Lamotrigine vs levetiracetam in female patients of childbearing age with juvenile absence epilepsy: A Bayesian reanalysis.

OBJECTIVE: Women of childbearing age with juvenile absence epilepsy (JAE) face treatment challenges due to limited access to safe and effective anti-seizure medications (ASMs). In a previous study we compared the effectiveness of levetiracetam (LEV) and lamotrigine (LTG) in women with idiopathic generalized epilepsy (IGE), highlighting a superiority of LEV in juvenile myoclonic epilepsy. In this study, we specifically reanalyzed, through a Bayesian approach and by expanding the previously published cohort, the comparative effectiveness of these ASMs as initial monotherapy in JAE. METHODS: We conducted a multicenter, retrospective, comparative effectiveness study on women of childbearing age diagnosed with JAE and prescribed LEV or LTG as the initial ASM. Inverse probability treatment weighting (IPTW) Bayesian Cox proportional hazard models were employed to evaluate treatment failure (TF) due to ineffectiveness and ASM retention. The patients' center of provenance and year of prescription were considered as random effect factors. Posterior probabilities and relative log-risk distribution were computed, and the distribution of posterior draws was analyzed to assess the evidence supporting LTG superiority over LEV. RESULTS: Of 123 patients, those treated with LTG (n = 67) demonstrated lower TF and higher ASM retention than those treated with LEV (n = 56), with the IPTW-weighted Bayesian Cox proportional hazards model showing a 99.2% posterior probability of LTG being superior on TF and a 99.5% probability on ASM retention. Additional analyses on ≥50% and ≥75% seizure reduction through IPTW-weighted Bayesian logistic regression largely confirmed these findings, whereas the two ASMs did not show evident differences in terms of seizure freedom. The two ASMs showed comparable safety profiles, with only a minority of patients discontinuing treatment due to side effects. SIGNIFICANCE: Bayesian reanalysis supports LTG as first-line monotherapy for JAE in women of childbearing age, emphasizing the importance of individualized treatment strategies in women with IGE. This study underscores the value of Bayesian methods in refining clinical research and treatment decisions.

Predictors of Seizure Recurrence in Women With Idiopathic Generalized Epilepsy Who Switch From Valproate to Another Medication.

BACKGROUND AND OBJECTIVES: To investigate the predictors of seizure recurrence in women of childbearing age with idiopathic generalized epilepsy (IGE) who switched from valproate (VPA) to alternative antiseizure medications (ASMs) and compare the effectiveness of levetiracetam (LEV) and lamotrigine (LTG) as VPA alternatives after switch. METHODS: This multicenter retrospective study included women of childbearing age diagnosed with IGE from 16 epilepsy centers. Study outcomes included worsening or recurrence of generalized tonic-clonic seizure (GTCS) at 12 months and 24 months after the switch from VPA to an alternative ASM. The comparative effectiveness of LEV and LTG as alternative ASM following VPA discontinuation was assessed through inverse probability treatment-weighted (IPTW) Cox regression analysis. RESULTS: We included 426 women with IGE, with a median (interquartile range) age at VPA switch of 24 (19-30) years and a median VPA dosage of 750 (500-1,000) mg/d. The most common reason for VPA switch was teratogenicity concern in 249 women (58.6%), and the most common ASM used in place of VPA was LEV in 197 (46.2%) cases, followed by LTG in 140 (32.9%). GTCS worsening/recurrence occurred in 105 (24.6%) and 139 (32.6%) women at 12 and 24 months, respectively. Catamenial worsening of seizures, higher VPA dosage during switch, multiple seizure types, and shorter duration of GTCS freedom before switch were independent predictors of GTCS recurrence or worsening at 12 months according to mixed multivariable logistic regression analysis. After internal-external validation through 16 independent cohorts, the model showed an area under the curve of 0.71 (95% CI 0.64-0.77). In the subgroup of 337 women who switched to LEV or LTG, IPTW Cox regression analysis showed that LEV was associated with a reduced risk of GTCS worsening or recurrence compared with LTG (adjusted hazard ratio 0.59, 95% CI 0.40-0.87, p = 0.008) during the 24-month follow-up. DISCUSSION: Our findings can have practical implications for optimizing counselling and treatment choices in women of childbearing age with IGE and may help clinicians in making informed treatment decisions in this special population of patients. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for women with IGE switching from VPA, LEV was associated with a reduced risk of GTCS worsening or recurrence compared with LTG.

Effects of Transcranial Direct Current Stimulation on Clinical Outcomes, Calcitonin Gene-Related Peptide, and Pituitary Adenylate Cyclase-Activating Polypeptide-38 Levels in Menstrual Migraine.

OBJECTIVES: Transcranial direct current stimulation (tDCS) has been suggested as an alternative treatment option for migraine. The present study aimed to evaluate the efficacy of tDCS on clinical outcomes in addition to calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating peptide 38 (PACAP-38) levels in individuals with menstrual-related migraine (MRM) for the first time. MATERIALS AND METHODS: In this parallel study, 58 female patients between the ages of 18 and 45 years, including 36 with MRM and 22 with nonmenstrual migraines (nMM), were recruited. Sessions of 2-mA 20-minute anodal tDCS were administered over the left dorsolateral prefrontal cortex within three consecutive days (1:1 active and sham stimulation). Migraine attack frequency, severity, analgesic usage, CGRP, and PACAP-38 levels of the patients were evaluated before and one month after tDCS. RESULTS: After tDCS, in the active group compared with the sham group, the frequency (p = 0.031), the severity of attacks (p = 0.003), the number of days with headache (p = 0.004), and the analgesic usage (p = 0.024) were all decreased. In both MRM and nMM groups, the frequency and severity of attacks and analgesic usage were decreased in those receiving active stimulation (p < 0.001 for each). CGRP and PACAP-38 levels were no different in the active group and the sham group after tDCS. CONCLUSIONS: tDCS was shown to be efficacious in migraine prophylaxis and a valuable option for migraine and MRM treatment. The absence of changes in serum CGRP and PACAP-38 levels suggests that tDCS efficacy may stem from distinct cerebral electrophysiological mechanisms.

Long-term prognosis of patients with photosensitive idiopathic generalized epilepsy.

OBJECTIVE: The long-term prognosis of photosensitive idiopathic generalized epilepsy (p-IGE) is generally considered favorable; however, its specific characteristics remain unclear. Our objective was to investigate the extended prognosis of p-IGE. METHODS: We analyzed the demographics, clinical, and electroencephalographic (EEG) data of consecutive patients who were diagnosed as having p-IGE, who were under follow-up for a minimum of 10 years and exhibited a photoparoxysmal response (PPR) in their EEGs. Prognostic data, epilepsy course types, and electroclinical variables were compared using appropriate statistical methods. RESULTS: The mean follow-up duration for 108 consecutive patients with p-IGE (74.1 % female) was 16.8 ± 6.5 years. The main syndromes within this cohort included juvenile myoclonic epilepsy (37 %), juvenile absence epilepsy (15.7 %), and epilepsy with eyelid myoclonia (EEM) (14.8 %). In terms of epilepsy course types, 27.8 % were in the relapse-remission group, and 13.9 % had never experienced remission. A low early remission rate (5.6 %) was evident, with the remaining half of the cohort categorized as the late remission group. Several significant poor prognostic factors were identified including self-induction, clinical symptoms accompanying PPR, asynchrony and focal findings in EEG discharges, a wide frequency range of PPR, the coexistence of three seizure types, the presence of accompanying focal seizure features, and a history of convulsive status epilepticus. CONCLUSIONS: Our long-term follow-up study, conducted within a substantial p-IGE group, unveiled newly proposed course types within this epilepsy category and highlighted significant poor prognostic factors related to photosensitivity. These findings furnish valuable insights for precise prognosis counselling and effective management strategies for patients with p-IGE.

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.

Caregiver burden and its predictors in adult epilepsy patients.

OBJECTIVE: The aim of this study was to evaluate caregiver burden and factors associated with caregiver burden in caregivers of adults with epilepsy. MATERIALS AND METHODS: This descriptive cross-sectional study was conducted with 107 patients with epilepsy and 107 their primary caregivers. Personal information form including sociodemographic data and Zarit Caregiver Burden Inventory (ZBI), were used for caregivers, and patient information form, Montreal Cognitive Assessment Scale (MoCA), Hospital Anxiety and Depression Scale (HADS), Epilepsy Quality of Life Scale (QoLIE-31) and Stigma Scale were used for patients. RESULTS: Caregiver burden was found to be related to gender (p = 0.047), marital status (p = 0.008), income (p = 0.003), education level (p = 0.05) age at onset of epilepsy (p = 0.025) and type of therapy (p = 0.005). The scale scores for cognitive functions (p < 0.001), stigma (p < 0.001), anxiety (p = 0.001), depression (p = 0.005), and quality of life (p < 0.001) of the patient showed significant correlations with caregiver burden. In addition, caregiver burden was found to correlate with some caregiver characteristics such as caregivers' age (p = 0.041), gender (p < 0.001), education (p < 0.001), income (p = 0.001) and relationship with the patient (p = 0.016). Time spent on caregiving per day was also positively correlated with caregiving burden (p < 0.001). In regression analysis, the gender of the caregiver, the gender of the patient, the stigma level of patient, and the type of treatment were found to be predictors of care burden (p < 0.05, R2 = 0.61). CONCLUSION: It was found that two-thirds of the families of patients with epilepsy experienced varying degrees of caregiver burden. In addition, it was determined that caregiver burden was associated with sociodemographic and numerous psychosocial factors of the patient as well as the caregiver. It is important that both the caregiver and the patient being cared for are closely evaluated in interventions to reduce the caregiver burden in patients with epilepsy.

Acute effect of transcranial direct current stimulation on photoparoxysmal response.

INTRODUCTION: Transcranial direct current stimulation (tDCS) is a non-invasive technique, used to modify the excitability of the central nervous system. The main mechanism of tDCS is to change the excitability by subthreshold modulation by affecting neuronal membrane potentials in the direction of depolarization or repolarization. tDCS was previously investigated as an alternative adjunctive therapy in patients with epilepsy. We aimed here to investigate the acute effect of tDCS on the photoparoxysmal response (PPR) in EEG. METHODS: We enrolled 11 consecutive patients diagnosed with idiopathic generalized epilepsy who had PPR on at least 2 EEGs. Three different procedures, including sham, anodal, and cathodal tDCS were applied to the patients at intervals of one week by placing the active electrode over Oz, for 2 mA, 20 minutes. Spike-wave indices (SWI) were counted by two researchers independently and were compared during intermittent photic stimulation (IPS) on EEGs both before and after the application. RESULTS: After cathodal tDCS, SWI increased compared to baseline EEG and sham EEG in 3 patients, and after anodal tDCS, SWI increased in 2 patients. Although the SWI values did not change significantly, 8 patients reported subjectively that the applications were beneficial for them and that they experienced less discomfort during photic stimulation after the sessions. There were no side effects except transient skin rash in one patient, only. CONCLUSIONS: In our sham controlled tDCS study with both cathodal and anodal stimulation, our data showed that there was no significant change in SWI during IPS, despite subjective well-being. tDCS' modulatory effect does not seem to act in the acute phase on EEG parameters after photic stimulation.

Glycine Receptor ß-Targeting Autoantibodies Contribute to the Pathology of Autoimmune Diseases.

BACKGROUND AND OBJECTIVES: Stiff-person syndrome (SPS) and progressive encephalomyelitis with rigidity and myoclonus (PERM) are rare neurologic disorders of the CNS. Until now, exclusive GlyRα subunit-binding autoantibodies with subsequent changes in function and surface numbers were reported. GlyR autoantibodies have also been described in patients with focal epilepsy. Autoimmune reactivity against the GlyRß subunits has not yet been shown. Autoantibodies against GlyRα1 target the large extracellular N-terminal domain. This domain shares a high degree of sequence homology with GlyRß making it not unlikely that GlyRß-specific autoantibody (aAb) exist and contribute to the disease pathology. METHODS: In this study, we investigated serum samples from 58 patients for aAb specifically detecting GlyRß. Studies in microarray format, cell-based assays, and primary spinal cord neurons and spinal cord tissue immunohistochemistry were performed to determine specific GlyRß binding and define aAb binding to distinct protein regions. Preadsorption approaches of aAbs using living cells and the purified extracellular receptor domain were further used. Finally, functional consequences for inhibitory neurotransmission upon GlyRß aAb binding were resolved by whole-cell patch-clamp recordings. RESULTS: Among 58 samples investigated, cell-based assays, tissue analysis, and preadsorption approaches revealed 2 patients with high specificity for GlyRß aAb. Quantitative protein cluster analysis demonstrated aAb binding to synaptic GlyRß colocalized with the scaffold protein gephyrin independent of the presence of GlyRα1. At the functional level, binding of GlyRß aAb from both patients to its target impair glycine efficacy. DISCUSSION: Our study establishes GlyRß as novel target of aAb in patients with SPS/PERM. In contrast to exclusively GlyRα1-positive sera, which alter glycine potency, aAbs against GlyRß impair receptor efficacy for the neurotransmitter glycine. Imaging and functional analyses showed that GlyRß aAbs antagonize inhibitory neurotransmission by affecting receptor function rather than localization.

Prevalence and Trajectories of Post-COVID-19 Neurological Manifestations: A Systematic Review and Meta-Analysis.

INTRODUCTION: The aim of this systematic review and meta-analysis was to evaluate the prevalence of thirteen neurological manifestations in people affected by COVID-19 during the acute phase and at 3, 6, 9 and 12-month follow-up time points. METHODS: The study protocol was registered with PROSPERO (CRD42022325505). MEDLINE (PubMed), Embase, and the Cochrane Library were used as information sources. Eligible studies included original articles of cohort studies, case-control studies, cross-sectional studies, and case series with ≥5 subjects that reported the prevalence and type of neurological manifestations, with a minimum follow-up of 3 months after the acute phase of COVID-19 disease. Two independent reviewers screened studies from January 1, 2020, to June 16, 2022. The following manifestations were assessed: neuromuscular disorders, encephalopathy/altered mental status/delirium, movement disorders, dysautonomia, cerebrovascular disorders, cognitive impairment/dementia, sleep disorders, seizures, syncope/transient loss of consciousness, fatigue, gait disturbances, anosmia/hyposmia, and headache. The pooled prevalence and their 95% confidence intervals were calculated at the six pre-specified times. RESULTS: 126 of 6,565 screened studies fulfilled the eligibility criteria, accounting for 1,542,300 subjects with COVID-19 disease. Of these, four studies only reported data on neurological conditions other than the 13 selected. The neurological disorders with the highest pooled prevalence estimates (per 100 subjects) during the acute phase of COVID-19 were anosmia/hyposmia, fatigue, headache, encephalopathy, cognitive impairment, and cerebrovascular disease. At 3-month follow-up, the pooled prevalence of fatigue, cognitive impairment, and sleep disorders was still 20% and higher. At six- and 9-month follow-up, there was a tendency for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache to further increase in prevalence. At 12-month follow-up, prevalence estimates decreased but remained high for some disorders, such as fatigue and anosmia/hyposmia. Other neurological disorders had a more fluctuating occurrence. DISCUSSION: Neurological manifestations were prevalent during the acute phase of COVID-19 and over the 1-year follow-up period, with the highest overall prevalence estimates for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache. There was a downward trend over time, suggesting that neurological manifestations in the early post-COVID-19 phase may be long-lasting but not permanent. However, especially for the 12-month follow-up time point, more robust data are needed to confirm this trend.

Peripheral blood regulatory B and T cells are decreased in patients with focal epilepsy.

Patients with focal epilepsy of unknown cause (FEoUC) may display T cell infiltration in post-surgery brain specimens and increased serum levels of pro-inflammatory cytokines produced by B and T cells, indicating potential involvement of adaptive immunity. Our study aimed to investigate the peripheral blood distribution of B and T cell subgroups to find clues supporting the distinct organization of adaptive immunity in FEoUC. Twenty-two patients with FEoUC and 25 age and sex matched healthy individuals were included. Peripheral blood mononuclear cells were immunophenotyped by flow cytometry. Expression levels of anti-inflammatory cytokines and FOXP3 were measured by real-time PCR. Carboxyfluorescein succinimidyl ester (CFSE) proliferation assay was conducted using CD4+ T cells. Patients with FEoUC showed significantly decreased regulatory B (Breg), B1a, plasmablast and regulatory T (Treg) cell percentages, and increased switched memory B and Th17 cell ratios. Moreover, CD4+CD25+CD49d- Tregs of FEoUC patients displayed significantly reduced TGFB1 and FOXP3, but increased IL10 gene expression levels. CD4+ helper T cells of patients with FEoUC gave more exaggerated proliferation responses to phytohemagglutinin, anti-CD3 and anti-CD28 stimulation. Patients with FEoUC display increased effector lymphocyte, decreased regulatory lymphocyte ratios, and impaired Treg function and enhanced lymphocyte proliferation capacity. Overall, this pro-inflammatory phenotype lends support to the involvement of adaptive immunity in FEoUC.

Diffusion tensor imaging in photosensitive and nonphotosensitive juvenile myoclonic epilepsy.

INTRODUCTION/BACKGROUND: Juvenile myoclonic epilepsy (JME) syndrome is known to cause alterations in brain structure and white matter integrity. The study aimed to determine structural white matter changes in patients with JME and to reveal the differences between the photosensitive (PS) and nonphotosensitive (NPS) subgroups by diffusion tensor imaging (DTI) using the tract-based spatial statistics (TBSS) method. METHODS: This study included data from 16 PS, 15 NPS patients with JME, and 41 healthy participants. The mean fractional anisotropy (FA) values of these groups were calculated, and comparisons were made via the TBSS method over FA values in the whole-brain and 81 regions of interest (ROI) obtained from the John Hopkins University White Matter Atlas. RESULTS: In the whole-brain TBSS analysis, no significant differences in FA values were observed in pairwise comparisons of JME patient group and subgroups with healthy controls (HCs) and in comparison between JME subgroups. In ROI-based TBSS analysis, an increase in FA values of right anterior corona radiata and left corticospinal pathways was found in JME patient group compared with HC group. When comparing JME-PS patients with HCs, an FA increase was observed in the bilateral anterior corona radiata region, whereas when comparing JME-NPS patients with HCs, an FA increase was observed in bilateral corticospinal pathway. Moreover, in subgroup comparison, an increase in FA values was noted in corpus callosum genu region in JME-PS compared with JME-NPS. CONCLUSIONS: Our results support the disruption in thalamofrontal white matter integrity in JME, and subgroups and highlight the importance of using different analysis methods to show the underlying microstructural changes.

Topiramate ban in women of childbearing potential with idiopathic generalized epilepsy: Does effectiveness offset the teratogenic risks?

Regulatory agencies have recently discouraged the prescription of topiramate (TPM) to women of childbearing potential with epilepsy due to growing evidence of the teratogenic and neurodevelopmental risks associated with its use during pregnancy. It remains, however, unclear whether the use of TPM in this population can be supported to some extent by its high effectiveness. In this multicenter, retrospective, cohort study performed at 22 epilepsy centers, we investigated the comparative effectiveness of TPM and levetiracetam (LEV) given as first-line antiseizure medication in a cohort of women of childbearing potential with idiopathic generalized epilepsy (IGE). A total of 336 participants were included, of whom 24 (7.1%) received TPM and 312 (92.9%) LEV. Women treated with TPM had significantly higher risks of treatment failure and treatment withdrawal and were less likely to achieve seizure freedom at 12 months compared to women treated with LEV. In conclusion, this study highlighted a low tendency among clinicians to use TPM in women of childbearing potential with IGE, anticipating the recently released restrictions on its use. Furthermore, the available data on effectiveness do not appear to support the use of TPM in this population.

Epilepsy with generalized tonic-clonic seizures alone: Electroclinical features and prognostic patterns.

OBJECTIVE: Epilepsy with generalized tonic-clonic seizures alone (GTCA) is a common but poorly characterized idiopathic generalized epilepsy (IGE) syndrome. Hence, we investigated electroclinical features, seizure outcome, and antiseizure medication (ASM) withdrawal in a large cohort of GTCA patients. METHODS: In this multicenter retrospective study, GTCA patients defined according to the diagnostic criteria of the International League Against Epilepsy (2022) were included. We investigated prognostic patterns, drug resistance at the last visit, and ASM withdrawal, along with their prognostic factors. RESULTS: We included 247 patients with a median (interquartile range [IQR]) age at onset of 17 years (13-22) and a median follow-up duration of 10 years (IQR = 5-20). Drug resistance at the last visit was observed in 40 (16.3%) patients, whereas the median latency to achieve 2-year remission was 24 months (IQR = 24-46.5) with a median number of 1 (IQR = 1-2) ASM. During the long-term follow-up (i.e., 202 patients followed ≥5-years after the first ASM trial), 69 (34.3%) patients displayed an early remission pattern and 36 (17.9%) patients displayed a late remission pattern, whereas 16 (8%) and 73 (36.3%) individuals had no-remission and relapsing-remitting patterns, respectively. Catamenial seizures and morning predominance of generalized tonic-clonic seizures (GTCS) independently predicted drug resistance at the last visit according to multivariable logistic regression. Treatment withdrawal was attempted in 63 (25.5%) patients, with 59 (93.7%) of them having at least a 12-month follow-up after ASM discontinuation. At the last visit, 49 (83%) of those patients had experienced GTCS recurrence. A longer duration of seizure freedom was the only factor predicting a higher chance of successful ASM withdrawal according to multivariable Cox regression. SIGNIFICANCE: GTCA could be considered a relatively easily manageable IGE syndrome, with a low rate of drug resistance and a high prevalence of early response to treatment. Nevertheless, a considerable proportion of patients experience relapsing patterns of seizure control, highlighting the need for appropriate counseling and lifestyle recommendations.

Olfactory function assessment of migraine patients by using the Sniffin' sticks test: A clinical study.

OBJECTIVE: This as a cross-sectional controlled clinical study. We hypothesis that the olfactory functions in migraine patients may differ from the healthy controls. In this study, we evaluated the olfactory functions by using a Sniffin' Sticks test battery, which is a reliable and semi quantitative test to evaluate for olfactory dysfunction. METHODS: Patients above 18 years of age who had migraine received a definitive diagnosis of migraine from experienced headache specialists based on the criteria of The International Classification of Headache Disorders-3 were included. Odor threshold, discrimination, and identification parameters were assessed using the "Sniffin' Sticks" test. RESULTS: One-hundred and one migraine patients (age [mean ± SD], 36.9 ± 10.4 years; range, 18-60 years) and sixty healthy volunteers (age 34.5 ± 13.2 years, range 18-65 years) participated in our study. The median odor threshold score [percentiles 25th-75th] was 8.3 [6.5-9.8] for the migraine group during attack free period and 4.5[3.6-6.0] for the control group. It was found that the migraine group had a median odor discrimination score of 10.0 [10.0-13.0] and the control group 12.0 [11.0-13.0]. These differences were statistically significant (p < 0.001 and p = 0.032 respectively). The median odor discrimination and identification scores were statistically significant higher for the participants with higher educational level group than in those of lower educational group (p < 0.0001). The median odor discrimination and identification scores of those without allodynia (12.0 [10.0-14.0] and 13.0 [10.0-13.0] respectively) were higher than that of those with allodynia (11.0 [9.0-12.0] and 11.0 [10.0-13.0] respectively) (p = 0.037 and p = 0.034 respectively). CONCLUSIONS: We found that the odor thresholds, discrimination and identification scores of the migraine group demonstrate differences from those of the healthy group and in relation to allodynia.

Real-life experiences with galcanezumab and predictors for treatment response in Turkey.

BACKGROUND: The complexity of clinical practice extends far beyond the controlled settings of trials, and there is a need for real-world studies aimed at identifying which patients will respond to anti-CGRP monoclonal antibodies in different countries. This study aimed to investigate the efficacy and safety of galcanezumab in treating migraine in a real-life setting in Turkey, as well as identify predictors of treatment response. METHODS: A total of 476 patients who diagnosed with migraine according to ICHD-3 criteria and treated with galcanezumab by headache specialists were voluntarily participated in this cross-sectional study. Galcanezumab is indicated for the prevention of migraine in adults who have at least 4 monthly migraine days in Turkey. All patients filled out a survey on Google Form that comprised 54 questions, addressing various aspects such as demographics, migraine characteristics, previous use of acute symptomatic medication, failures with preventive drug classes, comorbidities, most bothersome symptoms, as well as the interictal burden of migraine. RESULTS: Among the participants, 89.3% reported that galcanezumab treatment was beneficial for them. A decrease in the frequency (80.0%), severity (85.7%), and acute medication usage for migraine attacks (71.4%) was reported with galcanezumab treatment. An adverse effect related to galcanezumab was reported in 16.3% of cases, but no serious adverse reactions were observed. Remarkably, 14.3% of participants reported no longer experiencing any headaches, and 18.9% did not require any acute treatment while receiving galcanezumab treatment. A logistic regression model showed that male gender, lack of ictal nausea, and previous failure of more than 2 prophylactic agents may predict the non-responders. CONCLUSIONS: The first large series from Turkey showed that galcanezumab treatment is safe and effective in most of the patients diagnosed with migraine by headache experts in the real-life setting. Patients reported a significant decrease in both ictal and interictal burden of migraine and expressed satisfaction with this treatment.

Evaluation and treatment approaches for neurological post-acute sequelae of COVID-19: A consensus statement and scoping review from the global COVID-19 neuro research coalition.

Post-acute neurological sequelae of COVID-19 affect millions of people worldwide, yet little data is available to guide treatment strategies for the most common symptoms. We conducted a scoping review of PubMed/Medline from 1/1/2020-4/1/2023 to identify studies addressing diagnosis and treatment of the most common post-acute neurological sequelae of COVID-19 including: cognitive impairment, sleep disorders, headache, dizziness/lightheadedness, fatigue, weakness, numbness/pain, anxiety, depression and post-traumatic stress disorder. Utilizing the available literature and international disease-specific society guidelines, we constructed symptom-based differential diagnoses, evaluation and management paradigms. This pragmatic, evidence-based consensus document may serve as a guide for a holistic approach to post-COVID neurological care and will complement future clinical trials by outlining best practices in the evaluation and treatment of post-acute neurological signs/symptoms.

Levetiracetam vs Lamotrigine as First-Line Antiseizure Medication in Female Patients With Idiopathic Generalized Epilepsy.

Importance: After the recent limitations to prescribing valproate, many studies have highlighted the challenging management of female patients of reproductive age with idiopathic generalized epilepsy (IGE). However, no study, to the authors' knowledge, has addressed the comparative effectiveness of alternative antiseizure medications (ASMs) in these patients. Objective: To compare the effectiveness and safety of levetiracetam and lamotrigine as initial monotherapy in female patients of childbearing age with IGE. Design, Setting, and Participants: This was a multicenter, retrospective, comparative effectiveness cohort study analyzing data from patients followed up from 1994 to 2022. Patients were recruited from 22 primary, secondary, and tertiary adult and child epilepsy centers from 4 countries. Eligible patients were female individuals of childbearing age, diagnosed with IGE according to International League Against Epilepsy (2022) criteria and who initiated levetiracetam or lamotrigine as initial monotherapy. Patients were excluded due to insufficient follow-up after ASM prescription. Exposures: Levetiracetam or lamotrigine as initial monotherapy. Main Outcomes and Measures: Inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazards regression was performed to compare treatment failure (TF) among patients who received levetiracetam or lamotrigine as initial monotherapy. Results: A total of 543 patients were included in the study, with a median (IQR) age at ASM prescription of 17 (15-21) years and a median (IQR) follow-up of 60 (24-108) months. Of the study population, 312 patients (57.5%) were prescribed levetiracetam, and 231 (42.5%) were prescribed lamotrigine. An IPTW-adjusted Cox model showed that levetiracetam was associated with a reduced risk of treatment failure after adjustment for all baseline variables (IPTW-adjusted hazard ratio [HR], 0.77; 95% CI, 0.59-0.99; P = .04). However, after stratification according to different IGE syndromes, the higher effectiveness of levetiracetam was confirmed only in patients with juvenile myoclonic epilepsy (JME; IPTW-adjusted HR, 0.47; 95% CI, 0.32-0.68; P < .001), whereas no significant differences were found in other syndromes. Patients treated with levetiracetam experienced adverse effects more frequently compared with those treated with lamotrigine (88 of 312 [28.2%] vs 42 of 231 [18.1%]), whereas the 2 ASMs had similar retention rates during follow-up (IPTW-adjusted HR, 0.91; 95% CI, 0.65-1.23; P = .60). Conclusions and Relevance: Results of this comparative effectiveness research study suggest the use of levetiracetam as initial alternative monotherapy in female patients with JME. Further studies are needed to identify the most effective ASM alternative in other IGE syndromes.

COVID-19 vaccination-related headache showed two different clusters in the long-term course: a prospective multicenter follow-up study (COVA-Head Study).

BACKGROUND: Although acute headache following COVID-19 vaccination is widely acknowledged, the long-term progression of these headaches remains poorly understood. Our objective was to identify various phenotypes of prolonged or worsened headaches associated with COVID-19 vaccination and document any changes in these phenotypes over an extended period. Additionally, we aimed to document the diverse headache presentations among patients with pre-existing primary headaches. METHODS: A multinational, prospective observational study was conducted to investigate prolonged or worsened headaches associated with COVID-19 vaccination. Questionnaires assessing COVID-19 vaccination-related headaches at three time points (initial visit, 3rd month follow-up, and 6th month follow-up) were developed for the study. Headache specialists/clinicians evaluated patients using these questionnaires in a prospective manner. Repeated K-means cluster analysis was performed to identify patient profiles with prolonged or worsened headaches related to COVID-19 vaccination. RESULTS: Among the 174 patients included in the study, there was a female-to-male ratio of 128 (73.6%) to 46 (26.4%). The mean age of the patient group was 45.2 ± 13.3 years, and 107 patients (61.5%) had a pre-existing history of primary headaches. Through the analysis, two major clusters were identified based on headache characteristics at each visit. During the first visit (n = 174), Cluster 1 primarily comprised patients with a history of primary headaches, frontal localization of pain, throbbing pain type, more severe headaches accompanied by symptoms such as nausea, phonophobia, photophobia, and osmophobia, and worsened by physical activity. In contrast, Cluster 2 consisted of patients with longer headache durations (over one month) and a stabbing/pressing quality of pain. Patients in Cluster 1 had a higher prevalence of migraine as the pre-existing primary headache disorder compared to Cluster 2 (90.48% vs. 68.18%, respectively; p = 0.005). CONCLUSION: The identification of two distinct phenotypes of prolonged or worsened headaches related to COVID-19 vaccination can provide valuable clinical insights. Having an awareness of the potential worsening of headaches following COVID-19 vaccination, particularly in patients with a primary headache disorder such as migraine, can help clinicians and headache experts anticipate and adjust their treatment strategies accordingly. This knowledge can aid in preplanning treatment modifications and optimize patient care.

Continuous theta-burst stimulation in patients with drug-resistant epilepsy: A single-blind placebo-controlled cross-over pilot study.

OBJECTIVES: To evaluate the effect of continuous theta-burst stimulation (cTBS) in patients with drug-resistant epilepsy (DRE). METHODS: Twelve patients with DRE (five with idiopathic generalized and seven with focal epilepsy) were included in this cross-over design study and randomized to either first sham or first active stimulation, each applied for 5 consecutive days. A round coil over the vertex was used in generalized epilepsy or a figure-of-8 coil over the "epileptogenic area" in focal epilepsy. Sham stimulation was given by placing the coil 90° perpendicular to the head. The number of seizures, electroencephalography findings, Quality of Life in Epilepsy Inventory (QOLIE-84), and Symptom Check List (SCL-90) scores evaluated during the 8-12 weeks before and after active and sham stimulations were compared statistically. RESULTS: Eight patients could complete both active and sham stimulation periods of 5 days and two patients completed active stimulation sessions, without any significant adverse effects. The number of seizures significantly reduced after active cTBS, but not after sham stimulation, when compared with those recorded before the stimulation period. QOLIE scores were increased, but interictal epileptiform discharges and SCL-90 scores showed no difference after cTBS. Active stimulation was stopped in one patient after he experienced an aggravation of myoclonic seizures. CONCLUSIONS: cTBS seemed to be relatively safe and gave promising results in reducing the frequency of seizures in patients with both generalized and focal DRE. This time-saving technique may ease the introduction of repetitive transcranial magnetic stimulation into the routine practice of busy epilepsy clinics.