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      The effectiveness of anti-inflammatory and anti-seizure medication for individuals with single enhancing lesion neurocysticercosis: A meta-analysis and expert group-based consensus recommendations

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          Abstract

          Single brain enhancing lesions (SEL) are the most common presentation of neurocysticercosis (NCC) observed on neuroimaging in people presenting with epileptic seizures not only on the Indian sub-continent and in travelers returning from cysticercosis-endemic regions, but are also present in other parts of the world.

          The aim of this study, which consisted of a systematic review (CRD42019087665), a meta-analysis and an expert group consultation, was to reach consensus on the best anti-seizure medication and anti-inflammatory treatment for individuals with SEL NCC.

          Standard literature review methods were used. The Cochrane risk of bias tool was used and random effects model meta-analyses were performed. The quality of the body of evidence was rated using GRADE tables. The expert committee included 12 gender and geographically balanced members and recommendations were reached by applying the GRADE framework for guideline development.

          The 1–1.5-year cumulative incidence of seizure recurrence, cyst resolution or calcification following anti-seizure medication (ASM) withdrawal was not statistically different between ASM of 6, 12 or 24 months. In contrast, in persons whose cyst calcified post treatment, longer ASM decreased seizure recurrence. The cumulative incidence ratio (CIR) 1–1.5 years after stopping ASM was 1.79 95% CI: (1.00, 3.20) for patients given 6 versus 24 months treatment.

          Anti-inflammatory treatment with corticosteroids in patients treated with ASM compared to patients treated with ASM only showed a statistically significant beneficial effect on seizure reduction (CIR 0.44, 95% CI 0.23, 0.85) and cyst resolution (CIR 1.37, 95%CI: 1.07, 1.75).

          Our results indicate that ASM in patients with SEL NCC whose cysts resolved can be withdrawn, while patients whose cysts calcified seem to benefit from prolonged anti-seizure medication. Additional corticosteroid treatment was found to have a beneficial effect both on seizure reduction and cyst resolution.

          Author summary

          Neurocysticercosis is an infection of the brain with the tapeworm Taenia solium. On the Indian sub-continent, the majority of people suffering from neurocysticercosis only show one cyst (larval form of the parasite) in their brain and often present at clinics with epileptic seizures. There is still some debate on the best way to treat these cases to reduce the risk for seizure recurrence. The goal of this study was to review the literature on how well different durations of treatment with anti-seizure medication (ASM), combined or not with corticosteroids, work in order to reduce the seizure recurrence and eliminate the cyst from the brain. The results show that ASM for 24 months compared to 6 months favors reduced seizure recurrence in patients whose cysts calcified post treatment. Concerning anti-inflammatory treatment, corticosteroids were also found to have beneficial effects on seizure reduction. However, further high-quality randomized controlled trials with adequately long follow-up time are required for better evidence on best drug(s), dose and duration of ASM and corticosteroids for individuals with SEL NCC.

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          The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials

          Flaws in the design, conduct, analysis, and reporting of randomised trials can cause the effect of an intervention to be underestimated or overestimated. The Cochrane Collaboration’s tool for assessing risk of bias aims to make the process clearer and more accurate
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            Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

            David Moher and colleagues introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses
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              Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation

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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: VisualizationRole: Writing – original draft
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: VisualizationRole: Writing – original draft
                Role: ConceptualizationRole: MethodologyRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: ValidationRole: Writing – review & editing
                Role: ValidationRole: Writing – review & editing
                Role: ValidationRole: Writing – review & editing
                Role: ValidationRole: Writing – review & editing
                Role: ValidationRole: Writing – review & editing
                Role: ValidationRole: Writing – review & editing
                Role: ValidationRole: Writing – review & editing
                Role: ValidationRole: Writing – review & editing
                Role: ValidationRole: Writing – review & editing
                Role: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: ResourcesRole: SoftwareRole: ValidationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                31 March 2021
                March 2021
                : 15
                : 3
                : e0009193
                Affiliations
                [1 ] Department of Neurology, Center for Global Health, School of Medicine, Technical University of Munich, Munich, Germany
                [2 ] Centre for Global Health, Department of Community Medicine and Global Health, Institute of Health and Society, University of Oslo, Oslo, Norway
                [3 ] Center for Global Health, Universidad Peruana Cayetano Heredia, Lima, Peru, and Cysticercosis Unit, Instituto Nacional de Ciencias Neurológicas, Lima, Peru
                [4 ] Département de Pathologie et de Microbiologie, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, Canada
                [5 ] Département de médecine sociale et préventive, École de santé publique, université de Montréal, Montréal, Canada
                [6 ] Centre de Recherche en Santé Publique de l’Université de Montréal et du Centre Intégré Universitaire de Santé et des Services Sociaux de sud de l’île de Montréal, Montréal, Canada
                [7 ] Groupe de recherche en épidémiologie des zoonoses et santé publique (GREZOSP), Montréal, Canada
                [8 ] Department of Microbiology & Immunology, Medical University of the Americas, Nevis, West Indies
                [9 ] Department of Neurological Sciences, Christian Medical College, Vellore, India
                [10 ] Dayanand Medical College, Ludhiana, India
                [11 ] Infectious Disease Division, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, United States of America
                [12 ] Hospital for Tropical Diseases and the London School of Hygiene and Tropical Medicine, London, United Kingdom
                [13 ] Department of Veterinary Public Health and Food Safety, Faculty of Veterinary Medicine, Ghent University, Belgium
                [14 ] University of Medical Sciences and Technology, Khartoum, Sudan
                [15 ] Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institute of Health, United States of America
                [16 ] National Institute for Medical Research, Muhimbili Medical Research Centre, Dar es Salaam, Tanzania
                [17 ] University of Dar es Salaam, Mbeya College of Health and Allied Sciences, Mbeya, Tanzania
                [18 ] National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, China
                [19 ] Albert Einstein College of Medicine, Bronx, NY, United States of America
                Federal University of Ceará, Fortaleza, Brazil, BRAZIL
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0003-0471-6762
                https://orcid.org/0000-0002-2822-4730
                https://orcid.org/0000-0002-6529-1721
                https://orcid.org/0000-0003-2163-972X
                https://orcid.org/0000-0001-6661-3553
                https://orcid.org/0000-0002-9668-4632
                https://orcid.org/0000-0002-2523-233X
                https://orcid.org/0000-0001-8738-7903
                https://orcid.org/0000-0003-3131-6983
                Article
                PNTD-D-20-01812
                10.1371/journal.pntd.0009193
                8057605
                33788843
                46e9aa48-4833-4bca-8fce-070f7b639c67
                © 2021 Abraham et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 12 October 2020
                : 2 February 2021
                Page count
                Figures: 12, Tables: 3, Pages: 26
                Funding
                AA and JB received temporary consultancy fees from WHO and AA was partially funded by the German Federal Ministry of Education and Research (BMBF) [The Lancet One Health Commission 01KA1912]. We also acknowledge funding by BMBF [CYSTINET-Africa 01KA1618] supporting AA, ASW (Germany) and BN (Tanzania) and generating knowledge of neurocysticercosis management that contributed to the current systematic review and metanalysis as well as to the development of the WHO neurocysticercosis management guidelines. JB and HGG further acknowledge partial support by the Fogarty International Center (NIH Training grant D43 TW001140), Tropical Medicine Research Center Program (NIAID-NIH grant U19AI129909) and (NIAID-NIH grant 1R01AI116456-01). TN was supported by Intramural research program of the NIH. HC is funded by the Canada Research Chair in Epidemiology and One Health (CIHR/IRSC CRC 950–231857) and PSS was supported by the Indian council of Medical Research under Ad-hoc Research Grant (Neuroscience) (IRIS ID:2010-10530). This work was supported by WHO. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
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                Pharmaceutics
                Drug Therapy
                Steroid Therapy
                Corticosteroid Therapy
                Medicine and Health Sciences
                Clinical Medicine
                Signs and Symptoms
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                Medicine and Health Sciences
                Epidemiology
                Medical Risk Factors
                Biology and Life Sciences
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                2021-04-20
                All relevant data are within the manuscript and its Supporting Information files.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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