Early changes on electroencephalography in natalizumab-associated progressive multifocal leucoencephalopathy

2010 ◽  
Vol 16 (6) ◽  
pp. 749-753 ◽  
Author(s):  
Ingo Kleiter ◽  
Michael Schröder ◽  
Ralf Lürding ◽  
Gerhard Schuierer ◽  
David B Clifford ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Right Hemisphere ◽  
Jc Virus ◽  
Neuropsychological Testing ◽  
Neurological Deficits ◽  
Imaging Features ◽  
Progressive Multifocal Leucoencephalopathy ◽  
The Right ◽  
Multiple Sclerosis Patients ◽  
Virus Testing

Progressive multifocal leucoencephalopathy has become a growing concern in natalizumab-treated multiple sclerosis patients. Here, we describe a 35-year-old patient who was treated with 34 infusions of natalizumab before complaining about visual deterioration. MRI was non-diagnostic and JC virus testing initially was negative. Electroencephalography showed severe slowing of the right hemisphere, and neuropsychological testing revealed right frontal and temporal deficits. The diagnosis of progressive multifocal leucoencephalopathy was established 2 months later by typical MRI presentation and detection of JC virus DNA in the cerebrospinal fluid. Functional neurological deficits may precede imaging features and should prompt early consideration of progressive multifocal leucoencephalopathy.

scholarly journals Cortical morphology predicts placebo response in multiple sclerosis

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Mariya V. Cherkasova ◽  
Jessie F. Fu ◽  
Michael Jarrett ◽  
Poljanka Johnson ◽  
Shawna Abel ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Right Hemisphere ◽  
Placebo Response ◽  
Small World ◽  
Lesion Load ◽  
Transient Improvement ◽  
Related Quality ◽  
Brain Correlates ◽  
The Right ◽  
Multiple Sclerosis Patients

AbstractDespite significant insights into the neural mechanisms of acute placebo responses, less is known about longer-term placebo responses, such as those seen in clinical trials, or their interactions with brain disease. We examined brain correlates of placebo responses in a randomized trial of a then controversial and now disproved endovascular treatment for multiple sclerosis. Patients received either balloon or sham extracranial venoplasty and were followed for 48 weeks. Venoplasty had no therapeutic effect, but a subset of both venoplasty- and sham-treated patients reported a transient improvement in health-related quality of life, suggesting a placebo response. Placebo responders did not differ from non-responders in total MRI T2 lesion load, count or location, nor were there differences in normalized brain volume, regional grey or white matter volume or cortical thickness (CT). However, responders had higher lesion activity. Graph theoretical analysis of CT covariance showed that non-responders had a more small-world-like CT architecture. In non-responders, lesion load was inversely associated with CT in somatosensory, motor and association areas, precuneus, and insula, primarily in the right hemisphere. In responders, lesion load was unrelated to CT. The neuropathological process in MS may produce in some a cortical configuration less capable of generating sustained placebo responses.

scholarly journals Cortical morphology predicts placebo response in multiple sclerosis

2019 ◽  
Author(s):  
Mariya V. Cherkasova ◽  
Jessie F. Fu ◽  
Michael Jarrett ◽  
Poljanka Johnson ◽  
Shawna Abel ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cortical Thickness ◽  
Right Hemisphere ◽  
Functional Integration ◽  
Placebo Response ◽  
Small World ◽  
Lesion Load ◽  
Brain Correlates ◽  
The Right ◽  
Multiple Sclerosis Patients

ABSTRACTAlthough significant insights have been gained into the neural mechanisms of acute placebo responses, less is known about the mechanisms of longer-term placebo responses, such as those seen in clinical trials, or the interactions between these mechanisms and brain disease. We examined neuropathological and morphological brain correlates of placebo responses in a randomized clinical trial of a controversial endovascular treatment (“liberation therapy”) for multiple sclerosis. Patients were randomized to receive either balloon or sham extracranial venoplasty and followed for 48 weeks. The trial did not support therapeutic efficacy of venoplasty, but a subset of both venoplasty- and sham-treated patients reported an improvement in health-related quality of life that peaked at 12 weeks following treatment, suggesting a placebo response. Placebo responders had higher lesion activity than placebo non-responders. Although placebo responders did not differ from non-responders in terms of total normalized brain volume, regional grey or white matter volume or cortical thickness, graph theoretical analysis of cortical thickness covariance showed that placebo non-responders had a more homogenous cortical thickness topology with a more small-world-like architecture. In placebo non-responders, lesion load inversely predicted cortical thickness in primary somatosensory and motor areas, association areas, precuneus and insula, primarily in the right hemisphere. In placebo responders, lesion load was unrelated to cortical thickness. The neuropathological process in MS may result in a cortical configuration that is less suited to functional integration and less capable of generating a sustained placebo response.

scholarly journals JC Virus Seroprevalence and JCVAb Index in Polish Multiple Sclerosis Patients Treated with Immunomodulating or Immunosuppressive Therapies

2021 ◽  
Vol 10 (9) ◽  
pp. 1998
Author(s):  
Robert Bonek ◽  
Wojciech Guenter ◽  
Robert Jałowiński ◽  
Anna Karbicka ◽  
Anna Litwin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Jc Virus ◽  
Dimethyl Fumarate ◽  
Risk Category ◽  
Seroprevalence Rate ◽  
Immunomodulatory Drugs ◽  
Cross Sectional ◽  
Treatment Type ◽  
Multiple Sclerosis Patients ◽  
The Impact

The use of a highly-effective treatment for multiple sclerosis (MS) is associated with a severe risk of developing complications, such as progressive multifocal leukoencephalopathy (PML) caused by the John Cunningham virus (JCV). The aim of this study was to evaluate the correlation between anti-JCV Ab seroprevalence, anti-JCV AI, demographic and clinical factors as well as the type of therapy used in the Polish MS population. This is a multicentre, prospective and cross-sectional study involving 1405 MS patients. The seroprevalence of anti-JCV Ab and anti-JCV AI levels as well as AI categories were analysed with the use of a second-generation two-step ELISA test (STRATIFY JCV DxSelect). The overall prevalence of anti-JCV Ab was 65.8%. It was shown that seroprevalence increases with the patient’s age. The seroprevalence was significantly associated with the treatment type, and the highest values (76%) were obtained from immunosuppressant-treated patients. Overall, 63.3% of seropositive patients had an antibody index (AI) level of >1.5. In the seropositive patient group, the mean AI level amounted to 2.09. Similarly to the seroprevalence, AI levels correlated with the patient’s age; AI level for patients above 40 years old and from subsequent age quintiles plateaued, amounting to at least 1.55. Patients treated with immunosuppressants and immunomodulatory drugs obtained the highest (1.67) and lowest (1.35) AI levels, respectively. Of the immunosuppressants used, the highest mean AI levels were observed in mitoxantrone and cladribine groups, amounting to 1.75 and 1.69, respectively. In patients treated with immunomodulatory drugs, the lowest AI levels were observed in the dimethyl fumarate (DMF) group (1.11). The seroprevalence rate in the Polish MS population is one of the highest in Europe. The majority of seropositive patients had an anti-JCV Ab level qualifying them for a high-risk category. The highest mean AI levels are observed in patients receiving immunosuppressants, especially mitoxantrone and cladribine. Patients receiving immunomodulatory drugs have lower AI levels compared to treatment-naïve subjects, especially when treated with DMF. Further studies, especially longitudinal studies, are required to determine the impact of MS drugs on the seroprevalence of anti-JCV Ab and AI levels.

scholarly journals NRAMP1 Polymorphism and Viral Factors in Sardinian Multiple Sclerosis Patients

2008 ◽  
Vol 35 (4) ◽  
pp. 491-494 ◽  
Author(s):  
Maria Gazouli ◽  
Leonardo Sechi ◽  
Daniela Paccagnini ◽  
Stefano Sotgiu ◽  
Giannina Arru ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Autoimmune Disease ◽  
Promoter Region ◽  
Viral Infections ◽  
Jc Virus ◽  
Allelic Variation ◽  
Sardinian Population ◽  
Multiple Sclerosis Patients ◽  
Viral Sequences

Background:Multiple sclerosis (MS) is believed to be an autoimmune disease occurring in genetically predisposed individuals after an appropriate environmental exposure such as viral infections. Recent studies suggest a significant association between MS and the functional 5’-(GT)n polymorphism in the promoter region of the NRAMP1 gene. In the present study we aimed to evaluate the contribution of the allelic variation in the NRAMP1 promoter to MS susceptibility and to study the role of viral infection in relation to specific NRAMP1 genotypes, in a Sardinian cohort.Methods:Sixty MS patients and 66 healthy individuals were genotyped, and screened for the presence of Epstein-bar virus (EBV) and JC virus (JCV) sequences.Results:Consistent with previous autoimmune disease studies, allele 3 at the functional 5’(GT)n promoter region repeat polymorphism, was significantly overrepresented among MS patients when compared to controls (p=0.02). The EBV and JCV sequences were detected in 8/60 (13.33%) and in 4/60 (6.66%) of MS patients respectively and in 5/66 (7.57%) and in 0/66 of controls.Conclusion:The allelic variation in the NRAMP1 promoter may contribute to MS susceptibility in the Sardinian population. The viral sequences were not confined to a specific NRAMP1 genotype.

Agreement analysis comparing iPad LCVA and Sloan testing in multiple sclerosis patients

2017 ◽  
Vol 24 (8) ◽  
pp. 1126-1130 ◽  
Author(s):  
Neda Sattarnezhad ◽  
Samantha Farrow ◽  
Dorlan Kimbrough ◽  
Bonnie Glanz ◽  
Brian Healy ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Visual Acuity ◽  
T Test ◽  
Computerized Testing ◽  
Low Contrast ◽  
Significant Difference ◽  
Increased Sensitivity ◽  
The Right ◽  
Multiple Sclerosis Patients ◽  
Paired T Test

Background: Visual symptoms are common in multiple sclerosis (MS). Low-contrast visual acuity (LCVA) testing using Sloan charts has demonstrated increased sensitivity for visual deficits compared to high-contrast acuity testing. Computerized testing of visual acuity may facilitate use in the clinic setting. Objectives: To evaluate the agreement between an iPad-based and Sloan testing of LCVA in a cohort of MS patients. Methods: A total of 38 patients with relapsing-remitting MS were enrolled after providing informed written consent at Partners MS Center, Brigham and Women’s hospital. Monocular LCVA was measured using retroilluminated Sloan chart and iPad-based LogMAR chart. Number of correct letters and agreement between two measurements were assessed for each eye using Bland–Altman analysis and paired t-test. Results: For both eyes, there was no significant difference in number correct between the two measurements using a paired t-test, and there was high correlation between two measurements (oculus dextrus (OD) r = 0.89, p < 0.001; oculus sinister (OS) r = 0.78, p < 0.001). The limits of agreement were −7.9 to +8.5 letters for the right eye and −10.9 to +11.2 letters for the left eye. Conclusion: An iPad-based LCVA test shows good agreement with Sloan testing in MS patients.

Anti-JC virus antibody index changes in rituximab-treated multiple sclerosis patients

2018 ◽  
Vol 265 (10) ◽  
pp. 2342-2345 ◽  
Author(s):  
Ursela Baber ◽  
Andrew Bouley ◽  
Emily Egnor ◽  
Jacob A. Sloane
Keyword(s):  
Multiple Sclerosis ◽  
Jc Virus ◽  
Antibody Index ◽  
Virus Antibody ◽  
Index Changes ◽  
Multiple Sclerosis Patients

JC virus urinary excretion and seroprevalence in natalizumab-treated multiple sclerosis patients

2014 ◽  
Vol 21 (6) ◽  
pp. 645-652 ◽  
Author(s):  
Serena Delbue ◽  
Francesca Elia ◽  
Camilla Carloni ◽  
Valentina Pecchenini ◽  
Diego Franciotta ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Urinary Excretion ◽  
Jc Virus ◽  
Multiple Sclerosis Patients

Meeting Review: The management of multiple sclerosis in children: a European view

2010 ◽  
Vol 16 (10) ◽  
pp. 1258-1267 ◽  
Author(s):  
Angelo Ghezzi ◽  
Brenda Banwell ◽  
Alexey Boyko ◽  
Maria Pia Amato ◽  
Banu Anlar ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Relapse Rate ◽  
Significant Proportion ◽  
Open Label ◽  
Common View ◽  
High Relapse Rate ◽  
Paediatric Multiple Sclerosis ◽  
Hard Evidence ◽  
The Right ◽  
Multiple Sclerosis Patients

About 3—5% of all patients with multiple sclerosis experience the onset of their disease under the age of 16. A significant proportion of paediatric multiple sclerosis patients develop significant cognitive disturbances and persistent physical disability. The high relapse rate and the morbidity in the paediatric multiple sclerosis population has triggered the use of disease-modifying therapies that have been shown to reduce relapse rate, disease progression and cognitive decline in adult patients with multiple sclerosis. Hard evidence for the right treatment and its appropriate timing is scarce in paediatric multiple sclerosis. Nevertheless, expertise in this field has grown thanks to recent open-label trials and experience generated in specialized centres. In spring 2009, a first meeting was held in Rotterdam with clinicians from 11 European countries (one from Canada) that are all active in the management of paediatric multiple sclerosis. One of the aims was to generate a common view on the management of paediatric multiple sclerosis patients. The result of this meeting is presented here to help standardize treatment and to support clinicians with less experience in this field.

Outcome of no resection after long-term subdural electroencephalography evaluation in children with epilepsy

2011 ◽  
Vol 8 (3) ◽  
pp. 269-278 ◽  
Author(s):  
Elia M. Pestana Knight ◽  
Tobias Loddenkemper ◽  
Deepak Lachhwani ◽  
Prakash Kotagal ◽  
Elaine Wyllie ◽  
...  
Keyword(s):  
Right Hemisphere ◽  
Demographic Data ◽  
Neurological Deficits ◽  
Epileptogenic Zone ◽  
Dominant Hand ◽  
Resection Group ◽  
Group 2 ◽  
The Right ◽  
Permanent Neurological Deficit

Object The aim of this study was to identify the reasons for and predictors of no resection of the epileptogenic zone in children with epilepsy who had undergone long-term invasive subdural grid electroencephalography (SDG-EEG) evaluation. Methods The authors retrospectively reviewed the consecutive medical records of children (< 19 years of age) who had undergone SDG-EEG evaluation over a 7-year period (1997–2004). To determine the predictors of no resection, the authors obtained the clinical characteristics and imaging and EEG findings of children who had no resection after long-term invasive SDG-EEG evaluation and compared these data with those in a group of children who did undergo resection. They describe the indications for SDG-EEG evaluation and the reasons for no resection in these patients. Results Of 66 children who underwent SDG-EEG evaluation, 9 (13.6%) did not undergo subsequent resection (no-resection group; 6 males). Of these 9 patients, 6 (66.7%) had normal neurological examinations and 5 (55.6%) had normal findings on brain MR imaging. Scalp video EEG localized epilepsy to the left hemisphere in 6 of the 9 patients and to the right hemisphere in 2; it was nonlocalizable in 1 of the 9 patients. Indications for SDG-EEG in the no-resection group were ictal onset zone (IOZ) localization (9 of 9 patients), motor cortex localization (5 of 9 patients), and language area localization (4 of 9 patients). Reasons for no resection after SDG-EEG evaluation were the lack of a well-defined IOZ in 5 of 9 patients (4 multifocal IOZs and 1 nonlocalizable IOZ) and anticipated new permanent postoperative neurological deficits in 7 of 9 patients (3 motor, 2 language, and 2 motor and language deficits). Comparison with the resection group (57 patients) demonstrated that postictal Todd paralysis in the dominant hand was the only variable seen more commonly (χ2 = 4.781, p = 0.029) in the no-resection group (2 [22.2%] of 9 vs 2 [3.5%] of 57 patients). The no-resection group had a larger number of SDG electrode contacts (mean 126. 5 ± 26.98) as compared with the resection group (100.56 ± 25.52; p = 0.010). There were no significant differences in the demographic data, seizure characteristics, scalp and invasive EEG findings, and imaging variables between the resection and no-resection groups. Conclusions Children who did not undergo resection of the epileptogenic zone after SDG-EEG evaluation were likely to have normal neurological examinations without preexisting neurological deficits, a high probability of a new unacceptable permanent neurological deficit following resection, or multifocal or nonlocalizable IOZs. In comparison with the group that underwent resection after SDG-EEG, a history of Todd paralysis in the dominant hand and arm was the only predictor of no resection following SDG-EEG evaluation. Data in this study will help to better select pediatric patients for SDG-EEG and to counsel families prior to epilepsy surgery.

Structural ‘connectomic’ alterations in the limbic system of multiple sclerosis patients with major depression

2014 ◽  
Vol 21 (8) ◽  
pp. 1003-1012 ◽  
Author(s):  
Salvatore Nigro ◽  
Luca Passamonti ◽  
Roberta Riccelli ◽  
Nicola Toschi ◽  
Federico Rocca ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Major Depression ◽  
Diffusion Tensor ◽  
Negative Impact ◽  
Brain Connectivity ◽  
Strong Support ◽  
Imaging Data ◽  
Connectivity Patterns ◽  
The Right ◽  
Multiple Sclerosis Patients

Background: Major depression (MD) is a common psychiatric disorder in multiple sclerosis (MS). Despite the negative impact of MD on the quality of life of MS patients, little is known about its underlying brain mechanisms. Objective: We studied the whole-brain connectivity patterns that were associated with MD in MS. Alterations were mainly expected within limbic circuits. Methods: Diffusion tensor imaging data were collected in 20 MS patients with MD, 22 non-depressed MS patients and 16 healthy controls. We used deterministic tractography and graph analysis to study the white-matter connectivity patterns that characterized MS patients with MD. Results: We found that MD in MS was associated with increased local path length in the right hippocampus and right amygdala. Further analyses revealed that these effects were driven by an increased shortest distance between both the right hippocampus and right amygdala and a series of regions including the dorsolateral and ventrolateral prefrontal cortex, orbitofrontal cortex, sensory-motor cortices and supplementary motor area. Conclusion: Our data provide strong support for neurobiological accounts positing that MD in MS is mediated by abnormal ‘communications’ within limbic circuits. We also found evidence that MD in MS may be linked with connectivity alterations at the limbic-motor interface, a group of regions that translates emotions into survival-oriented behaviors.

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