Antiepileptic Drug Regimen Research Articles

OxcarNet: sinc convolutional network with temporal and channel attention for prediction of oxcarbazepine monotherapy responses in patients with newly diagnosed epilepsy

Objective.Monotherapy with antiepileptic drugs (AEDs) is the preferred strategy for the initial treatment of epilepsy. However, an inadequate response to the initially prescribed AED is a significant indicator of a poor long-term prognosis, emphasizing the importance of precise prediction of treatment outcomes with the initial AED regimen in patients with epilepsy.Approach. We introduce OxcarNet, an end-to-end neural network framework developed to predict treatment outcomes in patients undergoing oxcarbazepine monotherapy. The proposed predictive model adopts a Sinc Module in its initial layers for adaptive identification of discriminative frequency bands. The derived feature maps are then processed through a Spatial Module, which characterizes the scalp distribution patterns of the electroencephalography (EEG) signals. Subsequently, these features are fed into an attention-enhanced Temporal Module to capture temporal dynamics and discrepancies. A channel module with an attention mechanism is employed to reveal inter-channel dependencies within the output of the Temporal Module, ultimately achieving response prediction. OxcarNet was rigorously evaluated using a proprietary dataset of retrospectively collected EEG data from newly diagnosed epilepsy patients at Nanjing Drum Tower Hospital. This dataset included patients who underwent long-term EEG monitoring in a clinical inpatient setting.Main results.OxcarNet demonstrated exceptional accuracy in predicting treatment outcomes for patients undergoing Oxcarbazepine monotherapy. In the ten-fold cross-validation, the model achieved an accuracy of 97.27%, and in the validation involving unseen patient data, it maintained an accuracy of 89.17%, outperforming six conventional machine learning methods and three generic neural decoding networks. These findings underscore the model's effectiveness in accurately predicting the treatment responses in patients with newly diagnosed epilepsy. The analysis of features extracted by the Sinc filters revealed a predominant concentration of predictive frequencies in the high-frequency range of the gamma band.Significance. The findings of our study offer substantial support and new insights into tailoring early AED selection, enhancing the prediction accuracy for the responses of AEDs.

A novel AAV9-dual microRNA-vector targeting GRIK2 in the hippocampus as a treatment for mesial temporal lobe epilepsy

Mesial temporal lobe epilepsy (mTLE) is the most prevalent type of epilepsy in adults. First and subsequent generations of anti-epileptic therapy regimens fail to decrease seizures in a large number of patients suffering from mTLE, leaving surgical ablation of part of the hippocampus as the only therapeutic option to potentially reach seizure freedom. GluK2 has recently been identified as a promising target for the treatment of mTLE using gene therapy. Here, we engineered an adeno-associated virus serotype 9 vector expressing a cluster of two synthetic microRNAs (miRNAs), expressed from the human synapsin promoter, that target GRIK2 mRNA. Intra-hippocampal delivery of this vector in a mouse model of mTLE significantly reduced GRIK2 expression and daily seizure frequency. This treatment also improved the animals' health, reduced their anxiety, and restored working memory. Focal administration of the vector to the hippocampus of cynomolgus monkeys in GLP toxicology studies led to the selective transduction of hippocampal neurons with little exposure elsewhere in the brain and no transduction outside the central nervous system. Expression of miRNAs in hippocampal neurons resulted in substantially decreased GRIK2 mRNA expression. These data suggest that the intra-hippocampal delivery of a GMP-grade AAV9 coding for a synthetic miRNAs targeting GRIK2 is a promising treatment strategy for mTLE.

Drug-resistant epilepsy: Current concepts, pathogenesis, risk factors, outcomes of surgical treatment

Despite the wide choice of antiepileptic drugs (AEDs), a third of patients remain resistant to the effects of modern AEDs. Drug-resistant epilepsy (DRE) is characterized by the inability to control seizures in a patient when using at least two adequate AED regimens at an effective daily dose as monotherapy or in combination. In this case, the mechanisms responsible for drug resistance are mainly either increased excretion of AEDs by transporters from epileptogenic tissue (the multidrug transporter hypothesis) or a decrease in the sensitivity of drug receptors in epileptogenic brain tissue. It is assumed that there are other mechanisms, but they remain understudied. A number of factors are associated with the risk of DRE developing in patients with diagnosed epilepsy, including genetic, iatrogenic, brain malformations, and others. Patients with DRE have a higher probability of developing psychopathological disorders (depression, anxiety, psychosis), the proportion of which is significantly higher than in the general population. They have a 10-fold increased risk of death due to injury, cognitive decline, and sudden unexpected death in epilepsy (SUDEP). The priority treatment method for DRE is surgery. Early identification of DRE is critical for identifying potential treatment alternatives and determining whether a patient is a surgical candidate. Analysis of data from clinical and instrumental research of operated patients with DRE in the early and late postoperative period will allow us to identify factors of unfavorable outcome and to increase the effectiveness of treatment for this category of patients.The aim was to study and to summarize literature data on the pathogenesis and risk factors of drug resistance to antiepileptic drugs in patients with epilepsy, justifying the need for timely identification of drug resistance and referral of patients with drugresistant epilepsy to specialized centers for possible surgical treatment.

A Cross Sectional Study on Prescription Pattern of Antiepileptic Medication among Children of Southern Rajasthan in a Tertiary Care Teaching Hospital

Background: Drug utilization studies are powerful exploratory tools for establishing the role of drugs in society and also effective methods for assessing the prescribing pattern of clinicians. Around 4-10% of children suffer at least one seizure episode at 16 years of age. Even after the availability of several Antiepileptic drugs (AEDs), choosing the correct drug with accurate dosing will produce seizure-free generation. Hence, this study aims to examine the prescription patterns of drugs in epileptic children. Methods: This study was a cross sectional observational study. Children <16 years old visiting neurology department with a history of epileptic seizures and already on antiepileptic drug therapy were included in the study. The data comprised of demographic details, disease history, type of seizure, diagnosis, investigations done, along with prescribed medication noted in case record form. The total study duration was 13 months. Results: In this study, the maximum epilepsy encountering age in male and female children was below the 12-year age group, male predominance was higher than females (male 60.83% vs. female 39.16%). The majority of children were diagnosed with generalized tonic colonic seizures, 54.17%, followed by focal/or partial seizures, 39.17%. Sodium valproate 19.16%, carbamazepine 14.17%, oxcarbazepine 16.67%, and levetriacetam 13.33% were the most commonly prescribed single drug regimens for treating both types of seizures, followed by clobazam added as second and third adjuvant drug in resistant epilepsy to valproate 12.5%, oxcarbazepine 6.67%, and levetriacetam plus carbamazepine combination 5% respectively. Conclusion: Monotherapy was majorly followed in 70% of pediatric patients for maintaining better patient compliance. Both old and new AEDs regimens are prescribed for maintaining the quality of life in patients.

Comparative Analysis of Antihypertensive and Anticonvulsant Regimens in Managing Pre-eclampsia and Eclampsia: Insights from a Sudanese Retrospective Study.

BACKGROUND Preeclampsia presents with gestational proteinuria, usually after 20 weeks of gestation, and can be complicated by generalized tonic-clonic seizures of eclampsia. Particularly in countries with limited healthcare resources, preeclampsia and eclampsia are major causes of maternal morbidity and mortality. This retrospective study aimed to evaluate the presentation, management, and outcomes of 185 women with preeclampsia and eclampsia in 2 maternity hospitals in Omdurman, Sudan, between January and December 2020. MATERIAL AND METHODS An analytical retrospective study was conducted in 2 main maternity hospitals in Omdurman, Sudan, between January and December 2020. The study included 185 pregnant women with preeclampsia or eclampsia. Data on clinical and obstetric characteristics (history of the illness, comorbid diseases, parity, gravida, multifetal pregnancy, and laboratory investigations), medications used, and maternal and neonatal outcomes were obtained for the diagnosis. The data were analyzed using the SPSS version 27. RESULTS Results: The mean age was 27.2±6.3 years, with 42.7% primigravida, 30% had a triple-drug regimen, nifedipine was the most common antihypertensive (60.5%), and 17.3% of patients underwent observation only. The seizure rate was 20%, with 92.73% controlled with magnesium sulfate. The antihypertensive regimen before delivery was significantly associated with the mode of delivery (P=0.001) and maternal outcomes (P=0.047); the regimen used after delivery significantly achieved blood pressure control (P=0.043) and improved maternal outcomes (P=0.007), but not fetal outcomes. CONCLUSIONS Maternal outcomes were markedly affected by the antihypertensive drug regimens used and the patient's seizure control status, and use of anti-convulsants successfully controlled all seizures.

Phenytoin Toxicity Potentially Induced by Addition of Lacosamide in a Long-Term Anticonvulsant Regimen: A Case Report of Rare Drug Interaction

Phenytoin toxicity remains a critical concern when serum levels exceed therapeutic thresholds, with the contribution of drug interactions to this toxicity being well-established. However, the interaction between phenytoin and lacosamide, another anticonvulsant, has seldom been reported. This case report describes a 61-year-old male with a longstanding history of effective seizure control using phenytoin and primidone. Following a recent seizure, lacosamide was added to his regimen. Approximately one-month post-adjustment, the patient exhibited symptoms indicative of phenytoin toxicity, including ataxia, slurred speech, and diminished coordination. This case highlights the necessity for vigilance regarding potential drug interactions in patients with long-term anticonvulsant therapies and underscores the need for cautious regimen modifications. It also prompts further investigation into the mechanisms underlying the interaction between phenytoin and lacosamide to enhance patient safety and treatment efficacy.

The Use of Antiepileptic Drug for Postcranioplasty Seizure: A Systematic Review and Meta-analysis

Introduction: Cranioplasty, a common procedure following craniectomy, aims to repair cranial defects resulting from various causes, including trauma and raised intracranial pressure. Despite its routine application, cranioplasty is associated with complications, notably seizures. The incidence of postcranioplasty seizures (PCS) and the role of antiepileptic drug (AED) prophylaxis remain underexplored. This meta-analysis aims to evaluate the impact of AED prophylaxis on both early and late PCS. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic literature search on PubMed, Europe PMC, ClinicalTrials.gov, and EMBASE, yielding 1292 articles. Eligibility criteria included randomized clinical trials (RCTs) in English reporting PCS incidence with or without AED prophylaxis. The risk of bias was assessed using Cochrane’s RoB 2 tool. Statistical analysis employed RevMan 5.4 software. Results: Of the initially identified articles, two RCTs met the inclusion criteria, involving a total of 497 cases. AED prophylaxis significantly reduced the risk of early PCS (risk ratio [RR]: 0.15, confidence interval [CI]: 0.06–0.37, P < 0.0001), with no heterogeneity (I 2 = 0%, P = 0.78). However, there was no significant difference in late PCS incidence between the intervention and control groups (RR: 0.32, CI: 0.06–1.56, P = 0.16). No significant differences in abnormal liver function or blood test results were observed between groups. Conclusion: AED prophylaxis significantly reduces the risk of early PCS following cranioplasty, but its effectiveness in preventing late PCS remains uncertain. Further studies are warranted to determine optimal AED regimens and address the limitations of the current meta-analysis.

Personalized support programs with innovative digital tools to manage and monitor patients suffering from epilepsy: EpiOnApp case study

Epilepsy is one of the most common serious chronic neurological diseases affecting around 50 million people globally and 500,000 patients in Italy. It causes uncontrollable, unprovoked, and unpredictable seizures that reduce the quality of life of those afflicted.
 It is widely recognized that the most important strategy for controlling seizures and enhance well-being includes receiving and adhering to anti-seizure medications as well as making appropriate lifestyle adjustments. However it is estimated that 30–60% of patients do not adhere to their antiepileptic medication regimens. EpiOnApp is a digital Patients Support Program (PSP) designed to empower patients with epilepsy who are taking Cenobamate for their chronic condition to take control of their health care pathway, from inception throughout the duration of the treatment, and to have a meaningful dialogue with their neurologist by sharing health records and emotional states. Moreover, as patients may have limited mobility, they can order their therapy and have it home delivered in a very easy way, and they can benefit from continuous human support through the figure of a dedicated Care Manager. The advantage for the neurologist is that the platform stores seizure data, facilitating the drug titration and better assessing at the time of the follow-up visit. The efficacy of the program is currently being evaluated. So far, the level of satisfaction expressed by patients and neurologists shows that a well-designed and tailored PSP can address the challenge of improving long-term adherence, helping people with epilepsy through the on-boarding and initial treatment period, reducing discontinuation, and ultimately, delivering a better health outcome.

Fatal iatrogenic cerebral β-amyloid-related arteritis in a woman treated with lecanemab for Alzheimer’s disease

We report the case of a 79-year-old woman with Alzheimer’s disease who participated in a Phase III randomized controlled trial called CLARITY-AD testing the experimental drug lecanemab. She was randomized to the placebo group and subsequently enrolled in an open-label extension which guaranteed she received the active drug. After the third biweekly infusion, she suffered a seizure characterized by speech arrest and a generalized convulsion. Magnetic resonance imaging revealed she had multifocal swelling and a marked increase in the number of cerebral microhemorrhages. She was treated with an antiepileptic regimen and high-dose intravenous corticosteroids but continued to worsen and died after 5 days. Post-mortem MRI confirmed extensive microhemorrhages in the temporal, parietal and occipital lobes. The autopsy confirmed the presence of two copies of APOE4, a gene associated with a higher risk of Alzheimer’s disease, and neuropathological features of moderate severity Alzheimer’s disease and severe cerebral amyloid angiopathy with perivascular lymphocytic infiltrates, reactive macrophages and fibrinoid degeneration of vessel walls. There were deposits of β-amyloid in meningeal vessels and penetrating arterioles with numerous microaneurysms. We conclude that the patient likely died as a result of severe cerebral amyloid-related inflammation.

Analysis of maternal and fetal complications resulting from epilepsy and its management during pregnancy

Epilepsy is a brain disorder that occurs due to excessive electrical discharges and manifests itself in epileptic seizures. In pregnancy, seizure control can become more difficult due to the organic changes that occur during this period. The antiepileptic drug (AED) regimen used during pregnancy will influence fetal development, resulting in both congenital abnormalities and alterations in child development. The aim of this study was to analyze the potential maternal and fetal complications resulting from epilepsy itself and/or its clinical management during pregnancy. We analyzed 35 medical records and interviewed women with ICD G40.0 to G40.9 who became pregnant between 2005 and 2017. After data collection, statistical analysis was performed using Fisher's exact test and simple statistical analysis with the data obtained. It was concluded that the type of EAF, as well as its regimen with the greatest teratogenic potential, has still been widely used by pregnant women with epilepsy, demonstrating the need to raise awareness for better therapeutic management for these patients.

Antiepileptic Drugs as Potential Dementia Prophylactics Following Traumatic Brain Injury.

Seizures and other forms of neurovolatility are emerging as druggable prodromal mechanisms that link traumatic brain injury (TBI) to the progression of later dementias. TBI neurotrauma has both acute and long-term impacts on health, and TBI is a leading risk factor for dementias, including chronic traumatic encephalopathy and Alzheimer's disease. Treatment of TBI already considers acute management of posttraumatic seizures and epilepsy, and impressive efforts have optimized regimens of antiepileptic drugs (AEDs) toward that goal. Here we consider that expanding these management strategies could determine which AED regimens best prevent dementia progression in TBI patients. Challenges with this prophylactic strategy include the potential consequences of prolonged AED treatment and that a large subset of patients are refractory to available AEDs. Addressing these challenges is warranted because the management of seizure activity following TBI offers a rare opportunity to prevent the onset or progression of devastating dementias.

New insights on the potential anti-epileptic effect of metformin: Mechanistic pathway.

Epilepsy is a chronic neurological disease characterized by recurrent seizures. Epilepsy is observed as a well-controlled disease by anti-epileptic agents (AEAs) in about 69%. However, 30%-40% of epileptic patients fail to respond to conventional AEAs leading to an increase in the risk of brain structural injury and mortality. Therefore, adding some FDA-approved drugs that have an anti-seizure activity to the anti-epileptic regimen is logical. The anti-diabetic agent metformin has anti-seizure activity. Nevertheless, the underlying mechanism of the anti-seizure activity of metformin was not entirely clarified. Henceforward, the objective of this review was to exemplify the mechanistic role of metformin in epilepsy. Metformin has anti-seizure activity by triggering adenosine monophosphate-activated protein kinase (AMPK) signalling and inhibiting the mechanistic target of rapamycin (mTOR) pathways which are dysregulated in epilepsy. In addition, metformin improves the expression of brain-derived neurotrophic factor (BDNF) which has a neuroprotective effect. Hence, metformin via induction of BDNF can reduce seizure progression and severity. Consequently, increasing neuronal progranulin by metformin may explain the anti-seizure mechanism of metformin. Also, metformin reduces α-synuclein and increases protein phosphatase 2A (PPA2) with modulation of neuroinflammation. In conclusion, metformin might be an adjuvant with AEAs in the management of refractory epilepsy. Preclinical and clinical studies are warranted in this regard.

Patient with Epilepsy Showing Psychiatric Symptoms after Remission of Seizures and Normalization of Electroencephalography: The Phenomenon of Forced Normalization?

Psychiatric disorders are commonly observed in patients with epilepsy. Among them, the phenomenon known as forced normalization is scarce. Herein, we report the case of a 41-year-old patient who showed long-term first-onset psychiatric symptoms after seizure remission and normalization of electroencephalography. After changing the antiepileptic drug regimen and psychiatric treatment, the patient's symptoms regressed. However, the exact pathological mechanisms remain to be elucidated. Changing the regimen of antiepileptic drugs and long-term psychiatric treatment may help control this phenomenon.

A real-world pharmacovigilance study of severe cutaneous adverse reactions associated with antiepileptic drug combination therapy: data mining of FDA adverse event reporting system

ABSTRACT Background The aim of this study was to evaluate the association between antiepileptic drug combination regimens and severe cutaneous adverse reactions (SCAR). Research design and methods We gathered cases indication with epilepsy based on the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from 2004 to 2021. Disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and the information component (IC). Results Out of 128,262 reports were collected from the FAERS database, 104,278 cases were in the antiepileptic drugs group, and 23,984 cases were in the other primary suspected drugs group. A total of 20 combination regimens were associated with increased association of SCAR, top five of them were topiramate-phenytoin (ROR 57.62, 95% CI 30.93–107.34), lamotrigine-valproic acid (ROR 52.93, 95% CI 47.09–59.49), diazepam-phenobarbital (ROR 39.61, 95% CI 20.01–78.38), zonisamide-valproic acid (ROR 36.57, 95% CI 19.16–69.80), lamotrigine-diazepam (ROR 35.22, 95% CI 15.70–79.00). Conclusion The antiepileptic agent combinations may increase the incidence of SCAR and should be carefully evaluated in clinical practice. It is recommended to choose the combination regimens which have lower SCAR reporting rate for patients.

Treatment-Refractory Dravet Syndrome: Considerations for Novel Medications.

Before 2018, there were no U.S. Food and Drug Administration-approved medications for managing seizures in Dravet syndrome (DS). Common agents used in the antiepileptic drug regimens of patients with DS included clobazam, valproic acid, topiramate, and levetiracetam, among others; however, these agents alone rarely provide adequate seizure control. Management of seizures in DS changed in recent years with the approval of cannabidiol and stiripentol in 2018 and fenfluramine in 2020. This continuing education article summarizes available efficacy and safety data involving cannabidiol, stiripentol, and fenfluramine and provides a practical review of dosing strategies, pharmacokinetics, and monitoring interventions relevant to their use.

Prevalence of Non-adherence to Antiepileptic Drugs in Patients With Epilepsy Presenting to Emergency With Fits.

BackgroundEpilepsy is considered when a patient has at least two unprovoked seizures that occurred more than a day apart. Seizure control depends upon several factors, including adequate treatment and its dosage, patients' daily activities, and adherence to antiepileptic medications. The study aimed to assess the rate of adherence to antiepileptic drugs (AED) in patients with epilepsy.MethodologyA cross-sectional study was conducted at the Department of Neurology, Ayub Teaching Hospital, Abbottabad, Pakistan, between November 2019 and October 2020. All participants who presented to the emergency room with complaints of seizures, had a known diagnosis of epilepsy, aged above 18 years, with no cognitive dysfunction or severe psychiatric disorders were included in the study. Patients with other neurological disabilities (brain tumors, cerebral palsy, neuromuscular disorder) or severe psychotic episodes and those with undiagnosed cases of epilepsy were excluded from the study. A predefined proforma was used to assess the level of adherence and non-adherence among patients and they were then divided into their respective groups.ResultsA total of 150 participants were included in the study. Of patients, 110 were adherent to AED treatment while 40 were non-compliant. It was found that the most frequent cause of non-adherence was that patients forgot their pills (72.5%). Of patients, 7.5% stopped taking the medication when symptoms were relieved. About 12.5% reported affordability to be the reason for non-adherence. The rate of poor seizure control was significantly higher in non-adherent patients as compared to adherent patients (77.5% vs. 49.1%, p = 0.001). It was also found that a greater number of non-adherent patients experienced convulsive seizures in the past year as compared to those who were adherent to their medications (p = 0.006).ConclusionTo enhance treatment adherence, the practice of prescribing more simpler treatment regimens among physicians can result in better seizure control, as the complexity of the regimen is found to be a major challenge for adjustment of AED regimens in this regard.

Sodium Valproate-induced Eosinophilic Exudative Pleural Effusion

A 34-year-old woman presented with a 3-day history of dyspnea. She denied any preceding fever, night sweats, cough, pleurisy, or coryzal symptoms. She was maintained on sodium valproate 800 mg b.i.d., phenytoin 100 mg o.d., folate 5 mg o.d., and clonazepam 2 mg nocte for a known seizure disorder. Clinical examination and radiologic imaging revealed a large left-sided pleural effusion with the associated collapse of the left lower lung lobe. A chest tube was inserted for diagnostic and therapeutic purposes and ≈500 mls of serous fluid was drained. The pleural fluid analysis confirmed an exudative pleural effusion. Extensive evaluation excluded known causes of exudative pleural effusion, and a diagnosis of sodium valproate-induced pleural effusion was made. Sodium valproate was tapered off and topiramate was added to the patient’s antiepileptic regimen. We recommend physicians be cognizant of sodium valproate-associated pleural effusion, even in the setting of chronic use.

0852 Narcolepsy Type 1 in a Pediatric Patient with Temporal Lobe Epilepsy

Abstract Introduction Narcolepsy type-1 is clinically characterized by irrepressible daytime sleepiness and REM-sleep dissociation, including cataplexy. Cataplexy usually manifests as episodes of brief, symmetrical sudden loss of muscle tone with retained consciousness. It may be difficult to distinguish from seizure activity as they may share overlapping features. We discuss a pediatric patient with temporal lobe epilepsy with co-occuring Narcolepsy Type 1. Report of Cases: A 17-year-old boy with obesity and a history of focal epilepsy secondary to intracranial hemorrhage in the neonatal period status-post right parieto-occipital resection at age 11, presented with worsening fall episodes and feeling of imbalance Following surgery, his seizures improved, but he was having excessive sleepiness. At age 13, he started experiencing episodes of slurred speech, feeling of imbalance, “body heaviness and tongue heaviness” with occasional falls. He denied loss of consciousness, body shaking, stiffening, or incontinence. At age 17, he presented to medical attention due to increasing frequency of such episodes. Physical exam was significant for BMI 42.7 kg/m , Mallampati 4, tonsils 3+ bilaterally, and homonymous hemianopia. Epworth Sleepiness Scale: 22/24. Video EEG was negative for epileptiform discharges despite occurrence of above-mentioned episodes increasing the clinical suspicion of Narcolepsy. Polysomnography revealed sleep latency of 0 minutes, REM latency of 2.6 minutes, and mild OSA. Toxicology screen was negative. MSLT showed mean sleep latency of 1.2 minutes with 3 SOREMPs. CSF orexin could not be obtained due to technical constraints. He was diagnosed with Narcolepsy type-1 and started on Venlafaxine and Methylphenidate with resultant improvement in both daytime sleepiness, and the severity and frequency of cataplexy. However, his feeling of imbalance persisted, prompting repeat video EEG which demonstrated left temporal lobe seizure activity. Anti-epileptic regimen was optimized with improvement in sensation of imbalance. Conclusion Temporal lobe epilepsy and Narcolepsy Type-1 can have overlapping features that make it difficult to distinguish between the two. While exceedingly rare, the two entities may co-occur. Diagnostic and therapeutic management require coordination between Sleep Medicine and Neurology. While PSG, MSLT, and CSF Orexin can clarify the diagnosis of narcolepsy, neurologic work up should be pursued if symptoms are not completely attributable to Narcolepsy. Support (If Any)

Serum Calcium, Vitamin D3 and Bone Specific Alkaline Phosphatase Levels in Nigerian Children Treated with Antiepileptic Drugs: A Comparative Study

Background and Aim of the Study: Studies have shown that serum 25-hydroxycholecalciferol, calcium and bone-specific alkaline phosphatase (B-ALP) are altered in children on antiepileptic drugs (AEDs), and these could result in poor bone mineralization. The study aimed to determine the serum 25-hydroxycholecalciferol, calcium, and B-ALP levels among children on AEDs attending the paediatric neurology clinic of the University of Port Harcourt Teaching Hospital (UPTH).
 Methods: This cross-sectional analytical study was carried out from January 2018 to April 2019 on 100 children on AEDs and 100 age- and gender-matched healthy controls, aged 1.5 - 17 years. Data on socio-demography, AED regimen, and clinical examination findings of the subjects, their serum 25-hydroxycholecalciferol, calcium, and B-ALP levels were obtained and entered into a proforma. Data obtained were analysed using IBM SPSS version 20. Statistical significance was set at p-value of < 0.05.
 Results: The subjects had significantly lower mean serum 25-hydroxycholecalciferol and calcium and higher mean serum B-ALP levels than the controls, respectively. The mean serum 25-hydroxycholecalciferol was significantly lower in children on AED polytherapy. There was negative correlation between the duration of drug therapy and all serum biochemical indices but this was only significant for serum 25-hydroxycholecalciferol level (p = 0.027). Age significantly impacted negatively on serum 25-hydroxycholecalciferol, p = 0.036 and calcium levels, p = 0.009, but not on B-ALP (p = 0.392).
 Conclusion: Children on antiepileptic drugs in UPTH had lower mean serum 25-hydroxycholecalciferol and calcium levels but higher mean serum BALP level than healthy controls, as well as inverse relationship between duration of AED therapy and 25, hydroxycholecalciferol, calcium and B-ALP. We therefore recommend children with epilepsy on antiepileptic drugs have their serum 25-hydroxycholecalciferol, calcium and B-ALP levels monitored to enable early detection of any abnormalities.

Efficacy and safety of fenfluramine in the treatment of Dravet syndrome - literature review

Dravet Syndrome is a severe, drug-resistant, and rare epileptiform disorder that is typically presented in the first year of life in an otherwise healthy child. It is characterized by prolonged seizures that are often resistant to current anti-epileptic drug regimens, which made them poorly controlled, and almost 50% of patients experience at least four tonic-clonic seizures per month. There are three new medicines: stiripentol, cannabidiol, and fenfluramine, with documented efficacy and safety as adjunctive therapies in pharmacoresistant Dravet syndrome treatment.
 This study aimed to assess the efficacy and safety of fenfluramine in the treatment of Dravet syndrome. Our study material consisted of publications, which were found in PubMed, Google Scholar, and Embase databases. In order to find the proper publications, the search has been conducted with the use of a combination of keywords like: “fenfluramine”, “Dravet syndrome”, “epilepsy treatment”, “Dravet syndrome pediatric patients”. The first step was to find proper publications from the last 10 years. The second step was to carry out an overview of the found publications.
 Results of mentioned studies proved that in Dravet syndrome, fenfluramine provided a significantly greater reduction in convulsive seizure frequency compared with placebo. No patient developed valvular heart disease or pulmonary arterial hypertension, the side effects that occurred during its use were mild and the drug was generally well-tolerated. The bioequivalence and tolerability of single oral doses of fenfluramine hydrochloride oral solution in the fed and fasted states support drug administration without regard to meals. Fenfluramine may represent a new important treatment option for Dravet syndrome.