Predictors of drug-resistant epilepsy in childhood epilepsy syndromes: A subgroup analysis from a prospective cohort study.

OBJECTIVE: Previous studies assessing factors associated with drug-resistant epilepsy (DRE) were constrained by their amalgamation of all epilepsy syndromes in their analyses and the absence of uniform criteria for defining DRE. Our objective was to identify predictors of DRE among the four primary childhood epilepsy syndrome groups within a cohort of children with new onset seizures, using the International League Against Epilepsy (ILAE) definition of DRE and the recent classification of epilepsies. METHODS: This is a prospective study of 676 children with new onset seizures initiated on antiseizure medication. Patients were monitored for the occurrence of DRE according to the ILAE criteria and were categorized into one of four epilepsy groups: self-limited focal epilepsies (SeLFEs), genetic generalized epilepsies (GGEs), developmental epileptic encephalopathies (DEEs), and focal epilepsies. Cox regression analysis was performed to identify predictors of DRE within each epilepsy group. RESULTS: Overall, 29.3% of children were classified as having DRE, with the highest incidence observed among children diagnosed with DEEs (77.7%), followed by focal epilepsies (31.5%). Across the entire cohort, predictors of DRE included the presence of an epileptogenic lesion, a higher pretreatment number of seizures, experiencing multiple seizure types, presence and severity of intellectual and developmental delay, myoclonus, and younger age at epilepsy onset. Within the GGEs, only a younger age at seizure onset and experiencing multiple seizure types predicted DRE. Among focal epilepsies, predictors of DRE included the presence of an epileptogenic lesion, experiencing multiple seizure types, and having a greater number of pretreatment seizures. Within the DEEs, predictors of DRE were the occurrence of tonic seizures. Predictors of DRE within SeLFEs could not be identified. SIGNIFICANCE: This study indicates that different epilepsy syndromes are associated with distinct predictors of drug resistance. Anticipation of drug resistance within various groups is feasible using accessible clinical variables throughout the disease course.

Sexual health services in urban, suburban, and rural outpatient mental healthcare settings in New York: findings from a survey of practices and gaps.

We surveyed all licensed outpatient mental health programs in New York to examine sexual health services and training needs of providers. Gaps were found in processes for assessing whether patients were sexually active, engaging in sexual risk behaviours, and in need of HIV testing and pre-exposure prophylaxis. Significant differences between urban, suburban, and rural settings statewide were found in how the following sexual health services were delivered: education; on-site sexually transmitted infection screenings; and condom distribution and barriers to distribution. Staff training in sexual health services delivery is critically needed for optimal sexual health and recovery of patients in community mental healthcare.

Hippocampal injury and learning deficits following non-convulsive status epilepticus in periadolescent rats.

The effects of non-convulsive status epilepticus (NCSE) on the developing brain remain largely elusive. Here we investigated potential hippocampal injury and learning deficits following one or two episodes of NCSE in periadolescent rats. Non-convulsive status epilepticus was induced with subconvulsive doses of intrahippocampal kainic acid (KA) under continuous EEG monitoring in postnatal day 43 (P43) rats. The RKA group (repeated KA) received intrahippocampal KA at P43 and P44, the SKA group (single KA injection) received KA at P43 and an intrahippocampal saline injection at P44. Controls were sham-treated with saline. The modified two-way active avoidance (MAAV) test was conducted between P45 and P52 to assess learning of context-cued and tone-signaled electrical foot-shock avoidance. Histological analyses were performed at P52 to assess hippocampal neuronal densities, as well as potential reactive astrocytosis and synaptic dysfunction with GFAP (glial fibrillary acidic protein) and synaptophysin (Syp) staining, respectively. Kainic acid injections resulted in electroclinical seizures characterized by behavioral arrest, oromotor automatisms and salivation, without tonic-clonic activity. Compared to controls, both the SKA and RKA groups had lower rates of tone-signaled shock avoidance (p < 0.05). In contextual testing, SKA rats were comparable to controls (p > 0.05), but the RKA group had learning deficits (p < 0.05). Hippocampal neuronal densities were comparable in all groups. Compared to controls, both the SKA and RKA groups had higher hippocampal GFAP levels (p < 0.05). The RKA group also had lower hippocampal Syp levels compared to the SKA and control groups (p < 0.05), which were comparable (p > 0.05). We show that hippocampal NCSE in periadolescent rats results in a seizure burden-dependent hippocampal injury accompanied by cognitive deficits. Our data suggest that the diagnosis and treatment of NCSE should be prompt.

Norovirus: a novel etiologic agent in hemolytic uremic syndrome in an infant.

BACKGROUND: Hemolytic uremic syndrome is a rare thrombotic microangiopathy usually seen in infants and children below the age of 5 years. It usually follows a bout of bloody diarrhea caused by Shiga toxin producing E coli and is characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury. We report the first case of hemolytic uremic syndrome in an infant following Norovirus gastroenteritis. CASE PRESENTATION: A nine-month-old male infant, was admitted with an 8-day history of watery, non-bloody diarrhea, vomiting and decreased oral intake. Physical exam revealed normal blood pressure, pallor and generalized edema. Laboratory findings were significant for microangiopathic hemolytic anemia, thrombocytopenia and azotemia. Stool studies with Multiplex Qualitative reverse transcriptase PCR were positive for Norovirus GI/G II. His clinical course was unusually severe, complicated by oligoanuria and worsening uremia requiring peritoneal dialysis but with eventual complete recovery. CONCLUSIONS: To our knowledge this is the first case of Norovirus associated HUS in an infant. Given the ubiquity of this virus as a major cause of diarrhea, together with the increased availability of Multiplex Qualitative PCR in reference laboratories, it is quite possible that we shall be seeing more such cases in the future.

Prospective study of epilepsy with generalized tonic-clonic seizures alone: Clinical features, response to treatment, and likelihood of medication withdrawal.

OBJECTIVE: This prospective study aimed to delineate the demographics, natural progression, and treatment response of patients newly diagnosed with epilepsy with generalized tonic-clonic seizures alone (EGTCA). Furthermore, our objective includes assessing the seizure recurrence rate post antiseizure medication (ASM) discontinuation within this cohort, alongside exploring predictive factors for seizure relapse. METHODS: The study cohort, derived from an ongoing, prospective, multicenter investigation on children and adults with new-onset unprovoked seizures, included consecutive patients enrolled between March 2010 and March 2020, and meeting mandatory ILAE criteria for EGTCA diagnosis. Participants underwent a 3-h sleep-deprived video-EEG recording along with an epilepsy protocol brain magnetic resonance imaging (MRI) with repeat EEG at each follow-up. Cumulative time-dependent probabilities of seizure recurrence were calculated using Kaplan-Meier survival analysis. Logistic regression identified variables associated with seizure recurrence following ASM taper. RESULTS: Eighty-nine patients with a median age of 16 years were included, constituting 31% of those diagnosed with an idiopathic generalized epilepsy. Regarding the circadian distribution of seizures, 59.6% of patients exclusively experienced diurnal seizures, 12.4% exclusively nocturnal, and 28.1% experienced both diurnal and nocturnal seizures. Generalized spike-wave discharges (GSWD) were present in the initial EEG of 88% of patients. A GTC recurred in 14% of patients treated with ASM compared with 73% of untreated patients (p < 0.00001). ASM discontinuation was attempted in 50 patients after a median treatment duration of 3 years, with 44% experiencing a recurrence. Patient-initiated taper and a mixed circadian seizure pattern independently predicted a higher likelihood of recurrence post-ASM discontinuation. SIGNIFICANCE: Our findings underscore the importance of prompt treatment upon the diagnosis of EGTCA. Notably, lifelong treatment may not be imperative; patients seizure-free for at least 2 years, with the absence of GSWD on EEG, often maintained seizure freedom after ASM withdrawal, especially with physician-initiated tapering. PLAIN LANGUAGE SUMMARY: Seizures in individuals diagnosed with "epilepsy with generalized tonic-clonic seizures alone" (EGTCA) typically start during adolescence and often respond well to antiseizure medications. An electroencephalogram, which measure brain waves, will show abnormal discharges in most patients with EGTCA. Lifelong treatment with antiseizure medication is not necessary for everyone with EGTCA; approximately, 40% can successfully stop treatment without facing seizure recurrence. Patients who stop medication on their own have a higher risk of seizures returning compared with those who undergo cessation under a doctor's supervision.

Case report: Rapid recovery after intrathecal rituximab administration in refractory anti-NMDA receptor encephalitis: report of two cases.

Background: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is one of the most prevalent etiologies of autoimmune encephalitis. Approximately 25% of anti-NMDAR encephalitis cases prove refractory to both first- and second-line treatments, posing a therapeutic dilemma due to the scarcity of evidence-based data for informed decision-making. Intravenous rituximab is commonly administered as a second-line agent; however, the efficacy of its intrathecal administration has rarely been reported. Case summary: We report two cases of severe anti-NMDAR encephalitis refractory to conventional therapies. These patients presented with acute-onset psychosis progressing to a fulminant picture of encephalitis manifesting with seizures, dyskinesia, and dysautonomia refractory to early initiation of first- and second-line therapeutic agents. Both patients received 25 mg of rituximab administered intrathecally, repeated weekly for a total of four doses, with no reported adverse effects. Improvement began 2-3 days after the first intrathecal administration, leading to a dramatic recovery in clinical status and functional performance. At the last follow-up of 6 months, both patients remain in remission without the need for maintenance immunosuppression. Conclusion: Our cases provide evidence supporting the intrathecal administration of rituximab as a therapeutic option for patients with refractory anti-NMDAR encephalitis. Considering the limited penetration of intravenous rituximab into the central nervous system, a plausible argument can be made favoring intrathecal administration as the preferred route or the simultaneous administration of intravenous and intrathecal rituximab. This proposition warrants thorough investigation in subsequent clinical trials.

Role of Early Intravenous Immunoglobulins in Halting Clinical and Radiographic Disease Progression in Rasmussen Encephalitis.

BACKGROUND: Rasmussen encephalitis (RE) is a rare progressive presumed autoimmune disorder characterized by pharmacoresistant epilepsy and progressive motor and cognitive deterioration. Despite immunomodulation, more than half of the patients with RE ultimately require functional hemispherotomy. In this study, we evaluated the potential beneficial effects of early initiation of immunomodulation in slowing disease progression and preventing the need for surgical interventions. METHODS: A retrospective chart review over a 10-year period was conducted at the American University of Beirut Medical Center to identify patients with RE. Data were collected on seizure characteristics, neurological deficits, electroencephalography, brain magnetic resonance imaging results (including volumetric analyses for an objective assessment of radiographic progression), and treatment modalities. RESULTS: Seven patients met the inclusion criteria for RE. All patients received intravenous immunoglobulins (IVIGs) as soon as the diagnosis was entertained. Five patients with only monthly to weekly seizures at the time of IVIG initiation had favorable outcomes without resorting to surgery, along with a relative preservation of the gray matter volumes in the affected cerebral hemispheres. Motor strength was preserved in those patients, and three were seizure free at their last follow-up visit. The two patients who required hemispherotomy were already severely hemiparetic and experiencing daily seizures at the time of IVIG initiation. CONCLUSIONS: Our data suggest that the early initiation of IVIG as soon as a diagnosis of RE is suspected, and particularly before the appearance of motor deficits and intractable seizures, can maximize the beneficial effects of immunomodulation in terms of controlling seizures and reducing the rate of cerebral atrophy.

Early predictors of remission in children and adolescents with new-onset epilepsy: A prospective study.

PURPOSE: This study aims to identify predictive factors of a two-year remission (2YR) in a cohort of children and adolescents with new-onset seizures based on baseline clinical characteristics, initial EEG and brain MRI findings. METHODS: A prospective cohort of 688 patients with new onset seizures, initiated on treatment with antiseizure medication was evaluated. 2YR was defined as achieving at least two years of seizure freedom during the follow-up period. Multivariable analysis was performed and recursive partition analysis was utilized to develop a decision tree. RESULTS: The median age at seizure onset was 6.7 years, and the median follow-up was 7.4 years. 548 (79.7%) patients achieved a 2YR during the follow up period. Multivariable analysis found that presence and degree of intellectual and developmental delay (IDD), epileptogenic lesion on brain MRI and a higher number of pretreatment seizures were significantly associated with a lower probability of achieving a 2YR. Recursive partition analysis showed that the absence of IDD was the most important predictor of remission. An epileptogenic lesion was a significant predictor of non-remission only in patients without evidence of IDD, and a high number of pretreatment seizures was a predictive factor in children without IDD and in the absence of an epileptogenic lesion. CONCLUSION: Our results indicate that it is possible to identify patients at risk of not achieving a 2YR based on variables obtained at the initial evaluation. This could allow for a timely selection of patients who require close follow-up, consideration for neurosurgical intervention, or investigational treatments trials.

Causes of New-Onset Seizures and Their Treatment in Children With Non-CNS Malignancies: A Retrospective Study in a Tertiary Care Center.

BACKGROUND: Seizures occur in up to 13% of children with non-central nervous system (CNS) malignancies, but little is known about their causes and optimal diagnostic and therapeutic approaches. Here we sought to determine etiologies and clinical trajectories of new-onset seizures in this patient population. METHODS: A retrospective chart review over a 10-year period was conducted at the American University of Beirut Medical Center to identify children with non-CNS malignancies and at least one new-onset seizure. Data were collected on the underlying malignancy, seizure etiology, clinical course, treatments, electroencephalograms, and brain imaging. RESULTS: New-onset seizures occurred in 56 children (2-year median follow-up), most commonly in the context of acute lymphoblastic leukemia, lymphomas, and sarcomas. In 19 children, the first seizure consisted of status epilepticus. The most common etiologies were cerebrovascular accidents, posterior reversible encephalopathy syndrome, and metastasis. Forty-nine patients received anti-seizure medications (ASMs). Withdrawal of ASMs was successful in 19 children with normal initial or follow-up brain imaging but failed in three patients with persistent brain lesions. The remaining children, all of whom except two had structural brain abnormalities, received chronic ASMs and remained seizure free for a median period of 2 years at the last follow-up in survivors. CONCLUSIONS: Not only are seizures in children with non-CNS cancers often indicative of a serious brain insult, but they can also be challenging in the form of status epilepticus. An urgent diagnostic evaluation is therefore needed to expedite treatment, which should be tailored to the chronicity of the underlying cause.

Super refractory status epilepticus secondary to anti-GAD antibody encephalitis successfully treated with aggressive immunotherapy.

Antibodies against glutamic acid decarboxylase are reported in association with a number of neurological conditions including limbic encephalitis. We report a case of anti-GAD-antibody associated encephalitis presenting with super-refractory status epilepticus. We describe the clinical course, management, and the outcome. In addition, we review the presentation and outcomes of reported cases of anti-GAD encephalitis. Similar to the reported cases of anti-GAD encephalitis, our case was refractory to treatment with conventional antiseizure medication. Treatment with intravenous immune globulin (IVIG), high dose corticosteroids, and plasmapheresis had partial response, but escalation of treatment to the use of tocilizumab was associated with significant clinical improvement.

High-Dose Levetiracetam for Neonatal Seizures: A Retrospective Review.

BACKGROUND: Neonatal seizures are frequently encountered in the neonatal intensive care unit and may be associated with serious long-term neurological sequelae. Response to treatment continues to be modest, and treatment guidelines remain unclear. The use of levetiracetam has been on the rise in the past several years due to its favorable safety profile in the face of limited data on its efficacy and optimal dosing regimens. Unlike the older age groups, the benefit of escalating to high-dose levetiracetam of 80-100 mg/kg/day in neonates not responding to the standard used dosing regimen (40-60 mg/kg/day) is not studied. We sought to investigate the safety and efficacy of levetiracetam escalation to high dose regimens for neonatal seizures. METHODS: A retrospective chart review over a 7-year period was conducted at the American University of Beirut to identify neonates with electrographically proven seizures treated with levetiracetam. Data was collected on electroclinical seizure characteristics, underlying etiology, seizure control, other anti-seizure medications, and adverse effects. RESULTS: Electronic chart review revealed a total of 15 neonates with electrographically confirmed seizures treated with levetiracetam, with escalation to high doses in seven. As a first line drug, levetiracetam monotherapy terminated seizures in six out 10 neonates, two of whom had complete seizure cessation only after escalation to high doses of 80 or 100 mg/kg/day. When used in combination with other anti-seizure medications, four out of five neonates achieved complete seizure cessation upon escalation to high doses of levetiracetam. No adverse effects were noted. CONCLUSIONS: In neonates not responding to the standard used levetiracetam doses, incremental increases to 80-100 mg/kg/day may be considered. Prospective studies are needed to confirm the promising role of such high dosing regimens, and to better elucidate the role of levetiracetam in neonatal seizures.

Three Decades and Counting: HIV Service Provision in Outpatient Mental Health Settings.

OBJECTIVE: People with serious mental illness in the United States have higher human immunodeficiency virus (HIV) infection rates than the general U.S. population. This study aimed to assess delivery of HIV services in New York State's outpatient mental health programs. Greater access would enhance efforts to improve HIV prevention and care outcomes. METHODS: The authors surveyed directors of licensed outpatient mental health care programs statewide to investigate their HIV service delivery. Data were compared with surveys conducted in 1997 and 2004 in order to examine differences in services between geographic regions and time periods. RESULTS: Outpatient mental health programs have improved in the volume and range of HIV services offered, but their provision of preexposure prophylaxis, condoms, HIV testing, and HIV antiretroviral treatment monitoring has lagged. CONCLUSIONS: New York's initiative to end the HIV epidemic is not optimized to reach people with serious mental illness in settings designed for their care.