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.

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.

A global survey on the attitudes of neurologists and psychiatrists about functional/psychogenic/dissociative/nonepileptic-seizures/attacks, in the search of its name.

PURPOSE: We conducted an observational study to investigate the opinions of neurologists and psychiatrists all around the world who are taking care of patients with seizures [epilepsy and functional seizures (FS)]. METHODS: Practicing neurologists and psychiatrists from around the world were invited to participate in an online survey. On 29th September 2022, an e-mail including a questionnaire was sent to the members of the International Research in Epilepsy (IR-Epil) Consortium. The study was closed on 1st March 2023. The survey, conducted in English, included questions about physicians' opinions about FS and anonymously collected data. RESULTS: In total, 1003 physicians from different regions of the world participated in the study. Both neurologists and psychiatrists identified "seizures" as their preferred term. Overall, the most preferred modifiers for "seizures" were "psychogenic" followed by "functional" by both groups. Most participants (57.9%) considered FS more difficult to treat compared to epilepsy. Both psychological and biological problems were considered as the underlying cause of FS by 61% of the respondents. Psychotherapy was considered the first treatment option for patients with FS (79.9%). CONCLUSION: Our study represents the first large-scale attempt of investigating physicians attitudes and opinions about a condition that is both frequent and clinically important. It shows that there is a broad spectrum of terms used by physicians to refer to FS. It also suggests that the biopsychosocial model has gained its status as a widely used framework to interpret and inform clinical practice on the management of patients.

Another controller system for arterial pressure. AngII-vasopressin neural network of the parvocellular paraventricular nucleus may regulate arterial pressure during hypotension.

Angiotensin II (AngII) immunoreactive cells, fibers and receptors, were found in the parvocelluar region of paraventricular nucleus (PVNp) and AngII receptors are present on vasopressinergic neurons. However, the mechanism by which vasopressin (AVP) and AngII may interact to regulate arterial pressure is not known. Thus, we tested the cardiovascular effects of blockade of the AngII receptors on AVP neurons and blockade of vasopressin V1a receptors on AngII neurons. We also explored whether the PVNp vasopressin plays a regulatory role during hypotension in anesthetized rat or not. Hypovolemic-hypotension was induced by gradual bleeding from femoral venous catheter. Either AngII or AVP injected into the PVNp produced pressor and tachycardia responses. The responses to AngII were blocked by V1a receptor antagonist. The responses to AVP were partially attenuated by AT1 antagonist and greatly attenuated by AT2 antagonist. Hemorrhage augmented the pressor response to AVP, indicating that during hemorrhage, sensitivity of PVNp to vasopressin was increased. By hemorrhagic-hypotension and bilateral blockade of V1a receptors of the PVNp, we found that vasopressinergic neurons of the PVNp regulate arterial pressure towards normal during hypotension. Taken together these findings and our previous findings about angII (Khanmoradi and Nasimi, 2017a) for the first time, we found that a mutual cooperative system of angiotensinergic and vasopressinergic neurons in the PVNp is a major regulatory controller of the cardiovascular system during hypotension.

Smart devices/mobile phone in patients with epilepsy? A systematic review.

We systematically reviewed the existing literature on the safety of the use of smartphone, mobile phone/Internet, and Wi-Fi by people with epilepsy (PWE), according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Scopus, MEDLINE, and Google Scholar from the inception to April 9, 2021 were searched. These key words were used "epilepsy" OR "seizure" AND "Mobile Phone" OR "Cell Phone" OR "Smartphone" OR "Wi-Fi" OR "Electromagnetic" OR "Radiation." The primary search yielded 7766 studies; 33 studies were related. In total, 19 manuscripts were based on animal/computational studies and 14 articles reported human investigations. Among animal studies, 10 articles suggested detrimental effects by electromagnetic fields (EMFs) on brain function/seizure activity, while nine studies negated this hypothesis. Among human studies, seven studies suggested detrimental effects by EMFs on brain function/seizure activity, while seven studies negated this hypothesis. None of the studies provided a good level of evidence. In one human study, all seven patients with epilepsy and abnormal EEG during the sham exposure, had an increase in the number of epileptic events with exposure to mobile phone radiation. In another study of the detrimental effects of smart technology device overuse among school students, an association was found between reporting seizures and the hours of smart technology device use. While high-quality evidence on the safety of the use of smartphone, mobile phone/Internet, and Wi-Fi in PWE is lacking, prudent use of these technologies, including using wired hand-free sets or other exposure-reducing measures is recommended.

Cosmetic adverse effects of antiseizure medications; A systematic review.

BACKGROUND: We systematically reviewed the existing literature on the cosmetic adverse effects of antiseizure medications (ASMs) in order to depict a clear picture of these unwanted side effects of ASMs with a particular attention to hair loss, hirsutism, acne, and gingival hyperplasia. METHODS: This systematic review was prepared according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Scopus, MEDLINE, and Google Scholar from the inception to 25 March, 2021 were systematically searched. These key words (title/abstract) were used: "hair loss" OR "hirsutism" OR "acne" OR "gingival hyperplasia" AND "seizure" OR "epilepsy" OR "anriseizure" OR "antiepileptic". The exclusion criteria included: non-original studies, articles not in English, and animal studies. RESULTS: The primary search yielded 3938 studies; 127 studies were related to the topic and were included in the current systematic review. The most robust evidence on cosmetic adverse effects of ASMs were related to phenytoin (causing gingival hyperplasia, hirsutism, and acne) and valproate (causing hair loss and hirsutism); however, many other ASMs were also implicated in causing these cosmetic adverse effects. CONCLUSION: Antiseizure medications may be associated with various cosmetic adverse effects. Phenytoin and valproate are the most notorious ASMs in this regard; but, other ASMs have also been implicated in causing hair loss, hirsutism, acne, and gingival hyperplasia. Physicians should pay more attention to these significant adverse effects that may affect a patient's facial attractiveness, quality of life, and emotional state.

Roles of glutamate and GABA of the Kölliker-Fuse nucleus in generating the cardiovascular chemoreflex.

The Kölliker-Fuse (KF) nucleus is a part of the parabrachial complex, located in the dorsolateral pons. It is involved in the chemoreflex-evoked cardiovascular and respiratory changes, but the role of GABA and glutamate in cardiovascular chemoreflex has not been shown yet. This study was performed to determine the role of GABA, glutamate, and their interaction in the KF, in cardiovascular chemoreflex in anesthetized rat. The antagonists were microinjected into the KF, and arterial pressure, heart rate, and single-unit responses were recorded simultaneously. The chemoreflex was evoked by i.v. injection of KCN, consisted of a short pressor followed by long bradycardia responses. Both responses were significantly attenuated by injection of a synaptic blocker (CoCl2) into the KF, confirming involvement of the KF in generating the reflex. Microinjection of AP5, an NMDA receptor antagonist, into the KF significantly attenuated the pressor and bradycardia responses, while blocking the AMPA receptors by CNQX had no significant effect. Blockade of GABAA receptors by bicuculline methiodide (BMI) potentiated both responses. Co-injection of BMI and CNQX potentiated the responses too. Co-injection of BMI and AP5 had no significant effect on the pressor response but significantly attenuated the bradycardia response. In conclusion, the KF plays a role in generating cardiovascular chemoreflex via its glutamate NMDA but not AMPA receptors. GABA inhibits both components of this reflex through GABAA receptors. There is an interaction between GABAA and NMDA receptors in regulating the bradycardia response of the reflex. Single-unit results were also presented which were correlated with and supported the homodynamic findings.

Role of the Kölliker-Fuse nucleus in cardiovascular responses to hypoxia and baroreceptor activation in anesthetized rats.

Introduction: Parabrachial Kölliker-Fuse (KF) complex, located in dorsolateral part of the pons, is involved in the respiratory control, however, its role in the baroreflex and chemoreflex responses has not been established yet. This study was performed to test the contribution of the KF to chemoreflex and baroreflex and the effect of microinjection of a reversible synaptic blocker (Cocl2) into the KF in urethane anesthetized rats. Methods: Activation of chemoreflex was induced by systemic hypoxia caused by N2 breathing for 30 seconds "hypoxic- hypoxia methods" and baroreflex was evoked by intravenous injection (i.v.) of phenylephrine (Phe, 20 µg /kg/0.05-0.1 mL). N2 induced generalized vasodilatation followed by tachycardia reflex and Phe evoked vasoconstriction followed by bradycardia. Results: Microinjection of Cocl2 (5 mM/100 nL/side) produced no significant changes in the Phe-induced hypertension and bradycardia, whereas the cardiovascular effect of N2 was significantly attenuated by the injection of CoCl2 to the KF. Conclusion: The KF played no significant role in the baroreflex, but could account for cardiovascular chemoreflex in urethane anesthetized rats.

α2 Receptors in the lateral parabrachial nucleus generates the pressor response of the cardiovascular chemoreflex, effects of GABAA receptor.

The lateral parabrachial nucleus (LPBN) is a pontine area involved in cardiovascular chemoreflex. This study was performed to find the effects of reversible synaptic blockade of the LPBN on the chemoreflex responses, and to find the roles of GABAA receptor and α2-adenoreceptor (α2-AR) in chemoreflex. It also aimed to seek possible interaction between GABA and noradrenergic systems of the LPBN in urethane-anesthetized male rats. Cardiovascular chemoreflex was activated by intravenous injection of potassium cyanide (KCN, 80 µg/kg). The cardiovascular responses of chemoreflex were evaluated before (control), 5 and 15 min after microinjection of each drug (100 nl) into the LPBN. Microinjections of cobalt chloride (5 mM), a reversible synaptic blocker, into the LPBN greatly attenuated the chemoreflex pressor and bradycardic responses indicating that the LPBN plays a main role in chemoreflex. Local injection of yohimbine (10 nmol), an α2-AR antagonist, attenuated the pressor response with no effect on bradycardic response, suggesting that α2-adrenoreceptors are involved in producing the pressor response of the chemoreflex. Microinjection of bicuculline methiodide (BMI, 100 pmol), a GABAA antagonist, into the LPBN augmented the pressor response and attenuated the bradycardic response, indicating that GABA inhibits the sympathetic output to the heart and vasculature. Sequential injection of yohimbine and BMI had no significant effect on the pressor response but attenuated the bradycardia. In conclusion, the LPBN is essential for the chemoreflex responses. The pressor response of the chemoreflex, at least partly, is produced by α2- adenoreceptors. GABA in the LPBN inhibits the cardiovascular system. Finally, there is no interaction between GABAergic and adrenergic neurons of the LPBN in producing the cardiovascular chemoreflex.