Recurrent Ischemic Strokes due to Monogenic COL4A1 Mutation: The First Case Report from Latin America.

Introduction. Monogenic mutations as the cause of recurrent ischemic cerebral small-vessel disease with leukodystrophy are rare. COL4A1 gene mutations are a relatively new etiology of cerebrovascular lesions in young adults; however, any patient has been reported from Latin America. Case Presentation. We presented a Mexican young female with leukodystrophy and recurrent stroke secondary to COL4A1 monogenic mutation. Discussion/Conclusion. COL4A1 monogenic mutations are associated with cerebral small-vessel disease and other systemic manifestations. To date, there is little evidence to justify the treatment and prevention of recurrent strokes in patients with this mutation.

Clinical, Therapeutic, and Prognostic Experience in Patients With Glioblastoma.

BACKGROUND: Glioblastoma (GB) represents the most aggressive type of glioma with a poor prognosis despite the therapies used. As of today, data availability for therapeutic and prognosis experiences is limited. The cornerstone for this study is to create a framework overview of Mexico´s experience throughout 17 years of research. METHODS: Retrospective analysis from 2000 to 2017 including patients with a histological diagnosis of GB was performed. Data were collected from the ABC Medical Center and the Neurology and Neurosurgery National Institute. RESULTS: One hundred and thirty-seven patients were included with a mean age of 54 years. Histological diagnosis was made in all patients, of which 58.1% had a total resection, 31.6% had a partial resection, and 10.3% of them underwent biopsy. In all cases, patients received treatment under the following conditions: 10 patients were treated exclusively with stereotactic radiotherapy (RT). In 55 patients, a combination of RT and TMZ was used, the other 40 patients received RT plus CBP. Eighteen patients RT added to nitrosourea medication and lastly, 14 patients received a combination of RT/TMZ and Bevacizumab, a monoclonal antibody that inhibits the formation of blood vessels (BVZ). The progression-free survival (PFS) and overall survival (OS) were higher in the RT/TMZ/BVZ group (16.5 to 22.9 months) and the RT/TMZ group (11 to 17 months), the prognostic parameters included: Isocitrate dehydrogenase 1 mutation (IDH1), usage of BVZ and TMZ in the PLS and OS, considering as well, age range (<70 years) as a favorable prognostic factor. CONCLUSIONS: GB represents the most frequent intracranial neoplasia. Combined fractionated stereotactic RT added to Temozolomide and Bevacizumab received in our population reports favorable and superior results compared to the ones described in the literature. Further studies are necessary to know the biological behavior of our population.

Linfoma primario del sistema nervioso central: experiencia clínica en un centro neurológico / Primary central nervous system lymphoma: clinical experience in a neurological center

Introducción. El linfoma primario del sistema nervioso central es una variedad de linfoma no Hodgkin que representa el 4-5% de los tumores intracraneales y el 5% de todos los linfomas. Se origina en el encéfalo, los ojos, la leptomeninge y la médula espinal sin evidencia sistémica de actividad linfomatoide; el subtipo de linfoma mayoritariamente es de células de tipo B. Pacientes y métodos. Estudio descriptivo de los pacientes diagnosticados con linfoma cerebral primario que fueron atendidos en centros de tercer nivel en México entre los años 1980 y 2016. Se incluyó a los pacientes que contaran con cribado para búsqueda de linfoma sistémico. Los resultados se analizaron mediante frecuencias simples; en el caso del tiempo libre de enfermedad y supervivencia global, mediante curvas de Kaplan-Meier, y las diferencias entre curvas, mediante log rank. Resultados. En un total de 215 pacientes sólo hubo 74 casos. El 45% fueron mujeres y el 55%, hombres. El 36,7% eran mayores de 60 años. Las manifestaciones clínicas más frecuentes fueron déficit motor (60%) y alteraciones cognitivas (52%). La mayoría recibió alguna forma de quimioterapia (89%). El único factor significativo para respuesta radiológica y pronóstico clínico era el uso combinado de radioquimioterapia (p = 0,04493). Conclusión. El linfoma representa una patología tumoral con alta respuesta clinicorradiológica al tratamiento, aunque la respuesta no es duradera. Es fundamental su identificación temprana y el tratamiento multidisciplinario para el mejor pronóstico de estos pacientes

Introduction. Primary lymphoma of the central nervous system is a variety of non-Hodgkin’s lymphoma that accounts for 4-5% of intracranial tumours and 5% of all lymphomas. It has its origin in the brain, the eyes, the leptomeninges and the spinal cord with no systemic evidence of lymphomatoid activity; the subtype of lymphoma is predominantly of B-type cells. Patients and methods. We conducted a descriptive study of the patients diagnosed with primary brain lymphoma who were attended to at third-level centres in Mexico between the years 1980 and 2016. Patients who had been screened for systemic lymphoma were included. The results were analysed by means of simple frequencies, and disease-free and overall survival time was analysed by Kaplan-Meier curves; the differences among curves were analysed by means of log rank. Results. Of a total of 215 patients, there were only 74 cases. By sex, 45% were females and 55% were males. Regarding age, 36.7% were over 60 years old. The most frequent clinical manifestations were motor loss (60%) and cognitive disorders (52%). Most patients received some form of chemotherapy (89%). The only significant factor for radiological response and clinical prognosis was the combined use of radiochemotherapy (p = 0.04493). Conclusion. Lymphoma is a tumorous condition with a high clinicoradiological response to treatment, although the response is not long-lasting. Its early identification and multidisciplinary management are essential for a more favourable prognosis in these patients

The Comparative Treatment of Intraventricular Chemotherapy by Ommaya Reservoir vs. Lumbar Puncture in Patients With Leptomeningeal Carcinomatosis.

Object: Leptomeningeal Carcinomatosis (LCM) represents a state of systemic malignant disease with poor prognosis. The purpose of this study is to compare overall survival (OS) between intraventricular chemotherapy through Ommaya reservoir (OR) and chemotherapy through lumbar puncture (LP) in LCM. Patients and Methods: Forty adult patients with LCM were included. All patients underwent lumbar puncture and Magnetic resonance imaging (MRI). Thirty patients received chemotherapy through LP and 10 undergone colocation of Ommaya reservoir for intraventricular chemotherapy. Results: The most common symptom was headache (Present in 50%). The cranial nerves most affected were VI and VII. Leptomeningeal enhancement was the most frequent finding in MRI. The OS in the LP group was 4 months and Ommaya group was 9.2 months (p = 0.0006; CI:1.8-3), with statistical differences in favor to Intraventricular treatment. Proportional hazard regression showed that receiving chemotherapy through Ommaya reservoir was a protective factor (Hazard ratio = 0.258, Standard Error = 0.112, p = 0.002 and 95% CI 0.110-0.606). Using KPS as a factor did not affect the hazard ratio of Ommaya reservoir itself. Conclusions: OS was significantly higher in patients with Ommaya reservoir in spite of Karnofsky Performance Status (KPS) previous to chemotherapy. Therefore, intraventricular chemotherapy should be preferred over lumbar puncture chemotherapy administration if there are resources available.

Radioterapia más temozolomida o PCV en pacientes con oligodendroglioma anaplásico con codeleción 1p19q / Radiotherapy plus temozolomide or PCV in patients with anaplastic oligodendroglioma 1p19q codeleted

Introducción. La hipotonía constituye un signo habitual de enfermedad en el neonato. Ahora bien, se trata de un signo inespecífico: puede ser la manifestación inicial de una enfermedad neurológica o multisistémica. Objetivos. Estudiar las principales causas de la hipotonía neonatal y evaluar la exactitud diagnóstica de la anamnesis y la exploración física en el neonato hipotónico. Pacientes y métodos. Estudio retrospectivo de 22 años con recién nacidos afectados por hipotonía e ingresados en la unidad de cuidados intensivos neonatales. A partir de la anamnesis y de los datos recabados durante la exploración física, se hizo una clasificación inicial en condiciones de enmascaramiento del tipo de hipotonía: central, periférica o indeterminada. Resultados. El número de pacientes estudiados ascendió a 91. De ellos, 42 (46,2%) presentaban antecedentes de alteraciones prenatales: polihidramnios (28,6%), retraso del crecimiento intrauterino (21,4%) y presentación de nalgas (19%). Cincuenta y tres (58,2%) habían precisado reanimación al nacer. Los principales síntomas asociados consistieron en disnea (65,9%), dificultades de alimentación (36,5%) y escasez de movimientos espontáneos (22,4%). El diagnóstico definitivo se obtuvo en 64 neonatos (70,3%): el 81,3% mostraba hipotonía central, y el 18,7%, hipotonía periférica. El valor predictivo positivo de la clasificación inicial alcanzó el 97,9% en la hipotonía central y el 66,7% en la hipotonía periférica. La tasa de mortalidad fue del 8,8%, y resultó superior en el grupo de hipotonía periférica (58,3% frente a 1,3%). Conclusiones. La hipotonía neonatal aparece vinculada con una larga lista de trastornos. Una anamnesis minuciosa y una valoración neurológica cuidadosa brindan un alto valor predictivo diagnóstico que debe orientar el estudio etiológico

Introduction. Radiotherapy with procarbazine, lomustine, and vincristine (PCV) improves overall survival in patients with anaplastic oligodendroglioma 1p19q codeleted. Patients and methods. This retrospective analysis investigated outcomes in patients with anaplastic oligodendroglioma 1p19q codeleted compared two different protocols (radiotherapy plus temozolomide or PCV). The primary end points were overall survival and progression-free survival. Secondary endpoint was the radiological response. Results. A total of 48 patients were included. Mean age was 43 years (range: 19-66 years), 26 were male (54.1%). Twenty-one patients received PCV and 27 temozolomide. The baseline characteristics were not difference between the groups. The progression-free survival and overall survival in the PCV group were 7.2 and 10.6 years respectively and temozolomide were 6.1 and 9.2 years, both statistically significant. The radiological response was present in 80.9% in PCV arm and 70.2% in temozolomide arm there was not statistical differences. The multivariate Cox model showed only the significant parameters the use of PCV protocol. The toxicity grade 3 or 4 was present in 42.8% in PCV arm and 11.1% in temozolomide arm. Conclusions. The most common strategy in the Latin America community is the substitution of the PCV or temozolomide. This retrospective study showed superior efficacy of PCV than temozolomide. The Latin American community effort must be made to be able to have the drugs to available for using as a first line of treatment

[Primary Tumors of the Central Nervous System. Clinical Experience at a Third Level Center].

Background: Central nervous system (CNS) tumors are a group of neoplasms that originate from various cells in the CNS. The increasing incidence and prevalence of this type of tumor in developing countries are striking; however, there are few current studies in Latin America including Mexico estimating the impact of these pathological entities on the general population. Objective: The objective of the study was to study the characteristics of primary CNS tumors over a period of 52 years. Methods: A review of records from patients with a histopathological diagnosis of CNS neoplasm over a period of 52 years was conducted at a tertiary-care academic medical center. Patients were grouped by sex, age, and the tumor's anatomical location. Results: A sample of 9615 patients with tumor lesions was obtained; 51% were female, 49% were male, and their mean age was 42 years. The tumors with the highest prevalence were neuroepithelial tumors (38.6%), followed by meningeal tumors (22.8%). Neuroepithelial tumors accounted for 64% in the group of patients under 40 years of age and 56% among those above 40 years of age. The most frequently involved location was supratentorial, in 78.9% of cases. Conclusions: Although retrospective in nature and based on a small sample, this study reports the epidemiology and characteristics of primary brain tumors in the Mexican population.

Neuroprotective effect of dapsone in patients with acute ischemic stroke: a pilot study.

OBJECTIVES: In a previous study of brain ischemia in rats, dapsone (4,4'-diamino-diphenylsulfone) was associated with a neuroprotective effect. As dapsone is safe and relatively free of adverse reactions, we conducted a pilot clinical trial to assess the possibility of using this drug in patients with a cerebral infarction. METHODS: A double-blind, placebo-controlled, pilot clinical trial of dapsone was conducted from January 1999 to January 2000. Thirty patients with a CT or MRI documented ischemic stroke in the territory of the middle cerebral artery were included. Patients with >4 points of the National Institute of Health Stroke Scale (NIHSS) were randomly allocated to receive either a single dose of 200 mg dapsone or placebo. For follow-up, NIHSS on days 0, 2, 7 and 60, modified Rankin scale and Barthel index at day 60 were applied. Adverse reactions were also recorded. The main cut point was considered when a patient obtained a variation of 2 points for modified Rankin scale and 17 points for Barthel index. RESULTS: Fifteen patients received dapsone and 15 received placebo. Twenty-nine were followed up for 60 days and one patient in the treatment group died during follow-up. Favorable scores were achieved for treated patients by all different measures; NIHSS (p=0.032), Barthel (p=0.049) and Rankin scale (RR=0.182, 95% CI: 0.04 and 0.86). Best results were obtained when treatment started within the first 8-10 hours after stroke. No adverse reactions related to medication were reported. DISCUSSION: Dapsone appears as a useful and safe drug for the treatment of stroke patients. Results of this pilot trial are promising and support further research to define the role of dapsone as a neuroprotective drug.