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.

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.

[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.

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.

Inflammatory cytokines in the pathogenesis of periventricular leukomalacia.

BACKGROUND: Periventricular leukomalacia (PVL) affects the developing white matter of neonatal brain. Inflammatory and infectious conditions are implicated in the cause of PVL. METHODS: The authors investigated the in situ expression of proinflammatory cytokines (interleukin-1beta and -6, tumor necrosis factor alpha [TNFalpha]), adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1) and inflammatory cell markers (CD68, leukocyte common antigen, human leukocyte antigen II) in 19 neonatal brains with PVL. The authors compared the findings with matched non-PVL brains. RESULTS: The inflammatory reaction detected at the early stage of PVL extends until the latest phase of cystic cavitation, though at an attenuated level. There is high expression of TNFalpha and to a lesser extent interleukin-1beta; interleukin-6 remains undetectable. Cytokine immunoreactivity is detected in PVL cases both with and without infection. However, cytokine production was higher with infection. A different pattern of cytokine expression was observed in anoxic brains without PVL: TNFalpha immunoreactivity was significantly lower than the PVL group. CONCLUSIONS: An immune-mediated inflammatory process may play a role in PVL. TNFalpha, a myelinotoxic factor, may be the major mediator.

Childhood dermatomyositis: clinical course of 36 patients treated with low doses of corticosteroids.

Thirty-six patients with juvenile dermatomyositis, seen consecutively between 1983 and 1996 and treated initially with low doses of corticosteroids (prednisolone 1 mg/kg/day), were studied retrospectively to evaluate their long-term evolution and to identify factors predictive of the functional outcome. After a mean follow-up of 4.9 years, 28 (78%) of the patients were well without functional impairment; five patients had inactive disease but with persisting disabilities; and three patients had active disease despite several years of treatment. Fifteen children (42%) developed dystrophic calcifications which, in five of these patients, interfered with functions. These patients treated for juvenile dermatomyositis with a low dose corticosteroid regimen had an evolution identical to that of the published series of patients treated with higher doses and probably had a better quality of life. The best predictors of good functional recovery and minimal calcinosis were early treatment after the onset of symptoms and low creatine kinase serum level at the time of diagnosis.

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.

Infantile status epilepticus in Tunisia. Clinical, etiological and prognostic aspects.

This retrospective study includes 139 infants (74 girls and 65 boys) treated for status epilepticus at two University hospitals in Tunisia between 1990 and 1997. Their mean age was 11 months. The majority of seizures were generalized (74%) and lasted between 30 minutes and 1 hour (70%). The cause of status epilepticus was classified as acute symptomatic in 56, febrile in 57, remote symptomatic in nine, progressive neurologic in 10 and idiopathic in seven. Overall mortality was 15.8% and neurological sequelae were identified in 36% of the cases during the mean follow-up time of 3.5 years. The incidence of significant sequelae was a function of aetiology (especially acute symptomatic causes) and age (under 1 year of age). We conclude that the most frequent causes of infantile status epilepticus in Tunisia were fever and acute symptomatic causes. Status epilepticus among infants is an important public health problem, with significant associated mortality and morbidity. Management of status epilepticus can be improved by more rapid access to appropriate medical care.

[Central pontine myelinolysis: apropos of 2 case in children]. / Myélinolyse centropontine: à propos de deux observations chez l'enfant.

BACKGROUND: Central pontine myelinolysis has been rarely reported in children. This report concerns two children, aged 4 1/2 years. CASE REPORTS: The main clinical features were altered level of consciousness, tetraplegia and signs of brain stem dysfunctions. In both cases, magnetic resonance imaging (MRI) revealed hypersignal of protuberance in association with cerebellar lesion in one case and occipital lesion in the other, compatible with central and extrapontine myelinolysis. No underlying disease or electrolytic disorders was identified. Clinical outcome was good. Mental status was normal after 9 months for patient one and 4 months for patient two. The MRI abnormality was reduced at 9-month follow-up in patient two and unchanged at 4 months in patient one. CONCLUSION: The incidence of central pontine myelinolysis is probably underestimated in children. MRI allows a greater sensitivity in identifying areas of focal demyelination where diagnosis was previously only established by post mortem studies.

[Acute rhabdomyolysis disclosing polymyositis in children]. / Rhabdomyolyse aiguë révélatrice d'une polymyosite chez l'enfant.

UNLABELLED: Traumatic and non-traumatic rhabdomyolysis have been mostly reported in adults. Polymyositis rarely leads to rhabdomyolysis. CASE REPORT: We report the case of a 13-year-old girl with rhabdomyolysis. Full recovery was observed after symptomatic treatment. Nine months later she developed polymyositis. CONCLUSION: Long-term follow-up is necessary for rhabdomyolysis, even in those cases with an isolated occurrence caused by viral infection.

[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.

[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.

[Ischemic cerebral vascular accident caused by vertebral artery dissection]. / Accident vasculaire cérébral ischémique par dissection artérielle vertébrale.

BACKGROUND: Strokes due to vertebral artery lesions are not yet well known in children. CASE REPORT: We report on a case of post-traumatic vertebral artery dissection responsible for ischemic stroke in a 8-year old boy. Headache, vomiting and a brief loss of consciousness were the main initial signs. Neurological examination showed a locked-in syndrome. Cerebral imaging revealed lesions in cortical cerebellar hemisphere, cerebral pedoncular and protuberance. An arteriogram performed on day 10 showed left vertebral artery occlusion at C2 levels consistent with vertebral dissection. Antiagregants treatment was given. Neurological recovery was good. Pertinent clinical data of 24 children who had strokes due to a vertebral artery dissection are analysed. CONCLUSION: Vertebral artery dissection is presently a well-known cause of childhood strokes. Benefits from anticoagulants are now established.

[Syndrome of inappropriate macrophage activation associated with infantile visceral leishmaniasis]. / Syndrome d'activation inapropriee des macrophages associe à une leishmaniose viscerale infantile.

Hemophagocytosis has already been in cases of visceral leishmaniasis and thus may complicate search for diagnosis. We report a case of hemophagocytosis in a 20 month-old boy presenting with fever, hepatosplenomegaly, pancytopenia and coagulopathy. An initial diagnosis of kala-azar was refuted because of absence of biological inflammatory syndrome and negativity of bone-marrow aspiration. Specific serology for visceral leishmaniasis become positive. The boy was given stibogluconate for 21 days; he improves gradually with complete remission.

[Guillain-Barre syndrome in children. Report of 39 cases]. / Syndrome de Guillain-Barré chez l'enfant. Etude de 39 observations.

The authors report a retrospective study of 39 cases of Guillain-Barré syndrome in children. Including 23 boys and 16 girls. The mean age was 4 years (14 months to 10 years). A history of infection preceded the polyradiculoneuritis in 75% of cases. The mean duration of extensive phase and of the maximum paralysis was 10 days. A severe respiratory involvement was observed in 9 children and cranial nerve paralysis in 8 children. An early raised cerebrospinal fluid protein concentration was found in 95%. Electrodiagnostic studies, performed in 37 patients, showed nerve conduction velocity slowing in all cases. 28 children (73%) recovered clinically, 8 patients (20%) had residual deficits and 3 patients (7%) died.

[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.