The profile of epilepsy and its characteristics in children with neurocutaneous syndromes.

Objectives: The profile of seizures in neurocutaneous syndromes is variable. We aimed to define the characteristics of epilepsy in children with neurocutaneous syndromes. Materials and Methods: Cross-sectional study over 18 months at a tertiary care pediatric hospital, including children with neurocutaneous syndromes aged between 1 and 15 years, using the 2017-International League Against Epilepsy classification. Results: In 119 children with neurocutaneous syndromes, 94 (79%) had epilepsy. In eight children with neurofibromatosis one with epilepsy, 5 (62.5%) had generalized motor tonic-clonic seizures, 1 (12.5%) had generalized motor epileptic spasms, 1 (12.5%) had generalized motor automatism, and 1 (12.5%) had a focal seizure. In 69 children with tuberous sclerosis complex with epilepsy, 30 (43.5%) had generalized motor epileptic spasms, 23 (33.3%) had focal seizures, and nine (13.0%) had generalized motor tonic-clonic seizures. In 14 children with Sturge-Weber syndrome with epilepsy, 13 (92.8%) had focal seizures, and 1 (7.2%) had generalized motor tonic seizures. Statistically significant associations were found between epilepsy and intellectual disability (P = 0.02) and behavioral problems (P = 0.00). Conclusion: Profiling seizures in children with neurocutaneous syndromes are paramount in devising target-specific treatments as the epileptogenesis in each syndrome differs in the molecular pathways leading to the hyperexcitability state. Further multicentric studies are required to unravel better insights into the epilepsy profile of neurocutaneous syndromes.

Use of cost-effective software for lesion localization in brain surgery: Technical note.

Lesion localization has been an important aspect of neurosurgery and has advanced significantly with technological evolution. The journey started from the localization of lesion based on clinical findings to the current era where neuronavigation and virtual reality are being used for the purpose. However, the financial implications of these advanced equipments have made them inaccessible for patients in the majority of low- and middle-income countries. The authors describe techniques to use software, which are cost effective and can be used effectively for the localization of a lesion of the brain.

Charcot-Marie-Tooth Disease Type 4C and Autosomal Dominant Heterozygous Ichthyosis Vulgaris, with Bilateral Hearing Loss: A Novel Association with Review of Literature.

A 3-year-old boy, firstborn to nonconsanguineous parents, presented with motor development delay and floppiness of bilateral lower limbs since birth. No significant family history presented at time of check-up. He could stand with support, eat with a spoon without spillage, and speak in two-word sentences. There was no history suggestive of cranial nerve impairment. Examination revealed normal head circumference, dry, scaly skin lesions on the trunk, distal weakness with sluggish deep tendon reflexes in bilateral lower limbs, and a high stepping gait. Nerve conduction studies revealed demyelinating polyneuropathy. Brain stem-evoked response audiometry testing revealed auditory neuropathy. Clinical exome sequencing revealed a known pathogenic variant of 3325C > T in the SH3TC2 gene suggestive of Charcot-Marie-Tooth disease type 4C and ichthyosis vulgaris with a novel variant of 2218C > T in the FLG gene. We have reviewed the available literature for reported associations of Charcot-Marie-Tooth disease type 4C and ichthyosis vulgaris. This is probably the first reported association of Charcot-Marie-Tooth disease type 4C and ichthyosis vulgaris with bilateral hearing loss.

To Study the Distress, Anxiety, Depression, and Sleep Effects of the COVID-19 Pandemic on Essential Workers.

Essential care workers like police personnel, social workers, and office and administrative staff of health institutions are also at increased risk of coronavirus disease 2019 (COVID-19) exposure along with healthcare workers. The present study aims to estimate the distress, anxiety, depression, and sleep impact of COVID-19 pandemic on essential workers through an online survey. This cross-sectional study (included 369 participants) was conducted in Chandigarh through an online survey using three psychological scales: Peritraumatic Distress Inventory (PDI), Insomnia Severity Index, and Depression Anxiety Stress Scale. Three-hundred-sixty-nine frontline warriors from hospital and community settings were included in the study. The respondents include police personnel (274; 73.66%), office staff (24; 6.45%), social workers (53; 14.24%), and media staff (21; 5.65%). Maximum distress was reported by media/transport officials on duty (85.7%). The majority of them scored high (>14), and slightly less than one-fourth (23.8%) scored significantly abnormal (>23) on PDI. About 42.9% reported moderate insomnia, 52.4% exhibited severe anxiety, and 33.3% of media/transport participants reported severe depression. Psychological morbidity is high in media/transport and social workers working in the community during the COVID-19 pandemic.

Evaluation of utility of Invasive Electroencephalography for definitive surgery in patients with Drug-Resistant epilepsy: A Systematic Review and Meta-analysis.

When non-invasive tests are unable to define the epileptogenic zone in patients, intracranial electroencephalography (iEEG) is a method of localising the epileptogenic zone. Compared to non-invasive evaluations, it offers more precise information about patterns of epileptiform activity, which results in useful diagnostic information that supports surgical decision-making. The primary aim of the present study was to assess the utility of iEEG for definitive surgery for patients suffering from drug-resistant epilepsy (DRE). Online databases like PubMed, Medline, Embase, Scopus, Cochrane Library, Web of Science and IEEE explorer were searched for MeSH terms and free-text keywords. ROBINS I critical appraisal tool was used for quality assessment. Prevalence from different studies was pooled together using the inverse variance heterogeneity method. Eggers regression analysis and funnel plot were used to evaluate publication bias. The systematic review included eighteen studies, while the meta-analysis included ten studies to estimate the prevalence of seizure freedom (class I Engel) in patients undergoing surgery after iEEG. There were 526 patients in all that were included in the meta-analysis. The period of follow-up ranged from one to ten years. The overall pooled estimate of the prevalence of seizure freedom (class I Engel) in patients undergoing surgery after iEEG was 53% (95% CI: 44, 62). The results additionally demonstrated that twelve studies had a moderate risk of bias, whereas six studies had a low risk. Future studies are crucial to enhance our understanding of iEEG, guiding patient choices and unraveling their implications.

Familial hemiplegic migraine in Indian children-a tertiary center experience.

Familial hemiplegic migraine (FHM), an autosomal dominant subtype of hemiplegic migraine, is a channelopathy presenting with severe headache, visual field defect, paresthesia, unilateral motor deficit, encephalopathy, seizures and aphasia. This cross-sectional study was conducted over 10 months in children aged 1-18 years suspected of hemiplegic migraine at a tertiary care pediatric hospital. Fourteen children were screened and five children with genetically confirmed FHM were included. The symptoms in the study population were paroxysmal hemiparesis (5/5), headache (5/5) and focal seizures (1/5). The hemiplegia episodes lasted from 4 h to 7 days. The mean age at the onset of neurological symptoms was 6.8 ± 0.7 years and the mean age at diagnosis was 12.8 ± 1.7 years, with a mean delay of 6.1 ± 1.9 years for the diagnosis. Neuroimaging during acute episodes revealed accentuated gray, white differentiation in the contralateral cerebral hemisphere with mild effacement of sulcal spaces in T2/fluid-attenuated inversion recovery (FLAIR) images. Genetic testing revealed ATP1A2 mutations (FHM2) in 4/5 and SCN1A (FHM3) in 1/5 patients. All of them (5/5) were initiated on oral topiramate and had favorable treatment responses with a mean follow-up duration of 7 ± 1.4 months. Diagnosis of FHM is mainly clinical and can be confirmed by genetic analysis. Perfusion and diffusion-weighted MRI should be considered during acute headache episodes, as it is mostly normal in symptom-free periods. Routine MRI sequences like T1 weighted, T2 weighted, FLAIR and contrast remain normal even during acute attacks.

Prevalence and predictors of restless legs syndrome among patients having stable chronic obstructive pulmonary disease.

BACKGROUND: Patients having COPD share some factors, e.g., chronic hypoxemia, anemia of chronic disease and nicotine use, which are also the risk factors for RLS hence predispose them to experience RLS in higher then general population. There are limited studies with methodological constraints evaluating the prevalence and/or correlates of RLS among patients with COPD. METHODS: Consecutive adult patients of either gender, having stable COPD as per GOLD guidelines 2021, were assessed for RLS using IRLSSG (2014) criteria (excluding RLS mimics) and the severity of RLS was determined in participants having RLS. Phenomenology of RLS, past medical history and laboratory parameters were gathered. Insomnia and depression were assessed using the insomnia severity index and PHQ-9, respectively. RESULTS: Participants' (N = 210) mean age was 63.02 ± 8.19 years, and 83.8% of subjects were men. 12.9% of participants were found to have RLS. Among those having RLS, nearly half (51.9%) had moderate symptoms, and 18.5% experienced severe symptoms. RLS was more prevalent among younger, females, those having severe COPD, participants having exacerbation of COPD in the previous year, lower post-bronchodilator FEV1, higher dyspnea and COPD assessment test score. Multivariate analysis showed that younger age, female gender, lower post-bronchodilator FEV1, lower FEV1/FVC ratio and higher serum creatinine increased the odds of having RLS. Depressive symptoms were more frequent in participants having RLS. CONCLUSIONS: The present study found that the prevalence of RLS among patients with stable COPD was higher than the general population. Female gender, younger age, higher airflow limitation and higher serum creatinine (though in the physiological range) increase the odds of having RLS. Stable patients with COPD having these characteristics must be screened for RLS.

Evaluation of Hepatic Steatosis and Fibrosis Using Transient Elastography in Patients With Obstructive Sleep Apnea.

Objectives: Obstructive sleep apnea (OSA) is an independent risk factor for non-alcoholic fatty liver disease. This study was planned to assess proportion of patients with OSA that have hepatic steatosis and fibrosis, as measured by transient elastography, to explore variables influencing their development and to find out the polysomnography parameters that predict the need for transient elastography screening in OSA. Methods: Consecutive participants having polysomnography proven OSA were included in the study after screening for eligibility criteria. Data of the polysomnography were scored manually following standard criteria. Participants were subjected to transient elastography (Fibroscan®) and serum investigations after diagnostic polysomnography. The polysomnography, fibroscan®, and laboratory data were tabulated and analyzed. Results: A total of 71 participants were enrolled. 16.9% participants had mild OSA, 28.2% had moderate OSA, and remaining participants had severe OSA. Liver steatosis was found in 63.4% participants while hepatic fibrosis was noted in 9.9%. Oxygen desaturation index (ODI), apnea-hypopnea index (AHI), and percentage of sleep spent below 90% oxygen saturation (T90) were significantly associated with the presence of hepatic steatosis and fibrosis. Receiver operating curve (ROC) showed that at the cut-offs of 73 events/hr, 13% and 72.2 events/hr, AHI, T90 and ODI, predicted hepatic fibrosis with area under ROC of 0.960, 0.944, and 0.933, respectively (P < 0.001). Conclusions: Patients with OSA are at increased risk for development of hepatic steatosis and fibrosis. ODI, AHI, and T90 during polysomnography predict the presence of underlying hepatic fibrosis.

Ameliorating effect of pioglitazone on prenatal valproic acid-induced behavioral and neurobiological abnormalities in autism spectrum disorder in rats.

Autism spectrum disorder (ASD) is a neurodevelopment disorder that mainly arises due to abnormalities in different brain regions, resulting in behavioral deficits. Besides its diverse phenotypical features, ASD is associated with complex and varied etiology, presenting challenges in understanding its precise neuro-pathophysiology. Pioglitazone was reported to have a fundamental role in neuroprotection in various other neurological disorders. The present study aimed to investigate the therapeutic potential of pioglitazone in the prenatal valproic acid (VPA)-model of ASD in Wistar rats. Pregnant female Wistar rats received VPA on Embryonic day (E.D12.5) to induce autistic-like-behavioral and neurobiological alterations in their offspring. VPA-exposed rats presented core behavioral symptoms of ASD such as deficits in social interaction, poor spatial and learning behavior, increased anxiety, locomotory and repetitive activity, and decreased exploratory activity. Apart from these, VPA exposure also stimulated neurochemical and histopathological neurodegeneration in various brain regions. We administered three different doses of pioglitazone i.e., 2.5, 5, and 10 mg/kg in rats to assess various parameters. Of all the doses, our study highlighted that 10 mg/kg pioglitazone efficiently attenuated the autistic symptoms along with other neurochemical alterations such as oxidative stress, neuroinflammation, and apoptosis. Moreover, pioglitazone significantly attenuated the neurodegeneration by restoring the neuronal loss in the hippocampus and cerebellum. Taken together, our study suggests that pioglitazone exhibits therapeutic potential in alleviating behavioral abnormalities induced by prenatal VPA exposure in rats. However, further research is needed to fully understand and establish pioglitazone's effectiveness in treating ASD.

Zuranolone, a neuroactive drug, used in the treatment of postpartum depression by modulation of GABAA receptors.

BACKGROUND: Postpartum depression [PPD] is a prevalent and debilitating mood disorder that affects mothers in the weeks to months after childbirth. Zuranolone (Zurzuvae) is a novel pharmaceutical agent that was approved by the US FDA on 4 August 2023 for the management of PPD. This review article provides a comprehensive overview of zuranolone, focusing on its dosing, chemistry, mechanism of action, clinical trials, adverse drug reaction, and overall conclusion regarding its utility in the management of PPD. It also discusses the recommended dosing strategies to achieve optimal efficacy while minimizing adverse effects as the dosage regimen of zuranolone is critical for its therapeutic application. Moreover, it gives insights into neurobiological pathways involved in PPD. METHODOLOGY: Data from randomized controlled trials and observational studies was collected to provide a comprehensive understanding of zuranolone in the management and treatment of PPD. CONCLUSION: Zuranolone represents a promising therapeutic option for women suffering from postpartum depression. However, ongoing research and post-marketing surveillance are essential to further elucidate its long-term safety and efficacy. The integration of zuranolone into clinical practice may significantly improve the quality of life for mothers facing the challenges of postpartum depression.

Teaching NeuroImage: Neuroimaging Features of Wilson Disease.

A 13-year-old boy of nonconsanguineous parents presented with abnormal body movements, gait difficulty, and slurring of speech for 2 years. On examination, he had rigidity, dystonia, dysarthria, and drooling. Ophthalmologic examination revealed bilateral Kayser-Fleischer rings. He had elevated serum "free" copper levels (41.2 µg/dL [range:10-15]), 24-hour urine copper levels (895.7 µg/d [range:<60]), and reduced serum ceruloplasmin levels (4.3 mg/dL (range:20-40]). MRI revealed "face of giant panda" appearance (Figure A), T2-fluid attenuated inversion recovery hyperintensities (Figure, B and C), and frontal cystic encephalomalacic changes (Figure D), suggestive of Wilson disease (WD). Face of giant panda in WD, first described by Hitoshi et al.,1 is due to high signal intensity in tegmentum with normal signals in red nuclei forming the eyes, normal signals of pars reticulata (lateral portion) of substantia nigra forming the ears, and hypointensity of superior colliculus forming the chin.2 Bilateral cystic changes are less commonly reported in WD.3 Recognizing diverse neuroimaging signatures beyond well-known findings in WD enhances diagnostic accuracy.

Primary Diffuse Leptomeningeal Melanomatosis in an Indian Child With Review of Literature.

BACKGROUND: Primary diffuse leptomeningeal melanomatosis (PDLM) is an extremely rare, aggressive malignant neoplasia of the central nervous system. We report the first case of pediatric PDLM from India. METHODS: A review of literature was done to describe the 15 pediatric cases reported so far. RESULTS: A 12-year-old male child presented with fever, vomiting, and headache for 2 months. Cerebrospinal fluid examination was normal. An MRI of the brain revealed hydrocephalus, for which antitubercular therapy was started and external ventricular drainage followed by ventriculoperitoneal shunt was done. Repeat MRI revealed a suprasellar lesion, nodular enhancement of cranial nerves along with dural enhancement of spinal cord with arachnoiditis, and long-segment myelomalacia. Repeat cerebrospinal fluid examination was negative for malignant cells. During biopsy, blackish dura with diffuse blackish deposits in ventricle were noted. Histopathological examination revealed tumor cells with intracytoplasmic coarse brown pigment melanoma, frequent mitotic figures, and immunohistochemistry testing was positive for human melanoma black-45 and MelanA, suggestive of PDLM. He expired 4 months after the diagnosis. CONCLUSION: Diagnosing PDLM can be daunting in light of its slow but malignant progression mimicking TBM leading to improper management. However, the absence of any supportive microbiological evidence and failure to respond to the standard antitubercular therapy with subsequent progression of the symptoms should prompt the need for finding an alternative diagnosis. A targeted molecular diagnosis and precision medicine may provide a favorable outcome in children with PDLM.