Mackenzie C. Cervenka

Electrocorticographic functional mapping identifies human cortex critical for auditory and visual naming.

More comprehensive, and efficient, mapping strategies are needed to avoid post-operative language impairments in patients undergoing epilepsy surgery. Conservative resection of dominant anterior frontal or temporal cortex frequently results in post-operative naming deficits despite standard pre-operative electrocortical stimulation mapping of visual object (picture) naming. Naming to auditory description may better simulate word retrieval in human conversation but is not typically tested, in part due to the time demands of electrocortical stimulation mapping. Electrocorticographic high gamma (60-150 Hz) activity, recorded simultaneously through the same electrodes used for stimulation mapping, has recently been used to map brain function more efficiently, and has at times predicted deficits not anticipated based on stimulation mapping alone. The present study investigated electrocorticographic mapping of visual object naming and auditory descriptive naming within conservative dominant temporal or frontal lobe resection boundaries in 16 patients with 933 subdural electrodes implanted for epilepsy surgery planning. A logistic regression model showed that electrodes within traditional conservative dominant frontal or temporal lobe resection boundaries were significantly more likely to record high gamma activity during auditory descriptive naming than during visual object naming. Eleven patients ultimately underwent resection and 7 demonstrated post-operative language deficits not anticipated based on electrocortical stimulation mapping alone. Four patients with post-operative deficits underwent a resection that included sites where high gamma activity was observed during naming. These findings indicate that electrocorticographic mapping of auditory descriptive naming may reduce the risk of permanent post-operative language deficits following dominant temporal or frontal resection.

A decade of the modified Atkins diet (2003-2013): Results, insights, and future directions

The modified Atkins diet has been used since 2003 for the treatment of children and adults with refractory epilepsy.This “alternative” ketogenic diet is started in clinic, without fasting, hospitalization, and restriction of protein,calories, or fluid intake. Now after 10 years of continued use, approximately 400 patients have been reported in over 30 studies of the modified Atkins diet as treatment for intractable seizures, with results demonstrating similar efficacy to the ketogenic diet and improved tolerability. The modified Atkins diet is being increasingly used in the adult population. Clinical trials have provided insight into the mechanisms of action of dietary therapies overall. This review will discuss the past decade of experience with the modified Atkins diet as well as predictions for its role in the treatment of epilepsy a decade from now.

The ketogenic diet for medically and surgically refractory status epilepticus in the neurocritical care unit.

BackgroundRefractory status epilepticus carries a high risk of morbidity and mortality despite, and at times as a result of, aggressive pharmacologic interventions. Dietary therapies have been used for almost a century in children for controlling medically refractory seizures and status epilepticus and recent studies suggest efficacy and safety in adults as well.MethodsCase report and literature review.ResultsWe describe a case of medically and surgically refractory status epilepticus that was controlled after initiation of the ketogenic diet and maintenance with the modified Atkins diet in an adult in the neurocritical care unit.ConclusionsDietary therapy should be considered as a treatment option in adult patients with refractory status epilepticus.

Establishing an Adult Epilepsy Diet Center: Experience, efficacy and challenges.

OBJECTIVESnOver 250 medical centers worldwide offer ketogenic diets to children with epilepsy; however, access to these therapies has been extremely limited for adults until recent years. We examine our 5-year experience creating and implementing a dedicated Adult Epilepsy Diet Center designed to provide adults with epilepsy access to ketogenic diets.nnnMATERIAL AND METHODSnOutpatients seen at the Johns Hopkins Adult Epilepsy Diet Center from August 2010 thru September 2015 age 18years and older were enrolled in a prospective open-label observational study. Patients that also enrolled in ongoing clinical diet trials were excluded from this study. Participant demographics, diet type, urine and/or serum ketones, laboratory studies, seizure frequency, diet duration, reason for discontinuing diet therapy, and side effects were recorded. A subgroup analysis of participants that met International League Against Epilepsy (ILAE) criteria for drug-resistant epilepsy (DRE) and were treated de novo with a Modified Atkins Diet (MAD) was performed to compare outcomes with the current literature regarding efficacy of other antiseizure treatments for DRE.nnnRESULTSnTwo hundred and twenty-nine adults attended the Adult Epilepsy Diet Center, and 168 met inclusion criteria. Two-thirds (n=113, 67%) were women with an age range of 18-86years at the initial visit. Thirty-five participants (21%, n=133) were already on a therapeutic diet while 79% (n=133) were naïve to diet therapy at the time of the initial visit. Diet-naïve participants were typically prescribed MAD (n=130, 98%), unless unable to intake adequate oral nutrition, in which case they were prescribed KD (n=1) or a combination of oral MAD and ketogenic formula (n=2). Twenty-nine of 130 (22%) participants prescribed MAD elected not to start or were lost to follow-up, and 101 (78%) began MAD. A subgroup analysis was performed on one hundred and six participants naïve to diet therapy that met International League Against Epilepsy criteria for DRE, were able to tolerate oral nutrition, and were prescribed a MAD. Relative to the number of enrolled participants who had reliable follow-up results for a given duration (including those that ultimately elected not to start or were later lost to follow-up), at 3months, 36% of these participants responded (≥50% seizure reduction) to diet therapy, and 16% were seizure-free. At 1year, 30% responded, and 13% were seizure-free. At 4years, 21% responded, and 7% were seizure-free. Hyperlipidemia was the most common side effect (occurring in 39% of screened participants, including those on a therapeutic diet prior to the initial visit). Weight loss was also common (occurring in 19% of all participants treated with a ketogenic diet therapy) yet was often an intended effect.nnnSIGNIFICANCEnThis study, the largest series of adults with epilepsy treated with ketogenic diet therapies to date, provides evidence that ketogenic diets may be feasible, effective, and safe long-term in adults, although long-term adherence was limited and further adequately controlled studies are necessary to determine the efficacy of ketogenic diets in the treatment of adults with epilepsy.

Electroencephalography for diagnosis and prognosis of acute encephalitis

OBJECTIVESnTo confirm the previously identified EEG characteristics for HSV encephalitis and to determine the diagnostic and predictive value of electroencephalography (EEG) features for etiology and outcome of acute encephalitis in adults. In addition, we sought to investigate their independence from possible clinical confounders.nnnMETHODSnThis study was performed in the Intensive Care Units of two academic tertiary care centers. From 1997 to 2011, all consecutive patients with acute encephalitis who received one or more EEGs were included. Examination of the diagnostic and predictive value of EEG patterns regarding etiology, clinical conditions, and survival was performed. The main outcome measure was in-hospital death.nnnRESULTSnOf 103 patients with encephalitis, EEGs were performed in 76 within a median of 1 day (inter quartile range 0.5-3) after admission. Mortality was 19.7%. Higher proportions of periodic discharges (PDs) (p=0.029) and focal slowing (p=0.017) were detected in Herpes Simplex virus (HSV) encephalitis as compared to non-HSV encephalitis, while clinical characteristics did not differ. Normal EEG remained the strongest association with a low relative risk for death in multivariable analyses (RR<0.001, p<0.001) adjusting for confounders as coma, global cerebral edema and mechanical ventilation. None of the patients with a normal EEG had a GCS of 15.nnnCONCLUSIONSnNormal EEG predicted survival independently from possible confounders, highlighting the prognostic value of EEG in evaluating patients with encephalitis. EEG revealed higher proportions of PDs along with focal slowing in HSV encephalitis as compared to other etiologies.nnnSIGNIFICANCEnEEG significantly adds to clinical, diagnostic and prognostic information in patients with acute encephalitis.

Ictal propagation of high frequency activity is recapitulated in interictal recordings: Effective connectivity of epileptogenic networks recorded with intracranial EEG

Seizures are increasingly understood to arise from epileptogenic networks across which ictal activity is propagated and sustained. In patients undergoing invasive monitoring for epilepsy surgery, high frequency oscillations have been observed within the seizure onset zone during both ictal and interictal intervals. We hypothesized that the patterns by which high frequency activity is propagated would help elucidate epileptogenic networks and thereby identify network nodes relevant for surgical planning. Intracranial EEG recordings were analyzed with a multivariate autoregressive modeling technique (short-time direct directed transfer function--SdDTF), based on the concept of Granger causality, to estimate the directionality and intensity of propagation of high frequency activity (70-175 Hz) during ictal and interictal recordings. These analyses revealed prominent divergence and convergence of high frequency activity propagation at sites identified by epileptologists as part of the ictal onset zone. In contrast, relatively little propagation of this activity was observed among the other analyzed sites. This pattern was observed in both subdural and depth electrode recordings of patients with focal ictal onset, but not in patients with a widely distributed ictal onset. In patients with focal ictal onsets, the patterns of propagation recorded during pre-ictal (up to 5 min immediately preceding ictal onset) and interictal (more than 24h before and after seizures) intervals were very similar to those recorded during seizures. The ability to characterize epileptogenic networks from interictal recordings could have important clinical implications for epilepsy surgery planning by reducing the need for prolonged invasive monitoring to record spontaneous seizures.

Worldwide Dietary Therapies for Adults With Epilepsy and Other Disorders

During the 3rd International Symposium on Dietary Therapies held in Chicago, Illinois, there was a first-ever, half-day session devoted to the management of adults with epilepsy and other disorders with dietary treatments. Speakers from 3 different continents shared their successes, challenges, and future directions in their management of these patients. Diets used to treat adults included the classic ketogenic diet, the modified Atkins diet, and a low glycemic index treatment. The utility of dietary therapies was demonstrated not only in patients with epilepsy but also patients with propriospinal myoclonus, astrocytoma, type 2 diabetes, obesity, hyperlipidemia, and metabolic disorder. The session provided evidence that dietary therapies are safe and effective in adults.

The impact of the modified Atkins diet on lipid profiles in adults with epilepsy

Objectives: The modified Atkins diet (MAD) is a high fat, low carbohydrate ketogenic diet used to treat intractable seizures in children and adults. The long-term impact on fasting lipid profiles (FLPs) remains unknown. This study was designed to detect significant lipid changes in adults on MAD. Methods: Patients were observed prospectively. A FLP was obtained in all patients at the first visit then serially. Patients were started on a 20u2005g per day net carbohydrate limit MAD. They were screened for risk for coronary heart disease and counseled to reduce saturated fats by a registered dietitian if deemed at risk. Patients that remained on MAD for 3 or more months with one or more follow-up FLP were included. Results: Thirty-seven patients (14 male), mean age 33 years (SD 13, range 18–59) met study criteria. Median diet duration was 16 months (range 3–41). Total cholesterol and low-density lipoprotein (LDL) increased significantly over the first 3 months of MAD (Pu2009=u20090.01 and 0.008, respectively), but were not significantly different from baseline after 1 year of treatment (Pu2009=u20090.2 and Pu2009=u20090.5, respectively). High-density lipoprotein levels trended upward in the first 3 months (Pu2009=u20090.05) and triglycerides remained unchanged (Pu2009=u20090.5). In 12 patients followed for 3 or more years, no cardiovascular or cerebrovascular events were reported. Discussion: Although total cholesterol and LDL increased over the first 3 months of the MAD, these values normalized within a year of treatment, including in patients treated with MAD for more than 3 years.

Reliability of Early Cortical Auditory Gamma-Band Responses

OBJECTIVEnTo evaluate the test-retest reliability of event-related power changes in the 30-150 Hz gamma frequency range occurring in the first 150 ms after presentation of an auditory stimulus.nnnMETHODSnRepeat intracranial electrocorticographic (ECoG) recordings were performed with 12 epilepsy patients, at ≥1-day intervals, using a passive odd-ball paradigm with steady-state tones. Time-frequency matching pursuit analysis was used to quantify changes in gamma-band power relative to pre-stimulus baseline. Test-retest reliability was estimated based on within-subject comparisons (paired t-test, McNemars test) and correlations (Spearman rank correlations, intra-class correlations) across sessions, adjusting for within-session variability. Reliability estimates of gamma-band response robustness, spatial concordance, and reproducibility were compared with corresponding measurements from concurrent auditory evoked N1 responses.nnnRESULTSnAll patients showed increases in gamma-band power, 50-120 ms post-stimulus onset, that were highly robust across recordings, comparable to the evoked N1 responses. Gamma-band responses occurred regardless of patients performance on behavioral tests of auditory processing, medication changes, seizure focus, or duration of test-retest interval. Test-retest reproducibility was greatest for the timing of peak power changes in the high-gamma range (65-150 Hz). Reliability of low-gamma responses and evoked N1 responses improved at higher signal-to-noise levels.nnnCONCLUSIONSnEarly cortical auditory gamma-band responses are robust, spatially concordant, and reproducible over time.nnnSIGNIFICANCEnThese test-retest ECoG results confirm the reliability of auditory gamma-band responses, supporting their utility as objective measures of cortical processing in clinical and research studies.

Ketogenic Diets for Adults With Highly Refractory Epilepsy

The current review highlights the evidence supporting the use of ketogenic diets in the management of drug-resistant epilepsy and status epilepticus in adults. Ketogenic diet variants are compared and advantages and potential side effects of diet therapy are discussed.