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Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
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Multiple sclerosis with predominant, severe cognitive impairment.

Nathan P Staff1, Claudia F Lucchinetti, B Mark Keegan

  • 1Department of Neurology, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905, USA.

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Multiple sclerosis (MS) can present with severe cognitive impairment, often accompanied by psychiatric and cortical symptoms. This cognitive dysfunction may follow a subacute or chronic course, with limited response to standard therapies.

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Area of Science:

  • Neurology
  • Neuroimmunology
  • Cognitive Neuroscience

Background:

  • Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system.
  • Cognitive impairment is a common but often under-recognized symptom of MS.
  • Severe cognitive impairment as the primary manifestation is less understood.

Purpose of the Study:

  • To characterize the clinical, radiological, and demographic features of patients with multiple sclerosis (MS) presenting with severe cognitive impairment as their main disabling symptom.
  • To identify potential differences in presentation and course between subacute fulminant and chronic progressive forms of MS-related cognitive dysfunction.

Main Methods:

  • Retrospective case series of 23 patients diagnosed with definite MS (McDonald criteria) between 1996 and 2008.
  • Patients were selected based on severe cognitive impairment as the primary neurological symptom without other significant MS-related impairments or alternative causes.
  • Data collected included demographics, clinical course, psychiatric and cortical signs, and brain and spinal cord magnetic resonance imaging (MRI) findings.

Main Results:

  • The median age at first symptom was 33 years, and at severe cognitive impairment onset was 39 years.
  • Cognitive impairment presented as subacute fulminant (n=9) or chronic progressive (n=14), correlating with disease course.
  • Commonly observed were psychiatric (65%), cerebellar (57%), and cortical symptoms (39%). Diffuse cerebral atrophy and enhancing lesions were noted on MRI. Cigarette smoking was prevalent (67%).

Conclusions:

  • MS can manifest with severe cognitive dysfunction, prominent psychiatric and cortical signs, and either a subacute or chronic progressive course.
  • Immunomodulatory therapies showed limited efficacy in this cohort.
  • Cigarette smokers may be disproportionately represented in this MS phenotype.