Responsive neurostimulation in pediatric epilepsy: a systematic review and individual patient meta-analysis supplemented by a single institution case series in 105 aggregated patients.

PURPOSE: To assess responsive neurostimulation (RNS) efficacy in pediatric patients with drug-resistant epilepsy, comparing response (≥ 50% reduction in seizure frequency) rates between patients with two or fewer seizure foci and those with multifocal or generalized epilepsy. This study seeks to address the gap in knowledge regarding RNS effectiveness in pediatric populations. METHODS: A systematic review and meta-analysis included data from PubMed, Embase, and Web of Science through November 2023, including 17 retrospective studies and a case series of 24 patients from our practice for a total of 105 aggregated patients. The inclusion criteria of patients were age ≤ 18 and diagnosis of DRE. Exclusion criteria were nonhuman subjects and cases where RNS was not utilized to treat DRE. Study inclusion criteria were detailing the use of RNS and comparing patients with ≤ 2 foci with other focalities. Study exclusion criteria were failure to specify RNS lead placement or type of epilepsy. The risk of bias was assessed using the ROBINS-I tool for all non-randomized studies. Effect sizes and variances were aggregated to provide a comprehensive measure of RNS efficacy, and heterogeneity among the studies was assessed using I2 statistics and Cochran's Q test to evaluate the consistency of the findings. Statistical analyses were conducted using IBM SPSS. We analyzed demographics, epilepsy history, treatment outcomes, and RNS details using descriptive and inferential statistics, including Wilcoxon-Mann-Whitney, Fisher's exact, and chi-squared tests. This systematic review was not registered. RESULTS: Seventeen retrospective studies and a single-institution case series, encompassing 105 pediatric patients, were analyzed. Effect sizes and confidence intervals were calculated to quantify treatment effects. Analyses revealed that RNS reduces seizure frequency across a spectrum of pediatric epilepsy syndromes, irrespective of the seizures' focal, multifocal, or generalized origins. The effectiveness of RNS was not influenced by the patient's sex, age at epilepsy onset, or presence of neurological and psychiatric comorbidities. Prior vagus nerve stimulation surgery and the presence of an epileptic syndrome were factors associated with a lower likelihood of near-complete seizure remission with RNS, underscoring the complexities of treating patients with generalized epilepsies or previous interventional failures. The necessity of further research into individualized surgical strategies for patients was underscored by the mixed results of comparisons of electrode characteristics with responder rates. Limitations of our study include its reliance on retrospective studies, which introduces potential bias and limits the ability to infer causality. DISCUSSION: RNS is a safe and effective treatment in pediatric patients with DRE across demographic, comorbidity, and focality variability. FDA age and focality restrictions, along with patient and physician hesitancy, may be limiting the potential for effective treatment of pediatric DRE with RNS. Prospective randomized trials are recommended to validate these findings.

Shakespeare and sleep disorders.

Shakespeare was a consummate dramatist and profound observer of human behavior. He vividly described many clinical disorders, including those of sleep. His characters suffered from somnambulism, sleep apnea, insomnia, and nightmares. Sleep, to Shakespeare, was a blessing denied to many of his protagonists.

Cat-scratch encephalopathy.

We present a case of cat-scratch disease in a 9-year-old girl, complicated by encephalopathy and seizures. Bartonella (formerly Rochalimaea) henselae is the causative agent in cat-scratch disease; methods now available for detection of this pleomorphic, gram-negative bacterium, including polymerase chain reaction amplification and indirect fluorescence antibody testing, may lead to changes in standard criteria used to verify a diagnosis of cat-scratch disease.

Treatment of Bell palsy with prednisone: a prospective, randomized study.

Two hundred thirty-nine patients with Bell palsy were randomly distributed into prednisone-treated and control groups. Patients were followed until complete recovery or for 1 year. In the steroid-treated and control groups, respectively, incomplete recovery of facial strength occurred in 12 percent and 20 percent; motor synkinesis in 9 percent and 15 percent; autonomic synkinesis in 1 percent and 10 percent; and electromyographic evidence of severe denervation in 9 percent and 17 percent. The differences reached statistical significance only for autonomic synkinesis. In the total series recovery of facial strength was incomplete in 16 percent. Residual weakness was mild in 14 percent and moderate in 2 percent. No patient remained with severe weakness. Age, hyperacusis, and severity of the initial palsy were associated with an increased risk of poor outcome.

Management of multiple sclerosis across managed care and fee-for-service systems.

OBJECTIVE: To measure and compare care for adults with MS across managed care and fee-for-service (FFS) health systems. METHODS: The authors sampled adults with MS having physician visits over a 2-year period from a group model health maintenance organization (HMO) in southern California, from a midwestern independent practice association (IPA) model managed care plan, and from the FFS portion of the practices of a random sample of southern California neurologists. The authors mailed surveys to subjects in mid-1996; 930 of 1,164 (80%) of those eligible responded. The authors measured sociodemographic and clinical characteristics, management of recent changes in mobility, bladder control, and fatigue, use of a disease-modifying agent, assessment of general health symptoms and issues, and unmet information needs. The authors adjusted comparisons between systems for comorbidity, disease severity, and disease type. RESULTS: The groups differed on most sociodemographic and clinical characteristics. There were few differences in symptom management; differences that did exist tended toward more referrals or treatment for the FFS group. Access to the disease-modifying agent available at the time of the survey did not differ across systems, although patients' perceptions of the rationale for not using the drug did vary. General health issues and symptoms were more often assessed in the FFS and IPA systems than in the HMO, but improvement was needed across all three systems of care. There were substantial unmet information needs in all groups and especially high ones in the FFS and HMO samples. CONCLUSIONS: Strategies to improve care for people with MS should be developed and evaluated, particularly in areas like symptom assessment and meeting patient information needs. Where variations in service delivery exist, longitudinal studies are also needed to evaluate the potential impact on outcomes and to evaluate reasons for variation.

Behavior disturbance, phenobarbital, and febrile seizures.

Of 109 children treated daily with phenobarbital following the first fibrile convulsion, 42% developed a behavior disorder, usually hyperactivity. Daily phenobarbital therapy was prematurely discontinued in 54% of the children with behavior abnormality (20% of those treated). The behavior disturbance usually appeared within several months, was no correlated with high blood barbiturate levels, disappeared in 73%, and improved in all children when barbiturate therapy was discontinued. No characteristics of the child, the initial febrile seizure, or recurrence of febrile seizures were significantly correlated with the occurrence of the behavior disorder except for behavioral abnormality preceding the initial febrile convulsion. Eighteen percent of the children who received no phenobarbital developed behavior disorder, most often hyperactivity. The behavior disturbance spontaneously disappeared in 52%. Among these children not given phenobarbital, the group with normal behavior had a greater frequency of family history of seizures, especially febrile convulsions, and a lower frequency of preseizure behavior disturbance; abnormalities of pregnancy, labor, delivery, and neonatal period; delayed milestones; long seizures; abnormal results of neurological examination; abnormal EEG; and recurrent febrile seizures.

Long-term effect of phenobarbital on cognitive function in children with febrile convulsions.

Psychometric tests were performed on 50 children with a history of febrile convulsions. Twenty-five of these had received daily phenobarbital for a mean of 35 months; 25 had received no phenobarbital. The two groups were matched for sex, age at the time of testing, race, and socioeconomic status. The tests used were the Wechsler Preschool and Primary Scale of Intelligence (WPPSI), the Matching Familiar Figures Test, and the Children's Embedded Figures Test. There were no significant differences in test results between the two groups.

The value of phenobarbital in the child who has had a single febrile seizure: a controlled prospective study.

A group of 355 children who were seen after a first febrile convulsion at the Kaiser Foundation Foundation Hospitals in Southern California from 1970 to 1975 were randomly assigned to three treatment groups-daily phenobarbital, "intermittent" phenobarbital given at the onset of fever, and no phenobarbital. We found that 42% had a relative with a febrile seizure and 16% a relative with an afebrile convulsion. 13% had seizures which were either lateralized or longer than ten minutes. Parents were unaware of the fever prior to the seizure in about 30% of the cases. In 81% the preseizure duration of fever was less than 24 hours. The mean follow-up was 28 months, with a range of 6 to 70 months. There was no significant difference in the recurrence rate between children receiving "intermitent" as compared with no phenobarbital. The recurrence rate in children receiving daily phenobarbital was significantly decreased compared to either of the other two groups. Severe recurrent febrile seizures occurred in no children on daily phenobarbital and in 4.4% of the children receiving either intermittent or no phenobarbital. Parental resistance, compliance, and reversible hyperactivity were the main problems encountered with the continuous phenobarbital regimen.

Identification of deoxynucleoside-polyaromatic hydrocarbon adducts by capillary zone electrophoresis-Continuous Flow-fast atom bombardment mass spectrometry.

Capillary zone electrophoresis coupled to continuous flow-fast atom bombardment mass spectrometry is shown to have utility for the detection and characterization of adducts formed by the covalent attachment of four polyaromatic hydrocarbon (PAH) and amino-PAH compounds to deoxyguanosine. Normal scanning provided structural information for a 1.3 ng injection of a model adduct, while 1.3 ng of each of a mixture of adducts was sufficient to determine their molecular weights by monitoring the constant neutral loss of deoxyribose. Exploitation of this loss in the multiple reaction monitoring mode resulted in the detection of low picogram amounts of target adducts in mixtures.

Effect of ribavirin on Type 2 Herpesvirus hominis (HVH/2) in vitro and in vivo.

Ribavirin was found to inhibit five strains of HVH/2 tested in KB cells with the M1C range being 10-100 microgram/ml. In a mouse tail animal model, it effectively reduced HVH/2-induced lesions particularly at the peak lesion periods. Ribavirin was remarkably effective when intravaginal treatment was initiated late in the infection, which suggests that it may have potential for treatment of human cutaneous infections.

Determination of the carbohydrate composition and the disulfide bond linkages of bovine lactoperoxidase by mass spectrometry.

The extent and distribution of N-glycosylation and the nature of most of the disulfide bond linkages were determined for bovine lactoperoxidase through proteolytic and glycolytic digestions combined with matrix-assisted laser desorption/ionization mass spectrometric analysis. In addition, 98% of the primary sequence of the protein was confirmed. All five of the asparagines present in sequons were found to be glycosylated, predominantly by high mannose and complex structures. Six disulfide bonds were assigned, including Cys 32-Cys 45, Cys 146-Cys 156, Cys 150-Cys 174, Cys 254-Cys 265, Cys 473-Cys 530 and Cys 571-Cys 596.

Toward an expanded vision of clinical ethics education: from the individual to the institution.

This paper advances a new paradigm in clinical ethics education that not only emphasizes development of individual clinicians' skills, but also focuses on the institutional context within which health care professionals work. This approach has been applied to the goal of improving the care provided to critically and terminally ill adults. The model has been adopted by about thirty hospitals and nursing homes; additional institutions will soon join the program, entitled Decisions Near the End of Life. Here, we describe the history and rationale for this approach, its goals, pedagogical assumptions, and design.

Nancy Beth Cruzan: in no voice at all.

KIE: This article is one of four in this issue of the Hastings Center Report concerning Cruzan v. Harmon, the Missouri right to die case that was the first of its kind to be heard by the U.S. Supreme Court. Wolf, an associate for law at the Hastings Center, criticizes the Missouri Supreme Court's Cruzan decision refusing the parents of a women in a persistent vegetative state the authority to discontinue her tube feedings. She charges that by rejecting Cruzan's prior statements and her family's surrogate decision making, the Missouri court has stripped Cruzan of her voice, her family relationship, and her body. Cruzan has the chance to reclaim these if the U.S. Supreme Court listens to statements she made before the accident that rendered her unable to speak for herself, and listens to her parents as they attempt as surrogates to effectuate their daughter's wishes.^ieng

Ethics committees in the courts.

KIE: The role of ethics committees has been regarded in different ways by different state courts, especially in regard to withholding life sustaining treatment. In re L.H.R. was a Georgia case in which the state's supreme court said that ethics committee consultation was not needed in this or future similar cases. In the 1984 case of In re Torres, the Minnesota supreme court ruled that ethics committee determinations could be used as evidence, a finding also made in the Massachusetts cases of Saikewicz and In re Spring. Wolf proposes that ethics committee determinations should be admitted into evidence and then evaluated by the court on a case-by-case basis, with the judge deciding what weight the determination deserves.^ieng

Doing ethics in Italy.

KIE: The "Leadership in Bioethics" conference held at the Rockefeller Foundation's Villa Serbelloni, in Bellagio, Italy, in February 1988 brought together directors of centers of bioethics from Europe and the United States to lay the groundwork for cooperation on bioethical issues that are international in scope, and to discuss the establishment of a North American Association of Centers of Bioethics. Comparative international bioethics was also the topic of an April conference in Milan sponsored by the Istituto Scientifico H San Raffaele and a May meeting in Venice sponsored by the Balzan Foundation.^ieng

Methohexital: a practical review for outpatient dental anesthesia.

Methohexital is an ultrashort-acting barbiturate widely used in dentistry because of its rapid onset, predictable effects, and short duration of action. Like other barbiturates, methohexital exerts its effects through the gamma-aminobutyric acid (GABA) receptor complex. By binding to its own receptor on the complex, methohexital augments the inhibitory effect of GABA on neurons and additionally can exert a similar effect independent of GABA. After intravenous injection, maximal brain concentrations are achieved within 30 sec and then quickly fall as the drug is redistributed to other tissues, yielding a duration of action after a single dose of 4 to 7 min. Hepatic metabolism accounts for elimination of the drug. Methohexital at conventional doses in healthy individuals is a mild respiratory depressant with modest cardiovascular effects. Adverse effects, however, can include apnea, cardiovascular depression, laryngospasm, hiccough, and allergic-like reactions. Although more recently introduced drugs, such as midazolam, etomidate, and propofol, have specific advantages, methohexital remains a drug of choice for dental outpatient anesthesia because of its low cost, rapid onset, short duration, lack of secretory or emetic properties, and proven history.