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Multiple sclerosis masquerading as Alzheimer's type dementia: Clinical, radiological, and pathological findings

W. Oliver Tobin, Bogdan Popescu, Val J. Lowe, Istvan Pirko, Kejal Kantarci, Julie A. Fields, Bradley F. Boeve, Claudia F. Lucchinetti

Alzheimer's & Dementia Volume 10, Issue 4, Supplement, July 2014, Pages P630

Background:
We aim to report clinical, radiological and pathological findings on a patient with clinical features of Alzheimer's disease (AD), but with cortical demyelination as the primary pathological diagnosis. We shall demonstrate that cortical demyelination can mimic neurodegenerative disease.

Methods:
This 57-year-old woman presented with progressive cognitive decline and a background of a single episode of optic neuritis. Examination demonstrated a subtle left internuclear ophthalmoplegia, with no other focal neurological signs. T2-weighted brain MRI demonstrated periventricular and corpus callosum high signal.

Results: 
Spinal fluid oligoclonal band testing and IgG synthesis rate were normal. Cognitive decline was associated with cortical atrophy on serial MRI scans, without accumulation of T2 weighted white matter lesions over 13 years. The rate of increase in her ventricular volume (5.5 cm3/year; 95% CI, 5.0-6.0 cm3/year) was comparable to that of 46 subjects with amnestic mild cognitive impairment who progressed to AD. Progressive impairment in frontal and subcortical domains was demonstrated on neuropsychometric testing. Fluorodeoxyglucose positron emission tomography (FDG-PET) revealed temporal lobe hypometabolism. She was diagnosed with Alzheimer type dementia antemortem. Autopsy demonstrated chronic inactive-type demyelinated white matter lesions, with mild infiltration by activated microglia and lymphocytes, and fibrillary gliosis. Neurofibrillary tangles were moderate in the entorhinal cortex and hippocampus, and rare in the amygdala. Beta-amyloid deposits and TDP43 inclusion were absent, a finding inconsistent with the pathologic diagnosis of Alzheimer's or frontotemporal dementia. Myelin immunohistochemistry showed the presence of widespread and extensive cortical subpial demyelination (Figure 1). Subpial lesions affected the upper cortical layers and often extended to the entire width of the cortex, and involved multiple adjacent gyri of all cerebral lobes and type of cortices, but not the cerebellar cortex. Demyelinated lesions also involved the deep grey structures, the brainstem grey matter nuclei and the anterior horns of the spinal cord bilaterally.

Conclusions: 
Multiple sclerosis can cause severe cortical dysfunction, cortical demyelination and atrophy, which may mimic AD-related changes on standard imaging modalities and which may not be detected on autopsy without myelin immunohistochemistry. Progressive cognitive decline in patients with a history of episodic neurological dysfunction should prompt investigation for alternate diagnoses, including multiple sclerosis.

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About the Editors

  • Prof Timothy Vartanian

    Timothy Vartanian, Professor at the Brain and Mind Research Institute and the Department of Neurology, Weill Cornell Medical College, Cornell...
  • Dr Claire S. Riley

    Claire S. Riley, MD is an assistant attending neurologist and assistant professor of neurology in the Neurological Institute, Columbia University,...
  • Dr Rebecca Farber

    Rebecca Farber, MD is an attending neurologist and assistant professor of neurology at the Neurological Institute, Columbia University, in New...

This online Resource Centre has been made possible by a donation from EMD Serono, Inc., a business of Merck KGaA, Darmstadt, Germany.

Note that EMD Serono, Inc., has no editorial control or influence over the content of this Resource Centre. The Resource Centre and all content therein are subject to an independent editorial review.

The Grant for Multiple Sclerosis Innovation
supports promising translational research projects by academic researchers to improve understanding of multiple sclerosis (MS) for the ultimate benefit of patients.  For full information and application details, please click here

Journal Editor's choice

Recommended by Prof. Brenda Banwell

Causes of death among persons with multiple sclerosis

Gary R. Cutter, Jeffrey Zimmerman, Amber R. Salter, et al.

Multiple Sclerosis and Related Disorders, September 2015, Vol 4 Issue 5