Exploring shared triggers and potential etiopathogenesis between migraine and idiopathic/genetic epilepsy: Insights from a multicenter tertiary-based study.

INTRODUCTION: Migraine and epilepsy are two episodic disorders that share common pathophysiological mechanisms. The aim of our research was to assess the possible shared etiopathogenesis by analyzing the relations of headache, and seizure triggers, based on information obtained from a national cohort surveying the headache characteristics of 809 patients who had been diagnosed with idiopathic/genetic epilepsy. MATERIAL AND METHODS: Our study utilized data from a multi-center, nationwide investigation of headaches in 809 patients with idiopathic/genetic epilepsy. Out of these, 508 patients reported complaints related to any type of headache (333 Migraines, 175 Headaches of other types). In the initial phase of the study encompassing the entire sample of 809 epilepsy patients, differences in seizure triggers were assessed between the migraine group (n = 333) and the non-migraine group (n = 476). Additionally, the subsequent part of the study pertains to a subgroup of the entire patient group, namely those affected by all types of headaches (n = 508), and differences in headache triggers were assessed among migraine patients (n = 333) and those with other types of headaches (n = 175). Similar differences were observed between epilepsy patients with and without a family history of epilepsy. RESULTS: The most frequently reported seizure triggers in all I/GE group (n = 809) were stress (23%), sleep deprivation (22%) and fatigue (18%), respectively. The most frequently reported headache triggers in migraine patients were stress (31%), sleep deprivation (28%), and noise (26%). The occurrence of menstruation-triggered seizures in individuals with migraine and I/GE was found to be considerably higher than those without migraine. The most common triggers for seizure and headache among the individuals with a positive family history of epilepsy were determined to be light stimuli and sleep deprivation. CONCLUSION: In conclusion, our study provides valuable insights into the overlapping triggers including sleep patterns, stress levels, and menstrual cycles, etc. and potential shared etiology of migraine and I/GE. Recognizing these connections may facilitate the development of more precise therapeutic strategies and underscore the significance of adopting a holistic, multidisciplinary approach to the management of these intricate neurological conditions. Further research is essential to explore in greater depth the shared mechanisms underpinning these associations and their implications for clinical practice.

The effect of sleep disorders on quality of life in patients with epilepsy: A multicenter study from Turkey.

OBJECTIVE: We aimed to investigate sleep disorders in patients with epilepsy (PWE) and to investigate the effects of sleep disorders on quality of life. METHODS: In our multicenter study conducted in Turkey, 1358 PWE were evaluated. The demographic and clinical data of the patients were recorded. The Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory (BDI), and Quality of Life in Epilepsy Inventory-10 (QOLIE-10) were administered. RESULTS: The mean age of 1358 patients was 35.92 ±â€¯14.11 (range, 18-89) years. Seven hundred fifty-one (55.30 %) were women. Some 12.7 % of the patients had insomnia (ISI > 14), 9.6 % had excessive daytime sleepiness (ESS > 10), 46.5 % had poor sleep quality (PSQI > 5), and 354 patients (26.1 %) had depressive symptoms (BDI > 16). The mean QOLIE-10 score was 22.82 ±â€¯8.14 (10-48). Resistant epilepsy was evaluated as the parameter with the highest risk affecting quality of life Adjusted odds ratio (AOR = 3.714; 95 % confidence interval (CI): [2.440-5.652] < 0.001)). ISI (AOR = 1.184; 95 % CI: [1.128-1.243]; p < 0.001), ESS (AOR = 1.081; 95 % CI: [1.034-1.130]; p < 0.001), PSQI (AOR = 0.928; 95 % CI: [0.867 - 0.994]; p = 0.034), BDI (AOR = 1.106; 95 % CI: [1.084-1.129]; p < 0.001), epilepsy duration (AOR = 1.023; 95 % CI: [1.004-1.041]; p = 0.014), were determined as factors affecting quality of life. SIGNIFICANCE: Sleep disorders are common in PWE and impair their quality of life. Quality of life can be improved by controlling the factors that may cause sleep disorders such as good seizure control, avoiding polypharmacy, and correcting the underlying mood disorders in patients with epilepsy.

One Patient, Three Providers: A Multidisciplinary Approach to Managing Common Neuropsychiatric Cases.

BACKGROUND: Neuropsychiatric cases require a multidisciplinary approach for effective management. This paper presented case-based discussions on migraine, dementia, epilepsy, mood disorders, neuralgia, and psychosis from the perspectives of a family physician, neurologist, and psychiatrist. The goal was to highlight the importance of collaboration between healthcare providers in managing these complex cases. METHODS: The paper was based on the proceedings of the Mediterranean Neuropsychiatry Symposium, where experts from family medicine, neurology, and psychiatry came together for comprehensive case-based discussions. The CARE framework (Case Report, Appraisal, Research, and Education) was developed to guide reporting and evaluation of case reports in clinical practice. RESULTS: Six cases were presented and discussed, highlighting the importance of a multidisciplinary approach in managing neuropsychiatric cases. The cases included chronic migraine with medication overuse, memory dysfunction with language and behavioral problems, refractory epileptic seizures with subjective sensory symptoms, bipolar affective disorder with normal pressure hydrocephalus, postherpetic neuralgia in a case with bipolar affective disorder, and psychosis with recurrent attacks with the abuse of several substances. CONCLUSION: A biopsychosocial multidisciplinary approach is essential for managing neuropsychiatric cases effectively on behalf of the patients and public health of the country. The CARE framework can guide the reporting and evaluation of case reports in clinical practice, ensuring that patients receive comprehensive and effective care. Healthcare providers should collaborate to provide the best possible care for patients with complex and multifaceted needs.

Birth outcomes in pregnant women with epilepsy: A Nationwide multicenter study from Türkiye.

OBJECTIVE: The present study was aimed at investigating the effects of anti-seizure medications (ASMs), patient demographic characteristics, and the seizure type and frequency on the development of congenital malformations (CMs) in the infants of pregnant women with epilepsy (PWWE). METHODS: PWWE followed up at the neurology outpatient clinic of 21 centers between 2014 and 2019 were included in this prospective study. The follow-up of PWWE was conducted using structured, general pregnant follow-up forms prepared by the Pregnancy and Epilepsy Study Committee. The newborns were examined by a neonatologist after delivery and at 1 and 3 months postpartum. RESULTS: Of the infants of 759 PWWE, 7.2% had CMs, with 5.6% having major CMs. Polytherapy, monotherapy, and no medications were received by 168 (22.1%), 548 (72.2 %), and 43 (5.7 %) patients, respectively. CMs were detected at an incidence of 2.3% in infants of PWWE who did not receive medication, 5.7% in infants of PWWE who received monotherapy, and 13.7% in infants of PWWE who received polytherapy. The risk of malformation was 2.31-fold (95% confidence interval (CI): 1.48-4.61, p < .001) higher in infants of PWWE who received polytherapy. Levetiracetam was the most frequently used seizure medication as monotherapy, with the highest incidence of CMs occurring with valproic acid (VPA) use (8.5%) and the lowest with lamotrigine use (2.1%). The incidence of CMs was 5% at a carbamazepine dose <700 mg, 10% at a carbamazepine dose ≥700 mg, 5.5% at a VPA dose <750 mg, and 14.8% at a VPA dose ≥750 mg. Thus the risk of malformation increased 2.33 times (p = .041) in infants of PWWE receiving high-dose ASMs. SIGNIFICANCE: Birth outcomes of PWWE receiving and not receiving ASMs were evaluated. The risk of CMs occurrence was higher, particularly in infants of PWWE using VPA and receiving polytherapy. The incidence of CMs was found to be lower in infants of PWWE receiving lamotrigine.

Peri-ictal headache: An underestimated prognostic finding associated with idiopathic epilepsies.

OBJECTIVE: There are a handful of studies investigating peri-ictal headache (PIH) and its clinical associations in patients with idiopathic/genetic epilepsies (I/GE). This multi-center study aimed to investigate PIH, which is an ignored comorbid condition in patients with I/GE, by headache experts and epileptologists working together. METHODS: The data were collected from a cross-sectional large study, using two structured questionnaires for headache and epilepsy features, fulfilled by neurologists. Headaches were classified according to the International Classification of Headache Disorders, third edition, whereas seizure and syndrome types were diagnosed according to International League Against Epilepsy criteria. The patients with a headache starting 24 hours before the onset of the seizure (preictal) or within 3 hours after the seizure (postictal) were defined as patients with PIH. We compared demographic and clinical differences between two groups of patients with and without PIH statistically and used ROC curves to determine a threshold of the total number of seizure triggers associated with the occurrence of PIH. RESULTS: Among 809 (531 females, 65.6%) consecutive patients with I/GE, 105 (13%) patients reported PIH (22 preictal, 82 postictal headaches, and one with both types). Peri-ictal headache was more frequently reported by females and those having a family history of migraine or epilepsy, and it was significantly associated with lower rates of seizure freedom for more than five years, drug resistance, and use of polytherapy, remarkably. Moreover, ROC curves showed that having more than 3 seizure triggers was associated with the presence of PIH. CONCLUSION: Our findings revealed that PIH may be linked to poor outcomes in I/GEs and seems to be related to a lower ictal threshold precipitated by multiple triggers. Future prospective studies will illuminate the unknown underlying mechanisms and appropriate management strategies for PIH to improve the prognosis.

Headache in idiopathic/genetic epilepsy: Cluster analysis in a large cohort.

OBJECTIVE: The link between headache and epilepsy is more prominent in patients with idiopathic/genetic epilepsy (I/GE). We aimed to investigate the prevalence of headache and to cluster patients with regard to their headache and epilepsy features. METHODS: Patients aged 6-40 years, with a definite diagnosis of I/GE, were consecutively enrolled. The patients were interviewed using standardized epilepsy and headache questionnaires, and their headache characteristics were investigated by experts in headache. Demographic and clinical variables were analyzed, and patients were clustered according to their epilepsy and headache characteristics using an unsupervised K-means algorithm. RESULTS: Among 809 patients, 508 (62.8%) reported having any type of headache; 87.4% had interictal headache, and 41.2% had migraine. Cluster analysis revealed two distinct groups for both adults and children/adolescents. In adults, subjects having a family history of headache, ≥5 headache attacks, duration of headache ≥ 24 months, headaches lasting ≥1 h, and visual analog scale scores > 5 were grouped in one cluster, and subjects with juvenile myoclonic epilepsy (JME), myoclonic seizures, and generalized tonic-clonic seizures (GTCS) were clustered in this group (Cluster 1). Self-limited epilepsy with centrotemporal spikes and epilepsy with GTCS alone were clustered in Cluster 2 with the opposite characteristics. For children/adolescents, the same features as in adult Cluster 1 were clustered in a separate group, except for the presence of JME syndrome and GTCS alone as a seizure type. Focal seizures were clustered in another group with the opposite characteristics. In the entire group, the model revealed an additional cluster, including patients with the syndrome of GTCS alone (50.51%), with ≥5 attacks, headache lasting >4 h, and throbbing headache; 65.66% of patients had a family history of headache in this third cluster (n = 99). SIGNIFICANCE: Patients with I/GE can be clustered into distinct groups according to headache features along with seizures. Our findings may help in management and planning for future studies.

Diagnosis of comorbid migraine without aura in patients with idiopathic/genetic epilepsy based on the gray zone approach to the International Classification of Headache Disorders 3 criteria.

Background: Migraine without aura (MwoA) is a very frequent and remarkable comorbidity in patients with idiopathic/genetic epilepsy (I/GE). Frequently in clinical practice, diagnosis of MwoA may be challenging despite the guidance of current diagnostic criteria of the International Classification of Headache Disorders 3 (ICHD-3). In this study, we aimed to disclose the diagnostic gaps in the diagnosis of comorbid MwoA, using a zone concept, in patients with I/GEs with headaches who were diagnosed by an experienced headache expert. Methods: In this multicenter study including 809 consecutive patients with a diagnosis of I/GE with or without headache, 163 patients who were diagnosed by an experienced headache expert as having a comorbid MwoA were reevaluated. Eligible patients were divided into three subgroups, namely, full diagnosis, zone I, and zone II according to their status of fulfilling the ICHD-3 criteria. A Classification and Regression Tree (CART) analysis was performed to bring out the meaningful predictors when evaluating patients with I/GEs for MwoA comorbidity, using the variables that were significant in the univariate analysis. Results: Longer headache duration (<4 h) followed by throbbing pain, higher visual analog scale (VAS) scores, increase of pain by physical activity, nausea/vomiting, and photophobia and/or phonophobia are the main distinguishing clinical characteristics of comorbid MwoA in patients with I/GE, for being classified in the full diagnosis group. Despite being not a part of the main ICHD-3 criteria, the presence of associated symptoms mainly osmophobia and also vertigo/dizziness had the distinguishing capability of being classified into zone subgroups. The most common epilepsy syndromes fulfilling full diagnosis criteria (n = 62) in the CART analysis were 48.39% Juvenile myoclonic epilepsy followed by 25.81% epilepsy with generalized tonic-clonic seizures alone. Conclusion: Longer headache duration, throbbing pain, increase of pain by physical activity, photophobia and/or phonophobia, presence of vertigo/dizziness, osmophobia, and higher VAS scores are the main supportive associated factors when applying the ICHD-3 criteria for the comorbid MwoA diagnosis in patients with I/GEs. Evaluating these characteristics could be helpful to close the diagnostic gaps in everyday clinical practice and fasten the diagnostic process of comorbid MwoA in patients with I/GEs.

Acute Seizures in Cerebral Venous Sinus Thrombosis: Risk Factors and Prognosis.

BACKGROUND: Cerebral venous sinus thrombosis (CVST) often presents with acute seizures, and recurrent seizures may also be seen in the long term in some patients. The purpose of this retrospective study was to investigate the frequency and type of acute seizures and to define the risk factors. METHODS: Sixty-two patients diagnosed with CVST between September 2007 and October 2018 were retrospectively evaluated for the occurrence of acute seizures. Seizures which developed as a presenting symptom or occurred within 2 weeks of diagnosis were defined as acute seizures. Demographic, clinical, and radiologic characteristics were compared between patients with or without acute seizures. RESULTS: Twenty (32.3%) of the 62 CVST patients had acute seizures. Univariate analysis revealed a significant association between acute seizures and aphasia (P=0.03), motor deficit (P<0.001), sensory deficit (P=0.018), severe (≥3) modified Rankin Scale scores on admission (P=0.017), sagittal sinus thrombosis (P=0.037), cortical vein thrombosis (P<0.001), supratentorial lesions (P<0.001), and hemorrhagic lesions (P<0.001). Multivariate regression analysis identified supratentorial lesions (P=0.015, odds ratio: 9.131, 95% confidence interval: 1.525-54.687) and cortical vein thrombosis (P=0.034, odds ratio: 5.802, 95% confidence interval: 1.146-29.371) as independent factors for acute seizures. Although 25% of patients with acute seizures had recurrent seizures during hospitalization, only 2.6% of the 38 patients with long-term follow-up had recurrent seizures. CONCLUSIONS: Approximately one third of patients with CVST had acute seizures. Cortical vein thrombosis, supratentorial, and especially hemorrhagic lesions were the most significant risk factors associated with acute seizures. Although seizure recurrence may occur early in the course, long-term recurrence is rare in CVST.

Semiological characteristics of patients with psychogenic nonepileptic seizures: Gender-related differences.

Psychogenic nonepileptic seizures (PNES) are more prevalent among women, and diagnosis may sometimes be delayed by as much as seven years. Understanding the effect of gender on the presentation of a PNES may assist with diagnosis based on semiological details in the clinical setting. Although video-EEG monitoring (VEM) is the gold standard for diagnosing PNES, determining gender-related seizure semiology through careful history may prevent diagnostic delay while waiting for VEM. The aim of this study was to investigate gender-related differences in the semiology of PNES. Patients, all aged at least 16 years, diagnosed with PNES following VEM between December 2005 and November 2016 were included in this study. All patients' medical records and video-EEG-documented PNES were reviewed, and the presence or absence of semiological signs was recorded for each documented attack. Demographic features and semiological signs of PNES were compared between female and male patients. Forty-one patients (31 females, 10 males) aged 27.2 ±â€¯12.2 years (range: 16-65) were included in the study. Mean age at onset of PNES was higher for female patients than males, at 24.3 ±â€¯11.5 versus 17.5 ±â€¯3.2 years (p = 0.005). The median duration of PNES was longer for female patients than males, at 10 min (range: 5 s-120 min) versus 2 min (range: 10 s-60 min) (p = 0.016). The most common symptom was forced eye closure in both genders. No significant gender-specific differences were observed in terms of the type or semiology of PNES. Although there are no major gender-related differences in PNES semiology, our findings highlight the importance of greater caution, especially in male patients, when diagnosing PNES, remembering that onset may also occur at young ages and that a short seizure duration does not exclude PNES.

Does pain sensitivity increase during ictal period? Evidence from absence epileptic WAG/Rij rats.

OBJECTIVE: The hyperexcitable brain provides a common ground for comorbidity of pain syndromes and epilepsy. There are controversial reports about pain sensitivity during the ictal period. We analyzed the pain sensitivity during the ictal period in the genetic absence epilepsy animal model, Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. METHODS: The ictal and interictal pain sensitivities of symptomatic WAG/Rij rats (8 months old, n = 19) were determined and compared with those of age-matched control Wistar rats (n = 19). Pain sensitivity was assessed by applying heat stimulation to hind paws and measuring the paw-withdrawal latency using a thermal plantar analgesia meter in awake and freely moving animals. All measurements were made during the interictal and ictal periods and confirmed by simultaneous electroencephalography (EEG) through intracranially implanted electrodes. RESULTS: The nociceptive stimulus-induced withdrawal latency during the ictal period in absence epilepsy WAG/Rij rats was significantly shorter when compared with that during the interictal period (p = 0.007) and when compared with that in the control Wistar rats (p = 0.001). CONCLUSION: Our data indicate higher pain sensitivity during the ictal period in absence epilepsy rats. Considering the fact that subjects are less responsive during spike-wave discharges, there is a decrease in the level of consciousness and/or responsiveness ictally during all generalized genetic seizures, this increased pain sensitivity is rather surprising during the ictal period. Although the mechanism remains unknown, this novel finding deserves further investigation.

Epilepsy may cause increased pain sensitivity: Evidence from absence epileptic WAG/Rij rats.

OBJECTIVE: The comorbidity of epilepsy and pain disorders as well as effectiveness of certain therapeutic approaches in both conditions attracted attention to epilepsy-pain interactions. This lead to the discovery of significantly shared pathophysiological mechanisms although many aspects remain largely unknown. To test the hypothesis that epilepsy may be associated with altered pain sensitivity, we analyzed interictal pain sensitivity using epilepsy prone WAG/Rij rats, a genetic model exhibiting age-related-onset absence epilepsy. METHODS: Two series of experiments were conducted. In experiment I, pain sensitivity of symptomatic WAG/Rij rats were compared with age-matched control Wistar rats. In experiment II, pain sensitivity of WAG/Rij rats were monitored longitudinally when they were presymptomatic (at 2months) and symptomatic (after maturation, at 8months), and compared with age-matched control Wistar rats. Pain sensitivity was assessed by applying heat stimuli to hind paws and measuring the paw-withdrawal latency using thermal plantar analgesia meter in awake and freely moving animals. All pain measurements were made during the interictal period, confirmed by simultaneous electroencephalography through intracranially implanted electrodes. RESULTS: In experiment I, the interictal pain withdrawal latency of symptomatic WAG/Rij rats was significantly shorter than control Wistar rats (P<0.01). In experiment II, WAG/Rij rats had significantly shorter latency of withdrawal response than control Wistar rats, both at presymptomatic (P<0.05) and symptomatic stage (P<0.0001). Matured (8months old) control Wistar rats demonstrated significantly increased withdrawal latency compared to the 2months animals (P<0.01), but the WAG/Rij rats did not (P>0.5). CONCLUSION: Epileptic WAG/Rij rats present significantly increased pain sensitivity when compared to control Wistar rats, suggesting comorbidity of epilepsy and pain.

Prevalence of epilepsy in northeast Turkey.

The aim of this study was to determine the prevalence and clinical and socio-demographic characteristics of active epilepsy in the population, aged 15 and over, in the province of Trabzon in northern Turkey. We surveyed households and identified 34 epileptic patients (prevalence of 6/1,000), 28 of whom had active epilepsy (prevalence of 5/1,000). Only one case of hot water epilepsy was established among the 5,254 participants. Of the various seizure types, the most common were partial seizures (63%), over half of which were secondary generalised seizures. The largest syndromic category was that of localisation-related symptomatic cases (46%). Forty-six percent of cases were of unknown cause, and 16% were resistant to medication. The prevalence rate of active epilepsy in Trabzon is low compared to other parts of Turkey and other developing countries. This may be attributable to several factors, and particularly to variations among socio-economic factors. The population of Trabzon is regarded as relatively stable and homogenous, and socio-demographic and health data for the province of Trabzon are much better than those for the rest of the country.