Search Results (526)

Background/Objectives: Wilson’s disease (WD) is a rare autosomal recessive disorder of copper metabolism that results in hepatic, neurological, and psychiatric manifestations. Despite being described globally, data from the Middle East remains limited. This study presents the first comprehensive national cohort analysis of WD in Oman, examining clinical features, diagnostic challenges, treatment patterns, and long-term outcomes. Methods: A retrospective cohort study was conducted on 36 Omani patients diagnosed with WD between 2013 and 2020 at Sultan Qaboos University Hospital using AASLD diagnostic criteria. Clinical presentation, biochemical parameters, treatment regimens, and progression-free survival were analyzed. Results: The median age at diagnosis was 14.5 years, with a slight female predominance (55.6%). Clinical presentation varied: 25% had hepatic symptoms, 22.2% had mixed hepatic-neurological features, and 16.7% presented with neurological symptoms alone. Asymptomatic cases identified via family screening accounted for 33.3%. Diagnostic delays were most pronounced among patients presenting with neurological symptoms. A positive family history was reported in 88.9% of cases, suggesting strong familial clustering despite a low rate of consanguinity (5.6%). Regional distribution was concentrated in Ash Sharqiyah North and Muscat. Chelation therapy with trientine or penicillamine, often combined with zinc, was the mainstay of treatment. Treatment adherence was significantly associated with improved progression-free survival (p = 0.012). Conclusions: WD in Oman is marked by heterogeneous presentations, frequent diagnostic delays, and strong familial clustering. Early detection through cascade screening and sustained treatment adherence are critical for favorable outcomes. These findings support the need for national screening policies and structured long-term care models for WD in the region. Full article

Background and Objectives: Multiple sclerosis (MS) is a chronic immune-mediated neurological disorder that primarily affects young adults and is frequently accompanied by psychiatric comorbidities such as depression and anxiety, both of which significantly diminish patients’ quality of life (QoL). This study investigated the effect of two oral disease-modifying therapies (DMTs), fingolimod and cladribine, on mental health and QoL in patients with relapsing-remitting MS (RRMS). The aim of the study was to compare levels of depression, anxiety, and health-related quality of life (HRQoL) in RRMS patients treated with fingolimod or cladribine, and to evaluate their associations with clinical and radiological parameters. Materials and Methods: Eighty RRMS patients aged 18 to 50 years with Expanded Disability Status Scale (EDSS) scores of 3.0 or less, no recent disease relapse, and no history of antidepressant use were enrolled. Forty patients were treated with fingolimod and forty with cladribine. Depression and anxiety were assessed using the Hamilton Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HARS). QoL was evaluated using the Multiple Sclerosis QoL-54 (MSQOL-54) instrument. Additional clinical data, including MRI-based lesion burden, EDSS scores, age, disease duration, and occupational status, were collected. Results: No statistically significant differences were observed between the two groups regarding HDRS and HARS scores (p > 0.05). However, patients treated with fingolimod had significantly higher scores in the Energy/Fatigue subdomain (7.55 ± 2.02 vs. 6.56 ± 2.57, p = 0.046) and Composite Mental Health (CMH) score (64.73 ± 15.01 vs. 56.00 ± 18.93, p = 0.029) compared to those treated with cladribine. No significant differences were found in the independent items of the MSQOL-54. A negative correlation was identified between total lesion load and QoL scores. Conclusions: Although fingolimod and cladribine exert comparable effects on depression and anxiety levels, fingolimod may be associated with better mental health outcomes and reduced fatigue in RRMS patients. Furthermore, lesion burden and clinical parameters such as age and EDSS score may independently influence QoL, regardless of the DMT used. Full article

Pathogenic variants in the MAP1B gene have been associated with neurological impairment, including intellectual disability, attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, brain malformations, cognitive hearing loss, short stature, and dysmorphic features. However, few cases with detailed clinical characterization have been reported. We describe a 12-year-old boy carrying a loss-of-function MAP1B variant, presenting with severe elimination disorders despite normal intelligence. He was referred to the genetics service due to persistent elimination issues, including daytime urinary incontinence, nocturnal enuresis, and fecal incontinence. He had normal motor and cognitive development, with an IQ of 99; however, he also presented with ADHD, short stature, microcephaly, and myopia. Brain MRI revealed bilaterial subependymal periventricular nodular heterotopia (PVNH). Audiometry showed normal bilateral hearing. Testing fragile X syndrome (FXS) and karyotype analyses yielded normal results. Whole exome sequencing (WES) revealed a nonsense pathogenic variant in MAP1B (c.895 C>T; p.Arg299*). No other family members showed a similar phenotype; however, a great-uncle and a great-aunt had a history of nocturnal enuresis until age 10. The patient’s deceased mother had short stature and psychiatric disorders, and a history of consanguinity was reported on the maternal side. This case broadens the phenotypic spectrum associated with MAP1B syndrome, suggesting that elimination disorder, frequently reported in FXS, should also be evaluated in MAP1B pathogenic variant carriers. In addition, the presence of short stature also appears to be part of the syndrome. Full article

Memory is a fundamental neurological function, essential for animal survival. Over the course of vertebrate evolution, elaborations in the forebrain telencephalon create new memory mechanisms, meaning basal vertebrates such as amphibians must have a less sophisticated system of memory acquisition, storage, and retrieval than the well-known hippocampal-based circuitry of mammals. Personality also appears to be a fundamental vertebrate trait and is generally defined as consistent individual behavior over time and across life history stages. In anuran amphibians (frogs), personality studies generally ask whether adult frogs retain the personality of their tadpole stage or whether personality shifts with metamorphosis, an idea behavioral ecologists term adaptive decoupling. Using a multidisciplinary perspective and recognizing there are ~7843 species of frogs, each with some molecular, morphological, physiological, or behavioral feature that makes it unique, we review, clarify, and provide perspective on what we collectively know about memory and personality and their mechanisms in anuran amphibians. We propose four working hypotheses: (1) as tadpoles grow, new telencephalic neurons become integrated into functional networks, producing behaviors that become more sophisticated with age; (2) since carnivores tend to be more bold/aggressive than herbivores, carnivorous anuran adults will be more aggressive than herbivorous tadpoles; (3) each amphibian species, and perhaps life history stage, will have a set point on the Shy–Bold Continuum; and (4) around this set point there will be a range of individual responses. We also suggest that several factors are slowing our understanding of the variety and depth of memory and personality possibilities in anurans. These include the scala natura approach to comparative studies (i.e., the idea that one frog represents all frogs); the assumption that amphibians are no more than simple reflex machines; that study species tend to be chosen more for convenience than taxonomic representation; and that studies are designed to prove or disprove a construct. This latter factor is a particular hindrance because what we are really seeking as scientists is not the confirmation or refutation of ideas, but rather what those ideas are intended to produce, which is understanding. Full article

Introduction: Acute Myeloid Leukemia (AML) is a hematologic malignancy characterized by the clonal expansion of myeloid progenitors. While it primarily affects the bone marrow, extramedullary relapse occurs in 3–5% of cases, and it is linked to poor prognosis. Central nervous system (CNS) involvement presents diagnostic challenges due to nonspecific symptoms. CNS manifestations include leptomeningeal dissemination, nerve infiltration, parenchymal lesions, and myeloid sarcoma, occurring at any disease stage and frequently asymptomatic. Methods: A 62-year-old man with a recent history of AML in remission presented with diplopia and aching paresthesias in the left periorbital region spreading to the left frontal area. The diagnostic workup included neurological and hematological evaluation, lumbar puncture, brain CT, brain magnetic resonance imaging (MRI) with contrast, and dermatological evaluation with skin biopsy due to the appearance of nodular skin lesions on the abdomen and thorax. Results: Neurological evaluation showed hypoesthesia in the left mandibular region, consistent with left trigeminal nerve involvement, extending to the periorbital and frontal areas, and impaired adduction of the left eye with divergent strabismus in the primary position due to left oculomotor nerve palsy. Brain MRI showed an equivocal thickening of the left oculomotor nerve without enhancement. Cerebrospinal fluid (CSF) analysis initially showed elevated protein (47 mg/dL) with negative cytology; a repeat lumbar puncture one week later detected leukemic cells. Skin biopsy revealed cutaneous AML localization. A diagnosis of AML relapse with CNS and cutaneous localization was made. Salvage therapy with FLAG-IDA-VEN (fludarabine, cytarabine, idarubicin, venetoclax) and intrathecal methotrexate, cytarabine, and dexamethasone was started. Subsequent lumbar punctures were negative for leukemic cells. Due to high-risk status and extramedullary disease, the patient underwent allogeneic hematopoietic stem cell transplantation. Post-transplant aplasia was complicated by septic shock; the patient succumbed to an invasive fungal infection. Conclusions: This case illustrates the diagnostic complexity and poor prognosis of extramedullary AML relapse involving the CNS. Early recognition of neurological signs, including cranial nerve dysfunction, is crucial for timely diagnosis and management. Although initial investigations were negative, further analyses—including repeated CSF examinations and skin biopsy—led to the identification of leukemic involvement. Although neuroleukemiosis cannot be confirmed without nerve biopsy, the combination of clinical presentation, neuroimaging, and CSF data strongly supports the diagnosis of extramedullary relapse of AML. Multidisciplinary evaluation remains essential for detecting extramedullary relapse. Despite treatment achieving CSF clearance, the prognosis remains unfavorable, underscoring the need for vigilant clinical suspicion in hematologic patients presenting with neurological symptoms. Full article

In the last several decades, a number of animal models of neurological diseases have been proposed and validated to one degree or another. This review focuses on the olfactory bulbectomized rodent as a model of major depression, a disorder that, because of its prevalence, has been called the “common cold” of neurological diseases, though the disability it causes is far more profound. After describing the method, a brief history of this model and the various validity claims made for it are discussed. Though a legion of physiological and biochemical sequelae of bulbectomy and other animal models of depression have been reported, the focus of this review is behavioral. Therefore, the neurochemical and molecular aspects of the depression models mentioned in this review will not be explored in depth. Lastly, unresolved questions posed by the bulbectomy model are considered along with its utility in the study of other neurological diseases and its future prospects. Full article

The genus Datura L. has pharmacological activities due to its source of bioactive compounds. The effects of bioactive compounds can vary depending on species, geographical location, and environmental conditions. The purpose of this review is to summarize the most recent progress and to provide a comprehensive overview of studies concerning genetic alteration and bioactive compounds in the genus Datura, based on Scopus publications between 2015 and 2025. Throughout history, the genus Datura (Solanaceae) contains nine species of medicinal plants. A key component of elucidating the diversification process of congeneric species is identifying the factors that encourage species variation. A comparative gene family analysis provides an understanding of the evolutionary history of species by identifying common genetic/genomic mechanisms that are responsible for species responses to biotic and abiotic environments. The diverse range of bioactive compounds it contains contributes to its unique bioactivity. Datura contains tropane alkaloids (such as hyoscyamine and scopolamine), datumetine, withametelin, daturaolone, and atropine. Several compounds have been isolated and refined for use in treating various conditions as a result of recent progress in therapeutic development. Daturaolone, for example, is used to treat certain neurological disorders. In addition to providing renewed opportunities for the discovery of new compounds, these advancements also provide insights into the genetic basis for their biosynthesis. Our discussion also includes pitfalls as well as relevant publications regarding natural products and their pharmacological properties. The pace of discovery of bioactive compounds is set to accelerate dramatically shortly, owing to both careful perspectives and new developments. Full article

Background/Objectives: Out-of-hospital cardiac arrest (OHCA) is associated with high mortality, and outcomes may be influenced by underlying conditions such as cancer, hypertension (HTN), and diabetes mellitus (DM). This study aimed to evaluate whether HTN and DM modify the effects of post-resuscitation treatments—specifically targeted temperature management (TTM) and percutaneous coronary intervention (PCI)—on survival and neurological recovery in OHCA patients with a history of cancer. Methods: This retrospective cohort study analyzed data from the Korean national OHCA registry between January 2018 and December 2021. Adults aged ≥18 years with presumed cardiac-origin OHCA and a documented history of cancer—defined as any prior cancer diagnosis recorded in medical records regardless of remission status—were included. Multivariable logistic regression was used to examine associations between treatment and outcomes, and interaction effects were assessed using adjusted p-values to account for multiple testing. Results: Among the 124,916 EMS-assessed OHCA cases, 4115 patients met the inclusion criteria. TTM and PCI were both statistically associated with good neurological recovery (TTM: adjusted odds ratio [aOR], 1.69; 95% confidence interval [CI], 1.12–2.55; p < 0.05; PCI: aOR, 11.35; 95% CI, 7.98–16.14; p < 0.05). In interaction analyses, the benefit of TTM and PCI for achieving good neurological recovery was attenuated in patients with diabetes mellitus (DM; TTM: aOR, 0.59; 95% CI, 0.23–1.49; PCI: aOR, 4.94; 95% CI, 2.69–9.06) and hypertension (HTN; TTM: aOR, 0.94; 95% CI, 0.49–1.82; PCI: aOR, 7.47; 95% CI, 4.48–12.44), with adjusted p-values < 0.05 for all interactions. Conclusions: In OHCA patients with a history of cancer, TTM and PCI are associated with improved survival and neurological outcomes. However, the presence of comorbidities such as HTN and DM may attenuate these benefits. These findings support the need for individualized post-resuscitation care strategies that account for comorbid conditions. Full article

Background/Objectives: Access to specialized care for patients with cognitive impairment in remote areas is often limited. Despite the increasing adoption of telemedicine, standardized guidelines have not yet been specified. This study aimed to develop a comprehensive protocol for the specialized neurological, neuropsychological, and neuropsychiatric assessment of patients with cognitive disorders in remote areas through telemedicine. Methods: We analyzed data from (i) a comprehensive literature review of the existing recommendations, reliability studies, and telemedicine models for cognitive disorders, (ii) insights from a three-year experience of a specialized telemedicine outpatient clinic for cognitive movement disorders in Greece, and (iii) suggestions coming from dementia specialists experienced in telemedicine (neurologists, neuropsychologists, psychiatrists) who took part in three focus groups. A critical synthesis of the findings was performed in the end. Results: The final protocol included: technical and organizational requirements (e.g., a high-resolution screen and a camera with zoom, room dimensions adequate for gait assessment, a noise-canceling microphone); medical history; neurological, neuropsychiatric, and neuropsychological assessment adapted to videoconferencing; ethical–legal aspects (e.g., data security, privacy, informed consent); clinician–patient interaction (e.g., empathy, eye contact); diagnostic work-up; linkage to other services (e.g., tele-psychoeducation, caregiver support); and instructions for treatment and follow-up. Conclusions: This protocol is expected to serve as an example of good clinical practice and a source for official telemedicine guidelines for cognitive disorders. Ultimate outcomes include the potential enhanced access to specialized care, minimized financial and logistical costs, and the provision of a standardized, effective model for the remote diagnosis, treatment, and follow-up. This model could be applied not only in Greece, but also in other countries with similar healthcare systems and populations living in remote, difficult-to-access areas. Full article

Background: Post-concussion syndrome (PCS) and Functional Neurological Disorder (FND), including Functional Cognitive Disorder (FCD), are two frequently encountered but diagnostically complex conditions. While PCS is conceptualized as a sequela of mild traumatic brain injury (mTBI), FND/FCD encompasses symptoms incompatible with recognized neurological disease, often arising in the absence of structural brain damage. Yet, both conditions exhibit considerable clinical overlap—particularly in the domains of cognitive dysfunction, emotional dysregulation, and symptom persistence despite negative investigations. Objective: This review critically examines the shared and divergent features of PCS and FND/FCD. We explore their respective epidemiology, diagnostic criteria, and risk factors—including personality traits and trauma exposure—as well as emerging insights from neuroimaging and biomarkers. We propose the “Functional Overlay Model” as a clinical tool for navigating diagnostic ambiguity in patients with persistent post-injury symptoms. Results: PCS and FND/FCD frequently share features such as subjective cognitive complaints, fatigue, anxiety, and heightened somatic vigilance. High neuroticism, maladaptive coping, prior psychiatric history, and trauma exposure emerge as common risk factors. Neuroimaging studies show persistent network dysfunction in both PCS and FND, with overlapping disruption in fronto-limbic and default mode systems. The Functional Overlay Model helps to identify cases where functional symptomatology coexists with or replaces an initial organic insult—particularly in patients with incongruent symptoms and normal objective testing. Conclusions: PCS and FND/FCD should be conceptualized along a continuum of brain dysfunction, shaped by injury, psychology, and contextual factors. Early recognition of functional overlays and stratified psychological interventions may improve outcomes for patients with persistent, medically unexplained symptoms after head trauma. This review introduces the Functional Overlay Model as a novel framework to enhance diagnostic clarity and therapeutic planning in patients presenting with persistent post-injury symptoms. Full article

Over the past three turbulent decades, research has profoundly reshaped our understanding of chronic Toxoplasma gondii infection—traditionally regarded as harmless in immunocompetent individuals—unveiling its surprising impact on human health, performance, and behavior. This review emphasizes the effects of chronic Toxoplasma infection on physical and mental health, cognitive performance, and behavioral changes, highlighting key findings from studies investigating these domains, with a particular focus on both ultimate and proximate mechanisms underlying the observed effects. To this end, the primary focus will be on human studies; however, animal model studies will also be thoroughly considered when necessary and appropriate, to provide context and additional important information. Research demonstrates that chronic Toxoplasma infection may contribute to a broad spectrum of physical health issues. Ecological studies have revealed correlations between toxoplasmosis prevalence and increased morbidity and mortality from various conditions, including cardiovascular diseases, neurological disorders, and certain cancers. Large-scale cross-sectional studies have further shown that infected individuals report a higher incidence of numerous health complaints and diagnosed diseases, suggesting a significant impact on overall physical well-being. In addition to physical health, lifelong Toxoplasma infection (subclinical toxoplasmosis) has been implicated in cognitive impairments and behavioral changes. Studies have reported associations between infection and poorer performance in areas such as reaction time, processing speed, working memory, and executive function. Many of these behavioral changes likely relate to worsened health and a shift towards a “fast life history strategy.” These cognitive deficits can have significant implications for daily functioning and performance. Furthermore, the role of Toxoplasma infection in the development or exacerbation of mental health disorders has been extensively investigated. Meta-analyses, ecological studies, and large-scale observational studies have demonstrated associations between Toxoplasma infection and an increased risk of disorders such as schizophrenia and obsessive–compulsive disorder. While the precise mechanisms underlying these associations remain under investigation, research suggests that neuroinflammation and alterations in neurotransmitter systems are likely to play a role. Far from being harmless, subclinical toxoplasmosis is increasingly recognized as a hidden factor influencing human health, behavior, and cognitive performance—with implications that extend well beyond the individual to public health at large. Further research is warranted to elucidate the complex interplay between Toxoplasma infection, host physiology, and the development of various physical, cognitive, behavioral, and mental health conditions. Full article

Introduction: Methadone, a synthetic opioid used for opioid substitution therapy (OST), is typically associated with arrhythmias rather than direct myocardial depression. Neurological complications, especially with concurrent antipsychotic use, have also been reported. Acute left ventricular failure in young adults is uncommon and often linked to genetic or infectious causes. We present a rare case of reversible cardiogenic shock and cerebellar insult due to methadone toxicity. Case Presentation: A 37-year-old man with a history of drug abuse on OST with methadone (130 mg/day) was admitted to the ICU with hemodynamic instability, seizures, and focal neurological deficits. Diagnostic workup revealed low cardiac output syndrome and a right cerebellar insult, attributed to methadone toxicity. The patient received individualized catecholamine support. After 10 days in the ICU, he was transferred to a general ward for ongoing cardiac and neurological rehabilitation and discharged in stable condition seven days later. Conclusions: Methadone-induced reversible left ventricular failure, particularly when accompanied by cerebellar insult, is rare but potentially life-threatening. Early recognition and multidisciplinary management are essential for full recovery in such complex toxicological presentations. Full article

Background and Clinical Significance: Herein, we describe the clinical case of a 17-year-old patient with psychotic disorder secondary to cerebral venous thrombosis due to primary thrombophilia, which was related to protein S deficiency and a heterozygous MTHFR gene mutation with the p.Ala222Val variant. Case presentation: A 17-year-old female, with no history of previous illnesses, was admitted to the emergency service department due to a psychotic break. Psychiatric evaluation detected disorganized thought, euphoria, ideas that were fleeting and loosely associated, psychomotor excitement, and deviant judgment. On the fifth day, an inflammatory process in the parotid gland was detected, pointing out a probable viral meningoencephalitis, prompting antiviral and antimicrobial treatment. One week after antiviral and steroidal anti-inflammatory treatments, the symptoms’ improvement was minimal, which led to further neurological workup. MRI venography revealed a filling defect in the transverse sinus, consistent with cerebral venous thrombosis. Consequently, anticoagulation treatment with enoxaparin was initiated. The patient’s behavior improved, revealing that the encephalopathic symptoms were secondary to thrombosis of the venous sinus. Hematological studies indicated the cause of the venous sinus thrombosis was a primary thrombophilia caused by a heterozygous MTHFR mutation variant p.Ala222Val and a 35% decrease in plasmatic protein S. Conclusions: This case highlights the possible relationship between psychiatric and thrombotic disorders, suggesting that both the MTHFR mutation and protein S deficiency could lead to psychotic disorders. Early detection of thrombotic risk factors in early-onset psychiatric disorders is essential for the comprehensive management of patients. Full article

Background/Objectives: The relationship between OSA and adult hypertension has been extensively studied; however, it remains understudied in pediatric patients without OSA. The aim of this study is to identify factors associated with pediatric hypertension without OSA, through an IRB-approved retrospective chart review of patients who underwent polysomnography at Nemours Children’s Hospital, DE/NJ between January 2020 and July 2023. Methods: Eligibility criteria included children 8–17 years, completed PSG, and clinic visit blood pressure (BP). Anthropometrics, demographics, social determinants, and medical history were obtained from electronic medical records. Hypertension was defined as the average systolic and/or diastolic BP that is ≥95th percentile for gender, age, and height based on AAP Clinical Practice Guidelines. All variables were checked for normality. Chi-square tests for categorical data and Wilcoxon rank sum tests for continuous data were used to test significance between non-OSA non-hypertensives (NH) and hypertensives (H). p < 0.05 is considered significant. Results: Of 285 charts evaluated, 137 were classified as non-OSA. Patient information, including parents in household, smoking exposure, and food allergies, were statistically significant (p < 0.05) in hypertensive pediatric patients without OSA. Hypertension was significantly correlated (p < 0.05) with birth weight, BMI, daytime heart rate, systolic BP, and diastolic BP. Statistically significant differences (p < 0.05) were found in mental illnesses, neurological disease, and respiratory disease. Among polysomnography parameters, only nighttime heart rate was found to be statistically significant. Conclusions: The data suggests that in pediatric patients without OSA, there are multiple factors and co-morbidities associated with hypertension. These factors and co-morbidities warrant additional follow up in clinical practice to mitigate the risks of hypertension in pediatric patients. Full article

Background: Individuals with ADHD may perform poorly on tasks targeting executive functioning skills such as the ImPACT, which requires the test-taker to employ judgement in non-routine situations Objective: To determine whether ADHD serves as a mediating variable for increasing the likelihood of an invalid score. Materials and Methods: A total of 39,140 collegiate athletes and United States military cadets consented to the Concussion Assessment, Research, and Education (CARE) Consortium study. Participants completed the CARE Baseline Packet which included various sections through which study participants provide self-report data, including demographic, personal, and family history sections. The personal history portion of the CARE Baseline Packet addressed the participant’s neurological history, including self-reported diagnosis of ADHD and history of traumatic brain injury. Variables utilized for the current study included age, gender, race, ethnicity, the participant’s primary college sport, use of mouthguards for athletes competing in sports requiring them, and the presence of an ADHD diagnosis. Participants responded to a question, inquiring if they had ever been diagnosed by a medical professional with ADHD, ultimately producing a dichotomous yes/no response. Results: We found that participants with ADHD were more likely to produce invalid baseline scores (ß = −0.884; p < 0.001). Similar results were found when controlling for sex, race, age, sport played, mouthguard use, and number of previous concussions (ß = −0.786; p < 0.001). Sex, race, sport played, and mouthguard use each played a significant role in determining profile validity, independent of ADHD diagnosis. With ADHD removed from the model, age negatively affected the likelihood of a valid score (ß = −0.052; p = 0.048). Conclusions: Our study suggests that the relationship between age and ImPACT validity is explained by the presence of ADHD. Results support adjusting ImPACT’s validity thresholds for individuals with ADHD. Full article