Novel imaging finding and novel mutation in an infant with molybdenum cofactor deficiency: a mimicker of hypoxic ischaemic encephalopathy

Molybdenum cofactor deficiency is a rare metabolic disorder with neonatal onset seizures, developmental delay, microcephaly and spasticity. In this report, we describe a three-month-old infant presented with neonatal onset, poorly controlled seizures, developmental delay, microcephaly, spastic quadriparesis and visual insufficiency. Magnetic resonance imaging of brain had shown cystic encephalomalacia involving bilateral parieto-occipital lobe, and elevated lactate in magnetic resonance spectroscopy.  Restricted diffusion noted along the corticospinal tract in our case is a novel imaging finding in molybdenum cofactor deficiency.  Low serum uric acid and elevated urine sulphite excretion were observed. A novel homozygous mutation was detected in exon 4 of MOCS2 gene.Early infantile or neonatal onset seizures, developmental delay, microcephaly and cystic encephalomalacia in neuroimaging mimicking hypoxic ischaemic encephalopathy should raise the suspect for molybdenum cofactor deficiency. Screening of all neonates for urinary sulphite metabolites helps in early diagnosis and management. Early diagnosis and treatment with cyclic pyranopterin monophosphate could arrest the progression of this disease. More research is needed to explore further treatment options in this otherwise lethal disorder

KCNT1- related epilepsy: An international multicenter cohort of 27 pediatric cases

ObjectiveThrough international collaboration, we evaluated the phenotypic aspects of a multiethnic cohort of KCNT1- related epilepsy and explored genotype- phenotype correlations associated with frequently encountered variants.MethodsA cross- sectional analysis of children harboring pathogenic or likely pathogenic KCNT1 variants was completed. Children with one of the two more common recurrent KCNT1 variants were compared with the rest of the cohort for the presence of particular characteristics.ResultsTwenty- seven children (15 males, mean age = 40.8 months) were included. Seizure onset ranged from 1 day to 6 months, and half (48.1%) exhibited developmental plateauing upon onset. Two- thirds had epilepsy of infancy with migrating focal seizures (EIMFS), and focal tonic seizures were common (48.1%). The most frequent recurrent KCNT1 variants were c.2800G>A; p.Ala934Thr (n = 5) and c.862G>A; p.Gly288Ser (n = 4). De novo variants were found in 96% of tested parents (23/24). Sixty percent had abnormal magnetic resonance imaging (MRI) findings. Delayed myelination, thin corpus callosum, and brain atrophy were the most common. One child had gray- white matter interface indistinctness, suggesting a malformation of cortical development. Several antiepileptic drugs (mean = 7.4/patient) were tried, with no consistent response to any one agent. Eleven tried quinidine; 45% had marked (>50% seizure reduction) or some improvement (25%- 50% seizure reduction). Seven used cannabidiol; 71% experienced marked or some improvement. Fourteen tried diet therapies; 57% had marked or some improvement. When comparing the recurrent variants to the rest of the cohort with respect to developmental trajectory, presence of EIMFS, >500 seizures/mo, abnormal MRI, and treatment response, there were no statistically significant differences. Four patients died (15%), none of sudden unexpected death in epilepsy.SignificanceOur cohort reinforces common aspects of this highly pleiotropic entity. EIMFS manifesting with refractory tonic seizures was the most common. Cannabidiol, diet therapy, and quinidine seem to offer the best chances of seizure reduction, although evidence- based practice is still unavailable.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154940/1/epi16480_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154940/2/epi16480.pd

Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism-dystonia.

Although manganese is an essential trace metal, little is known about its transport and homeostatic regulation. Here we have identified a cohort of patients with a novel autosomal recessive manganese transporter defect caused by mutations in SLC39A14. Excessive accumulation of manganese in these patients results in rapidly progressive childhood-onset parkinsonism-dystonia with distinctive brain magnetic resonance imaging appearances and neurodegenerative features on post-mortem examination. We show that mutations in SLC39A14 impair manganese transport in vitro and lead to manganese dyshomeostasis and altered locomotor activity in zebrafish with CRISPR-induced slc39a14 null mutations. Chelation with disodium calcium edetate lowers blood manganese levels in patients and can lead to striking clinical improvement. Our results demonstrate that SLC39A14 functions as a pivotal manganese transporter in vertebrates.Action Medical ResearchThis is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1160

Subacute sclerosing panencephalitis in a child with human immunodeficiency virus (HIV) infection on antiretroviral therapy

Subacute Sclerosing Panencephalitis (SSPE) in HIV-infected children is a scarcely reported entity with previous reports describing fulminant course. The impact of highly active antiretroviral therapy (HAART) in altering its course remains unknown. We describe a child with HIV infection, who developed measles at 5 months of age and later developed SSPE at 14 years of age, remaining stable at 7 month follow-up, while on HAART for WHO (World Health Organisation) stage IV disease. The dynamics of HIV-related immunosuppression has an impact on the clinical course of SSPE. Contrary to reported cases of fulminant progression, a classic presentation with slow progression can be expected in children on HAART. We reemphasize the recommendation of “early measles vaccination” to prevent measles infection and subsequent SSPE in these children with an increasingly good life expectancy in the era of HAART

Predictors of outcome in children with status epilepticus during resuscitation in pediatric emergency department: A retrospective observational study

Objectives: To study the clinical profile and predictors of outcome in children with status epilepticus (SE) during resuscitation in pediatric emergency department. Materials and Methods: This retrospective study was carried out in a tertiary care teaching hospital. Admission and resuscitation data of children, aged between 1 month and 12 years, treated for SE, between September 2013 and August 2014, were extracted using a standard data collection form. Our SE management protocol had employed a modified pediatric assessment triangle to recognize and treat acute respiratory failure, cardiovascular dysfunction (CD), and subtle SE until all parameters resolved. Continuous positive airway pressure, fluid boluses based on shock etiology, inotropes, and cardiac safe anticonvulsants were the other modifications. Risk factors predicting mortality during resuscitation were analyzed using univariate and penalized logistic regression. Results: Among 610 who were enrolled, 582 (95.4%) survived and 28 (4.6%) succumbed. Grunt odds ratio (OR): 3.747 (95% confidence interval [CI]: 1.035−13.560), retractions OR: 2.429 (95% CI: 1.036−5.698), rales OR: 10.145 (95% CI: 4.027−25.560), prolonged capillary refill time OR: 3.352 (95% CI: 1.339−8.388), and shock requiring >60 mL/kg fluids OR: 2.439 (95% CI 1.040−5.721) were associated with 2−3 times rise in mortality. Inappropriate prehospital treatment and CD were the significant predictors of mortality OR: 7.82 (95% CI 2.10−29.06) and 738.71 (95% CI: 97.11−999), respectively. Resolution of CD was associated with improved survival OR: 0.02 (95% CI: 0.003−0.17). Conclusion: Appropriate prehospital management and treatment protocol targeting resolution of CD during resuscitation could reduce mortality in children with SE

Study of refractory status epilepticus from a tertiary care center

Objectives: To determine the proportion of refractory status epilepticus (RSE) and super-RSE (SRSE) among patients with status epilepticus (SE) and to analyze RSE and non-RSE (NRSE) in terms of etiology and predictors for RSE. Materials and Methods: Patients were identified from discharge summaries database with keywords of SE and records of the portable electroencephalogram (EEG) machine from January 2011 to March 2016. Results: Two hundred and eighteen events were included in the study with 114 (52.3%) males, bimodal age preponderance age <5 years 30%, and second peak in age 15–65 years 52.8%, preexisting seizures were present in 34.4% (n = 75). Nearly 77.1% had NRSE (n = 168) and 22.9% had RSE (n = 50). This included 17 patients with SRSE (n = 17, 7.8% of all SE). Central nervous system (CNS) infection was a single largest etiological group in SE (69/218, 31.7%). In RSE, autoimmune encephalitis (17/50) and CNS infection (13/50) were the largest groups. De novo seizures (P = 0.007), low sensorium at admission (P = 0.001), low albumin at admission (P = 0.002), and first EEG being abnormal (P = 0.001) were risk factors on bivariate analysis. An unfavorable status epilepticus severity score (STESS) was predictive for RSE (P = 0.001). On multivariate analysis, de novo seizures (P = 0.009) and abnormal EEG at admission (P = 0.03) were predictive for RSE. Conclusions: Fifty patients had RSE (22.9%), of which 17 went on to become SRSE (7.8%). Unfavorable STESS score was predictive for RSE on bivariate analysis. On multivariate analysis, de novo seizures and abnormal initial EEG were predictors of RSE