could improve survival and quality of life; refer urgently for expert assessment patients with asymmetrical painless progressive weakness or unexplained changes to swallowing
  • most patients visit their general practitioner first, typically with mild symptoms such as cramps, balance disturbance, reduced dexterity, or subtle cognitive changes including apathy
  • time from symptom onset to diagnosis ranges from 10 to 16 months, and signs often go unrecognised, with patients referred to other specialists, or given misdiagnoses

Reference:

• (1) NICE (January 2001). Guidance on the Use of Riluzole (Rilutek) for the treatment of Motor Neurone Disease.
• (2) Majoor-Krakauer D et al. Genetic epidemiology of amyotrophic lateral sclerosis.Clin Genet. 2003 Feb;63(2):83-101.
• (3) Tomik B et al. Pure primary lateral sclerosis--Case reports.Clin Neurol Neurosurg. 2008 Apr;110(4):387-91.
• (4) Orrell, R. & deBelleroche, JS. Superoxide dismutase and ALS. Lancet 1994;344: 1651-2.
• (5) Mahoney C J, Sleeman R, Errington W. Assessment of suspected motor neuron disease BMJ 2022; 379 :e073857 doi:10.1136/bmj-2022-073857
• (6) Ilieva H, Vullaganti M, Kwan J. Advances in molecular pathology, diagnosis, and treatment of amyotrophic lateral sclerosis BMJ 2023; 383 :e075037 doi:10.1136/bmj-2023-075037