A Prospective Study of Arterial Spin Labelling in Paediatric Posterior Fossa Tumour Survivors: A Correlation with Neurocognitive Impairment.

AIMS: Posterior fossa tumours (PFTs), which account for two-thirds of paediatric brain tumours, are successfully treated in about 70% of patients, but most survivors experience long-term cognitive impairment. We evaluated arterial spin labelling (ASL), a common, non-invasive magnetic resonance imaging (MRI) technique, as a biomarker of cognitive impairment in a paediatric PFT survivor population. MATERIALS AND METHODS: Sixty participants were prospectively analysed. PFT survivors were at least 5 years post-treatment and had been treated as appropriate for their age and type of tumour. Group 1 had received radiotherapy and Group 2 had not. Group 3 were healthy controls matched to Group 1 for age, sex and handedness. All participants underwent cognitive assessment and multimodal MRI, including an ASL perfusion sequence. We used semi-quantitative ASL methods to assess differences in mean perfusion in the thalamus, caudate, putamen and hippocampus. RESULTS: Statistically, no significant associations between cognitive data and radiation doses were identified. Compared with healthy controls, Group 1 patients had significantly lower overall mean perfusion values (20-30% lower, depending on the cerebral structure) and Group 2 had slightly lower mean perfusion values (5-10% lower). Perfusion values did not correlate with total prescribed irradiation doses nor with doses received by different cerebral structures. Episodic and semantic memory test scores were significantly lower in Group 1 and correlated with lower mean absolute perfusion values in the hippocampus (P < 0.04). CONCLUSIONS: These preliminary results indicate that radiotherapy affects the perfusion of specific cerebral structures and identify perfusion as a potential biomarker of hippocampus-dependent memory deficit.

Exploring Memory Systems After Pediatric Posterior Fossa Tumor: From Memory Profile Comparisons in Nonirradiated Versus Irradiated Patients to Episodic Memory Tests Capable of Detecting Radiation-induced Hippocampal Damage.

AIMS: Pediatric posterior fossa tumor (PFT) survivors experience long-term cognitive sequelae, including memory disorders, for which irradiation is one of the main risk factors. The aims of the present study were to (1) explore the profile of impairment in episodic, semantic, working and procedural memory systems in irradiated versus nonirradiated PFT survivors, and (2) test whether an autobiographical questionnaire and a two-phase ecological test (Epireal) assessing episodic memory are more sensitive to radiation-induced hippocampal damage than commonly used tests. MATERIALS AND METHODS: A total of 60 participants (22 irradiated PFT survivors, 17 nonirradiated PFT survivors, and 21 controls) were included in the prospective IMPALA study. They all underwent a broad battery of tests assessing the different memory systems in two 2-day sessions 3 weeks apart. We performed between-groups comparisons and analyzed impairment profiles, using -1.65 SDs as a cut-off. For irradiated patients, correlations were calculated between mean radiation doses to key brain structures involved in memory (hippocampus, cerebellum, and striatum) and corresponding memory scores. RESULTS: PBT survivors performed significantly more poorly than controls (p < 0.001) on conventional tests of episodic, semantic and working memory: 64% of irradiated patients and 35% of nonirradiated patients had a deficit in at least two memory systems, with episodic memory impairment being more specific to the irradiated group. Epireal had a larger effect size than the other episodic memory tests, allowing us to detect deficits in a further 18% of irradiated patients. These deficits were correlated with the mean radiation dose to the left hippocampus. CONCLUSION: Memory impairment is a frequent long-term cognitive sequela in PFT survivors, especially after radiation therapy. New ecological tests of episodic memory that are more sensitive to radiation-induced deficits than conventional tests could yield specific markers of the toxicity of medial temporal lobe irradiation.

Lyme neuroborreliosis in pediatrics: A retrospective, descriptive study in southwest France.

BACKGROUND: The neurological effects of Lyme borreliosis in children are varied and their clinical progression is not widely reported in the French literature. We carried out a retrospective study to describe the clinical characteristics of Lyme neuroborreliosis in children in southwest France and their clinical progression at 6 months. METHODS: This study was carried out at Toulouse University Hospital during the period 2006-2017 using patient records. Case definition was based on the combined French clinical and laboratory diagnostic criteria. RESULTS: In total, 26 children were included. The median age was 8 years (4-14 years). The different neurological symptoms reported were: meningoradiculitis (62%), which was usually associated with facial palsy (54%); isolated facial palsy (15%); isolated meningitis (8%); polyradiculoneuritis (4%); benign intracranial hypertension (4%) and myelomeningoradiculitis (4%). The most common functional symptoms were headaches (54%), the perception of asthenia (42%), neck pain (27%), and a loss of appetite (19%). Patients with laboratory meningitis (84%) often had no signs of meningism or headaches (38%). CONCLUSION: The majority of the cases involved meningoradiculitis but other, less common, neurological conditions have been described. The clinical signs suggestive of meningitis are not very marked and might delay the diagnosis.

Specific Cues Can Improve Procedural Learning and Retention in Developmental Coordination Disorder and/or Developmental Dyslexia.

The present study investigates procedural learning of motor sequences in children with developmental coordination disorder (DCD) and/or developmental dyslexia (DD), typically-developing children (TD) and healthy adults with a special emphasis on (1) the role of the nature of stimuli and (2) the neuropsychological functions associated to final performance of the sequence. Seventy children and ten adults participated in this study and were separated in five experimental groups: TD, DCD, DD, and DCD + DD children and adults. Procedural learning was assessed with a serial reaction time task (SRTT) that required to tap on a specific key as accurately and quickly as possible when stimuli appeared on the screen. Three types of stimuli were proposed as cues: the classical version of the SRTT with 4 squares aligned horizontally on the screen, giving visuospatial cues (VS cues), and two modified versions, with 4 letters aligned horizontally on the screen (VS + L cues) and letters at the center of the screen (L cues). Reaction times (RT) during the repeated and random blocks allowed assessing three phases of learning: global learning, specific learning and retention of the sequence. Learning was considered as completed when RT evolved significantly in the three phases. Neuropsychological assessment involved, among other functions, memory and attentional functions. Our main result was that learning and retention were not influenced by the available cues in adults whereas learning improved with specific cues in children with or without neurodevelopmental disorders. More precisely, learning was not completed with L cues in children with neurodevelopmental disorders. For children with DD, learning was completed with the VS and VS + L cues whereas for children with DCD (with or without DD), learning was completed with combined VS + L cues. Comorbidity between DD and DCD had no more impact on procedural learning than DCD alone. These results suggest that learning depends on the nature of cues available during practice and that cues allowing learning and retention depend on the type of disorder. Moreover, selective attention was correlated with RT during retention, suggesting that this neuropsychological function is important for procedural learning whatever the available cues.

[The outcome of children presenting with a prenatally diagnosed arachnoid cyst]. / Devenir des enfants présentant un kyste arachnoïdien de diagnostic anténatal.

AIM: Evaluate the outcome of children with prenatally diagnosed arachnoid cysts. MATERIAL AND METHODS: Retrospective study of seventeen cases of children who were diagnosed with an arachnoid cyst during prenatal MRI between July 1994 and January 2007 and followed up for a mean 6 years and 6 months. Follow-up was based on evaluation of clinical files and contacts with the physicians who were following the children. The children were divided into three groups: group 1 normal development, group 2: minor clinical signs, normal schooling, group 3: major clinical symptoms, schooling disturbed. RESULTS: Eight of the 17 patients included in this study underwent derivation surgery for the cyst. Eight of the 17 children were in group 1, and 3 in group 2. Four of the 6 children in group 3 had associated symptoms. Two of the children in group 3 present with a supratentorial cyst, and 4 with a cyst of the posterior fossa. CONCLUSION: The prenatal diagnosis of a arachnoid cyst should be accompanied by a search for associated lesions. The risk of hydroencephalitis should be explained to the parents.

Assessing the management of pediatric bone and joint infections according to French guidelines.

BACKGROUND: Short treatments for acute bone and joint infections (BJI) are recommended. We implemented a protocol in 2009 to improve diagnosis and bacteriological documentation, and to shorten antibiotic therapies as per French guidelines (French Pediatric Infectious Disease Group, GPIP). METHODS: To assess the impact of the new clinical protocol for BJI, we conducted a retrospective study from January 1st, 2006 to August 31st, 2012. Two successive cohorts were compared, before and after protocol implementation. All children suspected of community-acquired BJI were included. Confirmed osteomyelitis and septic arthritis required a positive bacterial isolate; otherwise, cases were considered probable. We compared clinical, biological, and radiological data; duration of antibiotic therapy and hospital length of stay; and complications and sequelae. RESULTS: A total of 377 children with suspected BJI were included. The bacteriological identification improved from 32% to 44% when patients were completely evaluated. Isolated bacteria were Staphylococcus aureus (53%), Kingella kingae (17%), Streptococcus pyogenes (15%), and Streptococcus pneumoniae (8%). Before protocol implementation, 70% of patients had a central venous line versus 9% after implementation. Mean duration of IV antibiotics (11 days versus 6 days), mean duration of total antibiotic therapy (45 days versus 32 days) and mean hospital length of stay (13 days versus 7 days) had significantly improved. CONCLUSION: Improvement in bacteriological diagnosis and shorter antibiotic regimens lead to shorter hospital length of stays with no additional morbidity. Simplifying the protocol and better diffusion among health professionals should contribute to shortening BJI treatment duration.

[Hallucinations: Etiological analysis of children admitted to a pediatric emergency department]. / Hallucinations : analyse étiologique chez des enfants admis en service d'accueil des urgences.

Children's hallucinations pose the dual challenge of diagnosing a possible medical emergency and a possible psychiatric disorder. PURPOSE: The main objective was to analyze the causes of such hallucinations in children presenting to a pediatric emergency department. MATERIAL AND METHODS: We conducted a single-center, observational, retrospective study including all children aged less than 15 years experiencing hallucinations and admitted to our tertiary level pediatric emergency department between 1 January 2007 and 31 December 2015. The data collected were demographic; medical: previous medical or psychiatric history, current medications, associated clinical or psychiatric symptoms, type and character of hallucinations, length and recurrence of hallucinatory phenomena; and other biological, radiological and neurological explorations. RESULTS: Sixty-eight patients were included (29 boys). The mean age was 9.1±3 years (range, 2-14 years and 10 months; median, 9.2 years). Admissions were seasonal with a bimodal distribution (a peak during springtime and another one during fall). Hallucinations were mainly visual (90%), acute (77%) and complex (63%). Visual hallucinations were associated with other types of hallucinations: auditory (n=17), somatosensory (n=7). Fifteen children had a psychiatric history and had already experienced hallucinatory phenomena (93%). Among 47 patients (69%), these hallucinations were associated with other symptoms: agitation (41%), headaches (28%), hyperthermia (21%) and negative symptoms of the schizophrenia spectrum (15%). On admission, 20 patients (29%) had one or more treatments under way (34 drugs, 41% known for hallucinogenic adverse effects). Neurological explorations were undertaken in half of the cases. Toxicological analysis prescribed in 19 children was positive in five cases (26%). Fifty-three percent of patients were hospitalized and 51 children received a specialized follow-up (by a neurologist and/or a psychiatrist). A nonpsychiatric origin of these hallucinations was diagnosed in 29 patients (43%): neurological causes (n=10), infectious diseases (n=10), intoxications (n=5) and a medication side effect (n=4). CONCLUSION: Hallucinations with a suspected underlying psychiatric cause differed on several factors: chronic duration (p=0.02), an onset after 10 years of age (p=0.004), previous identical episodes (p=0.014) and a parental psychiatric history (p=0.036), auditory hallucinations (p=0.0009), absence of fever (p=0.005), headaches (p=0.036) and the presence of negative symptoms of the schizophrenic spectrum (p=0.02).

[Severe nutritional rickets in young children: Resurgence of an old disease]. / Rachitisme carentiel sévère du nourrisson : de nouveau d'actualité.

Nutritional rickets remains a significant public health issue for children worldwide. Although it has almost disappeared in industrialized countries following routine vitamin D supplementation, recent evidence suggests an increasing incidence, especially in young children. In addition to the classical clinical consequences on bone and the growth plate, rickets may also be associated with life-threatening neurological and cardiac complications in the most severe forms. Consequently, early screening and treatment are required. Here, we report the case of a 2-year-old child who presented with severe nutritional rickets associated with seizure and cardiomyopathy. Family screening revealed rickets in all the siblings. This case report emphasizes the importance of being aware of this disease, notably in population with sociocultural risk factors.

Perturbation in dystrophin-associated glycoprotein complex in a boy with Becker muscular dystrophy.

We report on a boy with a BMD phenotype presenting with a deletion of exons 45-49 in the DMD gene. Immunofluorescence and Western blot analysis of a skeletal muscle sample revealed, as expected, truncated dystrophin with loss in the central rod domain, but with an unusual severe deficiency in the sarcoglycan complex, as in severe DMD. We discuss possible neighboring between dystrophin and associated proteins within their complex organization at the muscle membrane.

[Pseudotumor forms of neurosarcoidosis in children. Diagnostic difficulties and therapeutic management]. / Formes pseudo-tumorales de la neurosarcoïdose chez l'enfant. Difficultés diagnostiques et prise en charge thérapeutique.

In systemic sarcoidosis, neurologic manifestations are possible and occurred in 5 p. 100 of cases. The diagnosis is easier when sarcoiddosis is known, but in half case neurologic symptoms are inaugural. In these cases, involvement of other sites (liver, lung, eyes or skin) by the disease is needed to confirm sarcoidosis. Main manifestations in neurosarcoidosis are cranial nerve palsy, diabetes insipidus or chronic aseptic meningitis, but sometimes sarcoidosis can present as an intracranial mass. The diagnosis of neurosarcoidosis may be difficult and could be confused with infection (such tuberculosis or mycosis), with inflammatory diseases (such multiple sclerosis) or with neoplasm, particularly in case of oedema. Brain biopsy may be necessary in isolated neurosarcoidosis if no peripheral histology evidence of noncaseating granulomas has been obtained. Treatment with steroids alone is the best choice for initial therapy but must be prolonged. It is difficult to predict accurately the response to steroids and relapse may be possible after a long time. Other immunosuppressive therapeutics or radiotherapy have been used in patient with refractory neurosarcoidosis. Sequential magnetic resonance imaging is the useful mean for the follow-up of neurosarcoidosis.

[Association of venous angioma and cavernoma of the posterior fossa]. / Association d'un angiome veineux et d'un cavernome au niveau de la fosse postérieure.

BACKGROUND: Association of venous angioma to cavernous malformation is rare. If bleeding occurs, it must be assigned to the cavernous malformation. CASE REPORT: A 4 year-old boy suffered from an acute ataxia. Investigation showed a venous angioma and a cavernoma malformation in the posterior fossa. The patient was admitted again at the age of 8 years for a new episode of acute ataxia due to cerebellar hematoma. A conservative treatment was settled because of the risk of venous infarction. CONCLUSION: Venous angiomas are rarely symptomatic and are considered as normal venous variants. Indeed, the cavernomas are true malformations with a high bleeding potential. When both lesions are associated and bleeding occurs, only the cavernous malformation has to be removed if surgically accessible.

[Acute intermittent porphyria associated with epilepsy in a child: diagnostic and therapeutic difficulties]. / Porphyrie aiguë intermittente et épilepsie chez un même enfant: difficultés diagnostiques et thérapeutiques.

BACKGROUND: Acute intermittent porphyria is an autosomal dominant inborn error of heme biosynthesis. The diagnosis of acute porphyria is rare before puberty. Its association with epilepsy induces difficulties in diagnosis and seizure treatment. CASE REPORT: A case of acute intermittent porphyria in a 9-year old boy with epilepsy is reported. The diagnosis was made only after the third hospitalisation, with the measurement of enzyme activity and identification of family members with latent disease. Adjustment of antiepileptic treatment was necessary 7 months later. CONCLUSION: Most antiepileptic drugs are unsafe because they have demonstrated porphyrinogenicity. Low doses of clonazepam can be used in this situation.

[Alternating hemiplegia of childhoood and oculomotor anomalies]. / Hémiplégies alternantes de l'enfant et leurs anomalies oculo-motrices.

BACKGROUND: Alternating hemiplegia of childhood is a syndrome which begins in the first year of life. It is characterized by repeated attacks of uni-or bilateral hemiplegia or hemiparesia. In most cases paroxysmal manifestations are observed: movements or dystonia++ attacks, episodic nystagmus, abnormal eye movements and disturbance of the neurovegetative system, predominantly in the first year of life. ANALYSIS: In half of the cases, neurological anomalies begin during the neonatal period with a non characteristic aspect. Typical attacks take place after one year of life, sometimes associated with partial epilepsy. In a quarter of cases, the oculomotor anomalies have been known since early life. The diagnosis is made prior to one year on the basis of associated oculomotor anomalies and other symptoms without EEG arguments for epilepsy. Paroxysmal nystagmus is always found. One eye is affect in most cases, generally with horizontal and seldom with vertical movements of large variable pendular amplitude. One eye with nystagmus and the other with mydriasis is sometimes reported. Most attacks last from 30 sec to 3 min. Paroxysmal strabismus described in half of the cases seems to be generally unilateral internuclear transitory ophthalmoplegia. Finally, ocular deviations on the hemiparetic side are described. They are generally unique or sometimes associated with head deviation. Spontaneous blinking is reduced. CONCLUSION: Alternating hemiplegia of childhood is a non-epileptic sporadic, paroxysmal manifestation of unknown pathogenesis. Prognosis is poor. The presence of oculomotor signs suggests the diagnosis.

[Clear cell meningioma: recurrent intraspinal tumor in a child]. / Méningiome à cellules claires: tumeur rachidienne récidivante chez un enfant.

BACKGROUND: Meningiomas represent 1.5% to 4.3% of cerebral and medullar primary tumors in children. CASE REPORT: A 9-year-old girl had a history of thoracolumbar scoliosis. An intracanalar and extramedullar tumor was confined to the lumbar region. Resection identified a clear cell meningioma. A symptomatic and tumoral recurrence occurred 5 months later in the same region. After a second resection, the patient received radiotherapy. At 8 months follow-up, no recurrence was documented. CONCLUSIONS: A stiff and painful scoliosis can be predictive of expansive intracanalar tumor. The recurrent or multifocal evolution of clear cell meningioma show the "aggressive behavior" of this histological type. A preventive radiotherapy could be proposed, depending on the age of the patient and the localization of the tumor.

[Chronic meningococcemia: 3 cases in the immunocompetent child]. / Méningococcémie chronique: trois cas chez l'enfant immunocompétent.

UNLABELLED: Chronic meningococcemia is a part of extra meningeal manifestations of meningococcal disease. Its diagnosis can be difficult because of lack of sensitivity of blood cultures. CASE REPORT: Three cases, concerning immunocompetent children, respectively aged of 14, 10 and 4 years are reported. The clinical course was characterized by recurrent fever, inflammatory joint manifestations and diffuse maculopapules secondary centered by petechiae. Microbiological findings revealed in one case a positive throat culture and presence of meningococcal soluble antigens in blood and urine. In the other two cases, diagnosis was done after done after positive blood culture at the 7th, and 13th days of course. CONCLUSION: The diagnosis should be considered in any children with a prolonged, recurrent fever and cutaneous and joint manifestations even if blood cultures remain negative. The response to therapy by usual antimeningococcal antibiotics is dramatic and curative while a prolonged untreated course may be complicated by metastatic infection.

[Acute orbital myositis and idiopathic inflammatory pseudotumor in children: three cases]. / Myosite orbitaire aiguë et pseudotumeur inflammatoire idiopathique de l'enfant: trois cas.

UNLABELLED: Orbital pseudo-tumors account for approximately 8% of the orbital tumors. They are scarcely described in children and raise diagnostic dilemas, especially when they present as an isolated extra-ocular muscle swelling called idiopathic orbital myositis (IOM). CASE REPORTS: A diagnosis of inflammatory orbital pseudotumors (IOPT) was made in three children aged 7, 13 and 14 years from clinical and CT scan and/or MRI findings associated with histological data in two of them. Two of these IOPT presented as IOM. Analysis was made in a effort to eliminate intra-orbital tumors, especially rhabdomyosarcoma. CONCLUSION: The abrupt onset of the orbital signs, often related in the literature, was not a specific diagnostic criterion regarding to embryonic rhabdomyosarcoma. The inconstant presence of inflammatory signs and the absence of local osseous defect could be more discriminating. Although diagnostic procedure, including histological documentation, was difficult, even dangerous, surgical biopsy should be recommended. Eventually, considering the mandatory multidisciplinary care, steroid therapy response should be evaluated as a diagnostic test.

[Pseudo-periodic disease with hyperimmunoglobulinemia D: a never-ending story with probable prenatal onset]. / Pseudomaladie périodique avec hyperimmunoglobulinémie D: une histoire sans fin de début anténatal probable.

UNLABELLED: Diagnosis of inflammatory non-infectious diseases with a neonatal onset is often retrospective. It may lead to aggressive and iatrogenic procedures. PATIENT: A 6-year-old boy was suffering, since birth, from recurrent febrile attacks including rashes, gastrointestinal manifestations and inflammatory joint involvement. This syndrome, partially improved with steroids, could have been of antenatal onset. Since the age of 4 years, the patient is considered as having hyper-IgD syndrome (HIDS). DISCUSSION: HIDS must be distinguished from familial Mediterranean fever. Patients suffer from recurrent fever concomitant to inflammatory joint involvement, abdominal distress, skin lesions, swollen lymph nodes and hepatosplenomegaly (especially seen in children). All patients have high serum IgD (> 100 UI/mL) and IgA levels. Nevertheless, a high IgD level is not specific. Our case could also be part of the CINCA (chronic, infantile, neurological, cutaneous and articular) syndrome, which includes similar early manifestations associated with a constant neurological and frequent ophthalmological involvement and epiphyseal changes; to date, these last three manifestations are not present in our patient. CONCLUSION: HIDS and CINCA syndrome are not known to be modified by any effective therapeutic agent. When presenting at birth, these inflammatory diseases must be considered as entities with a rarely described potential severity.

[Optic pathway gliomas in neurofibromatosis type I. Longitudinal study of 30 cases in two multidisciplinary practices]. / Les gliomes des voies optiques dans la neurofibromatose de type 1. Etude longitudinale de 30 cas suivis dans deux consultations multidisciplinaires.

UNLABELLED: The aim of this study was to analyse the outcome of optic pathway gliomas in 30 children with neurofibromatosis type 1, the indications of treatment, and the follow-up and screening protocol. PATIENTS AND METHODS: All patients with a minimal two years follow-up (median six years, range two to 19 years), in two multidisciplinary consultations of Saint-Vincent-de-Paul (Paris) and Purpan (Toulouse) hospitals, were included in the study. In our series, we practiced systematic screening MRI in children under six years' of age or with neuropsychological deficiency that may imply an unreliable ophthalmological examination. RESULTS: Thirty-seven percent (11 patients) had progressive ophthalmological signs and were treated, and 63% (19 patients) were not progressive. Our study confirmed that most of optic pathway gliomas were stable during evolution, but rare cases may have bad prognosis. CONCLUSION: Our study supported the importance of close ophthalmological follow-up during childhood for which screening methods are discussed. There is a consensus to limit treatment for patients with progressive ophthalmological symptoms.

[Neurofibromatosis 1: recommendations for management]. / Neurofibromatose 1: recommandations de prise en charge.

Twenty experts, members of a French medical network devoted to neurofibromatosis 1 have elaborated recommendations for the management of the disease. Bibliography was obtained through a Medline of articles from 1966 to 1999 for the terms neurofibromatosis, NF1, neurofibroma and from textbooks. A consensual document was written taking into account extracted data. An annual careful clinical examination is recommended except in cases with complications. Screening investigations are not recommended due to the rarity of complications, generally symptomatic and easily detected during the clinical follow-up. The only controversial exception might be magnetic resonance imaging for early detection of optic pathway gliomas in young children. A co-ordinated follow-up in specialised multidisciplinary centres, providing patients with a rational management, is recommended.