Morvan syndrome and related disorders associated with CASPR2 antibodies
Jan. 18, 2022
At vero eos et accusamus et iusto odio dignissimos ducimus qui blanditiis praesentium voluptatum deleniti atque corrupti quos dolores et quas.
Alzheimer disease is the most common underlying condition for dementia and, pathologically, Alzheimer disease is attended by amyloid plaques and neurofibrillary tangles by definition. Many autopsy studies have reported brains with neurofibrillary tangles that are indistinguishable from those of Alzheimer disease, in the absence of amyloid beta plaques. For these brains, the neurofibrillary tangles are mostly restricted to structures in the medial temporal lobe, and brainstem. Clinical biomarkers are also finding evidence of tauopathy in the absence of amyloid beta-type amyloidogenesis, and associated studies are confirming the brain changes are associated with cognitive impairment. This condition is termed “primary age related tauopathy” or PART.
Symptoms in persons with PART usually range from normal to amnestic cognitive changes, with only a minority exhibiting profound impairment (unless additional comorbid pathologies are present, which is not unusual). PART is almost universally detectable at autopsy among elderly individuals who lack amyloid beta plaques; in advanced old age, approximately 25% of persons lack amyloid beta plaques.
As a rule, every person past 80 years of age (and the great majority over 50 years of age) (21) has some PART pathology--it is presumed to exist even in those with Alzheimer disease wherein the plaque or tangle pathology renders impossible the independent evaluation of the PART pathology. Those lacking amyloid plaques, but with more severe PART pathology (Braak NFT stages III or IV), are more likely to have lower MMSE scores and subjective memory complaints or MCI. If there are other pathologies and/or if the PART pathology is severe, it can contribute to MCI or full-blown dementia. The clinical-pathological correlation studies indicate the challenge of defining a “disease” versus “normal” state in advanced old age, and PART helps explain why the average (“normal”) and even above-average neurocognitive scores among nondemented persons becomes lower in advanced old age.
New data have emerged in 2 different areas related to PART: biomarkers and clinical-pathological correlations, and these are discussed below.
There also has been some debate in the field about this pathologic entity (17), although some degree of acceptance is widespread with more than 800 citations of the original paper from 2014 to 2021.
• PART is a pathologically defined entity that helps explain normative loss in cognitive function in advanced old age.
• Genetic contributors to PART do not include APOE (unlike Alzheimer disease).
• Clinical-pathological correlations indicate that PART usually has a more moderate outcome, ie, a less devastating clinical course, than Alzheimer disease.
• PART features tauopathy in medial temporal lobe and brainstem, resembling Alzheimer disease, but, by definition, there are no amyloid plaques.
• PART may be obscured by other pathologies, particularly Alzheimer disease.
• PART is ubiquitous among the non-Alzheimer disease elderly, but there is variation in severity between individuals.
PART was described in 2014 (13); however, patients with mild-to-moderate Alzheimer disease-type neurofibrillary degeneration in the medial temporal lobe, but lacking amyloid beta plaques, were previously described in European, Japanese, and North and South American cohorts (60; 02; 25; 31).
Prior terminology included “tangle-predominant senile dementia,” “tangle-only dementia,” “preferential development of neurofibrillary tangles without senile plaques,” and “senile dementia of the neurofibrillary tangle type” (SD-NFT), among other names (20; 60; 39; 02; 07; 25; 23; 15).
PART pathology appears to correlate with a clinical biomarker profile that has been termed “SNAP,” or “suspected nonamyloid pathology/pathophysiology,” describing persons with possible age-related neurodegeneration but lacking Alzheimer disease-type A-beta amyloidogenesis according to biomarkers (28; 35; 61; 26). However, there are other non-Alzheimer diseases that contribute to SNAP, and for a patient with profound cognitive impairments, PART would probably not be the only underlying disease.
Studies have helped underscore differences between Alzheimer disease and PART (05; 04), including the relatively benign clinical features of PART in comparison to Alzheimer disease.
Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.