Effects of midazolam on high-frequency oscillations in amygdala and hippocampus of epilepsy patients.

High-frequency oscillations (HFOs) are associated with normal brain function, but are also increasingly recognized as potential biomarkers of epileptogenic tissue. Considering the important role of interneuron activity in physiological HFO generation, we studied their modulation by midazolam (MDZ), an agonist of γ-aminobutyric acid type A (GABAA)-benzodiazepine receptors. Here, we analyzed 80 intracranial electrode contacts in amygdala and hippocampus of 13 patients with drug-refractory focal epilepsy who had received MDZ for seizure termination during presurgical monitoring. Ripples (80-250 Hz) and fast ripples (FRs; 250-400 Hz) were compared before and after seizures with MDZ application, and according to their origin either within or outside the individual seizure onset zone (SOZ). We found that MDZ distinctly suppressed all HFOs (ripples and FRs), whereas the reduction of ripples was significantly less pronounced inside the SOZ compared to non-SOZ contacts. The rate of FRs inside the SOZ was less affected, especially in hippocampal contacts. In a few cases, even a marked increase of FRs following MDZ administration was seen. Our results demonstrate, for the first time, a significant HFO modulation in amygdala and hippocampus by MDZ, thus giving insights into the malfunction of GABA-mediated inhibition within epileptogenic areas and its role in HFO generation.

Face-induced gamma oscillations and event-related potentials in patients with epilepsy: an intracranial EEG study.

BACKGROUND: To examine the pathological effect of a mesial temporal seizure onset zone (SOZ) on local and inter-regional response to faces in the amygdala and other structures of the temporal lobe. METHODS: Intracranial EEG data was obtained from the amygdala, hippocampus, fusiform gyrus and parahippocampal gyrus of nine patients with drug-refractory epilepsy during visual stimulation with faces and mosaics. We analyzed event-related potentials (ERP), gamma frequency power, phase-amplitude coupling and phase-slope-index and compared the results between patients with versus without a mesial temporal SOZ. RESULTS: In the amygdala and fusiform gyrus, faces triggered higher ERP amplitudes compared to mosaics in both patient groups and higher gamma power in patients without a mesial temporal SOZ. In the hippocampus, famous faces triggered higher gamma power for both groups combined but did not affect ERPs in either group. The differentiated ERP response to famous faces in the parahippocampal gyrus was more pronounced in patients without a mesial temporal SOZ. Phase-amplitude coupling and phase-slope-index results yielded bidirectional modulation between amygdala and fusiform gyrus, and predominately unidirectional modulation between parahippocampal gyrus and hippocampus. CONCLUSIONS: A mesial temporal SOZ was associated with an impaired response to faces in the amygdala, fusiform gyrus and parahippocampal gyrus in our patients. Compared to this, the response to faces in the hippocampus was impaired in patients with, as well as without, a mesial temporal SOZ. Our results support existing evidence for face processing deficits in patients with a mesial temporal SOZ and suggest the pathological effect of a mesial temporal SOZ on the amygdala to play a pivotal role in this matter in particular.

Resective epilepsy surgery in patients aged 50years and older - a retrospective study regarding seizure outcome, memory performance, and psychopathology.

PURPOSE: To assess clinical and demographic characteristics in two cohorts of elderly patients with drug-resistant focal epilepsy, undergoing resective epilepsy surgery (RES). Further, to determine seizure, neuropsychological, and mental health outcomes after RES and evaluate possible influencing factors. METHODS: Consecutive patients aged ≥50 years with temporal lobe epilepsy (TLE) who underwent curative RES in the Hamburg epilepsy surgery program (2004-2017) were identified. Data were retrospectively analyzed. Seizure outcome was classified according to ILAE and Engel outcome scales in patients with first-time surgeries and with reoperations. Previously reported predictors of the seizure outcome were evaluated using regression analyses. Changes in verbal memory were assessed for patients with complete pre- and postoperative datasets (n=30) using repeated-measures analysis of variance. For evaluation of possible predictors of psychopathologic changes after RES a regression analysis was conducted. RESULTS: Fifty-one elderly patients underwent RES of the temporal lobe, including twelve aged ≥60 years, and five with reoperations. After one year, 65% of the patients with first-time surgeries were seizure free and 91% had a favorable outcome. At last follow-up, 49% were seizure free since surgery. Three reoperated patients had an Engel I outcome. Seizure outcome was not dependent on age at surgery, duration of epilepsy, or other evaluated variables. There was no significant decline in the memory performance after surgery. Significant improvements in mental health were found. CONCLUSION: RES for drug-resistant TLE is safe, effective, and improves mental health also in patients aged ≥ 50 years. Thus, it should be evaluated as the treatment of choice also in this age group.

Use of the mixed reality tool "VSI Patient Education" for more comprehensible and imaginable patient educations before epilepsy surgery and stereotactic implantation of DBS or stereo-EEG electrodes.

PURPOSE: It is unknown which patient education strategy before epilepsy surgery or stereotactic electrode implantation is best for patients. This prospective and randomized clinical study investigates whether the use of the mixed reality tool "VSI Patient Education" (VSI PE) running on HoloLens® glasses is superior to the use of a rubber brain model as a 3-dimensional tool for patient education before epilepsy surgery and stereotactic electrode implantation. MATERIAL AND METHODS: 17 patients with indication for epilepsy surgery or stereotactic electrode implantation were included in the study and randomized into two groups. All patients were informed with both comparative tools VSI PE (apoQlar®) and a rubber brain model (3B Scientific®) in a chronological order depending on group assignment. Afterwards, the patient and, if present, a relative (12) each filled out a questionnaire. For statistical analysis, Wilcoxon rank-sum tests were performed. RESULTS: Patients found their patient education highly significantly more comprehensible (p = 0.001**, r = 0.84) and almost significantly more imaginable (p=0.020, r = 0.57), when their doctor used VSI PE compared to the rubber brain model. The patients felt significantly less anxious as a result of VSI PE (p = 0.008*, r = 0.64). Highly significantly more patients chose VSI PE as the preferred patient education tool (p < 0.001**, r = 0.91), and almost significantly more patients decided VSI PE to be the future standard tool (p = 0.020, r = 0.56). Significantly more relatives chose VSI PE as the preferred patient education tool (p = 0.004*, r = 0.83), and significantly more relatives decided VSI PE to be the future standard tool (p = 0.002*, r = 0.91). CONCLUSION: VSI Patient Education is a promising new mixed reality tool for informing patients before epileptic surgery or stereotactic electrode implantation in order to enhance comprehension and imagination and reduce fear and worries. It might strengthen patient commitment and have a positive influence on patients' decisions in favor of medically indicated surgical operations.

Octreotide: The IIH therapy beyond weight loss, carbonic anhydrase inhibitors, lumbar punctures and surgical/interventional treatments.

OBJECTIVE: Idiopathic intracranial hypertension (IIH) is characterized by elevated intracranial pressure without a space-occupying cerebral lesion, venous sinus thrombosis or hydrocephalus and with normally composited cerebrospinal fluid (CSF). Main symptoms are headache, sight disturbances and potential visual impairment. Weight loss, carbonic anhydrase inhibitors, lumbar punctures with CSF drain, CSF shunting, optic nerve sheath fenestration, and venous sinus stenting are common IIH therapies. Octreotide, a synthetic somatostatin analogue, also effectively suspends IIH symptoms. Here, treatment with octreotide on five so far inefficiently treated IIH patients is presented and discussed. METHODS: Five female patients with IIH and a history of failed therapy regimes were treated with octreotide, to be administered everyday subcutaneously for six months with identified doses high enough to suspend all clinical IIH symptoms. After tapering for two months, the further clinical course was to be monitored. RESULTS: All patients were IIH symptom-free under octreotide. After tapering, one patient remained IIH symptom-free; one patient became IIH symptom-free under intramuscular octreotide after failure of former therapy regimes; one patient became IIH symptom-free on low-dose carbonic anhydrase inhibitors; one patient had an allergic reaction and paused octreotide, after successful desensitization, tooth ache developed, forcing octreotide tapering; one patient had another shunt revision alleviating IIH symptoms. CONCLUSION: We confirmed that a) clinical IIH symptoms are suspended during octreotide exposure; b) 6-month administration can sustainably abolish IIH symptoms; c) desensitization is possible for octreotide allergy. When IIH symptoms reoccur after limited-time octreotide administration, re-application of formerly ineffective carbonic anhydrase inhibitors can suspend IIH symptoms. Intramuscular octreotide is a promising long-term therapy option.

Neuropsychological performance and seizure control after subsequent anteromesial temporal lobe resection following selective amygdalohippocampectomy.

OBJECTIVE: Selective amygdalohippocampectomy (sAHE) is a well-established treatment for temporal lobe epilepsy, commonly with favorable neuropsychological outcome. Yet, it is still unknown if subsequent resection of the anteromesial temporal lobe (AMTLR), when necessary, deteriorates neuropsychological performance in this selected group of patients. Thus, we evaluated the clinical and neuropsychological data of patients who, due to insufficient seizure control after sAHE, received a subsequent ipsilateral AMTLR and compared these findings with patients who did not receive a second resection (control group). METHODS: Patients' characteristics and neuropsychological data were assessed and analyzed in the reoperated as well as in the control group at each step of treatment. Experienced neuropsychologists conducted the standardized examination focusing on verbal, figural and working memory, speech fluency and attention. Preoperative diagnostics included further continuous video-electroencephalography monitoring, high-resolution magnetic resonance imaging and functional transcranial Doppler sonography. RESULTS: Eighty patients having received sAHE in our center from 11/2007 to 02/2013 were included in this study. Seventeen of these patients underwent subsequent AMTLR. Thirteen of these were available for follow-up after the second surgery and twelve had a comprehensive neuropsychological testing at all three steps. Analyzing the neuropsychological data revealed no significant differences compared with controls. On the individual level, the data demonstrated that improvement in a subdomain was more frequent than decline, if the performance had already deteriorated after the first procedure. Seizure control improved significantly (p < 0.001) in all patients after subsequent AMTLR resulting in seven patients being seizure-free at follow-up. SIGNIFICANCE: Subsequent AMTLR following sAHE can be a safe procedure to improve seizure outcome in selected patients. In our series the risk for further neuropsychological deterioration after the second procedure was low. The neuropsychological performance after the sAHE can be a valuable criterion to advise patients who are eligible for a second surgery on their risk of further cognitive decline.

Which contraception for women with epilepsy?

Clinical decision making which contraceptive regimen is optimal for an individual woman with epilepsy is one of the most challenging tasks when taking care of women with epilepsy. The bidirectional interactive potential of antiepileptic drugs (AEDs) and hormonal contraceptives needs to be taken into account. Enzyme inducing (EI)-AEDs may reduce the contraceptive efficacy of hormonal contraceptives. If combined oral contraceptives (COCs) are used in combination with EI-AEDs, it is recommended to choose a COC containing a high progestin dose, well above the dose needed to inhibit ovulation, and to take the COC pill continuously ("long cycle therapy"). But even with the continuous intake of a COC containing a higher progestin dose contraceptive safety cannot be guaranteed, thus additional contraceptive protection may be recommended. Progestin-only pills (POPs) are likely to be ineffective, if used in combination with EI-AEDs. Subdermal progestogen implants are not recommended in patients on EI-AEDs, because of published high failure rates. Depot medroxyprogesterone-acetate (MPA) injections appear to be effective, however they may not be first choice due to serious side effects (delayed return to fertility, impaired bone health). The use of intrauterine devices is an alternative method of contraception in the majority of women, with the advantage of no relevant drug-drug interactions. The levonorgestrel intrauterine system (IUS) appears to be effective, even in women taking EI-AEDs. Likelihood of serious side effects is low in the IUS users.

Treatment of photosensitivity.

Not all visually sensitive patients need antiepileptic drug treatment, and even those who do can benefit from additional preventive measures. Visually provoked seizures, in particular, can be prevented or treated by avoiding or altering the triggering stimulus. Apart from individual preventive measures (use of specific television or video screens, colored glasses, etc.), prevention and warning on a larger scale are helpful. The choice for drug treatment will depend on the type of stimulus, the environment in which the person has to live and work, the frequency and severity of seizures, and the type of epileptic syndrome. A review is given of all treatment options with focus on the specific nonpharmacologic and pharmacologic tools used in clinical practice.