Anticonvulsant Doses Research Articles

Thyroid Hormone Status in Children Taking Antiepileptic Drugs (AEDs): An Experience in a Tertiary Care Hospital of Bangladesh.

Introduction: Antiepileptic drugs (AEDs) may alter thyroid hormone homeostasis at the level of biosynthesis, release, transport, metabolism and excretion of thyroid hormones. The purpose of the study was to see the thyroid hormone status in children with epilepsy treating with common antiepileptic drugs. Materials & Method: The cross-sectional study was carried out in department of pediatric neurology, National Institute of Neurosciences and Hospital (NINS), Dhaka. One hundred and sixty epileptic children aged 1 year to 14 years who were on monotherapy or polytherapy with the most commonly used Antiepileptic drugs (AEDs) for at least 6 months or more were enrolled. Serum TSH and FT4 were measured in all selected patients with early morning serum sample. Result: Nearly one third of study subjects had thyroid dysfunction, most of which were Subclinical hypothyroidism (SCH). The frequency of SCH was 29.2% in carbamazepine(CBZ), 50% in oxcabazepine (OXC), 28.6% in phenobarbitone(PHB) and 13% in valproic acid (VPA) treated epileptic children. No child was found to have subclinical hypothyroidism with topiramate and ethosuximide monotherapy. Antiepileptic drugs (AEDs) monotherapy or polytherapy had no significant difference in alteration on thyroid hormone level. Use of CBZ for long duration significantly altered thyroid function. Doses of Antiepileptic drugs (AEDs) didn’t show any significant thyroid dysfunction. Conclusion: Commonly used Antiepileptic drugs (AEDs) in children with epilepsy were associated with alteration of thyroid hormones, most commonly subclinical hypothyroidism. BANGLADESH J CHILD HEALTH 2022; VOL 46 (2) : 58-64

Bone Marrow Nucleated Cells and Bone Marrow-Derived CD271+ Mesenchymal Stem Cell in Treatment of Encephalopathy and Drug-Resistant Epilepsy.

The broad spectrum of brain injuries in preterm newborns and the plasticity of the central nervous system prompts us to seek solutions for neurodegeneration to prevent the consequences of prematurity and perinatal problems. The study aimed to evaluate the safety and efficacy of the implantation of autologous bone marrow nucleated cells and bone marrow mesenchymal stem cells in different schemes in patients with hypoxic-ischemic encephalopathy and immunological encephalopathy. Fourteen patients received single implantation of bone marrow nucleated cells administered intrathecally and intravenously, followed by multiple rounds of bone marrow mesenchymal stem cells implanted intrathecally, and five patients were treated only with repeated rounds of bone marrow mesenchymal stem cells. Seizure outcomes improved in most cases, including fewer seizures and status epilepticus and reduced doses of antiepileptic drugs compared to the period before treatment. The neuropsychological improvement was more frequent in patients with hypoxic-ischemic encephalopathy than in the immunological encephalopathy group. Changes in emotional functioning occurred with similar frequency in both groups of patients. In the hypoxic-ischemic encephalopathy group, motor improvement was observed in all patients and the majority in the immunological encephalopathy group. The treatment had manageable toxicity, mainly mild to moderate early-onset adverse events. The treatment was generally safe in the 4-year follow-up period, and the effects of the therapy were maintained after its termination.

Efficacy of Gasserian Ganglion High‐Voltage, Long‐Duration Pulsed Radiofrequency Combined With Block on Acute/Subacute Zoster‐Related Trigeminal Neuralgia

Background: Trigeminal postherpetic neuralgia (TPHN) is a severe chronic pain that can lead to various socioeconomic consequences. Therefore, it is necessary to explore optimal treatment options for acute/subacute herpes zoster (HZ)–related trigeminal neuralgia and prevent the further development of TPHN. High‐voltage, long‐duration pulsed radiofrequency (HL‐PRF) of the Gasserian ganglion is a new surgical intervention used to treat PHN. A ganglion block has been reported to possess anti‐inflammatory effects and potential analgesic benefits.Methods: We included 83 patients with HZ‐related acute/subacute trigeminal neuralgia admitted from January 1, 2021, to June 1, 2023, and received Gasserian ganglion HL‐PRF combined with block. A 6‐month follow‐up was conducted, including Numerical Rating Scale (NRS) scores, Pittsburgh Sleep Quality Index (PSQI), the incidence of TPHN, the dosage of anticonvulsants and analgesics, efficacy, and adverse events.Results: All patients showed a significant decrease in postoperative NRS scores (p < 0.05). The NRS scores of the acute HZ group were consistently lower than those of the subacute HZ group at different time points (p < 0.01). The overall incidence of TPHN from the onset of HZ to 12 weeks is 21.68%. The incidence of TPHN in the acute phase group was 12.77%, significantly lower than the 33.33% in the subacute phase group (p = 0.024). The effective rate was 74.7% in all patients, at 3 months after the treatment. The effective rate was 82.98% in the acute phase group and 63.89% in the subacute phase group, showing a statistically significant difference (p = 0.047). The PSQI score of the acute group was consistently lower than that of the subacute group (p < 0.01). The dosage of analgesics and anticonvulsants used in the acute HZ group was lower than that in the subacute group (p < 0.01). All patients did not experience serious adverse reactions.Conclusions: Gasserian ganglion HL‐PRF combined with block can be an effective and safe technique to relieve the pain of acute/subacute zoster‐related trigeminal neuralgia and prevent the incidence of TPHN.

Temporo-Parietal Extraventricular Approach for Deep Brain Stimulation Targeting the Anterior Nucleus of the Thalamus: Institutional Experience.

The anterior nucleus of the thalamus (ANT) is a common target for deep brain stimulation (DBS) for drug-resistant epilepsy (DRE). However, the surgical approach to the ANT remains challenging because of its unique anatomy. This study aims to summarize our experience with the posterior temporo-parietal extraventricular (TPEV) approach targeting the ANT for DBS in DRE. We performed a retrospective analysis of patients with DRE who underwent ANT-DBS using the TPEV approach between January 2011 and February 2021. Subjects with at least 6-month follow-up were eligible. The final lead position and number of active contacts targeting the anteroventral nucleus (AV) of the ANT were assessed using Lead-DBS. Mean seizure frequency reduction percentage and responder rate (≥50% decrease in seizure frequency) were determined. Thirty-one patients (mean age: 32.9 years; 52% female patients) were included. The mean follow-up period was 27.6 months ± 13.9 (29, 16-36). The mean seizure frequency reduction percentage was 65% ± 26 (75, 50-82). Twenty-six of 31 participants (83%) were responders, P < .001. Two subjects (6%) were seizure-free for at least 6 months at the last evaluation. Antiepileptic drugs dose and/or number decreased in 17/31 subjects (55%). The success rate for placing at least 1 contact at AV was 87% (27/31 patients) bilaterally. The number of active contacts at the AV was significantly greater in the responder group, 3.1 ± 1.3 (3, 2-4) vs 1.8 ± 1.1 (2, 1-2.5); P = .041 with a positive correlation between the number of active contacts and seizure reduction percentage; r = 0.445, R 2 = 0.198, P = .012. The TPEV trajectory is a safe and effective approach to target the ANT for DBS. Future studies are needed to compare the clinical outcomes and target accuracy with the standard approaches.

Effect of SARS-CoV-2 infection on seizure, anxiety, and depression in 107 patients with epilepsy

ObjectiveTo study the effects of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) on epileptic seizures, anxiety, and depression in patients with epilepsy. MethodsBased on the inclusion and exclusion criteria, an ambispective cohort study was hereby conducted on patients with epilepsy infected with SARS-CoV-2 who visited the outpatient and ward of the Department of Neurology of Xinyang Central Hospital from December 2022 (when the domestic epidemic prevention and control policy was lifted) to February 2023. A face-to-face questionnaire survey involving factors including basic information, vaccination with inactivated COVID-19 vaccines, number of seizures within 2 months before and after SARS-CoV-2 infection, and scores of anxiety and depression was carried out. ResultsA total of 107 patients with epilepsy satisfying the inclusion and exclusion criteria completed the follow-up after 2 months. It was found that enrolled patients maintained the original dose of antiepileptic drugs, but the frequency of seizures after COVID-19 infection could not be controlled. After infection with SARS-CoV-2, the frequency of seizures in patients with epilepsy in 2 months increased compared with that before infection (P < 0.05). Meanwhile, compared with the vaccinated group, the high-frequency seizure rate of epilepsy in the unvaccinated group was higher. (P < 0.05), and the anxiety and depression scores of patients with epilepsy were worse than those before they were infected (P < 0.05). ConclusionBeing infected with SARS-CoV-2 can increase the number of seizures and aggravate the degree of anxiety and depression in patients with epilepsy. The inactivated vaccine is protective, and the inactivated SARS-CoV-2 vaccine can reduce the rate of high-frequency seizures.

Discussion of Acute Deficiency Syndrome Theory and its Clinical Application

Discussion of Acute Deficiency Syndrome Theory and its Clinical Application

Thalamic responsive neurostimulation for the treatment of refractory epilepsy: an individual patient data meta-analysis.

In recent years, the treatment of drug-resistant epilepsy (DRE) has made greater use of surgery and expanded options for neurostimulation or neuromodulation. Up to this point, responsive neurostimulation (RNS) has been very promising but has mainly used only the cortex as a target. In this individual patient data meta-analysis (IPDMA), the authors sought to establish if a novel RNS target, the thalamus, can be used to treat DRE. The literature regarding the management of DRE by targeting the thalamus with RNS was reviewed per IPDMA guidelines. Five databases were searched with keywords [((Responsive neurostimulation) OR (RNS)) AND ((thalamus) OR (thalamic) OR (Deep-seated) OR (Diencephalon) OR (limbic))] in March 2022. The median (interquartile range) age at implantation was 17 (13.5-27.5) years (n = 42) with an epilepsy duration of 12.1 (5.8-15.3) years. In total, 52.4% of patients had previously undergone epilepsy surgery, 28.6% had prior vagus nerve stimulation, and 2.4% had prior RNS. The median preimplant seizure frequency was 12 per week. The median seizure reduction at last follow-up was 73%. No study in this IPDMA reported complications, although 7 cases (16.3%) did require reoperation. Behavioral improvements and reduced antiepileptic drug dose or quantity were reported for 80% and 28.6% of patients, respectively. This review indicates that thalamic RNS may be safe and effective for treating DRE. Long-term and controlled studies on thalamic RNS for DRE would further elucidate this technique's potential benefits and complications and help guide clinical judgment in the management of DRE.

Adverse cutaneous reactions to psychotropic drugs

IntroductionPsychotropic drugs are not devoid of side effects, especially cutaneous reactions, some of which are severe, and can jeopardize functional and life prognosis. The Aim of this study is to highlight the epidemiological and clinical features of severe cutaneous adverse reactions (SCARs) due to psychotropic drugs. Materials and methodsWe carried out a retrospective study over a period of 10years, It concerned all patients hospitalized in our dermatology department for SCARs induced by psychotropic drugs. The imputability was confirmed by the French methodology of Bégaud et al. ResultsWe identified 41 cases, of which 18 patients (43.9%) were being treated with psychotropic drugs for the first time. The most incriminated psychotropic drugs were: carbamazepine (n=16), phenobarbital (n=8), lamotrigine (n=5). Clinical forms were: drug reaction with eosinophilia and systemic symptoms syndrome (n=30), Stevens–Johnson syndrome (n=4), overlap syndrome (n=1), drug-induced vasculitis (n=4), symmetrical drug-related intertriginous and flexural exanthema syndrome (n=1), photosensitivity (n=1). Complications were as follows: hepatic cytolysis (75%), cholestasis (60%), functional renal failure (43%). Carbamazepine was statistically correlated with renal damage and cholestasis (P=0.013) and phenobarbital was associated with a risk of hepatic cytolysis (P=0.027). ConclusionCutaneous side effects to psychotropic drugs remain rare<2%. In our study, we found that rapid or recent increase in dose of anticonvulsants, or the combination of several psychotropic drugs is the most common cause of SCARs. We also found that carbamazepine was more likely to cause renal damage and cholestasis, whereas chlorpromazine was statistically correlated with hepatic cytolysis.

Update of Antiepileptic Drug Dosing and Administration.

Update of Antiepileptic Drug Dosing and Administration.

Frontline Sodium Channel-Blocking Antiseizure Medicine Use Promotes Future Onset of Drug-Resistant Chronic Seizures

The mechanisms of treatment-resistant epilepsy remain unclear. We have previously shown that frontline administration of therapeutic doses of lamotrigine (LTG), which preferentially inhibits the fast-inactivation state of sodium channels, during corneal kindling of mice promotes cross-resistance to several other antiseizure medicines (ASMs). However, whether this phenomenon extends to monotherapy with ASMs that stabilize the slow inactivation state of sodium channels is unknown. Therefore, this study assessed whether lacosamide (LCM) monotherapy during corneal kindling would promote future development of drug-resistant focal seizures in mice. Male CF-1 mice (n = 40/group; 18-25 g) were administered an anticonvulsant dose of LCM (4.5 mg/kg, i.p.), LTG (8.5 mg/kg, i.p.), or vehicle (0.5% methylcellulose) twice daily for two weeks during kindling. A subset of mice (n = 10/group) were euthanized one day after kindling for immunohistochemical assessment of astrogliosis, neurogenesis, and neuropathology. The dose-related antiseizure efficacy of distinct ASMs, including LTG, LCM, carbamazepine, levetiracetam, gabapentin, perampanel, valproic acid, phenobarbital, and topiramate, was then assessed in the remaining kindled mice. Neither LCM nor LTG administration prevented kindling: 29/39 vehicle-exposed mice were kindled; 33/40 LTG-exposed mice were kindled; and 31/40 LCM-exposed mice were kindled. Mice administered LCM or LTG during kindling became resistant to escalating doses of LCM, LTG, and carbamazepine. Perampanel, valproic acid, and phenobarbital were less potent in LTG- and LCM-kindled mice, whereas levetiracetam and gabapentin retained equivalent potency across groups. Notable differences in reactive gliosis and neurogenesis were also appreciated. This study indicates that early, repeated administration of sodium channel-blocking ASMs, regardless of inactivation state preference, promotes pharmacoresistant chronic seizures. Inappropriate ASM monotherapy in newly diagnosed epilepsy may thus be one driver of future drug resistance, with resistance being highly ASM class specific.

Clocking Epilepsies: A Chronomodulated Strategy-Based Therapy for Rhythmic Seizures.

Epilepsy is a neurological disorder characterized by hypersynchronous recurrent neuronal activities and seizures, as well as loss of muscular control and sometimes awareness. Clinically, seizures have been reported to display daily variations. Conversely, circadian misalignment and circadian clock gene variants contribute to epileptic pathogenesis. Elucidation of the genetic bases of epilepsy is of great importance because the genetic variability of the patients affects the efficacies of antiepileptic drugs (AEDs). For this narrative review, we compiled 661 epilepsy-related genes from the PHGKB and OMIM databases and classified them into 3 groups: driver genes, passenger genes, and undetermined genes. We discuss the potential roles of some epilepsy driver genes based on GO and KEGG analyses, the circadian rhythmicity of human and animal epilepsies, and the mutual effects between epilepsy and sleep. We review the advantages and challenges of rodents and zebrafish as animal models for epileptic studies. Finally, we posit chronomodulated strategy-based chronotherapy for rhythmic epilepsies, integrating several lines of investigation for unraveling circadian mechanisms underpinning epileptogenesis, chronopharmacokinetic and chronopharmacodynamic examinations of AEDs, as well as mathematical/computational modeling to help develop time-of-day-specific AED dosing schedules for rhythmic epilepsy patients.

Effect of Targeted Embolization on Seizure Outcomes in Patients with Brain Arteriovenous Malformations.

Seizures are one of the most debilitating manifestations of brain arteriovenous malformations (AVMs). This study aimed to evaluate the effect of curative embolization on brain AVM patients presenting with seizures. The records of patients who underwent embolization for brain AVM from January 2012 to December 2020 were evaluated and patients presenting with seizures were interviewed. Patient responses were evaluated according to the International League Against Epilepsy (ILAE) and Engel classifications. Statistical analyses of factors associated with seizure outcomes and complications were performed using ANOVA and Fischer's exact tests. The mean age of the participants was 35.2 ± 10.7 years. More than 80% of the patients received no or suboptimal dosages of antiepileptic drugs (AEDs) prior to embolization. Positive seizure dynamics were observed in 50% of the patients post-procedure. A correlation was found between length of seizures in anamnesis and outcomes of both Engel and ILAE score, where shorter length was associated with better outcomes. Post-embolization hemorrhage was associated with initial presentation with hemorrhage. The embolization of brain AVMs had a positive effect on seizure presentation and a relatively low prevalence of complications. However, the results of the study are obscured by inadequate AED treatment received by the patients, which prompts prospective studies on the topic with careful patient selection.

662: PROPHYLAXIS FOR THE PREVENTION OF EARLY POSTTRAUMATIC SEIZURES IN TRAUMATIC BRAIN INJURY

Introduction: Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in children under 18 years of age. Early posttraumatic seizures (EPTS), seizures occurring within 7 days of initial neurologic injury, are a known complication following TBI. The goal of this study is to discern how efficacious prophylaxis with Levetiracetam or Fosphenytoin is in preventing EPTS in moderate to severe TBI in pediatric patients. Methods: A retrospective observational study at a Level 1 Pediatric Trauma Center was conducted with patients 0-5 years with moderate to severe TBI admitted to the PICU from January 1, 2015 – January 1, 2021. Moderate to severe TBI was defined as Glasgow Coma Scale (GCS) < 13. Patients were identified using ICD-9 and ICD-10 codes. Excluded were patients >5 years old, who presented to the ED with seizures, who received anti-epileptic drug (AED) after a seizure, with non-accidental trauma as the cause of TBI, who did not receive 7 days of AED prophylaxis or died within 7 days of hospital stay. The following points were collected and compared: initial GCS, AED dosage, time to 1st AED dose, occurrence of EPTS, and number of days into hospital stay EPTS occurred. Results: Of 244 patients identified with moderate/severe TBI, 50 patients met inclusion criteria. Subdural hematoma was the most common primary diagnosis (48%). 44 patients (88%) received Levetiracetam. 6 patients (12%) received Fosphenytoin. 5 patients (10%) had EPTS, 95% CI [1.8%, 18.2%]. These 5 patients had received Levetiracetam. The 6 patients that received Fosphenytoin did not have EPTS. Seizures were confirmed with electroencephalography and on average occurred 2.6 days into hospital course. Mean data points of the patients who experienced EPTS: Levetiracetam dose 32.6 mg/kg/day, presenting GCS score 7, and time to administration of 1st AED dose 243 minutes. Mean data points of the patients who did not experience EPTS: Levetiracetam dose 29.3 mg/kg/day, presenting GCS score 9, and time to administration of 1st AED dose 366 minutes. Conclusions: Patients who received Levetiracetam prophylaxis had a higher incidence of EPTS compared to patients who received Fosphenytoin prophylaxis. These patients also had a lower presenting GCS, potentially playing a role in the neuropathophysiology of EPTS.

Cannabidiol (CBD) Reduces Epileptic Seizures in the Asian Population: Cross-sectional Study for Intractable Epilepsy Patients in Japan

Purpose of study: Despite very strict cannabis regulations in Japan, some cannabidiol (CBD) products have been legally distributed since 2013 and taken by some epilepsy patients. However, its efficacy and safety have not been evaluated. Basic procedures: A self-administered questionnaire was sent to 38 patients with intractable epilepsy who were taking CBD. The questionnaire sought information on patient background (sex, age) and medical history (diagnosis, type of seizures), characteristics of CBD use (frequency, route of administration), and the safety of CBD use (adverse events, side effects). Patients were also asked about changes in seizure frequency, intensity, and duration; effect on sleep; effect on daytime activity/vitality; increase/decrease in antiepileptic drugs dosage; quality of life (QOL); and caregiver-assessed QOL. Findings: Responses were received from 28 of 38 patients. The median CBD intake was 12.0 mg/kg/day. Nine patients (32.1%) were suspected of having an adverse event, but all were mild and no patients discontinued CBD due to adverse events. Fifteen patients (53.6%) reported a decrease in seizure frequency, and 2 patients (7.1%) showed complete resolution of seizures. No significant correlation was found between the patient’s diagnosis and the seizure type or efficacy. Conclusions: This is the first cross-sectional study of CBD users in Japan, suggesting that CBD may be an effective option for Asian patients with refractory epilepsy, regardless of diagnosis or seizure type.

Retrospective Efficacy and Cost-Containment Assessment of 10 kHz Spinal Cord Stimulation (SCS) in Non-Surgical Refractory Back Pain Patients.

Non-surgical refractory back pain (NSRBP) is persistent, severe back pain that is not considered surgically correctable. Published studies have demonstrated clinically important long-term improvement in pain and functional capacity when 10kHz spinal cord stimulation (SCS) is used to treat NSRBP. This study examines if real-world patients in interventional pain practice obtain the same outcomes, and have any reduction in health care utilization (HCU) following 10kHz SCS implant. We conducted a retrospective chart review of 105 patients from two clinical sites who underwent implantation of 10kHz SCS for NSRBP. The three most frequent diagnoses were lumbosacral radiculopathy, degenerative disc disease (DDD)/discogenic back pain and foraminal stenosis. The complete set of patient-level electronic data, including clinical outcomes, HCU, and at least 12 months (12M) follow-up were available in 90 subjects. The 90 analyzed patients were 63.9 years old (median 67) with an average of 10.2 years since back pain diagnosis. Reported pain on the Visual Analog Scale (VAS) decreased from 7.78±1.3 cm to 3.4±2.4 cm at 12M after SCS implant (p<0.001). Opioid usage (n = 65) decreased from 57.9±89.9 mg to 34.3±66.4 mg MSO4 equivalents (p = 0.004) at 12M. There were 46 patients on various doses of anticonvulsants, mostly gabapentin. The average dose decreased from 1847.91±973.6 mg at baseline to 1297.9±1184.6 mg at 12M after implant (p = 0.016). HCU was analyzed comparing the 12M before to the 12M after implant. Number of office visits decreased from 10.83±8.0 per year to 8.86±7.64 (p = 0.036), number of procedures to control chronic pain decreased from 2.2±1.9 to 0.6±1.2 (p<0.001). There was no significant change in number of imaging procedures, hospital admissions, or days spent in the hospital. 10kHz SCS warrants consideration as a therapeutic option for NSRBP patients and appears to provide a substantial reduction in HCU in the year following implant.

Efficacy of indwelling trocar therapy for postherpetic neuralgia: A retrospective study of an acupuncture method.

Postherpetic neuralgia (PHN) is a common complication of herpes zoster. As a kind of continuous acupuncture, indwelling trocar therapy (ITT) involves inserting a trocar into the skin and retaining the soft cannula in the body for 24 h. However, the efficacy and safety of ITT on PHN require further verification. In this study, the medical records of 122 patients with PHN were retrospectively analyzed. Patients were divided into the control group (patients who received conventional drug therapy) and the ITT group (patients who underwent ITT combined with conventional drug therapy). The Visual Analog Scale (VAS), Quality of Sleep (QS), 36-Item Short Form Health Survey (SF-36), dosage of drug and adverse events were analyzed at days 1, 3, 7, 14, 28, 90, and 180 after treatment. The total efficiency rate (TER) was analyzed after 6months of follow-up. The VAS, QS and SF-36 scores in the ITT group improved substantially compared with those in the control group after 6months of follow-up (p < 0.001). The average dosage of anticonvulsants and analgesics decreased significantly in the ITT group (p < 0.001). The TER in the control group was 52.46%, compared with 73.77% in the ITT group (p < 0.05). There were no adverse events, such as bleeding and infection, observed in the ITT group. For PHN patients, the combination of ITT and medicine therapy reduced VAS, improved quality of life, increased the efficiency rate, remarkably reduced the dosage of traditional medicine, and had no significant side effects. In addition, ITT was more effective in patients with a short duration of PHN than in chronic PHN patients.

Cannabis-based magistral formulation is highly effective as an adjuvant treatment in drug-resistant focal epilepsy in adult patients: an open-label prospective cohort study.

The safety and efficacy of a formulation high in cannabidiol (CBD) and low in ∆9-tetrahydrocannabinol (THC) to treat drug-resistant epilepsy have been examined previously in children, but not in adult population. The aim of this study was to evaluate whether CBD-rich oil, as an add-on treatment to conventional antiepileptic drugs, was effective, safe, and well-tolerated in adults with drug-resistant focal epilepsy (DRFE). An open-label, prospective cohort, single-center in adult patients with DRFE, were receiving stable doses of antiepileptic drugs (AEDs). A cannabis based-magistral formulation (CBMF) (100 mg/ml CBD and THC <1.9 mg/ml) was administrated 0.1 ml sublingually every 12 hours, up-titrated weekly. The primary outcome was to establish a reduction in seizures frequency >50% at 12 weeks. Adverse-drug reactions monitoring was done. p-value <0.05 was statistically significant. Between August 2020 and July 2022, 44 (38.6%) patients completed >3 months of follow-up. The median daily dose of CBD was 200 mg, that of THC was 4 mg, and that of CBD per kilogram of weight was 3.7 mg. The median number of seizures per month before CBD treatment was 11, and after CBD treatment was 2.5 (p<0.001). A reduction in seizures >50% at 12 week was achieved in 79.5% of the patients. The median percentage change in seizure frequency per month was 84.1% at 12 weeks. Five patients reported any adverse-drug reactions. The CBMF is a highly effective and safety therapy to treat adult patients with DRFE. The reduction in seizures frequency is maintained over time.

THE EVALUATION OF ANTI-EPILEPTIC DRUGS DOSAGE IN MALNOURISHED CHILDREN: CASES IN INDONESIAN COMMUNITY OF EPILEPSY

Anti-epileptic drug (AED) has a narrow therapeutic index of drugs that a slight increase in dosage showed toxic effects. The therapeutic response is difficult to predict in malnutrition status because the patient with nutritional deficiency have more complicated problems likes hypoalbuminemia, macronutrient and micronutrients deficiency that affected the levels of AEDs. The nutritional deficiency could be a direct and indirect cause of ineffective AEDs therapy and also recurrent epilepsy. This study aims to describe the use of antiepileptic drugs in Indonesian children with poor nutritional status. The research design was observational studies with cross sectional random sampling to evaluate the AED doses of malnutrition status in children. All information was collected by spreading electronic forms and interviewing the parents by phone. The data were analyzed descriptively. Total of 8 malnourished children mostly included in the range of ages from &gt;2 to 12 years (n=5; 62.50%) with means 3,9±2,7 years. The study showed valproic acid was bigger used in monotherapy (n=5; 62,50%) than polytherapy with carbamazepine or sodium phenytoin and phenobarbital. The means estimation of valproic acid monotherapy concentration in females’ group (n=2; 33,33%) showed sub-therapeutics level were Cssmin 26,09±0,57 mg/L and Cssmax 64,17±1,39 mg/L, also the means in males’ group (n=2; 33,33%) of valproic acid monotherapy were Cssmin 22.07±2,71 mg/L and Cssmax 54.27±6.66 mg/L. All of them included in good clinical outcome of free seizure &gt; 6 months.

Pharmacovigilance in Pediatric Patients with Epilepsy Using Antiepileptic Drugs.

Objective: To investigate the occurrence of adverse effects of antiepileptic drugs (AEDs) in pediatric epileptic patients on mono- or polytherapy. Method: We evaluated eighty consecutive patients that met the following inclusion criteria: aged ≤18 years; diagnosed with epilepsy for at least one year; a stable dose of AED for at least three months; verbal consent to participation in the study. Patients were asked if they had experienced any adverse drug reaction (ADR) related to the AED. Afterward, regardless of the answer, they were interviewed based on a detailed semi-structured questionnaire about the presence of ADRs associated with the AED. The data were analyzed regarding the use of monotherapy or polytherapy. Results: Ninety-seven percent of the patients reported having experienced ADRs related to AEDs. The greatest number of seizures affected the group of patients treated with monotherapy (both at baseline and at followup), but the greatest number of ADRs were observed among patients treated with polytherapy. In patients on monotherapy, the most frequent ADRs reported at baseline included fatigue and somnolence, and among patients with polytherapy, it was fatigue and hair loss. Conclusion: Children on polytherapy were significantly more likely to develop ADRs compared to those on monotherapy, but a statistically significant improvement in seizure frequency was also observed in the group of patients on polytherapy. Pharmacovigilance is very important in children with AEDs, so that ADRs can be identified early and managed appropriately.

Evaluating Therapeutic Equivalence of Generic and Original Levetiracetam in Patients with Epilepsy: A Retrospective Study.

The brand interchangeability of antiepileptic drugs (AEDs) is a topic of debate, especially regarding their therapeutic equivalence. This study evaluates the efficacy and tolerability of generic levetiracetam compared to the brand-name equivalent in a routine clinical setting. We conducted a retrospective study, examining patients with stable seizure frequency who received generic levetiracetam after the brand-name drug. During the six-month substitution period, changes in seizure frequency, hospitalization due to seizure exacerbation, adverse events, composite outcomes related to adjusting the AED dosage, and switching back to original levetiracetam were analyzed. Seventy-five patients were enrolled; the majority (85.3%) had focal onset seizures, and almost half (49.3%) had refractory epilepsy. Six months after the substitution, the mean seizure frequency per month was not significantly different (3.15 ± 14.47 vs. 2.77 ± 11.41; p = 0.970). In patients with controlled seizures before the change, the seizure frequency increased significantly (0.56 ± 1.83 vs. 0.03 ± 0.16; p = 0.012). Adverse events occurred in six patients. We have observed recurrent seizures or adverse events from 14 days after the transition. The original drug return rates due to recurrent seizures and adverse events were 5.3% and 1.3%, respectively. Generic levetiracetam might not show therapeutic equivalence to the original molecule, especially in patients adequately controlled by the brand-name drug.