Pulmonary Embolism in Children: A Case Series.

BACKGROUND: Pulmonary embolism (PE) is a life-threatening event with a mortality of ~10%. It is relatively uncommon in children and literature regarding the condition is sparse. In adults, the classical clinical presentation is with pleuritic chest pain, hemoptysis, and dyspnea, whereas in children, the presentation is often nonspecific. MATERIALS AND METHODS: Clinical features, risk factors, and outcome of children with PE presenting to our unit between December, 19 and March, 2020 were recorded. RESULTS: Four children [mean age: 10 (6-16) years, 3 females], all presenting with tachycardia and dyspnea were diagnosed with PE. Different risk factors such as deep vein thrombosis, nephrotic syndrome, softtissue infection, and infective endocarditis (IE) were identified in all patients. One child died while others responded to anticoagulation. CONCLUSION: We aim to highlight the importance of timely recognition of PE in children with known risk factors for the same. Early recognition and timely treatment of PE are critical to save lives. HOW TO CITE THIS ARTICLE: Agrawal S, Shrivastava Y, Bolia R, Panda PK, Sharawat IK, Bhat NK. Pulmonary Embolism in Children: A Case Series. Indian J Crit Care Med 2020;24(12):1272-1275.

Systematic Review and Meta-analysis of Efficacy and Safety of Melatonin and Triclofos for Inducing Adequate Sedation for Sleep Electroencephalogram in Children.

Introduction Triclofos and melatonin are commonly used oral sedatives in children for obtaining a sleep electroencephalogram (EEG) record. There has been no systematic review till now to compare the efficacy and safety of these two medications. Objectives The review intended to compare the efficacy of oral triclofos and melatonin in children <18 years of age for inducing adequate sedation for obtaining a sleep EEG record. We also attempted to compare the adverse effects, impact on EEG record, the yield of epileptiform abnormalities, and sleep onset latency in both groups. Methods A systematic search was conducted on "MEDLINE/PUBMED, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Web of Science, and Google Scholar" till November 30, 2020, with the following keywords/the Medical Subject Headings (MESH) terms while searching: "sleep EEG," "electroencephalogram," "triclofos," "melatonin" OR "ramelteon" AND "epilepsy," "seizure," OR "convulsion." ROB 2.0 and ROBINS-I tool was used to determine the risk of bias. To assess heterogeneity in studies, Higgins and Thompson's I 2 method was utilized. When I 2 was more than 50%, a random effects model was utilized and a fixed-effect model was used for other parameters. To assess the presence of publication bias, Egger's test was used. Results For describing the efficacy of triclofos in 1,284 and melatonin in 1,532 children, we selected 16 articles. The indirect comparison between the pooled estimate of all children receiving individual medications revealed comparable efficacy in obtaining successful sleep EEG record with a single dose (90 vs. 76%, p = 0.058) and repeat dose ( p = 0.054), detection of epileptiform abnormalities ( p = 0.06), and sleep onset latency ( p = 0.06), but more proportion of children receiving triclofos had adverse effects ( p = 0.001) and duration of sleep was also higher with triclofos ( p = 0.001). Conclusion Efficacy of triclofos and melatonin are comparable in inducing sleep for recording EEG in children, although triclofos is more likely to cause adverse effects. However, the level of evidence is low for this conclusion and the weak strength of recommendation for the results of this review is likely to change in the future after completion of controlled trials exploring these two medications.

Efficacy and safety profile of selumetinib in symptomatic inoperable plexiform neurofibromas.

INTRODUCTION: Selumetinib is a MEK inhibitor, which is effective with an acceptable safety profile in reducing the volume of symptomatic inoperable plexiform neurofibromas in some clinical trials and also has been recently approved by FDA for use in children aged 2 years or older. However, no systematic review has yet been performed to provide a collective estimate of the results of all these trials. EVIDENCE ACQUISITION: Articles describing the use of selumetinib in patients with neurofibromatosis type-1 (NF1) with inoperable plexiform neurofibromas were searched from different electronic databases. The objectives were to provide a pooled estimate of efficacy evaluated by direct measurement and also by various functional measures, as well as the proportion of patients with adverse events. For determining pooled estimates, we included only studies with a minimum sample size of 15 with a prospective study design. EVIDENCE SYNTHESIS: A total of eight articles with 137 patients were found and 134 patients in six uncontrolled trials were included in the quantitative review. Out of these 26 were adults (69% male; 33.2±18.4 years, range 18-60 years) and 108 were in the pediatric age group (74% boys, 10.9±2.3 years, range-2-18 years,). Total 77.86% (95% CI: 55.91-99.81%) patients had a partial response, 71.24% (95% CI: 53.62-89.93%) had a confirmed partial response, and 56.25% (95% CI: 37.53-72.49%) had a durable partial response. The average time to initial response was 7.3±2.9 cycles (range, 4 to 20), and the median time to best response was 15.4±5.8 cycles (range, 4 to 36). The average change in neurofibroma volume at best response was -28.15% (95% CI: -17.95%, -38.34%, range, -55.1% to 2.2%). Progression-free survival was observed in 93.12% of patients at the time of data cut-off. Overall, 73.26% (95% CI: 54.07%, 92.45%) patients had improvement in at least one of the functional or patient-reported outcome assessments. The most common adverse effects were grade 1 and 2 gastrointestinal symptoms (65%), an asymptomatic increase in the creatine phosphokinase level (31%), paronychia (6%), and acneiform rash (17%). A total of 17% patients required dose reduction due to these toxic effects and 10.5% (95% CI: 4.0%, 17.0%) of patients discontinued due to toxic effects. CONCLUSIONS: Selumetinib can produce sustained shrinkage in the majority of patients with NF1 and symptomatic plexiform neurofibroma to provide clinically meaningful benefit in functional ability, with more robust evidence in children. The acceptable safety profile and absence of cumulative toxic effects permit long-term treatment with selumetinib.

Hereditary Sensory and Autonomic Neuropathy: A Case Series of Six Children.

Objectives: Hereditary sensory and autonomic neuropathy (HSAN) is a group of rare disorders affecting the sensory and autonomic neurons. Herein, we describe the clinical and genetic profile of six children with HSAN. Methods: Hospital records of six children diagnosed with HSAN over 7 years (2011-2018) were retrieved. Clinical features, electrophysiological studies, and genetic reports were collected from the case files. Results: The presenting clinical features in these six cases were developmental delay, recurrent febrile episodes, rhinitis, recurrent nonhealing ulcers, burns, self-mutilations, chronic osteomyelitis, and corneal ulcers. Electrophysiology studies showed predominant sensory axonal neuropathy. Autonomic features noted were recurrent fever, constipation, abdominal distension, hypertension, and vasomotor rhinitis. Genetic testing was done with next-generation sequencing in all six children. Causative genetic variants were identified in the NTRK1, PRDM12, DST gene, and a novel compound heterozygous variant in the FLVCR1 gene. The diagnosis of HSAN was delayed in most of our children due to variable presentation and lack of awareness among the treating paediatricians. Conclusions: Although the clinical presentation of HASN is highly variable, it is dominated by pain and temperature insensitivity and self-mutilation. Our report of six children with HSAN expands the existing knowledge on phenotype and genotype spectrum of HSAN.

Spastic Paraplegia-56 due to a Novel CYP2U1 Truncating Mutation in an Indian Boy: A New Report and Literature Review.

Spastic paraplegia-56 is a rare autosomal recessive disorder, caused by homozygous or compound heterozygous mutations in the CYP2U1 gene, located on chromosome 4. Till date, only 28 patients with this disorder have been reported in the literature. We report a new case of CYP2U1-related spastic paraplegia-56. We also reviewed previously published patients with this condition from various databases. Next-generation sequencing in the index child detected a novel homozygous two base pair deletion in exon 2 of the CYP2U1 gene that results in a frameshift and premature truncation of the protein 19 amino-acid downstream to codon 361. Together with the presented case, 29 were available for analysis. The mean age at the diagnosis was 17.84 ± 6.86 years. Intellectual disability/cognitive dysfunction and delayed walking or gait disturbance were the most common presenting features. Around half of the patients had neuroregression in between 1 and 2 years. It is clinically imperative to suspect this disease in children with early-onset spastic paraparesis, especially in cases accompanied by baseline development delay or cognitive impairment and consanguinity.

Isoniazid induced palmoplantar hyperhidrosis.

Secondary focal hyperhidrosis is usually due to peripheral or central neuronal defects and is a complex dysfunction of the parasympathetic and sympathetic nervous system. Palmoplantar hyperhidrosis has been described with various types of polyneuropathies such as diabetic but has not previously been described with isoniazid. We report a 15-year-old boy, being followed for neurotuberculosis, who presented with burning sensation and hyperhidrosis of both palms and soles five months after starting antitubercular therapy. With oral pyridoxine supplementation, the paraesthesia and hyperhidrosis reduced to minimal severity over the next four months. Before commencing antiperspirants, simple pyridoxine supplementation can lead to the reversal of symptoms in such cases.

Trichotillomania in a child with nephrotic syndrome: An unusual steroid induced psychiatric manifestation.

Steroid-induced psychosis is a known serious adverse effect seen commonly in adults but less commonly in children. We present a seven-year-old girl with steroid-dependent nephrotic syndrome who developed abnormal behaviour, trichotillomania, alopecia and mood changes. She was investigated to rule out other causes and treated with tapering steroids, fluoxetine and olanzapine. A marked improvement was noted after two months. Patients on long term or high dose steroids should be monitored for adverse psychological effects of steroids, as early recognition and intervention can improve the outcome.

The Expanding Spectrum of Dystrophinopathies: HyperCKemia to Manifest Female Carriers.

Background: X-linked dystrophinopathies have a wide spectrum of manifestation. The most common forms are severe Duchenne muscular dystrophy (DMD) and Becker's muscular dystrophy (BMD). However, less common manifestations are isolated cardiomyopathy, myalgia, cramps, rhabdomyolysis, hyperCKemia, and manifest female carriers. Materials and Methods: This case series is a part of an ongoing long-term prospective cohort of children with DMD and BMD from the year 2013. The clinical details are maintained in the clinic files and standard management protocols are followed. For this case series, clinical details were collected from the clinic files and recorded on a case record proforma. Details of cardiology, radiology, and genetic investigations were collected. Results: We report cases of classical DMD, BMD, manifest female carrier with proximal pelvic girdle weakness, a female carrier with isolated dilated cardiomyopathy, and infantile-onset asymptomatic hyperCKemia. We also report less common but notable clinical presentations of DMD, autism, intellectual disability, epilepsy, and asymptomatic transaminitis. Conclusions: It is important for clinicians to be aware of these less common clinical presentations for prompt diagnosis, and to avoid unnecessary investigations. Here, we report the clinical spectrum of dystrophinopathies seen in pediatric neuromuscular clinic and emphasize the variability and expanding knowledge about different manifestations of dystrophinopathies.

Toddler With Frequent Falls and Neuroregression: Imaging Clues!

Late infantile metachromatic leukodystrophy is an autosomal recessive disorder caused by a deficiency in the enzyme activity of Aryl sulfatase-A. The classical presentation is characterized by gait disturbance, frequent fall, toe walking, impaired swallowing and feeding, seizures, progressive neuroregression, decorticate posture and early death. Here we report a toddler who presented with frequent falls and cognitive regression. Magnetic resonance imaging (MRI) showed a striking leopard skin pattern. Recognition of this pattern on MRI in proper clinical context can serve as a clue to the diagnosis.

Primary Hypokalemic Periodic Paralysis: Long-term Management and Complications in a Child.

Hypokalemic periodic paralysis (HPP) is a rare genetically determined neuromuscular disorder caused by mutation in skeletal muscles calcium and sodium channels. It presents with recurrent episodes of flaccid paralysis. A 9-year-old girl presented with recurrent episodic flaccid quadriparesis with complete recovery in-between the episodes. Investigations during the acute episode revealed marked hypokalemia with electrocardiogram changes. Next-generation sequencing showed pathogenic missense mutation in CACNA1S gene. She responded well to oral potassium supplementation, acetazolamide, and spironolactone therapy. Muscle weakness in HPP is reversible, and long-term management reduces frequency of paralysis and prevents permanent weakness.

Bone mineral density and its influencing factors in children with idiopathic nephrotic syndrome: a prospective observational study.

Glucocorticoids are first-line therapy for children with idiopathic nephrotic syndrome (INS). These children are at risk of deranged bone metabolism and low bone mineral density (BMD). We studied 60 children with INS and divided them into two groups. Group 1 included 21 children (initial and infrequent relapsing) and group 2 included 39 children (frequent relapsing, steroid dependent and steroid resistant). Dual-energy X-ray absorptiometry of the lumbar spine was performed to assess BMD. Mean BMD Z-score was compared in both groups; this correlated significantly on univariate analysis with cumulative steroid dose, serum vitamin D levels and calcium supplementation. However, on multivariate analysis, serum vitamin D level was the only factor significantly predictive of low z-score.

Recurrent Streptococcus pneumoniae meningitis and Mondini dysplasia: Association or causation?

Mondini dysplasia is a developmental disorder of the inner ear structures and it is a rare cause of recurrent bacterial meningitis in children. A 10-year-old boy presented with acute febrile encephalopathy and right ear pain. In the past, he had suffered from two distinct episodes of pyogenic meningitis. On examination, he had signs of meningeal irritation and right ear sensorineural deafness. Magnetic resonance imaging of the brain and computerized tomography of the temporal bone was suggestive of Mondini dysplasia in the right ear. Our case highlights the need for (a) screening of hearing loss at the bedside by Rinne and Weber test in case of recurrent bacterial meningitis (b) searching for an underlying inner ear malformation if there is a hearing loss.