Fluid biomarkers in multiple system atrophy: A review of the MSA Biomarker Initiative

Laurens, Brice; Constantinescu, Radu; Freeman, Roy; Gerhard, Alexander; Jellinger, K. A.; Jeromin, Andreas; Krismer, Florian; Mollenhauer, Brit; Schlossmacher, Michael G.; Shaw, Leslie M.; Verbeek, Marcel M.; Wenning, Gregor K.; Winge, Kristian; Zhang, Jing; Meissner, Wassilios G.

doi:10.1016/j.nbd.2015.05.004

Cited by 71 publications

(51 citation statements)

References 101 publications

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“…There is increasing interest in the development of potential biomarkers in plasma and cerebrospinal fluid (CSF) for the diagnosis of MSA (Laurens et al, 2015). The most promising so far include plasma norepinephrine levels (Kaufmann et al, 2017b), plasma catecholaminergic vesicular storage levels (Goldstein et al, 2015), plasma and CSF neurofilament light chain (NfL) protein (Hansson et al, 2017; Hu et al, 2017), and plasma and CSF αSyn levels (Sun et al, 2014).…”

Section: Emerging Diagnostic Methodsmentioning

confidence: 99%

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: Emerging Diagnostic Methodsmentioning

confidence: 99%

Diagnosis of multiple system atrophy

Palma

Norcliffe‐Kaufmann

Kaufmann

2018

Autonomic Neuroscience

126

114

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“…A number of studies have sought candidate biomarkers using blood and cerebrospinal fluid (CSF), but no reliable biomarkers are currently available for diagnosis of MSA (reviewed in ref 50). Total α-synuclein levels in CSF have been often examined, but with inconsistent results.…”

Section: Differential Diagnosismentioning

confidence: 99%

“…50–55 Although no single biomarker is sensitive and specific, combinations of each biomarker could be more useful 50. A combination of DJ-1 and total tau showed high sensitivity (82%) and specificity (81%) for differentiating MSA from PD 56.…”

Section: Differential Diagnosismentioning

confidence: 99%

Recent advances in neuropathology, biomarkers and therapeutic approach of multiple system atrophy

Koga

Dickson

2017

J Neurol Neurosurg Psychiatry

105

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Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterised by a variable combination of autonomic failure, levodopa-unresponsive parkinsonism, cerebellar ataxia and pyramidal symptoms. The pathological hallmark is the oligodendrocytic glial cytoplasmic inclusion (GCI) consisting of α-synuclein; therefore, MSA is included in the category of α-synucleinopathies. MSA has been divided into two clinicopathological subtypes: MSA with predominant parkinsonism and MSA with predominant cerebellar ataxia, which generally correlate with striatonigral degeneration and olivopontocerebellar atrophy, respectively. It is increasingly recognised, however, that clinical and pathological features of MSA are broader than previously considered.In this review, we aim to describe recent advances in neuropathology of MSA from a review of the literature and from information derived from review of nearly 200 definite MSA cases in the Mayo Clinic Brain Bank. In light of these new neuropathological findings, GCIs and neuronal cytoplasmic inclusions play an important role in clinicopathological correlates of MSA. We also focus on clinical diagnostic accuracy and differential diagnosis of MSA as well as candidate biomarkers. We also review some controversial topics in MSA. Cognitive impairment, which has been a non-supporting feature of MSA, is considered from both clinical and pathological perspectives. The cellular origin of α-synuclein in GCI and a 'prion hypothesis' are discussed. Finally, completed and ongoing clinical trials targeting disease modification, including immunotherapy, are summarised.

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“…However, in other patients, especially in early cases, it is hard to make a secure diagnosis of MSA due to a lack of reliable biomarkers and the fact that many conditions can be confused with MSA . In this regard, to improve the clinical diagnosis of MSA, various ancillary investigations are used in clinical practice or are under development …”

Section: Introductionmentioning

confidence: 99%

“…3 In this regard, to improve the clinical diagnosis of MSA, various ancillary investigations are used in clinical practice or are under development. 1,4,5 With advances in magnetic resonance imaging (MRI) techniques in recent years, there has been increasing interest in using MRI to improve the diagnostic accuracy of MSA. Several MRI abnormalities on conventional MRI already are included in the current diagnostic criteria for MSA along with abnormalities of functional neuroimaging, including 18 F-flurodeoxyglucose positron-emission tomography (FDG-PET) and presynaptic dopaminergic imaging.…”

Section: Introductionmentioning

confidence: 99%

Role of Magnetic Resonance Imaging in the Diagnosis of Multiple System Atrophy

Kim

Jeon

Fung

2016

Movement Disord Clin Pract

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Background: Multiple system atrophy (MSA) is a rapidly progressing neurodegenerative disorder without effective disease-modifying therapies. Because of a lack of reliable diagnostic biomarkers, there has been increasing interest in using magnetic resonance imaging (MRI) to improve the diagnostic accuracy of MSA.Methods: This review summarizes recent literatures on the role of MRI in the diagnosis of MSA. Results: Several MRI abnormalities on conventional MRI already are included in the current diagnostic criteria for MSA. Other features on conventional MRI are also used to make a diagnosis of MSA or to rule out alternative diagnoses. On the other hand, some of the MRI findings that were previously considered suggestive of a diagnosis of MSA are now being challenged, because it turned out that they were not as specific to MSA as previously thought. More advanced MRI modalities, including susceptibility-weighted imaging, diffusion-weighted imaging, diffusion tensor imaging, voxel-based morphometry, and cortical thickness analysis, are now used to study the changes in the brains of patients with MSA. Furthermore, studies have produced promising results demonstrating the use of MRI as a tool for monitoring and assessing disease progression in MSA. Conclusions: MRI is useful and indispensable in the diagnosis of MSA and also possibly for monitoring disease progression. In this regard, well-designed, long-term, prospective studies on large numbers of patients are needed.

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Fluid biomarkers in multiple system atrophy: A review of the MSA Biomarker Initiative

Cited by 71 publications

References 101 publications

Diagnosis of multiple system atrophy

Diagnosis of multiple system atrophy

Recent advances in neuropathology, biomarkers and therapeutic approach of multiple system atrophy

Role of Magnetic Resonance Imaging in the Diagnosis of Multiple System Atrophy

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