Multisensorial Perception in Chronic Migraine and the Role of Medication Overuse

Multisensory processing can be assessed by measuring susceptibility to crossmodal illusions such as the Sound-Induced Flash Illusion (SIFI). When a single flash is accompanied by 2 or more beeps, it is perceived as multiple flashes (fission illusion); conversely, a fusion illusion is experienced when more flashes are matched with a single beep, leading to the perception of a single flash. Such illusory perceptions are associated to crossmodal changes in visual cortical excitability. Indeed, increasing occipital cortical excitability, by means of transcranial electrical currents, disrupts the SIFI (ie, fission illusion). Similarly, a reduced fission illusion was shown in patients with episodic migraine, especially during the attack, in agreement with the pathophysiological model of cortical hyperexcitability of this disease. If episodic migraine patients present with reduced SIFI especially during the attack, we hypothesize that chronic migraine (CM) patients should consistently report less illusory effects than healthy controls; drugs intake could also affect SIFI. On such a basis, we studied the proneness to SIFI in CM patients (n = 63), including 52 patients with Medication Overuse Headache (MOH), compared to 24 healthy controls. All migraine patients showed reduced fission phenomena than controls (P < .0001). Triptan MOH patients (n = 23) presented significantly less fission effects than other CM groups (P = .008). This exploratory study suggests that CM – both with and without medication overuse – is associated to a higher visual cortical responsiveness which causes deficit of multisensorial processing, as assessed by the SIFI.PerspectiveThis observational study shows reduced susceptibility to the SIFI in CM, confirming and extending previous results in episodic migraine. MOH contributes to this phenomenon, especially in case of triptans.     

Obsessive-Compulsive Disorder and Migraine With Medication-Overuse Headache

Objective.— A strong association has been demonstrated between migraine, particularly in the chronic form and with medication overuse, and either major depression or various anxiety disorders. However, there has been less systematic research on the links between migraine with medication-overuse headache (MOH) and obsessive-compulsive disorder (OCD). A drug-seeking behavior shares with OCD the compulsive quality of the behavior. We investigated the relationship between OCD and MOH in migraineurs.
Methods.— A structured questionnaire was administered to subjects with: episodic migraine (EM) (n = 30), chronic migraine (CM) (n = 24), and MOH with a previous history of EM (n = 33) and 29 control subjects. Psychiatric diagnoses were made by a senior psychiatrist blinded to the diagnosis of migraine. Psychiatric assessment of OCD illness was evaluated by means of The Yale-Brown Obsessive Compulsive Scale (Y-BOCS).
Results.— In the subgroup of patients with MOH, psychiatric comorbidity (anxiety and mood disorders) was prevalent compared with CM, EM, and controls ( P  < .0001). Subclinical OCD was significantly prevalent in MOH patients with respect to other groups ( P  < .0002). Higher scores in Y-BOCS, as a measure of severity of obsessive-compulsive symptoms, were found in both MOH and CM compared with controls and EM.
Conclusions.— The excess of psychiatric comorbidity in patients with MOH can be related either to medication overuse or to chronification of headache. Among anxiety disorders, we observed a high rate of subclinical OCD. However, a direct link between compulsive behavior and medication overuse cannot be established yet. OCD in MOH might be underdiagnosed and undertreated.     

Enhanced functional connectivity between habenula and salience network in medication-overuse headache complicating chronic migraine positions it within the addiction disorders: an ICA-based resting-state fMRI study

BackgroundMedication-overuse headache (MOH) is a relatively frequently occurring secondary headache caused by overuse of analgesics and/or acute migraine medications. It is believed that MOH is associated with dependence behaviors and substance addiction, in which the salience network (SN) and the habenula may play an important role. This study aims to investigate the resting-state (RS) functional connectivity between the habenula and the SN in patients with MOH complicating chronic migraine (CM) compared with those with episodic migraine (EM) and healthy controls (HC).MethodsRS-fMRI and 3-dimensional T1-weighted images of 17 patients with MOH + CM, 18 patients with EM and 30 matched healthy HC were obtained. The RS-fMRI data were analyzed using the independent component analysis (ICA) method to investigate the group differences of functional connectivity between the habenula and the SN in three groups. Correlation analysis was performed thereafter with all clinical variables by Pearson correlation.ResultsIncreased functional connectivity between bilateral habenula and SN was detected in patients with MOH + CM compared with patients with EM and HC respectively. Correlation analysis showed significant correlation between medication overuse duration and habenula-SN connectivity in MOH + CM patients.ConclusionsThe current study supported MOH to be lying within a spectrum of dependence and addiction disorder. The enhanced functional connectivity of the habenula with SN may correlate to the development or chronification of MOH. Furthermore, the habenula may be an indicator or treatment target for MOH for its integrative role involved in multiple aspects of MOH.     

Family History for Chronic Headache and Drug Overuse as a Risk Factor for Headache Chronification

Objectives.— To assess whether family history for chronic headache (CH) and drug overuse could represent a risk factor for headache chronification. Background.— Among factors investigated as risk factors for chronification of headache disorders, familial liability for CH and drug overuse has been rarely investigated. Patients and Methods.— A total of 105 consecutive patients with daily or nearly daily headache, and 102 consecutive patients with episodic headache matched by age, sex, and type of headache at onset, underwent a structured direct interview about family history for episodic headache, CH with and without medication overuse, substance abuse/dependence, and psychiatric disorders. Results.— In total, 80 out of 105 patients with CH received a diagnosis of medication overuse headache (MOH), 21 patients were classified as chronic migraine (CM), and 4 as chronic tension‐type headache (CTTH) without drug overuse. Some 38.1% of CH patients reported family history for CH vs only 13.7% of episodic headaches (P = .001). Familiality for CH with medication overuse was reported by 25.7% of cases vs 9.8% of controls (P = .0028). A familial history of substance abuse was reported by 20% of patients vs 5.9% of controls (P = .0026). In all, 28.7% of MOH patients reported family history for CH with medication overuse (P = .0014) and 21.2% for substance abuse (P = .002). Relatives of patients with MOH were more likely than control relatives to suffer from CH (OR = 4.19 [95% CI 2.05‐8.53]), drug overuse (OR = 3.7 [95% CI 1.66‐8.24]), and substance abuse (OR = 4.3 [95% CI 1.65‐11.19]). No differences regarding family history for episodic headache and for psychiatric disorders were found. No differences in family history for CH with drugs overuse and for substance abuse were found between CH patients without overuse and controls. Fifteen CH patients reported family history for alcohol abuse (P = .0003). Conclusions.— The significantly increased familial risk for CH, drug overuse, and substance abuse suggests that a genetic factor is involved in the process of headache chronification.     

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.     

Elimination of menstrual-related migraine beneficially impacts chronification and medication overuse

Objectives.— This study seeks to determine whether menstrual‐related migraine (MRM) has a discrete, attributable impact on migraine chronicity and medication overuse. Background.— Menstrual‐related migraine can be a disabling headache on its own; but when seen in headache clinics, it is often enmeshed in the setting of chronic migraine (CM) and medication overuse headache (MOH). Whereas nonspecific migraine preventives bestow their benefit uniformly, hormonal preventives (HPs)—when they are successful—address a discrete hormonal mechanism. They confer no known benefit to migraines that are not hormonally triggered. This selective property of HPs could potentially isolate MRM and segregate its effect on the overall clinical picture. Methods.— This is a retrospective review of 229 consecutive women seen in follow‐up for hormonal prevention of MRM at an academic headache center. Patients kept standardized diaries from which separate menstrual‐week (MW) and non‐menstrual week (nonMW) headache indices were calculated and compared. Resolution of MRM was defined by reduction of the MW headache index to a score not exceeding the nonMW headache indices. Consumption of all acute and preventive agents used in the preceding month was tallied. We performed post‐treatment comparisons of medication usage and headache characteristics among subjects in whom MRM was resolved and those in whom it was not resolved. Results.— At baseline, CM was present in 92% of subjects, 72% of whom also met criteria for MOH. Resolution of MRM was achieved in 81% of subjects who were compliant with HP and was associated with reversion to episodic migraine (59% vs 18%, P < .001) and resolution of medication overuse (54% vs 20%, P < .001). Resolution of MRM was associated with significant decreases in per capita consumption of triptans, opioids, all acute agents, and migraine preventive medications. Conclusions.— Resolution of MRM correlated not only with conversion of CM to an episodic pattern, but also with a significant reduction in medication usage. It offers preliminary evidence that hormonal regimens may have a beneficial role in prevention of MRM.     

Central sensitization of the trigeminal and somatic nociceptive systems in medication overuse headache mainly involves cerebral supraspinal structures

Trigeminal and somatic nociceptive systems were studied in controls (n=15), episodic migraine (n=16), analgesics (n=14) and triptan-induced medication overuse headache (MOH) (n=15) before and after withdrawal. Patients with MOH and comorbid depressive symptoms and depression without headache were studied to investigate the influence of depression. Trigeminal nociception was studied by simultaneous registration of pain-related cortical potentials (PREP) and nociceptive blink reflex (nBR) following nociceptive-specific electrical stimulation of the forehead. Somatic nociception was evaluated using PREP of upper limbs. We found facilitation of both trigeminal and somatic PREP but not of nBR in MOH, which normalized after withdrawal. No differences were found comparing analgesics vs. triptan MOH. No differences were observed between controls and patients with episodic migraine and depression without headache. A transient facilitation was found of trigeminal and somatic nociceptive systems in MOH, which was more pronounced on a supraspinal level.     

Chronic migraine plus medication overuse headache: two entities or not?

Chronic migraine (CM) represents migraine natural evolution from its episodic form. It is realized through a chronicization phase that may require months or years and varies from patient to patient. The transition to more frequent attacks pattern is influenced by lifestyle, life events, comorbid conditions and personal genetic terrain, and it often leads to acute drugs overuse. Medication overuse headache (MOH) may complicate every type of headache and all the drugs employed for headache treatment can cause MOH. The first step in the management of CM complicated by medication overuse must be the withdrawal of the overused drugs and a detoxification treatment. The goal is not only to detoxify the patient and stop the chronic headache but also to improve responsiveness to acute or prophylactic drugs. Different methods have been suggested: gradual or abrupt withdrawal; home treatment, hospitalization, or a day-hospital setting; re-prophylaxes performed immediately or at the end of the wash-out period. Up to now, only topiramate and local injection of onabotulinumtoxinA have shown efficacy as therapeutic agents for re-prophylaxis after detoxification in patients with CM with and without medication overuse. Although the two treatments showed similar efficacy, onabotulinumtoxinA is associated with a better adverse events profile. Recently, the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program proved that patients with CM, even those with MOH, are the ones most likely to benefit from onabotulinumtoxinA treatment. Furthermore, it provided an injection paradigm that can be used as a guide for a correct administration of onabotulinumtoxinA.     

New appendix criteria open for a broader concept of chronic migraine

After the introduction of chronic migraine and medication overuse headache as diagnostic entities in The International Classification of Headache Disorders, Second Edition, ICHD-2, it has been shown that very few patients fit into the diagnostic criteria for chronic migraine (CM). The system of being able to use CM and the medication overuse headache (MOH) diagnosis only after discontinuation of overuse has proven highly unpractical and new data have suggested a much more liberal use of these diagnoses. The International Headache Classification Committee has, therefore, worked out the more inclusive criteria for CM and MOH presented in this paper. These criteria are included in the appendix of ICHD-2 and are meant primarily for further scientific evaluation but may be used already now for inclusion into drug trials, etc. It is now recommended that the MOH diagnosis should no longer request improvement after discontinuation of medication overuse but should be given to patients if they have a primary headache plus ongoing medication overuse. The latter is defined as previously, i.e. 10 days or more of intake of triptans, ergot alkaloids mixed analgesics or opioids and 15 days or more of analgesics/NSAIDs or the combined use of more than one substance. If these new criteria for CM and MOH prove useful in future testing, the plan is to include them in a future revised version of ICHD-2.     

Depressive symptoms and insecure attachment as predictors of disability in a clinical population of patients with episodic and chronic migraine

OBJECTIVES: To define predictors of migraine-related disability in patients with episodic and chronic migraine referred to a specialty migraine clinic, focusing on depressive symptoms and insecure attachment style that, because of their association with responses to pain and physical illness, might be predictive of greater migraine-related disability. BACKGROUND: The Migraine Disability Assessment questionnaire (MIDAS) has proved to be a reliable and easy-to-use instrument to assess migraine-related disability. As clinicians are increasingly using MIDAS in their diagnostic and treatment decisions for patient care, an understanding of the factors influencing migraine-related disability is essential for a rationale use of such an instrument. METHODS: Two-hundred patients suffering from episodic migraine without aura (EM), and chronic migraine (CM) with and without medication overuse, and referred to a specialty headache clinic were evaluated using the MIDAS, the Beck Depression Inventory (BDI), and the Attachment Style Questionnaire (ASQ). Diagnosis of episodic and chronic migraine was operationally defined according to the International Headache Society (IHS) and Silberstein-Lipton criteria. RESULTS: Multiple regression analysis showed that, in the total sample, disability was higher in those patients with CM, more severe depressive symptoms, an insecure style of attachment (as reflected by a lower score on the ASQ confidence scale), and experiencing more severe headache pain intensity. In the subgroup of patients with episodic migraine, an insecure style of attachment emerged as the most significant predictor of disability (other significant predictors were female sex and number of headache days per month). In contrast, in the subgroup of patients with CM, the only significant predictor of the total MIDAS score was a greater severity of depressive symptoms. CONCLUSIONS: Our findings demonstrate the relevance of attachment style, an enduring psychological trait not evaluated in previous studies, in influencing the disability level in patients with migraine and confirm the role of comorbid depressive symptoms in modulating the impact of migraine on every day functioning.     

Low income and education levels may cause medication overuse and chronicity in migraine patients

BACKGROUND: Frequent analgesic drug intake, especially in migraine patients, may induce the risk of medication overuse headache (MOH). The various conditions that may affect the development and the features of MOH have not been determined yet. AIM: To compare MOH patients with migraine as pre-existing headache and episodic migraine patients according to socioeconomic and educational variables. METHODS: Forty-six MOH patients with migraine as pre-existing headache and 61 migraine patients were included into study. The headache characteristics, socioeconomic and educational variables of MOH and migraine groups and subgroups divided according to the education (low/high education subgroups), and income (low/high income subgroups) levels were evaluated. RESULTS: We found that mean duration of education was shorter in MOH patients than migraine patients. There was a negative correlation between duration of education and duration of MOH. The mean duration of MOH was longer and rate of low-income level was higher in patients with low-education level. The duration of education was lower in MOH patients with low income. The frequency of migraine attacks and low-income rate was also higher in low-educated migraine patients. The duration of education was shorter in migraine patients with low income. CONCLUSION: We report that migraineurs with low socioeconomic status may have risk of developing MOH. A better identification of patients at risk of drug-associated headache may contribute to improved health in a group of patients with MOH.     

Post-traumatic stress disorder in episodic and chronic migraine

OBJECTIVE: To assess and contrast the relative frequency of self-reported post-traumatic stress disorder (PTSD) in patients with episodic migraine and chronic/ transformed migraine. BACKGROUND: Several risk factors have been identified as risk factors for chronification of headache disorders. Childhood abuse has been suggested as a risk factor for chronic pain in adulthood. In addition depression, as well as several other psychiatric disorders, are co-morbid with migraine. Recent data suggest that PTSD may be more common in headache sufferers than in the general population. METHODS: This was a prospective, pilot study conducted at a headache center. Adult subjects with episodic, chronic, or transformed migraine were included. Demographic information, depression history, body mass index (BMI), and headache characteristics were obtained. PTSD was assessed using the life events checklist (LEC) and the PTSD checklist, civilian version (PCL-C). We contrasted the data from episodicmigraineurs and chronic/transformed migraine participants (CM) and conducted multivariate analyses, adjusting for covariates. RESULTS: Of the 60 participants included, 91.7% were female with a mean age of 41.4+/-12.5 years old. EM was diagnosed in 53.3% and CM in 46.7%. The mean BMI was not significantly different between groups. In contrast, the relative frequency of depression was significantly greater in subjects with CM (55.2%) than EM (21.9%, P=.016). There was no significant difference in the percentage of participants reporting at least 1 significant traumatic life event (LE) or in the mean number of traumatic LEs between EM and CM participants. However, the relative frequency of PTSD reported on the PCL in CM (42.9%) was significantly greater as compared to EM (9.4%, P=.0059. After adjusting for depression and other potential confounders, the difference remained significant P=.023). CONCLUSION: PTSD is more common in CM than in episodic migraineurs. This suggests that PTSD may be a risk factor for headache chronification, pending longitudinal studies to test this hypothesis.     

Topiramate in patients with episodic migraine: reducing the risk for chronic forms of headache

OBJECTIVE: The aim was to evaluate whether preventive treatment with topiramate in patients with episodic migraine reduces the risk of developing chronic forms of headache. BACKGROUND: Chronic forms of headache, including chronic migraine or medication overuse headache (MOH), are characterized by 15 or more headache days per month. Acute medication overuse has been shown to be a risk factor for developing chronic headache, but it is not known whether preventive treatment can reduce the risk of developing chronic forms of headache or the development of MOH. METHODS: Pooled data from 3 trials in patients with episodic migraine randomized either to treatment with 100 mg topiramate per day (n = 384) or with placebo (n = 372) were analyzed with regard to the number of headache days during a prospective 4-week baseline period and the individual final 4 weeks of each patient's treatment during the planned 26-week double-blind treatment period. RESULTS: The number of headache days per month in the topiramate versus the placebo-treated groups was 7.3 +/- 3.0 versus 7.3 +/- 3.1 during baseline and 4.1 +/- 4.2 versus 5.6 +/- 4.9 during the final 4 weeks, respectively (P < .001). At the end of the study, 8 versus 16 patients fulfilled International Headache Society criteria of chronic headache (odds ratio: 2.11, P= .082). Moreover, a significantly lower number of patients receiving topiramate treatment reported an increase in headache days per month by the end of the study when compared to placebo (66 vs 88 patients, respectively; odds ratio: 1.49, P < .05). Finally, the number of days with usage of acute medication was significantly lower in the topiramate arm compared with placebo (3.3 +/- 3.7 vs 4.3 +/- 3.6, respectively; P < .001). CONCLUSION: Preventive treatment with topiramate in patients with episodic migraine may reduce the risk of developing chronic forms of headache.     

Primary Headache Disorders- Part 2: Tension-type headache and medication overuse headache

In Part 2 of Primary Headache disorders, we discuss the fourth Primary Headache Disorder, Tension-Type Headache (TTHA). We are again using the ICHD-III (Beta) definitions of such headaches, taking into consideration episodic and chronic TTHA, as well as the presence or absence of pericranial muscle tenderness. We discuss the pathophysiology and pharmacotherapeutic treatment of TTHA, and the aspects of the Myofascial Pain Syndrome that enhance and help the development of TTHA. We then discuss Medication Overuse Headache (MOH), itself a Secondary headache disorder, but one that is extremely important as it assists with the chronification of both migraine and TTHA. Finally we discuss how to manage and treat those patients with MOH. Chronic migraine, which is TTHA, Migraine as well as, in many patients, MOH, is discussed along with the treatment of this multifaceted disorder.     

Efficacy of multidisciplinary treatment in a tertiary referral headache centre

Despite the high prevalence of headaches, multidisciplinary headache clinics are few and their efficacy still needs validation. We set out to describe the procedures, characterize the patients and evaluate the treatment results in Danish Headache Centre. All clinical records for patients discharged in 2002 were systematically reviewed. Diagnoses were classified in accordance with ICHD-II. Outcome results were analysed with respect to headache diagnoses, frequency, intensity, absence from work and medication use. Five hundred and five patients were included and 336 were eligible for the study. Mean age was 46 years and male/female ratio 1:2.4. For patients without medication overuse headache (MOH) a reduction in headache frequency (P<0.01) and intensity (P<0.05) was seen for frequent episodic and chronic tension-type headache (TTH), migraine, cluster and other headaches. No reduction was seen in post-traumatic headache. Absence from work decreased significantly for migraine (P<0.001) and frequent episodic TTH (P<0.05). For patients with MOH a reduction in headache frequency was seen for TTH and migraine (P<0.001). A specialized headache centre is valuable in treatment of patients with complex headache disorders.     

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.     

Chronic Migraine: An Update on Physiology,Imaging, and the Mechanism of Action of Two Available Pharmacologic Therapies

Several lines of research support the hypothesis that migraine is a spectrum of illness, with clinical symptoms that vary along a continuum from episodic migraine to chronic migraine. Physiologic changes may result in episodic migraine evolving into chronic migraine over months to years in susceptible individuals. With chronification, headache frequency increases, becoming more disabling and less responsive to therapy. Neurophysiologic and functional imaging research has reported that chronic migraine may be associated with severity‐specific metabolic, functional, and structural abnormalities in the brainstem. Without longitudinal studies, it is unclear whether these changes may represent a continuum of individual progression and/or are reversible. Furthermore, chronic migraine is associated with larger impairments in cortical processing of sensory stimuli when compared with episodic migraine, possibly caused by more pronounced cortical hyperexcitability. Progressive changes in nociceptive thresholds and subsequent central sensitization due to recurrent migraine attacks in vulnerable individuals contribute to the chronic migraine state. This may result in changes to baseline neurologic function between headache attacks, evident in both electrophysiological and functional imaging research. Patients experiencing migraine chronification may report increased non‐headache pain, fatigue, psychiatric disorders (eg, depression, anxiety), gastrointestinal complaints, and other somatic conditions associated with their long‐term experience with migraine pain. Recent research provides a foundation for differentiating episodic and chronic migraine based on neurophysiologic and neuroimaging tools. In this literature review, we consider these findings in the context of models designed to explain the physiology and progression of episodic migraine into chronic migraine, and consider treatment of chronic migraine in susceptible individuals. Advances in pharmacotherapy provide treatment options for chronic migraine. Of the currently available treatment options, only onabotulinumtoxinA and topiramate have received regulatory approval and have demonstrated efficacy in patients with chronic migraine, although the exact mechanisms of action are not fully elucidated.     

Overuse of acute migraine medications and migraine chronification

Among individuals with episodic migraine, the influence of excessive acute medication use on the development of chronic migraine depends upon within-person characteristics (eg, headache frequency), class of drug, and frequency of medication use. Available data suggest that opioids induce migraine chronification (progression), and the effect is dose dependent (critical dose around 8 days of exposure per month) and more pronounced in men. Barbiturates also induce migraine progression, and the effect is dose dependent (critical dose around 5 days of exposure per month) and more pronounced in women. Triptans induce migraine progression only in those with high migraine frequency at baseline (10–14 days per month), but not overall. NSAIDs protect against migraine progression unless individuals have 10 or more headache days per month (when they become inducers, rather than protective). Finally, caffeine-containing over-the-counter products increase risk of progression. While we await randomized trials, these findings should inform the choice of acute migraine treatments with the goal of reducing the risk of migraine progression to chronic migraine.     

Brainstem dysfunction in chronic migraine as evidenced by neurophysiological and positron emission tomography studies

BACKGROUND: The pathophysiology of chronic migraine (CM) is not fully understood. We aimed to examine transcranial magnetic stimulation (TMS) indices of cortical excitability in patients with CM and also performed PET studies to ascertain if there were any areas of activation and inhibition for possible correlation. METHODS: Excitability of the cortex was assessed by a reliable parameter of magnetic suppression of perceptual accuracy (MSPA) profiles using transcranial magnetic stimulation in 25 patients with CM. Of these 10 patients were also studied with ((18)F-FDG PET) scans. RESULTS: MSPA demonstrated decreased inhibition in CM compared to normal controls and episodic migraine. The percentage of letters reported correct at 100 ms was 84.37 for CM compared to 19.14 for normal controls and 57.41 for episodic migraine. The PET evaluation in 10 subjects demonstrated increased cerebral metabolism in areas of in the brainstem compared to the global flow. There were also decreased areas of cerebral metabolism in the medial frontal and parietal as well as the somatosensory cortex. CONCLUSIONS: Patients with CM appear to be characterized by reduced visual suppression correlating with high cortical excitability. In a cohort of these subjects there was brainstem activation and inhibition in certain areas of the cortex suggesting a potential dysfunction in the inhibitory pathways.     

Chronic migraine and medication overuse headache: clarifying the current International Headache Society classification criteria

Despite the recent advances in the understanding and classification of the chronic daily headaches, considerable controversy still exists regarding the classification of individual headaches, including chronic migraine (CM) and medication overuse headache (MOH). The original criteria, published in 2004, were difficult to apply to most patients with these disorders and were subsequently revised, resulting in broader clinical applicability. Nonetheless, they remain a topic of debate, and the revisions to the criteria have further added to the confusion. Even some prominent headache specialists are unsure which criteria to use. We aimed to explain the nature of the controversies surrounding the entities of CM and MOH. A clinical case will be used to illustrate some of the problems faced by clinicians in diagnosing patients with chronic daily headache.