[TK2 mutations and late onset myopathy: first description in a Mexican patient]. / Mutacion del gen TK2 y miopatia de inicio tardio: descripcion del primer caso mexicano.

TITLE: Mutacion del gen TK2 y miopatia de inicio tardio: descripcion del primer caso mexicano.

Choice of antiepileptic drugs affects the outcome in cancer patients with seizures.

BACKGROUND: Seizures in cancer patients may occur as a result of CNS primary or metastatic tumor, brain surgery, vascular disease, pharmacologic treatment (including chemotherapy), radiation therapy, or metabolic disorders. The aims of the study were to a) determine whether seizures in cancer patients have prognostic implications and b) study patient outcome based on the antiepileptic drug used. METHOD: This is a prospective comparative study that included adult cancer patients with and without seizures from May 2010 to November 2016 seen by the neuro-oncology unit at a cancer referral center. Variables included age, gender, oncologic characteristics, seizure features, treatment, and outcome. Parametric and non-parametric tests were used to compare groups, and Kaplan-Meier curves with the log-rank test were used to analyze survival. Cox multivariate regression tests were used to describe survival and compare groups. RESULTS: A total of 823 patients were included; 419 (51%) patients had at least one seizure and were compared with 404 (49%) who did not experience seizures. Of the seizure group, 53% had brain metastases, 36% did not have a brain tumor, and 11% had a primary brain tumor. No survival differences were noted among patients with brain metastases or primary tumor with or without seizures. In the seizure group, 249 (59%) required only one antiepileptic drug, whereas 134 (32%) required 2 or more. A better overall survival was identified for patients prescribed carbamazepine (p = 0.02), lamotrigine (p = 0.015), levetiracetam (p = 0.03), and valproic acid (p = 0.009). CONCLUSIONS: Patients with primary or metastatic brain tumors have the same overall survival with or without seizures. However, patients with seizures not treated with antiepileptics exhibit worse overall survival.

Increased Expression of Brain-Derived Neurotrophic Factor Transcripts I and VI, cAMP Response Element Binding, and Glucocorticoid Receptor in the Cortex of Patients with Temporal Lobe Epilepsy.

A body of evidence supports a relevant role of brain-derived neurotrophic factor (BDNF) in temporal lobe epilepsy (TLE). Magnetic resonance data reveal that the cerebral atrophy extends to regions that are functionally and anatomically connected with the hippocampus, especially the temporal cortex. We previously reported an increased expression of BDNF messenger for the exon VI in the hippocampus of temporal lobe epilepsy patients compared to an autopsy control group. Altered levels of this particular transcript were also associated with pre-surgical use of certain psychotropic. We extended here our analysis of transcripts I, II, IV, and VI to the temporal cortex since this cerebral region holds intrinsic communication with the hippocampus and is structurally affected in patients with TLE. We also assayed the cyclic adenosine monophosphate response element-binding (CREB) and glucocorticoid receptor (GR) genes as there is experimental evidence of changes in their expression associated with BDNF and epilepsy. TLE and pre-surgical pharmacological treatment were considered as the primary clinical independent variables. Transcripts BDNF I and BDNF VI increased in the temporal cortex of patients with pharmacoresistant TLE. The expression of CREB and GR expression follow the same direction. Pre-surgical use of selective serotonin reuptake inhibitors, carbamazepine (CBZ) and valproate (VPA), was associated with the differential expression of specific BDNF transcripts and CREB and GR genes. These changes could have functional implication in the plasticity mechanisms related to temporal lobe epilepsy.

Increased expression of BDNF transcript with exon VI in hippocampi of patients with pharmaco-resistant temporal lobe epilepsy.

A putative role of the brain-derived neurotrophic factor (BDNF) in epilepsy has emerged from in vitro and animal models, but few studies have analyzed human samples. We assessed the BDNF expression of transcripts with exons I (BDNFI), II (BDNFII), IV (BDNFIV) and VI (BDNFVI) and methylation levels of promoters 4 and 6 in the hippocampi of patients with pharmaco-resistant temporal lobe epilepsy (TLE) (n=24). Hippocampal sclerosis (HS) and pre-surgical pharmacological treatment were considered as clinical independent variables. A statistical significant increase for the BDNFVI (p<0.05) was observed in TLE patients compared to the autopsy control group (n=8). BDNFVI was also increased in anxiety/depression TLE (N=4) when compared to autopsies or to the remaining group of patients (p<0.05). In contrast, the use of the antiepileptic drug Topiramate (TPM) (N=3) was associated to a decrease in BDNFVI expression (p<0.05) when compared to the remaining group of patients. Methylation levels at the BDNF promoters 4 and 6 were similar between TLE and autopsies and in relation to the use of either Sertraline (SRT) or TPM. These results suggest an up-regulated expression of a specific BDNF transcript in patients with TLE, an effect that seems to be dependent on the use of specific drugs.