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A Protocol for Comprehensive Assessment of Bulbar Dysfunction in Amyotrophic Lateral Sclerosis (ALS)
Published on: February 21, 2011
Cognitive impairment in sporadic ALS: a pathologic continuum underlying a multisystem disorder
C M Wilson1, G M Grace, D G Munoz
1Neurodegeneration Research Group, John P. Robarts Research Institute, London, Ontario, Canada.
Neurology
|August 29, 2001
Summary
Cognitive impairment in Amyotrophic Lateral Sclerosis (ALS) is linked to increased ubiquitin-positive inclusions and superficial linear spongiosis (SLS), suggesting a disease continuum. SLS uniformly indicates cognitive issues in ALS patients.
Area of Science:
- Neuropathology
- Neurodegenerative Diseases
Background:
- Amyotrophic Lateral Sclerosis (ALS) is traditionally viewed as a motor neuron disorder.
- Clinical ALS can present with frontotemporal dementia, but its pathological basis is unclear.
- Ubiquitin-immunoreactive (Ub+) intraneuronal inclusions in cortical regions may mark cognitive impairment in ALS.
Purpose of the Study:
- To compare neuropathological features in cognitively impaired versus intact ALS patients.
- To identify pathological markers distinguishing ALS subpopulations.
- To investigate the relationship between cognitive status and neuropathology in ALS.
Main Methods:
- Compared neuropathology in four cognitively impaired ALS, four cognitively intact ALS, and four normal patients.
- Quantified ubiquitin-positive (Ub+) neuronal inclusions, dystrophic neurites, and superficial linear spongiosis (SLS).
- Examined cortical, hippocampal, and subcortical regions.
Main Results:
- Ub+ inclusions were more abundant in cognitively impaired ALS patients, especially in the cingulate gyrus.
- Superficial linear spongiosis (SLS) in cortical layers 1-2 reliably differentiated impaired from intact ALS patients.
- SLS correlated with microglial activation in impaired ALS patients.
Conclusions:
- Increased Ub+ inclusions and dystrophic neurites in ALS correlate with cognitive impairment, suggesting a disease continuum.
- Superficial linear spongiosis (SLS) is a consistent pathological feature associated with cognitive impairment in ALS.
- These findings link specific neuropathological changes to cognitive decline in ALS, a feature shared with frontotemporal dementia.
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