Neuropsychiatric Comorbidities Research Articles

Peripheral inflammation is accompanied by cerebral hypoperfusion in mice

IntroductionChronic pain is a disabling condition that is accompanied by neuropsychiatric comorbidities such as anxiety, depression, and cognitive decline. While the peripheral alterations are well-studied, we lack an understanding of how these peripheral changes can result in long-lasting brain alterations and the ensuing behavioral phenotypes. This study aims to quantify changes in cerebral blood perfusion using laser speckle contrast imaging (LSCI) in the murine Complete Freund's adjuvant (CFA) model of unilateral peripheral inflammation.MethodsTwenty four adult male and female C57BL/6 mice were randomly assigned to control (0.05 ml saline) or 1 of 3 experimental groups receiving CFA (0.01 ml, 0.05 ml, and 0.1 ml) on the right hindpaw. Three days after the intraplantar injections, animals were examined for signs of inflammation and subjected to craniotomy and in vivo LSCI of the parietal-temporal lobes.ResultsUnilateral administration of CFA resulted in signs of local inflammation as well as cerebral hypoperfusion in dose-dependent manner.DiscussionTo our knowledge, this is the first study using laser speckle contrast imaging to examine the effects of CFA-induced peripheral inflammation on cerebral blood perfusion. It serves as a first step in delineating the path by which insult to peripheral tissues can cause long-lasting brain plasticity via vascular mechanisms.

Effect of sex on neuropsychiatric comorbidities in childhood epilepsy.

Effect of sex on neuropsychiatric comorbidities in childhood epilepsy.

A Cross-Sectional Retrospective Review of Neuropsychiatric Comorbidities in Children With Non-Alcoholic Fatty Liver Disease.

This single-center cross-sectional retrospective chart review sought to define the prevalence of neuropsychiatric (NP) disorders among children with non-alcoholic fatty liver disease (NAFLD) compared to the general population. The prevalence rate of NP disorders was determined at diagnosis among children evaluated from 2006 to 2016. The NP disorder prevalence rates were compared to those reported in the 2016 National Survey of Children's Health (NSCH). 24.3% of 254 children with NAFLD reported to have at least 1 NP disorder compared to 16.9% of those in NSCH (relative risk [RR] = 1.44; P < .0001). More children had intellectual disability (ID) (4.5% vs 0.8%; RR = 5.43, P < .0001), depression (3.9% vs 2.2%; RR = 1.82, P = .0009), or autism spectrum disorder (ASD) (3.3% vs 2.0%; RR = 1.67, P = .047) in the Boston Children's Hospital (BCH) NAFLD cohort. The prevalence of 1 NP disorder was 29.4% in our cohort compared to 22.3% in NSCH (RR = 1.32; P = .007). Children with NAFLD have a higher rate of NP disorders compared to the general population.

Approach to Myoclonus Dystonia Syndrome: A European Reference Network Survey.

Myoclonus-dystonia syndrome (MDS) is a genetic movement disorder with childhood-onset, most frequently caused by SGCE defects. To evaluate the diagnostic and treatment strategies in MDS used by experts from the European Reference Network for rare neurological diseases (ERN-RND), and to assess the diagnosis and management experience in patients with MDS. Two different questionnaires were distributed: one among neurologists from ERN-RND, and another among patients and families with SGCE-related MDS. Twenty-nine adult and child neurologists from 14 countries, and 84 patients and caregivers from 12 countries, replied to the surveys. All the patients included in the analysis had SGCE-related MDS. The mean age was 30.8 years (SD 19,9; range 3-75). Sixty-nine percent of patients were diagnosed in childhood and 70% had a positive family history. Most participants suffered from predominant upper body myoclonus and focal/segmental dystonia, hindering daily activities in 80% of patients, such as handwriting, drinking, feeding, walking and speech. Botulinum toxin and DBS were effective options for managing movement disorders compared to pharmacological treatments. However, neither of these therapies were applied optimally. We found deficiencies in recognition and management of academic difficulties, and a high unemployment rate. Despite all but one patient reported psychiatric symptoms such as anxiety, depression or OCD, there was a lack of formal psychiatric evaluations. SGCE-MDS is a well-known neurological disorder among movement disorder specialists in Europe. Offering a multidisciplinary approach that tackles both movement disorders and neuropsychiatric comorbidities could enhance the diagnosis and treatment of patients with SGCE-MDS.

Sleep in the context of neuropsychiatric and primary medical comorbidity patterns among people with HIV.

Sleep in the context of neuropsychiatric and primary medical comorbidity patterns among people with HIV.

Leptin-dopamine interactions: unveiling the common link between type-2 diabetes and neuropsychiatric comorbidities.

Clinical evidence highlights the central nervous system as a key target in type-2 diabetes-related complications, yet the mechanisms underlying the increased prevalence of mood disorder issues, mainly depression, in patients with diabetes remain poorly understood. Leptin, an adiposity hormone known for its role in energy homeostasis, has been shown to improve insulin sensitivity and regulate blood glucose levels in diabetic populations. Beyond its metabolic effects, leptin also has the potential to mitigate psychiatric complications such as depression and anxiety. Notably, leptin receptors are predominantly expressed on dopamine (DA) neurons in the brain, hinting that leptin may orchestrate DA activity by serving as its endogenous modulator. This review examines the role of leptin as a potential common link between type-2 diabetes and mood disorders, particularly through its effects on DA function. This article proposes defective leptin signaling as a vital mechanism contributing to psychiatric complications and compromised DA functions in type-2 diabetes, highlighting leptin as a promising therapeutic target for addressing metabolic and psychiatric comorbidities.

Pruritus and Neuropsychiatric Symptoms Among Patients with Darier Disease-An Overlooked and Interconnected Challenge.

(1) Background: Darier disease (DD) is a rare autosomal dominant disorder caused by mutations in ATP2A2, a gene that encodes the sarco(endo)plasmic reticulum calcium-ATPase 2 enzyme, which disrupts calcium homeostasis in keratinocytes. Pruritus, a frequently overlooked symptom in DD, can lead to physical and emotional complications, especially in patients with DD who are genetically predisposed to psychiatric comorbidities. (2) Methods: This study aimed to analyze pruritus and other related symptoms in patients with DD and explore their correlation with neuropsychiatric conditions, psychological challenges, disease severity, and body surface area (BSA) involvement through a retrospective review of a tertiary center. (3) Results: Data from 76 patients (equal gender distribution, mean age 44 years) revealed a prevalence of pruritus of 90.8%, surpassing symptoms such as pain (34.3%) and malodor (43.4%). Burning sensations due to DD lesions were significantly correlated with the diagnosis of comorbid neuropsychiatric conditions (p = 0.047) and psychiatric medication use (p = 0.019). While pruritus correlated with disease severity and %BSA involvement, the findings were not statistically significant. Patients reporting pruritus had a significantly higher Dermatology Life Quality Index symptom score (2.4 ± 1.0), which is defined as the presence of itch, soreness, pain, or stinging, than those who did not (1.5 ± 0.6), indicating accurate symptom reporting. (4) Conclusions: In conclusion, a striking majority of patients with DD experience pruritus, with higher prevalence among those with neuropsychiatric challenges, severe Darier disease, and greater %BSA skin involvement. Clinicians should recognize pruritus as a key therapeutic target and adopt comprehensive treatment approaches that both address the neuropsychiatric comorbidities and the added psychological burden of pruritus in patients with DD.

Noradrenergic Locus Coeruleus-CA3 Activation Alleviates Neuropathic Pain and Anxiety- and Depression-Like Behaviors by Suppressing Microglial Neuroinflammation in SNI Mice.

Neuropathic pain (NP) arises from neuroimmune interactions following nerve injury and is often accompanied by anxiety and depression. The aim of the study is to evaluate the effects of the noradrenergic locus coeruleus (LC), a key regulator of pain and emotional states, projects extensively to the hippocampus. We investigated the effects of chronic NP on LC integrity and its projections to the hippocampal CA3 region in spared nerve injury (SNI) mice with behavioral tests, immunohistochemistry, neurochemical analyses, and Gq-DREADD. Chronic NP induced LC neuronal loss, reduced hippocampal norepinephrine (NE) release, and triggered microglial activation and neuroinflammation in CA3. Selective activation of LC-CA3 noradrenergic neurons using Gq-DREADD chemogenetics alleviated NP and comorbid anxiety- and depression-like behaviors. This intervention suppressed microglial activation, decreased proinflammatory cytokines (TNF-α and IL-1β), and restored NE levels in CA3. Our findings highlighted the therapeutic potential of targeting LC-CA3 projections to mitigate chronic NP and its neuropsychiatric comorbidities via modulation of hippocampal neuroinflammation.

Epilepsy, compulsion and oxytocin: Insights from behavioral sequences, using neuroethology and complexity systems approaches.

Epilepsy, compulsion and oxytocin: Insights from behavioral sequences, using neuroethology and complexity systems approaches.

Prevalence, Socio-Demographic Characteristics, and Co-Morbidities of Autism Spectrum Disorder in US Children: Insights from the 2020-2021 National Survey of Children's Health.

The primary goal of our study is to assess the national US prevalence of autism spectrum disorder (ASD), along with its socio-demographic characteristics, severity, and co-occurring medical and psychiatric disorders, using data from the 2020-2021 National Survey of Children's Health (NSCH). We analyzed 2020-2021 NSCH data to estimate the prevalence of ever-diagnosed and current ASD among 79,182 children and adolescents (3-17 years). Univariate and multivariate regression models were used to examine associations between medical and psychiatric co-morbidities, socio-demographic factors, and ASD severity. Adolescents (11-17 years) and males were more likely to have ASD, with males comprising 78.7% of the ASD group. The mean age of the sample was 10.1 ± 4.6 years, and 3.2% had an ASD diagnosis. Children from lower-income households and those with caregivers who completed only a high school education were more likely to have ASD. Nearly 96.4% of children with ASD had at least one co-morbid condition. The most common neuropsychiatric co-morbidities were developmental delay (64%), behavioral and conduct problems (57.8%), and anxiety disorder (45.7%), while the most common medical conditions were allergies (32.4%), genetic disorders (26.2%), and asthma (12.6%). Gender disparities in ASD presentation were evident that females with ASD were more likely to experience vision problems, cerebral palsy, epilepsy, depression, and intellectual disability but had lower odds of ADHD and anxiety problems. Greater ASD severity was linked to higher odds of intellectual disability (OR: 5.8, p < 0.001), developmental delay (OR: 5.0, p < 0.001), epilepsy, Down syndrome (OR: 3.4, p < 0.001), vision problems (OR: 2.5, p < 0.001), and genetic disorders (OR: 2.3, p < 0.001). This study provides updated prevalence estimates of ASD and highlights the high burden of co-morbidities, emphasizing the need for comprehensive, multidisciplinary approaches in ASD management. Additionally, our findings emphasize gender differences in ASD presentation, which should be considered in future research and clinical practice to ensure more tailored diagnostic and intervention strategies.

Impact of training healthcare professionals in the detection and management of neuropsychiatric comorbidities in people with HIV: The CONECTAR project in Spain.

Although anxiety, depression and insomnia in people with HIV (PWH) are prevalent and have a major impact on clinical outcomes and quality of life, physicians fail to evaluate them routinely. The CONECTAR Project [Neuropsychiatric Comorbidity (NPC): Key to Antiretroviral Treatment] aimed to improve NPC clinical care in PWH in Spain by upskilling healthcare professionals (HCPs). A group of HCPs developed a training programme, supported by national and international guidelines, to improve expertise on detecting and managing NPCs in PWH. The programme was conducted through workshops for physicians and nurses in various Spanish regions from April to November 2023; survey questionnaires were administered to physicians before the commencement of training and 15 days after. Later, a workshop was held for nurses who manage NPCs in PWH. The programme was completed by 64 physicians (22 had completed both questionnaires) and 11 nurses (no feedback obtained). Feedback from physicians reflected that the programme boosted awareness and self-perception of being more qualified, knowledgeable and able to use management tools and resources. Physicians also reported improved perception of time available for visits and more frequent enquiries about patients' NPC symptoms. Despite their satisfaction with the workshops, half of the physicians recognized the need for more training. The CONECTAR Project was a successful training programme that was well received and valued by HCPs who routinely manage NPCs in PWH. Institutions involved in HCP training to manage anxiety, depression and insomnia more effectively in PWH should consider similar proposals to reinforce clinical practices.

The epilepsy-autism phenotype associated with developmental and epileptic encephalopathies: New mechanism-based therapeutic options.

Epilepsy and autism often co-occur in genetic developmental and epileptic encephalopathies (DEEs), but their underlying neurobiological processes remain poorly understood, complicating treatment. Advances in molecular genetics and understanding the neurodevelopmental pathogenesis of the epilepsy-autism phenotype may lead to mechanism-based treatments for children with DEEs and autism. Several genes, including the newly reported PPFIA3, MYCBP2, DHX9, TMEM63B, and RELN, are linked to various neurodevelopmental and epileptic disorders, intellectual disabilities, and autistic features. These findings underscore the clinical heterogeneity of genetic DEEs and suggest diverse neurobiological mechanisms influenced by genetic, epigenetic, and environmental factors. Mechanisms linking epilepsy and autism include γ-aminobutyric acidergic (GABAergic) signaling dysregulation, synaptic plasticity, disrupted functional connectivity, and neuroinflammatory responses. GABA system abnormalities, critical for inhibitory neurotransmission, contribute to both conditions. Dysregulation of the mechanistic target of rapamycin (mTOR) pathway and neuroinflammation are also pivotal, affecting seizure generation, drug resistance, and neuropsychiatric comorbidities. Abnormal synaptic function and connectivity further underscore the epilepsy-autism phenotype. New treatment options targeting specific mechanisms linked to the epilepsy-autism phenotype are emerging. Genetic variants in potassium channel genes like KCNQ2 and KCNT1 are frequent causes of early onset DEEs. Personalized treatments like retigabine and quinidine have been explored with heterogeneous responses. Efforts are ongoing to develop more effective KCNQ activators and KCNT1 blockers. SCN1A genetic variants, particularly in Dravet syndrome, show potential for treatment of autistic symptoms with low-dose clonazepam, fenfluramine, and cannabidiol, although human trials have yet to consistently replicate animal model successes. Early intervention before the age of 3 years, particularly in SCN1A- and tuberous sclerosis complex-related DEEs, is crucial. Additionally, targeting the mTOR pathway shows promise for seizure control and managing epilepsy-associated comorbidities. Understanding the distinct autism spectrum disorder phenotype in DEEs and implementing early behavioral interventions are essential for improving outcomes. Despite genetic advances, significant challenges persist in diagnosing and treating DEE-associated epilepsy-autism phenotypes. Future clinical trials should adopt precision health approaches to improve neurodevelopmental outcomes.

A Pilot Study of Primary Ciliary Dyskinesia: Sleep-Related Disorders and Neuropsychiatric Comorbidities.

Sleep disorders are characterized by impaired quality, timing, and amount of sleep, resulting in daytime distress and functioning. Primary ciliary dyskinesia (PCD) is a rare genetic condition characterized by oto-sino-pulmonary manifestations with multiple comorbidities, including sleep disorders. Background/Objectives: This pilot study aims to assess sleep disorders and neuropsychiatric comorbidities in Puerto Rican patients with the RSPH4A (c.921+3_921+6delAAGT) PCD founder mutation. However, the literature on sleep-related disorders and their neuropsychiatric comorbidities in PCD is limited. Methods: A cohort of fifteen patients with the RSPH4A (c.921+3_921+6delAAGT) founder mutation (six pediatric, nine adults) were evaluated for sleep quality, cognitive, neurodevelopmental history, and mood-related manifestations, followed by diagnostic polysomnography for sleep-disordered breathing and other sleep-related disorder detection. Results: Twelve out of fifteen (12/15, 80%) patients presented with sleep-related disorders, particularly obstructive sleep apnea where the median Pediatric AHI was 1.25/h (IQR: 1.1-1.75/h), T < 90: 0.1 min (IQR: 0-1.9 min) and adult AHI 1.3 (IQR: 0.9-8), T < 90: 0.2 min (IQR: 0-3.5 min). PCD patients also presented complex sleep behaviors, and more than half had sleep-related movement manifestations such as sleep-related Bruxism, PLMS, among others. All pediatric patients with OSA met criteria for an anxiety disorder, with a GAD-7 of 13 (IQR: 10.5-15.8); this association was not clearly seen in adults. Conclusions: Patients with PCD RSPH4A exhibited multiple sleep and neuropsychiatric manifestations, particularly OSA, sleep-related movement disorders and complex sleep behaviors. Further studies are needed to determine if these manifestations result from obstructive breathing, sleep mechanism disruption, or other neurodevelopmental impairment associated with this ciliopathy.

Opioid Prescribing Disparity in Traumatically Injured Patients.

Opioid prescribing is understudied in trauma patients, where disadvantaged communities are overrepresented. In this study, we evaluated disparities in opioid administration after trauma. We conducted a retrospective cohort study of injured adults at a level I trauma center, 2018-2021. Opioids were quantified in milligram morphine equivalents (MME). Primary outcomes were receipt of opioids inpatient and at discharge, MMEs per hospital day, and, for patients prescribed opioids at discharge, MMEs and discharge pain control days. Multivariable logistic regression identified factors associated with overall receipt of opioids after injury, general linear modeling identified factors associated with MMEs received inpatient and at discharge, and negative binomial regression evaluated pain control days prescribed at discharge. Of 3,032 patients, 2,514 (82.92%) required opioids as an inpatient and 1,803 (71.72%) still required opioids the day of discharge. Of these, 1,310 (72.66%) were discharged with opioids. Black (β-24.94, 95%CI -37.25, -12.62, p<0.001) and Hispanic (β -21.96, 95%CI -39.21, -4.71, p=0.01) patients received lower MMEs while inpatient. Factors associated with lower odds of discharge with opioids included non-English language (OR 0.56, 95%CI 0.38, 0.82, p=0.003), substance use disorder (SUD) (OR 0.69, 95%CI 0.49, 0.97, p=0.03), neuropsychiatric comorbidities (OR 0.58, 95%CI 0.39, 0.87, p=0.008), and violent injury (OR 0.61, 95%CI 0.45, 0.85, p=0.003). On discharge, Black individuals (β -130.71, 95%CI -251.26, -10.17, p=0.03) received lower MMEs and patients with SUD (IRR 0.65, 95%CI 0.53, 0.80, p<0.001) received fewer pain control days. Trauma patients experienced disparities in opioid prescribing throughout hospitalization. Lower opioid doses were administered to non-white patients, while language, mental health comorbidities, and mechanism influenced discharge opioid prescriptions.

Comorbidity patterns and the risk of injurious falls in older people with atrial fibrillation: Findings from a Swedish nation-wide population-based study

Comorbidity patterns and the risk of injurious falls in older people with atrial fibrillation: Findings from a Swedish nation-wide population-based study

Genomics-informed neuropsychiatric care for neurodevelopmental disorders: Results from a multidisciplinary clinic.

Patients with neurodevelopmental disorders (NDDs) have high rates of neuropsychiatric comorbidities. Genomic medicine may help guide care because pathogenic variants are identified in up to 50% of patients with NDDs. We evaluate the impact of a genomics-informed, multidisciplinary, neuropsychiatric specialty clinic on the diagnosis and management of patients with NDDs. We performed a retrospective study of 316 patients from the University of California, Los Angeles Care and Research in Neurogenetics Clinic, a genomics-informed multidisciplinary clinic. Among the 246 patients who underwent genetic testing, 41.8% had a pathogenic or likely pathogenic variant. Patients had 62 different genetic diagnoses, with 12 diagnoses shared by 2 or more patients, whereas 50 diagnoses were found in only single patients. Genetic diagnosis resulted in direct changes to clinical management in all patients with a pathogenic or likely pathogenic variant, including cascade testing (30.6%), family counseling (22.2%), medication changes (13.9%), clinical trial referral (2.8%), medical surveillance (30.6%), and specialty referrals (69.4%). A genomics-informed model can provide significant clinical benefits to patients with NDDs, directly affecting management across multiple domains for most diagnosed patients. As precision treatments advance, establishing a genetic diagnosis will be critical for proper management. With the growing number of rare neurogenetic disorders, clinician training should emphasize core principles of genomic medicine over individual syndromes.

P0113 Maintained microglial homeostasis and adult neurogenesis despite chronic ileocolitis

Abstract Background Inflammatory bowel diseases (IBD), such as Crohn‘s disease and ulcerative colitis, are associated with neuropsychiatric comorbidities, including depression, anxiety, and Parkinson’s disease [1]. These are presumably mediated along the gut-immune-brain axis by the transition of inflammation across gastrointestinal and CNS-surrounding barriers, causing the activation of microglia [1]. Adult hippocampal neurogenesis, the generation of new neurons in the hippocampus throughout life, is impaired by peripheral inflammation [2] and linked to affective and neurodegenerative disorders [3]. In the context of IBD, adult hippocampal neurogenesis has only been investigated in chemically induced animal models mimicking ulcerative colitis, leading to heterogeneous results [1]. Methods In this study, we used the Casp8∆IEC ileocolitis mouse model which is characterized by a specific knockout of caspase 8 in intestinal epithelial cells, leading to ileocolitis that resembles Crohn’s disease [4]. We investigated the effects of ileocolitis on microglia and on adult neurogenesis in the hippocampal dentate gyrus (DG). The hippocampi of 14- and 24-week-old Casp8∆IEC mice were compared to wild-type (wt) mice using immunohistochemistry and immunofluorescence analyses. Microglial density and proliferation were assessed by quantifying ionized calcium-binding adapter molecule 1 (Iba1)+ and Iba1+Mcm2+ myeloid cells, respectively. Additionally, microglial phagocytic activation was examined by co-staining Iba1 with the lysosomal marker CD68. To evaluate adult hippocampal neurogenesis, progenitor cell proliferation and maturation were analyzed by quantifying Mcm2+ proliferating cells and doublecortin (DCX)+ neuroblasts in the DG. Cells undergoing cell death during maturation were quantified by co-staining DCX with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Results Microglial density and proliferation in the dentate gyrus region were preserved between Casp8∆IEC and wt mice at both 14 and 24 weeks of age. Likewise, microglial activation state and phagocytosis remained unchanged between the two groups at both time points Adult hippocampal neurogenesis was maintained between the two groups. The proliferation and maturation of progenitor cells, as well as the rate of cell death during maturation in the dentate gyrus, remained similar between Casp8∆IEC and wt mice. Conclusion These results demonstrate that key aspects of hippocampal immune function and adult hippocampal neurogenesis are resilient to experimental ileocolitis induced by the deletion of Casp8 in intestinal epithelial cells. References (1)Masanetz RK, Winkler J, Winner B, Günther C, Süß P. The Gut-Immune-Brain Axis: An Important Route for Neuropsychiatric Morbidity in Inflammatory Bowel Disease. Int J Mol Sci. 2022;23(19):11111. Published 2022 Sep 21. doi:10.3390/ijms231911111 (2)Ekdahl CT, Claasen JH, Bonde S, Kokaia Z, Lindvall O. Inflammation is detrimental for neurogenesis in adult brain. Proc Natl Acad Sci U S A. 2003;100(23):13632-13637. doi:10.1073/pnas.2234031100 (3)Toda T, Parylak SL, Linker SB, Gage FH. The role of adult hippocampal neurogenesis in brain health and disease. Mol Psychiatry. 2019;24(1):67-87. doi:10.1038/s41380-018-0036-2 (4)Günther C, Martini E, Wittkopf N, et al. Caspase-8 regulates TNF-α-induced epithelial necroptosis and terminal ileitis. Nature. 2011;477(7364):335-339. Published 2011 Sep 14. doi:10.1038/nature10400

Understanding Deep Endometriosis: From Molecular to Neuropsychiatry Dimension.

Endometriosis is a widely spread disease that affects about 8% of the world's female population. This condition may be described as a spread of endometrial tissue apart from the uterine cavity, but this process's pathomechanism is still unsure. Apart from classic endometriosis symptoms, which are pelvic pain, infertility, and bleeding problems, there are neuropsychiatric comorbidities that are usually difficult to diagnose. In our review, we attempted to summarize some of them. Conditions like migraine, anxiety, and depression occur more often in women with endometriosis and have a significant impact on life quality and pain perception. Interestingly, 77% of endometriosis patients with depression also have anxiety. Neuroimaging gives an image of the so-called endometriosis brain, which means alternations in pain processing and cognition, self-regulation, and reward. Genetic factors, including mutations in KRAS, PTEN, and ARID1A, influence cellular proliferation, differentiation, and chromatin remodeling, potentially exacerbating lesion severity and complicating treatment. In this review, we focused on the aspects of sciatic and obturator nerve endometriosis, the emotional well-being of endometriosis-affected patients, and the potential influence of endometriosis on dementia, also focusing on prolonged diagnosis. Addressing endometriosis requires a multidisciplinary approach, encompassing molecular insights, innovative therapies, and attention to its psychological and systemic effects.

Neuropsychiatric profile in tuberous sclerosis complex patients with epilepsy.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by mutations in the TSC1 or TSC2 genes, leading to dysregulation of the mTOR pathway and multisystemic manifestations. Epilepsy is a common neurologic feature of TSC, frequently accompanied by neuropsychiatric comorbidities. Understanding the relationship between epilepsy severity, TSC-associated neuropsychiatric disorders (TAND), and cognitive outcomes is crucial for optimizing patient care. A retrospective study was conducted at a pediatric tertiary care hospital in Qatar, involving 38 TSC patients (20 female, 18 male) aged 1-18 years, diagnosed between October 2018 and March 2020. Epilepsy severity was assessed using the Early Childhood Epilepsy Severity Scale (E-Chess), and TAND was evaluated using the TAND checklist. Genetic analysis was performed for all patients, and statistical analyses were used to explore correlations between epilepsy severity, TAND, and cognitive outcomes. The majority (82%) of TSC patients had epilepsy, with a mean onset age of 9.2 months. Uncontrolled seizures were associated with higher rates of intellectual disability and more pronounced TAND manifestations compared to controlled seizures. Autism spectrum disorder (ASD) was reported in 42% of the cohort, with significant correlations found between epilepsy severity and ASD-related domains on the TAND checklist. Intellectual disability was prevalent (67.6%), with variability attributed to genetic background and early severe neurological presentations. This study reinforces the link between epilepsy severity and neuropsychiatric comorbidities in TSC, confirming earlier findings. Significant correlations were observed between epilepsy severity and ASD-related domains, and the high prevalence of intellectual disability in TSC patients was highlighted. However, the relationship between ASD, TSC, and epilepsy remains complex and requires further investigation. Despite advances in treatment options, including mTOR inhibitors and newer antiepileptic drugs, unmet needs remain in the comprehensive care of TSC patients. Optimizing seizure control is a clear priority, but equally important is the need for addressing the cognitive and behavioral components of TAND. Early intervention with tailored, multidisciplinary approaches including neurology, psychiatry, psychology, and educational specialists could mitigate the long-term impact of these comorbidities, particularly in children. These approaches must be individualized to each patient's unique set of challenges, emphasizing not only seizure control but also psychosocial support and educational adaptation to improve their overall quality of life. This study sheds light on the intricate interactions between epilepsy severity, neuropsychiatric manifestations, and cognitive outcomes in TSC patients. The findings emphasize the need for tailored management approaches, focusing on early seizure control and comprehensive multidisciplinary care. Further research is required to clarify the mechanisms underlying these associations and to develop targeted interventions for improving the quality of life for individuals with TSC and epilepsy.

Neuropsychiatric comorbidities and TMS biomarker influence postsurgical seizure outcomes in children with refractory focal epilepsy

Neuropsychiatric comorbidities and TMS biomarker influence postsurgical seizure outcomes in children with refractory focal epilepsy