Childhood Neurological Disorders With Hyperhomocystinemia: A Case-Based Review.

Hyperhomocysteinemia is a rare neurometabolic syndrome with diverse manifestations in the pediatric age group, thereby posing a diagnostic challenge. Biochemical testing is imperative to guide plan of evaluation, which may include appropriate genetic testing, in inherited disorders. Through this case-based approach, we demonstrate the heterogeneity of clinical presentation, biochemical and genetic evaluation, and treatment strategies that may reverse this condition among children.

Improving Ineffective Erythropoiesis in Thalassemia: A Hope on the Horizon.

Beta-thalassemia is an inherited hemoglobinopathy characterized by the impaired synthesis of beta-globin chains of hemoglobin leading to chronic hemolytic anemia. The mainstay of treatment for most patients remains regular blood transfusions and iron chelation. This conventional therapy has many limitations and challenges. Allogeneic hematopoietic stem cell transplant (HSCT) is the only available curative treatment but the availability of a suitable donor, financial constraints, and a need for specialist physicians can be limiting factors. Gene therapy is an upcoming curative therapeutic modality. An increased understanding of the underlying pathophysiology and molecular mechanisms of thalassemia has paved the way for novel pharmacological agents targeting ineffective erythropoiesis. These drugs act by decreasing transfusion requirements and hence decrease transfusion-related complications. The present review intends to provide an insight into the recent advances in pharmacological agents targeting ineffective erythropoiesis. Literature was searched and relevant articles evaluating newer drugs in thalassemia were collected from databases, including Pubmed, Scopus, Prospero, Clinicaltrials.gov, Google Scholar, and the Google search engine. We used the following keywords: thalassemia, novel, treatment, drugs, and ineffective erythropoiesis during the initial search. Relevant titles and abstracts were screened to choose relevant articles. Further, the full-text articles were retrieved and relevant cross-references were scanned to collect information for the present review.

Can We Prevent Sudden Unexpected Death in Epilepsy (SUDEP)?

Sudden unexpected death in epilepsy (SUDEP) remains an important cause of epilepsy-related mortality, especially in patients with refractory epilepsy. The exact cause is not known, but postictal cardiac, respiratory, and brainstem dysfunctions are implicated. SUDEP prevention remains a big challenge. Except for low-quality evidence of preventive effect of nocturnal supervision for SUDEP, no other evidence-based preventive modality is available. Other potential preventive strategies for SUDEP include reducing the occurrence of generalized tonic-clonic seizures using seizure detection devices, detecting cardiorespiratory distress through respiratory and heart rate monitoring devices, preventing airway obstruction (safety pillows), and reducing central hypoventilation using selective serotonin reuptake inhibitors and adenosine and opiate antagonists. However, none of the above-mentioned modalities has been proven to prevent SUDEP. The present review intends to provide insight into the available SUDEP prevention modalities.

Advances in the Diagnosis and Management of Tubercular Meningitis in Children.

Tubercular meningitis (TBM) continues to be a common cause of neuromorbidity in children. There is no single diagnostic method that can rapidly detect Mycobacterium tuberculosis (M.tb) in TBM patients with high sensitivity and specificity. Newer diagnostic modalities like Xpert/RIF assay and Loop mediated isothermal amplification assay (LAMP) have gained an essential stand in molecular diagnostics due to their high specificity, modest sensitivity in cerebrospinal fluid (CSF) and quick availability of results. Intensified drug regimens using high dose rifampicin, fluoroquinolone and aspirin appear to be useful adjunct therapy but more pediatric clinical trials on large scale are needed to determine their appropriate place in pediatric TBM. The emergence of multi and extreme drug resistant M.tb strains further challenges the standard therapy. In this review authors summarize challenges of the currently used diagnostic methods and treatment for TBM and discuss the recent advances.

Atypical Childhood-onset Neuroaxonal Dystrophy in an Indian Girl.

A 7-year-old girl presented with progressive walking difficulties, spasticity, and cognitive decline with onset at 3 years of age. No seizures, vision, or hearing impairment were reported. The magnetic resonance imaging of the brain revealed cerebellar atrophy and evidence of iron deposition in the globi pallidi and substantia nigra. The clinico-radiological profile was suggestive of atypical childhood-onset neuroaxonal dystrophy. The patient was found to have compound heterozygous mutations in the PLA2G6 gene confirming the diagnosis.

Myocardial dysfunction as a predictor of the severity and mortality of hypoxic ischaemic encephalopathy in severe perinatal asphyxia: a case-control study.

Background: In perinatal asphyxia, hypoxia often leads to myocardial ischaemia. Few studies have assessed the degree of myocardial dysfunction in severely asphyxiated term neonates. Aim: To assess the extent of myocardial damage in newborns with severe perinatal asphyxia. Methods: A case-control study was conducted in asphyxiated newborns with hypoxic ischaemic encephalopathy (HIE) and in controls who were term non-asphyxiated newborns. Total (T) creatinine kinase (CK), CK-MB, troponin-T and 12-lead electrocardiography (ECG) and echocardiography were performed in both groups within 24-48 h after birth. The proportions of asphyxiated neonates with myocardial dysfunction and its relationship between severity of HIE and immediate outcome was compared. Results: Five of 23 asphyxiated neonates developed stage I, 10 stage II and eight stage III HIE. Serum levels of CK-T and CK-MB were raised in all 23 cases and troponin-T was raised in 13 (56.5%) HIE cases. ECG was abnormal in all cases and echocardiography in three (13%). Left ventricular ejection fraction (LVEF) and right ventricular ejection fraction (RVEF) were significantly decreased in all asphyxiated neonates. Eight (35%) patients died. Enzyme levels were higher and ECG and echocardiography abnormalities were common in infants with more severe HIE (p <0.05). Mean serum levels of CK-T and MB (p <0.001) and troponin-T (p =0.002) were higher in non-survivors. Mean LVEF and RVEF values were higher in survivors (p <0.001). All the controls had normal enzyme levels and echocardiography. ECG was abnormal in one control. Conclusion: Cardiac enzymes, ECG and echocardiography changes were associated with increasing severity of HIE and mortality.

Vitamin B12 Deficiency in Children With Infantile Spasms: A Case-Control Study.

There have been few case reports showing association of vitamin B12 deficiency with infantile spasms. We planned this study to see if there was an association of serum vitamin B12 deficiency in children with development of infantile spasms. Cases included children with infantile spasms of ages 6 months to 3 years. The controls were children in the same age group who had global developmental delay but no history of epileptic spasms. Mean serum vitamin B12, serum homocysteine, and urinary methylmalonic acid levels were measured in both groups and compared. Children with infantile spasms had lower mean serum vitamin B12 levels (354.1 pg/mL; standard deviation 234.1 pg/mL) as compared to children with global developmental delay without spasms (466.7 pg/mL; standard deviation 285.5 pg/mL) ( P value < .05). Mean serum homocysteine level (13.9 vs 7.8 µmol/L, P = .02) and mean urinary methylmalonic acid level (68.1 mmol/mol of creatinine vs 26.1 mmol/mol of creatinine, P = .03) were elevated in children with infantile spasms than in controls. Fourteen children (35.0%) with infantile spasms were vitamin B12 deficient compared with 3 (7.50%) controls ( P = .005). Thus, vitamin B12 deficiency may have an association with infantile spasms. More studies are needed before recommending routine measurement of serum B12 levels in children with infantile spasms.