When DLB, PD, and PSP masquerade as MSA

Koga, Shunsuke; Aoki, Naoya; Uitti, Ryan J.; Gerpen, Jay A. van; Cheshire, William P.; Josephs, Keith A.; Wszołek, Zbigniew K.; Langston, J. William; Dickson, Dennis W.

doi:10.1212/wnl.0000000000001807

Cited by 293 publications

(155 citation statements)

References 31 publications

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“…Recent reports revealed that only 62% of patients clinically diagnosed with MSA by community neurologists have the correct diagnosis at autopsy (Koga et al, 2015). The most common diseases misdiagnosed as MSA included PD, DLB and PSP.…”

Section: Discussionmentioning

confidence: 99%

“…Patients presenting with parkinsonism may be misdiagnosed as PD. The reverse also occurs; approximately 20% of patients with a clinical diagnosis of MSA turn out to have PD or DLB at autopsy (Koga et al, 2015). Patients presenting with the cerebellar phenotype can mimic other adult-onset ataxias due to alcohol, chemotherapeutic agents, lead, lithium, and toluene, or vitamin E deficiency, as well as paraneoplastic, autoimmune, or genetic ataxias (e.g., spinocerebellar ataxias, fragile X–associated tremor ataxia syndrome, or late-onset Friedreich ataxia) (Klockgether, 2010; Lin et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Diagnosis of multiple system atrophy

Palma

Norcliffe‐Kaufmann

Kaufmann

2018

Autonomic Neuroscience

126

114

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Multiple system atrophy (MSA) may be difficult to distinguish clinically from other disorders, particularly in the early stages of the disease. An autonomic-only presentation can be indistinguishable from pure autonomic failure. Patients presenting with parkinsonism may be misdiagnosed as having Parkinson disease. Patients presenting with the cerebellar phenotype of MSA can mimic other adult-onset ataxias due to alcohol, chemotherapeutic agents, lead, lithium, and toluene, or vitamin E deficiency, as well as paraneoplastic, autoimmune, or genetic ataxias. A careful medical history and meticulous neurological examination remain the cornerstone for the accurate diagnosis of MSA. Ancillary investigations are helpful to support the diagnosis, rule out potential mimics, and define therapeutic strategies. This review summarizes diagnostic investigations useful in the differential diagnosis of patients with suspected MSA. Currently used techniques include structural and functional brain imaging, cardiac sympathetic imaging, cardiovascular autonomic testing, olfactory testing, sleep study, urological evaluation, and dysphagia and cognitive assessments. Despite advances in the diagnostic tools for MSA in recent years and the availability of consensus criteria for clinical diagnosis, the diagnostic accuracy of MSA remains sub-optimal. As other diagnostic tools emerge, including skin biopsy, retinal biomarkers, blood and cerebrospinal fluid biomarkers, and advanced genetic testing, a more accurate and earlier recognition of MSA should be possible, even in the prodromal stages. This has important implications as misdiagnosis can result in inappropriate treatment, patient and family distress, and erroneous eligibility for clinical trials of disease-modifying drugs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Diagnosis of multiple system atrophy

Palma

Norcliffe‐Kaufmann

Kaufmann

2018

Autonomic Neuroscience

126

114

View full text Add to dashboard Cite

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“…This ambiguity leads to 20–40% diagnostic errors (1, 2), slow therapeutic progress (3) and suboptimal clinical outcomes. Complex neurological disorders such as multiple sclerosis (MS) are generally treated by a single disease modifying treatment (DMT), without understanding patient-specific drivers of disability.…”

Section: Introductionmentioning

confidence: 99%

Molecular‐based diagnosis of multiple sclerosis and its progressive stage

Barbour

Kósa

Komori

et al. 2017

Annals of Neurology

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Objective Biomarkers aid diagnosis, allow inexpensive screening of therapies and guide selection of patient-specific therapeutic regimens in most internal medicine disciplines. In contrast, neurology lacks validated measurements of the physiological status, or dysfunction(s) of cells of the central nervous system (CNS). Accordingly, patients with chronic neurological diseases are often treated with a single disease-modifying therapy without understanding patient-specific drivers of disability. Therefore, using multiple sclerosis (MS) as an example of a complex polygenic neurological disease, we sought to determine if cerebrospinal fluid (CSF) biomarkers are intra-individually stable, cell type-, disease- and/or process-specific and responsive to therapeutic intervention. Methods We used statistical learning in a modeling cohort (n=225) to develop diagnostic classifiers from DNA-aptamer-based measurements of 1128 CSF proteins. An independent validation cohort (n=85) assessed the reliability of derived classifiers. The biological interpretation resulted from in-vitro modeling of primary or stem cell-derived human CNS cells and cell lines. Results The classifier that differentiates MS from CNS diseases that mimic MS clinically, pathophysiologically and on imaging, achieved a validated area under receiver-operator characteristic curve (AUROC) of 0.98, while the classifier that differentiates relapsing-remitting from progressive MS achieved a validated AUROC of 0.91. No classifiers could differentiate primary-from secondary-progressive MS better than random guessing. Treatment-induced changes in biomarkers greatly exceeded intra-individual- and technical variabilities of the assay. Interpretation CNS biological processes reflected by CSF biomarkers are robust, stable, and disease- or even disease-stage specific. This opens opportunities for broad utilization of CSF biomarkers in drug development and precision medicine for CNS disorders.

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“…Most of these studies were based on a clinical series of tertiary centers; thus, they may be not representative of the general population of parkinsonism. In fact, even the UKPDSBRC are devoted to define only PD; however, little is known about the whole spectrum of parkinsonism; a recent study investigating the accuracy of the clinical diagnosis of MSA reported a diagnostic accuracy of 62% [36]. …”

Section: Discussionmentioning

confidence: 99%

Clinicopathologic discrepancies in a population‐based incidence study of parkinsonism in olmsted county: 1991‐2010

et al. 2017

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Objective To examine discrepancies between the clinical diagnosis of parkinsonism and neuropathological findings in a population-based cohort with parkinsonian disorders. Background The specific clinical diagnosis of parkinsonism is challenging, and definite confirmation requires neuropathological evaluation. Currently, autopsies are seldom performed, and most brain autopsies represent atypical or diagnostically unresolved cases. Methods We used a defined population-based incidence cohort with clinical parkinsonism (n=669) from the Rochester Epidemiology Project in Olmsted County, MN, 1991–2010. We reviewed reports of all patients who underwent neuropathologic examination at autopsy (n= 60; 9%) and applied consensus pathologic guidelines for neurodegenerative disease diagnosis. Results Among the 60 patients examined pathologically, the median time from the last recorded clinical diagnosis to death was 7 years (range from 2 to 17 years). Clinical-pathological concordance was found in 52 cases (86.7%), whereas 8 (13.3%) had a clinical-pathological discrepancy. Four patients with a clinical diagnosis of idiopathic Parkinson’s disease had no pathological evidence of Lewy bodies or α-synucleinopathy; of these, pathological diagnoses were Alzheimer’s disease (2 cases), progressive supranuclear palsy (1 case), and vascular parkinsonism (1 case). Two patients with clinical diagnoses of "dementia with Lewy bodies" and one patient with an "unspecified parkinsonism" had a pathological diagnosis of Alzheimer’s disease without concomitant α-synuclein lesions. One patient with clinically diagnosed "progressive supranuclear palsy" had indeterminate pathological findings without α-synuclein, Aβ- or tau-immunoreactive lesions at autopsy. Conclusions Overall, the clinical diagnoses of parkinsonian subtypes had good concordance with pathological confirmation (86.7%). However, clinical-pathological discrepancies were documented in 13.3%.

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When DLB, PD, and PSP masquerade as MSA

Cited by 293 publications

References 31 publications

Diagnosis of multiple system atrophy

Diagnosis of multiple system atrophy

Molecular‐based diagnosis of multiple sclerosis and its progressive stage

Clinicopathologic discrepancies in a population‐based incidence study of parkinsonism in olmsted county: 1991‐2010

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