Association of Serum Pyridoxal Phosphate Levels with Established Status Epilepticus.

BACKGROUND: The objective of this study was to determine the prevalence of pyridoxine deficiency, measured by pyridoxal phosphate (PLP) levels, in patients admitted to the hospital with established (benzodiazepine-resistant) status epilepticus (SE) (eSE) and to compare to three control groups: intensive care unit (ICU) patients without SE (ICU-noSE), non-ICU inpatients without SE (non-ICU), and outpatients with or without a history of epilepsy (outpatient). METHODS: This retrospective cohort study was conducted at the University of North Carolina Hospitals and Yale New Haven Hospital. Participants included inpatients and outpatients who had serum PLP levels measured during clinical care between January 2018 and March 2021. The first PLP level obtained was categorized as normal (> 30 nmol/L), marginal (≤ 30 nmol/L), deficient (≤ 20 nmol/L), and severely deficient (≤ 5 nmol/L). RESULTS: A total of 293 patients were included (52 eSE, 40 ICU-noSE, 44 non-ICU, and 157 outpatient). The median age was 55 (range 19-99) years. The median PLP level of the eSE group (12 nmol/L) was lower than that of the ICU-noSE (22 nmol/L, p = 0.003), non-ICU (16 nmol/L, p = 0.05), and outpatient groups (36 nmol/L, p < 0.001). Patients with eSE had a significantly higher prevalence of marginal and deficient PLP levels (90 and 80%, respectively) than patients in each of the other three groups (ICU-noSE: 70, 50%; non-ICU: 63, 54%; outpatient: 38, 21%). This significantly higher prevalence persisted after correcting for critical illness severity and timing of PLP level collection. CONCLUSIONS: Our study confirms previous findings indicating a high prevalence of pyridoxine deficiency (as measured by serum PLP levels) in patients with eSE, including when using a more restricted definition of pyridoxine deficiency. Prevalence is higher in patients with eSE than in patients in all three control groups (ICU-noSE, non-ICU, and outpatient). Considering the role of pyridoxine, thus PLP, in the synthesis of γ-aminobutyric acid and its easy and safe administration, prospective studies on pyridoxine supplementation in patients with eSE are needed.

Status epilepticus in pregnancy.

Status epilepticus is a frequent neurological emergency associated with a case fatality of about 10-15% depending on age, cause, and other factors, and a high burden for patients, caregivers, and society. In pregnancy, it can occur in two different clinical constellations: (1) In women with a history of epilepsy and (2) as new onset status epilepticus in pregnancy (NOSEP). Both entities are relatively rare but differ in terms of etiology. Here we describe the epidemiology, etiologies, diagnosis, clinical course with the maternal and fetal outcome, and the suggested management strategies for either manifestation. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022.

Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy.

OBJECTIVE: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years. METHODS: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory. RESULTS: Of 256 patients treated in the initial trials, 230 participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% (p < 0.0001, Wilcoxon signed rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. We found that 18.4% (47 of 256) experienced ≥1 year of seizure freedom, with 62% (29 of 47) seizure-free at the last follow-up and an average seizure-free period of 3.2 years (range 1.04-9.6 years). Overall QOL and epilepsy-targeted and cognitive domains of QOLIE-89 remained significantly improved (p < 0.05). There were no serious AEs related to stimulation, and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators (p < 0.05, 1-tailed χ2). CONCLUSIONS: Adjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low. CLINICALTRIALSGOV IDENTIFIER: NCT00572195. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.

Management of prolonged epileptic seizures and status epilepticus in palliative care patients.

Prolonged seizures and status epilepticus (SE) are relevant problems in palliative care. Timely recognition and effective early treatment with first- and second-line antiepileptic drugs (AEDs) may prevent unnecessary hospitalizations. Seizures should be recognized and addressed like any other symptom that causes discomfort or reduces quality of life. Use of alternative AED administration routes (buccal, intranasal, or subcutaneous) may offer possibilities for effective and individualized AED therapy, even during the last days of life. In hospice or home care, however, also intravenous treatment is possible via vascular access devices for long-term use. Aggressive unlimited intensive care unit (ICU) treatment of refractory SE in palliative patients is mostly not indicated. At worst, intensive care can be futile and possibly harmful: death in the ICU is often preceded by long and aggressive treatments. Metastatic cancer, old age, high severity of acute illness, overall frailty, poor functional status before hospital admission, and the presence of severe comorbidities all increase the probability of poor outcome of intensive care. When several of these factors are present, consideration of withholding intensive care may be in the patient's best interests. Anticipated outcomes influence patients' preferences. A majority of patients with a limited life expectancy because of an incurable disease would not want aggressive treatment, if the anticipated outcome was survival but with severe functional impairment. Doctors' perceptions about their patients' wishes are often incorrect, and therefore, advance care planning including seizure management should be done early in the course of the disease. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".

Status Epilepticus, Refractory Status Epilepticus, and Super-refractory Status Epilepticus.

PURPOSE OF REVIEW: Status epilepticus, refractory status epilepticus, and super-refractory status epilepticus can be life-threatening conditions. This article presents an overview of the three conditions and discusses their management and outcomes. RECENT FINDINGS: Status epilepticus was previously defined as lasting for 30 minutes or longer but now is more often defined as lasting 5 minutes or longer. A variety of potential causes exist for status epilepticus, refractory status epilepticus, and super-refractory status epilepticus, but all three ultimately involve changes at the cellular and molecular level. Management of patients with status epilepticus generally requires several studies, with EEG of utmost importance given the pathophysiologic changes that can occur during the course of status epilepticus. Status epilepticus is treated with benzodiazepines as first-line antiepileptic drugs, followed by phenytoin, valproic acid, or levetiracetam. If status epilepticus does not resolve, these are followed by an IV anesthetic and then alternative therapies based on limited data/evidence, such as repetitive transcranial magnetic stimulation, therapeutic hypothermia, immunomodulatory agents, and the ketogenic diet. Scores have been developed to help predict the outcome of status epilepticus. Neurologic injury and outcome seem to worsen as the duration of status epilepticus increases, with outcomes generally worse in super-refractory status epilepticus compared to status epilepticus and sometimes also to refractory status epilepticus. SUMMARY: Status epilepticus can be a life-threatening condition associated with multiple complications, including death, and can progress to refractory status epilepticus and super-refractory status epilepticus. More studies are needed to delineate the best management of these three entities.

Role of Intraoperative Neurophysiologic Monitoring in the Resection of Thalamic Astrocytomas.

BACKGROUND: The thalamus is a deep-seated and crucial structure for the sensorimotor system. It has been long considered a surgically inaccessible area because of the morbidity associated with surgical resections. Astrocytomas of the thalamus are usually treated with bioptic procedures followed by adjuvant treatments. Intraoperative neurophysiologic monitoring (IONM) allows safe and satisfactory resections of lobar gliomas, but few data are available for thalamic lesions. The aim of this study was to review the outcome of a small series of patients with thalamic astrocytomas that were treated with surgical resection with the aid of IONM. METHODS: Surgical resection with IONM was performed in 5 patients with thalamic astrocytomas (1 grade I, 1 grade II, 2 grade III, 1 grade IV). Two astrocytomas were in the dominant hemisphere. Preoperative and postoperative neuropsychological assessments were performed in 3 patients. IONM was tailored to the individual patient and consisted of transcranial motor evoked potential monitoring, cortical motor evoked potential monitoring, somatosensory evoked potential monitoring, direct electrical stimulation, electroencephalography, and electrocorticography. RESULTS: None of the patients experienced permanent motor deficits; 2 patients had a transient hemiparesis requiring rehabilitation; 1 patient had a transient aphasia, and 1 patient had permanent aphasia. None of the patients had intraoperative seizures, but 1 patient experienced postoperative transient status epilepticus. The extent of resection on postoperative volumetric magnetic resonance imaging was >70% in all cases. CONCLUSIONS: Surgical resection of thalamic astrocytomas appeared to be effective and relatively safe when guided by IONM. Larger series of patients are required to confirm these preliminary data.

Pyridoxine deficiency in adult patients with status epilepticus.

An 8-year-old girl treated at our facility for superrefractory status epilepticus was found to have a low pyridoxine level at 5 µg/L. After starting pyridoxine supplementation, improvement in the EEG for a 24-hour period was seen. We decided to look at the pyridoxine levels in adult patients admitted with status epilepticus. We reviewed the records on patients admitted to the neurological ICU for status epilepticus (SE). Eighty-one adult patients were identified with documented pyridoxine levels. For comparison purposes, we looked at pyridoxine levels in outpatients with epilepsy (n=132). Reported normal pyridoxine range is >10 ng/mL. All but six patients admitted for SE had low normal or undetectable pyridoxine levels. A selective pyridoxine deficiency was seen in 94% of patients with status epilepticus (compared to 39.4% in the outpatients) which leads us to believe that there is a relationship between status epilepticus and pyridoxine levels.

Complex febrile seizures: a practical guide to evaluation and treatment.

Febrile seizures are the most common type of childhood seizures, affecting 2% to 5% of children. A complex febrile seizure is one with focal onset, one that occurs more than once during a febrile illness, or one that lasts more than 10 to 15 minutes. Confusion still exists on the proper evaluation of a child presenting with a complex febrile seizure. There are ongoing research attempts to determine the link between complex febrile seizures and epilepsy. Further clarification and understanding of this disorder would be of great benefit to primary care providers and child neurologists.

Status epilepticus.

Status epilepticus is a common neurological emergency in childhood and associated with significant morbidity and mortality. Status epilepticus (SE) has been defined as continuous seizure activity lasting more than 30 min or 2 or more seizures in this duration without gaining consciousness between them. However, the operational definition has brought the time down to 5 min. Management can be broadly divided into initial stabilization, seizure termination, and evaluation and treatment of the underlying cause. Diagnostic evaluation and seizure control should be achieved simultaneously to improve outcome. Seizure termination is achieved by pharmacotherapy. Benzodiazepines are the first line drugs for SE. Commonly used drugs include lorazepam, diazepam, and midazolam. In children without an IV access, buccal or nasal midazolam or rectal diazepam can be used. Phenytoin as a second line agent is usually indicated when seizure is not controlled after one or more doses of benzodiazepines. If the seizures continue to persist, valproate, phenobarbitone or levetiracetam is indicated. Midazolam infusion is useful in refractory status epilepticus. Thiopentone, propofol or high dose phenobarbitone are considered for treatment of refractory status epilepticus. Prolonged SE is associated with higher morbidity and mortality. Long term neurological sequelae include epilepsy, behavioural problems, cognitive decline, and focal neurologic deficits.

Generalized convulsive status epilepticus in adults and children: treatment guidelines and protocols.

Generalized convulsive status epilepticus (GCSE) has a high morbidity and mortality, such that the rapid delivery of anticonvulsant therapy should be initiated within minutes of seizure onset to prevent permanent neuronal damage. GCSE is not a specific disease but is a manifestation of either a primary central nervous system (CNS) insult or a systemic disorder with secondary CNS effects. It is mandatory to look for an underlying cause. First-line therapies for seizures and status epilepticus include the use of a benzodiazepine, followed by an infusion of a phenytoin with a possible role for intravenous valproate or phenobarbital. If these first-line medications fail to terminate the GCSE, treatment includes the continuous infusion of midazolam, pentobarbital, or propofol.

Estado epiléptico no convulsivo infantil / Non convulsive status epilepticus in children

Introduction: Status Epilepticus (SE) is a medical emergency with high morbimortality. Non-convulsive Status Epilepticus (NCSE) is defined as electroencephalographic crises in the absence of clinical motor symptoms. Objective: A restrospective study of NCSE in our population. Patients and Methods: Charts of 30 patients in a Child Neurology Clinic seen between December 1999 and June 2008 were reviewed. According to the characteristics of the episode, they were classified as a) Typical absence, b) Atypical absence, c) Partial Complex episode. Results: Of the 30 patients, 15 (50%) were males. Median age was 46 months. Clinically, 63% of the children suffered from complex partial seizures, 30% atypical absences, 7% typical absences. Cryptogenic SE was most frequent (47%), with a mortality of 3%. Discussion: Pediatric patients have a higher risk of NCSE than adults do. Most patients already carried a diagnosis of Epilepsy, cerebral infarcts were the second most frequent cause of NCSE. They should all be monitored through EEGs. Neuroimages are of great value since outcome depends on the etiology. In summary, clinical suspicion, a history of epilepsy supported by an EEG (best if prolonged) allow early diagnosis and treatment.

Introducción: El Estado Epiléptico (EE) es una emergencia médica con alta morbimortalidad. El Estado Epiléptico No Convulsivo (EENC) es definido por la presencia de crisis electroencefalograficas en ausencia de crisis motoras clínicas. Objetivo: Realizar una descripción retrospectiva de los EENC que se presentaron en la población pediátrica atendida en nuestro centro. Pacientes y Método: Se revisaron los registros de 30 pacientes controlados neurología infantil que presentaron EENC entre diciembre de 1999 y junio de 2008. Según el tipo de crisis se clasificó en a) EENC ausencia típica; b) EENC ausencias atípicas y c) EENC parcial complejo. Según etiología se uso la clasificación de Hauser modificada. Resultados: Se analizaron 30 pacientes. Quince (50%) varones. La mediana de edad fue 46 meses. 63% fueron EENC parcial complejo, 30% EENC ausencias atípicas y 7% EENC ausencias típicas. El EE criptogénico fue el más frecuente (47%). La mortalidad fue de 3%. Discusión: Los pacientes pediátricos tienen mayor riesgo de EENC en relación a los adultos. La gran mayoría de los pacientes con EENC ya tenían el diagnóstico de epilepsia. Los infartos cerebrales fueron la segunda causa de EENC, estos deben ser monitorizados con EEG ante la sospecha de EENC. Las neuroimágenes para precisar el diagnóstico son de gran valor dado que el pronóstico de los pacientes con EENC depende de la etiología subyacente. En conclusión, la sospecha clínica, el antecedente de epilepsia y el apoyo con un EEG, especialmente prolongado, permite el diagnóstico oportuno y el tratamiento precoz.

Estado epiléptico: clasificación y pronóstico neurológico / Status Epilepticus: classification and neurological prognosis

Introducción: El estado epiléptico (EE) es una emergencia en la infancia con alta morbimortalidad, el pronóstico está determinado por el tipo de EE, edad y precocidad de tratamiento. Objetivos: Clasificar los EE según etiología y tipo de crisis. Relacionarlos con la evolución neurológica. Pacientes y Método: Se analizan las variables: tipo EE según crisis y etiología, edad, sexo, neuroimágenes y morbimortalidad en 25 pacientes hospitalizados por EE, entre Enero 1998 y Diciembre 2003. Resultados: La mediana para edad fue 33 meses (2-120 meses), relación M/F de 14/11. La distribución según tipo de crisis fue: EE convulsivo 76 por ciento, EE no convulsivo 26 por ciento. Según etiología: Remota 44 por ciento, aguda 40 por ciento, febril 12 por ciento, idiopática 4 por ciento. No hubo mortalidad. La incidencia de secuelas en pacientes previamente sanos fue de 35 por ciento, las secuelas se relacionaron con la etiología y las alteraciones en neuroimágenes. Conclusiones: El EE más frecuente según tipo de crisis es el EE Convulsivo y según etiología el EE de etiología remota. El pronóstico del EE en pacientes sanos está determinado por la etiología.

[Treatment of status epilepticus].

Status epilepticus (SE) is a condition requiring emergency care. There are convulsive SE, non-convulsive SE including complex partial status and absence status, non-convulsive electric SE and pseudostatus epilepticus, although convulsive SE is the most common. Diagnosis of status epilepticus of complex partial seizures (CPS) and absence seizures was significantly delayed because delays in seeking medical attention were common. The seizures were generalized convulsive SE in 84% and CPS status in 16%, and the overall mortality rate was 15% in 41 SE patients of our study. EEG monitoring is important to make or exclude the diagnosis of SE. Diazepam is the first choice medication and effective in the management of SE, and lately, lorazepam, midazolam, propofol and pentobarbital etc as emergency therapy. Phenytoin is also considered first-line agent in the emergency management of SE. Repetitive transcranial magnetic stimulation (rTMS) led to a prolonged latency for seizure induction after an intraperitoneal injection of pentylenetetrazol (PTZ) and effectively prevented the development of status epilepticus of PTZ-induced convulsions in the rats. Our data suggest that rTMS has suppressive effects on the neuronal excitability in rats. These effects are anticonvulsive and suggest the possibility of therapeutic use of rTMS in the patients with refractory seizures.