Congenital hepatic haemangioma leading to multiple organ failure in a neonate.

We report a case of a premature male newborn who died from multiple organ failure due to a large congenital hepatic haemangioma that was diagnosed by imaging. Congenital haemangioma is a vascular tumour. The liver is the second organ involved after the skin. This tumour can be asymptomatic but can also lead to death.

Predicting the clinical outcome of antenatally detected unilateral pelviureteric junction stenosis.

OBJECTIVE: To determine, in children with antenatally detected pelviureteric junction (PUJ) stenosis, what factors may be predictive for deterioration of differential renal function (DRF) in case of conservative treatment or improvement of DRF in case of pyeloplasty. METHODS: This study analyzed and compared the initial level of hydronephrosis, DRF, quality of renal drainage, and cortical transit with the late DRF outcome. We reviewed the medical charts of 161 consecutive children with antenatally diagnosed PUJ stenosis during a 10-year period (between 1997 and 2007). From this cohort, we retained 81 children with unilateral PUJ and strictly normal contralateral kidney, with a median follow-up of 67 months. Repeated ultrasounds, voiding cystourethrography, and radionuclide renograms were performed in all children. RESULTS: Fifty patients never underwent a surgical intervention (62%), whereas surgical repair (Anderson-Hynes dismembered pyeloplasty) was performed in 31 (38%). During conservative follow-up, DRF deterioration was observed in 11% of patients. After pyeloplasty, DRF improvement was observed in 25% of patients. Abnormal cortical transit was the only predictive factor of DRF deterioration in case of conservative approach, whereas the initial degree of hydronephrosis, or renal drainage, and the initial DRF level were not predictive. In children who were operated on, only impaired cortical transit was predictive of DRF improvement postoperatively. CONCLUSION: Conservative management of children with unilateral PUJ stenosis is a safe procedure. Impaired cortical transit although imperfect, seems the best criterion for identifying children for whom pyeloplasty is warranted.

Nonsyndromic bilateral and unilateral optic nerve aplasia: first familial occurrence and potential implication of CYP26A1 and CYP26C1 genes.

PURPOSE: Optic nerve aplasia (ONA, OMIM 165550) is a very rare unilateral or bilateral condition that leads to blindness in the affected eye, and is usually associated with other ocular abnormalities. Although bilateral ONA often occurs in association with severe congenital anomalies of the brain, nonsyndromic sporadic forms with bilateral ONA have been described. So far, no autosomal-dominant nonsyndromic ONA has been reported. The genetic basis of this condition remains largely unknown, as no developmental genes other than paired box gene 6 (PAX6) are known to be implicated in sporadic bilateral ONA. METHODS: The individuals reported underwent extensive ophthalmological, endocrinological, and neurologic evaluation, including neuroimaging of the visual pathways. In addition genomewide copy number screening was performed. RESULTS: Here we report an autosomal-dominant form of nonsyndromic ONA in a Belgian pedigree, with unilateral microphthalmia and ONA in the second generation (II:1), and bilateral ONA in two sibs of the third generation (III:1; III:2). No PAX6 mutation was found. Genome wide copy number screening revealed a microdeletion of maximal 363 kb of chromosome 10q23.33q23.33 in all affected individuals (II:1, III:1; III:2) and in unaffected I:1, containing three genes: exocyst complex component 6 (EXOC6), cytochrome p450, subfamily XXVIA, polypeptide 1 (CYP26A1), and cytochrome p450, subfamily XXVIC, polypeptide 1 (CYP26C1). The latter two encode retinoic acid-degrading enzymes. CONCLUSIONS: This is the first study reporting an autosomal-dominant form of nonsyndromic ONA. The diagnostic value of neuroimaging in uncovering ONA in microphthalmic patients is demonstrated. Although involvement of other genetic factors cannot be ruled out, our study might point to a role of CYP26A1 and CYP26C1 in the pathogenesis of nonsyndromic ONA.

Characteristics of first urinary tract infection with fever in children: a prospective clinical and imaging study.

BACKGROUND: Our objective is to provide the clinical characteristics, uropathogen frequencies, and antimicrobial resistance rates of first urinary tract infection (UTI) diagnosed in febrile Belgian children. The ability of noninvasive ultrasound to detect renal abnormalities and vesicoureteral reflux (VUR) in these patients was also assessed. METHODS: We prospectively followed (median, 20 months) 209 children treated for first febrile UTI. Renal ultrasound (US) and voiding cystourethrography examinations were performed in all patients. RESULTS: Among these children, 63% were females and 37% were males, and 75% of them had their first UTI before the age of 2 years. The most common causative agent was Escherichia coli (91% of cases) with high rate resistance to ampicillin (58%) and trimethoprim/sulfamethoxazole (38%). Of these children, 25% had evidence of VUR (15 boys and 38 girls). VUR was of low grade in 85% of cases. The overall performance of renal US as a diagnostic test to detect significant uropathies excluding low-grade VUR was excellent; the sensitivity attained 97% and the specificity 94%. CONCLUSION: Girls represent 63% of cases with first UTI. For 91% of UTIs, Escherichia coli is held responsible with a high rate of resistance to ampicillin and trimethoprim/sulfamethoxazole. US is an excellent screening tool that allows avoidance of unjustified voiding cystourethrography studies.

Growth retardation in untreated autosomal dominant familial neurohypophyseal diabetes insipidus caused by one recurring and two novel mutations in the vasopressin-neurophysin II gene.

OBJECTIVE: Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI), a disorder caused by mutations in the vasopressin (AVP)-neurophysin II (NPII) gene, manifests gradually during early childhood with progressive polyuria and polydipsia. Patients are usually treated with synthetic AVP analog. If unlimited access to water is provided, prognosis is usually good even in the absence of specific treatment. In this study, we describe three families with adFNDI, in which growth failure was a prominent complaint, on the clinical and molecular level. DESIGN/METHODS: Histories from affected and unaffected family members were taken. Height and weight of index patients were recorded longitudinally. Patients underwent water deprivation tests, magnetic resonance imaging, and genetic analysis. One mutant was studied by heterologous expression in cell culture. RESULTS: A total of ten affected individuals were studied. In two of the three pedigrees, a novel mutation in the AVP-NPII gene was found. The index children in each pedigree showed growth retardation, which was the reason for referral in two. In these cases, water intake was tightly restricted by the parents in an attempt to overcome suspected psychogenic polydipsia and to improve appetite. Once the children were treated by hormone replacement, they rapidly caught up to normal weight and height. CONCLUSIONS: Genetic testing and appropriate parent counseling should be enforced in adFNDI families to ensure adequate treatment and avoid chronic water deprivation, which causes failure to thrive.

Clinical, hormonal and imaging findings in 27 children with central diabetes insipidus.

UNLABELLED: Clinical, auxological, biological and neuroradiological characteristics of 27 children with central diabetes insipidus (CDI) were retrospectively analysed. Median age at diagnosis was 8.6 years (range: 0.3-16.1 years). Final aetiologies were postsurgical infundibulo-hypophyseal impairment (n=7), cerebral tumour (n=8), Langerhans cell histiocytosis (n=3), septo-optic dysplasia (n=1), ectrodactyly ectodermal dysplasia clefting syndrome (n=1), and idiopathic (n=7). In the non-postsurgical CDI patients, major cumulative and often subtle presenting manifestations were: polyuria (n=20), polydipsia (n=19), fatigue (n=11), nycturia (n=10), growth retardation (n=9), and headache (n=9). An associated antehypophyseal insufficiency, mainly somatotropic, was documented in 11 children. All patients except one who initially had a cerebral tomography, underwent magnetic resonance imaging revealing the lack of the physiological posterior pituitary hyperintense signal. One third of the idiopathic patients initially had a thickened pituitary stalk. All patients with idiopathic CDI were intensively followed up with 3-monthly physical examination, antehypophyseal evaluation, search for tumour markers, and cerebral MRI every 6 months. In one of them the pituitary stalk had normalized after 4.3 years. In one patient Langerhans cell histiocytosis was diagnosed after 7 months of follow-up, and in another patient a malignant teratoma was found after 2.4 years of follow-up. CONCLUSION: CDI may be the early sign of an evolving cerebral process. The association of polyuria-polydipsia should incite a complete endocrine evaluation and a meticulous MRI evaluation of the hypothalamo-hypophyseal region. A rigorous clinical and neuroradiologic follow-up is mandatory to rule out an evolving cerebral process and to detect associated antehypophyseal insufficiencies.

Reversible acute methotrexate leukoencephalopathy: atypical brain MR imaging features.

BACKGROUND: Unusual acute symptomatic and reversible early-delayed leukoencephalopathy has been reported to be induced by methotrexate (MTX). OBJECTIVE: We aimed to identify the occurrence of such atypical MTX neurotoxicity in children and document its MR presentation. MATERIALS AND METHODS: We retrospectively reviewed the clinical findings and brain MRI obtained in 90 children treated with MTX for acute lymphoblastic leukaemia or non-B malignant non-Hodgkin lymphoma. All 90 patients had normal brain imaging before treatment. In these patients, brain imaging was performed after treatment completion and/or relapse and/or occurrence of neurological symptoms. RESULTS: Of the 90 patients, 15 (16.7%) showed signs of MTX neurotoxicity on brain MRI, 9 (10%) were asymptomatic, and 6 (6.7%) showed signs of acute leukoencephalopathy. On the routine brain MRI performed at the end of treatment, all asymptomatic patients had classical MR findings of reversible MTX neurotoxicity, such as abnormal high-intensity areas localized in the deep periventricular white matter on T2-weighted images. In contrast, the six symptomatic patients had atypical brain MRI characterized by T2 high-intensity areas in the supratentorial cortex and subcortical white matter (n=6), cerebellar cortex and white matter (n=4), deep periventricular white matter (n=2) and thalamus (n=1). MR normalization occurred later than clinical recovery in these six patients. CONCLUSIONS: In addition to mostly asymptomatic classical MTX neurotoxicity, MTX may induce severe but reversible unusual leukoencephalopathy. It is important to recognize this clinicoradiological presentation in the differential diagnosis of acute neurological deterioration in children treated with MTX.

Postinfectious immune-mediated encephalitis after pediatric herpes simplex encephalitis.

We report a 3-year-old patient who presented a secondary acute neurological deterioration clinically characterized by a partial Kluver-Bucy syndrome, 1 month after the onset of herpes simplex encephalitis. This episode is unlikely due to continuation or resumption of cerebral viral replication but might be related to an immune-inflammatory process. In children, postinfectious immune-mediated encephalitis occurring after HSE are usually clinically characterized by choreoathetoid movements. This type of movement disorder was, however, not observed in this patient. On the basis of this case and a review of the literature, we hypothesize the existence of a spectrum of secondary immune-mediated process triggered by herpes simplex virus cerebral infection ranging from asymptomatic cases with diffuse white matter involvement to secondary acute neurological deteriorations with or without extrapyramidal features.

Complications of lumbar puncture in a child treated for leukaemia.

Lumbar puncture may lead to neurological complications. These include intracranial hypotension, cervical epidural haematomas, and cranial and lumbar subdural haematomas. MRI is the modality of choice to diagnose these complications. This report documents MRI findings of such complications in a child treated for leukaemia.

Comparison of gadobenate dimeglumine (Gd-BOPTA) with gadopentetate dimeglumine (Gd-DTPA) for enhanced MR imaging of brain and spine tumours in children.

BACKGROUND: Gadobenate dimeglumine (Gd-BOPTA) demonstrates superior enhancement of brain tumours in adult patients than Gd-DTPA. OBJECTIVE: To determine whether Gd-BOPTA has advantages over Gd-DTPA for enhanced MR imaging of paediatric brain and spine tumours. MATERIALS AND METHODS: Sixty-three subjects, aged 6 months to 16 years, who were enrolled in a prospective, fully blinded, randomized parallel-group phase III clinical trial, received 0.1 mmol/kg doses of either Gd-BOPTA (n=29) or Gd-DTPA (n=34). The MR images were acquired before and within 10 min of contrast agent injection. The primary objective was to compare the difference from pre-dose to post-dose lesion visualization between Gd-BOPTA and Gd-DTPA. Lesion visualization was determined as the sum of individual scores for three criteria of lesion morphological characteristics (lesion border delineation, internal morphology, and contrast enhancement), each assessed qualitatively using 4-point scales. Quantitative evaluation compared changes in lesion-to-background (LBR) and contrast-to-noise (CNR) ratios and per cent enhancement. Monitoring for adverse events and evaluation of vital signs and laboratory values was performed. RESULTS: Pre-dose to post-dose changes in lesion visualization were significantly better for Gd-BOPTA for both lesion level (2.68+/-2.17 vs. 1.05+/-1.90, P=0.0106) and patient level (2.55+/-2.18 vs. 1.14+/-1.68, P=0.0079) comparisons. The mean pre-dose to post-dose change in CNR was greater for Gd-BOPTA (9.13+/-15.36) than Gd-DTPA (2.18+/-9.90), but the difference was only marginally significant (P=0.0779; 95% CI: -0.553, 14.454) because of wide variations of signal intensity between lesions. Similar findings were obtained for LBR and per cent enhancement. No differences between the agents were noted in terms of safety parameters. CONCLUSIONS: At an equivalent dose Gd-BOPTA is significantly better than Gd-DTPA for visualization of enhancing CNS tumours in paediatric patients.

Hydroxyurea for sickle cell disease in children and for prevention of cerebrovascular events: the Belgian experience.

Hydroxyurea (HU) is considered to be the most successful drug therapy for severe sickle cell disease (SCD). Nevertheless, questions remain regarding its benefits in very young children and its role in the prevention of cerebrovascular events. There were 127 SCD patients treated with no attempt to reach maximal tolerated doses who entered the Belgian Registry: 109 for standard criteria and 18 who were at risk of stroke only. During 426 patient-years of follow-up for patients with standard criteria, 3.3 acute chest syndromes, 1.3 cerebrovascular events, and 1.1 osteonecrosis per 100 patient-years were observed. A subgroup of 32 patients followed for 6 years experienced significant benefit over this period. In each subgroup of children (younger than 2 years, 2-5, 6-9, and 10-19 years) followed for 2 years, clinical and biologic changes were similar, except for children younger than 2 years who had no total hemoglobin increase and remained at risk of severe anemia. In 72 patients evaluated by transcranial Doppler studies (TCD), 34 patients were at risk of primary stroke and only 1 had a cerebrovascular event after a follow-up of 96 patient-years. These results confirm the benefit of HU, even in very young children, and its possible role in primary stroke prevention.

Gait control in spinal palsy.

Developmental motor impairment with lower limb spasticity most commonly corresponds to cerebral palsy of the spastic diplegia type. Here we describe a 4-year-old girl whose locomotor phenotype reflects early cortico-spinal lesion at the spinal level. This child has developmental spastic paraparesis secondary to D4-D8 cord compression. We analysed her gait using the ELITE optoelectronic system and compared it to that of six normal age-matched controls and six age-matched children with leucomalacic spastic diplegia. Gait characteristics of the patient included preservation of head orientation and arm swing similar to findings in normal controls and contrasting with children with spastic diplegia. She also had truncal instability and displayed lack of selectivity in lower limb movement as in spastic diplegia and in contrast with normal controls. This may reflect differences in locomotor control between developmental spasticity of cerebral and spinal origin. The latter might correspond to spinal palsy defined as abnormal movement and posture secondary to non-progressive pathological processes affecting the immature spinal cord.

Cervical myelitis from herpes simplex virus type 1.

Although subacute ascending paralysis without sensory involvement is typically evocative of Guillain-Barré syndrome, it can alternatively be due to infection or inflammation of the spinal cord. We describe a 16-month-old female who presented with ascending flaccid paresis after an upper respiratory tract infection. She then developed signs of upper motor neuron involvement of the lower limbs associated with upper motor neuron involvement of the upper limbs. Motor nerve conduction and electromyographic studies of upper limbs demonstrated anterior horn cell involvement. Neuroimaging was consistent with cervical myelitis, and cerebrospinal fluid polymerase chain reaction was positive for herpesvirus-1. Although association with the primary infection of the respiratory tract may be fortuitous, possible neurotropic or hematogenous spread of herpesvirus-1 to the cervical spinal cord cannot be excluded. She then developed signs of upper motor neuron involvement of the lower limbs associatred with lower motor neuron involvement of the upper limbs [corrected].

Predictive value of electrophysiology in children with hypoxic coma.

Assessment of prognosis of children in hypoxic coma is difficult. The value of clinical evaluation is often limited. The usefulness of electrophysiologic tests has been documented mostly in adults and neonates and in cases of traumatic coma. We reviewed retrospectively 39 consecutive children with nontraumatic hypoxic coma to assess the prognostic value of EEG, visual, and auditory evoked potentials. Correlation between electrophysiology and neurologic outcome after mean follow-up period of 30 months was significant (r(s) = 0.6, P < 0.001). In contrast there was no correlation between Pediatric Risk of Mortality score (PRISM) and outcome (r(s) = -0.42, P = 0.8). Combining magnetic resonance imaging with electrophysiology further enhanced their prognostic value (r(s) = 0.69, P < 0.001). Neuroimaging was highly sensitive but less specific, and electrophysiologic tests were highly specific but less sensitive. We conclude that early electrophysiology can contribute to predicting outcome in pediatric hypoxic coma.

Nonsurgical cerebellar mutism (anarthria) in two children.

Cerebellar mutism (anarthria) is a well-described complication of posterior fossa tumor resection. It is accompanied by a characteristic behavior including irritability and autistic features. This syndrome is typically reversible within days to months. Underlying pathophysiology is unknown. We describe two children who presented with a similar clinical finding after nonsurgical cerebellar involvement, hemolytic-uremic syndrome in one and cerebellitis in the other. Postmortem pathologic findings in the first patient indicated cerebellar ischemic necrosis. Single-photon emission computed tomography in the second patient revealed diffuse cerebellar hypoperfusion with no supratentorial abnormalities, refuting a phenomenon of diaschisis between cerebellar and frontal connections. These findings confirm that this clinical syndrome may occur in a nonsurgical, nontraumatic context. They are consistent with recent integrative hypotheses explaining cerebellar anarthria.

Unilateral cortical necrosis following status epilepticus with hypoglycemia.

Isolated status epilepticus or severe hypoglycemia rarely causes irreversible focal neurologic deficits in children. We describe three children who presented with status epilepticus and prolonged hypoglycemia resulting in hemiplegia due to unilateral hemispheric damage. The non-vascular cortical topography of the lesions is consistent with selective neuronal necrosis, confirmed by histopathology in one patient. This suggests increased neuronal vulnerability to necrosis secondary to energy failure resulting from combination of hypoglycemia and status epilepticus.