Segmental facial infantile haemangiomas in the era of propranolol: evaluation at 6 years of age.

BACKGROUND: The long-term evolution of children with segmental facial infantile haemangioma (SFIH) treated with propranolol remains unstudied. OBJECTIVES: The objective of this study was to evaluate the neurodevelopmental features of children with SFIH treated with propranolol at 6 years of age. METHODS: This retrospective case series study was conducted from January 2008 to June 2020 using data from medical files, patient examinations and appointments spanning 6 years. To be included, patients should present SFIH and have previously received propranolol. A complete physical examination, magnetic resonance imaging (MRI) of the head, echocardiography and ophthalmologic examination should have been performed. Neurodevelopmental features were divided into cognition, audition, vision, orality, motor skills and the occurrence of new symptoms. RESULTS: Thirty children with SFIH were included. Of these, 11 presented criteria of PHACES. Evaluation of neurodevelopmental features of the children at 6 years of age showed learning difficulties in one case but grade skipping in three cases. There were six cases of unilateral hearing loss that had not been diagnosed at birth, two of oral difficulties and one of minor hypotonia. Early headache was primarily reported as the main new outcome. All children were treated with propranolol, with three following oral steroid therapy. No severe adverse effects were reported. The median length of treatment with propranolol was 16 months, and the median age at treatment cessation was 21 months. Analysis based on segment implication showed the median length of treatment to vary from 12 months (if S3 was spared) to 25 months (if at least S3 was involved). Vascular laser therapy was used in 16 patients (53.3%) and surgery in four. CONCLUSION: In this case series, children with SFIH, including patients with PHACES criteria, presented a good tolerance of propranolol, as well as encouraged neurodevelopmental data. Segmental implication appears to have a significant impact on treatment duration and associated complications.

[Hereditary neuropathy with liability to pressure palsies in childhood: Report of three cases]. / Neuropathie héréditaire par hypersensibilité à la pression : à propos de 3 observations chez l'enfant.

Hereditary neuropathy with liability to pressure palsy (HNPP) is an autosomal dominant neuropathy. It is characterized by recurrent sensory and motor nerve palsies, usually precipitated by minor trauma or compression. Even though rare in childhood, this disorder is probably underdiagnosed given its wide spectrum of clinical symptoms. We review three separate cases of HNPP diagnosed in children with various phenotypes: fluctuating and distal paresthesias disrupting learning at school, cramps related to intensive piano practice, and discrete muscle weakness with no functional complaint. Family history should be carefully reviewed to identify potential undiagnosed HNPP cases, as in our three reports. Electrophysiological study is essential for the diagnosis, with a double advantage: to confirm the presence of focal abnormalities in clinically symptomatic areas and to guide molecular biology by revealing an underlying demyelinating polyneuropathy. The diagnosis of HNPP is confirmed by genetic testing, which in 90% of cases shows a 1.5-Mb deletion of chromosome 17p11.2 including the PMP22 gene. Patients are expected to make a full recovery after each relapse. However, it is very important for both the patient and his or her family to establish a diagnosis in order to prevent recurrent palsy brought on by situations involving prolonged immobilizations leading to nerve compression.

[Gradenigo syndrome and petrositis in a child]. / Syndrome de Gradenigo au cours d'une apicite chez un enfant.

Gradenigo syndrome is caused by petrous inflammation, also called petrositis. It includes acute otitis media, diplopia, and homolateral retroorbital pain due to trigeminal and abducens nerve injury. We describe a child with petrositis secondary to acute otitis media. The lack of otoscopic abnormality and the presence of bilateral headache made the diagnostic difficult. After complementary investigations searching for an intracranial process, the diagnosis was made based on brain and skull base dimensional computed tomography.

[Neurological manifestations of an osteoid osteoma located on the femoral neck in an 8-year-old boy]. / Présentation neurologique d'un ostéome ostéoïde du col fémoral.

We report the case of an 8-year-old boy, suffering from nocturnal pain localized on the left groin and presenting as a limp over several months. Examination revealed diminished strength of the left leg, atrophy of the thigh and calf, and a diminished deep tendon reflex. The pain could be intense and the patient had found an analgesic position by pushing on his groin or by flexing his thigh on the pelvis. He could no longer run. He was unsuccessfully treated with carbamazepine and gabapentin. His evaluation included a negative abdominal ultrasound study and a normal spine and cerebral MRI. Electromyography was unremarkable. He finally underwent an MRI of the pelvis that revealed a hyperintense T2 signal of the left femoral neck; CT confirmed the diagnosis of osteoid osteoma. Radiofrequency ablation of the lesion was performed. His clinical state dramatically improved after the procedure. His walk is normal, without any limping. Deep tendon reflexes are normal, and he only presents residual pain. Physicians should be aware that osteoid osteoma may take the form of a slowly evolving neuropathy. We review the literature on this underestimated condition.

[Polymorphic expression of epilepsy and cognitive impairment in ring chromosome 20 syndrome]. / Polymorphisme d'expression de l'atteinte épileptique et cognitive du syndrome du chromosome 20 en anneau.

Ring chromosome 20 syndrome combines epilepsy with varying levels of mental retardation, behavioral disorders, and malformations. Epilepsy is generally serious, with frequent drug resistance. The pathophysiology of seizures remains unclear. Rearrangements of two epilepsy genes, CHRNA4 and KCNQ2, have been raised as the cause. We report the observation of one child, with a telomeric deletion 20p13, with no epileptic symptoms. Preservation of CHRNA4 and KCNQ2 gene activity could explain this distinctive feature.

[Vaccinal status in children with seizures: a retrospective study conducted in the Bordeaux child hospital]. / Statut vaccinal d'enfants ayant un antécédent de convulsion ou d'épilepsie débutante: étude rétrospective comparative réalisée au CHU de Bordeaux.

UNLABELLED: Vaccination is a common act in medicine. Some serious side effects are always feared in a preventive action, mainly among high-risk patients such as epileptic children or children having already experienced a seizure. OBJECTIVES: To study consequences of such background on the vaccine medical practice. POPULATION AND METHODS: A retrospective study comparing the vaccine statute of children with or without case history of seizures was carried out by the neurologic and paediatric emergencies departments. The study compared 55 with seizures versus 109 without. RESULTS: On the whole, the 2 groups were insufficiently vaccinated. A statistically significant difference was highlighted between the 2 groups for the vaccination coverage by vaccine DTP (diphtheria-tetanus-pertussis) (P=0.017) and MMR (measles-mumps-rubella) (P=0.004). However, concerning the vaccination against hepatitis B, no difference was found. CONCLUSION: The usual contra-indications of these vaccines do not explain this difference and progress must be made to improve the vaccination coverage of epileptic children.

[Acceptability and tolerance of sodium valproate, a new sustained-action granule formulation, in monotherapy for epileptic children from 3 years old]. / Acceptabilité et tolérance du valproate de sodium, granules à libération prolongée, en monothérapie chez l'enfant épileptique à partir de trois ans.

UNLABELLED: Sodium valproate (VPA) is an anti-epileptic drug which was until now administered to children as drinkable or injectable form. A new galenic form of this compound has been developed as microgranules with prolonged release (Micropakine)LP; MPK). This new galenic form of VPA allows a greater stability of the plasmatic rates, thus limiting the risk of amount-dependent adverse effects at the time of the peaks, and of less effectiveness at the time of the fall of the circulating rates. The main objective of this study was to evaluate the acceptability of the new galenic form of VPA, in monotherapy, for epileptic children with >or=3 years old. The evaluation was performed at day (D)90 by the patients using a hedonic visual scale. The secondary objectives were to evaluate the acceptability by the parents, the treatment compliance, the percentage of patients free of seizure at D 90, and the tolerance. Finally, the authors compared all these data to those recovered at the baseline in patients already treated by the previous drinkable VPA. A total of 307 patients were involved by 76 hospital neuropediatric physicians. The population was constituted by 110 children <5 years old and 197 children from 5 to 14 years old. MPK was well accepted for total population at D 90 (<5 years old: 83.3%; >or=5 years old: 80%). For patients previously treated by drinkable form of VPA (N=199), MPK was significantly better accepted than the drinkable form at D1 (<5 years, P=0.0189; >or=5 years, P<0.0001). Less difficulties were experienced by the parents to administrate MPK when compared to the drinkable form (P<0.001), mainly due to his neutral taste. Patients free of seizure at D 90 were 77% [70,3; 82,5]. Specially, fewer epileptic seizures were evidenced for all children previously treated at D1 by drinkable form of VPA. The treatment was well respected by the patients, which were compliant in 80% of the cases. The adherence to treatment was good since the treatment compliance was 87%. MPK was well tolerated. CONCLUSION: MPK in the microgranule form significantly improves the treatment acceptability with a good tolerance. Two daily intakes and neutral taste are two major advantages to favour the compliance in children, thus contributing to the efficacy of the antiepileptic treatment.

[Angelman syndrome and intracranial aneurysm: fortuitous association or commune genetic predisposition?]. / Syndrome d'Angelman et anévrisme intracrânien : association fortuite ou prédisposition génétique commune ?

Although the pathogenesis of cerebral aneurysms has been studied intensively, it is yet poorly understood. However, a genetic predisposition to this pathology has been often suspected. We describe a patient with both intracranial aneurysm and Angelman syndrome. Angelman syndrome is characterized by severe mental retardation, inappropriate laughter, absent speech, dysmorphic facial features and seizures. It is due to genetic abnormalities of chromosome 15. Cerebral aneurysms are sometimes associated with inherited diseases like autosomal dominant polycystic kidney disease. Moreover several candidate genes have been analysed, to search for genetic variants which might be associated with the occurrence of intracranial aneurysms. Our question is: is the association described in our observation fortuitous or do these diseases share a same genetic predisposition? Our observation also supports the hypothesis of a genetic participation in the genesis of cerebral aneurysms.

[Hereditary neuralgic amyotrophy: a paediatric and familial presentation of Parsonage-Turner syndrome]. / Névralgie amyotrophiante héréditaire ou forme pédiatrique familiale du syndrome de Parsonage et Turner.

Hereditary neuralgic amyotrophy is a rare disorder, characterized by recurrent attacks of pain in a brachial plexus distribution. We report the case of a 12-year-old boy with several attacks of pain and atrophy of the muscles of the shoulders. The age of onset of this disease is variable, most frequently in the second or third decade. Pediatric onsets, during the first decade are rare. The differences between the hereditary neuralgic amyotrophy and the sporadic Parsonage-Turner syndrome are painful recurrent episodes of weakness and similar familial cases. The analysis of several families has shown that hereditary neuralgic amyotrophy phenotype is heterogeneous and two different clinical courses can be discerned. Recent evidence indicates that HNA is genetically heterogeneous. Pathophysiology of the disease remains unclear, so the treatment is not clearly established.

Pulsed dye laser for Sturge-Weber syndrome.

Port wine stain of Sturge-Weber syndrome represents a cosmetic prejudice with social consequences. We have treated eight patients with a 585 nm pulsed dye laser. According to our experience, the treatment is not risky provided that adequate care is taken; the cosmetic result on the V1 port wine stain component is satisfactory.

[Botulinum toxin in the management of spastic hip adductors in non-ambulatory cerebral palsy children]. / Toxine botulinique dans la spasticité des adducteurs de hanche chez les enfants IMC et IMOC non marchants.

PURPOSE OF THE STUDY: Spasticity of the hip adductors is a challenging problem for children with severe motor impairment due to cerebral palsy. It inhibits motor development and is also a risk factor for hip dislocation. Botulinum toxin has been found to be an effective means of treating spastic pes equinus in walking cerebral palsy patients and could have other indications. We conducted a prospective study to determine the functional and orthopedic contribution of botulinum toxin in the treatment of spastic hip adductors in non-ambulatory cerebral palsy children. MATERIAL AND METHODS: The study included 11 quadriplegic children with cerebral palsy (mean age 5 years 9 months). Seven of the children had unilateral migration of the hip at study onset (> 40% radiographically). The children were given a single injection of botulinum toxin (Dysport: 20 units/kg/hip) in the adductor muscles (21 treated hips). The children were seen again at months 1, 3, 6 and 12 after treatment (with the exception of one patient not seen after the 6(th) month at the request of the parents). Spasticity was measured with the modified Ashworth scale. The motor level was determined with 8 position and motor items and with the GMFCS classification. Hip x-rays were obtained at study onset and once or twice during the follow-up. RESULTS: There were no adverse effects of the treatment. Spasticity decreased by one point or more on the Ashworth scale in 20 hips at month 1 and remained low at month 3 in 14, and at month 6 in 12 of the 21 hips treated. The effect of the anti-spasticity treatment faded out from the 6(th) to the 12(th) month. Three children who experienced pain in the lower limbs were definitively relieved after treatment. Nine children achieved functional improvement (progress in at least one of the motor items). Three children were able to walk with a walker and two of them improved from level IV to level III on the GMFCS. The best functional responses appeared to occur in the younger children and in those who had good results at months 3 and 6. Among the 7 children whose hip was displaced by more than 40%, 5 had an unfavorable radiological progression and underwent surgery. DISCUSSION: This study demonstrates that the botulinum toxin can be effective against spasticity of the hip adductors and that its effect is still significant 6 months after the injection in more than half the hips treated. It has an analgesic effect. This treatment has a functional impact even in children with severe motor impairment. The benefit has been modest but three children were able to progress to walking with a walker. The best functional results were observed in the younger children and in those whose spasticity had declined at month 3 and 6. It could thus be favored either by innate potential for motor development or by the treatment itself. The botulinum toxin did not improve the orthopedic prognosis of the children: 5 of the 7 with a risk of luxation worsened. Nevertheless, our study suggests that the botulinum toxin is a well-tolerated anti-spasticity treatment that is effective for the hip adductors providing an important contribution to the management of non-ambulatory cerebral palsy children.

Prenatal diagnosis of schizencephaly by fetal magnetic resonance imaging.

Schizencephaly is a neuronal migration anomaly characterized by gray matter lined clefts extending from the ventricle to the cortical surface leading to specific lesions, well demonstrated by imaging. The lips of the clefts can be fused or separated. Prognosis is related to the extend of the involved cortex. Both genetic and acquired factors can be responsible for this pathology. Three cases of antenatal diagnosed open schizencephaly are reported. Two cases are unilateral and one is bilateral. A cerebral anomaly has been detected in all cases by routine ultrasonography (US) revealing a ventricular dilatation with cortical associated abnormalities. Prenatal magnetic resonance imaging (MRI) permitted the diagnosis in the 3 cases. All cases had led to abortion because of the importance of the cortical defect. The aim of this report is to point out the importance of fetal MRI in the diagnosis of migration disorder and to discuss the medical implications. Indeed, MRI is better suited than US for the prenatal diagnosis of schizencephaly, being able to detect normal and abnormal brain cellular migration, especially with fast imaging (HASTE sequences). With its multiplanar imaging capability, MRI demonstrates the cleft extending from the pial surface to the ventricular ependyma and thus provides characteristic diagnosis of this disorder. Moreover, ventricular dilatation, a frequent anomaly detected by US should be completed with MRI in order to research a neuronal migration disorder.

[Multiple sclerosis: pathogenesis and manifestations in children]. / Sclérose en plaques: pathogénie et formes de révélation chez l'enfant.

Multiple sclerosis (MS) is rare in children and occurs exceptionally before ten years. Sex ratio (girl/boy) is around 2.5 to 3, higher than in adults. Brain stem dysfunction and meningeal symptoms are more commonly first manifestations of the disease than in adults. Optic neuritis is also a frequent early manifestation. The etiology of the disease remains unclear and none of the advanced hypotheses (infectious, genetic, environmental) can by themselves explain its occurrence. There is a genetic susceptibility which is probably linked to many genes leading to a low related risk (less than two). A viral trigger mechanism in a person with a genetic predisposition is possible. New therapies result from a better understanding of the closed immune mechanisms of the disease.

Interferon-beta treatment in patients with childhood-onset multiple sclerosis.

We present a report of the use of interferon-beta before 18 years of age in 16 patients with childhood-onset multiple sclerosis. This study demonstrated that the treatment is safe and well tolerated.

Infantile Alexander disease: spectrum of GFAP mutations and genotype-phenotype correlation.

Heterozygous, de novo mutations in the glial fibrillary acidic protein (GFAP) gene have recently been reported in 12 patients affected by neuropathologically proved Alexander disease. We searched for GFAP mutations in a series of patients who had heterogeneous clinical symptoms but were candidates for Alexander disease on the basis of suggestive neuroimaging abnormalities. Missense, heterozygous, de novo GFAP mutations were found in exons 1 or 4 for 14 of the 15 patients analyzed, including patients without macrocephaly. Nine patients carried arginine mutations (four had R79H; four had R239C; and one had R239H) that have been described elsewhere, whereas the other five had one of four novel mutations, of which two affect arginine (2R88C and 1R88S) and two affect nonarginine residues (1L76F and 1N77Y). All mutations were located in the rod domain of GFAP, and there is a correlation between clinical severity and the affected amino acid. These results confirm that GFAP mutations are a reliable molecular marker for the diagnosis of infantile Alexander disease, and they also form a basis for the recommendation of GFAP analysis for prenatal diagnosis to detect potential cases of germinal mosaicism.

X-linked myopathy with excessive autophagy: a clinicopathological study of five new families.

In 1988, Kalimo et al. (Ann Neurol 23 (1988) 258)described a new type of X-linked myopathy in a Finnish family. The clinical course was characterized by slow progression of muscle weakness without loss of ambulation in childhood and no evidence of cardiac, respiratory, or central nervous system involvement. Muscle fibers were not necrotic and showed excessive autophagic activity and exocytosis of the phagocytosed material. These authors proposed the name X-linked myopathy with excessive autophagy. Subsequently, only one French family has been reported with similar clinical and histopathological data. We report here five new families with a total of eight affected boys with the same clinical and histopathological features as reported in the original families. Histopathological findings of an asymptomatic mother are also reported. Vacuolar changes in muscle fibers result both from invaginations of the sarcolemma along with a variable component of basal lamina and from an autophagic process. The complement C5b-9 membrane attack complex associated with MHC class 1 antigen and calcium deposits is involved in muscle fiber damage. Among the X-linked myopathies, the identification of this new type is of great interest because of its favorable prognosis and unique morphological findings.

[Cerebellar vermis hypoplasia with extracerebral involvement (retina, kidney, liver): difficult to classify syndromes]. / Hypoplasies vermiennes avec atteintes extracérébrales (rétine, rein, foie): des syndromes difficiles à classer.

UNLABELLED: Congenital cerebellar vermis hypoplasias diversely associated with retinopathy, nephropathy and hepatopathy are rare syndromes of uncertain nosology. We report three new cases. CASE REPORTS: Case 1. A 3-month-old boy presented a brief nystagmus. At the age of 2 years, he had facial dysmorphia, hypotonia, ataxia, ocular motor apraxia and neurodevelopmental impairment with cerebellar vermis hypoplasia. The electroretinogram showed asymptomatic retinal involvement. At the age of 6 years, he developed chronic renal failure. The diagnosis of familial juvenile nephronophthisis was made by detection of a large homozygous deletion of the NPH1 region. Case 2. A term newborn boy presented apnea, tachypnea, hypotonia, nystagmus, ptosis, lack of visual contact and hepatomegaly. He had facial dysmorphia, bilateral optic coloboma with chorioretinal dysplasia and cerebellar vermis hypoplasia. There were cysts in the kidneys with increased echogenicity and lack of demarcation between the pyramids and the cortex. The liver was hyperechoic with fibrosis. At the age of 15 months, the child had severe developmental delay. He had bouts of fever. A search for a large homozygous deletion of the NPH1 region was negative. Case 3. A term newborn girl presented difficulty to suck, cyanosis, hypotonia and ptosis. Later, the child had a developmental delay. At the age of 6 years, she developed chronic renal failure (nephronophthisis). At the age of 23 years, she presented divergent strabismus, ataxia, mental retardation, slow ocular pursuit and facial dysmorphia. The neuroimaging showed a cerebellar vermis hypoplasia. A search for a large homozygous deletion of the NPH1 region was negative. CONCLUSION: The diagnosis of cerebellar vermis hypoplasia requires searching for retina, kidney and liver involvement. The large homozygous deletion of the NPH1 region has to be investigated if typical familial juvenile nephronophthisis is associated. Because cerebellar vermis hypoplasia with extracerebral involvements (retina, kidney, liver) is part of many different closely related syndromes, a clear molecular classification is necessary for accurate genetic counselling and an early prenatal diagnosis.