[Characteristics of tuberous sclerosis in children]. / Spécificités de la sclérose tubéreuse de Bourneville chez l'enfant.

Tuberous sclerosis complex is a genetic multisystem disease characterized by hamartic development of many organs, most notably the brain, heart, kidneys, lungs, and skin. This autosomic dominant disorder results from mutations in one of two genes, TSC1 and TSC2, coding for hamartin and tuberin, respectively. The hamartin-tuberin complex inhibits the mammalian target of rapamycin pathway, which controls cell growth and proliferation. The clinical presentation is highly variable and most features of tuberous sclerosis become evident only in childhood after the child is several years of age, limiting their usefulness for early diagnosis. The aim of this article is to define the pediatric clinical manifestations of tuberous sclerosis in correlation with patient age. Sometimes, a prenatal diagnosis can be made based on fetal ultrasound and MRI, which show cardiac and brain lesions. However, newborns are most often asymptomatic. In the 1st year, seizures are the most common symptoms, with a high incidence of infantile spasms. In children between 2 and 10 years of age, neurological symptoms are the most frequent with epilepsy, mental retardation, and autism, but extraneurological manifestations can be diagnosed. In adolescents, most features of tuberous sclerosis become evident and renal and pulmonary manifestations must be sought. The knowledge of age-dependent clinical features of tuberous sclerosis can provide an earlier diagnosis and improve the management of these patients with a special role for multidisciplinary consultation.

[Childhood periodic syndromes]. / Les syndromes périodiques de l'enfance.

This review focuses on the so-called "periodic syndromes of childhood that are precursors to migraine", as included in the Second Edition of the International Classification of Headache Disorders. Three periodic syndromes of childhood are included in the Second Edition of the International Classification of Headache Disorders: abdominal migraine, cyclic vomiting syndrome and benign paroxysmal vertigo, and a fourth, benign paroxysmal torticollis is presented in the Appendix. The key clinical features of this group of disorders are the episodic pattern and intervals of complete health. Episodes of benign paroxysmal torticollis begin between 2 and 8 months of age. Attacks are characterized by an abnormal inclination and/or rotation of the head to one side, due to cervical dystonia. They usually resolve by 5 years. Benign paroxysmal vertigo presents as sudden attacks of vertigo, accompanied by inability to stand without support, and lasting seconds to minutes. Age at onset is between 2 and 4 years, and the symptoms disappear by the age of 5. Cyclic vomiting syndrome is characterized in young infants and children by repeated stereotyped episodes of pernicious vomiting, at times to the point of dehydration, and impacting quality of life. Mean age of onset is 5 years. Abdominal migraine remains a controversial issue and presents in childhood with repeated stereotyped episodes of unexplained abdominal pain, nausea and vomiting occurring in the absence of headache. Mean age of onset is 7 years. Both cyclic vomiting syndrome and abdominal migraine are noted for the absence of pathognomonic clinical features but also for the large number of other conditions to be considered in their differential diagnoses. Diagnostic criteria, such as those of the Second Edition of the International Classification of Headache Disorders and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, have made diagnostic approach and management easier. Their diagnosis is entertained after exhaustive evaluations have proved unrevealing. The recommended diagnostic approach uses a strategy of targeted testing, which may include gastrointestinal and metabolic evaluations. Therapeutic recommendations include reassurance, both of the child and parents, lifestyle changes, prophylactic therapy (e.g., cyproheptadine in children 5 years or younger and amitriptyline for those older than 5 years), and acute therapy (e.g., triptans, as abortive therapy, and 10% glucose and ondansetron for those requiring intravenous hydration).

The prevalence of premonitory symptoms in paediatric migraine: a questionnaire study in 103 children and adolescents.

The prevalence and characterization of premonitory symptoms have not been rigorously studied in children and adolescents. Using a questionnaire, we retrospectively studied the prevalence of 15 predefined premonitory symptoms in a clinic-based population. In 103 children and adolescents fulfilling the International Classification of Headache Disorders, 2nd edn criteria for paediatric migraine, at least one premonitory symptom was reported by 69 (67%). The most frequently reported premonitory symptoms were face changes, fatigue and irritability. The mean number of premonitory symptoms reported per subject was 1.8 (median 2.2). Age, migraine subtype (with or without aura) and mean attack frequency per month had no effect on the mean number of premonitory symptoms reported per subject. In conclusion, premonitory symptoms are frequently reported by children and adolescents with migraine. Face changes seem to be a premonitory symptom peculiar to paediatric migraine.

[Syncope and pre-syncope in children and adolescents: a prospective study in a pediatric emergency care unit]. / Syncopes et lipothymies chez l'enfant et l'adolescent : étude prospective dans une unité d'urgence pédiatrique.

OBJECTIVES: To assess in a pediatric emergency care unit (PECU): 1. The frequency of syncope and pre-syncope, 2. The incidence of diagnoses, 3. The value of investigations and cardiology and neurology consultations. METHODS: The data of PECU patients aged 2 years to 15 years and 3 months were prospectively collected over 1 year. Standard electrocardiogram and serum glucose were compulsory investigations. Schellong's orthostatic test was performed whenever possible. RESULTS: One hundred and fity-nine children (mean age, 11+/-4 years) were included, accounting for 0.8% of the PECU's visits: 48% had syncope, 52% had pre-syncope. The most common cause was neurally mediated syncope - 98 patients (62%), with vasovagal syncope for 80 patients - followed by neurological causes: 29 patients (18%). Neither cardiac arrhythmia nor obstructive cardiomyopathy was diagnosed. There were discrepancies between cardiologists' and pediatricians' ECG interpretations in 9% of cases. Diagnoses differed between cardiologists and pediatricians in 54% of 41 consultations. Diagnoses differed between neurologists and pediatricians in 54% of 42 consultations. No investigation except Schellong's orthostatic test led to modification of a previous diagnosis. CONCLUSION: This study emphasizes that the routine workup of pediatric syncope should focus on the patient's history and physical examination. Diagnostic testing should be minimal: ECG and Schellong's orthostatic test. The leading cause was neurocardiogenic syncope.

[Antiepileptic drugs for the prevention of pediatric migraine]. / Les antiépileptiques dans le traitement préventif de la migraine de l'enfant.

Migraine, according to the criteria of the International Headache Society, occurs in about 5 to 10% of children and adolescents. Pediatric migraine can cause a significant impact on quality of life. As stated by the American Academy of Neurology and Child Neurology Society's migraine guidelines, situations for prophylaxis consideration include recurring migraines that significantly interfere with daily activities, despite acute therapy; frequent headaches; contraindication, overuse, or failure of acute therapy; adverse reactions to acute therapy; cost of acute and preventive therapies; patient preferences; and presence of uncommon migraine conditions. Preventive therapy may be warranted in as many as 30% of young patients with migraine seen in tertiary headache centers. Headache related disability can be measured by scoring systems such as the Pediatric Migraine Disability Assessment Scale. Numerous medications have been studied to prevent migraines in children, including antihistamines, antidepressants, and antihypertensive agents. However, few high quality clinical trials actually demonstrate efficacy in this population. Recently, many studies dealt with the use of antiepileptic drugs in this indication but there is a paucity of placebo controlled studies. Both topiramate (TPM) and divalproex sodium have been studied in a randomized-controlled study. Only TPM showed efficacy, though, clearly, further controlled trials are needed to confirm these data. Besides unproven efficacy, adverse effects of valproic acid, such as weight gain, somnolence, and alopecia may limit its use. Additional studies are warranted before recommending levetiracetam (LVT), zonisamide (ZNS) and gabapentin (GBP) agents for migraine prophylaxis in children and adolescents.

[Management of chronic daily headache in children and adolescents]. / Prise en charge des céphalées chroniques quotidiennes chez l'enfant et l'adolescent.

Chronic daily headache (CDH) affects 2 to 4% of adolescent females and 0,8 to 2% of adolescent males. CDH is diagnosed when headaches occur more than 4 hours a day, for greater than or equal to 15 headache days per month, over a period of 3 consecutive months, without an underlying pathology. It is manifested by severe intermittent headaches, that are migraine-like, as well as a chronic baseline headache. Silberstein and Lipton divided patients into four diagnostic categories: transformed migraine, chronic tension-type headache, new daily-persistent headache, and hemicrania continua. The second edition of the International Classification of Headache Disorders did not comprise any CDH category as such, but provided criteria for all four types of CDH: chronic migraine, chronic tension-type headache, new daily-persistent headache, and hemicrania continua. Evaluation of CDH needs to include a complete history and physical examination to identify any possibility of the headache representing secondary headaches. Children and adolescents with CDH frequently have sleep disturbance, pain at other sites, dizziness, medication-overuse headache and a psychiatric comorbidity (anxiety and mood disorders). CDH frequently results in school absence. CDH management plan is dictated by CDH subtype, the presence or absence of medication overuse, functional disability and presence of attacks of full-migraine superimposed. Reassuring, explaining, and educating the patient and family, starting prophylactic therapy and limiting aborting medications are the mainstay of treatment. It includes pharmacologic (acute and prophylactic therapy) and nonpharmacologic measures (biobehavioral management, biofeedback-assisted relaxation therapy, and psychologic or psychiatric intervention). Part of the teaching process must incorporate life-style changes, such as regulation of sleep and eating habits, regular exercise, avoidance of identified triggering factors and stress management. Emphasis must be placed on preventive measures rather than on analgesic or abortive strategies. Stressing the reintegration of the patient into school and family activities and assessing prognosis are other issues to address during the first visit. There are limited data evaluating the outcome of CDH in children and adolescents.

[Chronic daily headache in children and adolescents]. / Les céphalées chroniques quotidiennes de l'enfant et de l'adolescent.

Chronic daily headache (CDH) affects 2-4% of adolescent females and 0.8-2% of adolescent males. Chronic daily headache is diagnosed when headaches occur more than 4h/day, 15 headache days per month or more, over a period of 3 consecutive months, without an underlying pathology. It is manifested by severe intermittent, migraine-like headaches as well as by chronic baseline headaches. Both Silberstein-Lipton criteria and the second edition of the International Classification of Headache Disorders (ICHD) can be used to classify chronic daily headache in children and adolescents. Chronic daily headache is classified into four diagnostic categories: transformed (Silberstein-Lipton criteria)/chronic (ICHD) migraine, chronic tension-type headache, new daily persistent headache, and hemicrania continua. Children and adolescents with chronic daily headache frequently have sleep disturbance, pain at other sites, dizziness, medication-overuse headache, and a psychiatric comorbidity (anxiety and mood disorders). Chronic daily headache frequently results in school absence. Successful approaches to treatment include reassurance, education, use of preventative medication, avoidance of analgesics, and helping the child return to a functional daily routine and a regular school schedule.

[Antiepileptic drugs in pediatric migraine]. / Les antiépileptiques dans le traitement préventif de la migraine de l'enfant.

According to the criteria of the International Headache Society, migraine occurs in approximately 5 to 10% of children. As many as 30% of young patients with migraine experience such frequent and disabling attacks, or have unsatisfactory results and/or experience adverse effects with pharmacologic treatment of acute migraine attack, that daily preventive medications are required. Many studies have investigated the use of antiepileptic drugs in this indication but there is a paucity of placebo-controlled studies. So far, in the setting of migraine with and without aura, only flunarizine and topiramate have proved their efficacy in more than one placebo-controlled study. Uncontrolled studies suggest the possible efficacy of valproic acid, gabapentin, levetiracetam, zonisamide, and magnesium in preventive therapy of childhood periodic syndromes. Most of antiepileptic drugs used in pediatric preventive therapy are well tolerated. The most common adverse events are asthenia and somnolence.

Clinical features of primary headache in children: a multicentre hospital-based study in France.

The aim of this study was to evaluate the concordance between clinical diagnosis and the International Classification of Headache Disorders, 2nd edn (ICHD-II) in children and adolescents with primary headaches. This 6-month prospective multicentre study of 486 patients (mean 9.8 +/- 3.1 years; 52.6% girls) assessed the headache features through a structured questionnaire. In 398 patients with a single type of headache, headaches were bilateral (78.1%), frontal (62.4%), pulsatile (56.1%), with associated symptoms in 84.4%. The most frequently assigned diagnoses were migraine without aura (50.8%), probable migraine (14.1%), migraine with aura (11.1%) and frequent episodic tension-type headache (7.5%). For most of the diagnostic categories, the consistency of the investigator's diagnosis with the ICHD-II criteria was good (kappa > 0.6 and < or = 0.8) or excellent (kappa > 0.8). We conclude that migraine was predominant with regard to headache diagnoses repartition and that the ICHD-II seems usable in practice for evaluation of primary headache in French children and adolescents.

Small vessel abnormalities in alternating hemiplegia of childhood: pathophysiologic implications.

BACKGROUND: The pathophysiology of alternating hemiplegia of childhood (AHC) is unclear. The authors evaluated the skin and muscle biopsies from patients with AHC for vascular abnormalities. METHODS: Skin biopsy specimens from four patients ages 18 months, 8 years, 9 years, and 18 years and muscle biopsies from two of these patients were examined by electron microscopy and compared with healthy controls. RESULTS: Vascular abnormalities were found in both skin and muscle. Skin biopsies showed similar abnormalities in all four patients. Vacuoles were visible in the endothelium. The most striking abnormality was the presence in the tunica media of small and unevenly shaped vascular smooth muscle cells (VSMCs) containing intracytoplasmic vacuoles and, occasionally, apoptotic nuclei, with variations according to patient age. Moreover, most VSMCs had lost junctions with neighboring cells, and some were completely isolated. In vessels from muscle biopsies, the VSMCs showed vacuoles, residual osmiophilic deposits, and myofilament loss with substitution by vacuoles. CONCLUSIONS: The vascular abnormalities in our patients suggest a primary or secondary vascular pathophysiology to alternating hemiplegia of childhood. The vascular smooth muscle cells may be the initial target of the disease process.

[Ataxia-telangiectasia: a review]. / Ataxie-télangiectasie: de la clinique à la physiopathologie.

Ataxia-telangiectasia (AT) is an autosomal recessive inherited disease caused by mutational inactivation of the ATM gene. It is a multisystemic disease, characterized by progressive neurological dysfunction, especially in the cerebellum, oculo-cutaneous telangiectasia, immunodeficiency, recurrent sino-pulmonary infections and high incidence of neoplasms. The responsible gene, ATM, encodes a large protein that belongs to a family of protein kinases with a phosphatidylinositol 3-kinase (Pi3K) domain. ATM is a key regulator of cell cycle checkpoints that causes DNA repair or apoptosis. Several studies report ATM function in target cells (such as neurons, fibroblast, endothelium, germ cells, lymphocytes). The pleiotropic phenotypes of AT reflect the multifaceted activities of ATM protein. In nucleus (lymphocytes, fibroblasts, germ cells) ATM is involved in regulation of cell-cycle checkpoints; in cytoplasm ATM regulates redox state (neurons).

[Pharmacologic treatment of acute migraine attack in children]. / Traitement médicamenteux de l'accès migraineux chez l'enfant.

Migraine, according to the criteria of the International Headache Society, occurs in about 5 to 10% of children. Management of acute headache is only one of the parts of the treatment, along with identification of migraine precipitants, adjustments in lifestyle, and when necessary the use of preventive therapy, which can include non pharmacologic (relaxation or biofeedback) or pharmacologic treatment. In the acute migraine attack, a single dose of either ibuprofen 10 mg/kg or paracetamol 15 mg/kg has been shown to be effective, with only a few adverse effects. In severe migraine attacks, dihydroergotamine mesylate administered orally (20 to 40 microg/kg) or intravenously (maximum 1 mg/day) may be helpful, but there have been no large placebo-controlled trials of this treatment. Among the different triptans, it is the sumatriptan nasal spray whose efficacy has been best demonstrated. The most frequent adverse event is transitory unpleasant taste.

[Drug treatment of migraine in children: state of the art]. / Traitement de fond de la migraine de l'enfant: état des connaissances du traitement pharmacologique.

Migraine, according to the criteria of the International Headache Society, occurs in about 5-10% of children. Preventive therapy includes identification of migraine precipitants, possible adjustments in lifestyle, appropriate management of acute headache, and when necessary the use of pharmacologic agents. It should be started if migraine attacks are severe or frequent. Non-pharmacologic prophylactic treatment is the modality of choice, based on relaxation or biofeedback. Despite its high incidence, only a few controlled trials have investigated the prophylactic treatment of migraine in children. Only flunarizine (5 mg/day) has been shown to be effective in two double-blind, placebo-controlled trials. Some evidence also exists that propranolol (60 mg/day) and pizotifen (0.5-1.5 mg/day) are effective. For all other drugs studied in migraine prophylaxis, the results remain vague (e.g. amitriptyline), or suggest inefficacy (e.g. clonidine, tryptophane). Most of the drugs used in the treatment of migraine in children are well tolerated. The most common adverse effects are drowsiness and bodyweight gain.

[A study of 100 consecutive children presenting with learning disabilities]. / Analyse d'une population de 100 enfants adressés pour troubles d'apprentissage scolaire.

DESIGN: To determine the impact of a neuropediatrician view on diagnosis and management of learning disabilities. METHOD: Retrospective review of the medical records of the last 100 children attending for learning disabilities from 1st June 2000 through 31st May 2001. Assessment concerned school curriculum, type of management before consultation, diagnosis procedure and type of management following consultation. Differential diagnosis was made in 100% of cases following evaluation. RESULTS: The three main diagnoses were attentionnal deficit disorder with hyperactivity (39%), mental retardation (17%) and dyslexia (7%). Mental retardation and cerebral palsy diagnoses had not been made before consultation. Conversely, 70% of the diagnoses of dyslexia made before consultation were incorrect. Medical treatment was proposed in 38% of cases and modification in the management in 59% of cases. CONCLUSION: This study highlights the interest of a rigorous diagnosis procedure for learning disabilities, based on a neuropediatrics examination, a cognitive evaluation and phonological and lexical evaluation. It only may lead to an appropriate management.