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Clinical topography relationship in patients with parenchymal neurocysticercosis and seizures.

ABSTRACT: OBJECTIVE:Discordances between imaging findings of parenchymal neurocysticercosis and seizure expression have been reported, and as such the possibility that neurocysticercosis and seizures may frequently coexist by chance has been raised. In this study, we evaluate the topographic relationship between seizure foci based on semiology and electroencephalography with the location of parenchymal neurocysticercotic lesions. METHODS:Seizure information, neuroimaging (computed tomography and magnetic resonance imaging [MRI]) and electroencephalographic data from three randomized clinical trials of individuals with parenchymal neurocysticercosis and focal seizures were analyzed. Blinded epileptologists defined a potential seizure onset zone and a symptomatogenic zone for each individual based on semiology. The topographic relationship between semiology, either lesion location or areas of perilesional edema on baseline MRI, and electroencephalographic abnormalities were assessed. RESULTS:Fifty-eight patients with one or two parenchymal neurocysticercotic lesions were included in this study. From them, 50 patients (86%; 95% CI, 75%-93%) showed a clinical-topography relationship with the potential seizure onset zone, and 44 (76%) also with the symptomatogenic zone. From the eight patients with no topographic relationship, five had focal seizures 30 days before or after the baseline MRI and showed perilesional edema. All of these five patients showed a clinical-topography relationship between such seizures and an area of perilesional edema, making a total of 55 patients (95%; 95% CI, 85%-99%) with clinical-topography relationship when perilesional edema is considered. Most patients with focal epileptiform discharges (7/8, 88%) had a topographic association between electroencephalographic focality, the potential seizure onset zone and a cysticercotic lesion. CONCLUSION:Seizure semiology and focal epileptiform discharges are topographically related to neurocysticercotic lesions in most patients. These data strongly support seizure origin in the cortex surrounding these lesions.

SUBMITTER: Duque KR

PROVIDER: S-EPMC7063828 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Clinical topography relationship in patients with parenchymal neurocysticercosis and seizures.

Duque Kevin R KR Escalaya Alejandro L AL Zapata Willy W Burneo Jorge G JG Bustos Javier A JA Gonzales Isidro I Saavedra Herbert H Pretell E Javier EJ Garcia Hector H HH

Epilepsy research 20180628

<h4>Objective</h4>Discordances between imaging findings of parenchymal neurocysticercosis and seizure expression have been reported, and as such the possibility that neurocysticercosis and seizures may frequently coexist by chance has been raised. In this study, we evaluate the topographic relationship between seizure foci based on semiology and electroencephalography with the location of parenchymal neurocysticercotic lesions.<h4>Methods</h4>Seizure information, neuroimaging (computed tomograph ...[more]

PMID: 30007239

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Project description:BackgroundAntigen tests for diagnosis and disease monitoring in some types of neurocysticercosis (NCC) are useful but access to testing has been limited by availability of proprietary reagents and/or kits.Methods/principal findingsThree previously identified IgM-secreting hybridomas whose IgM products demonstrated specificity to Taenia solium underwent variable heavy and light chain sequencing and isotype conversion to mouse IgG. Screening of these recombinantly expressed IgG anti-Ts hybridomas, identified one (TsG10) with the highest affinity to crude Taenia antigen. TsG10 was then used as a capture antibody in a sandwich antigen detection immunoassay in combination with either a high titer polyclonal anti-Ts antibody or with biotinylated TsG10 (termed TsG10*bt). Using serum, plasma, and CSF samples from patients with active NCC and those from NCC-uninfected patients, ROC curve analyses demonstrated that the TsG10-TsG10-*bt assay achieved a 98% sensitivity and 100% specificity in detecting samples known to be antigen positive and outperformed the polyclonal based assay (sensitivity of 93% with 100% specificity). By comparing levels of Ts antigen (Ag) in paired CSF (n = 10) or plasma/serum (n = 19) samples from well-characterized patients with extra-parenchymal NCC early in infection and at the time of definitive cure, all but 2 (1 from CSF and 1 from plasma) became undetectable. There was a high degree of correlation (r = 0.98) between the Ag levels detected by this new assay and levels found by a commercial assay. Pilot studies indicate that this antigen can be detected in the urine of patients with active NCC.Conclusions/significanceA newly developed recombinant monoclonal antibody-based Ts Ag detection immunoassay is extremely sensitive in the detection of extra-parenchymal NCC and can be used to monitor the success of treatment in the CSF, serum/plasma and urine. The ability to produce recombinant TsG10 at scale should enable use of this antigen detection immunoassay wherever NCC is endemic.Clinical trial registrationClinicalTrials.gov Identifiers: NCT00001205 - & NCT00001645.

Project description:BackgroundThe ability of Taenia solium to modulate the immune system likely contributes to their longevity in the human host. We tested the hypothesis that the nature of the immune response is related to the location of parasite and clinical manifestations of infection.MethodologyPeripheral blood mononuclear cells (PBMC) were obtained from untreated patients with neurocysticercosis (NCC), categorized as having parenchymal or subarachnoid infection by the presence of cysts exclusively within the parenchyma or in subarachnoid spaces of the brain, and from uninfected (control) individuals matched by age and gender to each patient. Using multiplex detection technology, sera from NCC patients and controls and cytokine production by PBMC after T. solium antigen (TsAg) stimulation were assayed for levels of inflammatory and regulatory cytokines. PBMC were phenotyped by flow cytometry ex vivo and following in vitro stimulation with TsAg.Principal findingsSera from patients with parenchymal NCC demonstrated significantly higher Th1 (IFN-?/IL-12) and Th2 (IL-4/IL-13) cytokine responses and trends towards higher levels of IL-1?/IL-8/IL-5 than those obtained from patients with subarachnoid NCC. Also higher in vitro antigen-driven TNF-? secretion was detected in PBMC supernatants from parenchymal than in subarachnoid NCC. In contrast, there was a significantly higher IL-10 response to TsAg stimulation in patients with subarachnoid NCC compared to parenchymal NCC. Although no differences in regulatory T cells (Tregs) frequencies were found ex vivo, there was a trend towards greater expansion of Tregs upon TsAg stimulation in subarachnoid than in parenchymal NCC when data were normalized for the corresponding controls.Conclusions/significanceT. solium infection of the subarachnoid space is associated with an enhanced regulatory immune response compared to infection in the parenchyma. The resulting anti-inflammatory milieu may represent a parasite strategy to maintain a permissive environment in the host or diminish inflammatory damage from the host immune response in the central nervous system.

Project description:BackgroundNeurocysticercosis (NCC) is a parasitic infection of the human central nervous system, the most common form of which involves infection of the brain parenchyma with the larval form of the Taenia solium tapeworm. A causal relationship between such an NCC infection and the development of epilepsy in infected individuals is acknowledged, in part supported by high levels of comorbidity in endemic countries worldwide.MethodsThis study undertook a systematic review and critical analysis of the NCC-epilepsy relationship with the primary objective of quantifying the risk of developing epilepsy following NCC infection. A secondary aim was to analyse the proportions of NCC-associated epilepsy within different populations. Significant emphasis was placed on the importance of neuroimaging (CT or MRI) availability and use of clear guidelines for epilepsy diagnosis, in order to avoid overestimations of prevalence rates of either condition; a limitation identified in several previous studies.ResultsA common odds ratio of 2.76 was identified from meta-analysis of case-control studies, indicating that an individual infected with NCC has almost a three times higher risk of developing epilepsy than an uninfected individual. Furthermore, meta-analysis of studies identified a common proportion of 31.54% of epilepsy cases associated with NCC infection which suggests that amongst epileptic populations in at risk countries, approximately one-third may be associated with NCC infection.ConclusionA significant finding was the lack of good clinical data to enable accurate determination of a causal relationship. Even studies that were included had noticeable limitations, including a general lack of consistency in diagnostics, and lack of accurate epidemiological data. This review highlights a need for consistency in research in this field. In the absence of reliable estimates of its global burden, NCC will remain of low priority in the eyes of funding agencies - a truly neglected disease.

Dataset Information

Clinical topography relationship in patients with parenchymal neurocysticercosis and seizures.

Publications

Clinical topography relationship in patients with parenchymal neurocysticercosis and seizures.

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