Probable Chronic Migraine Research Articles

Association between migraine prevalence, treatment with proton-pump inhibitors and CYP2C19 phenotypes in UK Biobank

Proton-pump inhibitors (PPIs) are used to suppress gastric acid secretion in several gastrointestinal conditions. While these drugs are generally well tolerated, their long-term use may be associated with different adverse effects, including migraine. We analyzed the association between treatment with PPIs (omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole) and migraine prevalence in the UK Biobank cohort through a cross-sectional analysis (using baseline data for 468,280 participants, 16,390 of whom had migraine) and a longitudinal analysis (including 145,007 participants with no migraine at baseline, of whom 3786 had probable migraine without aura [MWOA] and 9981 probable migraine with aura [MWA] or both MWOA and MWA at an average follow-up time of 10.06 years). We also evaluated the modulating role of the metabolizer phenotype of CYP2C19, the major enzyme involved in PPI clearance. Treatment with PPIs was associated with higher migraine prevalence at baseline (odds ratio [OR] = 1.25, p < 0.0001). CYP2C19 rapid metabolizer phenotype was associated with lower prevalence of migraine exclusively in participants treated with PPIs (OR = 0.89, p = 0.029). In addition, treatment with PPIs was associated with higher incidence of both probable MWOA (OR = 1.24, p = 0.002) and MWA (OR = 1.43, p < 0.0001) at follow-up. Treatment with PPIs and CYP2C19 poor metabolizer status were associated with higher incidence of probable chronic migraine exclusively in men. Our results suggest a significant association between treatment with PPIs and migraine in this large population-based cohort and support a potential relevant role of gender and CYP2C19 phenotype.

Features of Primary Chronic Headache in Children and Adolescents and Validity of Ichd 3 Criteria.

Introduction: Chronic headaches are not a rare condition in children and adolescents with negative effects on their quality of life. Our aims were to investigate the clinical features of chronic headache and usefulness of the International Classification of Headache Disorders 3rd edition (ICHD 3) criteria for the diagnosis in a cohort of pediatric patients.Methods: We retrospectively reviewed the charts of patients attending the Headache Center of Bambino Gesù Children and Insubria University Hospital during the 2010–2016 time interval. Statistical analysis was conducted to study possible correlations between: (a) chronic primary headache (CPH) and demographic data (age and sex), (b) CPH and headache qualitative features, (c) CPH and risk of medication overuse headache (MOH), and (d) CPH and response to prophylactic therapies. Moreover, we compared the diagnosis obtained by ICHD 3 vs. ICHD 2 criteriaResults: We included 377 patients with CPH (66.4% females, 33.6% males, under 18 years of age). CPH was less frequent under 6 years of age (0.8%; p < 0.05) and there was no correlation between age/sex and different CPH types. The risk to develop MOH was higher after 15 years of age (p < 0.05). When we compared the diagnosis obtained by ICHD 2 and ICHD 3 criteria we found a significant difference for the undefined diagnosis (2.6% vs. 7.9%; p < 0.05), while the diagnosis of probable chronic migraine was only possible by using the ICHD2 criteria (11.9% of patients; p < 0.05). The main criterion which was not satisfied for a definitive diagnosis was the duration of the attacks less than 2 h (70% of patients younger than 6 years; p < 0.005). Amitriptyline and topiramate were the most effective drugs (p < 0.05), although no significant difference was found between them (p > 0.05).Conclusion: The ICHD 3 criteria show limitations when applied to children under 6 years of age. The risk of developing MOH increases with age. Although our “real word” study shows that amitriptyline and topiramate are the most effective drugs regardless of the CPH type, the lack of placebo-controlled data and the limited follow-up results did not allow us to conclude about the drug efficacy.

Primary Headaches in an Elderly Population Seeking Medical Care for Cognitive Decline.

To assess the prevalence of specific headache disorders in a population older than 65 years seeking consultation due to memory problems or cognitive impairment. We verified the occurrence of headache symptoms and the impact of headaches on daily life. Headaches were classified as per the International Classification of Headache Disorders, 2nd edition (ICHD-2). All patients were screened with the Mini-Mental State Examination (MMSE), followed by the Selective Reminding Test and neuroimaging. Participants with severe cognitive impairment or dementia were excluded. A total of 1,237 patients (51.6% women), with mean age of 75.6 years (SD = 6.9) were screened from January 2006 to December 2014. Of them, 302 (24.4%) patients suffered from headaches. Most common individual diagnoses were probable migraine (13.8%), episodic tension-type headache (3.4%), and episodic migraine (3.0%). Chronic migraine or probable chronic migraine happened in 3.5%, while chronic tension-type headache affected 0.6%. Most patients with headaches routinely used symptomatic medications (55.6%). Mean MMSE scores were similar in patients with or without headaches, or with different headache diagnoses. Headache disorders overall, frequent headaches, and headaches requiring treatment are commonly seen in the elderly seeking care for cognitive decline and should be properly assessed and managed.

Emotive and Behavior Problems in Adolescents with Chronic Daily Headache

Introduction: Many studies have examined the association between pediatric headache and psychopathology; some of them raised the possibility that headache frequency and severity could be worsened by a reduced psychological ability to mentally process emotions and affects. Aim: The aim of this study was to assess psychopathological comorbidity in adolescents with chronic daily headache (CDH) compared to adolescents with non-chronic headache. Method: We conducted a retrospective study of 42 patients (20 boys and 22 girls; mean age 14) and their mothers, consecutively first seen for therapy-resistant headache in our third-level Child Neuropsichiatry Unit National Neurological Institute “C. Mondino” of Pavia, between November 2012 to January 2014. They were assessed using Parent Child Behaviour Checklist (CBCL) and Youth Self-report (YSR). A detailed history was taken to assess the presence of headache, using criteria defined by International Headache Society (ICHD-3 beta). Results: 21 (50%) of 42 enrolled patients presented a form of Chronic Daily Headache – CDH: ten patients had Chronic Migraine, one Probable Chronic Migraine, eight adolescents Chronic Tension-type Headache and two girls Probable Chronic Tension-type Headache. They had at the YSR higher levels of Somatic Complaints (P=0.006), Thought Problems (P=0.003) and ADHD symptoms (P=0.049). Atthe CBCL,their mothersreported higherlevels of Somatic Complaints (P=0.045) and lower Total Competences (P=0.012). Conclusion: This study confirmed that CDH are associated with a higher level of impairment and with a heavier psychopathological burden. It is possible that the presence of a significant degree of alexythimia in these patients could be associated to the worsening both of headache and of psychopathological aspects.

Application of ICHD-II and revised diagnostic criteria to patients with chronic daily headache

The objective of this study was to evaluate how the criteria of the second edition of the International Classification of Headache Disorders (ICHD-II) and the revised criteria fit a sample of patients with chronic daily headache (CDH). One hundred and five patients with CDH in a tertiary headache centre were included. Headache was assessed using a semi-structured interview. Patients were classified according to the ICHD-II and to the new appendix criteria of the ICHD. Using the ICHDII, 91% of patients received a combination of diagnoses and 76% received only a probable diagnosis: 47% had probable chronic migraine (CM) with probable medication overuse headache (MOH), 28% had probable chronic tension-type headache (CTTH) with probable MOH, 20% had CTTH and 3.8% had CM. Using the new appendix criteria, 88.5% of patients required one diagnosis. Seventy-six percent of patients were classified as MOH, 17% had CTTH and 6.7% had CM. The classification of CDH remains controversial. Alternative criteria for CM with and without medication overuse are discussed.

The International Classification of Headache Disorders Revised Criteria for Chronic Migraine—Field Testing in a Headache Specialty Clinic

In the absence of a biological marker and expert consensus on the best approach to classify chronic migraine (CM), recent revised criteria for this disease has been proposed by the Headache Classification Committee of the International Headache Society. This revised criteria for CM is now presented in the Appendix. Herein we field test the revised criteria for CM. We included individuals with transformed migraine with or without medication overuse (TM+ and TM–), according to the criteria proposed by Silberstein and Lipton, since this criterion has been largely used before the Second Edition of the International Classification of the Headache Disorders (ICHD-2). We assessed the proportion of subjects that fulfilled ICHD-2 criteria for CM or probable chronic migraine with probable medication overuse (CM+), as well as the revised ICHD-2 (ICHD-2R) criteria for CM (15 days of headache, 8 days of migraine or migraine-specific acute medication use—ergotamine or triptans). We also tested the ICHD-2R vs. three proposals. In proposal 1, CM/CM+ would require at least 15 days of migraine or probable migraine per month. Proposal 2 required 15 days of headache per month and at least 50% of these days were migraine or probable migraine. Proposal 3 required 15 days of headache and at least 8 days of migraine or probable migraine per month. Of the 158 patients with TM–, just 5.6% met ICHD-2 criteria for CM. According to the ICHD-2R, a total of 92.4% met criteria for CM (P < 0.001 vs. ICHD-2). The ICHD-2R criterion performed better than proposal 1 (47.8% of agreement, P < 0.01) and was not statistically different from proposals 2 (87.9%) and 3 (94.9%). Subjects with TM+ should be classified as medication overuse headache (MOH), and not CM+, according to the ICHD-2R. Nonetheless, we assessed the proportion of them who had 8 days of migraine per month. Of the 399 individuals with TM+, just 10.2% could be classified as CM+ in the ICHD-2. However, most (349, 86.9%) had 8 days of migraine per month and could be classified as MOH and probable CM in the ICHD-2R(P < 0.001 vs. ICHD-2). We conclude that the ICHD-2R addresses most of the criticism towards the ICHD-2 and should be adopted in clinical practice and research. In the population where use of specific acute migraine medications is less common, the agreement between ICHD-2R CM and TM may be less robust.

Application of the ICHD‐II Criteria to the Diagnosis of Primary Chronic Headaches Via a Computerized Structured Record

The authors recently developed a software program designed to analyze clinical data from patients affected by primary headache. The program is based exclusively on the International Classification of Headache Disorders 2nd edition (ICHD-II) criteria. This software examines all the diagnoses of primary headaches on the basis of the variables needed to fulfill these mandatory criteria. We tested the software, Primary Headaches Analyser 1.0 INT (PHA), by entering and analyzing clinical data from 200 consecutive patients affected by primary chronic headaches and evaluating the corresponding output diagnoses. The diagnosis of chronic migraine (1.5.1) was obtained in 68 cases (34 %) and that of probable chronic migraine (1.6.5) plus probable medication-overuse headache (8.2.8) in 46 (23%). Chronic tension-type headache (2.3) and probable chronic tension-type headache (2.4.3) plus probable medication-overuse headache (8.2.8) were diagnosed in 24 (12%) and 2 (1%) patients, respectively. Moreover, 4 and 12 patients, respectively, received both the diagnosis of chronic migraine (1.5.1) plus chronic tension-type headache (2.3) and of probable migraine (1.6.1) without aura plus chronic tension-type headache (2.3). In the remaining 44 cases (22%), none of the chronic primary headaches disorders defined by ICHD-II received an output diagnosis from the program. This was due mainly to the fact that the criteria fulfilled were insufficient for the diagnoses of migraine without (1.1) aura plus chronic migraine or, more infrequently, chronic tension-type headache. Our software program permitted diagnoses of chronic migraine, chronic tension-type or their probable forms (with or without MOH) in 78% of 200 patients with headache 15 or more days per month. In the remaining cases the inability to provide a specific diagnosis may be explained in part by the fact that the criteria for both diagnoses are too stringent and do not accurately reflect variations of the headache pattern in these chronic forms.

Topiramato en cefalea crónica diaria por migraña

Chronic daily headache (CDH) includes primary headaches that last more than four hours with a frequency equal or superior to 15 days a month over the last three months. It has a prevalence of 4-5% in the general population and is a frequent reason for visiting the physician in headache units. To evaluate the effectiveness of topiramate, as the primary drug, in CDH due to probable chronic migraine with or without medication abuse. From the 447 patients with migraine in our database, we selected those: a) satisfying Silberstein criteria for CDH; b) that had not followed prior prophylactic treatment; and c) who were treated with topiramate as the primary drug. The mean number of days with headache and bouts of severe migraine in the fourth month of treatment using topiramate as compared to the month preceding treatment, as well as the percentage of responses and the rate of respondents in the fourth month were all analysed. Eighty-three patients (88% females) with a mean age of 38.0 +/- 14.13 years were selected. Medication abuse was reported in 44% of cases. At the fourth month of treatment, the mean number of days with headache dropped significantly from 20.8 to 7.9 (p < 0.0001) and the mean number of bouts of severe migraine diminished from 4.4 to 1.7 (p < 0.0001). The rate of respondents was 72%. Medication abuse continued in 14% of cases. Side effects were produced in 58% of patients and the dropout rate was 24%. Topiramate proved to be effective in the treatment of CDH due to probable chronic migraine and with probable medication abuse in de novo migraine patients.

Glial Cell Line-Derived Neurotrophic Factor and Somatostatin Levels in Cerebrospinal Fluid of Patients Affected by Chronic Migraine and Fibromyalgia

The aim of the present study was to verify cerebrospinal fluid (CSF) levels of glial cell line-derived neurotrophic factor (GDNF) and somatostatin, both measured by sensitive immunoassay, in: 16 chronic migraine (CM) patients, 15 patients with an antecedent history of migraine without aura diagnosed as having probable chronic migraine (PCM) and probable analgesic-abuse headache (PAAH), 20 patients affected by primary fibromyalgia syndrome (PFMS), and 20 control subjects. Significantly lower levels of GDNF and somatostatin were found in the CSF of both CM and PCM + PAAH patients compared with controls (GDNF =P < 0.001, P < 0.002; somatostatin = P < 0.002, P < 0.0003), without significant difference between the two groups. PFMS patients, with and without analgesic abuse, also had significantly lower levels of both somatostatin and GDNF (P < 0.0002, P < 0.001), which did not differ from those of CM and PCM + PAAH patients. A significant positive correlation emerged between CSF values of GDNF and those of somatostatin in CM (r = 0.70, P < 0.02), PCM + PAAH (r = 0.78, P < 0.004), and PFMS patients (r = 0.68, P < 0.008). Based on experimental findings, it can be postulated that reduced CSF levels of GDNF and somatostatin in both CM and PCM + PAAH patients can contribute to sustained central sensitization underlying chronic head pain. The abuse of simple or combination analgesics does not seem to influence the biochemical changes investigated, which appear to be more strictly related to the chronic pain state, as demonstrated also for fibromyalgia.

Field Testing Alternative Criteria for Chronic Migraine

The criteria for chronic migraine (CM), as proposed by the Second Edition of the International Classification of Headache Disorders (ICHD-2) is very restrictive, excluding most patients that evolve from episodic migraine. In this study we empirically tested three recent proposals for revised criteria for CM. We included individuals with transformed migraine (TM) with or without medication overuse, according to the criteria proposed by Silberstein and Lipton. All individuals had headache calendars for at least three consecutive months. We assessed the proportion of subjects that fulfilled ICHD-2 criteria for CM or probable chronic migraine with probable medication overuse (CM+). We also tested three proposals for making the CM criteria more inclusive. In proposal 1, CM/CM + would require at least 15 days of migraine or probable migraine per month. Proposal 2 suggests that CM/CM + would be classified in those with >or= 15 days of headache per month, where at least 50% of these days are migraine or probable migraine. Proposal 3 suggests that CM/CM + would be classified in those with chronic daily headache and at least 8 days of migraine or probable migraine per month. Among TM sufferers, 399 (62.5%) had TM with medication overuse, and just 10.2% were classified as CM+ 158 (37.5%) had TM without medication overuse; just nine (5.6%) met current ICHD-2 criteria for CM. Using the alternative criteria, proposal 1 included 48.7% of patients with TM without medication overuse; proposal 2 captured 88%, and proposal 3 classified 94.9% of these patients. For TM with medication overuse, the proportions for proposals 1-3 were, respectively, 37%, 81% and 91%. The differences were statistically significant, favouring proposal 3. Consistently, criteria for CM and CM+ should be revised to require at least 8 days of migraine or probable migraine per month, in individuals with 15 or more days of headache per month.

Preliminary results of a withdrawal and detoxification therapeutic regimen in patients with probable chronic migraine and probable medication overuse headache

Chronic migraine (CM) is an invalidating condition affecting a significant population of headache sufferers, frequently associated with medication overuse headache (MOH). Controlled trials and guidelines for the treatment of MOH are currently not available. We studied the efficacy of a therapeutic regimen for the withdrawal of the overused drug and detoxification in a sample of patients suffering from probable CM and probable MOH during admission in eight hospitals of Piemonte–Liguria–Valle d’Aosta. Fifty patients, 42 females (84%) and 8 males (16%), mean age at observation 50.66±13.08 years, affected by probable CM and daily medication overuse following IHS diagnostic criteria were treated as inpatients or in a day hospital. Headache index (HI) and daily drug intake (DDI) were used for evaluating the severity of headache and medication overuse. The patients were treated by abrupt discontinuation of the overused drug and by a therapeutic protocol including i.v. hydration, dexamethasone, metoclopramide and benzodiazepines for 7–10 days. Prophylactic medication was started immediately after admission. Analgesics or triptans were used under medical control only in cases of severe rebound headache. Diagnostic protocol included routine blood tests (at admission and at discharge), dosage of B12 and folic acid. Patients underwent follow-up controls one, three and six months after discharge. The initial diagnosis was probable CM in almost all patients included in the study (41 patients); in nine patients the diagnosis was not specified (coded only as CDH). The overused medications were simple analgesics in 17 cases (34%), combination analgesics in 19 cases (38%), triptans alone or with analgesics in 13 cases (26%) and ergotamine in 2 cases (4%). We collected data from 39 patients at first follow–up (1 month), 32 after 3 months and 14 after 6 months. Mean HI was 0.91 at admission, 0.22 at discharge, 0.38 after 30 days, 0.46 after 3 months and 0.48 after 6 months. Mean DDI was 2.80 at admission, 0.39 at discharge, 0.41 after 1 month, 0.52 after 3 months and 0.59 after 6 months. These results are on average positive and tend to remain stable with time. Although preliminary and obtained on a limited number of patients at 6–month follow–up, our results seem to be encouraging about the use of the proposed therapeutic protocol.

Cortical Inhibition Is Reduced in Chronic and Episodic Migraine and Demonstrates a Spectrum of Illness

The pathophysiological relationship between episodic migraine and chronic migraine is not fully understood. We aimed to examine transcranial magnetic stimulation (TMS) indices of cortical excitability in patients with episodic migraine (EM) and probable chronic migraine (PCM), and matched controls. Cortical excitability was assessed at baseline with two well-established methods: phosphene thresholds (PT) and magnetic suppression of perceptual accuracy (MSPA) profiles. Five EM patients, five PCM patients, and five normal controls participated in the main study. In addition, two patients were reassessed after 30 days of treatment with topiramate. Both PT and MPSA measures were consistent in indicating a continuum of excitability across the three groups: PCM patients had the highest excitability, followed by EM, then controls. In the two treated patients MPSA profiles appeared to normalize at a 100 mg dosage. Patients with PCM appear to be characterized by very high cortical excitability. This may contribute to their greatly increased attack frequency. TMS-based methods will be important for future research examining the evolution of chronic migraine from episodic migraine over time.

The Classification of Chronic Daily Headache in Adolescents—A Comparison Between the Second Edition of the International Classification of Headache Disorders and Alternative Diagnostic Criteria

To compare the second edition of the International Classification of Headache Disorders (ICHD-2) and the Silberstein-Lipton (S-L) criteria in the classification of adolescents with chronic daily headache (CDH). We reviewed the clinical records and the headache diaries of 170 adolescents (13 to 17 years) seen between 1998 and 2003 at a headache center. Relevant information was transferred to a standardized form that included operational criteria for the ICHD-2. CDH subtypes were classified according the criteria proposed by S-L into transformed migraine (TM) with (TM+) and without medication overuse (TM-), chronic tension-type headache (CTTH), new daily persistent headache (NDPH), and hemicrania continua (HC). From the 69 patients with TM- according the S-L criteria, most (71%) could be classified as chronic migraine (CM), while a minority of patients required a combination of diagnosis, mainly migraine and CTTH (14.4%). Of the patients with TM+, just 39.6% met the criteria for probable CM (PCM) with probable medication overuse (PMO). If instead of 15 migraine days per month, we considered 15 or more days of migraine or probable migraine, 84% of the subjects with TM- and 68.7% of those with TM+ could be classified. Of the 27 subjects classified as NDPH without medication overuse according to the S-L system, the majority (51.2%) were also classified as NDPH according the ICHD-2. Interestingly, three (11.1% of the subjects with NDPH without medication overuse) were classified as CM in the ICHD-2 because these patients had an abrupt onset of 15 or more days of migraine per month. All patients with NDPH with medication overuse according to the S-L criteria required a combination of diagnoses in the ICHD-2. All subjects with CTTH received a single diagnosis in both classification systems. (i) Among adolescents with TM, the majority (58.1%) could be classified as CM, according to the ICHD-2. These results were driven by TM without medication overuse. (ii) If the ICHD-2 criteria for CM are revised to require 15 days of migraine or probable migraine, the proportion of patients with TM- who meet the criteria for CM increases from 71% to 84%; for TM+, the proportion with probable chronic migraine and PMO increases from 30% to 68%. (iii) About half of the patients with NDPH according to the S-L criteria have too many migraine features to meet ICHD-2 criteria for NDPH.

Divalproex ER Prophylaxis in Migraineurs with Probable Chronic Migraine and Probable Medication‐Overuse Headache: A Case Series

This case series prospectively evaluated divalproex ER in 15 headache clinic migraine patients fulfilling International Headache Society criteria for probable chronic migraine and probable medication-overuse headache. Divalproex ER was initiated at 500 mg QHS and increased after Week 2 to 1000 mg QHS for a total treatment period of 2 months. Mean headache days per month dropped from 21.6 to 10.4 at month 1 and 8.9 at month 2. All 10 patients who completed the study rated their satisfaction with treatment as changed from unsatisfied at baseline to satisfied at study completion. The results of this study support the prophylactic efficacy of divalproex ER in migraine patients with probable chronic migraine and probable medication-overuse headache.