miR-217-casein kinase-2 cross talk regulates ERK activation in ganglioglioma.

Gangliogliomas (GGs) are the most commonly diagnosed long-term epilepsy-associated tumors (LEATs). Although molecular characterizations of brain tumors have identified few novel biomarkers among the LEATs, mechanisms of pathogenesis remain poorly understood. In this study, global microarray-based microRNA (miRNA) expression profile on a set of 9 GGs indicated 66 miRNAs to be differentially expressed in GG as compared to normal brain. The differences validated by qRT-PCR indicated microRNA-217 to be the most downregulated. Through insilico analysis, ERK1/2 and casein kinase (CK-2α) were predicted to be miR-217 regulated. As decreased miR-217 expression was concomitant with upregulated ERK1/2 and CK-2α levels in GG; the interplay between these molecules was investigated in primary human neural precursor cells to mimic the glioneuronal characteristics of these tumors. miR-217 over-expression-mediated decrease in pERK, CK-2α, and mGluR1 levels was accompanied with increase in glycogen accumulation. Importantly, increase in miR-217 levels upon CK-2α inhibition indicated inverse correlation between the two. Inhibition of CK-2α also decreased ERK and mGluR1 levels. By demonstrating, for the first time, the existence of miR-217-CK-2 cross talk and its effects on known epileptogenic factors, these findings provide a unique insight into the pathogenesis of ganglioglioma. By highlighting the role of CK-2 in affecting miR-217/ERK/mGluR1 interplay, this study suggests that targeting CK-2 may afford a novel strategy aimed at LEATs. KEY MESSAGES: Global microarray of ganglioglioma indicates downregulation of miR-217. Decreased miR-217 expression is concomitant with elevated CK-2α and Erk levels. Inverse correlation between miR-217 and CK-2α in primary human neural precursors. miR-217 agomir or CK-2α inhibition decreases pERK and mGluR1 levels. CK-2α affects miR-217/ERK/mGluR1 interplay in long-term epilepsy-associated tumors.

Changes in psychiatric comorbidity during early postsurgical period in patients operated for medically refractory epilepsy--a MINI-based follow-up study.

PURPOSE: The purpose of this study was to assess axis-I DSM-IV psychiatric disorders in patients at baseline and 3 months after surgery for medically refractory temporal lobe epilepsy. METHOD: The Mini International Neuropsychiatric Interview (MINI) and Quality of Life in Epilepsy Inventory-10 (QOLIE-10) were evaluated before and 3 months after surgery in 50 consecutive patients (21 females, 29 males) with medically refractory temporal lobe epilepsy (persistent seizures>2/month, despite treatment with ≥2 appropriate drugs in adequate doses for ≥2 years) who underwent surgery [anterior temporal lobectomy with amygdalo-hippocampectomy (for mesial temporal sclerosis in 40), electrocorticography-guided lesionectomy (for other lesions in 10)]. RESULTS: Twenty-six patients (52%) had an axis-I psychiatric disorder [26% depressive disorder, 28% anxiety disorder] at baseline, while 30 (60%) patients had an axis-I psychiatric disorder [28% depressive disorder, 28% anxiety disorder] at 3 months after surgery. Twenty percent developed a new psychiatric disorder, while 12% showed improvement postsurgery. Mean QOLIE-10 scores improved from 23.78 to 17.80 [24 (48%) patients showed ≥5-point improvement]. Thirty-four (68%) patients had no seizure, 6 (12%) had non-disabling seizures, while 2 (4%) had disabling seizures after surgery. High frequency of seizures prior to surgery (p<0.038) and seizure occurrence after surgery (p<0.055) predicted the presence of psychiatric disorders after surgery. No clinical characteristic could predict development of new psychiatric disorder after surgery. CONCLUSION: Psychiatric dysfunction in the early postsurgery period is seen in nearly half of patients undergoing surgery for temporal lobe epilepsy, is mild in nature, and does not adversely affect quality of life but may cause significant clinical problems when it arises de novo postsurgery.

Unidirectional whole body turning: a new lateralising sign in complex partial seizures.

BACKGROUND: The lateralising significance of unidirectional whole body turning in patients with complex partial seizures (CPS) arising from the temporal lobe was evaluated. METHODS: A total of 330 patients undergoing long term video-EEG study were included. "Unidirectional whole body turning" was defined as rotation of the trunk, head, and limbs by >90 degrees and lasting >10 s. EEG correlates, MRI, and SPECT findings were compared and outcome after surgery was noted for patients with follow up data for >1 year. RESULTS: Unidirectional whole body turning was observed in 13 patients with a mean age of 18+/-8 years. Concordance of the side of whole body turning with the EEG focus and MRI findings was observed in 11 of the 13 patients (84.7%) and in 26 of 28 seizures (92.8%). The six patients who underwent temporal lobectomy or resection of lesion, opposite to the direction of body turning, had good seizure outcome. CONCLUSION: Unidirectional whole body turning is a new lateralising sign in temporal lobe CPS with good predictive value for epileptogenic focus contralateral to the direction of turning.