Spatial and Ecological Factors Modulate the Incidence of Anti-NMDAR Encephalitis-A Systematic Review.

Anti-NMDAR encephalitis has been associated with multiple antigenic triggers (i.e., ovarian teratomas, prodromal viral infections) but whether geographic, climatic, and environmental factors might influence disease risk has not been explored yet. We performed a systematic review and a meta-analysis of all published papers reporting the incidence of anti-NMDAR encephalitis in a definite country or region. We performed several multivariate spatial autocorrelation analyses to analyze the spatial variations in the incidence of anti-NMDA encephalitis depending on its geographical localization and temperature. Finally, we performed seasonal analyses in two original datasets from France and Greece and assessed the impact of temperature using an exposure-lag-response model in the French dataset. The reported incidence of anti-NMDAR encephalitis varied considerably among studies and countries, being higher in Oceania and South America (0.2 and 0.16 per 100,000 persons-year, respectively) compared to Europe and North America (0.06 per 100,000 persons-year) (p < 0.01). Different regression models confirmed a strong negative correlation with latitude (Pearson's R = -0.88, p < 0.00001), with higher incidence in southern hemisphere countries far from the equator. Seasonal analyses showed a peak of cases during warm months. Exposure-lag-response models confirmed a positive correlation between extreme hot temperatures and the incidence of anti-NMDAR encephalitis in France (p = 0.03). Temperature analyses showed a significant association with higher mean temperatures and positive correlation with higher ultraviolet exposure worldwide. This study provides the first evidence that geographic and climatic factors including latitude, mean annual temperature, and ultraviolet exposure, might modify disease risk.

Temozolomide Plus Bevacizumab in Elderly Patients with Newly Diagnosed Glioblastoma and Poor Performance Status: An ANOCEF Phase II Trial (ATAG).

LESSONS LEARNED: Results suggest that the combination of bevacizumab plus temozolomide is active in terms of response rate, survival, performance, quality of life, and cognition in elderly patients with glioblastoma multiforme with poor performance status.Whether this combination is superior to temozolomide alone remains to be demonstrated by a randomized study. BACKGROUND: The optimal treatment of glioblastoma multiforme (GBM) in patients aged ≥70 years with a Karnofsky performance status (KPS) <70 is not established. This clinical trial evaluated the efficacy and safety of upfront temozolomide (TMZ) and bevacizumab (Bev) in patients aged ≥70 years and a KPS <70. MATERIALS AND METHODS: Patients aged ≥70 years with a KPS <70 and biopsy-proven GBM were eligible for this multicenter, prospective, nonrandomized, phase II trial of older patients with impaired performance status. Treatment consisted of TMZ administered at 130-150 mg/m2 per day for 5 days every 4 weeks plus Bev administered at 10 mg/kg every 2 weeks. RESULTS: The trial included 66 patients (median age of 76 years; median KPS of 60). The median overall survival (OS) was 23.9 weeks (95% confidence interval [CI], 19-27.6), and the median progression-free survival (PFS) was 15.3 weeks (95% CI, 12.9-19.3). Twenty-two (33%) patients became transiently capable of self-care (i.e., KPS >70). Cognition and quality of life significantly improved over time during treatment. Grade ≥3 hematological adverse events occurred in 13 (20%) patients, high blood pressure in 16 (24%), venous thromboembolism in 3 (4.5%), cerebral hemorrhage in 2 (3%), and intestinal perforation in 2 (3%). CONCLUSION: This study suggests that TMZ + Bev treatment is active in elderly patients with GBM with low KPS and has an acceptable tolerance level.

Uso de anticonvulsivantes en epilepsia secundaria a gliomas en adultos: serie de casos / Antiepileptic drugs use in adults with glioma - associated epilepsy: case series

RESUMEN INTRODUCCIÓN: La mayoría de gliomas difusos de bajo grado y un gran porcentaje de gliomas de alto grado desarrollan epilepsia en la historia natural de la enfermedad. Los anticonvulsivantes permiten el control de la epilepsia en la gran mayoría de pacientes con gliomas. Sin embargo, la politerapia anticonvulsivante es necesaria en aproximadamente 1/3 de casos, lo que puede potenciar la incidencia de efectos adversos neurocognitivos y afectar la calidad de vida. OBJETIVO: Establecer la frecuencia de epilepsia y el uso de anticonvulsivantes en un grupo de pacientes adultos con gliomas difusos que acuden a la consulta externa del Instituto Neurológico de Colombia. PACIENTES Y MÉTODOS: Estudio tipo serie de casos descriptivo retrospectivo que incluyó pacientes adultos con diagnóstico de glioma difuso con confirmación histológica atendidos en consulta externa entre agosto 2014 y enero 2016. Las características epidemiológicas, clínicas, radiológicas y terapéuticas fueron analizadas mediante estadística descriptiva y se utilizó el test exacto de Fisher para comparación de variables. RESULTADOS: Se incluyeron 42 pacientes (edad promedio 41 años, rango 15-71) incluyendo 15 gliomas grado II (7 astrocitoma, 4 oligodendroglioma, 2 gliomas mixtos, 2 gliomas no especificados) y 27 gliomas de alto grado (14 glioblastoma, 8 astrocitoma III, 3 oligodendroglioma, 2 gliomas mixtos). Durante la evolución de la enfermedad 36 (85 %) pacientes presentaron epilepsia sintomática. Las convulsiones fueron la manifestación clínica inicial en 28 (66 %) de casos siendo significativamente más frecuente en gliomas de bajo grado (93 % bajo grado vs. 51 % alto grado, p=0,07). El uso de monoterapia anticonvulsivante fue reportada en 23 casos (63 %). En el grupo de gliomas de bajo grado, solo 40 % respondieron a terapia con 1 solo medicamento, requiriendo politerapia más frecuentemente que los gliomas de alto grado (9 de 15 bajo grado vs. 4 de 21 alto grado, p=0,01) mientras que en gliomas de alto grado fue tratada con monoterapia en 80 %. CONCLUSIÓN: La epilepsia fue más frecuente en gliomas de bajo grado y este grupo requirió politerapia en la mayoría de casos comparado a gliomas de alto grado. Es necesario optimizar la terapia anticonvulsivante en pacientes con gliomas identificando los grupos de riesgo de pobre respuesta y evitando el uso de politerapia en aquellos con alta probabilidad de buena respuesta a la monoterapia.

SUMMARY INTRODUCTION: Seizures are frequent as initial symptom in low grade gliomas and it occurs commonly in follow-up in high grade glioma. Antiepileptic drugs achieve seizure control in most of cases. However, in aproximately 1/3 of cases multiple antiepileptic drugs are needed which could increase neurocognitive side effects and impair quality of life. Objectives: To establish frequency of seizures and antiepileptic drugs use in a group of patients with diffuse brain gliomas at the outpatient neurology department. PATIENTS AND METHODS: Retrospective, descriptive case series of adult patients with brain diffuse glioma confirmed by histological criteria. Clinical data was analised by descriptive statistics and Fisher's test was used to compare variables. RESULTS: We included 42 patients (age average 41 years, range 15-71) 15 grade II gliomas (7 astrocitoma, 4 oligodendroglioma, 2 mixed gliomas, 2 gliomas not specified) and 27 high-grade gliomas (14 glioblastoma, 8 astrocitoma III, 3 oligodendroglioma, 2 mixed gliomas). During follow-up 36 (85%) of patients had seizures and it was the initial symptom in 28 (66%) of cases significantly more frequent in low-grade gliomas (93% low grade vs 51 high grade, p=0.07). Overall, monotherapy with antiepileptic drugs were possible in 23 cases (63%). For low-grade glioma only 40% of patients responded to monotherapy whereas it was successful in 80% of high-grade gliomas (p=0.01). CONCLUSION: Seizures were more frequent in low-grade gliomas and often it required a combined antiepileptic drugs regimen to achieve epilepsy control compared to high-grade gliomas.

Relationships Between Dose Intensity, Toxicity, and Outcome in Patients with Oligodendroglial Tumors Treated with the PCV Regimen.

BACKGROUND/AIM: The drug combination of procarbazine, lomustine (CCNU) and vincristine (PCV) has been associated with efficacy in oligodendroglial gliomas (OG) when added to radiotherapy as the first line of treatment, despite the important toxicity of this treatment schedule. The aim of the present study was to analyze the tolerance, feasibility and impact of the dose intensity of the PCV regimen on outcome for patients with OG. PATIENTS AND METHODS: We retrospectively reviewed all patients with OG receiving PCV (CCNU=110 mg/m(2)) who were referred to our two Institutions. The total dose and dose adaptation, cycle delay, dose intensity, toxicity and discontinuation of CCNU were analyzed. Impacts on the outcome were evaluated. RESULTS: Between 2007 and 2011, 89 patients received PCV. PCV was administered at relapse in 73% of patients. Only 37% completed six cycles, 13.4% discontinued PCV because of toxicity, the other patients discontinued due to tumor progression. Cycle delay and dose reduction were observed for 62% and 70% patients, respectively. Grade 3 and 4 toxicities were observed in 38% and 8% patients, respectively. Among patients whose disease did not progress under the PCV regimen, discontinuation due to toxicity was significantly correlated to poor progression-free survival (PFS: p=0.023, hazard ratio=2.354) and poor overall survival (OS: p=0.021, hazard ratio=5.093). A factor that negatively impacted PFS was the absence of CCNU dose adaptation (p=0.001), while OS was negatively impacted by the absence of cycle delay (p=0.049) and grade 3/4 toxicities (p=0.045). CONCLUSION: Despite the efficacy of the PCV regimen, significant toxicity is associated with this schedule, which appears to impact its feasibility and efficacy. The optimal PCV schedule with the appropriate CCNU dose-intensity adaptation should be redefined taking into account this finding.

Dural Arteriovenous Fistula Mimicking a Brainstem Glioma.

BACKGROUND: Brainstem intracranial dural arteriovenous fistulas are extremely rare and can mimic a glioma at the time of presentation. CASE: We report a patient with an infiltrating brainstem lesion that finally revealed an intracranial dural arteriovenous fistula, with full neurological improvement after embolization. CONCLUSION: A careful radiological study looking for dilated vessels around the brainstem is necessary in the workup of an infiltrating brainstem lesion, in order to rule out intracranial dural arteriovenous fistula.

Significant heterogeneity in the geographical distribution of diffuse grade II/III gliomas in France.

Diffuse WHO grade II and III gliomas (DGII/IIIG) are rare tumors, with few specific epidemiological studies. We aimed at describing the geographical distribution of a homogeneous series of histologically confirmed DGII/IIIG, over a four-year period (2006-2009), at a national level. The methodology is based on a multidisciplinary national network already established by the French Brain Tumor DataBase and data collected directly from every neuropathology department. Personal home addresses were collected for confirmed cases. For each region, the incidence of DGII/IIIG was analyzed and standardized on the age and sex distribution of the French population. The number of patients with newly diagnosed, histologically confirmed DGII/IIIG was 4,790. The overall crude rate was 19.4/10(6). To enable international comparisons, standardized rates were calculated as follows: 19.8/10(6), 18.8/10(6) and 16.0/10(6) (reference population, Europe, US and world, respectively). The geographical distribution by region showed significant differences, with higher incidence rates in Northeast and central parts of France. This work is the first studying the geographical distribution of a pure series of DGII/IIIG at a national level. It demonstrates significant heterogeneity in the distribution, and raises the question of the role of environmental and/or genetic risk(s) factor(s) for DGII/IIIG.

Temozolomide after radiotherapy in recurrent "low grade" diffuse brainstem glioma in adults.

Diffuse brainstem glioma is a rare disease in adults. Radiotherapy (RT) is usually considered to be the standard treatment. However, the role of chemotherapy in treating relapses after RT is unclear, and this study aimed to assess the use of temozolomide (TMZ) in this situation. We conducted a retrospective analysis of patients from our database with "low grade" adult diffuse infiltrating brainstem glioma who received TMZ at relapse after failing RT. The patients were diagnosed by histology or MRI criteria compatible with a low-grade glioma. The tumors were localized in the pons, medulla oblongata or midbrain, excluding supratentorial or infratentorial tumors that had infiltrated the brainstem secondarily. The patients' clinical and radiological responses were assessed, and their progression free survival (PFS) and overall survival (OS) time were estimated. Fifteen adult patients (median age 34 years) fulfilled the inclusion criteria. Histological analysis was available in 5 cases and showed grade II oligodendroglioma (2 cases), grade II oligoastrocytoma (2 cases), and grade II astrocytoma (1 case). Ten patients were selected by MRI criteria only. All patients received RT as initial treatment and had a median PFS of 34.2 months (95 % CI 24.1-44.2). The median KPS at the time of relapse was 80. TMZ was administered orally at 150-200 mg/m(2) for 5 days, every 28 days. Clinical improvement after TMZ was observed in 9 cases (60 %), whereas radiological assessment detected responses in 6/15 cases, including 4 partial and 2 minor responses. The estimated median PFS after TMZ was 9.5 months (95 % CI 7.9-11), and the median OS was 14.4 months (95 % CI 10.5-18.2). Grade 3 thrombopenia was observed in 26 % of cases. TMZ could be useful after RT failure in adult patients with recurrent diffuse "low grade" brainstem glioma.

Molecular analysis of diffuse intrinsic brainstem gliomas in adults.

Diffuse intrinsic brainstem gliomas (DIBG) account for 1-2 % of adult gliomas. Their biological characteristics are scarcely understood and whether DIBG are biologically different from supratentorial gliomas remains to be established. We analyzed 17 DIBG samples for IDH1 R132H, alpha internexin, p53, and Ki67 expression, and, in a subset with sufficient DNA amount, for IDH1 and histone H3 mutational status, genomic profiling and MGMT promoter methylation status. A series of 738 adult supratentorial gliomas was used for comparison. Median age at diagnosis was 41 years (range 18.9-65.3 years). Median overall survival was 48.7 months (57 months for low-grade vs. 16 months for high-grade gliomas, p < 0.01). IDH1 sequencing revealed two mutations (IDH1 (R132G) , IDH1 (R132C) ) out of 7 DIBG whereas the R132H IDH1 enzyme was detected in 1/17 DIBG, suggesting that IDH1 mutations are mostly non R132H in DIBG (2/2), in contrast to supratentorial gliomas (31/313; p = 0.01). Mutations in histone genes H3F3A (encoding H3.3) and HIST1H3B (encoding H3.1) were found in 3/8 (37.5 %) of the DIBG (two H3F3A (K27M) and one HIST1H3B (K27M) ) versus 6/205 (2.9 %) of the supratentorial high-grade gliomas (four H3F3A (G34R) and two H3F3A (K27M) ) (p = 0.002). The CGH array showed a higher frequency of chromosome arm 1q gain, 9q gain and 11q loss in DIBG compared to the supratentorial high-grade gliomas, which had a less frequent chromosome 7 gain, and a less frequent chromosome 10 loss. No EGFR amplification was found. These data suggest that adult DIBG differ from adult supratentorial gliomas. In particular, histone genes (H3F3A (K27M) , HIST1H3B (K27M) ) mutations are frequent in adult DIBG whereas IDH1 (R132H) mutations are rare.

Contrast enhancement in 1p/19q-codeleted anaplastic oligodendrogliomas is associated with 9p loss, genomic instability, and angiogenic gene expression.

BACKGROUND: The aim of this study was to correlate MRI features and molecular characteristics in anaplastic oligodendrogliomas (AOs). METHODS: The MRI characteristics of 50 AO patients enrolled in the French national network for high-grade oligodendroglial tumors were analyzed. The genomic profiles and IDH mutational statuses were assessed using high-resolution single-nucleotide polymorphism arrays and direct sequencing, respectively. The gene expression profiles of 25 1p/19q-codeleted AOs were studied on Affymetrix expression arrays. RESULTS: Most of the cases were frontal lobe contrast-enhanced tumors (52%), but the radiological presentations of these cases were heterogeneous, ranging from low-grade glioma-like aspects (26%) to glioblastoma-like aspects (22%). The 1p/19q codeletion (n = 39) was associated with locations in the frontal lobe (P = .001), with heterogeneous intratumoral signal intensities (P = .003) and with no or nonmeasurable contrast enhancements (P = .01). The IDH wild-type AOs (n = 7) more frequently displayed ringlike contrast enhancements (P = .03) and were more frequently located outside of the frontal lobe (P = .01). However, no specific imaging pattern could be identified for the 1p/19q-codeleted AO or the IDH-mutated AO. Within the 1p/19q-codeleted AO, the contrast enhancement was associated with larger tumor volumes (P = .001), chromosome 9p loss and CDKN2A loss (P = .006), genomic instability (P = .03), and angiogenesis-related gene expression (P < .001), particularly for vascular endothelial growth factor A and angiopoietin 2. CONCLUSION: In AOs, the 1p/19q codeletion and the IDH mutation are associated with preferential (but not with specific) imaging characteristics. Within 1p/19q-codeleted AO, imaging heterogeneity is related to additional molecular alterations, especially chromosome 9p loss, which is associated with contrast enhancement and larger tumor volume.

Response assessment in recurrent glioblastoma treated with irinotecan-bevacizumab: comparative analysis of the Macdonald, RECIST, RANO, and RECIST + F criteria.

Traditionally, the most widely used criteria for response assessment in glioblastoma have been Macdonald and the Response Evaluation Criteria In Solid Tumors (RECIST). Recently, new criteria addressing contrast enhancement and fluid-attenuated inversion recovery (FLAIR)/T2 hyperintensity have been defined (the Response Assessment in Neuro-Oncology criteria) to better evaluate the effect of antiangiogenic therapy. Whether FLAIR/T2 imaging could also be helpful to refine RECIST criteria remains unresolved. This study proposed the RECIST + F criteria and compared the 4 methods (Macdonald, RECIST, RANO, and RECIST + F) to determine their agreement in identifying response and progression of recurrent glioblastomas to irinotecan-bevacizumab. Patients with recurrent glioblastoma treated with second-line irinotecan-bevacizumab were eligible. Clinical status, corticosteroid dose, and 1-dimensional and 2-dimensional measurements of tumor contrast enhancement and FLAIR hyperintensity were retrospectively assessed. Response and progression were determined according to each set of criteria. Seventy-eight patients were included. Response rates ranged from 34.2% with RECIST + F to 44.7% with Macdonald criteria. Agreement among the 4 methods in determining response and type of progression was high (kappa statistic > 0.75). One-third of patients exhibited nonenhancing progression with stable or improved contrast enhancement. Median progression-free survival was predicted by RECIST, at 13.6 weeks; RECIST + F, 12.3; Macdonald, 12.7; and RANO, 11.7 (P = .840). Intra- and interobserver correlations were high for both contrast enhancement and FLAIR hyperintensity measurements. There was a strong concordance among the different methods in determining response and progression to irinotecan-bevacizumab. Criteria integrating FLAIR hyperintensity tended, however, to reduce response rates and progression-free survival compared with criteria considering only contrast enhancement. The 1-dimensional approach appeared to be as valid as the 2-dimensional approach.

Adult brainstem gliomas.

Brainstem gliomas are uncommon in adults and account for only 1%-2% of intracranial gliomas. They represent a heterogeneous group of tumors that differ from those found in their pediatric counterparts. In adults, a low-grade phenotype predominates, which is a feature that likely explains their better prognosis compared to that in children. Because biopsies are rarely performed, classifications based on the radiological aspect of magnetic resonance imaging results have been proposed to establish treatment strategies and to determine outcomes: (a) diffuse intrinsic low-grade, (b) enhancing malignant glioma, (c) focal tectal gliomas, and (d) exophytic gliomas. Despite significant advances in neuroradiology techniques, a purely radiological classification remains imperfect in the absence of a histological diagnosis. Whereas a biopsy may often be reasonably avoided in the diffuse nonenhancing forms, obtaining histological proof seems necessary in many contrast-enhanced brainstem lesions because of the wide variety of differential diagnoses in adults. Conventional radiotherapy is the standard treatment for diffuse intrinsic low-grade brainstem gliomas in adults (the median survival is 5 years). In malignant brainstem gliomas, radiotherapy is the standard treatment. However, the possible benefit of combined radiotherapy and chemotherapy (temozolomide or other agents) has not been thoroughly evaluated in adults. The role of anti-angiogenic therapies in brainstem gliomas remains to be defined. A better understanding of the biology of these tumors is of primary importance for identifying homogeneous subgroups and for improving therapy options and outcomes.

[Anti-NMDA receptor paraneoplastic encephalitis: complete recovery after ovarian teratoma removal]. / Encefalitis paraneoplásica por anticuerpos contra el receptor de NMDA. Remisión completa después de la resección de un teratoma ovárico.

INTRODUCTION: A paraneoplastic syndrome characterized by neuropsychiatric symptoms, involuntary movements and seizures has been recently associated with antibodies targeting NMDA (N-methyl-D-aspartate) receptor in patients with an ovarian teratoma. Severe neurological impairment is frequent and treatment in the intensive care unit is often required because of ventilatory failure and life-threatening autonomic instability. Tumor removal is curative in many cases and neurological improvement is demonstrated shortly after surgery. CASE REPORT: Here we report on a patient with paraneoplastic encephalitis manifested by unconsciousness and coreo-athetosic movements related to NMDA receptor antibodies associated with an immature ovarian teratoma grade III. She made a complete recovery after oophorectomy, intravenous immunoglobulin and corticosteroids. CONCLUSIONS: Treatment of paraneoplastic syndromes is based on specific therapy for underlying tumor associated to immunomodulators. As in this case, anti-NMDA encephalitis may significantly improve after tumor removal and intra-venous immunoglobuline.

Epilepsia refractaria / Refractory epilepsy

La epilepsia refractaria o farmacorresistente es una condición frecuente en nuestra práctica neurológica cotidiana. Se considera que aproximadamente el 30% de pacientes con epilepsia de cualquier tipo van a persistircon crisis epilépticas a pesar de la terapia farmacológica. La definición de epilepsia farmacorresistente ha sido motivo de controversia entre los grupos de investigación a lo largo de las últimas décadas. La nueva propuesta de la Liga Internacional contra la Epilepsia (ILAE) para definir la falla del tratamiento médico y facilitar la selección de pacientes candidatos a procedimientos quirúrgicos es un gran avance hacia un mejor tratamiento para esta población. El objetivo del presente artículo es dar pautas que le permitan al neurólogo clínico identificar a los pacientes con epilepsia refractaria y dirigir los estudios diagnósticos que permitan seleccionar aquellos candidatos a un procedimiento quirúrgico curativo o paliativo. El éxito de dichos procedimientos está condicionado por la precisión diagnóstica en el protocolo prequirúrgico, donde el neurólogo desempeña un papel fundamental.

Drug resistant epilepsy is a very frequent condition seen at our clinical practice. Despite of antiepileptic drugsabout 30% of patients suffering from epilepsy will continue having seizures even if they are in combined schemes. The definition of pharmacoresistant epilepsy is subject of current controversy between researchgroups. However, the International League against Epilepsy (ILAE) has published recently a new consensusproposal defining drug resistant epilepsy. This new definition permits to select the group of patients that couldbe candidates to surgery. The aim of this review is to guide neurologists on the selection of patients sufferingfrom drug resistant epilepsy and to describe the main diagnosis procedures needs as preoperative assessment.

Gliomas del adulto: acercamiento al diagnóstico y tratamiento / Gliomas in adults: diagnostic and therapeutical

Los tumores cerebrales de origen glial son las neoplasias primarias más frecuentes del sistema nervioso central. Los avances en neuroradiología y la resonancia magnética permiten diagnosticar precozmente y ofrecer la posibilidad de un tratamiento oportuno. A pesar de su sombrío pronóstico, los nuevos tratamientos asociando cirugía, radioterapia y quimioterapia tienen un impacto positivo en la supervivencia y calidad de vida. Para glioblastomas la quimioterapia con temozolamida es una indicación terapéutica de primera línea asociándose a cirugía y radioterapia. Para los astrocitomas anaplásicos, oligodendrogliomas anaplásicos y gliomas mixtos la quimioterapia está indicada en segundo lugar después de la cirugía y radioterapia. A pesar de su grado de malignidad estas entidades guardan una quimiosensibilidad relativa. Las alteraciones genéticas de los gliomas de grado III establecen factores de buena respuesta a la quimioterapia. La deleción 1p19q en los oligodendriogliomas y gliomas mixtos, y la ausencia de expresión del gen methylguanin-methyltransferasa en glioblastomas se relacionan con un mejor pronóstico. En gliomas de grado II la indicación de quimioterapia como alternativa a la radioterapia en lesiones inoperables es un tema de actual investigación. La temozolamida produce respuestas clínicas a largo plazo mejorando la calidad de vida y retardando la progresión tumoral. El bevacizumab es un anticuerpo monoclonal dirigido contra el receptor del factor de crecimiento endotelial que ha demostrado efectividad en los glioblastomas recurrentes. Actualmente constituye una de las terapias más prometedoras para el tratamiento de los gliomas de alto grado, los estudios clínicos en curso intentan demostrar su efectividad como primera línea de tratamiento. El presente artículo hace una revisión de la clasificación, las características radiológicas y los tratamientos usados para el manejo de pacientes adultos con gliomas.

Gliomas are the most common primary malignancies of central nervous system. Progress in neuroradiology with use of magnetic resonance imaging allows establishing diagnosis in earlier when an opportune treatment can be perfformed. Even though prognosis is poor for this group of patients, evidence has showed that treatments with surgery, radiotherapy and chemotherapy have a significant impact in quality of life and survival. Chemotherapy by temozolomide is indicated in the treatment of glioblastoma associated to surgery and radiotherapy. In anaplastic astrocytomas, anaplastic oligodendrogliomas and oligoastrocytomas chemotherapy is a second line therapy if tumor progression after surgery and radiotherapy has occurred. Although their high malignancy grades these tumors have a relative sensibility to chemotherapy. Molecular genetics of grade III gliomas allow establishing good prognosis factors of response to chemotherapy. The 1p19q deletion in oligodendroglioma and oligoastrocitomas and the inhibition of protein methylguanin-methyltransferase in glioblastomas are associated with better prognosis. Chemotherapy in grade II gliomas as alternative to radiotherapy in non operable tumors is a subject of current clinical research. Temozolomide had showed to be effective in reducing size tumor and delaying progression to higher malignancy grades. Bevacizumab is a monoclonal antibody targeted against the endothelial growth factor receptor that have demonstrated efficacy in the treatment of recurrent glioblastomas. At present this therapy represents one of the most hopeful approaches to high grade gliomas and current clinical essays might found its place as a first line of chemotherapy in this group of patients. The aim of this review is to resume the main aspects in classification, radiological aspects and most useful treatment used in patient affected by gliomas.

Tumor disembrioplástico neuroepitelial y epilepsia focal de larga evolución: informe de caso y revisión en la literatura / Dysembrioplastic neuroephitelial tumor and long lasting focal epilepsy: case report an literature review

Se presenta el caso clínico de un paciente de 20 años con epilepsia focal sintomática de larga evolución con poco control de sus crisis por tratamiento médico irregular. Las imágenes de resonancia magnética evidenciaron lesión multiquística principalmente del lóbulo temporal izquierdo. Se tomó biopsia estereotáxica cerebral de la lesión; la histolopatología mostró un componente glioneural en una matriz mucinosa, y por tanto, se hizo el diagnóstico de tumor disembrioplástico neuroepitelial. El paciente logra control de las crisis con ácido valproico y carbamazepina, mejora su estado funcional, aunque persiste el déficit cognitivo previo. No se realizó resección quirúrgica por ser una lesión benigna muy extensa y por el adecuado control de las crisis con el tratamiento médico. Debe sugerirse siempre el diagnóstico de tumor disembrioplástico neuroepitelial, ante cualquier tumor glial, en un paciente con larga historia de crisis focales, que inicien antes de los 20 años, sin déficit neurológico y que la resonancia magnética cerebral muestre una lesión cortical microquística, localizada principalmente en lóbulo temporal.

The case of a 20 year old boy, with long-lasting focal symptomatic epilepsy and a poor control of his seizures, because of irregular adherence to the neurological treatment, is presented. Brain MRI showed a multi-cystic lesion, located mainly in the temporal lobe. A brain stereotaxic biopsy was performed, finding a specific neural gliosis in a mucin-like matrix. The diagnosis of dysembryoplastic neuroepithelial tumor was done. Patient had a good control of his seizures with valproic acid and carbamazepine. Patient improved his functional state; however his previous cognitive deficit remains unchanged. Surgical resection was not developed because the lesion is considered as very benign and because the control of his seizures. The diagnosis of dysembryoplastic neuroepithelial tumor should be kept in mind in a patient with a long history of focal seizures; mainly when seizures onset begin before 20 years old, without motor or sensory neurological deficit, and when the MRI shows a cortical multi-cystic lesion, without mass effect, located in the temporal lobe.