OBJECTIVE: To examine the efficacy and safety of perampanel (PER) in patients with post-stroke epilepsy (PSE), brain tumor-related epilepsy (BTRE), and post-traumatic epilepsy (PTE) using Japanese real-world data.
METHODS: The prospective post-marketing observational study included patients with focal seizures with or without focal to bilateral tonic-clonic seizures who received PER combination therapy. The observation period was 24 or 52 weeks after the initial PER administration. The safety and efficacy analysis included 3716 and 3272 patients, respectively. This post hoc analysis examined responder rate (50% reduction in seizure frequency), seizure-free rate (proportion of patients who achieved seizure-free), and safety in patients included in the post-marketing study who had PSE, BTRE, and PTE in the 4 weeks prior to the last observation.
RESULTS: Overall, 402, 272, and 186 patients were included in the PSE, BTRE, and PTE subpopulations, and 2867 controls in the \"Other\" population (etiologies other than PSE, BTRE, or PTE). Mean modal dose (the most frequently administered dose) values at 52 weeks were 3.38, 3.36, 3.64, and 4.04 mg/day for PSE, BTRE, PTE, and \"Other,\" respectively; PER retention rates were 56.2%, 54.0%, 52.6%, and 59.7%, respectively. Responder rates (% [95% confidence interval]) were 82% (76.3%-86.5%), 78% (70.8%-83.7%), 67% (56.8%-75.6%), and 50% (47.9%-52.7%) for PSE, BTRE, PTE, and \"Other,\" respectively, and seizure-free rates were 71% (64.5%-76.5%), 62% (54.1%-69.0%), 50% (40.6%-60.4%), and 28% (25.8%-30.1%), respectively. Adverse drug reactions tended to occur less frequently in the PSE (14.7%), BTRE (16.5%), and PTE (16.7%) subpopulations than in the \"Other\" population (26.3%).
CONCLUSIONS: In real-world clinical conditions, efficacy and tolerability for PER combination therapy were observed at low PER doses for the PSE, BTRE, and PTE subpopulations.
CONCLUSIONS: To find out how well the medication perampanel works and whether it is safe for people who have epilepsy after having had a stroke, brain tumor, or head injury, we used information from real-life medical situations in Japan. We looked at the data of about 3700 Japanese patients with epilepsy who were treated with perampanel. We found that perampanel was used at lower doses and better at controlling seizures, and had fewer side effects for patients with epilepsy caused by these etiologies than the control group.

BACKGROUND: Striatal hyperdopaminergia is implicated in the pathoetiology of schizophrenia, but how this relates to dopaminergic midbrain activity is unclear. Neuromelanin-sensitive MRI (NM-MRI) provides a marker of long-term dopamine function. We examined if midbrain NM-MRI contrast-to-noise ratio (NM-CNR) was higher in people with schizophrenia relative to controls and if this correlated with dopamine synthesis capacity.
METHODS: N=154 participants (n=74 individuals with schizophrenia and n=80 healthy controls) underwent NM-MRI of the substantia nigra and ventral tegmental area (SN-VTA). A subset of the schizophrenia group (n=38) also received [18F]-DOPA PET to measure dopamine synthesis capacity (Kicer) in the SN-VTA and striatum.
RESULTS: SN-VTA NM-CNR was significantly higher in patients with schizophrenia relative to controls (effect size=0.38, p=0.019). This effect was greatest for voxels in the medial and ventral SN-VTA. In patients, SN-VTA Kicer positively correlated with SN-VTA NM-CNR (r=0.44, p=0.005) and striatal Kicer (r=0.71, p<0.001). Voxelwise analysis demonstrated that SN-VTA NM-CNR was positively associated with striatal Kicer (r=0.53, p=0.005) and that this relationship appeared strongest between the ventral SN-VTA and associative striatum in schizophrenia.
CONCLUSIONS: Our results suggest that neuromelanin levels are higher in patients with schizophrenia relative to controls, particularly in midbrain regions that project to parts of the striatum which receive innervation from the limbic and association cortices. The direct relationship between measures of neuromelanin and dopamine synthesis suggests that these aspects of schizophrenia pathophysiology are linked. Our findings highlight specific mesostriatal circuits as the loci of dopamine dysfunction in schizophrenia and, thus, potential therapeutic targets.

ADHD and ASD are highly heritable and show a high co-occurrence and persistence into adulthood. This study aimed to identify pre and perinatal risk factors, and early psychosocial exposures related to later diagnosis of ADHD, ASD, and their co-occurrence. 16,365 children born 1997-1999 and their families, involved in the prospective population-based ABIS study (All Babies in Southeast Sweden), were included in this sub-study. Pre and perinatal factors and early environmental psychosocial exposures were collected from parental-questionnaires at birth and 1-year follow-up. Diagnoses from birth up to 23 years of age were obtained from the Swedish National Diagnosis Register in 2020. The cumulative incidence of ADHD, ASD, and their co-occurrence in the ABIS-cohort Study were 4.6%, 1.7%, and 1.1%, respectively. Being male was associated with an increased risk for ADHD, ASD, and their co-occurrence (aOR 1.30, 1.56, and 1.91, respectively), while higher household income reduced it (aOR 0.82, 0.73, and 0.64). Serious life events during pregnancy (aOR 1.40) and maternal smoking (aOR 1.51) increased the risk of ADHD, while older maternal age (aOR 0.96), higher parental education (aOR 0.72 maternal and aOR 0.74 paternal) and longer exclusive breastfeeding (aOR 0.72) reduced it. Non-Swedish paternal nationality (aOR 0.40) and higher maternal education (aOR 0.74) were associated with a lower risk of ASD, while a family history of autoimmune diseases increased the risk of the co-occurrence of both disorders (aOR 1.62). Obtained results suggest that the etiology of ADHD, ASD, and their co-occurrence is independently associated with environmental psychosocial predictors. The co-occurrence seems to overlap the etiology of ADHD, in which psychosocial determinants have a larger role, however, it is also independently influenced by a family history of autoimmune diseases.

OBJECTIVE: This study aimed to analyze the clinical characteristics, etiology, and treatment of midlife-onset epilepsy in a real-world setting at a single center in China.
METHODS: The clinical data of patients who attended the epilepsy clinic of the Department of Neurology, First Medical Center of Chinese PLA General Hospital from February 1999 to March 2023 were retrospectively analyzed. The clinical characteristics, etiology, and risk factors for midlife-onset epilepsy over the past 24 years were analyzed.
RESULTS: Of the 969 patients with onset at 45-64 years of age, 914 were diagnosed with epilepsy with at least two unprovoked seizures 24 h apart. Of those, 99.7% (911) were of focal origin. The median duration from the initial seizure to follow-up treatment was 2 months (interquartile range [IQR]: 1.0-6.0 months). Before commencing treatment, 30.2% (207/683) of patients experienced more than two seizures. A structural etiology was found in 66.3% (606/914) of patients. Cerebrovascular disease (CVD) and traumatic brain injury (TBI) accounted for 19.9% (182/914) and 16.6% (152/914) of the cases, respectively. Logistic regression analysis showed that patients with abnormal imaging (odds ratio [OR] 2.04; 95% confidence interval [CI] 1.25-3.32; p = .004), focal seizures (OR 2.98; 95%CI 1.82-4.87; p < .001), and seizure clusters (OR 2.40; 95%CI 1.21-4.73; p = .01) had poor drug responses. Treatment outcomes were generally better in patients with epilepsy after CVD (OR .49; 95%CI .28-.85; p = .01). Treatment initiation after two seizures (OR .70; 95%CI .42-1.15; p = .16) or 6 months after the first seizure (OR 1.17; 95%CI .66-2.09; p = .58) did not result in poor drug effectiveness.
CONCLUSIONS: Midlife-onset epilepsy is typically of focal etiology, with CVD being the most common cause, and tends to respond well to medication. The median duration from the initial seizure to follow-up treatment was 2 months. Over 30% of patients experienced more than two seizures before commencing treatment, but this did not affect subsequent outcomes.

Background: Ischemic heart disease (IHD) represents the main cause of heart failure (HF). A prognostic stratification of HF patients with ischemic etiology, particularly those with acute coronary syndrome (ACS), may be challenging due the variability in clinical and hemodynamic status. The aim of this study is to assess the prognostic power of the HLM score in a population of patients with ischemic HF and in a subgroup who developed HF following ACS. Methods: This is an observational, prospective, single-center study, enrolling consecutive patients with a diagnosis of ischemic HF. Patients were stratified according to the four different HLM stages of severity, and the occurrence of CV death, HFH, and worsening HF events were evaluated at 6-month follow-up. A sub-analysis was performed on patients who developed HF following ACS at admission. Results: The study included 146 patients. HLM stage predicts the occurrence of CV death (p = 0.01) and CV death/HFH (p = 0.003). Cox regression analysis confirmed HLM stage as an independent predictor of CV death (OR: 3.07; 95% IC: 1.54-6.12; p = 0.001) and CV death/HFH (OR: 2.45; 95% IC: 1.43-4.21; p = 0.001) in the total population of patients with HF due to IHD. HLM stage potentially predicts the occurrence of CV death (p < 0.001) and CV death/HFH (p < 0.001) in patients with HF following ACS at admission. Conclusions: Pathophysiological-based prognostic assessment through HLM score is a potentially promising tool for the prediction of the occurrence of CV death and CV death/HFH in ischemic HF patients and in subgroups of patients with HF following ACS at admission.

OBJECTIVE: This study aimed to give a full spectrum of orthopedic injuries associated with electric scooter (e-scooter) use and analyze related factors, report on follow-up data from the patient\'s perspective and make a comparative etiological analysis of young adult hip fractures.
METHODS: A total of 851 consecutive patients were admitted to the Emergency Department following e‑scooter injuries between January 2021 and July 2022, of whom 188 had 214 orthopedic injuries. The demographics, injury, and incident characteristics of these patients were collected. All fractures were classified as per the AO/OTA classification. Two groups were created as operatively or conservatively treated patients and data were comparatively analyzed. Follow-up examination incorporated a survey using binary questions on patients\' perspectives. An etiological comparative analysis of hip fractures in young adults admitted to the same center between 2016 and 2022 was conducted.
RESULTS: The median patient age was 25. Inexperienced drivers constituted 32% of the injured. The protective gear use rate was at 3%. Higher speed (p = 0.014) and age (p = 0.011) were significantly associated with operative treatment. A total of 39% of the operated patients could not return to preinjury physical function, while 74% regretted using an e‑scooter. The most common etiological factor for traumatic young hip fractures was fall from a height between 2016 and 2020, whereas it became e‑scooter accidents in 2021-2022.
CONCLUSIONS: The rate of e‑scooter-related operative treatment is high and leaves the patient in regret (84%) and a physically limited condition (39%). A speed limit of ≤ 15 km/h could decrease the rate of operative injuries. The e‑scooter was identified as the top etiological factor in the last 2 years for traumatic young hip fractures.
METHODS: II, Diagnostic cohort study.
UNASSIGNED: ZIEL: Ziel dieser Studie war es, das gesamte Spektrum orthopädischer Verletzungen im Zusammenhang mit der Nutzung von Elektrorollern (E-Scootern) zu erfassen und die damit zusammenhängenden Faktoren zu analysieren, über Follow-up-Daten aus der Sicht der Patienten zu berichten und eine vergleichende ätiologische Analyse von Hüftfrakturen bei jungen Erwachsenen durchzuführen.
METHODS: Zwischen Januar 2021 und Juli 2022 wurden insgesamt 851 Patienten nach Verletzungen durch E‑Scooter in die Notaufnahme eingeliefert, von denen 188 orthopädische Verletzungen hatten. Die demographischen Daten sowie die Verletzungs- und Unfallmerkmale dieser Patienten wurden erfasst. Alle Frakturen wurden gemäß der AO/OTA-Klassifikation klassifiziert. Es wurden zwei Gruppen gebildet: operativ oder konservativ behandelte Patienten, die Daten wurden vergleichend analysiert. Die Nachuntersuchung umfasste eine Umfrage mit binären Fragen zur Perspektive der Patienten. Es wurde eine vergleichende ätiologische Analyse von Hüftfrakturen bei jungen Erwachsenen durchgeführt, die zwischen 2016 und 2022 in dasselbe Zentrum eingeliefert wurden.
UNASSIGNED: Der Altersmedian der Patienten lag bei 25 Jahren. Unerfahrene Fahrer machten 32 % der Verletzten aus. Die Verwendung von Schutzausrüstung lag bei 3 %. Höhere Geschwindigkeit (p = 0,014) und Alter (p = 0,011) waren signifikant mit der operativen Behandlung verbunden. Insgesamt 39 % der operierten Patienten konnten ihre körperliche Funktion von vor der Verletzung nicht wiederherstellen, während 74 % die Benutzung eines E‑Scooters bereuten. Der häufigste ätiologische Faktor für traumatische junge Hüftfrakturen war zwischen 2016 und 2020 ein Sturz aus der Höhe, während es in den Jahren 2021–2022 E‑Scooter-Unfälle waren.
UNASSIGNED: Die Rate der E‑Scooter-bedingten operativen Behandlungen ist hoch und hinterlässt den Patienten mit Reue (84 %) und körperlich eingeschränktem Zustand (39 %). Eine Geschwindigkeitsbegrenzung von ≤ 15 km/h könnte die Rate der operativen Verletzungen verringern. Der E‑Scooter wurde in den letzten 2 Jahren als wichtigster ätiologischer Faktor für traumatische junge Hüftfrakturen identifiziert.
UNASSIGNED: II, Diagnostische Kohortenstudie.

BACKGROUND: Tuberculous lymphadenitis (TBLN) is the most common infectious etiology of peripheral lymphadenopathy in adults, in Turkiye. This study aimed to identify the demographic, clinical, and laboratory variables that differentiate TBLN from non-tuberculous lymphadenitis (NTBLN), as well as the etiology of lymphadenopathy in adults.
METHODS: Patients who were over 18 years old and were referred to the infectious disease outpatient clinics with complaints of swollen peripheral lymph nodes, and who underwent lymph node biopsy between 1 January 2010 and 1 March 2021, were included in this multicenter, nested case-control study.
RESULTS: A total of 812 patients at 17 tertiary teaching and research hospitals in Turkiye were included in the study. TBLN was the most frequent diagnosis (53.69%). The proportion of patients diagnosed with TBLN was higher among females; and among those who had a higher erythrocyte sedimentation rate, positive purified protein derivative test, and positive interferon-gamma release test result (p < 0.05). However, TBLN was less frequent among patients with generalized lymphadenopathy, bilateral lymphadenopathy, axillary lymphadenopathy, inguinal lymphadenopathy, hepatomegaly, splenomegaly, leukocytosis, and moderately increased C reactive protein levels (p < 0.05).
CONCLUSIONS: Identifying the variables that predict TBLN or discriminate TBLN from NTBLN will help clinicians establish optimal clinical strategies for the diagnosis of adult lymphadenopathy.

BACKGROUND: The increasing global incidence and prevalence of inflammatory bowel disease (IBD) necessitates an investigation into the potential influence of environmental risk factors on its origin.
OBJECTIVE: This multicenter case-control study aimed to investigate potential environmental risk factors contributing to IBD development in Turkey.
METHODS: The study included 156 Crohn\'s disease (CD), 277 ulcerative colitis (UC) patients, and 468 controls (matched for age and gender) from six hospitals\' gastroenterology departments. Data collection relied on the International Organization of IBD\'s questionnaire on environmental factors. Each environmental factor was initially analyzed using univariate and subsequently multivariate logistic regression models.
RESULTS: In the multivariate model, regular coffee consumption was associated with decreased odds for both CD (OR 0.28; 95% CI 0.14-0.55) and UC (OR 0.25; 95% CI 0.15-0.42). Stress was associated with UC (OR 3.27; 95% CI 1.76-6.10) and CD (OR 4.40; 95% CI 2.12-9.10) development. A history of childhood infectious diseases (gastroenteritis, upper respiratory tract infections, etc.) raised the odds for both CD (OR 9.45; 95% CI 2.51-35.6) and UC (OR 7.56; 95% CI 1.57-36.4). Conversely, consuming well/spring water (OR 0.22; 95% CI 0.10-0.50) and childhood antibiotic use (OR 0.41; 95% CI 0.18-0.93) showed a positive association against UC. Increased consumption of refined sugar and industrial food products emerged as risk factors for IBD. Smoking increased the risk for CD (OR 2.38; 95% CI 1.16-4.91), while ex-smoking increased the risk for UC (OR 3.16; 95% CI 1.19-8.37).
CONCLUSIONS: This study represents the first multicenter case-control study in Turkey examining the effects of environmental factors on IBD. It revealed that coffee consumption is positively associated, while stress and childhood infection-related diseases are risk factors. These findings, which are not supported by other studies, provide insight into the relationships between these factors and IBD.

OBJECTIVE: Recent findings suggest the incidence of first-episode psychotic disorders (FEP) varies according to setting-level deprivation and cannabis use, but these factors have not been investigated together. We hypothesized deprivation would be more strongly associated with variation in FEP incidence than the prevalence of daily or high-potency cannabis use between settings.
METHODS: We used incidence data in people aged 18-64 years from 14 settings of the EU-GEI study. We estimated the prevalence of daily and high-potency cannabis use in controls as a proxy for usage in the population at-risk; multiple imputations by chained equations and poststratification weighting handled missing data and control representativeness, respectively. We modeled FEP incidence in random intercepts negative binomial regression models to investigate associations with the prevalence of cannabis use in controls, unemployment, and owner-occupancy in each setting, controlling for population density, age, sex, and migrant/ethnic group.
RESULTS: Lower owner-occupancy was independently associated with increased FEP (adjusted incidence rate ratio [aIRR]: 0.76, 95% CI: 0.61-0.95) and non-affective psychosis incidence (aIRR: 0.68, 95% CI: 0.55-0.83), after multivariable adjustment. Prevalence of daily cannabis use in controls was associated with the incidence of affective psychoses (aIRR: 1.53, 95% CI: 1.02-2.31). We found no association between FEP incidence and unemployment or high-potency cannabis use prevalence. Sensitivity analyses supported these findings.
CONCLUSIONS: Lower setting-level owner-occupancy and increased prevalence of daily cannabis use in controls independently contributed to setting-level variance in the incidence of different psychotic disorders. Public health interventions that reduce exposure to these harmful environmental factors could lower the population-level burden of psychotic disorders.

OBJECTIVE: Infantile seizures cause great concern for both doctors and parents. In addition to modern neuroimaging and genetics, clinical tools helpful in predicting the course of the disease are needed. We prospectively studied the incidence, electroclinical characteristics and etiologies of epilepsy syndromes with onset before the age of 12 months and looked for prognostic determinants of outcome by age 24 months.
METHODS: From February 2017 through May 2019, we recruited all eligible infants diagnosed with epilepsy at our unit. Data on electroclinical studies, genetic investigations and drug response were gathered prospectively. The infants were given a structured neurological examination (Hammersmith Infantile Neurological examination [HINE] and Griffiths scales) at predetermined intervals until age 24 months at which age neurocognitive evaluation with Bayley scales was performed.
RESULTS: Included were 60 infants (27 female). The mean onset age of epilepsy was 5.3 (±2.5 standard deviation) months. The incidence of epilepsy in the population-based cohort was 131 (95% confidence interval 99-172)/100 000. Epilepsy syndrome was identified in 80% and etiology in 58% of infants. Self-limited infantile epilepsy was the second most common syndrome (incidence 18/100 000) after infantile epileptic spasms syndrome. PRRT2 was the most common monogenic cause. At age 24 months, 37% of the infants had drug-resistant epilepsy (DRE) and half had a global developmental delay (GDD). Abnormal first HINE was the strongest predictor of GDD, followed by DRE and identified etiology. DRE was associated with structural etiology and GDD. Those with normal first HINE and good response to treatment had favorable outcomes, irrespective of the identified etiology.
CONCLUSIONS: Our results support a high incidence of self-limited epilepsy in infancy and PRRT2 as the genetic cause in the first year of life. Notwithstanding the advances in etiological discovery, we want to highlight the importance of clinical evaluation as standardized neurological examination with HINE proved a valuable tool in prognostication.
CONCLUSIONS: One in every 700-800 babies develop epilepsy within the first year after birth. Our study identified an epilepsy syndrome in 80% and the cause of epilepsy in 60% of the participants. By age 2 years, over one-third of the children still experienced seizures, and almost half faced significant developmental delay. Structural brain abnormalities increased the likelihood of difficult epilepsy and developmental challenges. Babies whose epilepsy was caused by a gene defect varied widely in development and response to medications. Babies with normal neurological examination at first visit, especially if their seizures stopped quickly, had favorable development.