Matthew L. Romo

The relationship between neurocysticercosis and epilepsy: an endless debate

Neurocysticercosis (NC), or cerebral infection with Taenia solium, is an important public health problem worldwide. Among the neurological sequelae of NC, seizures have been described as the most common symptom. Acute symptomatic seizures often result from degeneration of a viable cyst; however, not all of these patients with acute or provoked seizures will develop epilepsy (i.e., recurrent unprovoked seizures). Because of the high prevalence of epilepsy and NC, a causal, as well as incidental relationship between the two may exist. The epileptogenicity of calcified cysts as well as the potential association between NC and hippocampal sclerosis necessitates future research. Antihelminthic treatment of NC results in disappearance of viable cysts in about one-third of patients with parenchymal disease, but a reduction in seizure recurrence has not been demonstrated in randomized controlled trials. Prevention is critical to reduce the burden of seizure and epilepsy related to NC.

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

BACKGROUND Randomized controlled trials have found an inconsistent effect of anthelmintic treatment on long-term seizure outcomes in neurocysticercosis. The objective of this study was to further explore the effect of albendazole treatment on long-term seizure outcomes and to determine if there is evidence for a differential effect by seizure type. METHODS In this trial, 178 patients with active or transitional neurocysticercosis cysts and new-onset symptoms were randomized to 8 days of treatment with albendazole (n=88) or placebo (n=90), both with prednisone, and followed for 24 months. We used negative binomial regression and logistic regression models to determine the effect of albendazole on the number of seizures and probability of recurrent or new-onset seizures, respectively, over follow-up. RESULTS Treatment with albendazole was associated with a reduction in the number of seizures during 24 months of follow-up, but this was only significant for generalized seizures during months 1-12 (unadjusted rate ratio [RR] 0.19; 95% CI: 0.04-0.91) and months 1-24 (unadjusted RR 0.06; 95% CI: 0.01-0.57). We did not detect a significant effect of albendazole on reducing the number of focal seizures or on the probability of having a seizure, regardless of seizure type or time period. CONCLUSIONS Albendazole treatment may be associated with some symptomatic improvement; however, this association seems to be specific to generalized seizures. Future research is needed to identify strategies to better reduce long-term seizure burden in patients with neurocysticercosis.

Routine drug and food interactions during antihelminthic treatment of neurocysticercosis: a reason for the variable efficacy of albendazole and praziquantel?

Neurocysticercosis (NC) or infection of the central nervous system with Taenia solium larvae is a leading cause of preventable seizures and epilepsy in endemic regions across the globe. Albendazole and praziquantel are commonly used antihelminthic agents to treat NC; however, viable cysts persist in the majority of patients, putting them at risk for future seizures and other neurological complications. Because of their pharmacokinetic profiles, albendazole and praziquantel have the potential to interact with many different drugs. During antihelminthic treatment, antiepileptic drugs and corticosteroids are commonly co‐administered to manage seizures and cerebral edema; however, the most commonly used agents from these drug classes are known to significantly alter plasma concentrations of albendazole and praziquantel. The overarching issue with drug interactions during the treatment of NC is whether or not they have clinical relevance, as the plasma concentrations of albendazole and praziquantel have not been directly linked with eradication of viable cysts. Future studies should attempt to evaluate the validity of a causal relationship between antihelminthic plasma concentrations and outcomes so that drug interactions can be better understood and managed and so that treatment can be optimized.

Parasitic diseases of the central nervous system: lessons for clinicians and policy makers.

ABSTRACT Parasitic diseases of the central nervous system are associated with high mortality and morbidity, especially in resource-limited settings. The burden of these diseases is amplified as survivors are often left with neurologic sequelae affecting mobility, sensory organs, and cognitive functions, as well as seizures/epilepsy. These diseases inflict suffering by causing lifelong disabilities, reducing economic productivity, and causing social stigma. The complexity of parasitic life cycles and geographic specificities, as well as overlapping clinical manifestations in the host reflecting the diverse pathogenesis of parasites, can present diagnostic challenges. We herein provide an overview of these parasitic diseases and summarize clinical aspects, diagnosis, therapeutic strategies and recent milestones, and aspects related to prevention and control.

Validity of a PCR assay in CSF for the diagnosis of neurocysticercosis

Objective: To prospectively evaluate the validity of a PCR assay in CSF for the diagnosis of neurocysticercosis (NC). Methods: We conducted a multicenter, prospective case-control study, recruiting participants from 5 hospitals in Cuenca, Ecuador, from January 2015 to February 2016. Cases fulfilled validated diagnostic criteria for NC. For each case, a neurosurgical patient who did not fulfill the diagnostic criteria for NC was selected as a control. CT and MRI, as well as a CSF sample, were collected from both cases and controls. The diagnostic criteria to identify cases were used as a reference standard. Results: Overall, 36 case and 36 control participants were enrolled. PCR had a sensitivity of 72.2% (95% confidence interval [CI] 54.8%–85.8%) and a specificity of 100.0% (95% CI 90.3%–100.0%). For parenchymal NC, PCR had a sensitivity of 42.9% (95% CI 17.7%–71.1%), and for extraparenchymal NC, PCR had a sensitivity of 90.9% (95% CI 70.8%–98.9%). Conclusions: This study demonstrated the usefulness of this PCR assay in CSF for the diagnosis of NC. PCR may be particularly helpful for diagnosing extraparenchymal NC when neuroimaging techniques have failed. Classification of evidence: This study provides Class III evidence that CSF PCR can accurately identify patients with extraparenchymal NC.

Pharmacologic androgen deprivation and cardiovascular disease risk factors: a systematic review

Pharmacologic androgen deprivation therapy (ADT) is widely used to treat prostate cancer. Observational studies suggest ADT is associated with cardiovascular disease and its risk factors; however, such studies may be subject to bias. Our objective was to evaluate the effect of ADT on cardiovascular disease risk factors using data from randomized controlled trials (RCTs).

Multifactorial basis of epilepsy in patients with neurocysticercosis

To the Editors: Nash et al. have renewed the theory to consider neurocysticercosis (NC) as a human model of epileptogenesis. This theory, which was proposed 25 years ago, has not prospered so far, despite the advances of medicine, because, among other reasons, NC is still a neglected disease. At the moment, the updated approach proposed by Nash et al. seems appropriate; however, there are some additional issues that should be considered. NC could not only be a human model of epileptogenesis, but also a model to identify biomarkers for the propensity to generate seizures (i.e., ictogenesis), which might predict the development of an epilepsy condition. In this context, it is critical to differentiate between acute symptomatic seizures and recurrent unprovoked seizures (i.e., epilepsy). It is well known that acute seizures are the most common symptom in NC patients, but most do not develop into epilepsy. Nash et al. describe a “mechanism of chronic epilepsy from acute seizures occurs as degenerating cyst develops into a calcification. . .” which is consistent with previous proposals. However, it is also important to remember that there are many clinical inconsistencies in the relationship between epilepsy and NC lesions. Parasite location may be remote from the potential epileptogenic region, and there is no correlation between the burden of lesions and the severity of the epilepsy. Patients with severe refractory seizures may have only one calcified lesion, and patients with multiple cysts or calcifications may have no seizures. Furthermore, calcified lesions are frequently encountered on computed tomography (CT) scans of asymptomatic individuals, which questions their epileptogenicity. The empirical observation of experienced neurologists from endemic countries is that NC and refractory epilepsy rarely coexist. This is consistent with a study of 512 patients in Brazil, which concluded that NC is an uncommon cause of intractable epilepsy and may represent only a coexistent pathology. The multifactorial concept proposed by Engel et al. based on the triad of epileptogenic abnormality, seizure threshold, and precipitating factors, could be applied for the development of seizures/epilepsy in patients with NC. In the context of NC, the epileptogenic abnormality relates to the number and localization of parasites, as well as their evolutionary phases over time (Fig. 1A). Seizures occur when these three factors interact. NC epileptogenic mechanisms result in a reduction of seizures threshold until seizures occur (i.e., ictogenesis) hastened by the host immunologic response with a cascade of events or precipitating factors, such as blood–brain barrier breakdown, brain inflammation, and reactive astrogliosis (Fig. 1B). Some patients may also have a genetic predisposition to maintain a low seizure threshold leading to the chronic epileptic process (i.e., epileptogenesis). Considering the large amount of asymptomatic cases of NC in the population (probably >50% of infected patients) and that few people with NC develop epilepsy, it is possible that most patients do not have a genetic predisposition to maintain a low seizure threshold and acute seizures do not evolve to epilepsy (Fig. 1C). Measures of potential biomarkers of NC (e.g., quantitative magnetic resonance imaging, qualitative electroencephalography [EEG], serial magnetization transfer imaging, substance P, Toll-like receptor polymorphism), taken at different points of the evolution of the cyst phases, might have a predictive value for development of seizures or epilepsy. Current information about epileptogenicity of NC is scarce and based on anecdotal cases, providing weak evidence for causal inference. Prospective cohort studies are needed to assess the association of different evolutionary phases of the parasite, potential genetic predisposition, and the role of precipitating factors in the development of seizures and epilepsy, along with the development of relevant animal models.

Characterizing Adults Receiving Primary Medical Care in New York City: Implications for Using Electronic Health Records for Chronic Disease Surveillance

Introduction Electronic health records (EHRs) from primary care providers can be used for chronic disease surveillance; however, EHR-based prevalence estimates may be biased toward people who seek care. This study sought to describe the characteristics of an in-care population and compare them with those of a not-in-care population to inform interpretation of EHR data. Methods We used data from the 2013–2014 New York City Health and Nutrition Examination Survey (NYC HANES), considered the gold standard for estimating disease prevalence, and the 2013 Community Health Survey, and classified participants as in care or not in care, on the basis of their report of seeing a health care provider in the previous year. We used χ2 tests to compare the distribution of demographic characteristics, health care coverage and access, and chronic conditions between the 2 populations. Results According to the Community Health Survey, approximately 4.1 million (71.7%) adults aged 20 or older had seen a health care provider in the previous year; according to NYC HANES, approximately 4.7 million (75.1%) had. In both surveys, the in-care population was more likely to be older, female, non-Hispanic, and insured compared with the not-in-care population. The in-care population from the NYC HANES also had a higher prevalence of diabetes (16.7% vs 6.9%; P < .001), hypercholesterolemia (35.7% vs 22.3%; P < .001), and hypertension (35.5% vs 26.4%; P < .001) than the not-in-care population. Conclusion Systematic differences between in-care and not-in-care populations warrant caution in using primary care data to generalize to the population at large. Future efforts to use primary care data for chronic disease surveillance need to consider the intended purpose of data collected in these systems as well as the characteristics of the population using primary care.

Ethics in global health outreach: three key considerations for pharmacists.

The objective of this article is to explore three key ethical tenets that pharmacists should consider prior to participating in global health outreach.

HIV testing preferences among long distance truck drivers in Kenya: a discrete choice experiment

ABSTRACT Providing HIV testing services to truck drivers in Africa is crucial but has proven challenging. The introduction of HIV self-testing promises to provide expanded service delivery options for clients, potentially increasing demand for services and expanding coverage – especially important for high-risk and difficult-to-reach populations. This study examines the preferences regarding HIV testing service delivery models, among long distance truck drivers to identify testing services that would appeal to this population. Using a discrete choice experiment, this study examines the drivers of choice regarding HIV counselling and testing among 305 truck drivers recruited from two roadside wellness clinics along major trucking routes in Kenya. Participants made trade-offs between characteristics of HIV testing service delivery models by making hypothetical choices in a series of paired HIV testing scenarios. Conditional logit models were used to identify the HIV testing characteristics driving the selection of preferred scenarios, as well as determine whether preferences interact with individual characteristics – especially HIV testing history. Participants preferred free, provider-administered HIV testing at a roadside clinic, using a finger-prick test, with in-person counselling, undertaken in the shortest possible time. The strongest driver of choice was the cost of the test. Those who had never tested previously preferred oral testing and telephonic counselling, while those who were not regular testers favoured clinic based – over self-testing. The results of this study indicate that for the majority of participants – most of whom had tested before – the existing services offered at roadside clinics were the preferred service delivery model. The introduction of oral self-testing increases the options available to truck drivers and may even improve testing uptake for some, especially among those who have never tested before. However, these findings suggest the impact on HIV testing uptake of introducing oral self-testing may be limited in this population.