scholarly journals Fingolimod-associated PML with mild IRIS in MS

2017 ◽  
Vol 5 (1) ◽  
pp. e415 ◽  
Author(s):  
Shuhei Nishiyama ◽  
Tatsuro Misu ◽  
Yukiko Shishido-Hara ◽  
Kazuo Nakamichi ◽  
Masayuki Saijo ◽  
...  
Keyword(s):  
White Matter ◽  
Immune Reconstitution ◽  
Jc Virus ◽  
Brain Mri ◽  
Subcortical White Matter ◽  
Precentral Gyrus ◽  
Fluid Attenuated Inversion Recovery ◽  
Viral Inclusions ◽  
Inflammatory Syndrome

Objective:To clarify the clinical, neuropathologic, and virologic characteristics of progressive multifocal leukoencephalopathy (PML) and its immune reconstitution inflammatory syndrome (IRIS) in a patient with fingolimod-treated MS.Methods:A case study.Results:A 34-year-old patient with MS using fingolimod for 4 years had a gradual progression of right hemiparesis and aphasia with a new subcortical white matter lesion in the precentral gyrus by initial MRI. Blood tests were normal, except for lymphopenia (160 cells/μL). One month after the cessation of fingolimod, brain MRI depicted a diffusely exacerbated hyperintensity on fluid-attenuated inversion recovery and diffusion-weighed imaging in the white matter with punctate gadolinium enhancement, suggesting PML-IRIS. A very low level of JC virus (JCV)-DNA (15 copies/mL) was detected in the CSF as judged by quantitative PCR. Brain tissues were biopsied from the left frontal lesion, which showed some small demyelinated foci with predominant loss of myelin-associated glycoprotein with infiltrations of lymphocytes and macrophages, but clear viral inclusion was not observed with hematoxylin-eosin staining. JCV-DNA was uniquely detectable in an active inflammatory demyelinating lesion by in situ hybridization, possibly suggesting an early phase of PML. DNA extracted from the brain sample was positive for JCV-DNA (151 copies/cell). It took 3 months to normalize the blood lymphocyte count. The patient was treated with 1 g of IV methylprednisolone for 3 days and a weekly oral dose (375 mg) of mefloquine, and her symptoms gradually improved.Conclusion:Low CSF JCV-DNA and unfound viral inclusions initially made her diagnosis difficult. The clinical course of fingolimod-associated PML may be associated with mild immune reconstitution.

Increased MRI-based cortical grey/white-matter contrast in sensory and motor regions in schizophrenia and bipolar disorder

2016 ◽  
Vol 46 (9) ◽  
pp. 1971-1985 ◽  
Author(s):  
K. N. Jørgensen ◽  
S. Nerland ◽  
L. B. Norbom ◽  
N. T. Doan ◽  
R. Nesvåg ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
White Matter ◽  
Linear Models ◽  
Subcortical White Matter ◽  
Precentral Gyrus ◽  
Average Group ◽  
Medication Dose ◽  
Weighted Magnetic Resonance Imaging ◽  
The Difference ◽  
Magnetic Resonance Imaging Mri

BackgroundSchizophrenia and bipolar disorder share genetic risk factors and one possible illness mechanism is abnormal myelination. T1-weighted magnetic resonance imaging (MRI) tissue intensities are sensitive to myelin content. Therefore, the contrast between grey- and white-matter intensities may reflect myelination along the cortical surface.MethodMRI images were obtained from patients with schizophrenia (n = 214), bipolar disorder (n = 185), and healthy controls (n = 278) and processed in FreeSurfer. The grey/white-matter contrast was computed at each vertex as the difference between average grey-matter intensity (sampled 0–60% into the cortical ribbon) and average white-matter intensity (sampled 0–1.5 mm into subcortical white matter), normalized by their average. Group differences were tested using linear models covarying for age and sex.ResultsPatients with schizophrenia had increased contrast compared to controls bilaterally in the post- and precentral gyri, the transverse temporal gyri and posterior insulae, and in parieto-occipital regions. In bipolar disorder, increased contrast was primarily localized in the left precentral gyrus. There were no significant differences between schizophrenia and bipolar disorder. Findings of increased contrast remained after adjusting for cortical area, thickness, and gyrification. We found no association with antipsychotic medication dose.ConclusionsIncreased contrast was found in highly myelinated low-level sensory and motor regions in schizophrenia, and to a lesser extent in bipolar disorder. We propose that these findings indicate reduced intracortical myelin. In accordance with the corollary discharge hypothesis, this could cause disinhibition of sensory input, resulting in distorted perceptual processing leading to the characteristic positive symptoms of schizophrenia.

scholarly journals Progressive multifocal leukoencephalopathy and immune reconstitution inflammatory syndrome in seven patients with sarcoidosis: a critical discussion of treatment and prognosis

2021 ◽  
Vol 14 ◽  
pp. 175628642110355
Author(s):  
Maike F. Dohrn ◽  
Gisa Ellrichmann ◽  
Rastislav Pjontek ◽  
Carsten Lukas ◽  
Jens Panse ◽  
...  
Keyword(s):  
Progressive Multifocal Leukoencephalopathy ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Opportunistic Infections ◽  
Jc Virus ◽  
Immunosuppressive Treatment ◽  
Interleukin 2 ◽  
Cerebral Magnetic Resonance Imaging ◽  
Virus Load ◽  
Inflammatory Syndrome

Progressive multifocal leukoencephalopathy (PML) is a subacute brain infection by the opportunistic John Cunningham (JC) virus. Herein, we describe seven patients with PML, lymphopenia, and sarcoidosis, in three of whom PML was the first manifestation of sarcoidosis. At onset, the clinical picture comprised rapidly progressive spastic hemi- or limb pareses as well as disturbances of vision, speech, and orientation. Cerebral magnetic resonance imaging showed T2-hyperintense, confluent, mainly supratentorial lesions. Four patients developed punctate contrast enhancement as a radiological sign of an immune reconstitution inflammatory syndrome (IRIS), three of them having a fatal course. In the cerebrospinal fluid, the initial JC virus load (8–25,787 copies/ml) did not correlate with interindividual severity; however, virus load corresponded to clinical dynamics. Brain biopsies ( n = 2), performed 2 months after symptom onset, showed spotted demyelination and microglial activation. All patients had lymphopenia in the range of 270–1150/µl. To control JC virus, three patients received a combination of mirtazapine and mefloquine, another two patients additionally took cidofovir. One patient was treated with cidofovir only, and one patient had a combined regimen with mirtazapine, mefloquine, cidofovir, intravenous interleukin 2, and JC capsid vaccination. To treat sarcoidosis, the four previously untreated patients received prednisolone. Three patients had taken immunosuppressants prior to PML onset, which were subsequently stopped as a potential accelerator of opportunistic infections. After 6–54 months of follow up, three patients reached an incomplete recovery, one patient progressed, but survived so far, and two patients died. One further patient was additionally diagnosed with lung cancer, which he died from after 24 months. We conclude that the combination of PML and sarcoidosis is a diagnostic and therapeutic challenge. PML can occur as the first sign of sarcoidosis without preceding immunosuppressive treatment. The development of IRIS might be an indicator of poor outcome.

scholarly journals Can post-mortem MRI be used as a proxy for in vivo? A case study

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Baayla D C Boon ◽  
Petra J W Pouwels ◽  
Laura E Jonkman ◽  
Matthijs J Keijzer ◽  
Paolo Preziosa ◽  
...  
Keyword(s):  
White Matter ◽  
Rating Scales ◽  
Brain Volume ◽  
Brain Mri ◽  
Post Mortem ◽  
Early Onset Alzheimer’S Disease ◽  
And Diffusion

Abstract Post-mortem in situ MRI has been used as an intermediate between brain histo(patho)logy and in vivo imaging. However, it is not known how comparable post-mortem in situ is to ante-mortem imaging. We report the unique situation of a patient with familial early-onset Alzheimer’s disease due to a PSEN1 mutation, who underwent ante-mortem brain MRI and post-mortem in situ imaging only 4 days apart. T1-weighted and diffusion MRI was performed at 3-Tesla at both time points. Visual atrophy rating scales, brain volume, cortical thickness and diffusion measures were derived from both scans and compared. Post-mortem visual atrophy scores decreased 0.5–1 point compared with ante-mortem, indicating an increase in brain volume. This was confirmed by quantitative analysis; showing a 27% decrease of ventricular and 7% increase of whole-brain volume. This increase was more pronounced in the cerebellum and supratentorial white matter than in grey matter. Furthermore, axial and radial diffusivity decreased up to 60% post-mortem whereas average fractional anisotropy of white matter increased approximately 10%. This unique case study shows that the process of dying affects several imaging markers. These changes need to be taken into account when interpreting post-mortem MRI to make inferences on the in vivo situation.

Progressive Multifocal Leukoencephalopathy Syndrome and Immune Reconstitution Inflammatory Syndrome

2013 ◽  
Author(s):  
Aaron E. Miller ◽  
Teresa M. DeAngelis
Keyword(s):  
Monoclonal Antibody ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Jc Virus ◽  
Radiographic Findings ◽  
Life Threatening ◽  
The Central Nervous System ◽  
Immunosuppressant Medications ◽  
Inflammatory Syndrome

Progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the central nervous system caused by the JC virus, typically manifests in severely immunocompromised conditions, ranging from HIV/AIDS to lymphoproliferative malignancies to the consequence of immunosuppressant medications such as natalizumab, a monoclonal antibody approved for the treatment of relapsing forms of MS. In this chapter, we discuss the typical symptomatology and radiographic findings of PML and how to distinguish it from those of MS. In addition, we review the management of PML in natalizumab-treated MS patients as well as the features of immune reconstitution inflammatory syndrome (IRIS), the potentially life-threatening consequence of natalizumab withdrawal in patients with PML.

Slowly progressive fatal PML-IRIS following antiretroviral initiation at CD4+ nadir of 350 cells/mm3 despite CD4+ cell count rise to 900 cells/mm3

2019 ◽  
Vol 30 (8) ◽  
pp. 810-813
Author(s):  
Mani Ratnesh Sandhu ◽  
Ronnye Rutledge ◽  
Matthew Grant ◽  
Amit Mahajan ◽  
Serena Spudich
Keyword(s):  
Cell Count ◽  
Immune Reconstitution ◽  
Opportunistic Infections ◽  
Jc Virus ◽  
Virus Antigen ◽  
Cd4 Cell Count ◽  
Cd4 Cell ◽  
Inflammatory Syndrome ◽  
Continuous Progression

AIDS-related progressive multifocal leukoencephalopathy (PML)-immune reconstitution inflammatory syndrome (IRIS) is a central nervous system inflammatory syndrome where immune response to John Cunningham (JC) virus antigen following antiretroviral therapy (ART) causes breakdown of the blood–brain barrier. We report a unique case of PML-IRIS, which presented with dystonic choreoathetosis after initiation of ART at a CD4+ cell count of 350 cells/mm3. This report shows continuous progression of the disease over a period of two years, despite robust immune reconstitution. The worsening of neurological symptoms, persistent positivity of JC virus in CSF, and progressive inflammatory picture on MR scans in the setting of a CD4+ cell count of 900 cells/mm3 highlight a different variant of PML-IRIS, and challenge the role of CD4+ cell count in diagnosing opportunistic infections in HIV/AIDS patients.

scholarly journals The predictive power of MRI criteria in the diagnosis of immune reconstitution inflammatory syndrome by the comparison of classification using the decision tree method and ROC analysis

2021 ◽  
Vol 12 (3) ◽  
pp. 16-25
Author(s):  
E. G. Bakulina ◽  
G. V. Kataeva ◽  
T. N. Trofimova
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Decision Tree ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Roc Analysis ◽  
Brain Mri ◽  
Predictive Values ◽  
The Central Nervous System ◽  
Inflammatory Syndrome

Introduction. Immune reconstitution inflammatory syndrome involving the central nervous system (CNS-IRIS) is a dangerous complication in HIV-infected patients on antiretroviral therapy (ART). The radiologic features of this syndrome have been little studied and are presented in isolated works. The diagnosis is difficult because there are no generally accepted criteria for IRIS. Our study is devoted to radiology of IRIS. Based on the results of brain MRI, together with clinical and laboratory data, MRI criteria for IRIS were formulated.Purpose and goals. To determine the prognostic value of MRI signs of CNS-IRIS using in a cohort of HIV-positive patients with neurological symptoms.Materials and methods. The analysis includes data from 68 HIV-infected patients who underwent brain MRI. In 14 of them were diagnosed IRIS with involvement of the central nervous system. To determine the diagnostic efficiency of the formulated MRI criteria, the STATISTICA program was used, decision trees were built, and a ROC analysis was performed.Results. Five decision tree models were built with different predictive values. The models took into account the categorical predictors (MRI criteria) in different order and quantity. The best performance has model #5, which can be considered a clinically useful predictive model.Conclusion. Brain MRI is an essential diagnostic step in HIV-infected patients on ART. It is necessary to expand the indications and conditions for radiological studies of the brain in patients with suspected immune reconstitution inflammatory syndrome.

Spaceflight-induced changes in white matter hyperintensity burden in astronauts

Neurology ◽  
2017 ◽  
Vol 89 (21) ◽  
pp. 2187-2191 ◽  
Author(s):  
Noam Alperin ◽  
Ahmet M. Bagci ◽  
Sang H. Lee
Keyword(s):  
White Matter ◽  
Brain Tissue ◽  
Space Shuttle ◽  
Brain Mri ◽  
Space Station ◽  
Automated Analysis ◽  
White Matter Hyperintensity ◽  
Long Duration ◽  
Mri Scans ◽  
Fluid Attenuated Inversion Recovery

Objective:To assess the effect of weightlessness and the respective roles of CSF and vascular fluid on changes in white matter hyperintensity (WMH) burden in astronauts.Methods:We analyzed prespaceflight and postspaceflight brain MRI scans from 17 astronauts, 10 who flew a long-duration mission on the International Space Station (ISS) and 7 who flew a short-duration mission on the Space Shuttle. Automated analysis methods were used to determine preflight to postflight changes in periventricular and deep WMH, CSF, and brain tissue volumes in fluid-attenuated inversion recovery and high-resolution 3-dimensional T1-weighted imaging. Differences between cohorts and associations between individual measures were assessed. The short-term reversibility of the identified preflight to postflight changes was tested in a subcohort of 5 long-duration astronauts who had a second postflight MRI scan 1 month after the first postflight scan.Results:Significant preflight to postflight changes were measured only in the long-duration cohort and included only the periventricular WMH and ventricular CSF volumes. Changes in deep WMH and brain tissue volumes were not significant in either cohort. The increase in periventricular WMH volume was significantly associated with an increase in ventricular CSF volume (ρ = 0.63, p = 0.008). A partial reversal of these increases was observed in the long-duration subcohort with a 1-month follow-up scan.Conclusions:Long-duration exposure to microgravity is associated with an increase in periventricular WMH in astronauts. This increase was linked to an increase in ventricular CSF volume documented in ISS astronauts. There was no associated change in or abnormal levels of WMH volumes in deep white matter as reported in U-2 high-altitude pilots.

Occipital epilepsy with subcortical atrophy in celiac disease

2020 ◽  
pp. 10.1212/CPJ.0000000000000942
Author(s):  
Alionka Bostan ◽  
Chiara Mabiglia ◽  
Adraa Nouini ◽  
Hélène Visée ◽  
Bernard Dan ◽  
...  
Keyword(s):  
Celiac Disease ◽  
White Matter ◽  
Brain Mri ◽  
Occipital Lobe ◽  
Subcortical White Matter ◽  
Gluten Free Diet ◽  
Epileptic Focus ◽  
Gluten Free ◽  
Lobe Atrophy

We report a 50-year-old man with celiac disease who presented with occipital epilepsy. Brain MRI showed right occipital subcortical white matter hyperintensities, consistent with the posterior epileptic focus suggested by the clinical features of the seizures and documented on EEG. Shortly after the introduction of gluten free diet the white matter abnormalities resolved. The patient went on to develop simultagnosia. Follow-up MRI showed right occipital lobe atrophy. This report emphasizes the importance of recognizing gluten associated neurologic manifestations and usefulness of gluten free diet.

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