Causes and prognosis of adults experiencing a first seizure in adulthood: A pilot cohort study conducted in five countries in Latin America.

There are limited data on first seizure (FS) among adults in low and middle-income countries. We describe findings from a prospective cohort study involving 180 adults presenting with seizures in emergency departments in five Latin American countries. Overall, 102 participants (56.7%) had acute symptomatic seizures (ASyS) while 78 (43.3%) had unprovoked seizures (UPS). Among patients with ASyS, 55 (53.9%) had structural causes, with stroke (n = 24, 23.5%), tumor (n = 10, 9.8%), and trauma (n = 3, 3%) being the most frequent. Nineteen patients (18.6%) had infectious causes, including four (4%) with meningoencephalitis, three (3%) neurocysticercosis, and two (2%) bacterial meningoencephalitis. Twenty patients (19.6%) had metabolic/toxic evidence, including four (4%) with uremic encephalopathy, two (2%) hyponatremia, and three (3%) acute alcohol intoxication. Immune dysfunction was present in seven (7%) patients and neurodegenerative in two (2%). Among participants with UPS, 45 (57.7%) had unknown etiology, 24 (30.7%) had evidence of structural disorders (remote symptomatic), four (5%) were related to infectious etiology (>7 days before the seizure), and five (6.4%) had genetic causes. During the 3- and 6-month follow-up, 29.8% and 14% of patients with UPS, respectively, experienced seizure recurrence, while 23.9% and 24.5% of patients with ASyS had seizure recurrence. Longer follow-up is necessary to assess seizure recurrence for patients with ASyS after the acute cause is resolved and to determine the 10-year risk of recurrence, which is part of the definition of epilepsy. PLAIN LANGUAGE SUMMARY: We monitored 180 adults who presented with their first seizure in emergency departments across five Latin American countries. Among these patients, 57% had acute symptomatic seizures, with structural causes such as stroke (23%), infection (17%), or tumor (10%) being more prevalent. Among the 43% with unprovoked seizures, 58% showed no identifiable acute cause, while 6.4% were due to genetics. Within 3 months after their initial seizure, 26.6% of individuals experienced a second seizure, with 11.9% continuing to have seizures in Months 3-6. Between Months 3 and 6, an additional 20% of patients encountered a second seizure. Research is needed to better understand the cause and prognosis of these patients to improve outcomes.

Multi-Annual Evaluation of Time Series of Sentinel-1 Interferometric Coherence as a Tool for Crop Monitoring.

Interferometric coherence from SAR data is a tool used in a variety of Earth observation applications. In the context of crop monitoring, vegetation indices are commonly used to describe crop dynamics. The most frequently used vegetation indices based on radar data are constructed using the backscattered intensity at different polarimetric channels. As coherence is sensitive to the changes in the scene caused by vegetation and its evolution, it may potentially be used as an alternative tool in this context. The objective of this work is to evaluate the potential of using Sentinel-1 interferometric coherence for this purpose. The study area is an agricultural region in Sevilla, Spain, mainly covered by 18 different crops. Time series of different backscatter-based radar vegetation indices and the coherence amplitude for both VV and VH channels from Sentinel-1 were compared to the NDVI derived from Sentinel-2 imagery for a 5-year period, from 2017 to 2021. The correlations between the series were studied both during and outside the growing season of the crops. Additionally, the use of the ratio of the two coherences measured at both polarimetric channels was explored. The results show that the coherence is generally well correlated with the NDVI across all seasons. The ratio between coherences at each channel is a potential alternative to the separate channels when the analysis is not restricted to the growing season of the crop, as its year-long temporal evolution more closely resembles that of the NDVI. Coherence and backscatter can be used as complementary sources of information, as backscatter-based indices describe the evolution of certain crops better than coherence.

Common infectious and parasitic diseases as a cause of seizures: geographic distribution and contribution to the burden of epilepsy

This educational review article aims to provide information on the central nervous system (CNS) infectious and parasitic diseases that frequently cause seizures and acquired epilepsy in the developing world. We explain the difficulties in defining acute symptomatic seizures, which are common in patients with meningitis, viral encephalitis, malaria, and neurocysticercosis, most of which are associated with increased mortality and morbidity, including subsequent epilepsy. Geographic location determines the common causes of infectious and parasitic diseases in a particular region. Management issues encompass prompt treatment of acute symptomatic seizures and the underlying CNS infection, correction of associated predisposing factors, and decisions regarding the appropriate choice and duration of antiseizure therapy. Although healthcare provider education, to recognize and diagnose seizures and epilepsy related to these diseases, is a feasible objective to save lives, prevention of CNS infections and infestations is the only definitive way forward to reduce the burden of epilepsy in developing countries.

Neurocysticercosis in Latin America: Current epidemiological situation based on official statistics from four countries.

BACKGROUND: Neurocysticercosis (NC) is one of the major parasitic diseases affecting the central nervous system and is endemic in much of Asia, sub-Saharan Africa, and Latin America. Its epidemiology is difficult to assess, although official registries are available in Brazil, Colombia, Ecuador, and Mexico. METHODOLOGY/PRINCIPAL FINDINGS: Using official statistics, we assessed trends in NC hospitalization rates during 1998-2019 in Brazil and Ecuador, during 2004-2019 in Mexico, and during 2009-2019 in Colombia. We also assessed the trend in NC mortality in Brazil (1998-2019), the trend in hospitalizations for NC in a Mexican tertiary-level hospital (Instituto Nacional de Neurología y Neurocirugía [INNN]; 1995-2019), and in Mexican primary care ambulatory clinics (1995-2019). Associations between NC hospitalization rates and the human development index (HDI) were also examined. In Brazil, Ecuador, and Mexico, statistically significant decreases in NC hospitalization rates were observed. In Mexico, a significant increase in the age of patients at INNN was observed, suggesting a decreasing incidence of recent infection. Conversely, a significant increase in NC hospitalization rate was observed in Colombia. HDI was not significantly associated with NC hospitalization rates when adjusting for time. CONCLUSIONS: The downward trends in NC cases in Brazil, Ecuador, and Mexico are encouraging, especially in the context of the PAHO/WHO plan of action to eliminate neglected tropical diseases from the region. On the other hand, in Colombia, the increased NC hospitalization rate is concerning and needs further evaluation so that the authorities can take specific measures. These results should encourage health authorities in other endemic countries to establish a system of official registries to identify where the need for a control program is most urgent. However, it is also important to remember that NC persists, although less frequently in some Latin American countries, and efforts to achieve its control must continue.

The worldwide epilepsy treatment gap: A systematic review and recommendations for revised definitions - A report from the ILAE Epidemiology Commission.

OBJECTIVE: In order to more appropriately apply and understand the "epilepsy treatment gap" (ETG) concept in current health systems, revised conceptual and operational definitions of ETG are timely and necessary. This article therefore systematically reviews worldwide studies of the ETG, distinguishing high-, middle-, and low-income regions, and provides recommendations for an updated International League Against Epilepsy (ILAE) definition of ETG. METHODS: A systematic review of the ETG was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. The search was conducted from January 1990 to July 2019, in the online databases of Ovid MEDLINE and Embase. Identified abstracts were reviewed in duplicate and data independently extracted using a standard proforma. Data describing treatment gap information including both diagnostic and therapeutic aspects of access to epilepsy treatment were recorded. Descriptive statistics are presented. RESULTS: The treatment gap reported in the 45 distinctive populations represented 33 countries. Treatment gap definitions varied widely. The reported ETGs ranged broadly from 5.6% in Norway to 100% in parts of Tibet, Togo, and Uganda. The wide range of reported ETGs was multifactorial in origin including true differences in the availability and utilization of health care among study populations, variations in operational definitions of the epilepsy treatment gap, and methodological differences in sampling and identifying representative epilepsy cases in populations. Significance and recommendations For the ETG to be a useful metric to compare levels of unmet epilepsy care across different countries and regions, a standardized definition must be adapted, recognizing some of the limitations of the current definitions. Our proposed definition takes into account the lack of effective health care insurance, the diagnostic gap, the therapeutic gap, quality-of-care, and other unmet health care needs."

New understanding about the relationship among neurocysticercosis, seizures, and epilepsy.

Epilepsy and neurocysticercosis are common neurological disorders and are major public health issues that contribute to the world's burden of disease. Acute symptomatic seizures, the main clinical manifestation of parenchymal neurocysticercosis, are caused by the host brain immune-inflammatory process in response to the death or degenerative phase of the parasite. Seizures may recur over the course of several months while the local inflammatory activity lasts. If the seizures recur once the acute process resolves, the patient can be diagnosed as having epilepsy. However, most acute symptomatic seizures secondary to neurocysticercosis do not evolve to epilepsy. Recent prospective studies suggest that the development of epilepsy, while more common than in the general population, is not as common in neurocysticercosis patients as originally suggested by cross-sectional studies. Antiparasitic treatment has been found to hasten the transition of cysts from the active phase to the degenerative phase and is associated with a short-term reduction in focal seizures after treatment. However, antiparasitic treatment has not been found to affect the transition from the degenerative phase to calcification, which is an epileptogenic substrate associated with subsequent epilepsy. In this narrative review, we critically appraise the relationship among neurocysticercosis, seizures, and epilepsy in the context of new developments in the literature.

Extraparenchymal human neurocysticercosis induces autoantibodies against brain tubulin and MOG35-55 in cerebral spinal fluid.

Neurocysticercosis (NC) presents two broad clinical entities: extraparenchymal (EP-NC) and parenchymal (P-NC). Using ELISA methodology, we demonstrate autoantibodies to tubulin and the Major oligodendrocyte glycoprotein (MOG) in the CSF of most, but not all, EP-NC samples. Levels of these autoantibodies were considerably reduced or absent in the P-NC samples. There was a striking correlation between levels of anti-tubulin and anti-MOG, and the significant correlation between the levels of autoantibodies and cellularity in the CSF, suggests that stimulation of the autoantibody response may be a function of cerebral inflammation. A hypothetical model to describe the pathogenesis of EP-NC is presented.

Could Differences in Infection Pressure Be Involved in Cysticercosis Heterogeneity?

The presentation of cysticercosis is very heterogeneous both between and within countries. Several host and parasite factors are involved in this heterogeneity. Differences in the intensity of infection pressure have not been studied thus far. We have compiled data that could demonstrate that differences in infection pressure are involved in the still high prevalence of parenchymal neurocysticercosis and ocular cysticercosis in some countries (which have a stable infection pressure) and in the high proportion of extraparenchymal neurocysticercosis in others (which have had a progressive decrease in infection pressure). Therefore, the distribution of clinicoradiological forms of cysticercosis could be a marker of the intensity of infection pressure and could help to determine in which countries control programs should be a priority.

A multistate joint model for interval-censored event-history data subject to within-unit clustering and informative missingness, with application to neurocysticercosis research.

We propose a multistate joint model to analyze interval-censored event-history data subject to within-unit clustering and nonignorable missing data. The model is motivated by a study of the neurocysticercosis (NC) cyst evolution at the cyst-level, taking into account the multiple cysts phases with intermittent missing data and loss to follow-up, as well as the intra-brain clustering of observations made on a predefined data collection schedule. Of particular interest in this study is the description of the process leading to cyst resolution, and whether this process varies by antiparasitic treatment. The model uses shared random effects to account for within-brain correlation and to explain the hidden heterogeneity governing the missing data mechanism. We developed a likelihood-based method using a Monte Carlo EM algorithm for the inference. The practical utility of the methods is illustrated using data from a randomized controlled trial on the effect of antiparasitic treatment with albendazole on NC cysts among patients from six hospitals in Ecuador. Simulation results demonstrate that the proposed methods perform well in the finite sample and misspecified models that ignore the data complexities could lead to substantial biases.

Anti-brain protein autoantibodies are detectable in extraparenchymal but not parenchymal neurocysticercosis.

Neurocysticercosis (NC) presents a spectrum of clinical manifestations, with two broad clinical entities based on the central nervous system location of the parasite: extraparenchymal (EP-NC) and parenchymal (P-NC). In this work, using quantitative immunoblot methodology, we demonstrate the presence of autoantibodies to brain proteins in CSF from EP-NC, but not P-NC, patients. There was striking correlation between the level of autoantibodies and the levels of the secreted metacestode glycoprotein HP-10, suggesting that the level of stimulation of the autoantibody response may be a function of the number of viable parasites. Nine corresponding proteins autoantigens were provisionally identified by mass spectroscopy.

A longitudinal analysis of albendazole treatment effect on neurocysticercosis cyst evolution using multistate models.

BACKGROUND: In neurocysticercosis, the larval form of the pork tapeworm Taenia solium appears to evolve through three phases-active, degenerative and sometimes calcification-before disappearance. The antihelmintic drug, albendazole, has been shown to hasten the resolution of active cysts in neurocysticercosis. Little is known about the time cysts take to progress through each phase, with or without treatment. METHODS: We reconfigured brain imaging data from patient level to cyst level for 117 patients in a randomized clinical trial of albendazole in which images were taken at baseline, 1, 6, 12 and 24 mo. Applying a multistate model, we modelled the hazard of a cyst evolving to subsequent cyst phases before the next imaging (vs no change). We examined the impact of albendazole treatment overall and by patient and cyst characteristics on the hazard. RESULTS: Albendazole accelerated the evolution from the active to degenerative phase (HR=2.7, 95% CI 1.3 to 6.5) and from the degenerative phase to disappearance (HR=1.9, 95% CI 1.1 to 3.9). Albendazole's impact was stronger for patients who were male, did not have calcified cysts at baseline and who had multiple cysts in different locations. CONCLUSIONS: This research provides a better understanding of where in the cyst trajectory albendazole has the greatest impact.

Exploring the complex associations over time among albendazole treatment, cyst evolution, and seizure outcomes in neurocysticercosis.

OBJECTIVE: To develop a causal model for the occurrence of neurocysticercosis (NC)-related seizures and test hypotheses generated from the model. METHODS: We used data from a randomized controlled trial comparing albendazole with placebo among patients newly diagnosed with NC. Based on our causal model, we explored the associations among albendazole treatment, NC cyst evolution, and seizure outcomes over 24 months of follow-up using generalized linear mixed effect models. RESULTS: We included 153 participants, of whom 51% received albendazole. The association between seizure outcomes and treatment over time demonstrated lack of linearity and heterogeneity, requiring the inclusion of time-treatment interaction terms for valid modeling. Participants in the albendazole group had fewer seizures overall and of partial onset at all time points compared with the placebo group, but the difference increased over the first few months following treatment, then decreased over time. Generalized seizures exhibited a more complex association; those in the albendazole group had fewer seizures compared with those in the placebo group for the first few months after treatment, and then the association reversed and those in the placebo arm had fewer seizures. Adjusting for the number of NC cysts in each phase resulted in an attenuation of the strength of association between albendazole and seizure outcomes, consistent with mediation. Among participants in whom all cysts had disappeared (n = 21), none continued to have seizures. SIGNIFICANCE: Albendazole treatment is associated with a possible reduction in focal seizures in the short term (3-6 months), perhaps by hastening the resolution of the cysts. However, the effect is not discernible over the long term, because most cysts either calcify or resolve completely, regardless of whether treated with albendazole. The stage of evolution of the cysticercus is an important consideration in the evaluation of albendazole effect on seizure outcome.

Monitoring treatment of Taenia solium- neurocysticercosis by detection of circulating antigens: a case report.

BACKGROUND: Parenchymal neurocysticercosis is a frequent cause of seizures in areas endemic for Taenia solium. At present there is scarce data on the evolution of the levels of circulating metacestodal antigen before, during and after treatment with anthelmintic drugs. CASE PRESENTATION: A patient with paucisymptomatic neurocysticercosis (NCC) diagnosed by Ag-ELISA, and confirmed by MRI images, was treated with praziquantel, albendazole and dexamethasone. The level of circulating T. solium antigen was determined weekly. Circulating antigen disappeared from his blood within 14 days after the start of the treatment and correlated with the involution of the cysticerci in the brain shown by imaging. Seventeen years later, the patient has not shown any side effect nor symptoms related to the treatment or to NCC. CONCLUSIONS: If this encouraging finding is confirmed in a larger series of patients, this technique could be used to determine parasitological cure after treatment and might complement or sometimes replace sequential MRI-imaging of the brain.

A modified lateral flow assay, using serum, for the rapid identification of human and bovine cysticercosis in the absence of false positives.

Background: Previously we reported the use of a monoclonal antibody-based (HP10) antigen (Ag) detection lateral flow assay (LFA) for the diagnosis of extraparenchymal neurocysticercosis (EP-NCC). The assay performed well when used with cerebrospinal fluid (CSF) samples but not with their paired serum samples, due to false-positive reactions in some known negative control cases. Methods: Our novel modification involves pretreatment of serum samples using a combination of sodium deoxycholate and dithiothreitol. Results: The modification overcomes the problem of false positives when using negative serum samples from clinically characterized cases of EP-NCC and bovine cysticercosis. In general, there was good agreement between HP10 Ag enzyme-linked immunosorbent assay (ELISA) and the HP10 Ag-LFA, but the HP10 Ag-ELISA was marginally more sensitive than the modified HP10 Ag-LFA. Conclusions: The modified HP10 Ag-LFA provides a field test for the rapid identification of endemic human and bovine cysticercosis.

Comparison of complementary diagnostic tests in cerebrospinal fluid and serum for neurocysticercosis.

The role of immunologic tests in the diagnosis of neurocysticercosis (NC) is controversial and few studies have made comparisons among them. The objective of this study was to compare immunological tests in both serum and cerebrospinal fluid (CSF) for the diagnosis of NC. We conducted a case-control study in Cuenca, Ecuador, enrolling patients with NC (N = 24) and matching them with other neurosurgical patients (N = 18). To detect cysticercal antigen, we used an HP10 antigen assay in serum and CSF ("HP10 Ag -serum -CSF") and a commercial antigen assay in serum (apDia, "ELISA-Ag-serum"), and to detect cysticercal DNA, we used a polymerase chain reaction (PCR) assay in CSF ("PCR-CSF"). Assay sensitivities were: HP10 Ag-serum (41.7%, 95% confidence interval [CI] 22.1-63.4), HP10 Ag-CSF (87.5%, 95% CI: 67.6-97.3), ELISA-Ag-serum (62.5%, 95% CI: 40.6-81.2), and PCR-CSF (79.2%, 95% CI: 57.9-92.9). Sensitivities were higher when limiting to participants with extraparenchymal NC. Specificity was 100% for all assays except ELISA-Ag-serum (72.2%). This preliminary study demonstrated the potential usefulness of the PCR and HP10 Ag assay in CSF, especially for extraparenchymal NC; thus, they could be considered as complementary diagnostic tools when neuroimaging is not conclusive.

New guidelines for the diagnosis and treatment of neurocysticercosis: a difficult proposal for patients in endemic countries.

INTRODUCTION: Recent guidelines for the diagnosis and treatment for neurocysticercosis (NC) from the Infectious Disease Society of America/American Society of Tropical Medicine and Hygiene were developed to be used in the United States and Canada, where only a small fraction of NC cases occur. Areas covered: The paper discusses the strengths and weakness of the proposed guidelines. Expert commentary: Although these new guidelines bring much needed attention to a neglected parasitic disease, some of the recommendations made are based on insufficient and/or inadequate evidence. The authors only recommend one specific immunological assay for use in the diagnosis of NC, when evidence clearly supports other options. The authors strongly recommend dual-anthelminthic for patients with multiple active parenchymal cysts on the basis of one clinical trial that was stopped early. The authors recommend surgical removal of cysts in the fourth ventricle and long-term treatment for subarachnoid NC despite their own admission that there is little evidence to support these recommendations. We propose that clinicians should approach some of the recommendations in the new guidelines with caution and call for the establishment of gold-standard guidelines that can be used and adapted for the diagnosis and treatment of patients with NC worldwide.

The primary prevention of epilepsy: A report of the Prevention Task Force of the International League Against Epilepsy.

Among the causes of epilepsy are several that are currently preventable. In this review, we summarize the public health burden of epilepsy arising from such causes and suggest priorities for primary epilepsy prevention. We conducted a systematic review of published epidemiologic studies of epilepsy of 4 preventable etiologic categories-perinatal insults, traumatic brain injury (TBI), central nervous system (CNS) infection, and stroke. Applying consistent criteria, we assessed the quality of each study and extracted data on measures of risk from those with adequate quality ratings, summarizing findings across studies as medians and interquartile ranges. Among higher-quality population-based studies, the median prevalence of active epilepsy across all ages was 11.1 per 1000 population in lower- and middle-income countries (LMIC) and 7.0 per 1000 in high-income countries (HIC). Perinatal brain insults were the largest attributable fraction of preventable etiologies in children, with median estimated fractions of 17% in LMIC and 15% in HIC. Stroke was the most common preventable etiology among older adults with epilepsy, both in LMIC and in HIC, accounting for half or more of all new onset cases. TBI was the attributed cause in nearly 5% of epilepsy cases in HIC and LMIC. CNS infections were a more common attributed cause in LMIC, accounting for about 5% of all epilepsy cases. Among some rural LMIC communities, the median proportion of epilepsy cases attributable to endemic neurocysticercosis was 34%. A large proportion of the overall public health burden of epilepsy is attributable to preventable causes. The attributable fraction for perinatal causes, infections, TBI, and stroke in sum reaches nearly 25% in both LMIC and HIC. Public health interventions addressing maternal and child health care, immunizations, public sanitation, brain injury prevention, and stroke prevention have the potential to significantly reduce the burden of epilepsy.

The effect of albendazole treatment on non-seizure outcomes in patients with symptomatic neurocysticercosis.

Background: There is little information about the impact of anthelminthic treatment on clinical symptoms other than seizures in neurocysticercosis (NC). We investigated the effect of albendazole on non-seizure symptoms experienced by patients with NC. Methods: Data are from a randomized controlled trial comparing albendazole plus prednisone with placebo plus prednisone for treatment of NC among 173 patients with active or transitional NC cysts and new-onset symptoms. We performed negative binomial regression to examine the number of follow-up visits when a symptom was reported, logistic regression to examine the probability of experiencing the symptom and Cox proportional hazards models to examine the time to first reporting the symptom. Results: Eighty-five percent of patients reported at least one non-seizure symptom at baseline. Those treated with albendazole had significantly lower odds of memory loss and/or confusion during months 1-24 (odds ratio [OR] 0.42, p=0.037) and significantly increased odds of anxiety and/or depression during months 1-12 (OR 1.87, p=0.049). No treatment difference existed in experiencing symptoms in general or in experiencing headaches, limb weakness or gait disturbances, vomiting, nausea and/or stomach pain or visual disturbances over the follow-up period. Conclusions: While the prevalence of non-seizure symptoms was high, albendazole treatment was associated with only two significant differences in the non-seizure symptoms over follow-up. Further research is needed to identify strategies to reduce the long-term symptom burden in patients with NC.