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Neurotoxicity Research Jun 2024Nonketotic hyperglycinemia (NKH) is an inherited disorder of amino acid metabolism biochemically characterized by the accumulation of glycine (Gly) predominantly in the... (Review)
Review
Nonketotic hyperglycinemia (NKH) is an inherited disorder of amino acid metabolism biochemically characterized by the accumulation of glycine (Gly) predominantly in the brain. Affected patients usually manifest with neurological symptoms including hypotonia, seizures, epilepsy, lethargy, and coma, the pathophysiology of which is still not completely understood. Treatment is limited and based on lowering Gly levels aiming to reduce overstimulation of N-methyl-D-aspartate (NMDA) receptors. Mounting in vitro and in vivo animal and human evidence have recently suggested that excitotoxicity, oxidative stress, and bioenergetics disruption induced by Gly are relevant mechanisms involved in the neuropathology of NKH. This brief review gives emphasis to the deleterious effects of Gly in the brain of patients and animal models of NKH that may offer perspectives for the development of novel adjuvant treatments for this disorder.
Topics: Hyperglycinemia, Nonketotic; Animals; Humans; Oxidative Stress; Energy Metabolism; Glycine; Brain
PubMed: 38949693
DOI: 10.1007/s12640-024-00711-5 -
JPMA. the Journal of the Pakistan... Jun 2024Functional neurological disorder is a condition in which a person experiences physical symptoms that cannot be fully explained by a medical condition. In Pakistan,... (Review)
Review
Functional neurological disorder is a condition in which a person experiences physical symptoms that cannot be fully explained by a medical condition. In Pakistan, domestic violence as well as emotional, physical and sexual abuse in children are prevalent. Despite legal and social support for victims, stigmatisation regarding seeking psychological help complicates the challenge. Some of the research culminated that patients with neurological disorder reported high level of sexual abuse and trauma. The symptomatology of functional neurological disorder is being ignored in Asian countries due to indigenous factors like poverty, lack of information on reporting abuse, poor law-enforcement and victim blaming. Functional neurological disorder can be manifested in various ways in the human body, such as blindness, paralysis, dystonia, swallowing difficulties, difficulty walking, motor symptoms affecting limbs, voice production, problems in sensory functions, problems in cognitive function, psychogenic non-epileptic seizures and even dementia, whereas differential diagnosis is established after screening for organicity. The common risk factors of functional neurological disorder may include psychosocial stressors, family history of functional neurological disorder, and significant life changes. It is critical to understand the disorder in reference to predisposing risk factors, cultural context, comorbidities and gender specification to diagnose and treat functional neurological disorder in time so that better intervention protocols could be devised to treat it efficiently.
Topics: Humans; Pakistan; Child; Conversion Disorder; Nervous System Diseases; Child Abuse; Risk Factors
PubMed: 38948985
DOI: 10.47391/JPMA.10083 -
World Journal of Transplantation Jun 2024In this editorial, we talk about a compelling case focusing on posterior reversible encephalopathy syndrome (PRES) as a complication in patients undergoing liver...
In this editorial, we talk about a compelling case focusing on posterior reversible encephalopathy syndrome (PRES) as a complication in patients undergoing liver transplantation and treated with Tacrolimus. Tacrolimus (FK 506), derived from , is a potent immunosuppressive macrolide. It inhibits T-cell transcription by binding to FK-binding protein, and is able to amplify glucocorticoid and progesterone effects. Tacrolimus effectively prevents allograft rejection in transplant patients but has adverse effects such as Tacrolimus-related PRES. PRES presents with various neurological symptoms alongside elevated blood pressure, and is primarily characterized by vasogenic edema on neuroimaging. While computed tomography detects initial lesions, magnetic resonance imaging, especially the Fluid-Attenuated Inversion Recovery sequence, is superior for diagnosing cortical and subcortical edema. Our discussion centers on the incidence of PRES in solid organ transplant recipients, which ranges between 0.5 to 5 +ACU-, with varying presentations, from seizures to visual disturbances. The case of a 66-year-old male status post liver transplantation highlights the diagnostic and management challenges associated with Tacrolimus-related PRES. Radiographically evident in the parietal and occipital lobes, PRES underlines the need for heightened vigilance among healthcare providers. This editorial emphasizes the importance of early recognition, accurate diagnosis, and effective management of PRES to optimize outcomes in liver transplant patients. The case further explores the balance between the efficacy of immunosuppression with Tacrolimus and its potential neurological risks, underlining the necessity for careful monitoring and intervention strategies in this patient population.
PubMed: 38947962
DOI: 10.5500/wjt.v14.i2.91146 -
Pancreatic Insulinoma Masquerading as Neurological Disease: Diagnosis and Treatment of a Rare Tumor.Cureus May 2024Insulinomas are rare functional pancreatic neuroendocrine tumors that typically manifest with classic hypoglycemic symptoms, such as diaphoresis, palpitations, and...
Insulinomas are rare functional pancreatic neuroendocrine tumors that typically manifest with classic hypoglycemic symptoms, such as diaphoresis, palpitations, and tremors. Although infrequent, neuroglycopenic symptoms associated with insulinomas have been reported, often leading to delayed diagnoses. Here, we present the case of a 31-year-old male with pancreatic insulinoma who experienced recurrent episodes of seizures and confusion preceded by diaphoresis, tremors, and palpitations. During these episodes, he was found to be hypoglycemic. Comprehensive evaluations, including brain and abdominal imaging, as well as biochemical and serological testing, were conducted. The findings confirmed a diagnosis of pancreatic insulinoma. The patient underwent surgical resection of the tumor, and a biopsy confirmed the insulinoma diagnosis. He remained asymptomatic during subsequent follow-ups.
PubMed: 38947643
DOI: 10.7759/cureus.61378 -
Cureus May 2024The papillary tumor of the pineal region (PTPR) is a rare neuroepithelial tumor originating from specialized ependymocytes. It primarily affects structures within the...
The papillary tumor of the pineal region (PTPR) is a rare neuroepithelial tumor originating from specialized ependymocytes. It primarily affects structures within the pineal region, including the pineal gland, epithalamus, quadrigeminal cistern, and posterior wall of the third ventricle. Here, we present a series of four cases characterized by symptoms associated with obstructive hydrocephalus such as headaches, seizures, visual disturbances, gait disturbances, and Parinaud syndrome. Imaging studies revealed lesions in the pineal region, prompting surgical intervention. Histopathological examination, including biopsy and intraoperative analysis, confirmed the diagnosis of PTPR. Despite advancements, the etiology and pathogenesis of PTPR remain incompletely understood, warranting further research to refine management strategies.
PubMed: 38947620
DOI: 10.7759/cureus.61308 -
Neuropsychiatric Disease and Treatment 2024Absence seizures are classically associated with behavioral arrest and transient deficits in consciousness, yet substantial variability exists in the severity of the... (Review)
Review
Absence seizures are classically associated with behavioral arrest and transient deficits in consciousness, yet substantial variability exists in the severity of the impairment. Despite several decades of research on the topic, the pathophysiology of absence seizures and the mechanisms underlying behavioral impairment remain unclear. Several rationales have been proposed including widespread cortical deactivation, reduced perception of external stimuli, and transient suspension of the default mode network, among others. This review aims to summarize the current knowledge on the neural correlates of impaired consciousness in absence seizures. We review evidence from studies using animal models of absence epilepsy, electroencephalography, functional magnetic resonance imaging, magnetoencephalography, positron emission tomography, and single photon emission computed tomography.
PubMed: 38947367
DOI: 10.2147/NDT.S391052 -
MedRxiv : the Preprint Server For... Jun 2024Since the initial description of related hemiplegic migraine (HM), the phenotypic spectrum has expanded from mild episodes in neurotypical individuals to potentially...
INTRODUCTION
Since the initial description of related hemiplegic migraine (HM), the phenotypic spectrum has expanded from mild episodes in neurotypical individuals to potentially life-threatening events frequently seen in individuals with developmental and epileptic encephalopathies. However, the overall longitudinal course throughout childhood remains unknown.
METHODS
We analyzed HM and seizure history in individuals with -related HM, delineating frequency and severity of events in monthly increments through a standardized approach. Combining these data with medication prescription information, we assessed the response of HM to different agents.
RESULTS
Our cohort involved 15 individuals between 3 and 29 years (163 patient years) and included 11 unique and two recurrent variants (p.R1349Q and p.V1393M; both 2). The age of first confirmed HM ranged from 14 months to 13 years (average 3 years). 25% of all HM events were severe (lasting >3 days) and 73% of individuals had at least 1 severe occurrence. Spacing of HM events ranged from 1 month to 14 years and changes in HM severity over time of showed increases or decreases of >2 severity levels in 12/122 events. Eight individuals had epilepsy, but severity of epilepsy did not correlate with frequency and severity of HM events. While levetiracetam ( 6) and acetazolamide ( 5) were the most frequently used medications, they did not show efficacy in HM prevention or HM severity reduction. However, verapamil ( 3) showed efficacy in preventing HM episodes (OR 2.68, CI 1.39-5.67).
SIGNIFICANCE
The longitudinal course of -related HM lacks recognizable patterns for timing and severity of HM events or correlation with seizure patterns. Our data underscores the unpredictability of -related HM, highlighting the need for close surveillance for reoccurring HM events even in individuals with symptom-free periods.
KEY POINTS
24% of hemiplegic migraines (HM) in related disorders are severe, involving cerebral edema and greater than 4 days to recover Timing and severity of HM are unpredictable, with large changes in severity between events, and age of onset ranging from 1-13 yearsEpilepsy occurred in 53% of individuals, with neither the timing nor severity of seizures correlated with HM.
PubMed: 38946946
DOI: 10.1101/2024.06.14.24308953 -
The Pan African Medical Journal 2024Epididymal tuberculosis is rare and often presents diagnostic difficulties. It may be indicative of a disseminated form of the infection, which is the case of our...
Epididymal tuberculosis is rare and often presents diagnostic difficulties. It may be indicative of a disseminated form of the infection, which is the case of our patient. A 19-year-old man, with no past medical history, was admitted for a swollen painful left scrotum that had been evolving for 8 months. He had undergone an orchiectomy and the anatomopathological examination was consistent with epididymal tuberculosis. The radiological investigations had revealed other localizations of the infection: lymphatic, pulmonary, parietal and osteoarticular tuberculosis. Anti-tuberculosis therapy was introduced. However, in the 4 month of treatment, the patient developed seizures. A cerebral magnetic resonance imaging was practiced, concluding to cerebral tuberculomas. Anti-tuberculosis treatment was continued associated to an anticonvulsant with a favourable outcome. The originality of our observation resides in the mode of revelation of a disseminated paucisymptomatic tuberculosis, by an epididymal localization, in an immunocompetent patient.
Topics: Humans; Male; Young Adult; Antitubercular Agents; Magnetic Resonance Imaging; Epididymis; Tuberculosis, Male Genital; Immunocompetence; Orchiectomy; Seizures; Anticonvulsants; Tuberculoma, Intracranial
PubMed: 38946746
DOI: 10.11604/pamj.2024.48.2.42965 -
Clinical Toxicology (Philadelphia, Pa.) Jul 2024The opioid receptor mu1 is a protein coding gene that can have different codes for a protein and may have variations (polymorphisms) affecting how opioids work. The aim...
INTRODUCTION
The opioid receptor mu1 is a protein coding gene that can have different codes for a protein and may have variations (polymorphisms) affecting how opioids work. The aim of this study was to investigate the prevalence of the most common opioid receptor mu1 polymorphism () and any relationship between this polymorphism and features following tramadol overdose.
MATERIALS AND METHODS
This was a cross-sectional study of patients admitted with tramadol poisoning to an Iranian hospital. These patients were not taking any other drugs or medications and had no history of seizures.
RESULTS
The results showed that among the 83 patients included in the study, 57 (69 per cent) had the AA genotype, 25 (30 per cent) had the AG genotype, and one (1 per cent) had the GG genotype for the opioid receptor mu1 polymorphism. Nausea and/or vomiting occurred in nine (11 per cent) patients and dizziness in 38 (46 per cent) patients. Serious adverse events included seizures in 51 (60 per cent) patients and respiratory failure requiring mechanical ventilation in 21 (25 per cent) patients. However, there was no significant association between the opioid receptor mu1 polymorphism and these adverse events.
DISCUSSION
In our study, the frequency of the A allele was greater than the G allele, and the AA genotype was more prevalent than AG. The GG genotype was the least common among the polymorphisms of opioid receptor mu1 . There was no significant association between the opioid receptor mu1 polymorphism and symptoms in tramadol-poisoned patients. Although these allele proportions are similar to the results reported in other Caucasian populations, they are dissimilar to the findings in Chinese and Singaporean populations. In these Asian studies, the predominant allele was the G allele. It has been suggested that a mutated G allele will decrease the production of opioid receptor mu1-related messenger ribonucleic acid and related proteins, leading to fewer mu-opioid receptors in the brain.
CONCLUSIONS
This study found no significant association between the opioid receptor mu1 polymorphism and adverse outcomes in tramadol-poisoned patients. However, more research is needed to draw more definitive conclusions due to the limited evidence and variability of opioid receptor mu1 polymorphisms in different populations.
PubMed: 38946467
DOI: 10.1080/15563650.2024.2366921 -
Epilepsia Open Jul 2024Epilepsy is a suitable target for gene panel sequencing because a considerable portion of epilepsy is now explained by genetic components, especially in syndromic cases....
OBJECTIVE
Epilepsy is a suitable target for gene panel sequencing because a considerable portion of epilepsy is now explained by genetic components, especially in syndromic cases. However, previous gene panel studies on epilepsy have mostly focused on pediatric patients.
METHODS
We enrolled adult epilepsy patients meeting any of the following criteria: family history of epilepsy, seizure onset age ≤ 19 years, neuronal migration disorder, and seizure freedom not achieved by dual anti-seizure medications. We sequenced the exonic regions of 211 epilepsy genes in these patients. To confirm the pathogenicity of a novel MTOR truncating variant, we electroporated vectors with different MTOR variants into developing mouse brains.
RESULTS
A total of 92 probands and 4 affected relatives were tested, and the proportion of intellectual disability (ID) and/or developmental disability (DD) was 21.7%. As a result, twelve probands (13.0%) had pathogenic or likely pathogenic variants in the following genes or regions: DEPDC5, 15q12-q13 duplication (n = 2), SLC6A1, SYNGAP1, EEF1A2, LGI1, MTOR, KCNQ2, MEF2C, and TSC1 (n = 1). We confirmed the functional impact of a novel truncating mutation in the MTOR gene (c.7570C > T, p.Gln2524Ter) that disrupted neuronal migration in a mouse model. The diagnostic yield was higher in patients with ID/DD or childhood-onset seizures. We also identified additional candidate variants in 20 patients that could be reassessed by further studies.
SIGNIFICANCE
Our findings underscore the clinical utility of gene panel sequencing in adult epilepsy patients suspected of having genetic etiology, especially those with ID/DD or early-onset seizures. Gene panel sequencing could not only lead to genetic diagnosis in a substantial portion of adult epilepsy patients but also inform more precise therapeutic decisions based on their genetic background.
PLAIN LANGUAGE SUMMARY
This study demonstrated the effectiveness of gene panel sequencing in adults with epilepsy, revealing pathogenic or likely pathogenic variants in 13.0% of patients. Higher diagnostic yields were observed in those with neurodevelopmental disorders or childhood-onset seizures. Additionally, we have shown that expanding genetic studies into adult patients would uncover new types of pathogenic variants for epilepsy, contributing to the advancement of precision medicine for individuals with epilepsy. In conclusion, our results highlight the practical value of employing gene panel sequencing in adult epilepsy patients, particularly when genetic etiology is clinically suspected.
PubMed: 38946282
DOI: 10.1002/epi4.12993