Sriram Ramgopal

Seizure detection, seizure prediction, and closed-loop warning systems in epilepsy

Nearly one-third of patients with epilepsy continue to have seizures despite optimal medication management. Systems employed to detect seizures may have the potential to improve outcomes in these patients by allowing more tailored therapies and might, additionally, have a role in accident and SUDEP prevention. Automated seizure detection and prediction require algorithms which employ feature computation and subsequent classification. Over the last few decades, methods have been developed to detect seizures utilizing scalp and intracranial EEG, electrocardiography, accelerometry and motion sensors, electrodermal activity, and audio/video captures. To date, it is unclear which combination of detection technologies yields the best results, and approaches may ultimately need to be individualized. This review presents an overview of seizure detection and related prediction methods and discusses their potential uses in closed-loop warning systems in epilepsy.

Risk factors associated with death in in-hospital pediatric convulsive status epilepticus

Objective To evaluate in-patient mortality and predictors of death associated with convulsive status epilepticus (SE) in a large, multi-center, pediatric cohort. Patients and Methods We identified our cohort from the KID Inpatient Database for the years 1997, 2000, 2003 and 2006. We queried the database for convulsive SE, associated diagnoses, and for inpatient death. Univariate logistic testing was used to screen for potential risk factors. These risk factors were then entered into a stepwise backwards conditional multivariable logistic regression procedure. P-values less than 0.05 were taken as significant. Results We identified 12,365 (5,541 female) patients with convulsive SE aged 0–20 years (mean age 6.2 years, standard deviation 5.5 years, median 5 years) among 14,965,571 pediatric inpatients (0.08%). Of these, 117 died while in the hospital (0.9%). The most frequent additional admission ICD-9 code diagnoses in addition to SE were cerebral palsy, pneumonia, and respiratory failure. Independent risk factors for death in patients with SE, assessed by multivariate calculation, included near drowning (Odds ratio [OR] 43.2; Confidence Interval [CI] 4.4–426.8), hemorrhagic shock (OR 17.83; CI 6.5–49.1), sepsis (OR 10.14; CI 4.0–25.6), massive aspiration (OR 9.1; CI 1.8–47), mechanical ventilation >96 hours (OR9; 5.6–14.6), transfusion (OR 8.25; CI 4.3–15.8), structural brain lesion (OR7.0; CI 3.1–16), hypoglycemia (OR5.8; CI 1.75–19.2), sepsis with liver failure (OR 14.4; CI 5–41.9), and admission in December (OR3.4; CI 1.6–4.1). African American ethnicity (OR 0.4; CI 0.2–0.8) was associated with a decreased risk of death in SE. Conclusion Pediatric convulsive SE occurs in up to 0.08% of pediatric inpatient admissions with a mortality of up to 1%. There appear to be several risk factors that can predict mortality. These may warrant additional monitoring and aggressive management.

Chronopharmacology of Anti-Convulsive Therapy

Approximately one-third of patients with epilepsy continue to have seizures despite antiepileptic therapy. Many seizures occur in diurnal, sleep/wake, circadian, or even monthly patterns. The relationship between biomarkers and state changes is still being investigated, but early results suggest that some of these patterns may be related to endogenous circadian patterns whereas others may be related to wakefulness and sleep or both. Chronotherapy, the application of treatment at times of greatest seizure susceptibility, is a technique that may optimize seizure control in selected patients. It may be used in the form of differential dosing, as preparations designed to deliver sustained or pulsatile drug delivery or in the form of ‘zeitgebers’ that shift endogenous rhythms. Early trials in epilepsy suggest that chronopharmacology may provide improved seizure control compared with conventional treatment in some patients. The present article reviews chronopharmacology in the treatment of epilepsy as well as future treatment avenues.

EEG abnormalities and seizures in genetically diagnosed Fragile X syndrome

We describe the seizure and EEG characteristics in a population of children with known Fragile X. The medical records of 135 genetically confirmed FXS patients receiving care in a Fragile X clinic and their available EEG reports were reviewed. The mean age was 5.94 years old including 18 males and 1 female. The mean age was 4–9 years old with an age range of 15 months to 13 years old. Twenty‐two patients (16.3%) in the series had parent‐reported behavior suspicious of seizures. Sixteen patients (14.1%, 1 female) had at least one EEG recorded for evaluation of clinical events suspicious for seizure, and three patients (2.2%) had an EEG in the context of a polysomnography for diagnosing sleep apnea. The mean age at EEG evaluation was 6.0 years (standard deviation 3.8 years). EEG findings included slowing of background rhythm (n = 9) and epileptiform discharges (n = 7). Four patients had normal EEGs (n = 4). Six patients (4.4% of the sample population) were diagnosed with epilepsy by both clinical seizure semiology and documented EEG abnormalities. Thirteen patients (68.4% of total) had episodes of staring and behavioral arrest with no EEG correlate, indicating non‐epileptic events. Of the eight patients who underwent a repeat EEG, five patients had showed normalization in the posterior dominant rhythm over time, two patients had unchanged findings and one patient had worsening of his EEG. Our data warrant further prospective validation.

Polymicrogyria-associated epilepsy: a multicenter phenotypic study from the Epilepsy Phenome/Genome Project.

Polymicrogyria (PMG) is an epileptogenic malformation of cortical development. We describe the clinical epilepsy and imaging features of a large cohort with PMG‐related epilepsy.

Circadian patterns of generalized tonic–clonic evolutions in pediatric epilepsy patients

OBJECTIVE To investigate the sleep/wake, day/night, and 24-h periodicity of pediatric evolution to generalized tonic-clonic seizures (GTC). METHODS Charts of 407 consecutive patients aged 0-21 years undergoing continuous video-EEG monitoring for epilepsy were reviewed for the presence of GTC evolution. Seizures were characterized according to 2001 ILAE terminology. Charts were reviewed for EEG seizure localization, MRI lesion, and for seizure occurrence in 3-h time blocks, out of sleep or wakefulness, and during the day (6 AM-6 PM) or night. Analysis was done with binomial testing. Regression models were fitted using generalized estimating equations with patients as the cluster level variable. RESULTS 71 patients (32 girls, mean age 12.63 ± 5.3 years) had 223 seizures with GTC evolution. Sleep/wake seizure distribution predicted tonic-clonic evolution better than time of day, with more occurring during sleep (p<0.001). Tonic-clonic evolution occurred most frequently between 12-3 AM and 6-9 AM (p<0.05). Patients with generalized EEG onset had more tonic-clonic evolution between 9 AM and 12 PM (p<0.05). Patients with extratemporal focal seizures were more likely to evolve during sleep (p<0.001); this pattern was not found in patients with temporal or generalized seizure onset on EEG. Patients without MRI lesions were more likely to evolve between 12 AM and 3 AM (p<0.05), in the sleeping state (p<0.001), and at night (p<0.05). Logistic regression revealed that sleep and older patient age were the most important predictors of GTC evolution. CONCLUSION GTC evolution occurs most frequently out of sleep and in older patients. Our results may assist in seizure prediction, individualized treatment patterns, and potentially complication and SUDEP prevention.

Genetics and genotype–phenotype correlations in early onset epileptic encephalopathy with burst suppression

We sought to identify genetic causes of early onset epileptic encephalopathies with burst suppression (Ohtahara syndrome and early myoclonic encephalopathy) and evaluate genotype–phenotype correlations.

Obstructive sleep apnea in infancy: A 7-year experience at a pediatric sleep center

To investigate the common indications for polysomnogram (PSG) associated co‐morbid conditions, evaluation strategies, treatment options, and outcomes in a series of infants diagnosed with obstructive sleep apnea (OSA) by a PSG.

Propranolol Therapy for Infantile Hemangioma.

ContextThere has been widespread interest surrounding the use of beta-blockers (i.e. propranolol, timolol, nadolol, acebutolol) in the treatment of infantile hemangiomas (IH).ObjectiveTo review literature evaluating treatment of IH with propranolol.Evidence AcquisitionWe conducted a literature search on PubMed and investigated for case reports, case series, and controlled trials by using search terms including “hemangioma” and “propranolol.”ResultsData suggest that beta-blockers are efficacious in cutaneous, orbital, subglottic, and hepatic hemangiomas and assist in the resolution of ulcerated hemangiomas. Improvement has also been documented in children with PHACE syndrome. Propranolol produces favorable results in children who do not respond to steroids and with no long-term adverse effects. Propranolol should be administered with caution due to rare but serious side effects including hypoglycemia, wheezing, hypotension, and bradycardia. Additionally, recurrence of lesions following the cessation of treatment has been documented.ConclusionsAlthough large-scale randomized controlled trials must be conducted in order to further evaluate the safety and the possible role of propranolol in the treatment of IH, the reviewed literature suggests that propranolol carries promise as a potential replacement for corticosteroids as first-line therapy or as a part of a multimodal approach.

Diurnal and sleep/wake patterns of epileptic spasms in different age groups

Purpose:  Epileptic spasms are seizures that occur predominantly in children and are characterized by clusters of brief axial movements. Epileptic spasms may occur in the context of a variety of syndromes. Previous research has found that epileptic spasms occur in a sleep/wake and diurnal rhythm. The purpose of this study was to identify these patterns in different age groups.