Highlighting the Dystonic Phenotype Related to GNAO1.

BACKGROUND: Most reported patients carrying GNAO1 mutations showed a severe phenotype characterized by early-onset epileptic encephalopathy and/or chorea. OBJECTIVE: The aim was to characterize the clinical and genetic features of patients with mild GNAO1-related phenotype with prominent movement disorders. METHODS: We included patients diagnosed with GNAO1-related movement disorders of delayed onset (>2 years). Patients experiencing either severe or profound intellectual disability or early-onset epileptic encephalopathy were excluded. RESULTS: Twenty-four patients and 1 asymptomatic subject were included. All patients showed dystonia as prominent movement disorder. Dystonia was focal in 1, segmental in 6, multifocal in 4, and generalized in 13. Six patients showed adolescence or adulthood-onset dystonia. Seven patients presented with parkinsonism and 3 with myoclonus. Dysarthria was observed in 19 patients. Mild and moderate ID were present in 10 and 2 patients, respectively. CONCLUSION: We highlighted a mild GNAO1-related phenotype, including adolescent-onset dystonia, broadening the clinical spectrum of this condition. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Screening for neurodevelopmental disorders in children with congenital heart disease.

The aim of this study was to evaluate the frequency of neurodevelopmental disorders (NDD) in children with significant congenital heart disease (CHD) and to determine associated factors to NDD and frequency of follow-up in developmental therapies. Two hundred and ten children with significant CHD aged from 6 to 66 months were enrolled over a period of six months. The Ages & Stages Questionnaire Third Edition in French (ASQ-3) was used to assess neurodevelopmental domains. NDD were defined if cut-off scores were ≤ - 1SD. - 1SD corresponded to "Monitor" range: children with minor or emerging disorders; - 2SD corresponded to "Refer" range: children exhibiting neurodevelopmental delays. Forty children were in "Monitor" range and 86 in "Refer" range. NDD rate was 60.0% (n = 126, 95% CI, 53.4 to 66.6%). There was no difference regarding CHD severity (p = 0.99). Only the presence of non-cardiac disease (OR = 2.14; 95% CI, 1.11 to 4.20) was associated with NDD. Forty-six children with NDD had no developmental follow-up (among them 21 were in "Refer" range (10%)) despite this being available.Conclusion: Children with significant CHD are at risk for NDD regardless of CHD severity. Systematic and early monitoring in a specific care program is required. Barriers that prevent access of care must be identified.Trial registration: Neurodevelopmental Disorders in Children With Congenital Heart Disease. NeuroDis-CHD. NCT03360370. https://clinicaltrials.gov/ct2/show/NCT03360370 What is Known: • Children with CHD are at risk for neurodevelopmental disorders and behavioural problems impacting their social adaptation, academic achievements and quality of personal and family life even in adulthood. What is New: • Children with CHD are at risk for neurodevelopmental disorders regardless of the complexity of the CHD. • Even with the availability of appropriate developmental services, children with CHD are not correctly followed, highlighting the need of a specific program of care for a better outcome. Local barriers that prevent access of care of those children must be identified.

Mutations in Citron Kinase Cause Recessive Microlissencephaly with Multinucleated Neurons.

Primary microcephaly is a neurodevelopmental disorder that is caused by a reduction in brain size as a result of defects in the proliferation of neural progenitor cells during development. Mutations in genes encoding proteins that localize to the mitotic spindle and centrosomes have been implicated in the pathogenicity of primary microcephaly. In contrast, the contractile ring and midbody required for cytokinesis, the final stage of mitosis, have not previously been implicated by human genetics in the molecular mechanisms of this phenotype. Citron kinase (CIT) is a multi-domain protein that localizes to the cleavage furrow and midbody of mitotic cells, where it is required for the completion of cytokinesis. Rodent models of Cit deficiency highlighted the role of this gene in neurogenesis and microcephaly over a decade ago. Here, we identify recessively inherited pathogenic variants in CIT as the genetic basis of severe microcephaly and neonatal death. We present postmortem data showing that CIT is critical to building a normally sized human brain. Consistent with cytokinesis defects attributed to CIT, multinucleated neurons were observed throughout the cerebral cortex and cerebellum of an affected proband, expanding our understanding of mechanisms attributed to primary microcephaly.

Differentiating Genetic Forms of Pontocerebellar Hypoplasia From Acquired Lesions Resembling Pontocerebellar Hypoplasia: Clinical, Neurodevelopmental, and Imaging Insight From 19 Extremely Premature Patients.

It is well established that extreme prematurity can be associated with cerebellar lesions potentially affecting the neurologic prognosis. One of the commonly observed lesions in these cases is pontocerebellar hypoplasia resulting from prematurity, which can pose challenges in distinguishing it from genetically caused pontocerebellar hypoplasia. This confusion leads to unacceptable and prolonged diagnostic ambiguity for families as well as difficulties in genetic counseling. Therefore, it is crucial to identify the clinical and neuroradiologic features allowing to differentiate between acquired and genetic forms of pontocerebellar hypoplasia in order to guide clinical practices and improve patient care. In this regard, we report in the present manuscript the clinical, developmental, and radiologic characteristics of 19 very premature children (gestational age <28 weeks, now aged 3-14 years) with cerebellar lesions and discuss the causal mechanisms. Our findings support the notion that a combination of specific clinical and radiologic criteria is essential in distinguishing between acquired and genetic forms of pontocerebellar hypoplasia.

Use of EEG in neonatal hypoxic-ischemic encephalopathy: A French survey of current practice and perspective for improving health care.

OBJECTIVES: Controlled therapeutic hypothermia (CTH) is a standard of care in the management of neonatal hypoxic-ischemic encephalopathy HIE in newborns after 36 weeks of gestational age (WGA) in France. The electroencephalogram (EEG) plays a major role in HIE diagnosis and follow-up. We conducted a French national survey on the current use of EEG in newborn undergoing CTH. METHODS: Between July and October 2021, an email survey was sent to the heads of the Neonatal intensive care units (NICUs) in metropolitan and overseas French departments and territories. RESULTS: Out of 67, 56 (83%) of NICUs responded. All of them performed CTH in children born after 36 WGA with clinical and biological criteria of moderate to severe HIE. 82% of the NICUs used conventional EEG (cEEG) before 6 h of life (H6), prior to CTH being performed, to inform decisions about its use. However, half of the 56 NICUs had limited access after regular working hours. 51 of the 56 centers (91%) used cEEG, either short-lasting or continuous monitoring during cooling, while 5 centers conducted only amplitude EEG (aEEG). Only 4 of 56 centers (7%) used cEEG systematically both prior to CTH and for continuous monitoring under CTH. DISCUSSION: The use of cEEG in the management of neonatal HIE was widespread in NICUs, but with significant disparities when considering 24-hour access. The introduction of a centralized neurophysiological on-call system grouping several NICUs would be of major interest for most centers which do not have the facility of EEG outside working hours.

Recanalization Treatments for Pediatric Acute Ischemic Stroke in France.

Importance: There is to date limited evidence that revascularization strategies are associated with improved functional outcome in children with acute ischemic stroke (AIS). Objectives: To report clinical outcomes and provide estimates of revascularization strategy safety and efficacy profiles of intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) in children with AIS. Design, Setting, and Participants: The KidClot multicenter nationwide cohort study retrospectively collected data of children (neonates excluded) with AIS and recanalization treatment between January 1, 2015, and May 31, 2018. Data analysis was performed from January 1, 2015, to May 31, 2019. Exposure: IVT and/or EVT. Main Outcomes and Measures: Primary outcome was day 90 favorable outcome (modified Rankin Scale [mRs] 0-2, with 0 indicating no symptoms and 6 indicating death). Secondary end points included 1-year favorable outcome (mRs, 0-2), mortality, and symptomatic intracerebral hemorrhage. Other measures included the Pediatric National Institutes of Health Stroke Scale (pedNIHSS), with pedNIHSS 0 indicating no symptoms, 1 to 4 corresponding to a minor stroke, 5 to 15 corresponding to a mild stroke, greater than 15 to 20: severe stroke, and the adult Alberta Stroke Program Early CT Score (ASPECTS), which provides segmental assessment of the vascular territory, with 1 point deducted from the initial score of 10 for every region involved (from 10 [no lesion] to 0 [maximum lesions]). Results: Overall, 68 children were included in 30 centers (IVT [n = 44]; EVT [n = 40]; 44 boys [64.7%]; median [IQR] age, 11 [4-16] years; anterior circulation involvement, 57 [83.8%]). Median (IQR) pedNIHSS score at admission was 13 (7-19), higher in the EVT group at 16 (IQR, 10-20) vs 9 (6-17) in the IVT only group (P < .01). Median time from stroke onset to imaging was higher in the EVT group at 3 hours and 7 minutes (IQR, 2 hours and 3 minutes to 6 hours and 24 minutes) vs 2 hours and 39 minutes (IQR, 1 hour and 51 minutes to 4 hours and 13 minutes) (P = .04). Median admission ASPECTS score was 8 (IQR, 6-9). The main stroke etiologies were cardioembolic (21 [30.9%]) and focal cerebral arteriopathy (17 [25.0%]). Median (IQR) time from stroke onset to IVT was 3 hours and 30 minutes (IQR, 2 hours and 33 minutes to 4 hours and 28 minutes). In the EVT group, the rate of postprocedure successful reperfusion (≥modified Treatment in Cerebral Infarction 2b) was 80.0% (32 of 40). Persistent proximal arterial stenosis was more frequent in focal cerebral arteriopathy (P < .01). Death occurred in 3 patients (4.4%). Median pedNIHSS reduction at 24 hours was 4 (IQR, 0-9) points. Intracerebral hemorrhage occurred in 4 patients and symptomatic intracerebral hemorrhage occurred in 1 patient, all in the EVT group. The median mRS was 2 (IQR, 0-3) at day 90 and 1 (IQR, 0-2) at 1 year, which was not significantly different between EVT and IVT only groups, although different in initial severity. Conclusions and Relevance: The findings of this cohort study suggest that use of EVT and/or IVT is safe in children with AIS.

Ultrasound diagnosis, management and prognosis in a consecutive series of 27 cases of fetal hydrops following maternal parvovirus B19 infection.

INTRODUCTION: Fetal hydrops caused by anemia from parvovirus B19 infection (FH-B19) is rare. Doppler measurement of the middle cerebral artery peak systolic velocity (PSV-MCA) improves its prenatal diagnosis, but its frequency and prognosis are still poorly known. Despite improved survival due to in utero transfusions, the possibility of late neurological sequelae makes prognosis uncertain. OBJECTIVES: To assess the frequency, management and prognosis of a consecutive series of FH-B19 observed over a 15-year period. METHODS: Retrospective study of 27 cases of FH-B19, that is, 3/100,000 births, 24 of them discovered during routine second-trimester ultrasound. All but 1 case (96.2%) had at least four of the six ultrasound signs that Saltzman et al. [Obstet Gynecol 1989;74:106-111] suggested as indicators of anemia. Of the fetuses tested, 80% had a PSV-MCA >1.5 MoM, also indicative of anemia. Of the 19 fetuses treated by exchange transfusions, 11 were liveborn compared with 2 of the 6 not so treated (57.8 vs. 33.3%, NS). The survival rate was higher during the second half of the study period (23.1 vs. 71.4%, p < 0.02) for less severe anemia (p < 0.03) and for repeated transfusions (p = 0.03). In our series, 1 case of prenatal cerebral atrophy was identified on screening. All 13 liveborn children appeared healthy at the age of 1 year. CONCLUSION: In cases of fetal hydrops, Saltzman et al.'s ultrasound criteria and PSV-MCA measurement made it possible to determine the likelihood that anemia is the cause of the hydrops and to measure its intensity. Use of these techniques allowed us to choose the most appropriate treatment (transfusion or not, depending on the degree of anemia), and survival improved notably in our series.

Comparison of seizure reduction and serum fatty acid levels after receiving the ketogenic and modified Atkins diet.

The ketogenic diet (KD) and the modified Atkins diet are effective therapies for intractable epilepsy. We compared retrospectively the KD and modified Atkins diet in 27 children and also assessed serum long chain fatty acid profiles. After 3 months, using an intent-to-treat analysis, the KD was more successful, with >50% seizure reduction in 11/17 (65%) vs. 2/10 (20%) with the modified Atkins diet, p=0.03. After 6 months, however, the difference was no longer significant: 7/17 (41%) vs. 2/10 (20%) (p=0.24). We observed a preventive effect of both diets on the occurrence of status epilepticus. After 1 and 3 months of either diet, responders experienced a significant decrease in serum arachidonic acid concentration compared to non-responders. The KD and modified Atkins diet led to seizure reduction in this small pilot series, with slightly better results after 3 months with the KD, but not after 6 months. The decrease of serum arachidonic acid levels might be involved in the anticonvulsive effects of KD or modified Atkins diet.

The location of DCX mutations predicts malformation severity in X-linked lissencephaly.

Lissencephaly spectrum (LIS) is one of the most severe neuronal migration disorders that ranges from agyria/pachygyria to subcortical band heterotopia. Approximately 80% of patients with the LIS spectrum carry mutations in either the LIS1 or DCX (doublecortin) genes which have an opposite gradient of severity. The aim of the study was to evaluate in detail the phenotype of DCX-associated lissencephaly and to look for genotype-phenotype correlations. Of the 180 male patients with DCX-related lissencephaly, 33 males (24 familial cases and nine cases with de novo mutations) were found with hemizygous DCX mutations and were clinically and genetically assessed here. DCX mutation analysis revealed that the majority of mutations were missense (79.2%), clustered in the two evolutionary conserved domains, N-DC and C-DC, of DCX. The most prominent radiological phenotype was an anteriorly predominant pachygyria or agyria (54.5%) although DCX-associated lissencephaly encompasses a complete range of LIS grades. The severity of neurological impairment was in accordance with the degree of agyria with severe cognitive impairment in all patients, inability to walk independently in over half and refractory epilepsy in more than a third. For genotype-phenotype correlations, patients were divided in two groups according to the location of DCX missense mutations. Patients with mutations in the C-DC domain tended to have a less severe lissencephaly (grade 4-5 in 58.3%) compared with those in the N-DC domain (grade 4-5 in 36.3%) although, in this dataset, this was not statistically significant (p = 0.12). Our evaluation suggests a putative correlation between phenotype and genotype. These data provide further clues to deepen our understanding of the function of the DCX protein and may give new insights into the molecular mechanisms that could influence the consequence of the mutation in the N-DC versus the C-DC domain of DCX.

Unusual clinical features in infantile Spinal Muscular Atrophies.

UNLABELLED: Spinal Muscular Atrophies (SMA) are a group of degenerative diseases primarily affecting the anterior horn cells of the spinal cord and resulting in muscle weakness and atrophy. Diagnostic criteria were proposed by the International SMA Consortium (ISMAC) to differentiate"classical" proximal SMA caused by homozygous deletion or conversion of the SMN1 gene (5q13) from atypical SMA unlinked to chromosome 5q (non-5q-SMA entities). The aim of our study was to emphasize the unusual clinical features encountered in infantile SMA. PATIENTS AND METHODS: We retrospectively analyzed 63 children with SMA hospitalized between 1985 and 2006. RESULTS: Forty-eight children suffered from classical SMA and 15 from atypical SMA, including 4 distal SMA, 2 scapuloperoneal SMA, one pontocerebellar hypoplasia type I, 7 neurogenic arthrogryposis multiplex congenita (2 of them associated with a central nervous system (CNS) involvement) and one undetermined case. CONCLUSION: This study confirmed the clinical variety of proximal SMA and put in perspective some exclusion criteria (CNS involvement, phrenic or facial palsy). Some symptoms allowed us to anticipate the normality of the SMN1 gene: improvement of motor condition, distal predominance and, more relatively, assymetry of motor weakness. Diagnosis difficulties were especially encountered in case of predominant distal deficit, arthrogryposis multiplex congenita and associated clinical abnormalities. Detailed phenotypical description and syndromic regrouping of cases of atypical SMA lead to a better understanding of underlying physiopathological processes and to the identification of other genes involved in infantile SMA.

Large spectrum of lissencephaly and pachygyria phenotypes resulting from de novo missense mutations in tubulin alpha 1A (TUBA1A).

We have recently reported a missense mutation in exon 4 of the tubulin alpha 1A (Tuba1a) gene in a hyperactive N-ethyl-N-nitrosourea (ENU) induced mouse mutant with abnormal lamination of the hippocampus. Neuroanatomical similarities between the Tuba1a mutant mouse and mice deficient for Doublecortin (Dcx) and Lis1 genes, and the well-established functional interaction between DCX and microtubules (MTs), led us to hypothesize that mutations in TUBA1A (TUBA3, previous symbol), the human homolog of Tuba1a, might give rise to cortical malformations. This hypothesis was subsequently confirmed by the identification of TUBA1A mutations in two patients with lissencephaly and pachygyria, respectively. Here we report additional TUBA1A mutations identified in six unrelated patients with a large spectrum of brain dysgeneses. The de novo occurrence was shown for all mutations, including one recurrent mutation (c.790C>T, p.R264C) detected in two patients, and two mutations that affect the same amino acid (c.1205G>A, p.R402H; c.1204C>T, p.R402C) detected in two other patients. Retrospective examination of MR images suggests that patients with TUBA1A mutations share not only cortical dysgenesis, but also cerebellar, hippocampal, corpus callosum, and brainstem abnormalities. Interestingly, the specific high level of Tuba1a expression throughout the period of central nervous system (CNS) development, shown by in situ hybridization using mouse embryos, is in accordance with the brain-restricted developmental phenotype caused by TUBA1A mutations. All together, these results, in combination with previously reported data, strengthen the relevance of the known interaction between MTs and DCX, and highlight the importance of the MTs/DCX complex in the neuronal migration process.

Postmeningitis subdural fluid collection in infants: changing pattern and indications for surgery.

OBJECT: Postmeningitis subdural fluid collection (PMSFC) is a classic complication of bacterial meningitis in infants. When the diagnosis was based solely on subdural puncture (SDP), its incidence was estimated to be as high as one half of the cases of meningitis, with Haemophilus influenzae as the most common causative bacterium. Knowledge concerning the diagnostic and bacteriological characteristics of PMSFC has expanded greatly since the introduction of computerized imaging and the use of the anti-H. influenzae vaccine; however, in no recent study have the authors reappraised this clinical entity with regard to diagnosis, bacteriology, and indications for surgery. METHODS: The authors reviewed their cases of PMSFC in infants in which a diagnosis was made based on computerized tomography findings and confirmed with SDP. They treated PMSFC using placement of a subdural drain whenever the collection was either clinically eloquent or exerted a mass effect on the brain. In the 26 years preceding the study, the authors had treated 29 patients younger than 16 months of age for PMSFC. Eight patients required SDP only, 20 underwent surgical drainage, and five required craniotomy. In six cases, the fluid was grossly purulent; in the others, it was clear, xanthochromatic, or hemorrhagic. Cultures were positive for Streptococcus pneumoniae in only two cases. Although H. influenzae was the most common bacterium at the beginning of the series, Neisseria meningitidis has become more prevalent since vaccination against the former became widespread. Based on their data the authors estimate that 5% of N. meningitidis infections in infants are complicated by a significant PMSFC. CONCLUSIONS: At present, PMSFCs are most often caused by N. meningitidis. Temporary surgical drain placement is advised for all cases in which a significant mass effect is apparent on imaging.

Spectrum of pontocerebellar hypoplasia in 13 girls and boys with CASK mutations: confirmation of a recognizable phenotype and first description of a male mosaic patient.

BACKGROUND: Pontocerebellar hypoplasia (PCH) is a heterogeneous group of diseases characterized by lack of development and/or early neurodegeneration of cerebellum and brainstem. According to clinical features, seven subtypes of PCH have been described, PCH type 2 related to TSEN54 mutations being the most frequent. PCH is most often autosomal recessive though de novo anomalies in the X-linked gene CASK have recently been identified in patients, mostly females, presenting with intellectual disability, microcephaly and PCH (MICPCH). METHODS: Fourteen patients (12 females and two males; aged 16 months-14 years) presenting with PCH at neuroimaging and with clinical characteristics unsuggestive of PCH1 or PCH2 were included. The CASK gene screening was performed using Array-CGH and sequencing. Clinical and neuroradiological features were collected. RESULTS: We observed a high frequency of patients with a CASK mutation (13/14). Ten patients (8 girls and 2 boys) had intragenic mutations and three female patients had a Xp11.4 submicroscopic deletion including the CASK gene. All were de novo mutations. Phenotype was variable in severity but highly similar among the 11 girls and was characterized by psychomotor retardation, severe intellectual disability, progressive microcephaly, dystonia, mild dysmorphism, and scoliosis. Other signs were frequently associated, such as growth retardation, ophthalmologic anomalies (glaucoma, megalocornea and optic atrophy), deafness and epilepsy. As expected in an X-linked disease manifesting mainly in females, the boy hemizygous for a splice mutation had a very severe phenotype with nearly no development and refractory epilepsy. We described a mild phenotype in a boy with a mosaic truncating mutation. We found some degree of correlation between severity of the vermis hypoplasia and clinical phenotype. CONCLUSION: This study describes a new series of PCH female patients with CASK inactivating mutations and confirms that these patients have a recognizable although variable phenotype consisting of a specific form of pontocerebellar hypoplasia. In addition, we report the second male patient to present with a severe MICPCH phenotype and a de novo CASK mutation and describe for the first time a mildly affected male patient harboring a mosaic mutation. In our reference centre, CASK related PCH is the second most frequent cause of PCH. The identification of a de novo mutation in these patients enables accurate and reassuring genetic counselling.

LIS1-related isolated lissencephaly: spectrum of mutations and relationships with malformation severity.

OBJECTIVE: With the largest data set of patients with LIS1-related lissencephaly, the major cause of posteriorly predominant lissencephaly related to either LIS1 mutation or intragenic deletion, described so far, we aimed to refine the spectrum of neurological and radiological features and to assess relationships with the genotype. DESIGN: Retrospective study. Subjects A total of 63 patients with posteriorly predominant lissencephaly. INTERVENTIONS: Of the 63 patients, 40 were found to carry either LIS1 point mutations (77.5%) or small genomic deletions (20%), and 1 carried a somatic nonsense mutation. On the basis of the severity of neuromotor impairment, epilepsy, and radiological findings, correlations with the location and type of mutation were examined. RESULTS: Most patients with LIS1 mutations demonstrated posterior agyria (grade 3a, 55.3%) with thin corpus callosum (50%) and prominent perivascular spaces (67.4%). By contrast, patients without LIS1 mutations tended to have less severe lissencephaly (grade 4a, 41.6%) and no additional brain abnormalities. The degree of neuromotor impairment was in accordance with the severity of lissencephaly, with a high incidence of tetraplegia (61.1%). Conversely, the severity of epilepsy was not determined with the same reliability because 82.9% had early onset of seizures and 48.7% had seizures more often than daily. In addition, neither the mutation type nor the location of the mutation were found to predict the severity of LIS1-related lissencephaly. CONCLUSION: Our results confirm the homogeneity profile of patients with LIS1-related lissencephaly who demonstrate in a large proportion Dobyns lissencephaly grade 3a, and the absence of correlation with LIS1 mutations.

Antenatal diagnosis of a third ventricular mass: fetus in fetu or teratoma?

BACKGROUND: Fetus in fetu (FIF) is a rare condition in medicine where an aberrant monozygotic twining results in inclusion of a degenerated fetus inside its twin bearer. Whereas FIF is generally defined as a fetiform vertebrate mass, teratoma is considered as a tumor composed of disorganized tissues derived from the three embryological layers. Recent data plead for a common origin and suggest a continuum between FIF and teratoma. CASE HISTORY: We describe the case of an intraventricular mass diagnosed by prenatal imaging and associated with triventricular hydrocephalus. Surgical removal of a non-vertebrate mass covered by normal skin was performed when the child was 15 months old. Now aged of 30 months, the child continues to develop normally. Histological data were in favor of a FIF. DISCUSSION: We discuss the diagnosis, pathogenesis, and prognosis in the light of data from the recent literature. CONCLUSIONS: Aberrant monozygotic twining leading to inclusion of a degenerate fetus inside its twin bearer results in FIF or teratomas. Surgical removal represents the main treatment. Intracranial FIF remains an extremely rare congenital condition, with a favorable oncological prognosis; the developmental prognosis appears conditioned by the absence of other malformation, the small size of the lesion, and the early management of intracranial hypertension.

French general practitioners' management of children's migraine headaches.

OBJECTIVES: This study sought to examine the treatment of children with migraine headaches in a prospective sample of children referred to a tertiary center for headaches. BACKGROUND: Despite the wide diffusion of guidelines for headache management in children, their application in general practice is far from optimal. METHODS: This prospective study analyzed previous headache treatment by general practitioners in 151 consecutive children (F/M: 0.82; mean age 10.4 +/- 3.2 years) referred for migraines to the Lille University Hospital Neuropediatric department between October 1, 2003, and November 30, 2005. The physician completed a questionnaire according to the parents' responses to questions about previous advice about life-style adjustments (diet, exercise, and sleep hygiene) and abortive and prophylactic treatment. Questions about abortive treatment covered ergot derivatives, triptans, and 3 aspects of ibuprofen use-appropriate dose (ie, more than 7.5 mg/kg), recommendation to administer the drug early in attacks, and warnings about drug abuse. Under the topic of prophylactic treatment, we asked about information from general practitioners about preventive therapy and advice to keep a headache diary. RESULTS: Fewer than 15% of patients had received advice about life-style adjustments. Only 30.3% had received ibuprofen at a correct dose (more than 7.5 mg/kg); only 26.5% were told to use it early during the headache; and only 9.1% were warned about drug abuse. Ergot derivatives were prescribed to 4.6% of children and triptans to 9.1%. Families of 17.9% reported that the general practitioners gave them information about prophylactic treatment. Only 8.0% were advised to keep a headache diary. CONCLUSION: This study shows the need to increase the role and the involvement of family doctors in the management of primary headache in children in general, and of pediatric migraine in particular.