Normal Pressure Hydrocephalus Following Cranial Radiation: Identification of Shunting Responders.

BACKGROUND: We examined cognitive, brain MRI, and lumbar infusion test (LIT) features to identify predictors of response to ventriculoperitoneal shunting (VPS) in long-term cancer survivors with suspected normal pressure hydrocephalus (NPH) following cranial radiotherapy (RT). METHODS: Patients who completed cranial RT at least 2 years before with clinically suspected NPH and an Evans' index (EI) ≥ 0.30 underwent a cognitive and a cerebrospinal fluid (CSF) volumetric (MRI) analysis (n = 36). For those in whom VPS was placed (n = 14), we explored whether adding a CSF volumetric analysis to classical MRI and LIT (Tap Test) features would better identify VPS responders. RESULTS: Nearly 80% exhibited cognitive impairment. The CSF volume at NPH diagnoses was significantly larger in the group of VPS responders (p = 0.04). The addition of CSF volume to NPH diagnoses increased accuracy to 93%, with a positive and negative predictive value of 91% and 100%, respectively. CONCLUSION: The addition of a quantitative MRI analysis of CSF volume to classical MRI and LIT NPH criteria, along with a high clinical suspicion of NPH, may help to identify VPS responders, thus improving the clinical management and prognosis of long-term survivors.

Cognitive and brain structural changes in long-term oligodendroglial tumor survivors.

BACKGROUND: We identify cognitive impairment and MRI structural brain changes in long-term oligodendroglial tumor survivors treated with radiation therapy (RT) alone (21%) or with chemotherapy (CT) (79%). METHODS: Oligodendroglial tumor patients (based on the World Health Organization [WHO] 2007 classification) who completed RT ± CT at least 2 years before the study initiation, were classified into 3 groups according to the time treatment was completed: Group 1 = 2-5 years (n = 22), Group 2 = 6-10 years (n = 13), and Group 3 >10 years (n = 13). All patients had a cross-sectional neuropsychological evaluation (n = 48) and a longitudinal volumetric analysis (gray matter [GM; n = 34]) between postsurgical and last follow-up MRI. White matter (WM) changes on MRI were assessed using a qualitative scale. RESULTS: There were no differences regarding tumor or treatment-related characteristics between groups. Six of 22 patients (27.3%) in Group 1; 5/13 (38.5%) in Group 2; and 9/13 (69.2%) in Group 3 had cognitive impairment that was considered severe in 3/22 patients (13.6%) in Group 1; 4/13 (30.8%) in Group 2; and 6/13 (46.2%) in Group 3. Patients in Groups 2 and 3 showed significant GM atrophy and more leukoencephalopathy than Group 1. Cognitive deficits were associated with brain atrophy and WM changes. CONCLUSIONS: Long-term oligodendroglial tumor survivors who underwent standard RT ± CT treatment, mainly >5 years of its completion, present cognitive impairment, especially on memory and executive functions, associated with late GM and WM damage, thus highlighting the need of developing future strategies in patients with oligodendroglial tumor and long expected survival.

Neurotoxicidad cognitiva inducida por la radioterapia cerebral en adultos / Radiation-induced cognitive toxicity in adults

La toxicidad cognitiva inducida por la radioterapia craneal es una de las limitaciones mas importantes del tratamiento radioterapico y con mas impacto sobre la calidad de vida de los largos supervivientes de tumores cerebrales. Esta revision incluye una actualizacion del diagnostico clinico y radiologico de la toxicidad radioinducida con la incorporación de baterias neuropsicologicas y tecnicas avanzadas en neuroimagen. Ambas herramientas han permitido en los últimos anos no solo una mejor definicion de la disfuncion cognitiva, sino tambien la identificacion de los cambios anatomicos y funcionales asociados. La fisiopatologia subyacente implica diferentes estirpes celulares y vias de senalizacion molecular, y el mecanismo es multifactorial. Aunque no existe actualmente una estrategia terapeutica que haya demostrado una clara eficacia, varios estudios, incluyendo los que proponen respetar el hipocampo o el uso de la memantina, han resultado prometedores. Profundizar en el estudio de la toxicidad cognitiva inducida por la radioterapia permitira definir mejor los pacientes que se benefician de la radioterapia, asi como estudiar nuevas dianas terapeuticas para mejorar la calidad de vida de los pacientes con dano cerebral radioinducido

Cognitive toxicity induced by cranial radiation is one of the most important limitations of radiation therapy and has a significant impact on brain tumor survivors’ quality of life. This review comprehends an up to date of recent studies including complete neuropsychological battery and/or advanced neuroimaging techniques. These studies identified critical anatomical and/or functional brain areas related to radiation-induced brain injury, thus improving clinical and radiological diagnosis. Pathophysiological mechanisms underlying cognitive toxicity are complex and involve different cell lines and molecules. Although there is no currently therapeutic strategy that has a demonstrated efficacy, several studies including sparing of hippocampus or the use of memantine are quite promising. A better knowledge of the characteristics of cognitive toxicity induced by cranial radiation, will help us to identify patients who will benefit from treatment and also to examine new therapeutic targets in order to improve patients’ quality of life

Hypoglycemic seizures and epilepsy in type I diabetes mellitus.

PURPOSE: (1) To determine the characteristics of seizures and/or epilepsy among patients with adult onset type 1 diabetes mellitus (T1DM), and (2) to determine glutamic acid decarboxylase antibody (antiGADab) titres and other autoimmune characteristics of T1DM patients with seizure and/or epilepsy. METHODS: Patients were recruited after reviewing the databases of one Diabetes Unit and two Epilepsy Units. Prevalence of suffering epilepsy and/or seizures was calculated in the group of adult onset T1DM patients seen consecutively in the Diabetes Unit. Serum antiGADab titres were determined in all patients. RESULTS: Among the 229 T1DM patients, two had suffered hypoglycemic seizures (0.87%) and two unprovoked seizures (0.87%). We recruited 11 of these T1DM patients. Five reported only hypoglycemic seizures, and 6 temporal lobe epilepsy (TLE). Mean antiGADab titres in patients with T1DM and hypoglycemic seizures were lower (18.42 IU) than in those with T1DM and TLE (29.200 IU), p: 0.006. Patients with T1DM and TLE suffered more other autoimmune diseases than those with T1DM and hypoglycemic seizures, p: 0.015. CONCLUSIONS: Hypoglycemic seizures are rare in T1DM patients. AntiGADab titres do not differ from the general diabetic population. Patients with high titres of antiGADab are more likely to develop TLE.

Short communication: focal encephalitis related to viral escape and resistance emergence in cerebrospinal fluid in a patient on lopinavir/ritonavir monotherapy with plasma HIV-1 RNA suppression.

Monotherapy with boosted protease inhibitors has emerged as an antiretroviral therapy simplification alternative for selected patients, endorsed by the results of some randomized clinical trials. However, there are some concerns about the efficacy of such a strategy in achieving successful viral suppression in those anatomic compartments or reservoirs in which antiretroviral drug penetration is lower, such as the central nervous system (CNS). Several studies have demonstrated better neurocognitive performance in patients receiving antiretroviral drugs with better cerebrospinal fluid (CSF) penetration. Nevertheless, cases of CSF viral escape accompanied by moderate or severe neurological symptoms have been reported with both standard triple therapy and boosted protease inhibitor (PI) monotherapy, and it is not well established whether ritonavir-boosted protease inhibitor (PI/r) monotherapy is associated with a higher risk of symptomatic CSF viral escape or not. Herein, we present a case of viral rebound and resistance emergence exclusively in CSF associated with an unusual clinical manifestation of focal encephalitis in a patient with plasma HIV-1 RNA suppression while receiving lopinavir/ritonavir monotherapy. Clinical resolution and CSF viral suppression were observed after switching to a genotype-guided combined antiretroviral regimen with good CSF penetration.