cannabidiol and Status-Epilepticus

To summarize and evaluate clinical experiences with refractory status epilepticus in which cannabidiol (CBD) was utilized for cessation of seizure activity.. A comprehensive literature review was performed on PubMED, MEDLINE, Scopus, and CINAHL between May - June 2022 with the assistance of a medical reference librarian using the following search terms: "Cannabidiol" [MAJR], "Status Epilepticus" [MAJR], "New-Onset Refractory Status Epilepticus", and "cannabidiol." Reports that provided dosing regimens and patient outcomes were included.. Thirty-two articles were screened. Five articles were selected for inclusion in this review and detailed the clinical courses of 11 patients. Five of the 11 patients received CBD during the chronic epilepsy stage, while the remaining 6 received it during a period of acute status epilepticus. Patients were trialed on an average of 9 anti-epileptic drugs prior to CBD administration, after which 9 of the 11 patients experienced a reduction of seizure activity. Dosing of CBD ranged between 5-25 mg/kg/day and was titrated based on patient response to therapy. Adverse effects were relatively benign and were generally limited to gastrointestinal discomfort, reported after seizure cessation.. CBD may provide a potentially efficacious and safe management strategy in refractory status epilepticus, including patients with new-onset refractory status epilepticus and febrile infection-related epilepsy syndrome. A potential for drug-drug interactions between CBD and anti-epileptic drugs warrants judicious monitoring. Additional research is necessary to determine a definitive dosing strategy for this agent.

Topics: Cannabidiol; Drug Resistant Epilepsy; Encephalitis; Humans; Seizures; Status Epilepticus

The hippocampus is one of the most susceptible regions in the brain to be distraught with status epilepticus (SE) induced injury. SE can occur from numerous causes and is more frequent in children and the elderly population. Administration of a combination of antiepileptic drugs can abolish acute seizures in most instances of SE but cannot prevent the morbidity typically seen in survivors of SE such as cognitive and mood impairments and spontaneous recurrent seizures. This is primarily due to the inefficiency of antiepileptic drugs to modify the evolution of SE-induced initial precipitating injury into a series of epileptogenic changes followed by a state of chronic epilepsy. Chronic epilepsy is typified by spontaneous recurrent seizures, cognitive dysfunction, and depression, which are associated with persistent inflammation, significantly waned neurogenesis, and abnormal synaptic reorganization. Thus, alternative approaches that are efficient not only for curtailing SE-induced initial brain injury, neuroinflammation, aberrant neurogenesis, and abnormal synaptic reorganization but also for thwarting or restraining the progression of SE into a chronic epileptic state are needed. In this review, we confer the promise of cannabidiol, an active ingredient of Cannabis sativa, for preventing or easing SE-induced neurodegeneration, neuroinflammation, cognitive and mood impairments, and the spontaneous recurrent seizures.

Topics: Animals; Cannabidiol; Comorbidity; Disease Models, Animal; Epilepsy; Humans; Status Epilepticus

Febrile infection-related epilepsy syndrome (FIRES) is a rare and catastrophic clinical syndrome occurring in previously healthy patients. Aetiology is still unknown and outcome usually poor. We describe a case of myoclonic prolonged super refractory status epilepticus (P-SRSE) in FIRES in a patient admitted to the paediatric intensive care unit of Padova, Italy.. A previously healthy 14-year-old girl with onset of myoclonic status epilepticus after a mild febrile illness was admitted to our hospital with a diagnosis of FIRES. Extensive diagnostic work-up was inconclusive. Status epilepticus and electroclinical seizures recurred every time weaning from anaesthetic agents was attempted. Eventually, a vagal nerve stimulator (VNS) was implanted and cannabidiol (CBD) administered, 43 days and 70 days after P-SRSE onset, respectively. Two days after CBD introduction, status epilepticus weaned and the girl rapidly regained complete consciousness showing a brilliant and unexpected recovery. At last follow-up, 12 months later, she is 8-months seizure free on multiple antiseizure medications, has only mild neuropsychological impairment with no neurological and intellective deficit.. To our knowledge, this represents a unique case with an extremely favourable evolution with a possible effect of the association of VNS and CBD to traditional antiseizure medications.

Topics: Adolescent; Cannabidiol; Child; Drug Resistant Epilepsy; Encephalitis; Female; Humans; Immune System Diseases; Seizures; Status Epilepticus; Vagus Nerve Stimulation

Febrile infection-related epilepsy syndrome (FIRES) is a prolonged refractory status epilepticus (SE) that develops among healthy individuals after a febrile infection. FIRES treatment is challenging due to its poor response to antiseizure medications (ASMs) and anesthetic drugs. The use of cannabidiol (CBD) as an adjunctive treatment has been suggested, albeit data about its role in the acute phase is lacking. This report describes the use of purified CBD in the acute phase of two pediatric cases of FIRES and their long-term outcome. Both children were treated with several ASMs, immunomodulators, anesthetics, and nonpharmacological treatment (ketogenic diet). CBD was administered, as an adjunctive treatment, through nasogastric tube about 30 days after onset. SE resolved within 3 days of reaching the target dose and both were seizure-free for 1 year after. Although it is difficult to define the extent to which each previous therapy contributed to recovery, in both cases CBD therapy was a turning point, reinforcing its potential role as add-on treatment in the acute phase of FIRES.

Topics: Anesthetics; Cannabidiol; Child; Drug Resistant Epilepsy; Encephalitis; Epileptic Syndromes; Humans; Seizures; Status Epilepticus

Topics: Acute Disease; Cannabidiol; Drug Resistant Epilepsy; Humans; Status Epilepticus

Anti-seizure medications (ASMs) can cause non-convulsive status epilepticus (NCSE), but account for less than 5% of all NCSE cases. We present a 63-year-old, right-handed male with a history of intractable focal epilepsy since age seven years old, whose bouts of NCSE were triggered by cannabidiol (CBD) adjunctive therapy. His most common seizure types included focal myoclonic or tonic seizures with vocalization, usually with awakening, which occurred on a monthly basis despite the combination of tiagabine, perampanel, levetiracetam, lacosamide and clonazepam. After CBD was initiated, he began to exhibit episodes of prolonged confusion, at times with myoclonic or tonic seizures. Increasing CBD doses led to more frequent and prolonged episodes. The confusional episodes occurred predominantly in the morning, with spontaneous resolution by the afternoon. During one of these episodes, he was hospitalized, and NCSE was confirmed by video-EEG monitoring. CBD was withdrawn and the patient had no further episodes of NCSE. While CBD can cause NCSE, the medication interaction between CBD and tiagabine also needs to be considered.

Topics: Anticonvulsants; Cannabidiol; Child; Confusion; Drug Resistant Epilepsy; Electroencephalography; Humans; Male; Middle Aged; Seizures; Status Epilepticus; Tiagabine

To evaluate the effectiveness and tolerability of cannabidiol (CBD) in patients with developmental and epileptic encephalopathies, including Dravet syndrome (DS), and Lennox-Gastaut syndrome (LGS), in a Spanish Expanded Access Program (EAP).. This was a multicenter, retrospective, observational study of patients treated with purified CBD in 14 hospitals across Spain. Patients with (1) written informed consent and (2) at least 6 months follow-up before the closure of the database were included. Primary effectiveness endpoints included reductions (100 %, ≥75 %, ≥50 %, ≥25 %, or 0 %) or worsening in seizure frequency (all seizure types and most disabling seizures) at 1-, 3-, 6-, and 12-month visits and at the last visit, and median relative seizure reduction between baseline and last visit. Secondary effectiveness endpoints included retention rate, reduction in seizure severity, status epilepticus, healthcare utilization, and quality of life. Primary safety endpoints included rates of adverse events (AEs) and AEs leading to discontinuation.. One hundred and two patients (DS 12 %; LGS 59 %; other epilepsy syndromes 29 %) with a mean age of 15.9 years were enrolled. Patients were highly refractory to antiseizure medications (ASMs); mean number of prior failed ASMs was 7.5 (SD 3.7). The mean CBD dose was 13.0 mg/kg/day at the last visit. The proportion of patients with ≥50 % reduction in the total number of seizures from baseline was 44.9 % at 6 months and 38.9 % at 12 months. The median number of total seizures per month reduced by 47.6 % from baseline to the last visit. At 12 months, seizure severity was lower in 33/54 patients (61.1 %) and unchanged in 17/54 patients (31.5 %). Quality of life, based on the CAVE scale, increased from a mean score of 17.9 ± 4.7 (n = 54) at baseline to 21.7 ± 5.5 (n = 51) at the last patient visit (21.2 % improvement). The mean treatment retention time was 10.3 months. There were no statistically significant changes in the number of status epilepticus episodes, but lower healthcare utilization was observed. Adverse events occurred in sixty-eight patients (66.7 %), and the most common were somnolence (34.3 %) and diarrhea (12.7 %). Cannabidiol was discontinued exclusively due to AEs in 7.8 % of patients, increasing to 25.5 % when both lack of efficacy and AEs were considered together.. Cannabidiol demonstrated promising effectiveness and tolerability in patients with developmental and epileptic encephalopathies taking part in a Spanish EAP.

Topics: Adolescent; Adult; Anticonvulsants; Cannabidiol; Child; Epilepsies, Myoclonic; Epilepsy; Humans; Lennox Gastaut Syndrome; Quality of Life; Retrospective Studies; Seizures; Status Epilepticus; Treatment Outcome

Febrile infection-related epilepsy syndrome (FIRES) is a rare catastrophic epileptic encephalopathy that presents suddenly in otherwise normal children and young adults causing significant neurological disability, chronic epilepsy, and high rates of mortality. To suggest a therapy protocol to improve outcome of FIRES, workshops were held in conjunction with American Epilepsy Society annual meeting between 2017 and 2019. An international group of pediatric epileptologists, pediatric neurointensivists, rheumatologists and basic scientists with interest and expertise in FIRES convened to propose an algorithm for a standardized approach to the diagnosis and treatment of FIRES. The broad differential for refractory status epilepticus (RSE) should include FIRES, to allow empiric therapies to be started early in the clinical course. FIRES should be considered in all previously healthy patients older than two years of age who present with explosive onset of seizures rapidly progressing to RSE, following a febrile illness in the preceding two weeks. Once FIRES is suspected, early administrations of ketogenic diet and anakinra (the IL-1 receptor antagonist that blocks biologic activity of IL-1β) are recommended.

Topics: Adolescent; Cannabidiol; Child; Child, Preschool; Diet, Ketogenic; Drug Resistant Epilepsy; Encephalitis; Epileptic Syndromes; Humans; Immune System Diseases; Infant; Interleukin 1 Receptor Antagonist Protein; Seizures, Febrile; Status Epilepticus

Purified cannabidiol is a new antiepileptic drug that has recently been approved for use in patients with Lennox-Gastaut and Dravet syndromes, but most published studies have not extended beyond 12-16 weeks.. The objective of this study was to evaluate the long-term safety, tolerability, and efficacy of cannabidiol in children with epilepsy.. Patients aged 1-17 years with refractory epilepsy were enrolled in an open-label prospective study through individual patient and expanded access programs between April 2013 and December 2014. Seizure types were video-electroencephalogram confirmed prior to enrollment. After a 28-day evaluation period, during which baseline seizure frequency was assessed, cannabidiol was given as add-on therapy at 5 mg/kg/day and titrated weekly by 5-mg/kg increments to a dose of 25 mg/kg/day. Blood tests were performed at baseline, after 1, 2, and 3 months, and every 3 months thereafter. Trough concentrations of concomitant antiepileptic drugs were measured at baseline, after 1, 2, and 3 months of therapy, and as clinically indicated afterwards. Concomitant antiepileptic drugs, ketogenic diet ratio, and vagal nerve stimulator settings remained unchanged during the baseline period and the first 3 months of treatment, unless there was a significant increase in plasma concentrations. Seizure frequency was reported daily in seizure diaries by parents or caregivers. Clinical assessments occurred after 15 days of treatment, at 1 month, at 3 months, and every 3 months thereafter. Diaries of seizure frequency and adverse events were reviewed at each visit. The primary efficacy outcome was a reduction in seizure frequency and responders were defined as those patients achieving a > 50% reduction in motor seizures.. Twenty-six children were enrolled. Most had genetic epilepsies with daily or weekly seizures and multiple seizure types. All were refractory to prior antiepileptic drugs (range 4-11, mean 7), and were taking two antiepileptic drugs on average. Duration of therapy ranged from 4 to 53 months (mean 21 months). Adverse events were reported in 21 patients (80.8%), including reduced appetite in ten (38.4%), diarrhea in nine (34.6%), and weight loss in eight (30.7%). Four (15.4%) had changes in antiepileptic drug concentrations and three had elevated aspartate aminotransferase and alanine aminotransferase levels when cannabidiol was administered together with valproate. Serious adverse events, reported in six patients (23.1%), included status epilepticus in three, catatonia in two, and hypoalbuminemia in one. Fifteen patients (57.7%) discontinued cannabidiol for lack of efficacy, one because of status epilepticus, and one for severe weight loss. The retention rate declined rapidly in the first 6 months and more gradually thereafter. At 24 months, the number of patients continuing cannabidiol as adjunctive therapy was nine of the original 26 (34.6%). Of these patients, seven (26.9%) had a sustained > 50% reduction in motor seizures, including three (11.5%) who remain seizure free.. Over a 4-year period, cannabidiol was effective in 26.9% of children with otherwise refractory epilepsy. It was well tolerated in about 20% of patients, but 80.8% had adverse events, including 23.1% with serious adverse events. Decreased appetite and diarrhea were frequent along with weight loss that became evident only later in the treatment.

Topics: Adolescent; Anticonvulsants; Cannabidiol; Child; Child, Preschool; Drug Therapy, Combination; Epilepsy; Female; Humans; Infant; Male; Prospective Studies; Seizures; Status Epilepticus; Treatment Outcome; United States; Valproic Acid

Epilepsy is a progressive neurological disease characterized by recurrent seizures and behavioral comorbidities. We investigated the antiseizure effect of cannabidiol (CBD) in a battery of acute seizure models. Additionally, we defined the disease-modifying potential of chronic oral administration of CBD on associated comorbidities in the reduced intensity status epilepticus-spontaneous recurrent seizures (RISE-SRS) model of temporal lobe epilepsy (TLE).. We evaluated the acute antiseizure effect of CBD in the maximal electroshock seizure, 6-Hz psychomotor seizure, and pentylenetetrazol acute seizure tests, as well as the corneal kindling model of chronic seizures in mice following intraperitoneal administration. Median effective or behavioral toxic dose was determined in both mice and rats. Next, we tested an intravenous preparation of CBD (10 mg/kg single dose) in a rat model of pilocarpine-induced status epilepticus. We defined the effect of chronic CBD administration (200 mg/kg orally) on spontaneous seizures, motor control, gait, and memory function in the rat RISE-SRS model of TLE.. CBD was effective in a battery of acute seizure models in both mice and rats following intraperitoneal administration. In the pilocarpine-induced status epilepticus rat model, CBD attenuated maximum seizure severity following intravenous administration, further demonstrating CBD's acute antiseizure efficacy in this rat model. We established that oral CBD attenuated the time-dependent increase in seizure burden and improved TLE-associated motor comorbidities of epileptic rats in the RISE-SRS model without affecting gait. Chronic administration of CBD after the onset of SRS ameliorated reference memory and working memory errors of epileptic animals in a spatial learning and memory task.. The present study illustrates that CBD is a well-tolerated and effective antiseizure agent and illustrates a potential disease-modifying effect of CBD on reducing both seizure burden and associated comorbidities well after the onset of symptomatic seizures in a model of TLE.

Topics: Animals; Anticonvulsants; Behavior, Animal; Cannabidiol; Disease Models, Animal; Epilepsy; Epilepsy, Temporal Lobe; Kindling, Neurologic; Memory, Short-Term; Mice; Pilocarpine; Rats; Seizures; Status Epilepticus

Febrile infection-related epilepsy syndrome (FIRES) is a devastating epilepsy affecting normal children after a febrile illness. FIRES presents with an acute phase with super-refractory status epilepticus and all patients progress to a chronic phase with persistent refractory epilepsy. The typical outcome is severe encephalopathy or death. The authors present 7 children from 5 centers with FIRES who had not responded to antiepileptic drugs or other therapies who were given cannabadiol (Epidiolex, GW Pharma) on emergency or expanded investigational protocols in either the acute or chronic phase of illness. After starting cannabidiol, 6 of 7 patients' seizures improved in frequency and duration. One patient died due to multiorgan failure secondary to isoflourane. An average of 4 antiepileptic drugs were weaned. Currently 5 subjects are ambulatory, 1 walks with assistance, and 4 are verbal. While this is an open-label case series, the authors add cannabidiol as a possible treatment for FIRES.

Topics: Acute Disease; Anticonvulsants; Cannabidiol; Child; Chronic Disease; Drug Resistant Epilepsy; Epileptic Syndromes; Fever; Humans; Infections; Male; Status Epilepticus; Treatment Outcome

Topics: Adolescent; Anticonvulsants; Cannabidiol; Drug Resistant Epilepsy; Electroencephalography; Humans; Magnetic Resonance Imaging; Male; Status Epilepticus