Zonisamide prophylaxis in refractory pediatric headache

INTRODUCTION: Currently, no medications are approved for pediatric headache prophylaxis in the United States. Zonisamide is an antiepileptic drug with preliminary studies suggesting some efficacy in the adult headache population. METHODS: A retrospective chart review was conducted on refractory headache patients in our multidisciplinary Headache Clinic who were treated with zonisamide, an antiepileptic drug, for headache prophylaxis. Records were reviewed for pertinent data including patient history, diagnosis, prior treatment regimens, and zonisamide response, along with headache frequency. RESULTS: Twelve patients were identified (8 girls); mean age was 13.5 years. Eight of the 12 patients had a positive response to zonisamide with greater than 50% reduction in headaches from pretreatment values. CONCLUSION: Zonisamide had some efficacy in headache reduction. It was well tolerated with only minor side effects. Further prospective studies with zonisamide are warranted in refractory pediatric headache patients.     

Chronic daily headache in children and adolescents presenting to tertiary headache clinics

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.     

Diagnosis of migraine in children attending a pediatric headache clinic

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.     

Depression scores following migraine treatment in patients attending a specialized center for headache and neurology

OBJECTIVE: To determine the changes in clinical characteristics and depression levels among patients following treatment for migraine. BACKGROUND: Epidemiologic studies have provided consistent evidence regarding an association between migraine and depression. In Puerto Rico, however, migraine has not yet been systematically investigated. METHODS: A chart review of 144 Puerto Rican patients who presented with migraine, diagnosed according to the International Headache Society criteria, and depression over a 2-year period was performed. The level of depression, before and after migraine treatment, was evaluated using the Zung Self-rating Depression Scale. RESULTS: The mean age of patients was 37.0 +/- 14.4 years; 77.1% were women. More than half (52.8%) reported severe headache and 56.9% reported a monthly frequency of five attacks or more. Nearly 9% were using antidepressant therapy and 8% were under psychiatric treatment. The mean Zung index score at baseline was 50.6 +/- 10.9. Following treatment with triptans, the intensity and frequency of migraine and the Zung index score decreased significantly (P<.00001). A trend for a greater reduction in Zung index scores among patients receiving triptan medications for more than a year was demonstrated (P =.07). CONCLUSIONS: These results indicate that migraine treatment with triptans appears to be effective in decreasing the headache frequency and intensity, and depression levels, independent of antidepressant medication use or psychiatric treatment.     

Endothelin receptor A -231 G>A polymorphism: no linkage to primary pediatric headache

OBJECTIVE: To assess whether the biallelic -231 G>A polymorphism of the endothelin type A receptor (EDNRA) gene, previously shown to be a marker of increased risk for developing migraine, has a role in the susceptibility to primary pediatric headache. BACKGROUND: Several studies suggest that endothelin has a role in migraine. A recent association study has shown that the biallelic -231 G>A polymorphism of the EDNRA gene is associated to migraine in an elderly population. METHODS: A total of 126 consecutive unrelated pediatric patients affected by primary headache, classified according to the International Headache Society criteria in migraine (migraine with aura, n = 3; migraine without aura, n = 80), and tension-type headache (episodic tension-type headache, n = 36; chronic tension-type headache, n = 7) patients, were recruited to the study. Sixty-seven healthy blood donors were used as a control group. Genomic DNA was extracted from buccal swabs or blood samples and analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the above-mentioned polymorphism. Allele and genotype frequencies for primary headache patients were analyzed in comparison with the control group. RESULTS: No significant differences were found in the distribution of the EDNRA -231 G>A polymorphic variant when considering both genotype (migraine chi2 = 2.78, P = .25; tension-type headache chi2 = 3.58, P = .17) and allelic frequencies (migraine chi2 = 1.48, P = .22; tension-type headache chi2 = 0.39, P = .56). Furthermore, no significant genotype-related difference was found in relation to clinical features, such as age at onset, frequency, and length of the attacks. CONCLUSIONS: Our study shows that the -231 G>A polymorphism in the EDNRA gene is neither associated with primary juvenile headache nor significantly correlated with main clinical features characteristic of the headache pathology in pediatric settings.     

Treatment of primary headache disorders with intravenous valproate: initial outpatient experience

OBJECTIVES: To evaluate the effectiveness of intravenous valproate in managing moderate to severe headaches. BACKGROUND: Despite major strides in the understanding of primary headache disorders, there have been few additions to acute headache management other than introduction of the triptans. An intravenous antiepileptic preparation, sodium valproate, has been reported to be effective in the management of status epilepticus and acute headache. METHODS: Between March 13, 2000 and October 11, 2000, we prospectively treated, in a nonrandomized and open-label study, every patient with a moderate to severe headache (4 or greater on a visual analog scale of head pain from 1 to 10) who wanted treatment with intravenous valproate. Using a verbal visual analog scale for pain (0 = no headache and 10 = most severe headache), we measured head pain before treatment and at time of discharge. The treating nurse monitored vital signs and side effects. A positive response was defined as a 50% or greater reduction at discharge in baseline pain. Information was collected regarding patient demographics, type of headache (according to criteria of the International Headache Society and that recently proposed for chronic headache), observation time in the treatment suite, cumulative dose of valproate, and use of concurrent medications. Univariable and multivariable correlates of response to treatment were identified using logistic regression analysis. RESULTS: One hundred thirty treatments were given to 89 women and 17 men, aged 17 to 76 years; 92 patients received only one treatment. Valproate doses ranged between 300 and 1200 mg. Thirty-three patients (31%) presented with episodic migraine, with or without aura; 45 patients (42%) presented with chronic daily headache with a history of episodic migraine, with or without aura (transformed migraine); 22 (21%) with unclassifiable chronic headache; 2 (2%) with episodic cluster headache; and 4 (4%) with chronic tension-type headache. For first treatments only, 61 patients (57.5%) responded to treatment, whereas for all treatments, 82 patients (63.1%) responded. Age and gender did not affect likelihood of response, whereas increasing duration of treatment (P=.003) and the additional use of analgesics (P=.021) were each negatively associated with response. Among headache types, unclassifiable chronic headache segregated from all other classified headaches in terms of poor response. Aside from rare dizziness (n = 2) and one spell interpreted as a pseudoseizure, no side effects were noted. CONCLUSIONS: Intravenous valproate is a safe, rapidly effective, abortive headache agent. It appears to be an effective analgesic for identifiable primary headaches, especially episodic headache, and less effective for unclassifiable chronic headache. Randomized, double-blind, controlled studies are warranted.     

From migraine to chronic daily headache: the biological basis of headache transformation

Migraine headache carries the potential of transforming into chronic daily headache (CDH) over a period of time. Although several risk factors for migraine progression to CDH have been identified, the biological basis of this transformation is unknown. In this review, the consequences of stressful life events and medication overuse, 2 risk factors associated with the development of CDH, on brain processes involved in headache are examined. The extensive overlap in both neural circuitry and cellular events that occur with stress, medication overuse, and migraine provide insight into potential mechanisms that may lead to CDH. Particular attention is devoted to the effect of stress and medication overuse on peripheral and central neuroimmune interactions that can facilitate pain signaling. These interactions include the degranulation of mast cells in the dura, causing the sensitization of primary afferent neurons, as well as the activation of glial cells in the brain that can lead to central sensitization. It is hypothesized that the biological processes involved in migraine headache are directly impacted by stress, medication overuse, and other risk factors, resulting in a reduced threshold for induction of headache and transformation of episodic migraine to CDH.     

Management of primary chronic headache in the general population: the Akershus study of chronic headache

Primary chronic headaches cause more disability and necessitate high utilisation of health care. Our knowledge is based on selected populations, while information from the general population is largely lacking. An age and gender-stratified cross-sectional epidemiological survey included 30,000 persons aged 30–44 years. Respondents with self-reported chronic headache were interviewed by physicians. The International Classification of Headache Disorders was used. Of all primary chronic headache sufferers, 80% had consulted their general practitioner (GP), of these 19% had also consulted a neurologist and 4% had been hospitalised. Co-occurrence of migraine increased the probability of contact with a physician. A high Severity of Dependence Scale score increased the probability for contact with a physician. Complementary and alternative medicine (CAM) was used by 62%, most often physiotherapy, acupuncture and chiropractic. Contact with a physician increased the probability of use of CAM. Acute headache medications were taken by 87%, while only 3% used prophylactic medication. GPs manage the majority of those with primary chronic headache, 1/5 never consults a physician for their headache, while approximately 1/5 is referred to a neurologist or hospitalised. Acute headache medication was frequently overused, while prophylactic medication was rarely used. Thus, avoidance of acute headache medication overuse and increased use of prophylactic medication may improve the management of primary chronic headaches in the future.     

Prophylactic pharmacological treatment of chronic daily headache

Objective.—To review all the prophylactic pharmacological treatments for chronic daily headache from the past decade.
Background.—Chronic daily headache is among the most common diagnoses seen in specialized headache centers. Prior to 1988, there were no criteria for the diagnosis of chronic tension-type headache and chronic daily headache. An expanded chronic daily headache classification has been proposed.
Methods.—A MEDLINE search was performed using the following key words: chronic daily headache, intractable headache, transformed migraine, chronic tension headache, and chronic tension-type headache. We limited our review to those studies published in English in the last decade, including published abstracts and letters to the editor. Double-blind studies carried out prior to 1988 were also included.
Results.—Pharmacological treatments for chronic daily headache include antidepressants (tricyclics, tetracyclics, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors), anticonvulsants, muscle relaxants, 5-HT₁ agonists, ergots, 5-HT₂ antagonists, antianxiety agents, and miscellaneous drugs. Many of these reports are anecdotal, and most are open rather than double-blind studies.
Conclusions.—There is a great variety of pharmacological treatments available for chronic daily headache. Only the antidepressants have been extensively studied. Other medications may be used if these fail. Recommendations based on our experience at the Headache Unit of the Montefiore Medical Center are outlined here.     

Migraine and chronic daily headache management: a qualitative study of patients' perceptions

AIM: The aim of the study was to gain insight into the patients' perceptions of migraine and chronic daily headache (CDH) management. METHODS: Thirteen, semi-structured and individual interviews with seven migraine and five CDH patients were carried out and analysed in QSR NUD*IST5, using a grounded theory methodology. RESULTS: The participants described using five areas of management: 1) health care use; 2) medication use; 3) alternative therapies; 4) social support; and 5) lifestyle and self-help. The participants described their expectations, preferences, worries and (dis)satisfaction in relation to these five areas of management. The participants adapted headache management to suit their needs and preferences, making migraine and CDH management highly individual and giving the headache patient a central role within their own care. CONCLUSION: Health care is changing towards a greater involvement of the patients in their own care. Therefore, it is important to increase understanding of the patients' perspective of chronic diseases, including migraine and CDH. The results from this study inform health care professionals of the range of their patients' needs and preferences. This knowledge can be used to shape clinical practice, to develop patient education programmes and to further research efforts into issues that are important to the headache patient.     

Death by managed care--denial of hospitalization for headache

A 47-year-old man with a severe headache disorder, taking meperidine injections 8 to 12 times a day and approximately 6 butalbital-containing tablets per day, was denied hospitalization for the management of headache and died while awaiting evaluation for detoxification by a psychiatric facility. The criteria for hospitalization and the implications of the denial of care by insurance companies are explored. The biases against the publication of such cases are reviewed.     

Medication overuse headache and chronic migraine in a specialized headache centre: field-testing proposed new appendix criteria

The classification subcommittee of the International Headache Society (IHS) has recently suggested revised criteria for medication overuse headache (MOH) and chronic migraine (CM). We field tested these revised criteria by applying them to the headache population at the Danish Headache Centre and compared the results with those using the current criteria. For CM we also tested two alternative criteria, one requiring > or = 4 migraine days/month and > or = 15 headache days/month, the second requiring > or = 15 headache days/month and > or = 50% migraine days. We included 969 patients with migraine or tension-type headache (TTH) among 1326 patients treated and dismissed in a 2-year period. Two hundred and eighty-five patients (30%) had TTH, 265 (27%) had migraine and 419 (43%) had mixed migraine and TTH. The current criteria for MOH classified 86 patients (9%) as MOH, 98 (10%) as probable MOH and 785 (81%) as not having MOH after a 2-month drug-free period. Using the appendix criteria, 284 patients (29%) were now classified as MOH, no patients as probable MOH and 685 (71%) as not having MOH. For CM only 16 patients (3%) fulfilled the current diagnostic criteria. This increased to 42 patients (7%) when we applied the appendix criteria. Using the less restrictive criteria of > or = 4 migraine days and > or = 15 headache days, 88 patients (14%) had CM, whereas the more restrictive criteria of > or = 15 headache days and > or = 50% migraine days resulted in 24 patients (4%) with CM. Our data suggest that the IHS has succeeded in choosing new criteria for CM which are neither too strict, nor too loose. For MOH, a shift to the appendix criteria will increase the number of MOH patients, but take into account the possibility of permanent changes in pain perception due to medication overuse and the possibility of a renewed effect of prophylactic drugs due to medication withdrawal. We therefore recommend the implementation of the appendix criteria for both MOH and CM into the main body of the International Classification of Headache Disorders.     

Characteristic and overlapping features of migraine and tension-type headache

OBJECTIVE: This epidemiological survey was conducted to investigate comprehensive characteristic and overlapping features of migraine and tension-type headache (TTH) disorders classified based on International Classification of Headache Disorders-II. METHODS: The stratified cohort of this study was composed of 2504 schoolchildren aged 10 to 17 years. A 38-item questionnaire inquiring all characteristic features of primary headache syndromes mandatory for classification was applied to selected 483 children with recurrent headache in the last 6 months. RESULTS: Migraine was diagnosed in 227 (47.0%) of 483 children and TTH in 154 (31.9%). Out of 125 children with definite migraine, 73 (58.4%) reported tension-type symptoms and 94 (68.1%) of 138 children with definite TTH reported migraine-type symptoms. Pressing pain (21%) and lack of aggravation of pain by physical activity (34%) were the major tension-type features in patients with migraine. Throbbing quality (43%) and aggravation by physical activity (30%) determined the main migraine-type features in patients with TTH. CONCLUSION: The frequent co-occurrence of migraine and TTH symptoms suggests the presence of a common pathogenesis.