Reversible cerebral vasoconstriction syndrome associated with fingolimod treatment in relapsing–remitting multiple sclerosis three months after childbirth

Kraemer, Markus; Weber, Ralph; Herold, Michèle; Berlit, Peter

doi:10.1177/1352458515600249

Cited by 17 publications

(13 citation statements)

References 7 publications

(12 reference statements)

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“…10/mm 3 (10/ mm 3 -29/mm 3 ). Oligoclonal bands were positive in two patients; one of these had a comorbid multiple sclerosis [4]. Cytological analysis revealed a lymphomonocytic pleocytosis in four cases and granulocytes and lymphocytes in one patient.…”

Section: Resultsmentioning

confidence: 91%

“…Seven of 10 patients were considered to be exposed to RCVS, provoking triggers such as postpartal status (two patients) and vasoactive medication or drugs such as fluoxetine, tiotropium bromide or consumption of cannabis. In one patient RCVS occurred in the context of medication with fingolimod, which has been incriminated as a provoking factor elsewhere [4]. Strokes were detected in nine of 10 patients; one patient showed cortical subarachnoid haemorrhage in two locations.…”

Section: Resultsmentioning

confidence: 98%

“…In one patient RCVS occurred in the context of medication with fingolimod, which has been incriminated as a provoking factor elsewhere [4]. All showed multi-focal vasoconstriction (in duplex ultrasound, magnetic resonance angiography or conventional angiography).…”

Section: Resultsmentioning

confidence: 99%

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Cerebrospinal fluid findings in reversible cerebral vasoconstriction syndrome: a way to differentiate from cerebral vasculitis?

Kraayvanger

Berlit

Albrecht

et al. 2018

Clinical and Experimental Immunology

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Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by an acute onset of severe headache and multi-focal segmental vasoconstriction of cerebral arteries resolving within 12 weeks. Diagnostic criteria include normal or near-normal findings in cerebrospinal fluid (CSF) analysis, especially leucocyte levels < 10/mm³. Distinguishing RCVS from primary angiitis of the central nervous system (PACNS) is essential to avoid unnecessary and sometimes unfavourable immunosuppressive treatment. We reviewed retrospectively the clinical and diagnostic data of 10 RCVS patients who presented in our neurological department from 1 January 2013 to February 2017. The main purpose was to verify whether CSF leucocyte counts < 10/mm³ serve to discriminate RCVS from PACNS. Five of six patients who underwent lumbar puncture presented with CSF leucocyte levels ≥ 10/mm³. Two patients had a history of misinterpretation of CSF pleocytosis as cerebral vasculitis and of immunosuppressive treatment. A complete restitution of cerebral vasoconstriction was evident in all. No patient had further cerebral strokes or bleedings without immunosuppressive treatment over more than 12 weeks. Despite the established diagnostic criteria, RCVS can manifest with CSF leucocyte levels > 10/mm³. Careful anamnesis and the response of 'vasculitis-like angiography' to nimodipine given as a test during angiography and as oral medication are key to differentiate RCVS from cerebral vasculitis.

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Section: Resultsmentioning

confidence: 91%

Section: Resultsmentioning

confidence: 98%

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Cerebrospinal fluid findings in reversible cerebral vasoconstriction syndrome: a way to differentiate from cerebral vasculitis?

Kraayvanger

Berlit

Albrecht

et al. 2018

Clinical and Experimental Immunology

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“…A variety of rare AEs associated with fingolimod treatment have been reported as single case reports or small case series including but not limited to posterior reversible encephalopathy syndrome, 68 cryptococcal meningoencephalitis and disseminated cryptococcosis, 69 , 70 Kaposi sarcoma, 71 tumefactive demyelination, 72 – 74 severe autoimmune hemolytic anemia, 75 asthma deterioration, 76 amenorrhea, 77 peripheral vascular adverse effects, 78 ecchymotic angioedema-like cutaneous lesions, 79 reversible cerebral vasoconstriction syndrome, 80 lymphomatoid papulosis, 81 and hemophagocytic syndrome (this rare disorder due to cytokine dysregulation has been reported in association to infection in two patients treated with fingolimod for 9 and 15 months, respectively, both with fatal outcome). 82 , 83…”

Section: Fingolimod Safety and Tolerabilitymentioning

confidence: 99%

Clinical efficacy, safety, and tolerability of fingolimod for the treatment of relapsing-remitting multiple sclerosis

Gajofatto¹,

Turatti²,

Monaco³

et al. 2015

DHPS

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Fingolimod is a selective immunosuppressive agent approved worldwide for the treatment of relapsing-remitting multiple sclerosis (MS), a chronic and potentially disabling neurological condition. Randomized double-blind clinical trials have shown that fingolimod significantly reduces relapse rate and ameliorates a number of brain MRI measures, including cerebral atrophy, compared to both placebo and intramuscular interferon-β1a. The effect on disability progression remains controversial, since one Phase III trial showed a significant benefit of treatment while two others did not. Although fingolimod has a very convenient daily oral dosing, the possibility of serious cardiac, ocular, infectious, and other rare adverse events justified the decision of the European Medicines Agency to approve the drug as a second-line treatment for MS patients not responsive to first-line therapy, or those with rapidly evolving course. In the United States, fingolimod is instead authorized as a first-line treatment. The aim of this review is to describe and discuss the characteristics of fingolimod concerning its efficacy, safety, and tolerability in the clinical context of multiple sclerosis management.

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“…To diagnose newly-onset IDD during puerperium, a combination of acute neurological function impairment, typical neuroimaging changes, evidence of positive serum antibodies is needed. Furthermore, it is essential to rule out reversible posterior leukoencephalopahy syndrome[67] and other intracranial multifocal diseases. Although previous reports confirmed that epidural anesthesia and cesarean delivery were innocuous, cesarean section was the main delivery way in this study.…”

Section: Discussionmentioning

confidence: 99%

Insights into Initial Demyelinating Episodes of Central Nervous System during Puerperium

Chen

Liu

et al. 2017

Chinese Medical Journal

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Background:Inflammatory demyelinating disease of central nervous system (CNS) is an inflammatory disease characterized by a high childbearing female predominance. Labor-related alterations for postpartum demyelinating attacks are not entirely clear. This study aimed to summarize clinical features of female patients of reproductive age with initial CNS inflammatory demyelinating attacks during puerperium.Methods:Fourteen female patients with initial demyelinating events during puerperium between January 2013 and December 2016 were retrospectively studied. Records of clinical features, neuroimaging, serum antibodies, cerebrospinal fluid (CSF) findings, annualized relapse rate (ARR), and treatment were analyzed.Results:Among 14 patients, 5 patients were diagnosed with multiple sclerosis (MS), four as neuromyelitis optica (NMO), two as longitudinal extensive transverse myelitis, two as clinical isolated syndrome (CIS), and one as acute brainstem syndrome. All the 14 puerperal female patients presented with more than one manifestation of hemiplegia, paraplegia, uroschesis, visual loss or dysarthria, and with mild to moderate abnormalities of CSF. Attacks occurred during the first trimester postpartum and cesarean section was the main delivery way (n = 10). Median Expanded Disability Status Scale (EDSS) scores were 5.0 (range: 2.0–9.0) at the onset and 2.5 (range: 0–7.0) at the end of follow-ups. Patients with MS and CIS had a significantly lower EDSS scores than patients with NMO spectrum disorders (P < 0.05). Median ARR was 0.46 (range: 0–1.16); all patients had a low ARR (0.49 ± 0.34, 95% confidence interval: 0.29–0.69) with standardized treatments.Conclusion:Labor-related alterations in the mother's immune system might result in newly-onset demyelinating diseases of central nervous system.

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Reversible cerebral vasoconstriction syndrome associated with fingolimod treatment in relapsing–remitting multiple sclerosis three months after childbirth

Cited by 17 publications

References 7 publications

Cerebrospinal fluid findings in reversible cerebral vasoconstriction syndrome: a way to differentiate from cerebral vasculitis?

Cerebrospinal fluid findings in reversible cerebral vasoconstriction syndrome: a way to differentiate from cerebral vasculitis?

Clinical efficacy, safety, and tolerability of fingolimod for the treatment of relapsing-remitting multiple sclerosis

Insights into Initial Demyelinating Episodes of Central Nervous System during Puerperium

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