Interactions between antiseizure medications and foods and drinks: A systematic review.

Antiseizure medications (ASMs) constitute the principal of treatment for patients with epilepsy, where long-term treatment is usually necessary. The purpose of this systematic review is to provide practical and useful information regarding various aspects of the interactions between ASMs and foods and drinks. MEDLINE and ScienceDirect, from the inception to July 15, 2023, were searched for related publications. In both electronic databases, the following search strategy was applied, and the following keywords were used (in title/abstract): "food OR drink" AND "antiepileptic OR antiseizure." The primary search yielded 738 studies. After implementing our inclusion and exclusion criteria, we could identify 19 studies on the issue of interest for our endeavor. Four studies were identified in the recheck process and not by the primary search. All studies provided low level of evidence. Interactions between foods and ASMs are a common phenomenon. Many factors may play a role for such an interaction to come to play; these include drug properties, administration route, and administration schedule, among others. Drugs-foods (-drinks) interactions may change the drug exposure or plasma levels of drugs (e.g., grapefruit juice increases carbamazepine concentrations and the bioavailability of cannabidiol is increased 4-5 folds with concomitant intake of fat-rich food); this may require dosage adjustments. Interactions between ASMs and foods and drinks may be important. This should be taken seriously into consideration when consulting patients and their caregivers about ASMs. Future well-designed investigations should explore the specific interactions between foods (and drinks) and ASMs to clarify whether they are clinically important. PLAIN LANGUAGE SUMMARY: Interactions between antiseizure medications and foods and drinks may be important. This should be taken into consideration in patients with epilepsy.

How does COVID-19 vaccination affect long-COVID symptoms?

OBJECTIVE: The current study aimed to identify the association between COVID-19 vaccination and prolonged post-COVID symptoms (long-COVID) in adults who reported suffering from this condition. METHODS: This was a retrospective follow-up study of adults with long-COVID syndrome. The data were collected during a phone call to the participants in January-February 2022. We inquired about their current health status and also their vaccination status if they agreed to participate. RESULTS: In total, 1236 people were studied; 543 individuals reported suffering from long long- COVID (43.9%). Chi square test showed that 15 out of 51 people (29.4%) with no vaccination and 528 out of 1185 participants (44.6%) who received at least one dose of any vaccine had long long- COVID symptoms (p = 0.032). CONCLUSIONS: In people who have already contracted COVID-19 and now suffer from long-COVID, receiving a COVID vaccination has a significant association with prolonged symptoms of long-COVID for more than one year after the initial infection. However, vaccines reduce the risk of severe COVID-19 (including reinfections) and its catastrophic consequences (e.g., death). Therefore, it is strongly recommended that all people, even those with a history of COVID-19, receive vaccines to protect themselves against this fatal viral infection.

Historical roots of the stigma of epilepsy: A review of the classic Iranian literature.

BACKGROUND: The stigma toward epilepsy is a daily challenge for people with epilepsy (PWE) and can influence the well-being and prognosis of these individuals. However, the cultural origins of such stigma have sparsely been examined. In this study, we aimed to investigate the classic Persian literature to gain insight into the historical and cultural beliefs and opinions regarding epilepsy as a determinant in developing stigma towards PWE. METHODS: In this narrative review of the classic Persian literature, we investigated the opinions and beliefs regarding epilepsy and PWE. In February 2023, we searched https://ganjoor.net (an open-access database of Iranian literature) for the relevant literary materials (poem and prose) using the Persian translation of the terms epilepsy (Sar'e) and epileptic (Masroo'e). Two clinical researchers went through the results and extracted the related materials under the supervision of two experts in Persian literature. A bilingual academic translated the included literary materials from Persian to English. RESULTS: Our search yielded 57 literature materials by 31 poets and writers from the 4th to 14th Hijri centuries, roughly coinciding with the past Gregorian millennium (1000-2000 AC). We classified the literary concepts related to epilepsy stigma into five subgroups: (i) a simile for pain and suffering; (ii) an atonement for blasphemous beliefs or a disease caused by supernatural power; (iii) a sign of madness, insanity, and lack of wisdom; (iv) a celestial observation; and (v) a subject for jokes. CONCLUSIONS: Classic Persian literature considered epilepsy as a simile for suffering and a sign of insanity that is caused by blasphemous beliefs or celestial objects, with PWE classified as insane and unwise. While such depictions became less prevalent after the 14th century CE, they can give rise to misconceptions and negative stigma toward PWE and should be addressed in modern culture. Each society should critically investigate its socio-cultural origins of stigma and rectify such misbeliefs.

Depression, anxiety, stress, and suicide risk in patients with functional seizures vs. those with epilepsy.

BACKGROUND: We aimed to investigate the rates of positive screening for depression, anxiety, stress, and suicide risk in adults with seizures [i.e., well-matched groups of patients with focal epilepsy vs. idiopathic generalized epilepsy (IGE) vs. functional seizures (FS)]. METHODS: This was a cross sectional study. Patients, 19-55 years of age, with a diagnosis of IGE, focal epilepsy or FS were investigated at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from September 2022 until January 2023 and during their follow-up visits. We used the validated Farsi version of DASS-21 (Depression-Anxiety-Stress Scale) to investigate and screen for depression, anxiety, and stress in these patients. We also used the Beck Scale for Suicide Ideation (BSSI). RESULTS: Forty patients with focal epilepsy, 40 persons with IGE, and 40 individuals with FS were included. Depression and anxiety were more prevalent among patients with FS compared with those with epilepsy. The rate of stress among patients with FS was not significantly different compared with that in patients with epilepsy. The suicide risks were not significantly different between the groups either. CONCLUSION: Patients with FS are at high risk for psychiatric comorbidities that is comparable or even worse than that in patients with epilepsy. Specific validated scales to screen for psychiatric comorbidities and suicide risk should be integral components of the evaluation and treatment of all patients with seizures.

Coexistence of temporal lobe epilepsy and idiopathic generalized epilepsy.

OBJECTIVE: We investigated the frequency of coexistence of temporal lobe epilepsy (TLE) and idiopathic generalized epilepsy (IGE) in a retrospective database study. We also explored the underlying pathomechanisms of the coexistence of TLE and IGE based on the available information, using bioinformatics tools. METHODS: The first phase of the investigation was a retrospective study. All patients with an electro-clinical diagnosis of epilepsy were studied at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2023. In the second phase, we searched the following databases for genetic variations (epilepsy-associated genetic polymorphisms) that are associated with TLE or syndromes of IGE: DisGeNET, genome-wide association study (GWAS) Catalog, epilepsy genetic association database (epiGAD), and UniProt. We also did a separate literature search using PubMed. RESULTS: In total, 3760 patients with epilepsy were registered at our clinic; four patients with definitely mixed TLE and IGE were identified; 0.1% of all epilepsies. We could identify that rs1883415 of ALDH5A1, rs137852779 of EFHC1, rs211037 of GABRG2, rs1130183 of KCNJ10, and rs1045642 of ABCB1 genes are shared between TLE and syndromes of IGE. CONCLUSION: While coexistence of TLE and IGE is a rare phenomenon, this could be explained by shared genetic variations.

Antiseizure Effects of Peganum harmala L. and Lavandula angustifolia.

Peganum harmala L. and Lavandula angustifolia are two traditional herbs with probable antiseizure effects. This study evaluated the effects of these two herbal extracts on pentylenetetrazol- (PTZ-) induced seizures in mice. We prepared hydroalcoholic extracts using P. harmala seeds and the aerial parts of L. angustifolia and then randomly divided 190 mice into 19 groups. Normal saline (10 mg/kg), diazepam (2 mg/kg), P. harmala (2.5, 5, 10, 15, 30, 45, and 60 mg/kg), and L. angustifolia (200, 400, 600, and 800 mg/kg) were intraperitoneally (IP) administrated 30 min before an IP administration of PTZ (90 mg/kg). Animals were observed for behavioral changes for one hour. In addition, the effects of flumazenil and naloxone on the antiseizure activity of P. harmala and L. angustifolia were assessed. P. harmala showed antiseizure activity at the dose of 10 mg/kg; it prolonged the seizure latency and decreased the seizure duration. The mortality protection rate was 90% for this herbal extract. L. angustifolia (600 mg/kg) prolonged the seizure latency and decreased both seizure duration and mortality. Neither flumazenil nor naloxone significantly reversed the antiseizure activities of P. harmala and L. angustifolia. In mice, the hydroalcoholic extracts of P. harmala and L. angustifolia showed antiseizure activity against PTZ-induced seizures. We could not delineate the exact antiseizure mechanisms of these extracts in the current study.

Hypothalamic hamartoma surgery in a setting with limited resources.

BACKGROUND: Three years ago (in 2020), we at the epilepsy center in Shiraz, Iran, started an endeavor to initiate a surgical program for patients with hypothalamic hamartoma (HH). We discussed that although minimally invasive techniques are desired, they are not available in the nation. We decided to proceed with open disconnection and resection surgery techniques. The current manuscript presents the results of the HH surgery program at our center as a case series. METHODS: This study included all patients with a diagnosis of HH who were referred to Shiraz Epilepsy Center with drug-resistant epilepsy and who underwent HH surgery from October 2020 to January 2023 at our epilepsy center, Namazi Hospital, Shiraz, Iran. RESULTS: Seven patients were included. All patients had gelastic seizures. Four patients (57%) underwent total resection of HH, and the lesions were disconnected and partially resected in three other patients (43%). Three patients (43%) became seizure-free after surgery, and three patients (43%) had more than 50% reduction in their seizure frequencies. Three patients (43%) had no post-operative complications. Only one patient (14.3%) suffered from a permanent postoperative complication (right hemiparesis). The mortality rate was zero. Five parents (71%) were satisfied with the surgery outcomes. CONCLUSION: Hypothalamic hamartoma surgery is feasible even in centers with limited resources if a close collaboration exists between the epileptology and neurosurgery teams. Careful planning based on the expertise of the team members and the available resources is required to foster success.

Polymorphism of glucocorticoid receptor gene (rs41423247) in functional seizures (psychogenic nonepileptic seizures/attacks).

OBJECTIVE: We investigated the association between the glucocorticoid receptor (GR) gene, also known as the nuclear receptor subfamily 3, group C, member 1 (NR3C1), rs41423247 polymorphism, and functional seizures (psychogenic nonepileptic seizures/attacks) in a case-control study. We hypothesized that the tested polymorphism has significant associations with functional seizures (psychogenic nonepileptic seizures/attacks) independent from comorbid depression. METHODS: Seventy patients with functional seizures (psychogenic nonepileptic seizures/attacks), 70 with major depressive disorder (MDD), and 70 healthy controls (HCs) were studied. Their DNAs were analyzed for NR3C1 rs41423247 polymorphism. RESULTS: Genotype and allele frequencies of rs41423247 were different between the three groups. G allele carriers were more frequent in patients with functional seizures (psychogenic nonepileptic seizures/attacks) and those with MDD compared to HCs (p = 0.0001). However no significant difference was observed with respect to allele distributions between functional seizures (psychogenic nonepileptic seizures/attacks) and MDD groups (p = 0.391). CC genotype was less often associated with functional seizures (psychogenic nonepileptic seizures/attacks) versus HC: Codominant model; p = 0.001, OR = 0.11, 95% CI = 0.05-0.24, and -2loglilkelihood = 231.7. In comparison between functional seizures (psychogenic nonepileptic seizures/attacks) group and other (MDD + HC) groups, we observed a significant association between CG genotype and functional seizures (psychogenic nonepileptic seizures/attacks) (Codominant model; p = 0.001, OR = 5.63, 95% CI = 2.60-12.40 and -2loglikelihood = 245.99). SIGNIFICANCE: Patients with functional seizures (psychogenic nonepileptic seizures/attacks) and those with MDD were significantly more often G allele carriers in rs41423247 compared with HCs. We observed a significant association between CG genotype and functional seizures (psychogenic nonepileptic seizures/attacks). However, we could not exclude the possibility of confounding effects of depression. Future genetic studies of patients with functional seizures (psychogenic nonepileptic seizures/attacks) should include a comparison group with depression in addition to a comparison group of HCs.

Epilepsy classification using artificial intelligence: A web-based application.

OBJECTIVE: The purpose of the current endeavor was to evaluate the feasibility of using easily accessible and applicable clinical information (based on history taking and physical examination) in order to make a reliable differentiation between idiopathic generalized epilepsy (IGE) versus focal epilepsy using machine learning (ML) methods. METHODS: The first phase of the study was a retrospective study of a prospectively developed and maintained database. All patients with an electro-clinical diagnosis of IGE or focal epilepsy, at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2022, were included. The first author selected a set of clinical features. Using the stratified random portioning method, the dataset was divided into the train (70%) and test (30%) subsets. Different types of classifiers were assessed and the final classification was made based on their best results using the stacking method. RESULTS: A total number of 1445 patients were studied; 964 with focal epilepsy and 481 with IGE. The stacking classifier led to better results than the base classifiers in general. This algorithm has the following characteristics: precision: 0.81, sensitivity: 0.81, and specificity: 0.77. SIGNIFICANCE: We developed a pragmatic algorithm aimed at facilitating epilepsy classification for individuals whose epilepsy begins at age 10 years and older. Also, in order to enable and facilitate future external validation studies by other peers and professionals, the developed and trained ML model was implemented and published via an online web-based application that is freely available at http://www.epiclass.ir/f-ige.

Genetics of Functional Seizures; A Scoping Systematic Review.

BACKGROUND: Evidence on the genetics of functional seizures is scarce, and the purpose of the current scoping systematic review is to examine the existing evidence and propose how to advance the field. METHODS: Web of science and MEDLINE were searched, from their initiation until May 2023. The following key words were used: functional neurological disorder(s), psychogenic neurological disorder(s), functional movement disorder(s), psychogenic movement disorder(s), functional seizures(s), psychogenic seizure(s), nonepileptic seizure(s), dissociative seizure(s), or psychogenic nonepileptic seizure(s), AND, gene, genetic(s), polymorphism, genome, epigenetics, copy number variant, copy number variation(s), whole exome sequencing, or next-generation sequencing. RESULTS: We identified three original studies. In one study, the authors observed that six (5.9%) patients with functional seizures carried pathogenic/likely pathogenic variants. In another study, the authors observed that, in functional seizures, there was a significant correlation with genes that are over-represented in adrenergic, serotonergic, oxytocin, opioid, and GABA receptor signaling pathways. In the third study, the authors observed that patients with functional seizures, as well as patients with depression, had significantly different genotypes in FKBP5 single nucleotide polymorphisms compared with controls. CONCLUSION: Future genetic investigations of patients with functional seizures would increase our understanding of the pathophysiological and neurobiological problems underlying this common neuropsychological stress-associated condition.

Drug-resistant epilepsy: Definition, pathophysiology, and management.

There are currently >51 million people with epilepsy (PWE) in the world and every year >4.9 million people develop new-onset epilepsy. The cornerstone of treatment in PWE is drug therapy with antiseizure medications (ASMs). However, about one-third of PWE do not achieve seizure control and do not respond well to drug therapy despite the use of appropriate ASMs [drug-resistant epilepsy (DRE)]. The aims of the current narrative review are to discuss the definition of DRE, explain the biological underpinnings and clinical biomarkers of this condition, and finally to suggest practical management strategies to tackle this issue appropriately, in a concise manner.

Work difficulties, work restrictions, and disability benefits in people with functional seizures: A survey study.

Purpose: Functional seizures (FS) cause significant long-term disability and clinicians offer differing views on proper work restrictions and qualifications for disability benefits in this population. We assess the views and perspectives of experienced disability and work limitations in people living with functional seizures. Methods: Between (4/29/2020-1/13/2021) an open-access 21-item internet survey was conducted via FNDHope.org; allowing for people living with self-reported functional seizures to remark on topics of work difficulties, work restrictions, qualifications for disability benefits, and driving. Demographic information was collected, and univariate and multivariate logistic regressions were used to evaluate potential predictors of current employment status. Results: One hundred eighteen (118) responses were received, of which 92 (84.4%) completed > 50% of the survey; they were predominantly (92%) female. Most respondents (88%) reported some personal difficulty at work and nearly all (99%) believed that others with FS would experience difficulties in the workplace. A majority (71%) felt that work restrictions should apply to people living with active FS, at least in certain lines of work. Most (64%) felt people with FS should qualify for disability benefits; however, 35% stated work accommodations or a new job compatible with FS was more appropriate. Of those who felt people with FS should qualify for disability, 60% thought recipients should remain eligible for disability while symptomatic and 38% felt benefits should be lifelong. In univariate and multivariate logistic regressions, older age was predictive of unemployment (univariate OR 0.95 ± 0.02, 95% CI 0.92-0.98, p-value 0.002). Conclusion: Our results suggest that work difficulties are common in people with FS, with older age being a predictor of unemployment. A majority of people with FS support work restrictions for those with their disorder, at least in some lines of work. In comparison to a prior study of clinicians, a higher percentage of people with FS supported work restrictions. These results may help facilitate productive discussions between people with FS, providers, and policymakers regarding appropriate work and disability limitations.

Attention deficit hyperactivity disorder in patients with seizures: Functional seizures vs. epilepsy.

BACKGROUND: We investigated the rates of positive screening for attention deficit-hyperactivity disorder (ADHD) in adults with seizures [i.e., focal epilepsy vs. idiopathic generalized epilepsy (IGE) vs. functional seizures (FS)]. We hypothesized that the rates of positive screening for ADHD are different between these three groups of patients. METHODS: This was a cross sectional study. Patients, 19 to 55 years of age, with a diagnosis of IGE, focal epilepsy or FS were investigated at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from September 2022 until January 2023 and during their follow-up visits. We used the validated Persian version of Adult ADHD Self-Report Scale (ASRS v1.1)15 to investigate and screen for ADHD in these patients. RESULTS: Forty patients with focal epilepsy, 40 with IGE, and 40 with FS were included. Attention deficit-hyperactivity disorder (ADHD) screening was positive in 35% of patients with FS, in 30% of those with focal epilepsy (compared with FS, p = 0.633), and in 10% of patients with IGE (compared with FS, p = 0.007). CONCLUSION: Adult patients with functional seizures and those with focal epilepsy are at a high risk of self-reporting experiences that could be characteristic of ADHD. Screening tools [e.g., Adult ADHD Self-Report Scale (ASRS v1.1)] are useful to help clinicians address seizure comorbidities such as ADHD. However, a clinical diagnosis of ADHD should be ascertained in a patient with positive screening.

Adult epilepsy.

Epilepsy is a common medical condition that affects people of all ages, races, social classes, and geographical regions. Diagnosis of epilepsy remains clinical, and ancillary investigations (electroencephalography, imaging, etc) are of aid to determine the type, cause, and prognosis. Antiseizure medications represent the mainstay of epilepsy treatment: they aim to suppress seizures without adverse events, but they do not affect the underlying predisposition to generate seizures. Currently available antiseizure medications are effective in around two-thirds of patients with epilepsy. Neurosurgical resection is an effective strategy to reach seizure control in selected individuals with drug-resistant focal epilepsy. Non-pharmacological treatments such as palliative surgery (eg, corpus callosotomy), neuromodulation techniques (eg, vagus nerve stimulation), and dietary interventions represent therapeutic options for patients with drug-resistant epilepsy who are not suitable for resective brain surgery.

The new International League Against Epilepsy (ILAE) definition of Lennox-Gastaut syndrome: Practical implications and limitations.

PURPOSE: There are three major changes in the new definition of Lennox-Gastaut syndrome (LGS) compared with the traditional definition: (1) onset prior to 18 years, (2) must include tonic seizure, (3) generalized slow spike-waves (SSW) and (instead of or) generalized paroxysmal fast activity (GPFA) on electroencephalography (EEG). We investigated the practical implications and potential limitations of the new LGS definition based on a large cohort of patients in an exploratory study. METHODS: This was a retrospective database study. All patients with an electro-clinical diagnosis of LGS (based on its traditional definition) at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran were included (from 2008 until 2020). Patients were reclassified based on the new definition of LGS. RESULTS: In total, 3737 patients were registered. Based on its traditional definition, 300 patients were diagnosed as having LGS. According to the new definition of LGS, only 96 patients (32% of the traditional cohort) had LGS. One patient, who had other criteria, had and age at onset of 21 years; 29 patients (9.7%) did not have SSW in their EEGs; 139 people (46.3%) did not have GPFA in their EEGs; and, 111 patients (37%) did not report having tonic seizures. CONCLUSION: The new International League Against Epilepsy (ILAE) definition of LGS has some important practical implications and limitations. Before reinforcing and making this new definition compulsory in future research and clinical practice, more work is needed to enlighten various aspects of such changes in the definition of this epilepsy syndrome.

How to successfully establish an epilepsy care center in resource-limited countries: A scoping systematic review.

PURPOSE: The aim of the current study was to systematically review the literature on establishing epilepsy care centers in resource-limited nations in the world and to provide a comprehensive roadmap on this significantly needed endeavor. This work may provide guidance on how to develop an epilepsy care center in other resource-limited places in the world. METHODS: Web of science, Science Direct, and MEDLINE (accessed from PubMed) from inception to March 2023 were systematically searched for relevant published manuscripts. In all electronic databases, the following search strategy was implemented and these key words were used (title/abstract): epilepsy AND resource. The inclusion criteria were all original studies and articles written in English. RESULTS: We could identify nine manuscripts on how to successfully establish an epilepsy care center in resource-limited countries. Two models were identified for such an endeavor: developing a team of trained healthcare professionals (e.g., in Iran, India, China, Vietnam) or a twin affiliation between an advanced epilepsy surgery program in a developed country and a starting program in a developing country (e.g., in Georgia, Tunisia). CONCLUSION: In order to successfully establish an epilepsy care center in resource-limited countries four pillars are needed: presence of skillful healthcare professionals, having access to basic investigative technologies (i.e., MRI and EEG), a careful planning, and raising awareness.