scholarly journals Cerebrospinal fluid analysis in 108 patients with progressive multifocal leukoencephalopathy

2020 ◽  
Author(s):  
Nora Möhn ◽  
Luo Yi ◽  
Thomas Skripuletz ◽  
Philipp Schwenkenbecher ◽  
Anne Ladwig ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Cell Count ◽  
Normal Pressure ◽  
Control Group ◽  
Fluid Analysis ◽  
Immunodeficiency Virus ◽  
The Central Nervous System ◽  
Insight Into

Abstract Background: Progressive multifocal leukoencephalopathy (PML) is caused by an opportunistic infection with JC polyoma virus (JCPyV) and mainly affects immunocompromised patients. It leads to pronounced demyelination of the central nervous system (CNS) resulting in severe disability or even death. Detection of JCPyV DNA in the cerebrospinal fluid (CSF) is usually accepted as proof for the diagnosis of PML. Routine CSF parameters, like CSF cell count, protein concentration, Qalbumin, or intrathecal immunoglobulin synthesis are mostly considered normal. However, this has not been investigated systematically. Methods: We analyzed routine CSF parameters in a cohort of 108 PML patients that were treated at four different neurological centers in Germany. The patients exhibited different underlying conditions with natalizumab-treated multiple sclerosis (n=54) and human immunodeficiency virus (HIV)-infection (n=25) being the most frequent. The data were collected at the respective centers in accordance with local requirements and then jointly analyzed. The total PML cohort was compared with a control group of patients with normal pressure hydrocephalus (NPH) and idiopathic intracranial hypertension (IIH). Multiple sclerosis and HIV patients were additionally compared with their own non-PML control groups. Results: The PML group showed an elevated cell count (p<0.001) compared to the control group, however, this effect was mainly driven by HIV-PML patients. This subgroup also demonstrated a significantly higher proportion of patients with a disturbed blood-CSF-barrier function. Conclusions: This comprehensive, retrospective study on CSF diagnostic analysis in PML patients provides insight into the CSF of those patients. It demonstrates that CSF composition in PML patients may be specific for the underlying condition that predisposes for the development of PML and thus data have to be interpreted in this context.

scholarly journals Cerebrospinal fluid analysis in 108 patients with progressive multifocal leukoencephalopathy

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Nora Möhn ◽  
Yi Luo ◽  
Thomas Skripuletz ◽  
Philipp Schwenkenbecher ◽  
Anne Ladwig ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Cell Count ◽  
Normal Pressure ◽  
Control Group ◽  
Fluid Analysis ◽  
Immunodeficiency Virus ◽  
The Central Nervous System ◽  
Insight Into

Abstract Background Progressive multifocal leukoencephalopathy (PML) is caused by an opportunistic infection with JC polyoma virus (JCPyV) and mainly affects immunocompromised patients. It leads to pronounced demyelination of the central nervous system (CNS) resulting in severe disability or even death. Detection of JCPyV DNA in the cerebrospinal fluid (CSF) is usually accepted as proof for the diagnosis of PML. Routine CSF parameters, like CSF cell count, protein concentration, Qalbumin, or intrathecal immunoglobulin synthesis are mostly considered normal. However, this has not been investigated systematically. Methods We analyzed routine CSF parameters in a cohort of 108 PML patients that were treated at four different neurological centers in Germany. The patients exhibited different underlying conditions with natalizumab-treated multiple sclerosis (n = 54) and human immunodeficiency virus (HIV)-infection (n = 25) being the most frequent. The data were collected at the respective centers in accordance with local requirements and then jointly analyzed. The total PML cohort was compared with a control group of patients with normal pressure hydrocephalus (NPH) and idiopathic intracranial hypertension (IIH). Multiple sclerosis and HIV patients were additionally compared with their own non-PML control groups. Results The PML group showed an elevated cell count (p < 0.001) compared to the control group, however, this effect was mainly driven by HIV-PML patients. This subgroup also demonstrated a significantly higher proportion of patients with a disturbed blood-CSF-barrier function. Conclusions This comprehensive, retrospective study on CSF diagnostic analysis in PML patients provides insight into the CSF of those patients. It demonstrates that CSF composition in PML patients may be specific for the underlying condition that predisposes for the development of PML and thus data have to be interpreted in this context.

scholarly journals Results of cerebrospinal fluid analysis in 108 patients with progressive multifocal leukoencephalopathy

2020 ◽  
Author(s):  
Nora Möhn ◽  
Luo Yi ◽  
Thomas Skripuletz ◽  
Philipp Schwenkenbecher ◽  
Anne Ladwig ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Cell Count ◽  
Normal Pressure ◽  
Control Group ◽  
Fluid Analysis ◽  
Immunodeficiency Virus ◽  
Natalizumab Treatment ◽  
The Central Nervous System

Abstract Background: Progressive multifocal leukoencephalopathy (PML) is caused by an opportunistic infection with JC polyoma virus (JCPyV) and mainly affects immunocompromised patients. It leads to pronounced demyelination of the central nervous system (CNS) resulting in severe disability or even death. Detection of JCPyV DNA in the cerebrospinal fluid (CSF) is usually accepted as proof for the diagnosis of PML. Values from routine CSF parameters, like CSF cell count, protein concentration, Qalbumin, or intrathecal immunoglobulin synthesis are mostly considered as normal. However, this has not been investigated systematically. Methods: We therefore analyzed those standard CSF parameters in a cohort of 108 PML patients that were treated at four different neurological centers in Germany. The patients exhibited different underlying conditions with natalizumab treatment in multiple sclerosis (n=54) and human immunodeficiency virus (HIV)-infection (n=25) being the most frequent. The data were collected at the respective centers in accordance with local requirements and then jointly analyzed. The results of the total PML cohort were compared with a control group of patients with normal pressure hydrocephalus (NPH) and idiopathic intracranial hypertension (IIH). Multiple sclerosis and HIV patients were additionally compared with their own non-PML control groups. Results: The PML group showed an elevated cell count (p<0.001) compared to the control group, however, this effect was mainly driven by HIV-PML patients. This subgroup also demonstrated a significantly higher proportion of patients with a disturbed blood-CSF-barrier function. Conclusions: This comprehensive, retrospective study on CSF diagnostic results in PML patients provides insight into the CSF findings in patients with PML. It demonstrates that CSF changes in PML patients may be specific for the underlying condition that predisposes for the development of PML and thus data have to be interpreted in this context.

scholarly journals Results of Cerebrospinal Fluid Analysis in 108 Patients With Progressive Multifocal Leukoencephalopathy

2020 ◽  
Author(s):  
Nora Möhn ◽  
Luo Yi ◽  
Thomas Skripuletz ◽  
Philipp Schwenkenbecher ◽  
Anne Ladwig ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Cell Count ◽  
Normal Pressure ◽  
Control Group ◽  
Immunoglobulin Synthesis ◽  
Fluid Analysis ◽  
Natalizumab Treatment ◽  
Csf Lactate ◽  
The Central Nervous System

Abstract Background: Progressive multifocal leukoencephalopathy (PML) is caused by an opportunistic infection with JC polyoma virus (JCPyV) and mainly affects immunocompromised patients. It leads to pronounced demyelination of the central nervous system (CNS) resulting in severe disability or even death. Detection of JCPyV DNA in the cerebrospinal fluid (CSF) is usually accepted as proof for the diagnosis of PML. Values from routine CSF parameters, like CSF cell count, protein concentration, Qalbumin levels, or intrathecal immunoglobulin synthesis are mostly considered as normal; however, this has not been investigated systematically. Methods: We therefore analyzed those standard CSF parameters in a cohort of 108 PML patients that were treated at four different neurological centers in Germany. The patients exhibited different underlying conditions with natalizumab treatment in multiple sclerosis (n=54) and human immunodeficiency virus (HIV)-infection (n=25) being the most frequent. The data were collected at the respective centers in accordance with local requirements and then jointly analyzed. The results of the total PML cohort were compared with a control group of patients with normal pressure hydrocephalus (NPH) and idiopathic intracranial hypertension (IIH) or an HIV group without PML, respectively. Results: The PML group showed an elevated cell count (p<0.001) compared to the control group, however, this effect was mainly driven by HIV-PML patients. This subgroup also demonstrated a significantly higher proportion of patients with a disturbed blood-CSF-barrier function. Immune reconstitution syndrome (IRIS) occurred in 41/108 patients and was characterized by a trend for an increase in CSF cell count (p=0.052), CSF lactate (p=0.052), and an augmented intrathecal immunoglobulin synthesis. Conclusions: This comprehensive, retrospective study on diagnostic results in PML patients provides insight into the CSF findings in patients with PML. It demonstrates that CSF changes in PML patients may be specific for the underlying condition that predisposes for the development of PML and thus data have to be interpreted in this context.

scholarly journals Targeted metabolomic profiling of cerebrospinal fluid from patients with progressive multifocal leukoencephalopathy

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242321
Author(s):  
Yi Luo ◽  
Nora Möhn ◽  
Amani Al-Mekhlafi ◽  
Sven Schuchardt ◽  
Thomas Skripuletz ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Demyelinating Disease ◽  
Statistical Significance ◽  
Virus Detection ◽  
Normal Pressure ◽  
Csf Biomarkers ◽  
Diagnostic Biomarkers ◽  
Metabolomic Profiling ◽  
The Central Nervous System

Progressive multifocal leukoencephalopathy (PML), caused by JC polyomavirus, is a demyelinating disease of the central nervous system that primarily affects oligodendrocytes. It can cause significant morbidity and mortality. An early diagnosis is of high relevance as timely immune reconstitution is essential. However, diagnosis can be challenging if virus detection via cerebrospinal fluid (CSF) PCR remains negative. Hence, identifying CSF biomarkers for this disease is of crucial importance. We applied a targeted metabolomic screen to CSF from 23 PML patients and eight normal pressure hydrocephalus (NPH) patients as controls. Out of 188 potentially detectable metabolites, 48 (13 amino acids, 4 biogenic amines, 1 acylcarnitine, 21 phosphatidylcholines, 8 sphingolipids, and the sum of hexoses) passed the quality screen and were included in the analyses. Even though there was a tendency towards lower concentrations in PML (mostly of phosphatidylcholines and sphingomyelins), none of the differences between PML and controls in individual metabolite concentrations reached statistical significance (lowest p = 0.104) and there were no potential diagnostic biomarkers (highest area under the ROC curve 0.68). Thus, CSF metabolite changes in PML are likely subtle and possibly larger group sizes and broader metabolite screens are needed to identify potential CSF metabolite biomarkers for PML.

scholarly journals Study of oligoclonal bands restricted to the cerebrospinal fluid in multiple sclerosis patients in the city of São Paulo

2009 ◽  
Vol 67 (4) ◽  
pp. 1017-1022 ◽  
Author(s):  
Paulo Diniz da Gama ◽  
Luís dos Ramos Machado ◽  
José Antonio Livramento ◽  
Hélio Rodrigues Gomes ◽  
Tarso Adoni ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Sao Paulo ◽  
Oligoclonal Bands ◽  
Control Group ◽  
São Paulo ◽  
The Central Nervous System ◽  
Different Populations ◽  
Multiple Sclerosis Patients ◽  
The City

The frequency of oligoclonal bands (OCB) restricted to the cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS) varies widely in different populations. The objective of this study was to determine the frequency of these OCB in a group of MS patients in the city of São Paulo. Techniques used to detect OCB consisted of isoelectric focusing followed by immunoblotting. Oligoclonal bands were found in 49 (54.4%) out of 90 patients with clinically definite MS; in (31.2%) of the 16 patients with clinically isolated syndrome; in 7 (17.9%) of 39 patients with inflammatory disorders of the central nervous system (IDCNS), and in none of the individuals with no neurological condition (control group). The specificity of the method was 100% when compared to the control group and 82.1% when compared to the IDCNS group. These results suggest that the frequency of CSF OCB is much lower in Brazilian MS patients from São Paulo city than that reported in MS series from Caucasian populations.

scholarly journals Atypical Multiple Sclerosis Lesions or Progressive Multifocal Leukoencephalopathy Lesions: That Is the Question

2020 ◽  
Vol 8 ◽  
pp. 232470962093980 ◽  
Author(s):  
Stefania Federica De Mercanti ◽  
Dario Gned ◽  
Manuela Matta ◽  
Marco Iudicello ◽  
Emanuele Franchin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Case Reports ◽  
Brain Mri ◽  
Brain Magnetic Resonance Imaging ◽  
Dimethyl Fumarate ◽  
Diagnostic Process ◽  
Suspected Case ◽  
Fluid Analysis

Progressive multifocal leukoencephalopathy (PML) is a serious infective disease of the central nervous system that may occur in case of severe immunosuppression or after some treatment for multiple sclerosis (MS) with natalizumab, dimethyl fumarate, and fingolimod. In these case reports, we highlight the importance of differential diagnosis between PML and MS lesions in order to provide rapidly the best treatment option, by discussing the finding of brain (magnetic resonance imaging) MRI suggestive for PML in 2 MS patients, one treated with dimethyl fumarate and the other during natalizumab withdrawal. In both cases, although brain MRI was highly suggestive for PML, the detection of John Cunningham virus-DNA copies in cerebrospinal fluid resulted in negative result. These case reports illustrate the diagnostic process in case of suspected PML, as both patients were diagnosed with suspected PML during a routine brain MRI control, and highlights the importance of providing a strict brain MRI follow-up during dimethyl fumarate treatment, although only a few cases of PML during this therapy have been detected, and during natalizumab suspension phase. In clinical practice, in case of a radiologically suspected case of PML, although not confirmed by the cerebrospinal fluid analysis, the best approach could be to perform a close radiological and clinical monitoring before starting a new MS therapy.

scholarly journals Integrated Lipidomics and Metabolomics Analysis of Tears in Multiple Sclerosis: An Insight into Diagnostic Potential of Lacrimal Fluid

2019 ◽  
Vol 20 (6) ◽  
pp. 1265 ◽  
Author(s):  
Ilaria Cicalini ◽  
Claudia Rossi ◽  
Damiana Pieragostino ◽  
Luca Agnifili ◽  
Leonardo Mastropasqua ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mass Spectrometry ◽  
Cerebrospinal Fluid ◽  
Biological Fluids ◽  
Extraction Procedure ◽  
Multifactorial Diseases ◽  
Targeted Analysis ◽  
Diagnostic Potential ◽  
The Central Nervous System ◽  
Insight Into

Metabolomics based on mass spectrometry represents an innovative approach to characterize multifactorial diseases, such as multiple sclerosis (MuS). To date, the most important biomarker source for MuS diagnosis is the cerebrospinal fluid. However, an important goal for research is to identify new molecules in more easily accessible biological fluids. A very interesting biofluid in MuS is represented by tears, considered as an intermediate fluid between the cerebrospinal fluid and serum. In this work, we developed a merged strategy for the analysis of lipids containing choline by Liquid Chromatography coupled to Tandem Mass Spectrometry (LC-MS/MS), as well as for the targeted analysis of free carnitine, acylcarnitines and aminoacids by direct infusion mass spectrometry. Samples for both metabolomics and lipidomics approaches were obtained in a single extraction procedure from tears of patients affected by MuS and healthy controls. Tear lipidomics showed 30 phospholipids significantly modulated and, notably, many sphingomyelins resulted lower in MuS. Moreover, the metabolomics approach carried out both on tears and serum highlighted the diagnostic potential of specific aminoacids and acylcarnitines. In conclusion, the metabolic profiling of tears appears to reflect the pathological conditions of the central nervous system, suggesting that the molecular repository of tears can be considered as a source of potential biomarkers for MuS.

scholarly journals Cerebrospinal fluid analysis in the context of CNS demyelinating diseases

2013 ◽  
Vol 71 (9B) ◽  
pp. 685-688 ◽  
Author(s):  
Sandro Luiz de Andrade Matas ◽  
Felipe von Glehn ◽  
Gustavo Bruniera Peres Fernandes ◽  
Carlos Augusto Senne Soares
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Acute Disseminated Encephalomyelitis ◽  
Demyelinating Diseases ◽  
Cerebrospinal Fluid Analysis ◽  
Inflammatory Lesions ◽  
Fluid Analysis ◽  
The Central Nervous System

The central nervous system demyelinating diseases are a group of disorders with different etiologies, characterized by inflammatory lesions that are associated with loss of myelin and eventually axonal damage. In this group the most studied ones are multiple sclerosis (MS), neuromyelitis optic (NMO) and acute disseminated encephalomyelitis (ADEM). The cerebrospinal fluid is essential to differentiate between these different syndromes and to define multiple sclerosis, helping to assess the probability of Clinical Isolated Syndrome turn into multiple sclerosis.

scholarly journals HIV infection and multiple sclerosis: a case with unexpected “no evidence of disease activity” status

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199957
Author(s):  
Fernando Labella ◽  
Fernando Acebrón ◽  
María del Carmen Blanco-Valero ◽  
Alba Rodrígez-Martín ◽  
Ángela Monterde Ortega ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Hiv Infection ◽  
Disease Activity ◽  
Demyelinating Disease ◽  
Clinical Course ◽  
Disease Modifying Drugs ◽  
Immunodeficiency Virus ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Disease Modifying

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system whose etiology remains unclear. It has been suggested that MS can be triggered by certain viruses; however, human immunodeficiency virus (HIV) infection is associated with reduced incidence of MS. We present the case of a young patient diagnosed with active relapsing-remitting MS whose clinical course substantially improved following HIV infection and treatment. The patient achieved no evidence of disease activity status without any disease-modifying drugs. Both HIV-induced immunosuppression and antiretroviral therapy may have attenuated the clinical course in this patient.

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