Dietary carbohydrates in the management of epilepsy.

PURPOSE OF REVIEW: The role of dietary carbohydrates in the management of epilepsy is intrinsically linked to the ketogenic diet. The ketogenic diet has been in use for well over a century now. There have been numerous adaptations to the diet. It is crucial to understand the indications and role of the ketogenic diet in the management of epilepsy. RECENT FINDINGS: There have been new studies that have looked at the role of ketogenic ratios in seizure control. In addition, there has been new evidence in the role of using the ketogenic diet therapy instead of antiseizure medications. These data highlight that the ketogenic diet should be tailored for patients and caregivers. When used appropriately, it can result in a significant improvement in seizure control as well as cognitive and developmental gains. SUMMARY: The ketogenic diet therapy has undergone numerous revisions and reiterations from its initial reported use in patients a century ago. This has enabled us to tailor the diet specific to each patient's underlying diagnosis.

Sudden Unexpected Death in Epilepsy: Pathogenesis, Risk Factors, and Prevention.

Sudden unexpected death in epilepsy (SUDEP) is a tragic and unexpected cause of death in patients with a known diagnosis of epilepsy. It occurs in up to 6.3 to 9.3/1,000 patients with drug-resistant epilepsy. The main three risk factors associated with SUDEP are the presence of generalized tonic-clonic seizures, the presence of a seizure in the past year, and an intellectual disability. There are several mechanisms that can result in SUDEP. The most likely sequence of events appears to be a convulsive seizure, overactivation of the autonomic nervous system, cardiorespiratory dysfunction, and death. While the risk of SUDEP is relatively high in patients with drug-resistant epilepsy, studies indicate that more than 50% of patients and caregivers are unaware of the diagnosis. Counseling about the diagnosis and preventative measures at the time of diagnosis is important. There are numerous interventions that may reduce the risk of SUDEP, including conservative measures such as nocturnal surveillance with a bed partner (where applicable) and automated devices. Optimizing seizure control with antiseizure medications and surgical interventions can result in a reduced risk of SUDEP.

Dietary Treatments for Epilepsy.

The ketogenic diet is one of the four major treatments for epilepsy, along with antiseizure medications, neuromodulation, and surgery. Ketogenic diet therapy has been proven to be a safe and effective antiseizure regimen for a century. There are multiple methods to administer the diet and the initiation should be individualized for each patient. The diet has been shown to be an effective treatment of choice for Glut1 deficiency, pyruvate dehydrogenase deficiency, infantile spasms, and superrefractory status epilepticus among others. This review discusses the administration of ketogenic diet therapy and highlights its role for specific epilepsy syndromes.

Effects of stimulation intensity on intracranial cortico-cortical evoked potentials: A titration study.

OBJECTIVE: The aim of the present study was to investigate the optimal stimulation parameters for eliciting cortico-cortical evoked potentials (CCEPs) for mapping functional and epileptogenic networks. METHODS: We studied 13 patients with refractory epilepsy undergoing intracranial EEG monitoring. We systematically titrated the intensity of single-pulse electrical stimulation at multiple sites to assess the effect of increasing current on salient features of CCEPs such as N1 potential magnitude, signal to noise ratio, waveform similarity, and spatial distribution of responses. Responses at each incremental stimulation setting were compared to each other and to a final set of responses at the maximum intensity used in each patient (3.5-10 mA, median 6 mA). RESULTS: We found that with a biphasic 0.15 ms/phase pulse at least 2-4 mA is needed to differentiate between non-responsive and responsive sites, and that stimulation currents of 6-7 mA are needed to maximize amplitude and spatial distribution of N1 responses and stabilize waveform morphology. CONCLUSIONS: We determined a minimum stimulation threshold necessary for eliciting CCEPs, as well as a point at which the current-dependent relationship of several response metrics all saturate. SIGNIFICANCE: This titration study provides practical, immediate guidance on optimal stimulation parameters to study specific features of CCEPs, which have been increasingly used to map both functional and epileptic brain networks in humans.

Seizure Action Plans for Pediatric Patients With Epilepsy: A Randomized Controlled Trial.

OBJECTIVES: Seizure action plans help patients and caregivers better self-manage their epilepsy. We hypothesized that providing pediatric patients and their caregivers with a seizure action plan would reduce unplanned health care utilization and decrease the impact of epilepsy. METHODS: We developed a seizure action plan for use in pediatric epilepsy patients. A prospective cohort was randomly assigned to receive a seizure action plan in addition to standard epilepsy care or to standard epilepsy care alone. All caregivers were surveyed using the Modified Impact on Families (MIF) questionnaire at enrollment, 3 months, and 12 months. Health care utilization measures and Modified Impact on Families questionnaire scores were compared between the 2 groups. RESULTS: Fifty-four patients received a seizure action plan and standard care, whereas 48 received standard care alone. The groups had similar demographics. There was a significantly higher proportion of overall clinic appointment no shows in the standard care group vs the seizure action plan group (P = .04); however, other significant differences in health care utilization were not found. Among patients with low seizure frequency (12 or fewer seizures per year), Seizure comfort scores on the Modified Impact on Families questionnaire were significantly higher at 12 months among the seizure action plan group compared to the standard care group. SIGNIFICANCE: Caregivers for patients with epilepsy receiving a seizure action plan were more comfortable regarding seizure care and missed fewer appointments. However, differences in health care utilization were not present. The seizure action plan appears to have more impact in patients who experience lower seizure frequencies. Further studies evaluating the impact as well as assessing caregivers' perceptions of the seizure action plan using a larger sample are needed.

Utility of long-term video-EEG monitoring for children with staring.

OBJECTIVE: Staring spells are a common reason for referral to overnight epilepsy monitoring unit (EMU) evaluation. However, inpatient EMU admissions are expensive and time consuming. This study determined what percentage of those referred for staring had a confirmed epileptic seizure on long-term video-EEG monitoring (LTM) and developed a scoring system to help prioritize which patients should undergo this procedure. METHODS: We performed a four-year retrospective chart review of all children at a tertiary pediatric hospital who received LTM (long-term monitoring) for the purposes of characterizing staring. The two goals were to: a) assess how often an LTM admission captured a staring spell that was diagnosed as a seizure and b) determine if any baseline factors predicted this particular positive result. We coded several characteristics of the most recent prior routine EEG if available. We also coded parental reports of the duration, frequency, and breakability of the events as well as post-ictal mental status and the presence/absence of automatisms. Finally, we coded previous neurological and psychiatric diagnoses and medications, as well as family history of epilepsy. RESULTS: Of the 276 admissions, only 29 (11%) captured a staring spell and diagnosed it as seizure. Several baseline variables predicted the likelihood of this positive result. Based on this information, we created a scoring system as follows: -3 points if the previous EEG was normal, -1 point if the child took a medication for a psychiatric condition, +1 point if the child took an anti-epileptic drug for epilepsy, and +1 point if the spells lasted less than 1min. If the total score was zero or less, staring spells diagnosed as seizures rarely occurred (less than 5% of the studies). SIGNIFICANCE: Our scoring system shows how consideration of prior EEG findings, medication history, and staring spell duration can help prioritize patients for LTM admission to evaluate if staring spells are epileptic seizures.

Inflammation drives renal scarring in experimental pyelonephritis.

Acquired renal scarring occurs in a subset of patients following febrile urinary tract infections and is associated with hypertension, proteinuria, and chronic kidney disease. Limited knowledge of histopathology, immune cell recruitment, and gene expression changes during pyelonephritis restricts the development of therapies to limit renal scarring. Here, we address this knowledge gap using immunocompetent mice with vesicoureteral reflux. Transurethral inoculation of uropathogenic Escherichia coli in C3H/HeOuJ mice leads to renal mucosal injury, tubulointerstitial nephritis, and cortical fibrosis. The extent of fibrosis correlates most significantly with inflammation at 7 and 28 days postinfection. The recruitment of neutrophils and inflammatory macrophages to infected kidneys is proportional to renal bacterial burden. Transcriptome analysis reveals molecular signatures associated with renal ischemia-reperfusion injury, immune cell chemotaxis, and leukocyte activation. This murine model recapitulates the cardinal histopathological features observed in humans with acquired renal scarring following pyelonephritis. The integration of histopathology, quantification of cellular immune influx, and unbiased transcriptional profiling begins to define potential mechanisms of tissue injury during pyelonephritis in the context of an intact immune response. The clear relationship between inflammatory cell recruitment and fibrosis supports the hypothesis that acquired renal scarring arises as a consequence of excessive host inflammation and suggests that immunomodulatory therapies should be investigated to reduce renal scarring in patients with pyelonephritis.