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"Preclinical" MSA in definite Creutzfeldt-Jakob disease
Roberta Rodriguez-Diehl1, Maria Jesus Rey, Alexandre Gironell
1Neurological Tissue Bank, University of Barcelona SCT - Hospital Clínic, Barcelona, Spain.
Abstract:
Multiple system atrophy (MSA) is a sporadic alpha-synucleinopathy clinically characterized by variable degrees of parkinsonism, cerebellar ataxia and autonomic dysfunction. The histopathological hallmark of MSA is glial cytoplasmic inclusion (GCI). It is considered to represent the earliest stage of the degenerative process in MSA and to precede neuronal degeneration. Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal, rapidly progressive dementia generally associated with ataxia, pyramidal and extrapyramidal symptoms and myoclonus. Definite diagnosis needs neuropathological demonstration of variable degrees of spongiform degeneration of neuropil, neuronal loss, astro- and microgliosis, and the presence of abnormal deposits of the misfolded prion protein PrP(res) . Both diseases, CJD and MSA are infrequent among neurodegenerative diseases. In the present report we describe clinical and neuropathological findings of a previously healthy 64-year-old woman who developed symptoms of classical CJD. At post mortem examination, the brain showed in addition to classical methionine/methionine PrP(res) type 1 (MM1) sCJD changes and moderate Alzheimer-type pathology, features of "preclinical" MSA with minimal histopathological changes. These were characterized by discrete amounts of alpha-synuclein immunoreacive glial cytoplasmic inclusions in the striato-nigral system, isolated intraneuronal inclusions in pigmented neurons of the substantia nigra, as well as some vermiform intranuclear inclusions. To our knowledge, this is the first report on the coexistence of definite sCJD and "minimal changes" MSA in the same patient.
Insights
This report details the first known case of coexisting definite sporadic Creutzfeldt-Jakob disease (sCJD) and minimal changes of Multiple System Atrophy (MSA) in a single patient, identified through post-mortem examination.
Area of Science:
- Neuropathology
- Neurodegenerative Diseases
- Alpha-synucleinopathies
Background:
- Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by parkinsonism, ataxia, and autonomic dysfunction, with glial cytoplasmic inclusions (GCIs) as a hallmark.
- Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly fatal dementia presenting with neurological symptoms, diagnosed by spongiform changes and prion protein deposits.
- Both sCJD and MSA are infrequent neurodegenerative conditions.
Observation:
- A 64-year-old woman presented with classical sCJD symptoms.
- Post-mortem examination revealed MM1 sCJD pathology and moderate Alzheimer's disease changes.
- Additionally, minimal histopathological features of MSA were observed, including alpha-synuclein positive GCIs and intraneuronal inclusions.
Findings:
- The study reports the first documented instance of concurrent definite sCJD and "preclinical" or minimal change MSA in one individual.
- The findings highlight the presence of early-stage MSA pathology alongside established sCJD and Alzheimer's pathology.
- This case provides unique neuropathological insights into the co-occurrence of distinct neurodegenerative processes.
Implications:
- This case challenges our understanding of the potential overlap and progression of different neurodegenerative diseases.
- Further research may elucidate the mechanisms underlying the coexistence of alpha-synucleinopathies and prion diseases.
- Understanding these co-occurrences is crucial for accurate diagnosis and potential therapeutic strategies in complex neurodegenerative cases.
