Elevated basal glutamate and unchanged glutamine and GABA in refractory epilepsy: Microdialysis study of 79 patients at the yale epilepsy surgery program.

OBJECTIVE: Aberrant glutamate and γ-aminobutyric acid (GABA) neurotransmission contribute to seizure generation and the epileptic state. However, whether levels of these neurochemicals are abnormal in epileptic patients is unknown. Here, we report on interictal levels of glutamate, glutamine, and GABA in epilepsy patients at seizure onset and nonepileptic sites, cortical lesions, and from patients with poorly localized neocortical epilepsies. METHODS: Subjects (n = 79) were medically refractory epilepsy patients undergoing intracranial electroencephalogram evaluation. Microdialysis probes (n = 125) coupled to depth electrodes were implanted within suspected seizure onset sites and microdialysis samples were obtained during interictal periods. Glutamate, glutamine, and GABA were measured using high-performance liquid chromatography. Probe locations were subsequently classified by consensus of expert epileptologists. RESULTS: Glutamate levels were elevated in epileptogenic (p = 0.03; n = 7), nonlocalized (p < 0.001), and lesional cortical sites (p < 0.001) when compared to nonepileptogenic cortex. Glutamate was also elevated in epileptogenic (p < 0.001) compared to nonepileptogenic hippocampus. There were no statistical differences in GABA or glutamine, although GABA levels showed high variability across patients and groups. INTERPRETATION: Our findings indicate that chronically elevated extracellular glutamate is a common pathological feature among epilepsies with different etiology. Contrary to our predictions, GABA and glutamine levels were not decreased in any of the measured areas. Whereas variability in GABA levels may in part be attributed to the use of GABAergic antiepileptic drugs, the stability in glutamine across patient groups indicate that extracellular glutamine levels are under tighter metabolic regulation than previously thought. Ann Neurol 2016;80:35-45.

Percutaneous endoscopic gastrostomy in oropharyngeal cancer patients treated with intensity-modulated radiotherapy with concurrent chemotherapy.

BACKGROUND: The clinical benefit of routine placement of prophylactic percutaneous endoscopic gastrostomy (pPEG) tubes was assessed in patients with oropharyngeal cancer (OPC) who are undergoing intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy. METHODS: From 1998 through 2009, 400 consecutive patients with OPC who underwent chemoradiation were included. Of these, 325 had a pPEG and 75 did not (nPEG). Weight and albumin change from baseline to mid-IMRT, end of IMRT, 1 month post-IMRT, and 3 months post-IMRT were evaluated. The treating physicians prospectively recorded acute and late toxicities. RESULTS: Significantly lower absolute weight loss at end of IMRT (6.80 kg vs 8.38 kg, P = .007), 1 month post-IMRT (9.06 kg vs 11.33 kg, P = .006), and 3 months post-IMRT (11.10 kg vs 13.09 kg, P = .044) was noted in the pPEG versus nPEG groups. This benefit in reduction of percent weight loss was consistently significant only among patients with BMI < 25. Significant differences were noted in hospital admission rate (15.1% vs 26.7%, P = .026) and volume of nonchemotherapy hydration (8.9 liters vs 17.2 liters, P = .004). There were no differences in percent albumin change, acute dysphagia, acute mucositis, acute xerostomia, chronic dysphagia, radiation treatment duration, and overall survival. Multivariate analysis noted age >55 years (P < .001), female sex (P < .001), and T3/4 category disease (P < .001) were significantly associated with prolonged PEG use. CONCLUSIONS: Although pPEG reduced absolute and percent weight loss and need for hospitalizations in our cohort of patients with OPC undergoing chemoradiation, no differences were noted in radiation treatment duration, toxicity, and overall survival. Prolonged PEG use correlated with age >55 years, female sex, and T3/T4 tumors.