Taenia solium Metacestode Factor as Probable Cause of Temporal Lobe Epilepsy.

This article analyzes data from scientific publications (mainly reviews) concerning the link between human neurocysticercosis and epilepsy. Along with data from our own studies on experimental hippocampal sclerosis induced by a Taenia crassiceps metacestode factor in mice, it explores the connection between mechanisms that likely favor the development of epilepsy in cases of human neurocysticercosis. The data from both sources suggest the idea that the T. solium metacestode factor causes hippocampal sclerosis and later epilepsy in humans with neurocysticercosis.

A prospective cohort study to assess the frequency and risk factors for calcification in single lesion parenchymal neurocysticercosis.

BACKGROUND: Calcified neurocysticercosis (NCC) predisposes patients to an enduring state of epilepsy. The predictors for calcification in parenchymal neurocysticercosis are not well defined. METHOD: In this prospective cohort study, consecutive children with single-lesion parenchymal NCC were enrolled and followed up for one year. All patients were investigated with brain 3 T-MRI and electroimmunotransfer blot (EITB). Clinical follow-ups were performed every 3 months. Radiology was repeated at the 6-month and one-year follow-ups. The proportion of calcified lesions at one year and the predictors of calcification were studied. RESULT: During the study period from June 2013 to December 2015, 93 children with single lesion parenchymal NCC were enrolled. At presentation, 90 % of the lesions were in the colloidal stage, and 71 % of the lesions had moderate to severe perilesional oedema. All children had 6 months of follow-up, and 86 (92.5 %) had one year of follow-up. Seizure recurrence was present in 13 (14 %) children. Follow-up radiology at one year showed lesion resolution in 51 (59 %) lesions and calcification in 28 (32.5 %) lesions. Children with calcified lesions during follow-up had a higher odds of seizure recurrences {OR, 95 % CI 3.6(2.3-5.6)}. The presence at baseline of diffusion restriction {OR, 95% CI 2.9 (1.01-8.8)}, scolex or wall calcification in the T2 Star weighted angiography MRI images {OR, 95% CI 3.7 (1.7-8.2)} and >10 mm size of the lesion {OR, 95 % CI 2.4 (1.2-5.01)} predicted lesion calcification. CONCLUSION: Children with calcification of the parenchymal NCC lesions have a higher risk for seizure recurrence during follow-up. The presence of diffusion restriction, calcified nidus in the colloidal nodular stage, and >10 mm size of the lesion at baseline predicted calcification of the lesion during follow-up.

Assessing the burden and spatial distribution of Taenia solium human neurocysticercosis in Ecuador (2013-2017).

BACKGROUND: Estimating the burden of neglected tropical diseases is a valuable tool to support policymakers in the resource allocation for control and elimination of these diseases. Spatial analysis allows to identify the geographical distribution patterns of infectious and parasitic diseases within a country and allows to assess their possible correlation with other health disorders. Despite being neurocysticercosis (NCC) considered as the most important parasitic disease of the nervous system, few efforts have been addressed to assess the real burden of NCC in endemic countries, to date, there are no studies estimating the burden of NCC in South America. In this study we aimed to use the Disability Adjust Life Years (DALY) and spatial indicators as tools to measure the impact of human neurocysticercosis in Ecuador between 2013 and 2017. METHODS: Mortality, morbidity and spatial data from the national agency of statistics were used to estimate the burden of disease of NCC during a five-year period (2013-2017). NCC cases and its two main sequelae, epilepsy and migraine headache, were stratified by sex and age group to calculate the DALY associated to NCC using the DALY package in R. SATSCAN software was used to assess spatial clusters of NCC and its possible neurological sequelae as epilepsy, status epilepticus, migraine and hydrocephalus. PRINCIPAL FINDINGS: The burden of human neurocysticercosis ranged from 56201 [95% CI 29961-89333] to 59612 [95% CI 31854-94689] DALY per year, corresponding to 3.54 to 3.56 DALY per 1000 population. Average yearly incidence rates per 10 000 person-years were 0.23 [95% CI 0.21-0.26] for NCC, 4.89 [95% CI 4.78-5.00] for epilepsy, 0.130 [95% CI 0.11-0.15] for status epilepticus, 0.62 [95% CI 0.58-0.66] for migraine headache, and 1.02 [95% CI 0.98-1.07] for hydrocephalus. Most important significant spatial clusters (p<0.0001) were located in the southern region of the highlands of the country. CONCLUSION/SIGNIFICANCE: This is the first study in South America to calculate estimates for burden of NCC and one of the few using spatial analysis to show the importance of sequelae other than epilepsy that play an important role in the impact of human neurocysticercosis.

Unique Characteristics of Epilepsy Development in Neurocysticercosis.

The parasitic helminth infection neurocysticercosis (NCC) is the most common cause of adult-acquired epilepsy in the world. Despite the serious consequences of epilepsy due to this infection, an in-depth review of the distinct characteristics of epilepsy due to neurocysticercosis has never been conducted. In this review, we evaluate the relationship between NCC and epilepsy and the unique characteristics of epilepsy caused by NCC. We also discuss recent advances in our understanding of NCC-related epilepsy, including the importance of anti-inflammatory therapies, the association between NCC and temporal lobe epilepsy, and the recent discovery of biomarkers of severe epilepsy development in individuals with NCC and seizures.

Host immune responses during Taenia solium Neurocysticercosis infection and treatment.

Taenia solium cysticercosis and taeniasis (TSCT), caused by the tapeworm T. solium, is a foodborne and zoonotic disease classified since 2010 by WHO as a neglected tropical isease. It causes considerable impact on health and economy and is one of the leading causes of acquired epilepsy in most endemic countries of Latin America, Sub-Saharan Africa, and Asia. There is some evidence that the prevalence of TSCT in high-income countries has recently increased, mainly due to immigration from endemic areas. In regions endemic for TSCT, human cysticercosis can manifest clinically as neurocysticercosis (NCC), resulting in epileptic seizures and severe progressive headaches, amongst other neurological signs and/or symptoms. The development of these symptoms results from a complex interplay between anatomical cyst localization, environmental factors, parasite's infective potential, host genetics, and, especially, host immune responses. Treatment of individuals with active NCC (presence of viable cerebral cysts) with anthelmintic drugs together with steroids is usually effective and, in the majority, reduces the number and/or size of cerebral lesions as well as the neurological symptoms. However, in some cases, treatment may profoundly enhance anthelmintic inflammatory responses with ensuing symptoms, which, otherwise, would have remained silent as long as the cysts are viable. This intriguing silencing process is not yet fully understood but may involve active modulation of host responses by cyst-derived immunomodulatory components released directly into the surrounding brain tissue or by the induction of regulatory networks including regulatory T cells (Treg) or regulatory B cells (Breg). These processes might be disturbed once the cysts undergo treatment-induced apoptosis and necrosis or in a coinfection setting such as HIV. Herein, we review the current literature regarding the immunology and pathogenesis of NCC with a highlight on the mobilization of immune cells during human NCC and their interaction with viable and degenerating cysticerci. Moreover, the immunological parameters associated with NCC in people living with HIV/AIDS and treatments are discussed. Eventually, we propose open questions to understand the role of the immune system and its impact in this intriguing host-parasite crosstalk.

Systematic Review and Meta-Analysis of Management Strategies and Outcomes in Adult Spinal Neurocysticercosis.

OBJECTIVE: Spinal involvement in neurocysticercosis is rare and can lead to debilitating injury if not diagnosed and treated early. We aim to provide the reader with a thorough analysis of the best available evidence regarding patient characteristics, optimal treatment modality, and outcomes in cases of spinal neurocysticercosis. METHODS: A systematic review of the literature using PubMed, Google Scholar, and Web of Science electronic databases was made according to the PRISMA guidelines. An illustrative case of intramedullary-cervical spinal disease is also presented for illustrative purposes. RESULTS: A total of 46 reports of 103 patients fitting the screening criteria were identified. Isolated spinal involvement was seen in 46.15% of patients. Most infections (76.92%) had an intradural extramedullary localization, with 43.27% of cases involving >1 spinal cord level. The most common presenting symptoms were motor deficits (77.88%), pain syndromes (64.42%), and sensory deficits (53.85%). Combined surgical resection and pharmacologic therapy was the most frequently used treatment modality (49.04%) and had the highest proportion of patients reporting symptomatic improvement at follow-up (78.43%). Combination therapy had a significantly higher rate of neurologic recovery compared with surgery alone (P = 0.004) or medical treatment (P = 0.035). CONCLUSIONS: Spinal involvement in neurocysticercosis should be considered in patients from or who traveled to endemic areas presenting with ring-enhancing lesions. Combined treatment with surgery followed by cysticidal and steroid medication seems to be superior to surgery or medical treatment in isolation and seems to provide the highest chances of recovery.

Abdominal epilepsia partialis continua in neurocysticercosis.

Epilepsia partialis continua (EPC) of abdominal muscles is a rare entity with variable clinical localization and aetiology. A 25-year-old man presented with sudden onset of intermittent focal myoclonic movements involving the abdominal muscles on the right side exclusively, lasting from 20 minutes to an hour. Brain MRI revealed a ring-enhancing lesion, suggestive of cysticercal granuloma over the left precentral gyrus. The patient fulfilled the revised diagnostic criteria for definitive diagnosis of neurocysticercosis. EEG did not show focal abnormalities during the events. Episodes of EPC were controlled with difficulty using 600 mg oxcarbazepine, 200 mg lacosamide, and 2,000 mg levetiracetam. The patient received antiparasitic therapy with albendazole (15 mg/kg for two weeks) and oral dexamethasone (0.1 mg/kg) for two weeks which was then tapered. The involvement of the primary motor cortex during ictal propagation may account for this curious phenomenon. This is the first report of abdominal EPC in a patient with inflammatory granuloma as a result of neurocysticercosis.

Historical perspective: The British contribution to the understanding of neurocysticercosis.

Neurocysticercosis, or brain infestation with the larval stage of Taenia solium, is the most common risk factor for epilepsy in many endemic regions of the world. Hardly any cases are seen in Western developed countries, including Britain. However, a sizeable number (n = 450) was seen among British soldiers returning from deputation to India, then a British colony, first reported by Col. MacArthur at the Queen Alexandria Military Hospital in 1931. Here, we review the influence of the perceptive observations of British Army medics on the understanding of the parasitic disorder. The majority of these people presented with epilepsy. Among the contributions of the army medics were establishing the diagnosis, initially by histological examination of subcutaneous and muscular infestation, and later by radiography, clarifying the prognosis and the role of medical and surgical treatments and uncovering the close relationship between the larval (cysticercosis) and adult (intestinal tapeworm) stages of T. solium.

Detection of Taenia solium DNA in the Urine of Neurocysticercosis Patients.

Neurocysticercosis (NCC), caused by Taenia solium larvae that reside in the central nervous system, results in serious public health and medical issues in many regions of the world. Current diagnosis of NCC is complex requiring both serology and costly neuroimaging of parasitic cysts in the brain. This diagnostic pipeline can be problematic in resource-constrained settings. There is an unmet need for a highly sensitive and clinically informative diagnostic test to complement the present diagnostic approaches. Here, we report that T. solium-derived cell-free DNA is readily detectable in the urine of patients with the subarachnoid and parenchymal forms of NCC, and discuss the potential utility of this approach in enhancing and refining T. solium diagnostics.

Hippocampal sclerosis induced in mice by a Taenia crassiceps metacestode factor.

An experimental Taenia crassiceps mouse model was used to assess the role of Taenia solium metacestode factor (Fac) in human neurocysticercosis. Intraperitoneal infection with T. crassiceps metacestodes or subcutaneous inoculation with a T. crassiceps metacestode factor (Fac) produced significant impairment of performance (learning) in the Barnes maze and induced bilateral hippocampal sclerosis in mice. Several staining techniques revealed important cell dispersion, extensive apoptosis and cell loss in the dentate gyrus, hilus and CA1-CA3 regions of both hippocampi, as well as intense deterioration of the adjacent cortex. An outstanding disruption of its histoarchitecture in the surrounding tissue of all these regions and apoptosis of the endothelial cells were also observed.

Blood-brain barrier disruption and angiogenesis in a rat model for neurocysticercosis.

Neurocysticercosis (NCC) is a helminth infection affecting the central nervous system caused by the larval stage (cysticercus) of Taenia solium. Since vascular alteration and blood-brain barrier (BBB) disruption contribute to NCC pathology, it is postulated that angiogenesis could contribute to the pathology of this disease. This study used a rat model for NCC and evaluated the expression of two angiogenic factors called vascular endothelial growth factor (VEGF-A) and fibroblast growth factor (FGF2). Also, two markers for BBB disruption, the endothelial barrier antigen and immunoglobulin G, were evaluated using immunohistochemical and immunofluorescence techniques. Brain vasculature changes, BBB disruption, and overexpression of angiogenesis markers surrounding viable cysts were observed. Both VEGF-A and FGF2 were overexpressed in the tissue surrounding the cysticerci, and VEGF-A was overexpressed in astrocytes. Vessels showed decreased immunoreactivity to endothelial barrier antigen marker and an extensive staining for IgG was found in the tissues surrounding the cysts. Additionally, an endothelial cell tube formation assay using human umbilical vein endothelial cells showed that excretory and secretory antigens of T. solium cysticerci induce the formation of these tubes. This in vitro model supports the hypothesis that angiogenesis in NCC might be caused by the parasite itself, as opposed to the host inflammatory responses alone. In conclusion, brain vasculature changes, BBB disruption, and overexpression of angiogenesis markers surrounding viable cysts were observed. This study also demonstrates that cysticerci excretory-secretory processes alone can stimulate angiogenesis.

Clinical topography relationship in patients with parenchymal neurocysticercosis and seizures.

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.

Carotid Taenia solium Oncosphere Infection: A Novel Porcine Neurocysticercosis Model.

Neurocysticercosis (NCC), the infection of the human central nervous system (CNS) with larval cysts of Taenia solium causes widespread neurological morbidity. Animal models are crucial for studying the pathophysiology and treatment of NCC. Some drawbacks of current NCC models include differences in the pathogenesis of the model and wild-type parasite, low rates of infection efficiency and lack of reproducibility. We describe a novel porcine model that recreates infection in the CNS with high efficiency. Activated oncospheres, either in a high (45,000-50,000) or low (10,000) dose were inoculated in the common carotid artery of 12 pigs by ultrasound-guided catheterization. Following oncosphere injection, either a high (30 mL) or low (1-3 mL) volume of saline flush was also administered. Cyst burden in the CNS was evaluated independently according to oncosphere dose and flush volume. Neurocysticercosis was achieved in 8/12 (66.7%) pigs. Cyst burden in the CNS of pigs was higher in the high versus the low oncosphere dose category (median: 4.5; interquartile ranges [IQR]: 1-8 and median: 1; IQR: 0-4, respectively) and in the high versus the low flush volume category (median 5.5; IQR: 1-8 and median: 1; IQR: 0-2, respectively), although not statistically different. All cysts in the CNS were viable, whereas both viable and degenerated cysts were found in the musculature. Carotid injection of activated oncospheres in pigs is effective in reproducing NCC. Oncosphere entry into the CNS by way of vasculature mimics wild-type infection, and provides a useful alternative for future investigations on the pathogenesis and antiparasitic treatment of NCC.

EEG Patterns in Patients With Calcified Neurocysticercosis With or Without Hippocampal Atrophy.

PURPOSE: To assess whether hippocampal atrophy develops in conjunction with clinical or subclinical epileptiform or encephalopathic activity in subjects with neurocysticercosis (NCC). METHODS: Using a population-based and nested case-control study design, scalp EEGs and brain MRIs were performed in Atahualpa residents aged ≥40 years, who have imaging-confirmed NCC (case patients), as well as in age- and sex-matched NCC-free control subjects. RESULTS: Sixty-two case patients and 62 control subjects were included. Encephalopathic EEG patterns were more common in five NCC subjects with epilepsy than in those without a history of seizures. Epileptiform EEG activity was noted in one patient with NCC but in none of the control subjects. This subject's focal epileptiform discharges correlated with the location of calcified cysticerci in the brain parenchyma, and the hippocampus ipsilateral to the epileptiform discharges was more atrophic than the contralateral hippocampus. The degree of hippocampal atrophy in patients with NCC without a history of seizures was significantly greater than in control subjects (P < 0.01) and tended to be even greater in patients with NCC with a history of seizures. CONCLUSIONS: Hippocampal atrophy may not be exclusively related to seizure activity in patients with NCC. Other mechanisms, such as recurrent bouts of inflammation around calcified cysticerci, might explain the association between NCC and hippocampal atrophy.

Clinical and neuroimaging predictors of seizure recurrence in solitary calcified neurocysticercosis: A prospective observational study.

BACKGROUND: Solitary calcified neurocysticercosis is a common cause of seizures in the developing countries. Factors responsible for seizure recurrence in patients with solitary calcified neurocysticercosis are not known. We evaluated the clinical, neuroimaging and biochemical predictors of seizure recurrence. METHODS: This was a prospective observational study. Patients with new-onset seizures and a solitary calcified neurocysticercosis were included. Patients were evaluated clinically; baseline electroencephalography and magnetic resonance imaging of brain were done for all patients.. The patients were followed for 1year. Seizure recurrence was defined as the recurrence of an episode of seizure at least 1 week after the initiation of the anti-epileptic drugs. RESULTS: Fifty-four patients with a mean age of 20.43±7.34years were included. Thirteen patients developed seizure recurrence during the follow-up period. On univariate analysis, status epilepticus at presentation (p=0.025), size of the lesion >10mm (p=0.015), presence of perilesional edema (p<0.001) and scolex (p=0.033) were significantly associated with seizure recurrence. On multivariate analysis, only presence of perilesional edema (p=0.018, odds ratio=12.122, 95% confidence interval 1.521-96.639) was an independent predictor of seizure recurrence. CONCLUSION: Status epilepticus at presentation is associated with an increased risk of seizure recurrence. Neuroimaging features like presence of perilesional edema and scolex can similarly predict seizure recurrence. These neuroimaging features can serve as potential surrogate markers to define therapy in these patients. The findings of our study might be helpful in stratifying patients with a higher risk of seizure recurrence, especially those who may require a more aggressive management.

Headaches More Common among Epilepsy Sufferers with Neurocysticercosis than Other Structural Brain Lesions.

Neurocysticercosis is a leading cause of seizures and epilepsy in the developing world. Cysticercosis is endemic in many regions of Central and South America, sub-Saharan Africa, India, and Asia. Neurocysticercosis is of emerging importance because globalization has increased travel between Hawai'i and disease-endemic areas. Headache and epilepsy are two of the most common complications of neurocysticercosis infection. Currently, it is not known if epilepsy patients with neurocysticercosis are more likely to have headaches than those with other structural brain lesions or those with no structural brain abnormalities. This study was designed to investigate whether epilepsy patients with neurocysticercosis report co-morbid headaches more frequently than those with other or with no structural brain lesions. A retrospective cross-sectional study of all patients treated at a community based neurology clinic for epilepsy during a three-month period was performed. One-hundred sixty patients were included in the analytical study. Co-morbid headaches were more commonly present among those with neurocysticercosis (40%) than those with other structural lesions and those with no structural brain abnormalities (19% and 22%, respectively; P = .031). Headache frequency among those reporting co-morbid headaches did not differ significantly between the groups. Prevalence of co-morbid headaches is greater among epilepsy patients with neurocysticercosis than those with other structural brain lesions or no structural brain abnormality. Epilepsy patients with neurocysticercosis may be especially vulnerable to development of headaches and a thorough headache history should be obtained to help screen for affected individuals.

Migraña y neurocisticercosis, ¿causalidad o casualidad? / Migraine and neurocysticercosis: causality or casualty?

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Disease behaviours of sows naturally infected with Taenia solium in Tanzania.

Neurocysticercosis (NCC) is a disease caused by the zoonotic parasite Taenia solium lodging in the central nervous system. Both humans and pigs can get NCC. The impact of the disease in pigs has so far been little explored. The aim of this study was to describe the effect of NCC on social and feeding behaviours as well as the pattern of activity as indicators of reduced welfare in naturally infected sows. In total 13 T. solium naturally infected and 15 non-infected control sows were videotaped for 2 consecutive weeks using close circuit television cameras at research facilities at Sokoine University of Agriculture, Morogoro, Tanzania. Videos were analysed at the beginning, in the middle and at the end of the 2 week recording period. For each time point, videos were analysed during feeding, while the enrichment was provided, and by recording every half an hour the sows' behaviours performed over the course of a whole day. Sows with NCC spent significantly less time at the feeding trough, especially during the second half of the feeding period. Infected sows were also more passive e.g. lying and standing still significantly more during a whole day period and showed social isolation compared to non-infected control sows by performing behaviours more distant to their nearest neighbour. Results of this study indicated that NCC changed the behaviour of infected sows. The behavioural changes are indicative of decreased welfare. Efforts to reinforce the animal welfare aspect are needed as this has so far been neglected.