Search Results (66)

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

Epilepsy affects over 12 million children worldwide, with approximately 30% classified as having drug-resistant epilepsy (DRE), often accompanied by neuropsychiatric comorbidities that severely impact quality of life. The endocannabinoid system (ECS) functions as a multifaceted neuromodulatory network regulating neuronal excitability, synaptic plasticity, and immune homeostasis from early life through adolescence and into aging. In pediatric epilepsies, alterations in ECS components, particularly CB1 receptor expression and endocannabinoid levels, reveal disorder-specific vulnerabilities and therapeutic opportunities. Cannabidiol (CBD), a non-psychoactive compound from Cannabis sativa, has shown strong preclinical and clinical efficacy in treating DRE and is approved for Dravet syndrome, Lennox–Gastaut syndrome, and Tuberous Sclerosis Complex. Other ECS-based strategies, such as the use of CB1 receptor-positive allosteric modulators, can selectively enhance endogenous cannabinoid signaling where and when it is active, potentially reducing seizures in conditions like Dravet and absence epilepsy. Similarly, FAAH and MAGL inhibitors may help restore ECS tone without directly activating CB1 receptors. Precision targeting of ECS components based on regional expression and syndrome-specific pathophysiology may optimize seizure control and associated comorbidities. Nonetheless, long-term pediatric use must be approached with caution, given the critical role of the ECS in brain development. Full article

Rare genetic movement disorders usually manifest early in life with dystonia, parkinsonism, chorea, or a combination thereof. These are often associated with neurodevelopmental delay, intellectual disability, speech problems, retinal abnormalities, seizures, ataxia, spasticity, or systemic features. Due to their vast number and pheno–genotypic heterogeneity, the diagnosis of these disorders can be challenging. However, recognising their core motor phenomenology as well as clinical, laboratory, and neuroradiological clues can expedite appropriate diagnostic workup, molecular diagnosis, and adequate treatment. In this review, we outline diagnostic clues to rare movement disorders (RMDs), focusing on those that present mainly with dystonia, parkinsonism, or paroxysmal dyskinesia due to genetic causes. Additionally, we provide a decision tree approach linking clinical, genetic, and imaging testing. Finally, we highlight selected RMDs that should not be missed, as they possess established treatments that can hinder their progression, prevent irreversible or life-threatening sequelae and, in certain cases, lead to complete symptom remission. Full article

Introduction: Tuberous sclerosis complex (TSC) is a rare multisystemic genetic disorder characterized by the formation of benign tumors in various organs, including the central nervous system, skin, kidneys, and heart. The diagnosis is based on well-defined clinical criteria, such as those from Schwartz (2007) updated in 2012 by the International Tuberous Sclerosis Complex Consensus Group. The study aims to investigate the clinical, imaging, and molecular characteristics of patients diagnosed with tuberous sclerosis and to explore the correlation between specific genetic mutations (TSC1 and TSC2 genes) and the severity of clinical manifestations. Material and Methods: This is a retrospective longitudinal study of 13 patients diagnosed with tuberous sclerosis, identified in the records of the Bihor Regional Center for Medical Genetics (BRCMG) within the Bihor County Emergency Clinical Hospital from 1984 to 2024. Clinical, imaging, and molecular features were assessed. Patients were evaluated by a multidisciplinary team, including a geneticist, pediatrician, neurologist, psychiatrist, and psychologist. Clinical and imaging data were retrospectively collected from the congenital malformations and genetic disease records of BRCMG Bihor and statistically analyzed. Results: All patients showed clinical and imaging signs consistent with the diagnosis of tuberous sclerosis. Neurological manifestations were present in 83% of patients, including epilepsy and cognitive delays. Renal lesions were detected in 46% of cases, and dermatological lesions, such as facial angiofibromas, were observed in 69% of patients. Mutational variants identified in the TSC2 gene correlated with a more severe clinical presentation, including severe intellectual disability and treatment-resistant seizures, compared to variants in the TSC1 gene. Conclusions: Our study, although involving a small number of patients, highlights the clinical heterogeneity of tuberous sclerosis and the importance of a multidisciplinary approach in patient management. Early diagnosis and ongoing monitoring are essential to improving the quality of life for patients. Further studies are needed to assess the impact of therapeutic interventions and genetic correlations within the studied population. Full article

Background and Objectives: Febrile seizures (FS) are neuronal disturbances frequently associated with abnormal electroencephalographic activity (EEG) as spike-wave discharges (SWDs). Fish oil (FO) has high amounts of omega-3 fatty acids (θ-3), and its effects on FS alterations are poorly understood. The aim of this work was to evaluate the effect of long-term FO supplementation on the EEG of the amygdala of adult male rats with early-life FS. Materials and Methods: Progenitor female Wistar rats, from puberty to gestation and delivery, were fed daily with a commercial diet supplemented with either fish oil (FO), palm oil (PO), or deionized water (CTRL). After parturition, male pups were exposed for 30 min to hyperthermia (HP) and then returned to their dams. After weaning, pups were fed a commercial diet and the respective treatments up to 155 days of age when electrodes were implanted in the amygdala. Results: During early life HP, the PO and CTRL groups reached maximal core temperature (CT) in comparison with the FO group. Furthermore, the FO group only has fewer myoclonus and long latency to adopt an uncontrolled posture. At an adult age, the FO group with early-life FS scored shorter periods of SWDs in amygdala EEG but without seizures and presented minor values of absolute power than the PO and CTRL groups. Conclusions: In adult rats, the long-term supplementation of FO minimizes the deleterious behavioral effects caused by early-life FS and decreases the occurrence and amplitude of SWDs in the EEG of the amygdala. Full article

The co-occurrence of autism spectrum disorder (ASD) and epilepsy is a complex neurological condition that presents significant challenges for both patients and clinicians. ASD is a group of complex developmental disorders characterized by the following: (1) Social communication difficulties: challenges in understanding and responding to social cues, initiating and maintaining conversations, and developing and maintaining relationships. (2) Repetitive behaviors: engaging in repetitive actions, such as hand-flapping, rocking, or lining up objects. (3) Restricted interests: focusing intensely on specific topics or activities, often to the exclusion of other interests. (4) Sensory sensitivities: over- or under-sensitivity to sensory input, such as sounds, touch, tastes, smells, or sights. These challenges can significantly impact individuals’ daily lives and require specialized support and interventions. Early diagnosis and intervention can significantly improve the quality of life for individuals with ASD and their families. Epilepsy is a chronic brain disorder characterized by recurrent unprovoked (≥2) seizures that occur >24 h apart. Single seizures are not considered epileptic seizures. Epilepsy is often idiopathic, but various brain disorders, such as malformations, strokes, and tumors, can cause symptomatic epilepsy. While these two conditions were once considered distinct, growing evidence suggests a substantial overlap in their underlying neurobiology. The prevalence of epilepsy in individuals with ASD is significantly higher than in the general population. This review will explore the epidemiology of this comorbidity, delve into the potential mechanisms linking ASD and epilepsy, and discuss the implications for diagnosis, treatment, and management. Full article

Background/Objectives: Cardiac rhabdomyoma (CR), the most frequently occurring fetal cardiac tumor, is often an early marker of tuberous sclerosis complex (TSC). This study evaluates outcomes of fetuses with prenatally diagnosed cardiac tumors managed at a single tertiary center. Methods: Medical records of fetuses diagnosed with cardiac tumors between 2009 and 2024 were retrospectively reviewed. Results: Sixteen cases were identified, with a median follow-up of 6.7 years. TSC was confirmed in 14 cases (88%). Multiple tumors were observed in 13 cases (81%), while 3 cases (19%) had solitary tumors. Both non-TSC cases involved solitary tumors. Cardiac complications (arrhythmias, conduction disorders, and hemodynamic abnormalities) occurred in 38% of cases prenatally and 69% postnatally, with larger tumor diameters significantly associated with complications (p = 0.02). No fetal hydrops or mortality occurred; however, one child died at age five due to a seizure. Postnatal tumor regression occurred in 56% of cases and complete regression in 38% by a median age of 2.3 years (range: 0.6–4.4). One tumor remained stable. Brain MRI revealed TSC-related changes in all TSC-affected patients except one, who had a developmental brain anomaly. Most TSC patients experienced epilepsy (71%) and developmental delays. Conclusion: While CRs are typically benign and regress spontaneously, their strong association with TSC highlights the importance of early diagnosis and family counseling. TSC-related epilepsy and psychomotor delays significantly impair the quality of life. Early mTOR inhibitor therapy offers promise in mitigating TSC-related complications and improving outcomes. Full article

Introduction: Refractory epilepsy is common in children with Autism Spectrum Disorder (ASD), significantly affecting their cognitive development and quality of life. Surgical interventions provide a therapeutic option, but it remains unclear which technique offers the best outcomes for this population. Objective: To compare the efficacy and safety of four surgical techniques—lesionectomy, temporal lobectomy, extratemporal cortical resection, and functional hemispherectomy—in children with refractory epilepsy, both with and without ASD, and evaluate their impact on cognitive and behavioral development and quality of life. Methodology: A retrospective study was conducted with 120 children diagnosed with refractory epilepsy, equally divided between those with and without ASD. Patients were assigned to one of four surgical groups (n = 15 per group) based on the intervention performed. Data on demographic and clinical characteristics, as well as one-year postoperative outcomes—including seizure control (Engel classification), intelligence quotient (WISC-V), adaptive behavior (Vineland-II), and quality of life (PedsQL)—were collected. Statistical analyses were applied to compare the results among groups, and logistic regression was used to identify the predictors of seizure freedom. Results: Lesionectomy and temporal lobectomy groups showed significantly higher rates of seizure freedom (80% and 73%, respectively) compared to extratemporal resection (60%) and functional hemispherectomy (67%). These groups also presented significant improvements in intelligence quotient, adaptive behavior, quality of life, and reductions in ASD symptoms (p < 0.01). Perioperative complications were notably lower in the lesionectomy and temporal lobectomy groups (7%) compared to extratemporal resection and functional hemispherectomy (40%; p = 0.007). Significant predictors of seizure freedom included the presence of structural anomalies on neuroimaging and a shorter duration of epilepsy before surgery (p < 0.05). Conclusions: Lesionectomy and temporal lobectomy are highly effective and safer surgical techniques for managing refractory epilepsy in children with ASD, providing significant benefits in seizure control, cognitive development, and quality of life. Importantly, the outcomes observed are not exclusive to children with ASD but likely reflect broader efficacy across pediatric epilepsy populations. The early identification of surgical candidates and comprehensive preoperative evaluations are essential for optimizing outcomes, emphasizing the importance of individualized treatment planning and further comparative research to validate these findings. Full article

Introduction: Epstein–Barr virus (EBV) usually causes mild, self-limiting, or asymptomatic infection in children, typically infectious mononucleosis. The severe course is more common in immunocompromised patients. Neurological complications of primary infection, reactivation of the latent infection, or immune-mediated are well-documented. However, few published cases of fatal EBV encephalitis exist. Case presentation We report a case of a 5.5-year-old immunocompetent girl with fulminant EBV encephalitis fulfilling the criteria for the recently proposed subtype Acute Fulminant Cerebral Edema: (AFCE). The child presented with fever, vomiting, altered mental status, and ataxia. Her initial brain CT (computed tomography) scan was normal. On day 2 she developed refractory status epilepticus requiring intubation, ventilation, and sedation for airway protection and seizure control. Magnetic resonance imaging (MRI) scan showed cytotoxic brain edema. Despite intensive treatment, including acyclovir, ceftriaxone, hyperosmotic therapy (3% NaCl), intravenous immunoglobulins (IVIG), corticosteroids, as well as supportive management, on day 5 she developed signs of impending herniation. Intensification of therapy (hyperventilation, deepening sedation, mannitol) was ineffective, and a CT scan demonstrated generalized brain edema with tonsillar herniation. EBV primary infection was confirmed by serology and qPCR in blood samples and post-mortem brain tissue. An autopsy was consistent with the early phase of viral encephalitis. Conclusions This case confirms that normal or non-specific CT and MRI scans do not exclude encephalitis diagnosis if clinical presentation fulfills the diagnostic criteria. The implementation of prophylactic anticonvulsants could improve outcomes. Intracranial pressure (ICP) monitoring should be considered in AFCE for better ICP management. Decompressive craniectomy might be a life-saving option in refractory cases. An encephalitis management algorithm is proposed. Full article

The glycosylphosphatidylinositol (GPI) is a glycol–lipid that anchors several proteins to the cell surface. The GPI-anchor pathway is crucial for the correct function of proteins involved in cell function, and it is fundamental in early neurogenesis and neural development. The PIG gene family is a group of genes involved in this pathway with six genes identified so far, and defects in these genes are associated with a rare inborn metabolic disorder manifesting with a spectrum of clinical phenotypes in newborns and children. Among them, the PIGO gene encodes for phosphatidylinositol glycan anchor biosynthesis class O protein (PIGO), an enzyme participating in this cascade, and the loss of its function often leads to a severe clinical picture characterized by global developmental delay, seizures, Hirschsprung disease, and other congenital malformations. To date, 19 patients with confirmed PIGO deficiency have been described in the literature with a host of clinical and radiological manifestations. We report a case of a male term newborn with two compound heterozygous variants of the PIGO genes, presenting with encephalopathy, drug-resistant epilepsy, and gastrointestinal abnormalities. Brain MRI first showed diffusion restriction in the ponto-medullary tegmentum, ventral mesencephalon, superior cerebellar peduncles, cerebral peduncles, and globi pallidi. This pattern of lesion distribution has been described as part of the neuroradiological spectrum of PIG genes-related disorders. However, after one month of life, he also showed a previously undescribed MRI pattern characterized by extensive cortical and subcortical involvement of the brain hemispheres. The presence of two different mutations in both the PIGO genes may have been responsible for the particularly severe clinical picture and worse outcome, leading to the death of the newborn in the sixth month of life despite therapeutic attempts. This case expands the neuroradiological spectrum and may bring new insights on glycosylation-related disorders brain manifestations. Full article

Sturge–Weber syndrome (SWS) is a rare congenital neurocutaneous disorder typically caused by a somatic mosaic mutation in R183Q GNAQ. At-risk children present at birth with a capillary malformation port-wine birthmark. The primary diagnostic characteristic of the disorder includes leptomeningeal enhancement of the brain, which demonstrates abnormal blood vessels and results in impaired venous drainage and impaired local cerebral perfusion. Impaired cerebral blood flow is complicated by seizures resulting in strokes, hemiparesis and visual field deficits, hormonal deficiencies, behavioral impairments, and intellectual disability. Therefore, anti-seizure medication in combination with low-dose aspirin is a common therapeutic treatment strategy. Recently published data indicate that the underlying mutation in endothelial cells results in the hyperactivation of downstream pathways and impairment of the blood–brain barrier. Cannabidiol (CBD) has been used to treat medically refractory seizures in SWS due to its anti-seizure, anti-inflammatory, and neuroprotective properties. Pilot research suggests that CBD improves cognitive impairment, emotional regulation, and quality of life in patients with SWS. Recent preclinical studies also suggest overlapping molecular pathways in SWS and in CBD, suggesting that CBD may be uniquely effective for SWS brain involvement. This review aims to summarize early data on CBD’s efficacy for preventing and treating epilepsy and neuro-cognitive impairments in patients with SWS, likely molecular pathways impacted, and provide insights for future translational research to improve clinical treatment for patients with SWS. Full article

Introduction: We report the case of a neonate diagnosed with severe hemophilia A (HA) and conduct a literature review of cases of severe HA presenting at the neonatal age to help define the clinical diagnostic findings and existing differences between the sporadic and familial onset of this condition. Report of a Case: A 6-day-old newborn presented with worsening pallor, inappetence, and hyporeactivity for 48 h. The diagnosis was severe hemophilia A (HA), leading to an unfavorable outcome. A literature review focusing on case reports and series focusing on the clinical expression of HA in neonates was conducted, documenting clinical presentation, family history, and outcomes. Literature review: Forty patients were included. HA was observed in five cases (12.5%) of very preterm births (≤32 weeks) and in four cases (10%) of moderately or late preterm births. Seventeen patients (43%) had a family history, with inheritance being sporadic (21 newborns, 53%) or acquired (2 cases, 4%). Clinical onset typically occurred within the first week of life (approximately 8 out of 10 cases), while only three cases (7.5%) had onset after the first month. Inherited cases presented with hemorrhagic states (nine cases), hypovolemic shock (five cases), or intracranial hypertension (two cases). Sporadic cases showed localized bleeding (11 cases), hypovolemic shock (5 cases), or neurological symptoms like seizures and anisocoria (5 cases). Acquired cases included severe intracranial hemorrhage in one case. Conclusions: Neonatal HA can manifest with severe symptoms and rapid progression, making early diagnosis crucial. Non-specific signs and the absence of coagulophaty disorders in family history can delay diagnosis. Symptoms like prolonged bleeding, cutaneous hematomas, or intracranial bleeding necessitate ruling out major coagulopathy, and neurological signs require immediate imaging to exclude intracranial bleeding. Full article

Pediatric genetic epilepsies, such as CDKL5 Deficiency Disorder (CDD), are severely debilitating, with early-onset seizures occurring more than ten times daily in extreme cases. Existing antiseizure drugs frequently prove ineffective, which significantly impacts child development and diminishes the quality of life for patients and caregivers. The relaxation of cannabis legislation has increased research into potential therapeutic properties of phytocannabinoids such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). CBD’s antiseizure properties have shown promise, particularly in treating drug-resistant genetic epilepsies associated with Lennox–Gastaut syndrome (LGS), Dravet syndrome (DS), and Tuberous Sclerosis Complex (TSC). However, specific research on CDD remains limited. Much of the current evidence relies on anecdotal reports of artisanal products lacking accurate data on cannabinoid composition. Utilizing model systems like patient-derived iPSC neurons and brain organoids allows precise dosing and comprehensive exploration of cannabinoids’ pharmacodynamics. This review explores the potential of CBD, THC, and other trace cannabinoids in treating CDD and focusing on clinical trials and preclinical models to elucidate the cannabinoid’s potential mechanisms of action in disrupted CDD pathways and strengthen the case for further research into their potential as anti-epileptic drugs for CDD. This review offers an updated perspective on cannabinoid’s therapeutic potential for CDD. Full article

Background: Fragile X Syndrome (FXS) is the leading monogenetic cause of autism spectrum disorder (ASD) and is associated with seizures. We examined the impact of repeated seizures on the behavioral and molecular changes in male Fmr1 knockout (KO) mice and wild-type (WT) mice. Methods: Seizures were induced by administering three flurothyl seizures per day across postnatal days (PD) 7–11, for a total of 15 seizures. In adulthood, mice were tested in a battery of behavioral tasks to assess long-term behavioral deficits. Results: The two-hit impact of a Fmr1 knockout and seizures resulted in decreased anxiety-like behavior in the elevated plus maze test and a longer latency to their first nose poke (repetitive behavior). Seizures resulted in decreased activity, decreased repetitive behavior (grooming and rearings), and decreased social behavior, while they also increased habituation to auditory stimuli and increased freezing in delayed fear conditioning in both KO and control mice. KO mice displayed increased repetitive behavior in the open field task (clockwise revolutions) and repeated nose pokes, and decreased anxiety in the open field test. No differences in mTOR signaling were found. Conclusions: These findings further illuminate the long-term effects of synergistic impact of two hits on the developing brain. Full article

Among the non-communicable neurological diseases, epilepsy is characterized by abnormal brain activity with several peripheral implications. The role of peripheral inflammation in the relationship between seizure development and nonalcoholic fatty liver disease based on sex difference remains still overlooked. Severe early-life infections lead to increased inflammation that can aggravate epilepsy and hepatic damage progression, both related to increased odds of hospitalization for epileptic patients with liver diseases. Here, we induced a post-natal-day 3 (PND3) infection by LPS (1 mg/kg, i.p.) to determine the hepatic damage in a genetic model of young epileptic WAG/Rij rats (PND45). We evaluated intra- and inter-gender differences in systemic and liver inflammation, hepatic lipid dysmetabolism, and oxidative damage related to mitochondrial functional impairment. First, epileptic rats exposed to LPS, regardless of gender, displayed increased serum hepatic enzymes and altered lipid profile. Endotoxin challenge triggered a more severe inflammatory and immune response in male epileptic rats, compared to females in both serum and liver, increasing pro-inflammatory cytokines and hepatic immune cell recruitment. Conversely, LPS-treated female rats showed significant alterations in systemic and hepatic lipid profiles and reduced mitochondrial fatty acid oxidation. The two different sex-dependent mechanisms of LPS-induced liver injury converge in increased ROS production and related mitochondrial oxidative damage in both sexes. Notably, a compensatory increase in antioxidant defense was evidenced only in female rats. Our study with a translational potential demonstrates, for the first time, that early post-natal infections in epileptic rats induced or worsened hepatic disorders in a sex-dependent manner, amplifying inflammation, lipid dysmetabolism, and mitochondrial impairment. Full article