Search

Stably transfected Chinese hamster ovary cells expressing either the substance P receptor or neurokinin A receptor were constructed, isolated, and characterized. Equilibrium ligand binding studies performed on whole cells demonstrated that cell lines expressing either of these receptors contained a single class of high-affinity binding sites with an apparent KD of 0.16 nM for the substance P receptor and an apparent KD of 2.1 nM for the neurokinin A receptor. The higher affinity of substance P for its receptor was accounted for by both a greater association rate constant and a lesser dissociation rate constant. The time course and extent of ligand-stimulated inositol 1,4,5-trisphosphate mass increases in both cell lines were similar and displayed rapid and transient kinetics. Ligand-stimulated cyclic AMP accumulation was also apparent in the cell lines, although the time course and magnitude of the responses were substantially different, with the neurokinin A receptor mediating a greater and more prolonged response. These studies establish the presence of functional substance P receptors and neurokinin A receptors in the stably transfected cell lines and provide evidence for agonist-dependent differential stimulation of second messenger responses.

Headaches in children, adolescents and adults are quite common. The study and characterization of childhood headaches, however, entered an era of increased interest with the adoption of the first edition of the International Classification of Headache Disorders [1]. The initial description of headaches in humans is quite old. Ancient writings in an epic poem from the Sumerian area dating back to 3000 BC describe what appear to be migraine-type headaches (i.e. ‘the sick headache’).

Migraine can be a disabling pain condition that episodically and often unpredictably impacts patients. For teens, this can mean missed activities. Teens may withdraw from activities with friends and from school work. In adults with migraine, it is believed that there may be a connection between migraine and depression. It is unclear whether these two conditions simply occur together, or whether one causes the other. Suicidal ideation, or thinking about suicide, is more common during the teen years. These issues in the teen years are difficult because teens are still developing. The presence of an ongoing health condition, especially if it is under-recognized, like migraine, may add further complications. There always needs to be an awareness of these issues when caring for teens with migraine. In this issue of Neurology ®, a study by Dr. Wang and coauthors (Migraine and suicidal ideation in adolescents aged 13 to 15 years. Neurology 2009;72:1146–1152) examined the connections between migraine and suicidal ideation in teens aged 13 to 15 years. The goal of this study was to compare how often teens with migraine had suicidal ideation compared to teens in general. The authors wanted to see whether teens with migraine had more suicidal ideation and whether there were factors that could predict who of those teen sufferers would be at greatest risk. The authors surveyed nearly 4,000 teens in middle school (seventh to ninth grade) in Taiwan. This is a large sample of the over 9,000 middle school children of this age in the area. They included teens in urban and rural schools. The survey was designed to describe headaches, migraine, chronic daily headaches, and psychological or emotional issues in the teens. The teens completed the surveys …

The aim of this study was to evaluate the impact of gender and age on headache characteristics and disability. Headache characteristics were assessed at an initial visit to a paediatric specialty care centre and five follow-up visits. A total number of 4121 patients were evaluated. Fifty-eight per cent of the sample was female. Boys were younger at their first headache and initial visit. They more frequently described headache pain as squeezing and location as top of the head. Girls reported more frequent and longer headaches. Girls more often described headache pain as sharp and location as back of the head. Age accounted for more variance than gender in headache severity, duration, frequency and disability. Gender differences exist in headache characteristics. Age is also an important factor in the variability in characteristics and disability. Longitudinal studies are needed to describe further the natural history of headaches in childhood and compare outcome between genders.

Objective.— To assess the effectiveness of aggressive therapy of status migraine in children and adolescents. Background.— Inpatient management of pediatric status migraine and intractable headache is limited because of a lack of studies and guidelines. Adult treatment is often based on anecdotal experience, although a few controlled studies have been reported. Added to that is the discomfort of general pediatricians and neurologists in using available effective treatments in pediatric patients (such as dihydroergotamine: DHE). Methods.— Charts of all patients admitted to the neurology service, at Cincinnati Children's Hospital Medical Center—Department of Neurology, for inpatient treatment for intractable headache/status migraine over a 6-week period were reviewed. Demographics, evaluation, diagnosis, and treatment used were tabulated. Data on the effectiveness of the treatments provided were evaluated. Thirty-two total consecutive charts were retrospectively reviewed during that period. Results.— Upon discharge, 74.4% of the patients were headache-free. The mean severity of the pain upon discharge was 1.02 ± 2.22 (using the 0-10 pain scale). Conclusion.— From our review, DHE is very effective in treating and aborting an episode of status migraine and should be offered to children and adolescent patients who have failed their usual abortive therapy to prevent further severe disability that mainly affects their schooling and social activities.

During the formation of an inhibitory complex with neutrophil elastase, alpha 1 antitrypsin (alpha 1 AT) undergoes a structural rearrangement and the resulting alpha 1 AT-elastase complex becomes endowed with chemoattractant activities, mediates an increase in synthesis of alpha 1 AT, and is rapidly cleared from the circulation. In previous studies we have provided evidence that these biological activities involve the recognition of a conformation-specific domain in the alpha 1 AT molecule by a cell surface receptor on human hepatoma HepG2 cells and human monocytes. The receptor has been termed the serpin-enzyme complex (SEC) receptor because it also recognizes complex of serpins antithrombin III, alpha 1 anti-chymotrypsin, and C1 inhibitor with their cognate enzymes. Because a pentapeptide domain of alpha 1 AT (amino acids 370-374, Phe-Val-Phe-Leu-Met) is sufficient for binding to the SEC receptor and the sequence of this domain is remarkably similar to those of substance P, several other tachykinins, bombesin, and the amyloid-beta peptide, we have examined the possibility that these other ligands bind to the SEC receptor. The results indicate that substance P, several other tachykinins, and bombesin compete for binding to, and cross-linking of, the SEC receptor. The SEC receptor is distinct from the substance P receptor by several criteria. There is no substance P receptor mRNA in HepG2 cells; the SEC receptor is present in much higher density on receptor-bearing cells and binds its ligands at lower affinity than the substance P receptor; the SEC receptor is much less restricted in the specificity with which it recognizes ligand; ligands for the SEC receptor including peptide 105Y (based on alpha 1 AT sequence 359-374), alpha 1 AT-protease complexes, and bombesin do not compete for binding of substance P to a stable transfected cell line expressing the substance P receptor. Finally, we show here that the amyloid-beta peptide competes for binding to the SEC receptor but does not bind to the substance P receptor, therein raising the possibility that the SEC receptor is involved in certain biological activities, including the recently described neurotrophic and neurotoxic effects ascribed to the amyloid-beta peptide.

The gene for the rat substance P receptor has been cloned, its genomic structure determined, and the patterns of mRNA expression extensively analyzed. Unlike many genes encoding G protein-coupled receptors, the protein-coding region of this gene is divided into five exons consisting of 965, 195, 151, 197, and 2,010 base pairs. The substance P receptor gene extends more than 45 kilobases in length, and the splice sites for the exons occur at the borders of the sequences encoding putative membrane-spanning domains. The transcription initiation site has been defined by solution hybridization-nuclease protection and nucleotide sequence analyses, and lies downstream of a conventional TATA sequence. Substance P receptor mRNA levels in various tissues have been quantitated using solution hybridization-nuclease protection assays and were found to comprise from 0.00008 to 0.0016% of total RNA levels. Relatively high levels of substance P receptor mRNA are seen in the urinary bladder and the sublingual salivary gland, whereas moderate levels are observed for the submandibular salivary gland, striatum, hippocampus, midbrain, and olfactory bulb with lower levels in the remainder of the central nervous system and alimentary canal. These results are discussed in relation to the evolutionary role of multiple exons for a G protein-coupled receptor and with regard to the locations and mechanisms of substance P receptor gene expression.

Objective.— To use a case–control design to evaluate the emotional and behavioral functioning of children with migraine. Background.— Research has indicated that children with migraine are at increased risk for emotional and behavioral problems such as depression and anxiety; however, methodological limitations in sample definitions, measurement strategies, and comparison groups remain problematic. Method.— Forty-seven participants diagnosed with migraine at a pediatric headache center participated in a home-based study of child functioning using standardized measures. Mothers and fathers of these children participated, as did control families recruited from among classmates. Results.— Indications of increased emotional and behavioral difficulties for children with migraine were found, primarily from the perspective of mothers. Exploratory analyses found several associations between mother and child perceptions of difficulties and persistence of headache symptoms following initiation of multidisciplinary headache treatment. Conclusions.— Continued concern regarding emotional well-being of children with migraine is warranted, but more work is needed to understand the differing perspectives of family members. Particular attention to emotional well-being is needed for children whose headache symptoms persist despite multidisciplinary treatment.

Background – Genomic analysis using microarray tools has the potential benefit of enhancing our understanding of neurological diseases. The analysis of these data is complex due to the large amount of data generated. Many tools have been developed to assist with this, but standard methods of analysis of these tools have not been established. Objective – This study analyzed the sensitivity and specificity of different analytical methods for gene identification and presents a standardized approach. Methods – Affymetrix HG-U133 plus 2.0 microarray datasets from two neurological diseases – chronic migraine and new-onset epilepsy – were used as source data and methods of analysis for normalization of data and identification of gene changes were compared. Housekeeping genes were used to identify non-specific changes and gender related genes were used to identify specific changes. Results – Initial normalization of data revealed that 5–10% of the microarray were potential outliers due to technical errors. Two separate methods of analysis (dChip and Bioconductor) identified the same microarray chips as outliers. For specificity and sensitivity testing, performing a per-gene normalization was found to be inferior to standard preprocessing procedures using robust multichip average analysis. Conclusions – Technical variation in microarray preprocessing may account for chip-to-chip and batch-to-batch variations and outliers need to be removed prior to analysis. Specificity and sensitivity of the final results are best achieved following this identification and removal with standard genomic analysis techniques. Future tools may benefit from the use of standard tools of measurement.

Substance P is a member of the tachykinin peptide family and participates in the regulation of diverse biological processes. The polymerase chain reaction and conventional library screening were used to isolate a complementary DNA (cDNA) encoding the rat substance P receptor from brain and submandibular gland. By homology analysis, this receptor belongs to the G protein-coupled receptor superfamily. The receptor cDNA was expressed in a mammalian cell line and the ligand binding properties of the encoded receptor were pharmacologically defined by Scatchard analysis and tachykinin peptide displacement as those of a substance P receptor. The distribution of the messenger RNA for this receptor is highest in urinary bladder, submandibular gland, striatum, and spinal cord, which is consistent with the known distribution of substance P receptor binding sites. Thus, this receptor appears to mediate the primary actions of substance P in various brain regions and peripheral tissues.

A family history of migraine is very frequently noted when evaluating a child for recurrent headaches. This implies an inherited or genetic basis as a component to the underlying pathophysiology. A variety of techniques have begun to elucidate this contribution, including historical observation, population-based studies including family and twin studies, gene polymorphism association studies, and specific gene identification for isolated migraine subtypes. This line of investigation should progress in the future to a better understanding of migraine and clarification of the diagnostic subtypes for a genotype-phenotype association.

Objective.—The aim of the present study was to assess sleep patterns and the prevalence of sleep problems in adolescents with primary headaches using a validated sleep screening instrument, as well as to test the association between headache and pain features and adolescent sleep behaviors. Background.—Sleep disturbance is a common complaint that has long been associated with primary headaches, but there exists limited evidence of the headache-sleep relationship among teens. Methods.—Sixty-nine adolescents aged 13 to 17 years (M= 14.7; SD= 1.4) were evaluated for headaches at 2 pediatric neurology departments (90% migraine; 10% tension-type headache diagnoses). Participants completed the School Sleep Habits Questionnaire and a standardized questionnaire regarding headache characteristics. Results.—Sleep complaints were prevalent among adolescents with headaches including insufficient total sleep (65.7%), daytime sleepiness (23.3%), difficulty falling asleep (40.6%), and night wakings (38%). Statistically significant relationships between headache characteristics (eg, frequency, pain intensity) and teen sleep behaviors also emerged. Conclusions.—Our findings provide further support for an association between headache and sleep disturbances among adolescents with primary headaches. This information may provide further understanding of the nature and course of the patient's headache experience, as well as facilitate treatment planning to include recommendations for promoting good sleep hygiene.

BACKGROUND: Coenzyme Q10 (CoQ10) has been suggested to be effective in the prevention of migraine, and levels can be quantified with standardized reference ranges. OBJECTIVE: This study documents the prevalence of CoQ10 deficiency in migraine headache and examines the potential effectiveness of supplementation. METHODS: We assessed patients attending a tertiary care center with frequent headaches for CoQ10 deficiency. We recommended patients with low CoQ10 levels begin supplementation with CoQ10 as part of their multidisciplinary treatment plan. We assessed response to treatment including correction of CoQ10 deficiency, overall headache improvement, and headache disability. RESULTS: CoQ10 was measured in 1550 patients (mean age 13.3 +/- 3.5, range 3 to 22 years). The mean total CoQ10 level was 0.60 +/- 0.20 microg/mL (range 0.21 to 1.77 microg/mL). Of these patients, 32.9% were below the reference range. Patients with low CoQ10 were recommended to start 1 to 3 mg/kg per day of CoQ10 in liquid gel capsule formulation. In a subset of patients who returned for timely follow-up (mean, 97 days), the total CoQ10 level improved to 1.20 +/- 0.59 microg/mL (P < .0001), while the headache frequency improved from 19.2 +/- 10.0 to 12.5 +/- 10.8 (P < .001) and headache disability assessed with PedMIDAS improved from 47.4 +/- 50.6 to 22.8 +/- 30.6 (P < .001). CONCLUSIONS: Deficiency of CoQ10 may be common in pediatric and adolescent migraine. Determination of deficiency and consequent supplementation may result in clinical improvement. Further analysis involving more scientifically rigorous methodology will be required to confirm this observation.

Once the correct diagnosis of migraine in a child is established, a treatment plan can be developed. This often entails a combination of acute therapies, preventive therapies, and biobehavioral interventions. Goals of treatment should be clearly established for the patients and parents, and realistic time courses discussed. Overall outcome in terms of disability and quality of life also may need to be addressed and included within the evaluation and management scheme.

Sequencing of the human genome and new microarray technology make it possible to assess all genes on a single chip or array. Recent studies show different patterns of gene expression related to different tissues and diseases, and these patterns of gene expression are beginning to be used for diagnosis and treatment decisions in various types of lymphoid and solid malignancies. Because of obvious problems obtaining brain tissue, progress in genomics of neurological diseases has been slow. To address this, we demonstrated that different types of acute injury in rodent brain produced different patterns of gene expression in peripheral blood. These animal studies have now been extended to human studies. Two groups have shown that there are specific genomic profiles in the blood of patients after ischemic stroke that are highly sensitive and specific for predicting stroke. Other recent studies demonstrate specific genomic profiles in the blood of patients with Down syndrome, neurofibromatosis, tuberous sclerosis, Huntington disease, multiple sclerosis, Tourette syndrome, and others. In addition, data demonstrate specific profiles of gene expression in the blood related to different drugs, toxins, and infections. Although all of these studies are still preliminary basic scientific endeavors, they suggest that this approach will have clinical applications to neurological diseases in humans.

Migraine in the pediatric population remains substantially underdiagnosed and undertreated. The recently revised International Classification of Headache Disorders is a step in the right direction to improve our diagnostic accuracy. This article reviews the practical diagnostic issues related to migraine in the pediatric population.

Headache is one of the most common health concerns in children and adolescents, yet remains underrecognized as a disease. A variety of factors, including the unique aspects of childhood headaches, contribute to this underrecognition.Improving recognition of childhood and adolescent headaches and using a standardized approach for their evaluation is expected to lead to the appropriate diagnosis and subsequent additional evaluation and management to improve the overall outcome in children and adolescents with headaches. Building on limited studies in children and adolescents and translating adult studies to children can assist in designing a multidisciplinary treatment plan.This review focuses on some of the unique aspects of evaluating children and adolescents with headaches; the impact of these headaches on school, home, and family function; determination of disability and influence of comorbid conditions; and development of a treatment plan that incorporates acute, preventive, and biobehavioral management tools.

Pediatric headache is a common health problem in children, with a significant headache reported in more than 75% by the age of 15 years. Pediatric migraine occurs in up to 10.6% of children between the ages of 5 and 15 years and in up to 28% of adolescents between the ages of 15 and 19 years. Given this high frequency, the impact of this disease on the lives of these children and their parents can be quite significant. This impact can be assessed with disease-specific disability and impairment as well as disease non-specific effects on quality of life. The goal of evaluation should be recognition of this impact, whereas the goal of management should be effective treatment that minimizes the impact of this disorder in the short term and for the life of the patient.

The diagnosis of migraine headache in childhood rests on criteria similar to those used in migraine in adults. It is important, however, to appreciate several fundamental differences. These differences include the duration of attack, which is often far shorter than in an adult, and the location of the attack, which may be bilateral in many children. The treatment of children and adolescents with migraines includes treatment modalities for acute attacks, preventive medications when the attacks are frequent, and biobehavioral modes of therapy to address long-term management of the disorder. The controlled clinical trials of medications in pediatric migraine have suffered from high placebo response rates that may be related to the sites conducting the study (ie, headache specialist vs clinical research organizations). The medications have proved to be safe in the pediatric age group. Treatment modalities for acute migraine include over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs), as well as the oral triptans such as sumatriptan succinate, rizatriptan benzoate, and zolmitriptan and the nasal spray formulations of sumatriptan and zolmitriptan. Subcutaneous sumatriptan and parenteral dihydroergotamine have also been used limitedly. Preventive treatment for patients with frequent or disabling migraines (or both) includes the antidepressants amitriptyline hydrochloride and nortriptyline hydrochloride, the anticonvulsants divalproex sodium and topiramate, and the antihistaminic agent cyprohepatine hydrochloride. Biobehavioral approaches aimed at addressing the fundamental lifestyle issues and nonpharmacologic approaches to management are fundamental to long-term success.

The objective was to develop and validate a patient-based grading scale for PedMIDAS. PedMIDAS was administered to 329 children, who rated their overall disability based on the adult MIDAS grades. This patient-based rating and PedMIDAS scores were compared to develop the grading scale. Headache disability was rated little to none, 49.5%; mild, 26.7%; moderate, 15.8%; and severe, 7.9%, with PedMIDAS raw scores of 4.9 ± 6.3, 17.8 ± 14.9, 40.6 ± 34.2, and 91.4 ± 69.8. Convergence of these results yielded an empirically derived grading system: Grade I, 0-10; II, 11-30; III, 31-50 and IV, > 50. Higher grades corresponded to an increased need for prophylactic treatment. A patient-based grading scale further increases the utility of PedMIDAS in assessing migraine disability in children, so that it can be widely used in routine clinical evaluation and management.

Objective.—The aim of the present study was to investigate the prevalence of sleep disturbances in children with migraine headaches and to describe individual differences in sleep behaviors based on headache features (eg, frequency, duration, intensity). Background.—A relationship between migraine headaches and sleep disturbances has been suggested in both children and adults, but there is a lack of research examining the relationship between specific headache features and the range of sleep behaviors in children. Methods.—One hundred eighteen children, aged 2 to 12 years (mean, 9.1; standard deviation, 2.3) were evaluated for headaches at two pediatric neurology departments. Parents completed the Children’s Sleep Habits Questionnaire and a standardized questionnaire regarding headache characteristics. Results.—Parents reported a high rate of sleep disturbances in children, including sleeping too little (42%), bruxism (29%), child co-sleeping with parents (25%), and snoring (23%). Children with migraine headaches experienced more sleep disturbances compared to published healthy control norms. After controlling for child demographics, we found that the frequency and duration of migraine headaches predicted specific sleep disturbances, including sleep anxiety, parasomnias, and bedtime resistance. Conclusions.—Children with migraine headaches have a high prevalence of sleep disturbances. The direction of the relationship between headaches and sleep is unknown. Regardless, interventions targeting sleep habits may improve headache symptoms, and effective treatment of headaches in children may positively impact sleep.

Background.—Adults with chronic daily headache often describe a transformation from episodic migraine and partial retention of migrainous features. Although chronic daily headache has not been investigated as carefully in the pediatric population, one study showed a predominance of coexisting daily headache and episodic migraine, without a clear history of transformation. Objective.—To identify the clinical features of chronic daily headache in children and adolescents, to evaluate the efficacy of current headache classification criteria, and to compare the features of coexistent daily and episodic headaches so as to determine whether they represent separate syndromes or different stages in the “transformation” process. Design.—We surveyed 189 consecutive patients, 18 years of age or younger, who presented for initial evaluation of daily or near daily headache at one of 9 tertiary headache clinics. Data were collected in semistructured interviews employing a standard questionnaire and analyzed using Statistical Analysis Systems and Stata statistical software computer programs. Results.—Of the patients enrolled, 70% were female and 87% were white. Mean age was 13.0 ± 3.1 years. Male gender was associated with a higher degree of reported disability. A family history of headache (typically migraine) was described in 79%. Use of nonsteroidal anti-inflammatory drugs 5 days per week or more was reported by 44% of patients. The International Headache Society (IHS) criteria failed to classify 64% of patients and criteria proposed by Silberstein et al failed to classify 31% of patients. Participating physicians misclassified patients according to criteria of the IHS and Silberstein et al in one third of cases. Nearly one quarter of patients reported two separate headache types with distinguishing characteristics. “Baseline” headache was present 27.3 ± 4.1 days per month with a mean pain intensity of 5.9 ± 2.1 on a 10-point scale. Superimposed episodic headache occurred 4.7 ± 3.8 days per month with a mean pain intensity of 8.4 ± 1.4, and was more often accompanied by other migrainous symptoms. After logistic regression to control for pain intensity, the only statistically significant difference between the two headache types was a lower prevalence of tension-type head pain with the superimposed headache. Conclusions.—Our data suggest that rather than having two coexistent headache types, children and adolescents with chronic daily headache have a single syndrome that, in many cases, will paroxysmally worsen and gather migrainous features.

The primary aim of this study was to describe pain characteristics, coping strategies, depression, and functional disability in children and adolescents with chronic pain and to examine potential factors that are associated with functional disability in a pediatric pain population. The secondary aim of this study was to compare functional disability in two chronic pain conditions: localized musculoskeletal pain and chronic daily headaches.The participants in this study were 73 pediatric pain patients with a variety of chronic pain conditions. Subjects in the second part of the study were a subset of patients (N = 44) from the pain clinic sample with chronic localized musculoskeletal pain and a subset of patients (N = 38) from the headache center of the same hospital who had chronic daily headaches.Patients completed self-report measures of pain intensity, depression, coping strategies, coping efficacy, and functional disability.Results indicated that chronic pain had a substantial impact on the children's lives and that depression was strongly associated with functional disability. Maladaptive coping was correlated with depression and disability; however, maladaptive coping was not independently associated with functional disability. A comparison between the two groups found significant differences in pain intensity and functional disability. The localized musculoskeletal pain group reported higher levels of disability and more difficulty coping than the chronic daily headache group.The implications for treatment of chronic pain in children are discussed with an emphasis on greater attention to developmental issues and their relation to coping, emotional functioning, and disability in pediatric pain. Further research examining differences in coping and disability between different pediatric pain groups is also warranted.

Den Nutzen von kognitiver Verhaltenstherapie (KVT) und Amitriptylin einerseits im Vergleich zu Amitriptylin und edukativen Masnahmen (EM) andererseits untersuchte die Arbeitsgruppe um S. Powers von der Abteilung fur Verhaltenstherapie und klinische Psychologie des Kinderkrankenhauses von Cincinnati in Ohio. Sie zeigten, dass KVT in Kombination mit Amitriptylin zu einer geringeren Anzahl an Kopfschmerztagen und Migrane-assoziierten Beschwerden bei Kindern und Jugendlichen fuhrte als Amitriptylin in Kombination mit EM.

Objective.—To assess the tolerability and effectiveness of nasal sumatriptan in the treatment of migraine in 5- to 12-year-old children. Background.—Although headaches are a common disorder and occur in up to 10.6% of children, many of the new migraine abortive agents have not been well evaluated in this population. It has recently been reported that nasal sumatriptan is effective in the treatment of migraine in adolescents. In younger children, it is yet to be characterized. In addition, many children have significant amounts of vomiting with their migraines, limiting their use of oral medications. Design and Methods.—Children with headache were evaluated by a child neurologist, child psychologist, and pediatric nurse practitioner. Clinical and International Headache Society diagnoses were established for each child. Patients with headaches that were either unresponsive to oral medications or had significant vomiting were treated with nasal sumatriptan. Initial administration and tolerability were performed in the Headache Center at Cincinnati's Children's Hospital Medical Center. Patients or their parents were contacted to assess the overall effectiveness of nasal sumatriptan after home administration. Results.—Ten patients aged between 5 and 12 years (mean, 9.9 years) received either a 5-mg (n = 2) or 20-mg (n = 8) dose of sumatriptan. All 10 patients had a clinical diagnosis of migraine; 7 met the International Headache Society criteria for migraine. The mean age of headache onset was 6.6 years. A total of 57 headaches were treated; 47 (82.5%) responded to sumatriptan. Of the patients who treated headaches, the mean number of headaches treated was 5.2, while the mean number of responsive headaches was 4.3. One patient had no response, 2 patients had a 50% response, and 6 patients had 100% response to the nasal sumatriptan. Three patients reported persistent “bad taste.” Conclusions.—This report demonstrates that nasal sumatriptan may be effective in aborting migraine in young children (aged 5 to 12 years). It also suggests that there may be subgroups for which it works well. This information suggests that double-blind, placebo-controlled studies are necessary to determine the overall effectiveness of nasal sumatriptan in this age group.

The International Headache Society (IHS) criteria for migraine are not sufficient to diagnose migraine in children. Specifically, the duration and localization of the headache are different in children and adults with migraine. This study compared the formal IHS criteria with pediatric-amended IHS criteria and IHS criteria with the duration factor removed in children younger than 18 years. In addition, the older criteria by Vahlquist and by Prensky and Sommer were also compared. Finally, clinical diagnosis of migraine was compared with IHS criteria with the duration factor removed. The study showed that many children with a shorter duration headache have migraine and also that a number of children with a very long duration of headaches still fit the diagnosis of migraine. Unilateral headache is quite uncommon. The majority of children with migraine complained of bilateral headaches. It is concluded that the IHS criteria for pediatric migraine should be revised. We suggest making the duration factor a minor criteria for migraine in children or to exclude headaches lasting longer than 72 hours only in children younger than 15 years.

Lifestyle factors, long implicated in the onset and exacerbation of headache disorders in adults, have rarely been studied in adolescents. In this issue of Neurology ®, Robberstad and coworkers1 report a large, cross-sectional school-based study assessing the relationships of lifestyle factors to the prevalence and frequency of 3 headache types (migraine, tension-type headache, and “nonclassifiable headache”). Their study, conducted in a sample of 5,847 Norwegian adolescents, ranging in age from 13 to 18 years, examined the separate and combined effects of low physical activity, smoking, and being overweight. The study is a vital step toward a better understanding of lifestyle effects and the potential for behavioral interventions for adolescents with headache disorders. Negative lifestyle factors were surprisingly common, with low physical activity in 31%, smoking in 19%, and being overweight in 16% of this adolescent sample. When examined one at a time, each of these factors was associated with an increased prevalence of migraine, tension-type headache, and nonclassifiable headache in both boys and girls. The effects of each factor were similar in magnitude for each headache type. This lack of specificity for headache type raises the possibility that these lifestyle factors may be associated not just with headache but with all-cause pain. The authors also combined their lifestyle factors into a 4-point lifestyle status scale based on the number of negative factors present. The very poor …

Objective.—To study the effectiveness of a standardized dose of amitriptyline, 1 mg/kg, for childhood headaches. Background.—Amitriptyline has been shown to be effective for the prophylaxis of migraine in adults. Studies in children, however, have been quite limited. In adults, the suggested effective dose range is 10 to 150 mg. In children, a standardized dosage is often not used, resulting in a dosage range in clinical practice that often varies from a very low dose to a dose equivalent to that used in adults. Methods.—Children with more than three headaches per month were treated with amitriptyline, slowly increasing the dose to 1 mg/kg per day. The frequency, severity, and duration of their headaches were initially evaluated and subsequently measured at each follow-up evaluation. Two hundred seventy-nine children had headaches occurring frequently enough to indicate prophylactic treatment. Of these children, 192 (68.8%) were treated with amitriptyline. The average age at presentation was 12.0 (± 3.0) years. The ratio of boys to girls was 1:1.74. The average frequency of headaches was 17.1 (± 10.1) days per month. The average severity was 6.84 (± 1.67) on a 10-point pain scale. The average duration was 11.5 (± 15.0) hours. The most frequent diagnoses using International Headache Society criteria were migraine (60.6%), migraine with aura (7.9%), and tension-type headache (10.4%). Of these children, 146 have been seen for at least one follow-up examination, occurring on average 67.3 (± 32.3) days after beginning prophylactic treatment. Results.—A total of 84.2% of the children reported an overall perception of being better, while 11.6% reported being the same. The frequency of headaches improved to 9.2 (± 10.0) days per month. The average severity was reduced to 5.1 (± 2.1), and the average duration was reduced to 6.3 (± 11.1) hours. If daily or continuous headaches were excluded, the improvements were more marked. Minimal side effects were reported from these children and their families. Long-term evaluation (156 to 415 days) showed continued sustained improvement. Conclusions.—Amitriptyline is an effective prophylactic medication for children with frequent headaches. A standardized dosing regimen results in a significant number of children responding with minimal side effects. The children are able to tolerate this dosing scheme and demonstrate good adherence to a dosing schedule of once a day.

Chronic daily headache (CDH) affects up to 4% of adults and between 1% and 2% of middle-school children.1 Children with CDH often have a history of episodic migraine or a family history of migraines. The headache characteristics in patients with CDH can vary between patients as well as within an individual patient. Their headaches may present as severe intermittent migraine attacks, intermittent low severity headaches, continuous headache pain, or as a combination of these headache types.2 This variation continues to make this condition remarkably challenging to understand and to treat. When the patient and his or her family are in the office, 3 main questions arise: why did this happen, how can we treat it, and when will it go away? Several studies have begun to address these questions, but these studies have often …

For adults, primary headaches have been associated with both socioeconomic and health factors. Oftentimes it is difficult to determine whether the socioeconomic component is a contributor to the impact of the headache or whether the headaches influence the socioeconomic status. For migraine this is complicated by the underlying genetic etiology and the separation of this genetic family history from the socioeconomic family history. Population-based epidemiology studies have attempted to sort out the degree of contribution of these multiple factors. In this issue of Neurology , Bigal et al. examine these roles in adolescents as part of the American Migraine Prevalence and Prevention (AMPP) study.1 Migraine is a common pain condition that significantly burdens an individual, his or her family, and society.2–4 Migraine frequently starts in childhood and adolescence; the prevalence increases and peaks in the most socioeconomic productive years for adults. This combination not only creates increased cost and utilization of medical services, but …