The ventral tegmental area (VTA) is a central hub in reward and motivation, integrating heterogeneous neuronal populations and projection-defined circuits to regulate learning, decision-making, and addiction. This review synthesizes anatomical organization and cellular diversity (dopaminergic, GABAergic, and glutamatergic neurons, including multitransmitter co-release), and maps major efferent pathways constituting the mesolimbic and mesocortical systems. We highlight computational roles of VTA activity, including reward prediction errors, incentive salience, and context memory integration, and summarize drug class-specific mechanisms that perturb VTA output. We then outline time-dependent neuroadaptations across mesocorticolimbic networks and discuss therapeutic implications spanning pharmacological, behavioral, and emerging circuit-targeted interventions. Together, these perspectives frame the VTA as a projection- and state-dependent controller whose dysfunction underlies core features of substance use disorders and other reward-related psychopathologies, pointing toward precision, circuit-informed treatments.
Objective: To develop a machine learning-based model for predicting epileptic seizures by analyzing electroencephalogram (EEG) signals and classifying the interictal and preictal phases. Methods: The EEG signals were analyzed in both the time and frequency domains using advanced feature extraction techniques. Three different machine learning approaches were employed, with special focus on long short-term memory (LSTM) networks. Features were extracted and classified to differentiate between seizure and non-seizure phases. The proposed models were evaluated using the publicly available CHB-MIT EEG dataset. The study was conducted between September 2022 and September 2024. Results: Among the tested models, the LSTM-based approach using the full-feature extraction pipeline achieved the highest prediction accuracy of 97.73%. This performance demonstrates strong potential for real-time seizure forecasting. Conclusion: Machine learning, particularly LSTM models, can accurately predict epileptic seizures by analyzing EEG signal patterns. These findings support the development of automated seizure prediction systems that could significantly improve the quality of life for epilepsy patients.
Objectives: To define prognostic factors that affect clinical outcome of patients after surgical resection of spinal intramedullary ependymoma. Methods: A retrospective multi-center study, including all cases operated on from 2007 through 2024 at 3 institutes. Data on surgical factors included: resection extent, intraoperative neurophysiology monitoring methods, and intraoperative/postoperative complications. Results: A total of 19 patients were included with a mean age of 37.8 years (SD = 13.2, range 8-57 years). The majority of ependymomas (n = 14, 73.7%) were in the cervical region. The most common presenting symptoms included pain in 14 patients (73.7%), sensory deficits in 11 patients (57.8%), and motor deficits 10 patients (52.6%). As per preoperative McCormick grading, 31.6%, 10.5%, and 31.6% were grade I, II, and III, respectively. Postoperatively, 57.9% of patients improved to McCormick grade I. Total gross tumor resection was achieved in 15 participants (78.9%). Syndromes, specifically neurofibromatosis type II, were significantly associated with a chance of recurrence (p = 0.004) and the need for a second surgery (p = 0.018). Conclusion: The preoperative neurological status correlates significantly with the postoperative outcome of the patient.
Objective: To assess burnout (BU) and sleep deprivation (SD) among neurology residents and their impact on clinical performance (CP). This study is based on a neurology residents from Saudi Arabia. Methods: This multi-centric, cross-sectional study invited 214 registered neurology residents in the country; 179 participated in the study. The Maslach Burnout Inventory (MBI), the Pittsburgh Sleep Quality Index (PSQI), and the Medical Council of Canada's Physicians' Self-Assessment Questionnaire (PSAQ) were used to evaluate burnout (BU) and sleep deprivation (SD) among neurology residents and their impact on clinical performance (CP). Results: Of the total 214 registered neurology residents, 179 participated in the study. About 50% reported irregularity in daily meals, while >50% failed to exercise due to time constraints. More than 80% of residents had moderate-to-high levels of emotional exhaustion (EE) and depersonalisation (DP), and 90% had low personal accomplishment (PA). The global PSQI score of 9.3 resulted from mediocre sleep quality, poor sleep duration, high sleep latency and daytime dysfunction. Moreover, 83.2% of residents complained of SD and opined that it affects their mental capability at work. Regarding residents' CP, 49.44% were high performers, while the proportion of low performers was marginally higher at 50.56%. The rampant prevalence of moderate-to-high EE and DP and poor PSQI scores had a significantly negative correlation with residents' CP (p= 0.0168, 0.0011 and 0.0441, respectively), CP correlated positively with PA levels (p=0.0045). Conclusion: Moderate to high levels of BU prevail among neurology residents in Saudi Arabia. A high number of neurology residents suffer from sleep disturbances. Both BU and SD exert a detrimental impact on neurology residents' CP, which adversely affects the quality of neurological care delivered by the burned-out and sleep-deprived residents.
Objective: To explore current practices and barriers in pediatric neuro-oncology care coordination, and to identify opportunities to optimize care pathways. Timely coordination between pediatric neurosurgery and oncology is critical for optimal outcomes in children with central nervous system (CNS) tumors. However, in many centers, pediatric oncologists are not involved until after surgery, which contributes to treatment delays and repeated procedures. Methods: A cross-sectional survey was conducted among neurosurgeons and pediatric oncologists in Saudi Arabia. The questionnaire addressed the timing of oncological involvement, neuroimaging practices, cerebrospinal fluid (CSF) cytology collection, and opinions on care coordination solutions. Results: A total of 62 responses were obtained. Only 29% of the participants reported presurgical oncology involvement in their typical practice, whereas 58% indicated that involvement occurred only after the final pathology results were obtained. Neuroimaging protocols varied: only 56.5% always performed dedicated CNS tumor magnetic resonance imaging (MRI) protocols before surgery, and spinal MRI was often delayed. CSF cytology practices were inconsistent, and major barriers included the lack of multidisciplinary tumor boards and the belief that oncology input before pathology is unnecessary. Over 88% of the respondents supported the use of presurgical tumor boards as a solution. Conclusion: There is substantial heterogeneity in pediatric neuro-oncology coordination practices. Efforts to promote early oncology consultations, standardized imaging protocols, and integrated care discussions may bridge critical gaps in care delivery.
Objective:To compare the accuracy and clinical outcomes of proximal catheter placement using neuronavigation guidance versus the traditional free-hand technique in patients undergoing ventriculoperitoneal shunt (VPS) surgery. Methods:We performed a single-surgeon, before-after cohort study: free-hand cases (2013-2019) and neuronavigation cases (2020-2024). Ethics approval was obtained (İzmir Bakİrçay University; Approval No. 2407; 20 Aug 2025). The primary endpoint was a composite of first-attempt ventricular entry and absence of postoperative day-1 (POD1) Grade-3 malposition. Secondary endpoints included grades, 12-month proximal tip dysfunction, and operative duration. Results:Fifty-two patients were included (neuronavigation N = 24; free-hand N = 28). Composite success was 100% (24/24) with neuronavigation versus 64.3% (18/28) free-hand (RR 1.54, 95% CI 1.16-2.03; p = 0.00095), risk difference +35.7% (NNT≈3). Grade-3 malposition occurred in 0% (0/24) versus 32.1% (9/28) (p = 0.002); Grades 1-2 (no Grade-3) were 100% versus 67.9% (RR 1.46, 95% CI 1.12-1.89). Optimal (Grade-1) placement was 70.8% versus 32.1% (RR 2.20, 95% CI 1.21-4.00; p = 0.0115). Twelve-month proximal tip dysfunction occurred in 8.3% versus 25.0% (RR 0.33, 95% CI 0.08-1.46). Operative time was longer with neuronavigation by +10.49 minutes (95% CI +7.40 to +13.58). Conclusion:In this before-after, single-surgeon series, neuronavigation improved first-pass success and eliminated malposition, with an approximate 10-minute time penalty; multicenter confirmation is warranted. Given the retrospective, historically controlled design, residual confounding and time-related practice changes may persist; nonetheless, the magnitude of effect supports considering neuronavigation when resources and workflow allow in routine practice.
Objectives: To characterize the clinical, histopathological, and molecular features of infant-type hemispheric glioma (IHG) and explore any overlaps it might have with other types of pediatric gliomas. Methods: Data from the Children's Brain Tumor Network (CBTN) were analyzed (last accessed in January 2025), with a focus on patients aged 0-4 years with gliomas, glioneuronal tumors, or ependymomas. This analysis encompassed the clinical, histological, and molecular profiles of the cases, including those with recurrent tumors. The study scrutinized the tumor circumscription, grading features, and molecular alterations, along with the Methylation Class, using methylation profiling via the Heidelberg v12.5 and v12.8 classifiers. Results: IHG is predominantly well-circumscribed, but recurrence may lead to infiltrative growth. Novel findings include the acquisition of additional genetic alterations in recurrent IHG, which alters prognosis. One case exhibited progression to a pleomorphic xanthoastrocytoma-like profile, while another acquired glioblastoma-like infiltrative pattern and TP53 mutations, associated with a more aggressive course. Distinguishing IHG from desmoplastic infantile ganglioglioma/astrocytoma (DIG/A) and Pediatric High-Grade Gliomas (pHGG) remains challenging, particularly in the absence of molecular data. Conclusion: This study emphasizes the heterogeneity of IHG and underscores the necessity for molecular surveillance in recurrent instances. The findings aid in refining diagnostic criteria and understanding the prognostic implications of genetic alterations in IHG.
Objective: This study aims to identify risk factors linked to the increasing prevalence of multiple sclerosis (MS) in Saudi Arabia. Multiple sclerosis is a chronic autoimmune condition affecting the central nervous system, marked by inflammation and damage to nerves and the myelin sheath. Method: A case-control study conducted from September 2022 to January 2024 included 832 participants- 263 diagnosed with MS and 569 controls. Controls were matched by age, gender, residence, and employment status. Data was collected using a validated questionnaire, with written consent obtained from participants aged 18 and older. Logistic regression analysis was used to ascertain risk factors. Results: Out of 832 participants, 263 (31.6%) were diagnosed with MS. The greatest percentage of MS cases occurred in the 25-34 age range (37.7%). After adjusting for potential confounders, smoking was significantly associated with increased MS risk (AOR = 2.34, 95% CI: [1.22-4.48], p = 0.01), as were vitamin D deficiency (AOR = 1.97, 95% CI: [1.31-2.98], p<0.0 0), and a history of childhood sexual abuse (AOR = 1.96, 95% CI: [1.11-3.45], p = 0.02). Conversely, vitamin D supplementation was associated with a substantial reduction in MS risk (AOR = 0.17, 95% CI: [0.10-0.28], p < 0.001), as was coffee consumption (AOR = 0.53, 95% CI: [0.30-0.96], p < 0.04). Conclusion: Smoking, vitamin D deficiency, and a history of childhood sexual abuse increase MS risk, while vitamin D supplementation and coffee consumption reduce it. Further research is essential to confirm these findings.
Objectives:To guide medical students and interns interested in neurology by identifying the key attributes of an ideal neurology candidate from the perspectives of neurology program directors (PDs). Methods:In this cross-sectional study, former and current neurology PDs were contacted across Saudi Arabia to complete a self-administered survey sent via email or text. The survey included seven questions: six on PD demographics and a seventh with 51 items evaluating candidate attributes on a 7-point Likert scale from disadvantage to advantage. Results:Thirty-two neurology PDs filled out the questionnaire. Among the key attributes PDs prioritized in a candidate is their letter of recommendation, preferably from a neurologist working at the same center where the candidate applied (mean = 2.44 ± 1.01); this was followed by the teamwork traits demonstrated by the candidate during their interview (mean = 2.34 ± 1.00) and, finally, clerkships completed as an intern in neurology at the same hospital where the candidate applied (mean = 2.28 ± 1.11). A significant regional difference was found regarding candidates who undertook international medical licensing examinations, which was observed as a disadvantage in the central region but as an advantage in the eastern and western regions (p = 0.002) of Saudi Arabia. Conclusion:The PDs prioritized candidates' skills, educational background, and genuine interest in neurology. Regional differences in the importance of international licensing exams reflect varied expectations. Future global studies could help refine and unify selection criteria for a fairer process.
Objectives:To assess the clinical characteristics, aetiologies, and disposition outcomes of patients presenting with altered mental status (AMS) in an academic emergency department, as well as to explore factors associated with hospitalization, intubation, and mortality. Methods:This retrospective cross-sectional study included 142 AMS patients presenting to the Emergency Department of (Blinded for Review) between December 2019 and December 2022. Adults (≥18 years) with documented AMS were enrolled, excluding those who died upon arrival or with iatrogenic AMS. Demographic, clinical presentation, comorbidity, medication, aetiology, intervention, and disposition outcome data, were extracted from the electronic System for Integrated Health Information. Results:The cohort (N = 142, mean age of 44.7 ± 21.1 years) was predominantly male (58.5%), and 83.1% of patients developed symptoms within 1 hour. Chronic comorbidities included diabetes (28.9%) and hypertension (28.2%), with frequent use of antihypertensives (23.2%), insulin (17.6%), and anticonvulsants (18.3%). Aetiologies were neurological (24.6%), drug abuse (24.6%), cardiovascular (15.5%), and endocrine/metabolic (12.0%). Most patients were discharged (81.7%), but the mortality rate was 4.2%. Intubation rate was 5.6%, of which intubation was primarily for traumatic AMS patients (37.5%), and all the intubated patients were male (p = 0.021). Males accounted for 83.3% of fatalities. Conclusion:The present study identified key AMS patterns, including high-risk aetiologies (cardiovascular and traumatic) and male-dominated disparities (intubation and mortality). These findings advocate for aetiology-specific protocols and reassessment of potential sex biases in acute care.
Neuroinflammation plays a critical role in the pathogenesis of neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis. This review explores the underlying mechanisms of neuroinflammation, with a focus on the roles of microglia, astrocytes, peripheral immune cell infiltration, and cytokine release. The complex interplay between oxidative stress and chronic inflammation accelerates neurodegeneration, contributing to disease progression. Microglial activation, initially protective, becomes harmful when sustained over time, driving chronic inflammation. Similarly, astrocytes once considered passive are now recognized for their active involvement in both inflammatory and neuroprotective responses, depending on their activation state. Prolonged activation of microglia and astrocytes compromises blood-brain barrier integrity, facilitating immune cell infiltration and amplifying inflammatory cascades, thereby worsening neuronal damage. We also detail the molecular mediators of the vicious cycle linking oxidative stress and chronic inflammation, including redox-sensitive transcription factors and mitochondrial dysfunction. Furthermore, the reviewed mechanisms highlight a pathogenic feedback loop, wherein oxidative stress and neuroinflammation fuel each other through NF-κB and Nrf2 pathways, suggesting that dual-target therapeutic strategies may be most effective. This review synthesizes evidence to propose that the failure to resolve neuroinflammation, driven by a self-reinforcing loop between oxidative stress and glial dysfunction, represents a critical, targetable node common to PD, AD, and MS.
Objective:To explore the correlation between diversity of the gut microbiota and key markers of inflammation and intestinal mucosal injury in pediatric febrile seizures (FS). Methods:This study compared 15 FS children (FS group) and 15 healthy individuals (normal control group). The participants underwent 16S rDNA sequencing to analyze gut microbiota profiles. ELISA was employed to measure peripheral blood concentrations of the pro-inflammatory cytokines TNF-α and IL-6, as well as intestinal mucosal injury indicators such as endotoxin (BT), D-lactate (D-Lac), and diamine oxidase (DAO). Analysis assessed the correlation between gut microbiota composition, inflammatory factors, and indicators of intestinal mucosal damage in FS. Results:Analysis of the FS group revealed a distinct gut microbiota profile compared to the control group, with notable variations in abundance at the phylum level. A marked decrease in the abundance of Patescibacteria was observed in the FS group. LEfSe clustering tree analysis revealed enrichment of Bacteroides in the FS group, suggesting an association with FS. Serum levels of IL-6, TNF-α, BT, D-Lac, and DAO in children with FS were higher than those in controls, (P<0.05). A Spearman analysis found that the altered microbiota of the FS group was correlated with increased expression of IL-6, BT, D-Lac, and DAO (P<0.05). Conclusion:Children with FS have disrupted gut microbiota, and this dysbiosis is correlated with inflammation and intestinal mucosal damage.
Background: The International League Against Epilepsy in 2014, defined epilepsy in any patient who has experienced one unprovoked seizure and has a probability of further seizures similar to the general recurrence risk (at least 60%) after 2 unprovoked seizures occurring over the next 10 years. Epilepsy patients are classified into 2 groups: early post-stroke seizures (EPSS), including patients who experience a seizure within 1 week of stroke onset, and late PSS (LPSS), including those who have a seizure more than 1 week after the stroke. Methods: This retrospective, record-based study was conducted between January 2021 and December 2024. A total of 486 stroke patients were screened. After excluding 241 patients with prior brain tumors, surgeries, or stroke events, 245 patients were included. Data were collected using a structured checklist covering demographic characteristics, seizure risk factors, stroke type and mechanism, seizure type, and timing of PSE diagnosis. Statistical analyses were performed using SPSS. Chi-square tests and logistic regression were used to evaluate the associations between risk factors and PSE development. Results: Of the 245 patients, 17 (6.9%) developed PSE. Among them, 41.2% were classified as having EPSS and 58.8% as having LPSE. Most PSE patients were men and married. Most seizures were of an unknown type. A statistically significant association was found between the mechanism of stroke and the development of PSE (p = 0.021), particularly cardioembolic and atherosclerotic (thrombotic) stroke. Other variables including age, sex, ICU admission, and comorbidities did not show statistically significant associations. Conclusion: The incidence of PSS in this study was 6.9%. LPSS was more common than EPSS. The development of PSE was significantly associated with stroke mechanisms, particularly cardioembolic and thrombotic stroke, whereas other risk factors showed no significant relationship.
Objective: To evaluate the efficacy and safety of erenumab, a monoclonal antibody that targets the calcitonin gene-related peptide (CGRP) receptor, in patients with treatment-resistant chronic migraine and medication overuse headache. Methods: A single-center, retrospective observational study conducted at University Medical Center on 73 patients with both medication-overuse headache and treatment-resistant chronic migraine who failed at least three oral preventive medications and/or botulinum toxin injections. Clinical data were extracted from the medical records and patient interviews. The patients received monthly erenumab injections 70 mg. Key outcomes included monthly migraine days, headache severity (visual analog scale [VAS]), headache impact test (HIT-6), acute medication use, and global impression of change (PGIC) over a 3-month follow-up period. Results: Significant reductions were observed in monthly migraine days (mean: 12.3 days, p<0.001), HIT-6 scores (mean: 21 points, P <0.001), headache severity (VAS score reduction: 6.1, P <0.001), and acute medication use (mean: 14.8 days, P <0.0 01). Most patients reported a "very good" or "good" improvement with minimal side effects. Conclusion: Erenumab demonstrated substantial efficacy and safety in reducing the frequency and severity of chronic migraine with medication overuse, improving the quality of life, and decreasing acute medications use. These findings support its role as a valuable therapeutic option for this challenging condition.
This review explores the relationship between underweight status and stroke risk and outcomes. Although the impact of obesity on stroke is well-documented, the harmful effects of being underweight are often overlooked. Drawing on evidence from observational studies, case-control studies, and meta-analyses, this review highlights that underweight individuals face increased mortality, poorer functional recovery, and higher rates of major adverse cardiovascular events and recurrent strokes post-stroke. Challenges in stroke prediction for this population are examined, including the limited research focus, shortcomings of existing risk assessment tools such as the CHA2DS2-VASc score, and population-specific factors affecting underweight prevalence and outcomes. The review identifies key research gaps, emphasizing the need for longitudinal studies encompassing diverse populations to inform tailored preventive strategies and improve risk assessment. It concludes by advocating for individualized risk assessment approaches that integrate nutritional status and targeted interventions to reduce the elevated stroke risks associated with being underweight.
Objectives: To investigate the occurrence and characteristics of seizures using routine electroencephalograms (EEGs) in intensive care unit (ICU) patients. Methods: We conducted a retrospective analysis on routine, portable EEGs of 188 adult ICU patients (53% male) in a large tertiary hospital in Riyadh, Kingdom of Saudi Arabia. We compared variables of interest using a t-test and chi-squared analyses and explored significant associations using binary logistic regression analysis. Results: We found significant associations between the occurrence of seizures on EEGs and several variables, including patient age, ICU admission due to status epilepticus, history of epilepsy or previous neurosurgical procedure, coma state, and convulsions at the time of EEG (p < 0.05). Logistic regression analysis revealed that age, ICU admission due to status epilepticus, and a history of epilepsy were independently associated with the occurrence of seizures on EEG. Epileptiform abnormalities were observed in 14.9% of patients; periodic abnormalities were identified in 14.3%. Electrographic seizures were evident in 11.2% of patients, and 63 comatose patients did not exhibit any evidence of seizures in their EEGs. Conclusion: Routine EEGs play a vital role in investigating altered mental status in ICU patients, particularly for seizure evaluation. Age, ICU admission due to status epilepticus, and a history of epilepsy are significant factors associated with seizure occurrence on EEG. Future studies should validate these findings and explore the comparative effectiveness of routine and continuous EEGs in ICU settings.
Objective: Epilepsy is a neurological disorder with profound impacts on various aspects of life. It may lead to significant medical and psychiatric comorbidities, one of which is personality disorders (PDs). This study aims to assess the prevalence of Cluster C PDs among adult patients with epilepsy (PWE) at a tertiary care hospital in Riyadh, Saudi Arabia. Method: This cross-sectional study, conducted between January 2024 and April 2025, enroled 360 adult PWE using convenience sampling. The study tool included the Structured Clinical Interview for DSM Disorders criteria, along with additional demographic and epilepsy-related questions developed by the research team. Results: Cluster C PDs were identified in 30. 6% of the participants. Obsessive-compulsive PD was the most prevalent (17. 8%), followed by avoidant PD (9.7%). No significant gender difference was found in the prevalence of PDs (p > 0.05). Educational level and employment status were significantly associated with PDs (p=0.036 and 0.014, respectively). Participants with PDs had a longer mean epilepsy duration than those without PDs (p < 0.05). Conclusion: Cluster C PDs are prevalent among PWE, with lower educational levels, longer epilepsy duration, and unemployment being significantly associated with a higher prevalence. Screening for PDs among PWE is therefore warranted to enable earlier detection and intervention.
Children with cerebral palsy experience nutritional challenges that affect protein intake and may contribute to poor muscle mass and growth faltering. Since protein plays a major role in preserving muscle mass and supporting growth, ensuring adequate intake is critical. A comprehensive literature search was conducted for observational studies published between 2006 and 2025. The reviewed studies results were grouped into: [1] Protein intake, with values ranging from 0.66 to 4.1 g/kg/day, with higher intake observed among ambulatory or orally fed children, [2] Nutritional Status and Body Composition, as reduced muscle was reported in children with severe motor impairment, and [3] functional performance, as children with lower GMFCS levels had better protein intake and anthropometric measures. While current evidence suggests that protein intake may enhance body composition and support growth, there are still literature gaps regarding tailored protein needs. This review summarizes protein intake and its outcomes in CP.
Objective:To determine the efficacy and safety of vagus nerve stimulation (VNS) for reducing the frequency of seizures and complications in drug-resistant epilepsy. Methods:This was a retrospective case series study conducted in King Abdullah Medical City from January 2015 to December 2021 hospital record. All patients undergoing VNS were enrolled according to inclusion and exclusion criteria. Patients were followed up for 12 months, and the seizure frequency and number of epileptic drugs used were evaluated. A paired sample t-test was applied to compare the outcome variables considering p-value < 0.05 as significant. Results:Among 9 enrolled patients, four were females, and five were males. The mean age of the patients was 23.9 ± 10.8 years. The average number of drugs used before VNS was 3, while it was 2 after VNS. However, a statistically significant (p = 0.08) reduction was not achieved. The mean seizure frequency before and after VNS was 14.4 ± 4.0 and 2.2 ± 3.2 at the 12-month follow-up visit (p < 0.05). The seizure frequency was statistically significantly reduced since the p-value was less than 0.05. No significant complications or death were observed. Conclusion:The VNS is a safe and effective adjuvant therapy for reducing the frequency of seizures in patients with drug-resistant epilepsy.
