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Previous studies have described the association of onchocerciasis (caused by Onchocerca volvulus) with epilepsy, including nodding syndrome, although a clear etiological link is still missing. Cases are found in different African countries (Tanzania, South Sudan, Uganda, Democratic Republic of the Congo, Central African Republic and Cameroon). In our study we investigated immunological parameters (cytokine, chemokine, immunoglobulin levels) in individuals from the Mahenge area, Tanzania, presenting with either epilepsy or nodding syndrome with or without O. volvulus infection and compared them to O. volvulus negative individuals from the same endemic area lacking neurological disorders. Additionally, cell differentiation was performed using blood smears and systemic levels of neurodegeneration markers, leiomodin-1 and N-acetyltyramine-O, β-glucuronide (NATOG) were determined. Our findings revealed that cytokines, most chemokines and neurodegeneration markers were comparable between both groups presenting with epilepsy or nodding syndrome. However, we observed elevated eosinophil percentages within the O. volvulus positive epilepsy/nodding syndrome patients accompanied with increased eosinophilic cationic protein (ECP) and antigen-specific IgG levels in comparison to those without an O. volvulus infection. Furthermore, highest levels of NATOG were found in O. volvulus positive nodding syndrome patients. These findings highlight that the detection of distinct biomarkers might be useful for a differential diagnosis of epilepsy and nodding syndrome in O. volvulus endemic areas. Trial-registration:NCT03653975. Author summary: A lot of epidemiological studies suggest that an infection with the filarial nematode Onchocerca volvulus is a risk factor for a certain form of epilepsy which includes the nodding syndrome. The seizures occur suddenly in previously healthy children between the ages of 3 and 18 years and the disease is an important public health problem in onchocerciasis-endemic regions with inadequate or lacking onchocerciasis elimination programmes. So far, no exact pathophysiological mechanisms were detected that shed light on how the parasite can trigger the seizures, although many factors have been investigated. However, most studies lack an accurate determination of an active/chronic O. volvulus infection; rather, they rely on the presence of circulating antibodies, which is only evidence of previous exposure to the parasite (and therefore positive in most people living in endemic areas. Within our study, we included participants from the Mahenge area, Tanzania, who were displaying epilepsy/nodding syndrome in absence or presence of a PCR-determined O. volvulus infection. We could show that the group of O. volvulus infected patients displayed higher levels of eosinophils, antigen-specific immunoglobulin levels as well as increased levels of a worm-related metabolic product (NATOG), which might be used as a potential diagnostic biomarker of the disease in future studies. [ABSTRACT FROM AUTHOR]

Background: Neurocysticercosis (NCC), a zoonotic disease caused by the pork tapeworm T. solium, represents one of the most common causes of secondary epilepsy but remains often undiagnosed due to lack of awareness and diagnostic facilities. Methodology: We pooled data from four cross-sectional studies on epilepsy and NCC in eastern Africa. Study sites were in Uganda, Malawi and in Tanzania (Dar es Salaam and Haydom). The study in Uganda and Malawi were community-based, the two studies in Tanzania were hospital-based. The same questionnaire was used for assessment of clinical characteristics of patients with epilepsy. Computed tomography (CT) scans and serological testing were performed in order to diagnose NCC. Results: Overall, 1,179 people with epilepsy were included in our analysis. Of those, 941 PWE underwent CT scanning and were pooled for NCC analysis. Seventy patients were diagnosed with NCC, but NCC prevalence differed considerably between sites ranging from 2.0% (95%CI 0.4% to 3.6%) in Dar es Salaam to 17.5% (95%CI 12.4% to 22.6%) in Haydom. NCC prevalence did not show any association with sex but increased with age and was higher in rural than urban settings. In addition, being a farmer, non-Muslim, eating pork and living with pigs close by was associated with a higher NCC prevalence. PWE with NCC experienced their first epileptic seizure around 3 years later in life compared to PWE without NCC and their epileptic seizures seemed to be better controlled (p<0.001). There was no difference between focal onset seizures and focal signs on neurological examination in both groups (p = 0.49 and p = 0.92, respectively). The rT24H-EITB had a sensitivity for the detection of NCC of 70% (95% confidence interval [CI] 51 to 84%), the LLGP of 76% (95%CI 58 to 89%) and the antigen ELISA of 36% (95% CI 20 to 55%). Conclusions: NCC is prevalent among PWE in eastern Africa, although it may not be as common as previously stated. Demographic characteristics of PWE with NCC differed from those without NCC, but semiological characteristics and results on neurological examination did not differ compared to PWE without NCC. Interestingly, seizures seemed to be less frequent in PWE with NCC. Being aware of those differences and similarities may help triaging PWE for neuroimaging in order to establish a diagnosis of NCC. Author summary: Neurocysticercosis is a neglected zoonotic disease caused by the pork tapeworm Taenia solium. Patients with neurocysticercosis show a wide range of symptoms, from asymptomatic to severely affected by epileptic seizures, progressive headache or focal neurological deficits. Epileptic seizures are particularly common and up to 30% of people with epilepsy have neurocysticercosis in areas endemic for Taenia solium. The disease is often undiagnosed in Africa because of a lack of diagnostic opportunities (serological tests and neuroimaging). Furthermore, symptoms are too unspecific to diagnose patients solely based on clinical characteristics. Moreover, radiological features of neurocysticercosis differ between continents and have not been described yet for African populations. In this study, for the first time, we describe radiological but also clinical features of patients with epilepsy and neurocysticercosis in eastern Africa. We found that in Tanzania, Malawi and Uganda, neurocysticercosis is common in people with epilepsy although less common than previously reported. Also, most patients with neurocysticercosis have multiple parenchymal lesions and clinical features of people with epilepsy and neurocysticercosis do not differ substantially from people with epilepsy without neurocysticercosis. [ABSTRACT FROM AUTHOR]

Purpose: Enteral nutrition (EN) often fails to achieve nutritional goals in neurocritical care patients. We sought to investigate the safety and utility of supplemental parenteral nutrition (PN) in subarachnoid hemorrhage (SAH) patients. Materials and methods: Data of 70 consecutive patients with non-traumatic SAH admitted to the neurological intensive care unit of a tertiary referral center were prospectively collected and retrospectively analyzed. We targeted the provision of 20–25 kilocalories per kilogram bodyweight per day (kcal/kg/d) by enteral nutrition. Supplemental PN was given when this target could not be reached. Nutritional data were analyzed for up to 14 days of ICU stay. Hospital complications were tested for associations with impaired enteral feeding. The amounts of EN and PN were tested for associations with the level of protein delivery and functional outcome. Repeated measurements within subjects were handled utilizing generalized estimating equations. Results: Forty (27 women and 13 men) of 70 screened patients were eligible for the analysis. Median age was 61 (IQR 49–71) years, 8 patients (20%) died in the hospital. Thirty-six patients (90%) received PN for a median duration of 8 (IQR 4–12) days. The provision of 20 kcal/kg by EN on at least 1 day of ICU stay was only achieved in 24 patients (60%). Hydrocephalus (p = 0.020), pneumonia (p = 0.037) and sepsis (p = 0.013) were associated with impaired enteral feeding. Neither the amount nor the duration of PN administration was associated with an increased risk of severe complications or poor outcome. Supplemental PN was associated with significantly increased protein delivery (p<0.001). In patients with sepsis or pneumonia, there was an association between higher protein delivery and good functional outcome (p<0.001 and p = 0.031), but not in the overall cohort (p = 0.08). Conclusions: Enteral feeding was insufficient to achieve nutritional goals in subarachnoid hemorrhage patients. Supplemental PN was safe and associated with increased protein delivery. A higher protein supply was associated with good functional outcome in patients who developed sepsis or pneumonia. [ABSTRACT FROM AUTHOR]

Nakalanga syndrome is a condition that was described in Uganda and various other African countries decades ago. Its features include growth retardation, physical deformities, endocrine dysfunction, mental impairment, and epilepsy, amongst others. Its cause remains obscure. Nodding syndrome is a neurological disorder with some features in common with Nakalanga syndrome, which has been described mainly in Uganda, South Sudan, and Tanzania. It has been considered an encephalopathy affecting children who, besides head nodding attacks, can also present with stunted growth, delayed puberty, and mental impairment, amongst other symptoms. Despite active research over the last years on the pathogenesis of Nodding syndrome, to date, no convincing single cause of Nodding syndrome has been reported. In this review, by means of a thorough literature search, we compare features of both disorders. We conclude that Nakalanga and Nodding syndromes are closely related and may represent the same condition. Our findings may provide new directions in research on the cause underlying this neurological disorder. [ABSTRACT FROM AUTHOR]

Dominik Stelzle was supported by the Federal Ministry of Education and Research, Germany, Grant 01KA2112B, within the Cysticercosis Network of Sub-Saharan Africa (CYSTINET-Africa). Correction: Characteristics of people with epilepsy and Neurocysticercosis in three eastern African countries-A pooled analysis It should read as follows: This study was funded by the German Research Foundation (DFG) [https://www.dfg.de/] within the research grant (WI 3427/1-1) "Neurocysticercosis in sub-Saharan Africa" (ASW) and by the Bill and Melinda Gates Foundation [https://www.gatesfoundation.org/] (ASW, WH) within the research grant (1017886) "Integrated Control of Cysticercosis in sub-Saharan Africa". [Extracted from the article]

Background: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in vascular remodeling, (neuro)inflammation, blood-brain barrier breakdown and neuronal apoptosis. Proinflammatory mechanisms are suggested to play an important role during early brain injury and cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). This study aimed to analyze MMP-3, MMP-9, TIMP-1 and TIMP-3 in patients with SAH and their respective association with cerebral vasospasm (CVS). Methods: Blood samples were collected in 20 SAH patients on days 1 to 7, 9, 11, 13 and 15 and 20 healthy age and gender matched volunteers. Serum MMPs and TIMPs were analyzed using enzyme-linked immunosorbent assay. Doppler sonographic CVS was defined as a mean blood flow velocity above 120 cm/sec in the middle cerebral artery. When discharged from hospital and at 6 month follow-up neurological outcome was evaluated using the Glasgow Outcome Score and the modified Rankin Scale. Results: MMP-9 was higher in SAH patients compared to healthy controls (p<0.001). Patients with CVS (n = 11) had elevated MMP-9 serum levels compared to patients without CVS (n = 9, p<0.05). Higher MMP-9 was observed in the presence of cerebral ischemia associated with cerebral vasospasm (p<0.05). TIMP-1 was increased in patients with SAH on day 4 (p<0.05). There was an imbalance of the MMP-9/TIMP-1 ratio in favor of MMP-9 in SAH patients, in particular those with CVS (p<0.001). MMP-3 and TIMP-3 were significantly lower in SAH patients throughout day 4 and day 7, respectively (p<0.05). We did not find an association between MMP-, TIMP levels and neurological outcome after 6 months. Conclusions: MMP-3 and -9 are differentially regulated in SAH patients with both enzymes showing peak levels correlating with the development of CVS. The inhibitors TIMP-1 and -3 were low during the acute phase after SAH and increased later on which might suggest a preponderance of pro-inflammatory mechanisms. [ABSTRACT FROM AUTHOR]

Background: Neurocysticercosis (NCC) is the most common cause of acquired epilepsy in Taenia solium endemic areas, primarily situated in low-income countries. Diagnosis is largely based upon the "Del Brutto diagnostic criteria" using the definitive/probable/no NCC diagnosis approach. Neuroimaging and specific T. solium cysticercosis antibody detection results are at the mainstay of this diagnosis, while antigen detection in serum has never been included. This study aimed at evaluating the addition of antigen detection as a major diagnostic criterion, especially in areas where neuroimaging is absent. Methods: The B158/B60 monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA) for the detection of circulating cysticercus antigen was carried out retrospectively on serum samples collected during a hospital-based study from 83 people with epilepsy (PWE) in an endemic area. Results: The addition of antigen results as a major criterion allowed the correct diagnosis of definitive NCC in 10 out of 17 patients as opposed to 0/17 without antigen results in the absence of neuroimaging. A sensitivity of 100% and a specificity of 84% were determined for the diagnosis of active NCC using antigen ELISA. While the use of a higher cutoff improves the specificity of the test to 96%, it decreases its sensitivity to 83%. Conclusions: In areas where neuroimaging is absent, NCC diagnosis according to the existing criteria is problematic. Taking into account its limitations for diagnosis of inactive NCC, antigen detection can be of added value for diagnosing NCC in PWE by supporting diagnostic and treatment decisions. Therefore, we recommend a revision of the "Del Brutto diagnostic criteria" for use in resource poor areas and suggest the inclusion of serum antigen detection as a major criterion. Author Summary: Neurocysticercosis is a parasitic infection of the central nervous system and a common cause of epilepsy in Taenia solium cysticercosis endemic countries. According to the current diagnostic criteria proposed by Del Brutto and colleagues, the diagnosis of neurocysticercosis is mainly based on neuroimaging and detection of specific antibodies. Unfortunately, especially neuroimaging is rarely available in endemic countries. The authors analyzed the value of a test that detects antigens that are excreted by living cysts in people with epilepsy. Different diagnostic scenarios and cut-off values are discussed with the respective sensitivity and specificity of the test. When using the antigen-detecting test, considerably more people with epilepsy were diagnosed correctly with neurocysticercosis. There are some concerns about possible false positive results in other cases. The test was useful for the detection of people with living cysts (active neurocysticercosis), who need further diagnostic evaluation and specific treatment. The authors recommend the addition of this test in the diagnostic criteria for neurocysticercosis. [ABSTRACT FROM AUTHOR]

Cerebral malaria (CM) is associated with a high rate of transient or persistent neurological sequelae. Nogo-A, a protein that is highly expressed in the endoplasmic reticulum (ER) of the mammalian central nervous system (CNS), is involved in neuronal regeneration and synaptic plasticity in the injured CNS. The current study investigates the role of Nogo-A in the course of experimental CM. C57BL/6J mice were infected with Plasmodium berghei ANKA blood stages. Brain homogenates of mice with different clinical severity levels of CM, infected animals without CM and control animals were analyzed for Nogo-A upregulation by Western blotting and immunohistochemistry. Brain regions with Nogo-A upregulation were evaluated by transmission electron microscopy. Densitometric analysis of Western blots yielded a statistically significant upregulation of Nogo-A in mice showing moderate to severe CM. The number of neurons and oligodendrocytes positive for Nogo-A did not differ significantly between the studied groups. However, mice with severe CM showed a significantly higher number of cells with intense Nogo-A staining in the brain stem. In this region ultrastructural alterations of the ER were regularly observed. Nogo-A is upregulated during the early course of experimental CM. In the brain stem of severely affected animals increased Nogo-A expression and ultrastructural changes of the ER were observed. These data indicate a role of Nogo-A in neuronal stress response during experimental CM. [ABSTRACT FROM AUTHOR]

Neurocysticercosis (NCC) is a major cause of epilepsy in regions where pigs are free-ranging and hygiene is poor. Pork production is expected to increase in the next decade in sub-Saharan Africa, hence NCC will likely become more prevalent. In this study, people with epilepsy (PWE, n = 212) were followed up 28.6 months after diagnosis of epilepsy. CT scans were performed, and serum and cerebrospinal fluid (CSF) of selected PWE were analysed. We compared the demographic data, clinical characteristics, and associated risk factors of PWE with and without NCC. PWE with NCC (n = 35) were more likely to be older at first seizure (24.3 vs. 16.3 years, p = 0.097), consumed more pork (97.1% vs. 73.6%, p = 0.001), and were more often a member of the Iraqw tribe (94.3% vs. 67.8%, p = 0.005) than PWE without NCC (n = 177). PWE and NCC who were compliant with anti-epileptic medications had a significantly higher reduction of seizures (98.6% vs. 89.2%, p = 0.046). Other characteristics such as gender, seizure frequency, compliance, past medical history, close contact with pigs, use of latrines and family history of seizures did not differ significantly between the two groups. The number of NCC lesions and active NCC lesions were significantly associated with a positive antibody result. The electroimmunotransfer blot, developed by the Centers for Disease Control and Prevention, was more sensitive than a commercial western blot, especially in PWE and cerebral calcifications. This is the first study to systematically compare the clinical characteristics of PWE due to NCC or other causes and to explore the utility of two different antibody tests for diagnosis of NCC in sub-Saharan Africa. Author Summary: Neurocysticercosis, a preventable and treatable disease, is one of the main causes of epilepsy in low income countries. In these countries, the diagnosis of epilepsy is often based on clinical presentation and interviews as neuroimaging is rarely available. It is crucial to distinguish people with epilepsy due to neurocysticercosis from other people with epilepsy by clinical symptoms and/or serology, because the former warrants a specific approach both in terms of diagnosis and treatment. The authors compared the demographic and clinical data of the two groups and found that people with epilepsy due to neurocysticercosis are older, more likely to consume pork, and respond better to anti-epileptic treatment. Additionally, the authors compared two antibody tests for cysticercosis with computed tomography images, which showed a higher sensitivity of the CDC electroimmunotransfer blot compared to a commercial western blot. The number of neurocysticercosis lesions was significantly associated with a positive antibody result in both tests. In summary, this research describes clinical characteristics of people with epilepsy and neurocysticercosis and assesses the usefulness of two immunoblots in those patients. This has implications not only for the diagnosis of neurocysticercosis in low income countries, but also for future epidemiological research. [ABSTRACT FROM AUTHOR]