Variant Intestinal-Cell Kinase in Juvenile Myoclonic Epilepsy.

BACKGROUND: In juvenile myoclonic epilepsy, data are limited on the genetic basis of networks promoting convulsions with diffuse polyspikes on electroencephalography (EEG) and the subtle microscopic brain dysplasia called microdysgenesis. METHODS: Using Sanger sequencing, we sequenced the exomes of six members of a large family affected with juvenile myoclonic epilepsy and confirmed cosegregation in all 37 family members. We screened an additional 310 patients with this disorder for variants on DNA melting-curve analysis and targeted real-time DNA sequencing of the gene encoding intestinal-cell kinase ( ICK). We calculated Bayesian logarithm of the odds (LOD) scores for cosegregating variants, odds ratios in case-control associations, and allele frequencies in the Genome Aggregation Database. We performed functional tests of the effects of variants on mitosis, apoptosis, and radial neuroblast migration in vitro and conducted video-EEG studies in mice lacking a copy of Ick. RESULTS: A variant, K305T (c.914A→C), cosegregated with epilepsy or polyspikes on EEG in 12 members of the family affected with juvenile myoclonic epilepsy. We identified 21 pathogenic ICK variants in 22 of 310 additional patients (7%). Four strongly linked variants (K220E, K305T, A615T, and R632X) impaired mitosis, cell-cycle exit, and radial neuroblast migration while promoting apoptosis. Tonic-clonic convulsions and polyspikes on EEG resembling seizures in human juvenile myoclonic epilepsy occurred more often in knockout heterozygous mice than in wild-type mice (P=0.02) during light sleep with isoflurane anesthesia. CONCLUSIONS: Our data provide evidence that heterozygous variants in ICK caused juvenile myoclonic epilepsy in 7% of the patients included in our analysis. Variant ICK affects cell processes that help explain microdysgenesis and polyspike networks observed on EEG in juvenile myoclonic epilepsy. (Funded by the National Institutes of Health and others.).

EFHC1 variants in juvenile myoclonic epilepsy: reanalysis according to NHGRI and ACMG guidelines for assigning disease causality.

PURPOSE: EFHC1 variants are the most common mutations in inherited myoclonic and grand mal clonic-tonic-clonic (CTC) convulsions of juvenile myoclonic epilepsy (JME). We reanalyzed 54 EFHC1 variants associated with epilepsy from 17 cohorts based on National Human Genome Research Institute (NHGRI) and American College of Medical Genetics and Genomics (ACMG) guidelines for interpretation of sequence variants. METHODS: We calculated Bayesian LOD scores for variants in coinheritance, unconditional exact tests and odds ratios (OR) in case-control associations, allele frequencies in genome databases, and predictions for conservation/pathogenicity. We reviewed whether variants damage EFHC1 functions, whether efhc1-/- KO mice recapitulate CTC convulsions and "microdysgenesis" neuropathology, and whether supernumerary synaptic and dendritic phenotypes can be rescued in the fly model when EFHC1 is overexpressed. We rated strengths of evidence and applied ACMG combinatorial criteria for classifying variants. RESULTS: Nine variants were classified as "pathogenic," 14 as "likely pathogenic," 9 as "benign," and 2 as "likely benign." Twenty variants of unknown significance had an insufficient number of ancestry-matched controls, but ORs exceeded 5 when compared with racial/ethnic-matched Exome Aggregation Consortium (ExAC) controls. CONCLUSIONS: NHGRI gene-level evidence and variant-level evidence establish EFHC1 as the first non-ion channel microtubule-associated protein whose mutations disturb R-type VDCC and TRPM2 calcium currents in overgrown synapses and dendrites within abnormally migrated dislocated neurons, thus explaining CTC convulsions and "microdysgenesis" neuropathology of JME.Genet Med 19 2, 144-156.

ICD coding for epilepsy: past, present, and future--a report by the International League Against Epilepsy Task Force on ICD codes in epilepsy.

The World Health Organization (WHO) International Classification of Diseases (ICD) has been used to classify causes of morbidity and mortality such as epilepsy for more than 50 years. The aims of this critical commentary are to do the following: (1) Introduce the ICD classification, summarize the ICD-9 and ICD-10 codes for epilepsy and seizures, and discuss the challenges of mapping epilepsy codes between these two versions; (2) discuss how the ICD-9 and ICD-10 relate to the revised International League Against Epilepsy (ILAE) terminology and concepts for classification of seizures and epilepsies; (3) discuss how ICD-coded data have been used for epilepsy care and research and briefly examine the potential impact of the international ICD-10 clinical modifications on research; (4) discuss the upcoming ICD-11 codes and the role of the epilepsy community in their development; and (5) discuss how the ICD-11 will conform more closely to the current ILAE terminology and classification of the epilepsies and seizures and its potential impact on clinical care, surveillance, and public health and research.

The quest for juvenile myoclonic epilepsy genes.

Introduced into a specific population, a juvenile myoclonic epilepsy (JME) mutation generates linkage disequilibrium (LD). Linkage disequilibrium is strongest when the JME mutation is of recent origin, still "hitchhiking" alleles surrounding it, as a haplotype into the next thousands of generations. Recombinations decay LD over tens of thousands of generations causing JME alleles to produce smaller genetic displacements, requiring other genes or environment to produce an epilepsy phenotype. Family-based linkage analysis captures rare epilepsy alleles and their "hitchhiking" haplotypes, transmitted as Mendelian traits, supporting the common disease/multiple rare allele model. Genome-wide association studies identify JME alleles whose linkage disequilibrium has decayed through thousands of generations and are sorting out the common disease/common allele versus rare allele models. Five Mendelian JME genes have been identified, namely, CACNB4, CASR, GABRa1, GABRD, and Myoclonin1/EFHC1. Three SNP alleles in BRD2, Cx-36, and ME2 and microdeletions in 15q13.3, 15q11.2, and 16p13.11 also contribute risk to JME.

Consensus on diagnosis and management of JME: From founder's observations to current trends.

An international workshop on juvenile myoclonic epilepsy (JME) was conducted in Avignon, France in May 2011. During that workshop, a group of 45 experts on JME, together with one of the founding fathers of the syndrome of JME ("Janz syndrome"), Prof. Dr. Dieter Janz from Berlin, reached a consensus on diagnostic criteria and management of JME. The international experts on JME proposed two sets of criteria, which will be helpful for both clinical and scientific purposes. Class I criteria encompass myoclonic jerks without loss of consciousness exclusively occurring on or after awakening and associated with typical generalized epileptiform EEG abnormalities, with an age of onset between 10 and 25. Class II criteria allow the inclusion of myoclonic jerks predominantly occurring after awakening, generalized epileptiform EEG abnormalities with or without concomitant myoclonic jerks, and a greater time window for age at onset (6-25years). For both sets of criteria, patients should have a clear history of myoclonic jerks predominantly occurring after awakening and an EEG with generalized epileptiform discharges supporting a diagnosis of idiopathic generalized epilepsy. Patients with JME require special management because their epilepsy starts in the vulnerable period of adolescence and, accordingly, they have lifestyle issues that typically increase the likelihood of seizures (sleep deprivation, exposure to stroboscopic flashes in discos, alcohol intake, etc.) with poor adherence to antiepileptic drugs (AEDs). Results of an inventory of the different clinical management strategies are given. This article is part of a supplemental special issue entitled Juvenile Myoclonic Epilepsy: What is it Really?

Mutations in EFHC1 cause juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is the most frequent cause of hereditary grand mal seizures. We previously mapped and narrowed a region associated with JME on chromosome 6p12-p11 (EJM1). Here, we describe a new gene in this region, EFHC1, which encodes a protein with an EF-hand motif. Mutation analyses identified five missense mutations in EFHC1 that cosegregated with epilepsy or EEG polyspike wave in affected members of six unrelated families with JME and did not occur in 382 control individuals. Overexpression of EFHC1 in mouse hippocampal primary culture neurons induced apoptosis that was significantly lowered by the mutations. Apoptosis was specifically suppressed by SNX-482, an antagonist of R-type voltage-dependent Ca(2+) channel (Ca(v)2.3). EFHC1 and Ca(v)2.3 immunomaterials overlapped in mouse brain, and EFHC1 coimmunoprecipitated with the Ca(v)2.3 C terminus. In patch-clamp analysis, EFHC1 specifically increased R-type Ca(2+) currents that were reversed by the mutations associated with JME.

Global synergistic actions to improve brain health for human development.

The global burden of neurological disorders is substantial and increasing, especially in low-resource settings. The current increased global interest in brain health and its impact on population wellbeing and economic growth, highlighted in the World Health Organization's new Intersectoral Global Action Plan on Epilepsy and other Neurological Disorders 2022-2031, presents an opportunity to rethink the delivery of neurological services. In this Perspective, we highlight the global burden of neurological disorders and propose pragmatic solutions to enhance neurological health, with an emphasis on building global synergies and fostering a 'neurological revolution' across four key pillars - surveillance, prevention, acute care and rehabilitation - termed the neurological quadrangle. Innovative strategies for achieving this transformation include the recognition and promotion of holistic, spiritual and planetary health. These strategies can be deployed through co-design and co-implementation to create equitable and inclusive access to services for the promotion, protection and recovery of neurological health in all human populations across the life course.

Revising the ICD-10 codes for epilepsy and seizures.

The World Health Organization is currently revising the International Classification of Disease, 10th Revision (ICD-10). A Neurology Task Force Advisory Group [TAG] has been charged with producing a revision that reflects scientific advances and new concepts of pathophysiology since 1992. The ICD codes are used globally to report mortality and morbidity statistics, and they play a vital role in health care planning, training, and allocation of health care resources in many countries. Although used by physicians and hospitals at all levels, the primary users of the ICD codes are primary health care providers, which, particularly in low income countries, include nurses, clinical assistants, and health officers. The TAG, which consists of representatives of major international subspecialty groups such as the International League Against Epilepsy (ILAE), has published draft codes that are available online for public comment.

Hyperglycosylation and reduced GABA currents of mutated GABRB3 polypeptide in remitting childhood absence epilepsy.

Childhood absence epilepsy (CAE) accounts for 10% to 12% of epilepsy in children under 16 years of age. We screened for mutations in the GABA(A) receptor (GABAR) beta 3 subunit gene (GABRB3) in 48 probands and families with remitting CAE. We found that four out of 48 families (8%) had mutations in GABRB3. One heterozygous missense mutation (P11S) in exon 1a segregated with four CAE-affected persons in one multiplex, two-generation Mexican family. P11S was also found in a singleton from Mexico. Another heterozygous missense mutation (S15F) was present in a singleton from Honduras. An exon 2 heterozygous missense mutation (G32R) was present in two CAE-affected persons and two persons affected with EEG-recorded spike and/or sharp wave in a two-generation Honduran family. All mutations were absent in 630 controls. We studied functions and possible pathogenicity by expressing mutations in HeLa cells with the use of Western blots and an in vitro translation and translocation system. Expression levels did not differ from those of controls, but all mutations showed hyperglycosylation in the in vitro translation and translocation system with canine microsomes. Functional analysis of human GABA(A) receptors (alpha 1 beta 3-v2 gamma 2S, alpha 1 beta 3-v2[P11S]gamma 2S, alpha 1 beta 3-v2[S15F]gamma 2S, and alpha 1 beta 3-v2[G32R]gamma 2S) transiently expressed in HEK293T cells with the use of rapid agonist application showed that each amino acid transversion in the beta 3-v2 subunit (P11S, S15F, and G32R) reduced GABA-evoked current density from whole cells. Mutated beta 3 subunit protein could thus cause absence seizures through a gain in glycosylation of mutated exon 1a and exon 2, affecting maturation and trafficking of GABAR from endoplasmic reticulum to cell surface and resulting in reduced GABA-evoked currents.

Reduction in rate of epilepsy from neurocysticercosis by community interventions: the Salamá, Honduras study.

PURPOSE: Epilepsy is highly prevalent in developing countries like Honduras, with few studies evaluating this finding. This population-based study evaluated the impact of an 8-year public health and educational intervention program in reducing symptomatic epilepsies in rural Salamá, Honduras. METHODS: We used the capture and recapture method including review of charts, previous databases, key informants from the community, and a second house-to-house survey for epilepsy. Epilepsy incidence and prevalence day after the interventions was May 5, 2005. Residents with active epilepsy with onset after May 1997 were offered neurologic evaluation, electroencephalography, and brain tomography. New data over 8 years were compared to preintervention data from the initial baseline 1997 study utilizing prevalence ratios and confidence intervals. Other calculations utilized chi square or Fisher's exact tests. KEY FINDINGS: Thirty-three of 36 patients with onset of active epilepsy after 1997 accepted evaluations to determine etiology. Symptomatic etiology was found in 58.3%. Neurocysticercosis (NCC) was again the most frequent cause (13.9%), followed by perinatal insults (11.1%). Epilepsy secondary to NCC was significantly reduced from 36.9% in 1997 (p = 0.02). The incidence (35.7/100,000) and prevalence (11.8/1,000) of active epilepsy were not significantly reduced when compared to the incidence (92.7/100,000) and prevalence (15.4/1,000) of active epilepsy in 1997. SIGNIFICANCE: Our cohort appears to indicate that health and educational community interventions can reduce preventable epilepsy from NCC in a hyperendemic population in a low-resource, developing country. Plans are underway for the Honduran Government to institute this rural model countrywide.

Standards for epidemiologic studies and surveillance of epilepsy.

Worldwide, about 65 million people are estimated to have epilepsy. Epidemiologic studies are necessary to define the full public health burden of epilepsy; to set public health and health care priorities; to provide information needed for prevention, early detection, and treatment; to identify education and service needs; and to promote effective health care and support programs for people with epilepsy. However, different definitions and epidemiologic methods complicate the tasks of these studies and their interpretations and comparisons. The purpose of this document is to promote consistency in definitions and methods in an effort to enhance future population-based epidemiologic studies, facilitate comparison between populations, and encourage the collection of data useful for the promotion of public health. We discuss: (1) conceptual and operational definitions of epilepsy, (2) data resources and recommended data elements, and (3) methods and analyses appropriate for epidemiologic studies or the surveillance of epilepsy. Variations in these are considered, taking into account differing resource availability and needs among countries and differing purposes among studies.

Characterization of adult patients with Guillain-Barré syndrome during the arboviral infection outbreaks in Honduras.

Arbovirus infections have been associated with a wide spectrum of neurological manifestations. Among these, Guillain-Barré syndrome (GBS) is one of the most common. This study describes the characteristics of GBS associated with arbovirus infections during the outbreak which occurred in Honduras from January 2016 to February 2019. This was an observational retrospective study of adult patients who were diagnosed with GBS during that time. The diagnosis of GBS was based upon the criteria first published by Asbury, et al. and subsequently revised as the Brighton Criteria. A total of 91 patients with GBS constituted the study population. RT-PCR tests for ZIKV, CHIKV, and DENV arboviruses were performed in 47 (52%) of the patients. Of the tested population, 8/47 were positive for one of the arboviruses (5/8 for ZIKV, 3/8 for CHIKV; 0/8 for DENV). The clinical profile of the eight cases with GBS and arboviral infection did not differ significantly from the GBS patients who tested negative for ZIKV and CHIKV. In the cases with GBS and ZIKV, a parainfectious onset of the disease was suggested. Although not a strikingly large number of patients with GBS and arbovirus infection were seen, the close temporal relationship in these eight cases suggests an arbovirus (ZIKV and CHIKV) etiology.

Hydroxychloroquine/ chloroquine as a treatment choice or prophylaxis for Covid-19 at the primary care level in developing countries: A Primum non Nocere dilemma.

The Food and Drug Administration (FDA) warned against the use of Hydroxychloroquine or chloroquine for Covid-19 outside of a hospital or a clinical trial setting due to the risk of QT interval prolongation, ventricular tachycardia and the increased risk of these complications when combined with some antibiotics such as azithromycin. Several studies have reported no benefit of Hydroxychloroquine or chloroquine, when used alone or with a macrolide in COVID-19 hospitalized patients. Despite these warnings, in several developing countries the official guidelines for treatment of Covid-19 patients at the primary care level recommend Hydroxychloroquine and azithromycin, among other treatments, as the first-choice for mild symptomatic Covid-19 patients, asymptomatic contacts or for prophylaxis. In our opinion there is a primum non nocere dilemma during this Covid-19 pandemic. In order to solve this bioethical problem, we strongly recommend that a randomized controlled trial in a primary care setting be carried out as a matter of urgency in these areas of the world.

DNA variants in coding region of EFHC1: SNPs do not associate with juvenile myoclonic epilepsy.

PURPOSE: Juvenile myoclonic epilepsy (JME) accounts for 3 to 12% of all epilepsies. In 2004, we identified a mutation-harboring Mendelian gene that encodes a protein with one EF-hand motif (EFHC1) in chromosome 6p12. We observed one doubly heterozygous and three heterozygous missense mutations in EFHC1 segregating as an autosomal dominant gene with 21 affected members of six Hispanic JME families from California and Mexico. In 2006, similar and three novel missense mutations were reported in sporadic and familial Caucasian JME from Italy and Austria. In this study, we asked if coding single nucleotide polymorphisms (SNPs) of EFHC1 also contribute as susceptibility alleles to JME with complex genetics. METHODS: We screened using denaturing high-performance liquid chromatography (DHPLC) and then directly sequenced the 11 exons of EFHC1 in 130 unrelated JME probands, their 352 family members, and seven exons of EFHC1 in 400-614 ethnically matched controls. We carried out case-control association studies between 124 unrelated Hispanic JME probands and 552-614 ethnically matched controls using four SNPs, rs3804506, rs3804505, rs1266787, and rs17851770. We also performed family-based association on SNPs rs3804506 and rs3804505 in 84 complete JME families using the Family-Based Association Test (FBAT) program. RESULTS: We found no statistically significant differences between JME probands and controls in case-control association and no genetic transmission disequilibria in family-based association for the tested SNPs. In addition, we identified four new DNA variants in the coding region of EFHC1. CONCLUSION: The four coding SNPs, rs3804506, rs3804505, rs1266787, and rs17851770, of EFHC1 may not be susceptibility alleles for JME.

Adherence and complementary and alternative medicine use among Honduran people with epilepsy.

Adherence to antiepileptic drugs (AEDs) and use of complementary and alternative medicine (CAM) among Hondurans with epilepsy were evaluated. Our epilepsy cohort of 274 outpatients was surveyed to determine demographics, epilepsy treatment history, adherence, and use of CAM. Nonadherence to epilepsy therapy was reported by 121, with unavailability of AEDs (48%) the most common reason. CAM was reportedly used by 141, with prayer, herbs, and potions being common. Forty-nine rural Miskito Hondurans without epilepsy were also interviewed to gain an understanding of their beliefs and longstanding practices regarding epilepsy. Seventeen (34.7%) attributed epilepsy to the supernatural; only three knew of an AED. Widespread nonadherence to evidence-based epilepsy treatments in Honduras can be attributed to inadequate education, AED unavailability, insufficient resources, cultural beliefs, and wide use of CAM. A comprehensive epilepsy education program and improved access to evidence-based AEDs represent initial priorities to improve the Honduran epilepsy treatment gap.

A trauma registry experience from the main referral center of Honduras: A call for action.

BACKGROUND: Honduras is one of the most violent countries in the world and it has limited epidemiological data that describes the extent of intentional and unintentional injuries. This research is needed to develop and inform prevention programs in Honduras, as well as to spread international awareness. METHODS: A cross-sectional study was carried out on a paper-based injury surveillance system (InSS) with the help of Honduras' University Medical School Hospital (UMSH), the main referral medical center in Tegucigalpa-Honduras. Descriptive statistics and bivariate analysis were carried out using data from all registered injuries in 2013. RESULTS: Of the 17,971 injuries reported, intentional injuries made up 18.14% of all injuries. Interpersonal violence from gun violence, robberies, and physical altercations accounted for 14.68%. Self-inflicted injuries made up 3.46% of injuries, with suicide falls and poison intoxications being the most frequent (1.9% and 1.2%, respectively). Sexual harassment was minimally reported (0.27%, n = 48). Unintentional injuries made up 81.79% of the total injuries. The most common causes of unintentional injuries were falls (38.01%) and road traffic injuries (16.65%). Motorocyclists made up 35.4% of those injured by road traffic accidents. In general, injuries occured during the weekend and mainly affected men during the ages when they would be most likely to work and maintain jobs. The modified Kampala trauma score (M-KTS) showed that most of the injuries were mild (range 3-11), with 59.59% of the patients with a M-KTS of 9, and an overall mortality rate of 0.65% (n = 117). CONCLUSION: The description of injuries provides the basis for prevention. The disproportionate number of unintentional injuries (4:1) seen in Honduras' referral hospital calls for further research in: 1) trauma care logistics and emergency systems, 2) mortality and lethality of intentional injuries, and 3) analysis of the types of unintentional injuries. Further research is necessary to evaluate interventions and identify the socioeconomic effects of injuries in the region.

Stroke epidemiology, prevention, and management strategies at a regional level: Latin America and the Caribbean.

Stroke is a major health problem in Latin American and Caribbean countries. In this paper, we review the epidemiology, aetiology, and management of stroke in the region based on a systematic search of articles published in Spanish, Portuguese, and English. Stroke mortality is higher than in developed countries but rates are declining. Population-based studies show variations in incidence of strokes: lower rates of ischaemic stroke and similar rates of intracranial haemorrhages, compared with other regions. A significant proportion of strokes in these populations can be attributed to a few preventable risk factors. Some countries have published national clinical guidelines, although much needs to be done in the organisation of care and rehabilitation. Even though the burden of stroke is high, there is a paucity of information for implementing evidence-based management. The Global Stroke Initiative, the WHO STEPS Stroke surveillance, and WHO-PREMISE projects provide opportunities for surveillance at institutional and community levels.

Developing a neurology training program in Honduras: a joint project of neurologists in Honduras and the World Federation of Neurology.

One of the major barriers to the provision of quality care for patients with neurological disorders in developing countries is a low ratio of neurologists per inhabitants, the World Health Organization recommends one neurologist per 100,000. In 1998 Honduras had one neurologist per 325,000 inhabitants and all the neurologists were trained outside the country. The Education Committee of the World Federation of Neurology (WFN), in collaboration with the Postgraduate Direction of the National Autonomous University of Honduras, the Honduran Neurological Association, and the Honduran Secretary of Health helped establish the country's first Neurology Training Program in 1998. This program was established using a problem- and epidemiological-oriented methodology with oversight by an external WFN review board. By 2006 the program has resulted in a 31% increase in the national neurologist ratio per inhabitant, significantly improved the quality of patient care and promoted research in the neurosciences. The Honduras Neurology Training Program has provided a valuable model for other developing countries with similar needs for neurological care. Based on this Honduras experience, members of the Education Committee of the WFN have established guidelines for neurology training programs in developing countries.

Juvenile myoclonic epilepsy subsyndromes: family studies and long-term follow-up.

The 2001 classification subcommittee of the International League Against Epilepsy (ILAE) proposed to 'group JME, juvenile absence epilepsy, and epilepsy with tonic clonic seizures only under the sole heading of idiopathic generalized epilepsies (IGE) with variable phenotype'. The implication is that juvenile myoclonic epilepsy (JME) does not exist as the sole phenotype of family members and that it should no longer be classified by itself or considered a distinct disease entity. Although recognized as a common form of epilepsy and presumed to be a lifelong trait, a long-term follow-up of JME has not been performed. To address these two issues, we studied 257 prospectively ascertained JME patients and encountered four groups: (i) classic JME (72%), (ii) CAE (childhood absence epilepsy) evolving to JME (18%), (iii) JME with adolescent absence (7%), and (iv) JME with astatic seizures (3%). We examined clinical and EEG phenotypes of family members and assessed clinical course over a mean of 11 +/- 6 years and as long as 52 years. Forty per cent of JME families had JME as their sole clinical phenotype. Amongst relatives of classic JME families, JME was most common (40%) followed by grand mal (GM) only (35%). In contrast, 66% of families with CAE evolving to JME expressed the various phenotypes of IGE in family members. Absence seizures were more common in family members of CAE evolving to JME than in those of classic JME families (P < 0.001). Female preponderance, maternal transmission and poor response to treatment further characterized CAE evolving to JME. Only 7% of those with CAE evolving to JME were seizure-free compared with 58% of those with classic JME (P < 0.001), 56% with JME plus adolescent pyknoleptic absence and 62% with JME plus astatic seizures. Long-term follow-up (1-40 years for classic JME; 5-52 years for CAE evolving to JME, 5-26 years for JME with adolescent absence and 3-18 years for JME with astatic seizures) indicates that all subsyndromes are chronic and perhaps lifelong. Seven chromosome loci, three epilepsy-causing mutations and two genes with single nucleotide polymorphisms (SNPs) associating with JME reported in literature provide further evidence for JME as a distinct group of diseases.

New spectrum of the neurologic consequences of Zika.

Zika virus infection represents a new neuropathological agent with association to a wide spectrum of neurological complications: a) Congenital Zika Syndrome by affecting the neural stem cells of the human fetal brain; b) Guillain-Barré Syndrome by an autoimmune response against peripheral myelin and/or axonal components or probable direct inflammatory reaction; c) Encephalitis/meningoencephalitis and myelitis by a direct viral inflammatory process on the central nervous system; d) Sensory neuropathy by infecting directly the peripheral neurons and causing substantial cell death and pathogenic transcriptional dysregulation; e) Acute Disseminated Encephalomyelitis and optic neuropathy; f) Seizures and Epilepsy and g) childhood arterial ischemic stroke by probable inflammatory reaction and endothelial injury.