Therapeutic hypothermia in children: Which indications remain in 2018?

Experimental studies on therapeutic hypothermia in acute brain injury reported positive outcomes and identified two potential benefits, namely, reduction in seizure incidence and in intracranial pressure. Translating this evidence to humans is challenging, especially for conditions in pediatric patients, such as cardiac arrest, traumatic brain injury, and status epilepticus, among others. This narrative review aimed to discuss the current indications and benefits of therapeutic hypothermia in acute brain injury in the pediatric population (i.e., beyond the neonatal period) by analyzing the neurologic outcome and mortality data obtained from previous studies.

PPP1R21 homozygous null variants associated with developmental delay, muscle weakness, distinctive facial features, and brain abnormalities.

We present 3 children with homozygous null variants in the PPP1R21 gene. A 3-year-old girl had profound developmental delay, hypotonia and weakness, poor feeding, recurrent chest infections and respiratory failure, rotatory nystagmus, absent reflexes, and a homozygous nonsense variant c.2089C>T (p.Arg697*). A 2-year-old boy had profound developmental delay, weakness and hypotonia, recurrent chest infections and respiratory distress, undescended testes, rotatory nystagmus, hyporeflexia, and a homozygous nonsense variant c.427C>T (p.Arg143*). An 11-year-old girl with profound developmental delay, weakness and hypotonia, stereotypic movements, growth failure, hyporeflexia, and a homozygous frameshift variant c.87_88delAG (p.Gly30Cysfs*4). In addition, these children shared common facial features (thick eyebrows, hypertelorism, broad nasal bridge, short nose with upturned nasal tip and broad low-hanging columella, thick lips, low-set ears, and coarse facies with excessive facial hair), and brain abnormalities (cerebellar vermis hypoplasia, ventricular dilatation, and reduced white matter volume). Although PPP1R21 has not yet been linked to human disease, the consistency in the phenotype of individuals from unrelated families, the nature of the variants which result in truncated proteins, and the expected vital role for PPP1R21 in cellular function, all support that PPP1R21 is a novel disease-associated gene responsible for the phenotype observed in these individuals.

[Management of peripheral facial nerve palsy in children]. / Prise en charge de la paralysie faciale périphérique chez l'enfant.

Peripheral facial nerve palsy may (secondary) or may not have a detectable cause (idiopathic facial palsy or Bell's palsy). Idiopathic facial palsy is the common form of facial palsy. It remains diagnosis by exclusion. The prognosis is more favourable in children than in adults. We present current diagnostic procedures and recommendations regarding treatment in children.

[Vitamin-responsive epilepsies: an update]. / Épilepsies vitamino-sensibles.

Inborn error of metabolism may produce a complex clinical picture in which epilepsy is only one of the various neurologic manifestations including developmental delay/regression, mental retardation, and movement disorders. However, metabolic epilepsies may dominate the clinical presentation. A specific diagnosis of metabolic disorders in epileptic patients may provide the possibility of specific treatments that can improve seizures. In a few metabolic diseases such as vitamin-responsive epilepsies, epilepsy responds to specific treatments based on supplementation of cofactors. Certain rare vitamin-responsive inborn errors of metabolism may present as early encephalopathy with anticonvulsant-resistant seizures. These include pyridoxine-dependent seizures, pyridoxal-phosphate-dependent seizures, folinic acid-responsive seizures, and biotinidase deficiency. This review discusses our current understanding of these vitamin-responsive epilepsies.

[Steroid therapy for hydrocephalus due to acute cerebellitis in a child]. / Cérébellite aiguë sévère compliquée d'une compression du tronc cérébral et d'hydrocéphalie d'évolution favorable sous corticothérapie.

Severe acute inflammatory cerebellitis is a rare but life threatening disease. We report the case of a 8-year-old boy presenting with cerebellitis and acute cerebellar swelling complicated by brain stem compression and hydrocephalus. Outcome was good on steroid therapy.

[Pneumococcal meningitis mortality in children. Prognostic factors in a series of 73 cases]. / Mortalité par méningites à pneumocoque chez l'enfant. Facteurs pronostiques à propos d'une série de 73 observations.

OBJECTIVE: Despite advances in antibiotic therapy strategies and pediatric intensive care, prognosis of Streptococcus pneumoniae meningitis remains very poor. To determine the factors associated with hospital mortality of children with pneumococcal meningitis. METHODS: We conducted a retrospective study of 73 cases of childhood pneumococcal meningitis admitted in 4 teaching hospitals in the center of Tunisia during a 8-year period (1995-2002). RESULTS: Hospital mortality was 13.7% (10 of 71 patients), and neurologic sequela were observed in 34.5% of survivors. Based on univariable analysis, five variables were associated with the outcome: Pediatric Risk of Mortality score (p < 0.001), coma (p=0.0009), use of mechanical ventilation (p=0.0001), convulsions (p = 0.0449), and shock (p=0.0085). In multivariable analysis, only 2 factors were independently associated with in-hospital mortality: Pediatric Risk of Mortality score and the use of mechanical ventilation. 11.8% of pneumococcal isolates were intermediate and resistant to penicillin. Non-susceptible pneumococcus strains to penicillin and the use of steroids were not associated significantly with the mortality rate. CONCLUSIONS: Pneumococcal meningitis remains a devastating childhood disease. Two variables were independently associated with the in-hospital death in our series (high Pediatric Risk of Mortality score, and the use of mechanical ventilation). According to these data we may recommend the inclusion of vaccination against streptococcus pneumonia in the children's immunization program in Tunisia.

Cerebral venous sinus thrombosis in children: risk factors, presentation, diagnosis and outcome.

Neuroimaging and management advances require review of indications for excluding cerebral venous sinus (sinovenous) thrombosis (CSVT) in children. Our goals were to examine (i) clinical presentations of CSVT, (ii) prothrombotic risk factors and other predisposing events, (iii) clinical and radiological features of brain lesions in CSVT compared with arterial stroke, and (iv) predictors of outcome. We studied 42 children with CSVT from five European paediatric neurology stroke registries. Patients aged from 3 weeks to 13 (median 5.75) years (27 boys; 64%) presented with lethargy, anorexia, headache, vomiting, seizures, focal signs or coma and with CSVT on neuroimaging. Seventeen had prior chronic conditions; of the 25 previously well patients, 23 had recent infections, eight became dehydrated and six had both. Two children had a history compatible with prior CSVT. Anaemia and/or microcytosis (21 probable iron deficiency, five haemolytic, including two with sickle cell disease and one with beta-thalassaemia) was as common (62%) as prothrombotic disorder (13/21 screened). High factor VIII and homozygosity for the thermolabile methylene tetrahydrofolate reductase polymorphism were the commonest prothrombotic disorders. The superficial venous system was involved in 32 patients, the deep in six, and both in four. Data on the 13 children with bland infarction and the 12 with haemorrhage in the context of CSVT were compared with those from 88 children with ischaemic (AIS) and 24 with haemorrhagic (AHS) arterial stroke. In multiple logistic regression, iron deficiency, parietal infarction and lack of caudate involvement independently predicted CSVT rather than arterial disease. Five patients died, three acutely, one after recurrence and one after 6 months being quadriparetic and blind. Follow-up ranged from 0.5 to 10 (median 1) years. Twenty-six patients (62%) had sequelae: pseudotumour cerebri in 12 and cognitive and/or behavioural disabilities in 14, associated with epilepsy in three, hemiparesis in two and visual problems in two. Eighteen patients, including six with haemorrhage, were anticoagulated. Older age [odds ratio (OR) 1.54, 95% confidence limits (CI) 1.12, 2.13, P = 0.008], lack of parenchymal abnormality (OR 0.17, 95% CI 0.02, 1.56, P = 0.1), anticoagulation (OR 24.2, 95% CI 1.96, 299) and lateral and/or sigmoid sinus involvement (OR 16.2, 95% CI 1.62, 161, P = 0.02) were independent predictors of good cognitive outcome, although the last predicted pseudotumour cerebri. Death was associated with coma at presentation. Of 19 patients with follow-up magnetic resonance (MR) venography, three had persistent occlusion, associated with anaemia and longer prodrome. A low threshold for CT or MR venography in children with acute neurological symptoms is essential. Nutritional deficiencies may be modifiable risk factors. A paediatric anticoagulation trial may be required, after the natural history has been further established from registries of cases with and without treatment.

[Ischemic colitis and hemophagocytosis complicating Kawasaki disease]. / Colite ischémique et syndrome d'hémophagocytose compliquant une maladie de Kawasaki.

UNLABELLED: Gastrointestinal manifestations of Kawasaki disease are usually limited to stomatitis, paralytic ileus, and hydrops of the gallbladder. We report a case of Kawasaki disease complicated with hemophagocytosis and ischemic colitis. CASE REPORT: A 5-year-old girl with Kawasaki disease presented with hemophagocytosis that responded to gamma-globulin therapy. On day 4 she had abdominal pain and diarrhea. CT scan showed features suggesting ischemic colitis. Symptoms resolved on total parenteral nutrition. CONCLUSION: Ischemic colitis and hemophagocytosis are potential severe complications of Kawasaki disease.

Genetic heterogeneity of megalencephalic leukoencephalopathy and subcortical cysts.

Reported are the clinical, neuroradiologic, and molecular findings in 18 patients with megalencephalic leukoencephalopathy and subcortical cysts (MLC) syndrome. Marked clinical intrafamilial and interfamilial variability in mutation-proven cases was found. A broad spectrum of pathogenetic mutations (missense, splice site, insertion, and deletions) were identified in the MLC1 gene, enlarging the spectrum of allelic variants without a straightforward genotype-phenotype correlation. Five patients did not harbor mutations in MLC1, supporting the existence of at least one other MLC locus.

[Familial hypertrophic cardiomyopathy associated with Wolff-Parkinson-White syndrome]. / Cardiomyopathie hypertrophique familiale associée à un syndrome de Wolff-Parkinson-White.

Familial hypertrophic cardiomyopathy (HCM) with Wolff-Parkinson-White (WPW) syndrome is extremely rare and associated with a high risk of ventricular tachyarrhythmia and sudden death. We report a familial form of hypertrophic cardiomyopathy associated with Wolff-Parkinson-White syndrome in two siblings 7 and 12-year-old. These patients showed progression to left ventricular dilatation. Early recognition and treatment of such forms can improve such evolution and the risk of sudden death.

[Familial hypertrophic cardiomyopathy associated with Wolff-Parkinson-White syndrome revealing type II glycogenosis]. / Myocardiopathie hypertrophique familiale associée à un syndrome de Wolf-Parkinson-White révélant une glycogénose type II.

UNLABELLED: Symptoms of the late infantile form of type II glycogen storage disease are mainly due to functional impairment of skeletal muscle. Cardiac muscle can be involved in the late stage of the disease. CASE REPORT: We report the cases of two siblings seven and 12 years old with type II glycogen storage disease. The initial symptoms were hypertrophic cardiomyopathy with Wolf-Parkinson-White syndrome. CONCLUSION: Hypertrophic cardiomyopathy may be the form of presentation of the late infantile form of type II glycogen storage disease. The risk of sudden death is high.

Interleukin-2 in the pathogenesis of perinatal white matter damage.

Proinflammatory cytokines were reported to be implicated in the pathogenesis of perinatal white matter lesions. The authors document for the first time the in situ detection of interleukin-2 and interleukin-2 receptor (IL-2R) in these human white matter lesions. These results suggest that interleukin-2, reported to be toxic to oligodendrocytes and myelin, could play a role in the molecular cascade leading to white matter damage in periventricular leukomalacia.

Critical illness neuromuscular disease: clinical, electrophysiological, and prognostic aspects.

BACKGROUND: Critical illness neuromuscular disease, which has been recognised as a distinct clinical entity in adults, remains poorly described in children. AIMS: To assess retrospectively the clinical, electrophysiological, and prognostic features of the disease. METHODS: Retrospective study in a children's university hospital. RESULTS: Five critically ill patients presented with generalised paralysis, associated with long lasting failure to breathe in three. The cause of the generalised paralysis was critical illness neuropathy in two, acute myopathy in two, and mixed neuromyopathy in one. CONCLUSIONS: Neuromuscular disease should be suspected in critically ill children with muscle weakness. Because corticosteroids and muscle relaxants appear to trigger some types of intensive care unit neuromuscular disease in children, their use should be restricted or administered at the lowest doses possible.

Primary antiphospholipid syndrome presenting as complicated Henoch-Schönlein purpura.

A child showing signs of Henoch-Schönlein purpura developed a right tibiofibular vascular thrombosis. Antiphospholipid antibody tests were positive for both lupus anticoagulant and anticardiolipin antibodies. This suggests that an antiphospholipid syndrome should be considered in cases of Henoch-Schönlein purpura and antiphospholipid antibodies should be measured to determine whether prophylactic antithrombotic measures are needed to prevent thrombotic manifestations.

Kawasaki disease with predominant central nervous system involvement.

A 4-year-old female was hospitalized with clinical and electroencephalographic evidence of acute encephalopathy. Five days later the classic signs of Kawasaki disease appeared. The neurologic outcome in this female was poor despite early treatment with immunoglobulin. Like many other vasculitidies, Kawasaki disease can have predominant neurologic symptoms as the initial presentation and during the subsequent evolution of the condition.