Postdrome symptoms in pediatric migraine: A questionnaire retrospective study by phone in 100 patients.

Background No study dedicated to postdrome symptoms of migraine attacks is available in children and adolescents. Objective To study the resolution phase of the migraine attack in children and adolescents. Methods 100 children and adolescents with ICHD-3 beta migraine without and/or with typical aura were included. Each patient, and one of her/his parents, were interviewed by phone about the postdrome phrase of their last six months' migraine attacks. They were specifically instructed to distinguish symptoms that had begun before and went on after migraine headache cessation (referred to as persistent symptoms), and symptoms whose onset was strictly after headache cessation (referred to as true postdromes). Results 91% of patients reported persistent symptoms, with a mean of 2.9 and a median of 2; asthenia, cognitive difficulties, pallor, cognitive slowing, anorexia, somnolence, and nausea were the most frequently reported. They lasted less than 12 h in 71% of patients. True postdromes were reported by 82% of patients, with a mean of 2.6 and a median of 2; thirst, somnolence, visual disturbances, food craving, paraesthesias, and ocular pain being the most frequently reported. They lasted less than 12 h in 94% of patients. Conclusions This study showed that children and adolescents with migraine had both frequent persistent symptoms and true postdromes. Both were notably different from those reported in adults.

Experts' opinion about the primary headache diagnostic criteria of the ICHD-3rd edition beta in children and adolescents.

BACKGROUND: The 2013 International Classification of Headache Disorders-3 (ICHD-3) was published in a beta version to allow the clinicians to confirm the validity of the criteria or to suggest improvements based on field studies. The aim of this work was to review the Primary Headache Disorders Section of ICHD-3 beta data on children and adolescents (age 0-18 years), and to suggest changes, additions, and amendments. METHODS: Several experts in childhood headache across the world applied different aspects of ICHD-3 beta in their normal clinical practice. Based on their personal experience and the literature available on pediatric headache, they made observations and proposed suggestions for the primary headache disorders section of ICHD-3 beta data on children and adolescents. RESULTS: Some headache disorders in children have specific features which are different from those seen in adults and which should be acknowledged and considered. Some features in children were found to be age-dependent: clinical characteristics, risks factors and etiologies have a strong bio psycho-social basis in children and adolescents making primary headache disorders in children distinct from those in adults. CONCLUSIONS: Several recommendations are presented in order to make ICHD-3 more appropriate for use with children.

Experts' opinion about the pediatric secondary headaches diagnostic criteria of the ICHD-3 beta.

BACKGROUND: The 2013 International Classification of Headache Disorders-3 was published in a beta version to allow clinicians to confirm the validity of the criteria or suggest improvements based on field studies. The aim of this work was to review the Secondary Headache Disorders and Cranial Neuralgias and Other Headache Disorders sections of ICHD-3 beta data on children and adolescents (age 0-18 years) and to suggest changes, additions, and amendments. METHODS: Several experts in childhood headache across the world applied different aspects of ICHD-3 beta in their normal clinical practice. Based on their personal experience and the available literature on pediatric headache, they made observations and proposed suggestions for the mentioned headache disorders on children and adolescents. RESULTS: Some headache disorders in children have specific features, which are different from adults that should be acknowledged and considered. Some features in children were found to be age-dependent: clinical characteristics, risks factors and etiologies have a strong bio psychosocial basis in children and adolescents making primary headache disorders in children distinct from those in adults. CONCLUSIONS: Several recommendations are presented in order to make ICHD-3 more appropriate for use in children.

Further delineation of eye manifestations in homozygous 15q13.3 microdeletions including TRPM1: a differential diagnosis of ceroid lipofuscinosis.

The 15q13.3 heterozygous microdeletion is a fairly common microdeletion syndrome with marked clinical variability and incomplete penetrance. The average size of the deletion, which comprises six genes including CHRNA7, is 1.5 Mb. CHRNA7 has been identified as the gene responsible for the neurological phenotype in this microdeletion syndrome. Only seven patients with a homozygous microdeletion that includes at least CHRNA7, and is inherited from both parents have been described in the literature. The aim of this study was to further describe the distinctive eye manifestations from the analysis in the three French patients diagnosed with the classical 1.5 Mb homozygous microdeletion. Patients' ages ranged from 30 months to 9 years, and included one sib pair. They all displayed a remarkably severe identifiable clinical phenotype that included congenital blindness and convulsive encephalopathy with inconstant abnormal movements. The ophthalmological examination revealed a lack of eye tracking, optic nerve pallor, an immature response with increased latencies with no response to the checkerboard stimulations at the visual evoked potential examination, and a distinctive retina dystrophy with a negative electroretinogram in which the "b" wave was smaller than the "a" wave after a dark adapted pupil and bright flash in all patients. Clear genotype-phenotype correlations emerged, showing that this eye phenotype was secondary to homozygous deletion of TRPM1, the gene responsible for autosomal recessive congenital stationary night blindness. The main differential diagnosis is ceroid lipofuscinosis.

The prevalence of triggers in paediatric migraine: a questionnaire study in 102 children and adolescents.

The prevalence and characterization of migraine triggers have not been rigorously studied in children and adolescents. Using a questionnaire, we retrospectively studied the prevalence of 15 predefined trigger factors in a clinic-based population. In 102 children and adolescents fulfilling the Second Edition of The International Headache Classification criteria for paediatric migraine, at least one migraine trigger was reported by the patient and/or was the parents' interpretation in 100% of patients. The mean number of migraine triggers reported per subject was 7. Mean time elapsed between exposure to a trigger factor and attack onset was comprised between 0 and 3 h in 88 patients (86%). The most common individual trigger was stress (75.5% of patients), followed by lack of sleep (69.6%), warm climate (68.6%) and video games (64.7%). Stress was also the most frequently reported migraine trigger always associated with attacks (24.5%). In conclusion, trigger factors were frequently reported by children and adolescents with migraine and stress was the most frequent.

Hemiplegic Migraine Associated With PRRT2 Variations: A Clinical and Genetic Study.

BACKGROUND AND OBJECTIVE: PRRT2 variants have been reported in a few cases of patients with hemiplegic migraine. To clarify the role of PRRT2 in familial hemiplegic migraine, we studied this gene in a large cohort of affected probands. METHODS: PRRT2 was analyzed in 860 probands with hemiplegic migraine, and PRRT2 variations were identified in 30 probands. Genotyping of relatives identified a total of 49 persons with variations whose clinical manifestations were detailed. RESULTS: PRRT2 variations were found in 12 of 163 probands who previously tested negative for CACNA1A, ATP1A2, and SCN1A variations and in 18 of 697 consecutive probands screened simultaneously on the 4 genes. In this second group, pathogenic variants were found in 105 individuals, mostly in ATP1A2 (42%), followed by CACNA1A (26%), PRRT2 (17%), and SCN1A (15%). The PRRT2 variations included 7 distinct variants, 5 of which have already been described in persons with paroxysmal kinesigenic dyskinesia and 2 new variants. Eight probands had a deletion of the whole PRRT2 gene. Among the 49 patients with variations in PRRT2, 26 had pure hemiplegic migraine and 16 had hemiplegic migraine associated with another manifestation: epilepsy (8), learning disabilities (5), hypersomnia (4), or abnormal movement (3). Three patients had epilepsy without migraine: 2 had paroxysmal kinesigenic dyskinesia without migraine, and 1 was asymptomatic. DISCUSSION: PRRT2 should be regarded as the fourth autosomal dominant gene for hemiplegic migraine and screened in any affected patient, together with the 3 other main genes. Further studies are needed to understand how the same loss-of-function PRRT2 variations can lead to a wide range of neurologic phenotypes, including paroxysmal movement disorder, epilepsy, learning disabilities, sleep disorder, and hemiplegic migraine.

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.

Study on management of pediatric migraine by general practitioners in northern France.

The study explored the awareness of the Haute Autorité de Santé (High Health Authority, HAS) guidelines for migraine management in children among a random sample of 100 general practitioners (GPs) dichotomised in an urban and a rural group. A questionnaire conducted by phone included questions on knowledge of pediatric migraine acute treatment and preventive therapy, referral to a child neurologist as well as GPs awareness of HAS recommendations in general. Although 45% of GPs argued they were prescribing ibuprofen as first-line abortive drug, only 3% were aware of the recommended dose. Only 48% of GPs were agreeing to initiate preventive therapy. Fifty percent of GPs stated that they knew HAS guidelines but only 24% stated that they had read them. The only significant difference between urban and rural GPs concerned the initiation of preventive therapy. Continuing educational programmes on the implementation of pediatric migraine guidelines is strongly needed.

Treatment of primary headache in children: a multicenter hospital-based study in France.

The aim of this 6-month, prospective, multicenter study of 398 children and adolescents with primary headaches was to collect data on headache treatment in neuropediatric departments. Treatments were compared before and after consultation. Prior to consultation, the acute treatments that had been prescribed most frequently were paracetamol (82.2% of children) and non-steroidal anti-inflammatory drugs treatment (53.5%); 10.3% had received a prophylactic treatment. No differences in either acute or prophylactic treatment with respect to headache diagnosis were observed. After the neuropediatric consultation, paracetamol was replaced by a non-steroidal anti-inflammatory drug in about three-quarters of cases and by triptan in about one-quarter of cases. The number of children prescribed a prophylactic treatment nearly doubled, whereas there was a 5-fold and 23-fold increase in psychotherapy and relaxation training, respectively, between pre-referral and referral. We conclude that specific treatments were underused for primary headache.

Pediatric vs. Adult Prodrome and Postdrome: A Window on Migraine Pathophysiology?

Few studies have been conducted on the prodromal and postdromal phases of the migraine attack in children and adolescents. Using a questionnaire, we found that 67% of 103 children and adolescents with migraine reported at least one prodromal symptom, with a mean number per subject of 1.8 (median 2.2). The most frequently reported prodromal symptoms were face changes, fatigue and irritability. In pediatric patients selected as having prodrome, fatigue, mood change and neck stiffness were the most frequently reported prodromal symptoms. Using a different design, Laurell et al. found that 71% of 137 pediatric patients reported at least one prodromal symptom with a mean number per subject of 1.9 ± 2.0. Studying postdrome was fraught with unexpected difficulties as our preliminary research showed. Patients reported 2 groups of symptoms occurring during the resolution phase of the headache: symptoms whose onset was before headache cessation and were persisting after it, and symptoms whose onset was after headache cessation. We referred to the former as persistent symptoms and to the latter as true postdromes. Ninety-one per cent of patients reported persistent symptoms, with a mean of 6.0 and a median of 2, asthenia, pallor, cognitive difficulties, anorexia, somnolence, and nausea being the more frequently reported. True postdromes were reported by 82% of patients, with a mean of 2.6 and a median of 2, thirst, somnolence, visual disturbances, food craving, paraesthesias, and ocular pain being the most frequent reported. Interestingly, several prodromal and postdromal symptoms are also encountered during the aura classic and/or accompany the headache phase. Functional imaging in migraine has showed that the activations in areas such as hypothalamus or brainstem may begin before headache onset and/or persist after headache relief. Thus, one may wonder whether prodromal and postdromal symptoms may indicate the involvement of the limbic system, dopaminergic pathways, the hypothalamus and the brainstem. Differences between children, adolescents and adults might contribute to the understanding of migraine neurobiology.

A 6.9 Mb 1qter deletion/4.4 Mb 18pter duplication in a boy with extreme microcephaly with simplified gyral pattern, vermis hypoplasia and corpus callosum agenesis.

We here report a boy presenting with developmental delay, growth retardation, facial dysmorphisms, vermis hypoplasia, micropolygyria and corpus callosum agenesis. Conventional and high resolution cytogenetic analyses were normal but high resolution oligonucleotide array-CGH, performed at the age of 4 years, allowed the characterisation of a de novo 6.9 Mb 1qter deletion/4.4 Mb 18pter duplication. Numerous 1qter deletions have already been described associated with brain malformations. Among 1q44 deleted genes, AKT3 is the strongest candidate gene for vermis hypoplasia and corpus callosum agenesis.

Epilepsia partialis continua and defects in the mitochondrial respiratory chain.

UNLABELLED: Epilepsia partialis continua (EPC) is characterized by continuous myoclonic or clonic jerks repeated at short intervals followed by a slowly progressive neurological disorder. We report three patients with EPC and a defect in the mitochondrial respiratory chain. METHODS: Clinical, neuroradiological, and biochemical data were reported. RESULTS: The patients presented continuous myoclonic jerks at age of 8 months, 11 months and 6 years, respectively. Two of the three patients had a previous developmental delay. Neurological examination at first admission revealed extrapyramidal symptoms in all patients. Initial biological investigations suggested mitochondrial dysfunction. Initial EEG showed a continuous discharge of periodic spikes (0.5-1Hz). MRI studies were initially normal then progressed to cerebral hemiatrophia. EEG revealed both correlation and absence of correlation between spikes or sharp waves and myoclonic jerks. The activity of one or several complexes of the mitochondrial respiratory chain was reduced in the muscle samples of the three patients. No mutation of mtDNA was found. CONCLUSION: Our report suggests that EPC can be due to mitochondrial respiratory chain disorders. Some clinical findings and initial investigations were indicative of a disorder of mitochondrial metabolism. Previous developmental delay, extrapyramidal symptoms and other organ involvement should suggest a possible mitochondrial etiology of EPC. In case of infant presenting EPC, mitochondrial respiratory chain disorder should be considered first.

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.

Subdural effusion in a CNS involvement of systemic juvenile xanthogranuloma: a case report treated with vinblastin.

Juvenile xanthogranuloma (JXG) is one of the most common non-Langerhans cell histiocytosis in children. Usually cutaneous, there are disseminated forms. However, neurological localization remains exceptional. A 7-month-old boy had been admitted for subdural effusion due to non-accidental head injury and skin nodular lesions. A biopsy of a skin lesion was considered suggestive of JXG. Skin, eyes, brain, lungs, liver, and testicles were involved. Systemic treatment of JXG was begun with vinblastine. It allowed the regression of skin, lung, and CNS lesions. At age of 11 years, he had not reappearance of the xanthogranuloma. This report emphasizes the possible presentation of xanthogranuloma with subdural effusions, the organs which should be examined in case of disseminated forms and the efficiency of vinblastin.

Chronic daily headache in French children and adolescents.

To characterize the clinical profile, comorbidity and aggravating factors, and outcomes, a consecutive series of 34 French children and adolescents with chronic daily headache was studied. Of 206 referred over an inclusive interval of 2 years for the evaluation of headaches, 34 merited a diagnosis of chronic daily headache, which was defined as persistent or daily headaches of at least 3 months in duration. The overwhelming majority were female (61.8%), with a mean age at diagnosis of 10.5+/-3.1 years (range, 2.9-14.8 years). According to the Silberstein-Lipton criteria, transformed migraine was the etiology in 61.8%, whereas according to the second edition of the International Classification of Headache Disorders, chronic migraine accounted for 50% of cases. Stressors were recognized in 82%. Analgesic abuse was evident in 52.9%. Of the 29 for whom follow-up information was available, headaches resolved or greatly improved in 93.1%. Children and adolescents with chronic daily headache are thus a small subset of children with headache seen in general ambulatory practice. They tend to be girls in the midteen years experiencing a transformed migraine complicated by analgesic abuse, suggesting potential preventability. Simple measures, which can include reassurance and analgesia education, can be expected to result in improvement and eventual resolution of headache symptoms.

Trigger Factors in Childhood Migraine: A Prospective Clinic-Based Study From North of France.

The objective was to study the prevalence and characterization of pediatric migraine triggers and to compare results to this retrospective study. A total of 101 pediatric patients with ICHD-II migraine with and/or without aura were instructed to prospectively complete a diary dealing with attacks triggers for a 3-month period. Each subject reported at least 1 trigger (range: 1-14) with a total number of 532 attacks and a median per subject of 3. Lack of sleep (51.4%), stress (44.6%), warm climate (41.9%), noise (32.4%), and excitation (29.7%) were the most frequently reported. The delay between trigger exposure and attack onset was between 0 and 3 hours in 67.6% of attacks. This prospective study confirmed the findings of the authors' previous study, with the exception that number of triggers was smaller, probably due to recall bias. The 4 most frequent triggers (lack of sleep, stress, hot weather, and noise) were identical in both studies.