Focal-to-bilateral tonic-clonic seizures and High-grade CMV-infection are poor survival predictors in Tumor-related Epilepsy Adult-type diffuse gliomas-A single-center study and literature review.

Introduction: Previous studies have reported a correlation between a high-grade CMV-infection and an unfavorable prognosis in glioblastoma (GB). Coversely, epilepsy has been associated with a more favorable outcome in GB patients. Despites epilepsy and CMV share similar molecular mechanisms in GB tumoral microenvironment, the correlation between Tumor-Related-Epilepsy (TRE) and CMVinfection remains unexplored. The aim of our study is to examine the correlation between the dregree of CMV infection and seizure types on the survival of TRE Adult-type-diffuse-glioma. To achieve this objective, we conducted a comprehensive literature review to assess our results regarding previous publications. Methods: We conducted a retrospective-observational study on TRE Adult-type-diffuse-gliomas treated at a single center in Mexico from 2010 to 2018. Tumor tissue and cDNA were analyzed by immunochemistry (IHC) for CMV (IE and LA antigens) at the Karolinska Institute in Sweden, and RT-PCR for CMV-gB in Torreon Mexico, respectively. Bivariate analysis (X2-test) was performed to evaluate the association between subtypes of Adult-type-diffuse-glioma (IDH-mut grade 4 astrocytoma vs. IDH-wt glioblastoma) and the following variables: type of hemispheric involvement (mesial vs. neocortical involvement), degree of CMV infection (<25%vs. >25% infected-tumoral cells) and seizure types [Focal awareness, focal impaired awareness, and FBTCS]. Kaplan Meier and Cox analyses were performed to determine the risk, p < 0.05 was considered statistically significant. Results: Sixty patients with TRE Adult type diffuse gliomas were included (80% IDH-wt glioblastoma and 20% IDH-mut grade 4astrocytomas). The mean age was 61.5 SD ± 18.4, and 57% were male. Fifty percent of the patients presented with mesial involvement of the hemysphere. Seizure types included focal awareness (15%), focal impaired awareness (43.3%), and FBTCS (41.7%). Ninety percent of cases were treated with Levetiracetam and 33.3% presented Engel-IA postoperative seizure control. More than 90% of samples were positive for CMV-immunohistochemistry (IHC). However, all cDNA analyzed by RT-PCR return negative results. The median of overall survival (OS) was 15 months. High-grade CMV-IE infection (14 vs. 25 months, p<0.001), mesial involvement (12 vs. 18 months, p<0.001), and FBTCS were associated with worse OS (9 vs.18 months for non-FBTCS). Multivariate analysis demonstrated that high-grade CMV infection (HR = 3.689, p=0.002) and FBTCS (HR=7.007, p<0.001) were independent unfavorable survival factors. Conclusions: CMV induces a proinflammatory tumoral microenvironment that contributes to the developmet of epilepsy. Tumor progression could be associated not only with a higher degree of CMV infection but also to epileptogenesis, resulting in a seizure phenotype chracterized by FBTCS and poor survival outcomes. This study represents the first survival analysis in Latin America to include a representative sample of TRE Adult-type diffuse gliomas considering CMV-infection-degree and distinguishing features (such as FBTCS) that might have potential clinical relevance in this group of patients. Further prospective studies are required to validate these results.

Neurococcidiomycosis in children with hydrocephalus: assessment of functional outcome, quality of life and survival in relation to neuroimaging findings.

PURPOSE: Coccidioidal meningitis (CM) is an uncommon disease frequently misdiagnosed. Neuroimaging and mortality are not considered in detail in previous pediatric CM series. Our objective is to evaluate outcome of pediatric neurococcidiomycosis in relation to neuroimaging findings. METHODS: We performed a prospective, observational, cross-sectional study in children with hydrocephalus and CM treated at Specialties Hospital in Torreon, Mexico (between 2015 and 2020). The outcome was evaluated by Hydrocephalus Outcome Questionnaire (HOQ) and the modified Rankin Scale (mRS). Follow-up was established at the first shunt surgery and survival since CM diagnosis confirmation. Neuroimaging was analyzed in relation to clinical data, outcome and survival. Kaplan-Meier analysis was performed with IBM-SPSS-25. RESULTS: Ten pediatric cases with CM and hydrocephalus were reported. Aged 6-228 months, 60% were female. Mean number of surgeries was 4.3 SD ± 3 (range 1-15). Asymmetric hydrocephalus was the most common neuroimaging finding (70%), followed by cerebral vasculitis (20%) and isolated fourth ventricle (IFV) (20%). The mean HOQ overall score was 0.338 SD ± 0.35. A minimum follow-up of 18 months was reported. Mean survival was 13.9 SD ± 6.15 months (range 3-24). Poor survival was correlated with asymmetric hydrocephalus (p = 0.335), cerebral vasculitis (p = 0.176), IFV (p < 0.001), bacterial superinfection (p = 0.017), lower mRS scores at hospital discharge (p = 0.017) and during follow-up (p = 0.004). The mortality rate was 20%. CONCLUSIONS: We report the largest series in Latin America of pediatric CM and hydrocephalus. Asymmetric hydrocephalus, IFV and cerebral vasculitis are complications that increase mortality and must be early diagnosed for a timely surgical and medical treatment. HOQ and mRS could be alternative scales to evaluate outcome in these patients. After a long follow-up (18 months), survival remained poor after diagnosis confirmation in our series.

Hydrocephalus in Mexican children with Coccidioidal Meningitis: Clinical, serological, and neuroimaging findings.

BACKGROUND: Coccidioidal meningitis (CM) is a fungal infectious disease that rarely affects children. Even in endemic areas, coccidiomycosis rarely affects the pediatric population. However, 40% of affected children develop hydrocephalus. Here, we describe the clinical, serological, and neuroimaging findings in a series of Mexican children admitted to our neurosurgical service with hydrocephalus and subsequently diagnosed with CM. METHODS: We report a prospective series of pediatric patients with hydrocephalus secondary to CM in an endemic area at the north of Mexico. Our report includes children with CM who were hospitalized from 2015 to 2019 in a regional hospital in Torreón, Coahuila. Clinical evolution was monitored for 1 year after hospital discharge. RESULTS: Our series include five children with CM (2-17-years-old, three female), who were hospitalized for hydrocephalus and developed intracranial hypertension. The most frequent neuroimaging findings were leptomeningeal enhancement (5/5) and basal arachnoiditis (4/5), followed by asymmetric hydrocephalus (3/5), abnormalities in fourth ventricle morphology (3/5), and cerebral vasculitis (2/5). CM was diagnosed by positive serology or pathology studies. All children were initially managed with fluconazole and a shunt was placed for management of hydrocephalus. Four patients recovered without permanent neurological deficits and one subject developed persistent vegetative state. One year after hospital discharge, none of the subjects died. CONCLUSION: This series contributes to the limited number of pediatric CM cases reported in the literature, and describes neuroimaging findings in the pediatric population. The cases here presented show that the identification of Coccidioides as causal agent in pediatric meningitis is crucial for targeted treatment and can affect dramatically neurological prognosis. Furthermore, our report stresses that even in endemic areas pediatric coccidiomycosis represents a diagnostic challenge, which is further exacerbated by the limited availability of resources in these regions. Therefore, a positive immunoglobulin G by enzyme immunoassay is enough for diagnosis of CM in endemic areas without access to CF.