Search

Objective: The etiopathogenesis of systemic sclerosis (SSc) is unknown. Platelet-derived growth factor receptors (PDGFRs) are overexpressed in patients with SSc. Because PDGFRα is targeted by the adeno-associated virus type 5 (AAV5), we investigated whether AAV5 forms a complex with PDGFRα exposing epitopes that may induce the immune responses to the virus-PDGFRα complex., Methods: The binding of monomeric human PDGFRα to the AAV5 capsid was analyzed by in silico molecular docking, surface plasmon resonance (SPR), and genome editing of the PDGFRα locus. AAV5 was detected in SSc lungs by in situ hybridization, immunohistochemistry, confocal microscopy, and molecular analysis of bronchoalveolar lavage (BAL) fluid. Immune responses to AAV5 and PDGFRα were evaluated by SPR using SSc monoclonal anti-PDGFRα antibodies and immunoaffinity-purified anti-PDGFRα antibodies from sera of patients with SSc., Results: AAV5 was detected in the BAL fluid of 41 of 66 patients with SSc with interstitial lung disease (62.1%) and in 17 of 66 controls (25.75%) (P < 0.001). In SSc lungs, AAV5 localized in type II pneumocytes and in interstitial cells. A molecular complex formed of spatially contiguous epitopes of the AAV5 capsid and of PDGFRα was identified and characterized. In silico molecular docking analysis and binding to the agonistic anti-PDGFRα antibodies identified spatially contiguous epitopes derived from PDGFRα and AAV5 that interacted with SSc agonistic antibodies to PDGFRα. These peptides were also able to bind total IgG isolated from patients with SSc, not from healthy controls., Conclusion: These data link AVV5 with the immune reactivity to endogenous antigens in SSc and provide a novel element in the pathogenesis of SSc., (© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: To summarize the available evidence on disability, quality of life (QoL), and economic burden on societies of cluster headache (CH), and to present which tools have been used to measure these domains with indications for future research., Background: CH is a rare and severe primary headache. The focus of research on this disorder has historically been on understanding its complex pathophysiological mechanisms, whereas personal and global healthcare impact, disability, and QoL received little attention., Methods: We reviewed the available literature published up to 2019, identifying primary research addressing QoL, disability, impact, or impairment in daily life due to episodic CH (ECH) or chronic CH (CCH), and its societal impact., Results: CH produces a significant impact on sufferers QoL, disability, and work-related aspects, with a stronger impact on CCH than ECH. The CH-related disability appears to be greater than is seen in subjects with other primary headache disorders., Conclusions: Information about patient-reported outcomes is rarely collected in patients with CH. An effort to improve the amount of information on the lived experience of patients with CH is needed and CH-specific disability and QoL measures require development., (© 2020 American Headache Society.)

Objective: This article reviews current headache disability measures and clinical need, as well as presenting the rationale for a new measure addressing work-related disability in migraine patients and the steps devoted to this aim., Background: Episodic and chronic migraine (EM and CM) constitute an enormous economic burden to societies, and the vast majority of this burden is attributable to indirect costs, ie those associated with productivity loss. A measure of work-related disability is therefore needed to quantify the impact of EM and CM on patients' ability to carry out work tasks., Methods: We briefly present the advantages and disadvantages of the disability measures that have been most commonly used for this purpose and the rationale for developing a new measure., Results: The entire process of development of HEADWORK, a questionnaire designed to assess work-related disability, is presented together with short-term sensitivity to change., Conclusions: Current headache disability measures need improvement. HEADWORK is a valid, reliable, and sensitive questionnaire to address the amount and severity of work-related difficulties and of the factors contributing to such difficulties. HEADWORK is suitable for daily clinical practice, epidemiological research and for clinical trials, and potentially to define work-related disability weights for the calculation of migraine indirect costs., (© 2020 American Headache Society.)

Background and Purpose: The cost of medication overuse headache (MOH) is underestimated. Our aim was to address the cost-effectiveness of a structured treatment protocol and to present annual cost estimates., Methods: Patients were enrolled on the occasion of a structured treatment protocol, were administered a research protocol addressing direct and indirect costs and were followed up for 3 months., Results: Of 176 enrolled patients, 138 completed the study. The 3-month cost per patient fell from €2989 to €1160: the difference was €696 per month for patients treated in the ward and €466 for those treated in day-hospital; thus it takes 2-3 months to compensate for the protocol's cost. The per-person annual costs of MOH were €10 533 (95% confidence interval €8700-12 406): direct healthcare costs accounted for 44.8% and indirect costs for 51.5% of the total MOH cost. The annual MOH cost for Italy is estimated at €13.5 billion (95% confidence interval €11.1-15.9 billion)., Conclusion: The cost of MOH around the period of a structured treatment protocol is much higher compared to previous estimates. Our protocol is cost-effective for reducing the economic burden of MOH., (© European Academy of Neurology 2019.)

Objective: To clarify whether the clinical response after the first 2 cycles with Onabotulinumtoxin A can accurately predict the long-term response., Background: Onabotulinumtoxin-A (OBT-A) is an approved preventive treatment option for chronic migraine (CM). Nowadays, it remains to be clarified if the treatment has to be prolonged for at least an entire year (4 injections every 3 months - ie, quarterly, as proposed in the PREEMPT trials) or it can be halted after the second or third injection if not clinically effective., Design and Methods: We conducted a multicenter observational cohort study based on real-life data on the usage of OBT-A in CM patients from 2 Italian headache centers, Roma Campus Bio-Medico and Milano Besta, adopting the whole 4-injections protocol. We performed a retrospective analysis of medical records of consecutive patients treated in the 2 centers. The main statistical analysis aimed to evaluate longitudinal measures related to headache (monthly headache frequency, monthly number of analgesic drugs, MIDAS). We hypothesized from our clinical practice with OBT-A that only 2 cycles of treatment were not enough to actually define the non-responder status to botulinum toxin A and that probably a longer time of treatment is needed to get the condition of long-term (delayed) responder., Results: We considered 115 patients from the 2 centers: 53 in Roma and 62 in Milano. Regarding the main analysis, a clear improvement in each measure was obtained at the 6 months assessment and maintained up to 12 months. Comparing patients with <30% and ≥30% reduction in headache frequency between T0 and T2 or T4 (respectively, "Non-Responders" and "Responders"), we found that the agreement between the classification Responders/Non-Responders at T2 and T4 was not very high (79/104 = 76.0%, with a "moderate" Cohen's Kappa of 0.51), suggesting that the status at T4 is not fully predictable by the status at T2 (λ = 0.47). Responders for headache frequency at T4 were 54.8%. Among Responders at T2, Responders at T4 were 47/62 = 75.8% (95% CI: 64.5%, 85.5%), while among Non-Responders at T2, Responders at T4 were 10/42 = 23.8% (95% CI: 11.9%, 38.1%). Similarly, even when considering the 50% reduction in painkillers consumption or in MIDAS total score between T0 and T2 as possible prognostic factors, the changes occurring at T4 are not strongly predictable by those at T2., Conclusions: A ≥30% reduction in headache frequency at T2 cut-off is not adequate in predicting a late response to treatment: more than a quarter of excluded patients would miss a clinical improvement with an ongoing treatment, while in a similar percentage of Responders the treatment would lose efficacy. Results from our real-life study suggest that we possibly have to postpone the definition of Responder/Non-Responder to OBT-A at least after 1 year of treatment (4 cycles)., (© 2019 American Headache Society.)

Background: It is common clinical experience that, after structured withdrawal, some patients with chronic migraine and medication overuse headache (CM with MOH) are more prone than others to relapse and to be in need of further structured treatments. Our aim was to explore similarities and differences between frequent relapsers (FRs) and non-frequent relapsers (NFRs) by considering their point of view, perceptions, and perspective of their subjective experience with relapse into CM with MOH., Methods: Patients were consecutively recruited on occasion of a structured withdrawal treatment and were interviewed individually about their headache experience and their perspectives on relapse into CM with MOH. We considered FR those patients requiring 2 or more structured withdrawals for MOH within 3 years. A narrative approach with no preconceived coding schemes was employed. To facilitate coding, categorization and organization of data the software QRS NVivo 11.0 was used: themes were defined as common to FR and NFR, or peculiar (by frequency or content) to one of the 2 groups., Results: Sixteen patients (13 women; mean age of 53) were interviewed: 7 were classified as FRs. A total of 22 themes emerged from 552 single quotations (the 10 most relevant covered 82% of the entire body of quotations). Four themes were commonly reported by both FR and NFR patients, and 6 were peculiar to one group only. Common aspects included issues connected to the dilemma between disclosing, concealing and the feelings of isolation around MOH, the idea of being addicted to medication, presence of anxiety, and the attempt to use non-pharmacological therapies as an alternative to medication. Peculiar aspects included causal attribution (FRs attributed headache to uncontrollable factors); future expectations at the time point of withdrawal (FRs were generally resigned); high-performance functioning (FRs believed they are "forced" to reach high levels of performance as a consequence of others' inability); coping strategies (FRs tended to "passively accept" problems and showed avoidance-related behaviors). Moreover, FRs were less frequently aware of their problems and described more frequently depressive symptoms., Conclusions: Our results highlight that some differences between FR and NFR patients with CM and MOH exist. Frequent relapsers among patients with CM and MOH reported some important peculiarities of the lived experience of having chronic migraine; clinicians should recognize these psychosocial aspects such as social relationships, future expectations, the experience of illness, medication management, and how the withdrawal experience is regarded, as they may be associated with frequent relapse into MOH., (© 2018 American Headache Society.)

Background: Behavioral treatments in the management of primary headache disorders in adults and children are increasingly being recognized as effective; however, the level and durability of their effectiveness is still a matter of debate. This review aims to provide more updated information on the effects of behavioral therapies in adults and adolescents with primary headache disorders, with a special focus on new and emerging behavioral treatments., Methods: We searched SCOPUS for peer-reviewed papers that reported randomized controlled trial or observational studies addressing behavioral treatment for headache disorders published in the period January 2010 to October 2017., Results: A total of 22 publications, in which 2110 participants were recruited, were included in the review. Most of the studies referred to cognitive behavioral therapies, and a reduction of headache frequency higher than 35% was generally reported irrespective of the approach. In addition, valuable impact disability and quality of life was observed, as well as improvements in depression, anxiety, self-efficacy, and intake of medications., Conclusions: Behavioral approaches are effective and less prone to produce side or harmful effects, which makes them a valid option particularly for women who are pregnant or nursing, people with other chronic conditions requiring pharmacological treatments putting them at risk for drug-drug interactions, and children., (© 2018 American Headache Society.)

Background: Studies addressing relapse rates conflate relapse into chronic migraine (CM) and medication overuse (MO), and the consequent need to repeat withdrawal. We aim to identify 12-months predictors of relapse into CM (based on headaches frequency) separately from occurrence of another structured withdrawal., Methods: Hospitalized patients with CM-MO under withdrawal were enrolled. Candidate predictors included demographic, disability, quality of life, depression scores, general self-efficacy, social support, headaches frequency and intensity, class of overused medications, history of withdrawal treatment in the three years prior to enrollment, attendance to emergency room (ER) between enrollment and follow-up, nonattendance to outpatient neurological examinations. Logistic regressions was used to address the significant predictors for the two outcomes., Results: Complete data were available for 177 patients: 60 (33.9%) relapsed into CM, 38 (21.5%) underwent another withdrawal treatment. Recent history of withdrawal treatments, ER admission after discharge and high baseline BDI-II scores were significant predictors in both models. In addition to this, high baseline headache frequency predicted relapse into another withdrawal treatment., Conclusions: Predictors or relapse into CM and of occurrence of another withdrawal by 12-months are somehow similar. It is important to assess presence of recent previous withdrawal treatments and to plan regular follow-up afterwards, in particular for patients with high headache frequency and relevant mood disturbances: in this way, it will be more likely that situations requiring further structured withdrawal treatments can be identified before patients have to refer to ER., (© 2016 American Headache Society.)

Objective: Reactive oxygen species (ROS) contribute to the pathogenesis of fibrosis in systemic sclerosis (SSc; scleroderma), and NADPH oxidase (NOX) is an important source of ROS. Since the role of single NOX isoforms has not been previously investigated in SSc, this study was undertaken to assess the expression of NOX in SSc fibroblasts compared to normal healthy cells and to analyze their role in cell activation., Methods: Expression of NOX isoforms in dermal fibroblasts from patients with SSc and healthy control subjects was analyzed by real-time polymerase chain reaction, immunoblotting, and immunofluorescence. NOX isoforms were silenced using small interfering RNA. Production of ROS was measured by fluorometry and confocal microscopy., Results: Scleroderma fibroblasts showed up-regulation of NOX-2 and NOX-4 protein and messenger RNA (mRNA) expression. Treatment of the cells with diphenyleneiodonium, a nonselective inhibitor of flavin-containing enzymes, and silencing of NOX2 and NOX4 decreased the production of ROS as well as the expression of type I collagen and α-smooth muscle actin in SSc fibroblasts. ROS generated by NOX-2 and NOX-4 were involved in DNA damage and activation of a DNA repair checkpoint. Incubation of healthy control fibroblasts with platelet-derived growth factor (PDGF) or with IgG isolated from SSc patient serum enhanced the expression of NOX2 and NOX4 mRNA, via ROS, in a time-dependent manner. Treatment with actinomycin D, a transcription inhibitor, reversed the effects of PDGF stimulation but not the effects of SSc IgG., Conclusion: Both NOX2 and NOX4 generate ROS in SSc fibroblasts and play a critical role in cell activation and DNA damage. Expression of NOX-2 and NOX-4 in SSc fibroblasts is maintained by a ROS-mediated loop., (© 2015, American College of Rheumatology.)

Background: Chronic migraine with medication overuse (CM-MO) impairs quality of life (QoL) and causes disability. Psychosocial variables such as depressive symptomatology, self-efficacy, and social support have been sparingly investigated, and their impact on disability and QoL is unknown., Methods: Patients with CM-MO under withdrawal were consecutively enrolled. Standardized measures of disability and QoL were used as outcomes; psychosocial (ie, mood state, self-efficacy, social support) and clinical (ie, headache frequency and intensity) variables were considered as associated variables. Associations between these variables, disability, and QoL were tested with Pearson's correlations. Hierarchical multiple regression was used to assess the cumulative contribution of psychosocial variables on disability and QoL variation when added to clinical variables., Results: One hundred ninety-four patients were enrolled; 82.5% were females and mean age was 43.9. Disability and QoL were moderately or little correlated to clinical and psychosocial variables. Models based on clinical variables explained 7.5-14.3% of disability and QoL variation, with pain intensity being the only significant predictor; when psychosocial variables were added, the explained variation increased to 21.5-35.2%, with depressive symptomatology always having independent predictive power and perceived social support having independent predictive power in the regression model over role-prevention component of QoL., Conclusions: Adding information on psychosocial variables to headache features improved our ability to understand disability and QoL of CM-MO patients. We deem that the inclusion of psychosocial variables in standard evaluation protocols may contribute to the global assessment of CM-MO patients, and eventually to their success in reducing the personal and social impact of this condition. Future longitudinal studies are needed to confirm this hypothesis., (© 2015 American Headache Society.)

Objective: To describe a short-term "real-life" longitudinal evolution of migraine course, quality of life, and disability in a sample of patients attending to a specialty center and to evaluate the association between the changes in patient-reported outcomes, number of reported headaches, their severity, and treatment consumption., Background: Clinical trials demonstrated that symptomatic and preventive therapies reduce migraine headache frequency and severity, thus improving quality of life and reducing disability. However, the longitudinal trajectory of health outcomes of patients under specific treatments but out of the setting of a clinical trial is almost unexplored., Design: Longitudinal observational study with a 3-month follow-up., Methods: Adult patients suffering from migraine, both with and without aura, were consecutively enrolled and administered the Migraine Disability Assessment, World Health Organization Disability Assessment Schedule, second version, and the Medical Outcome Survey 36-Item Short-Form Health Survey. Analysis of variance for repeated measures was used to assess longitudinal differences between baseline and the 3-month follow-up at employed assessments, number of days with headache in the previous 3 months and average judgment on attacks' severity, number of triptans and anti-inflammatory drugs consumed for acute treatment of attacks; effect size was used to determine magnitude of change. Baseline differences between completers and non-completers was evaluated with the independent-sample t-test. Pearson's correlation was used to cross-sectionally assess the association between total number of headache in the previous 6 months, average headache severity, total number of triptans and anti-inflammatory drugs taken, and the scores observed at follow-up for the 3 assessment instruments. The independent-sample t-test was used to assess cross-sectional differences between subjects taking preventive therapy and those taking only acute ones for total number of headaches, their severity, and total number of triptans and anti-inflammatory taken, considering scores referred to the 3-month follow-up evaluation., Results: One hundred and two patients were enrolled (85.3% females; mean age 43.5) and 85 patients (85.9% females; mean age 44.3) completed the 3-month follow-up; no relevant differences between completers and non-completers were observed. Small changes (effect size <0.50) were observed in longitudinal analysis, in particular for World Health Organization Disability Assessment Schedule scales, while frequency and severity of headaches were substantially stable. Few significant correlations were observed, in particular between the total number of days with headache and Migraine Disability Assessment score (0.54; P < .01), and between the total number of days with headache and the total number of triptans taken (0.46; P < .01). Compared with patients taking acute medication only, those on preventive therapy reported worse general health (mean 50.3, standard deviation [SD] 21.0 compared with mean 63.8, SD 16.5; t = 3.31, P = .001) and consumed less anti-inflammatory drugs (mean 3.5, SD 5.6 compared with mean 7.5, SD 9.1; t = 2.25, P = .014)., Conclusions: In this study, migraine frequency and intensity were almost stable over 3 months, and an evident trend toward improvement was found in disability and in some health-related quality of life aspects, particularly in the social activity domain. Our results clearly indicate that continuity of care has a positive impact on patients' health status and functioning, also in stable patients already on anti-migraine therapy, and that the use of patient-oriented outcome measures is a viable way to capture such improvements., (© 2012 American Headache Society.)

Background: The impact of migraine on patients' daily life has been evaluated in several studies. The relationship between disability and health-related quality of life (HRQoL) in patients with migraine, however, has not been systematically evaluated., Objective: To assess the impact of migraine on patients' HRQoL and disability patterns and to describe the relationship between disability and HRQoL in patients with migraine attending a specialty Italian headache center according to the biopsychosocial model of disability endorsed by the International Classification of Functioning, Disability and Health., Methods: In this observational study, adult patients with migraine were consecutively recruited. Disability was measured with the MIDAS (Migraine Disability Assessment) and the WHO-DAS II (World Health Organization Disability Assessment Schedule), HRQoL with the SF-36 (Medical Outcome Survey 36-item Short-Form Health Survey). Spearman's rank correlation between MIDAS score, SF-36 and WHO-DAS II scales was performed to evaluate the relationships between quality of life and disability. The impact of migraine on disability and HRQoL was assessed by comparing WHO-DAS II and SF-36 scores against Italian normative values, and by evaluating the different disability and HRQoL profiles in patients with different severity of migraine, defined according to migraine frequency and pain intensity., Results: A total of 102 patients with migraine (87 females) were enrolled. Mild to moderate correlations were reported between WHO-DAS II and SF-36's PCS (r = -0.67, P < .01) and MCS (r = -0.36, P < .05) scales; MIDAS score correlations to SF-36's PCS (r = -0.44, P < .01) and MCS (not significant) were lower than WHO-DAS II summary score. The correlation between MIDAS score and the WHO-DAS II summary score was mild (r = -0.36, P < .05). The majority of HRQoL and disability scales (with the exception of SF-36's Physical Functioning, and WHO-DAS II Getting along with people scales) scored significantly lower than normative values. A trend towards worsening of both HRQoL and disability, consistent with increasing migraine severity, was reported (Mann-Whitney's U = 119.5 for MIDAS; U= 113.0 for WHO-DAS II summary score, both with P < .01; U = 152.9 for PCS; U = 171.0 for MCS, both with P< .05), Conclusions: In migraineurs attending an Italian specialty headache clinic, disability scores were worse and HRQoL scores lower than those of the general population, and worsened consistently with increased migraine severity. Measures of HRQoL and disability evaluate different psychosocial aspects of migraine and researchers should continue to employ them in public health and clinical research on migraine. They provide information on a poorly recognized part of migraine's burden, where economic impact is minimal but there are important effects on patients' daily lives in terms of interpersonal relationships, perceived quality of life and emotional status., (© 2010 American Headache Society.)

Background: There is a well-known association between migraine with aura (MA) and right-to-left shunt (RILES) because of patent foramen ovale (PFO). The occurrence of MA attacks after microbubble (MB) injection during contrast-enhanced transcranial Doppler (ce-TCD) has been recently described., Objectives: The aim of this study was to analyze the prevalence of RILES in a consecutive cohort of MA patients and to characterize the occurrence of MA attacks after diagnostic ce-TCD., Methods: A total of 159 consecutive MA patients underwent ce-TCD with air-mixed saline to disclose RILES. RILES was characterized in terms of MB amount (small-moderate or large) and occurrence at rest and/or during Valsalva maneuver (permanent or latent)., Results: RILES was revealed in 79/159 patients (∼ 50%). Permanent RILES were detected in 56/79 (71%) and latent RILES in 23/79 (29%) MA patients. The occurrence of a typical MA attack was overall observed in 12/159 patients (7.5%; 95% CI: 4-12.8%), but arose only in RILES-positive ones, immediately after ce-TCD (12/79; 15.2%; P< .001). All 12 patients had permanent RILES (12/56; 21.4%; P= .015) and MA attack was mostly observed in large RILES-positive patients, even without statistical significance (P= .118)., Conclusions: Microembolic air load could act as a trigger of MA attack. According to recent studies and to the clinical characteristics observed in our patients, microembolization because of MB injection might provoke a decrease in cerebral oxygen saturation, thus triggering cortical spreading depression and, thereafter, MA attack. Larger and prospective studies will be necessary to confirm our data and observe a wider correlation.

Objective: To investigate allodynia in patients with different primary headaches., Background: Many migraineurs have allodynia during headache attacks; some may have allodynia outside attacks; allodynia may also be associated with other primary headaches., Methods: A total of 260 consecutive primary headache patients presenting for the first time at a headache center, and 23 nonheadache controls answered written questions (subsequently repeated verbally) to determine the presence of acute and interictal allodynia., Results: We divided the patients into: episodic migraine (N = 177), subdivided into only migraine without aura (N = 114) and those sometimes or always reporting migraine with aura (N = 63); episodic tension-type headache (N = 28); chronic headaches (headache > or = 15 days/month, N = 52), including chronic migraine, chronic tension-type headache, and medication-overuse headache; and other headache forms (N = 3). Acute allodynia was present in 132 (50.7%), significantly more often in patients sometimes or always suffering migraine with aura, and those with chronic headache forms, compared to patients with migraine without aura and episodic tension-type headache. Interictal allodynia was present in 63 (24.2%) patients, with significantly higher frequency in those having migraine with aura attacks than controls and common migraine patients., Conclusions: Allodynia is not specific to migraine but is frequent in all headache patients: acute allodynia was reported in half those interviewed and in over a third of patients in each headache category; interictal allodynia was reported by nearly 25%.

Objectives: To determine the clinical status, with respect to pain indices and disability level, of chronic migraine patients with medication overuse who were treated 3 years previously., Background: Patients who have chronic migraine accompanied by medication overuse are particularly difficult to treat. Investigations are limited in number, few have included follow-up beyond 6 months, and almost none have examined whether treatment leads to concurrent improvements in disability and functional impairment. In a prior report, we described the clinical course of 84 such patients followed for 1 full year after treatment., Methods: These same 84 patients were followed for 2 additional years to assess longer term maintenance of effects, using measurement procedures identical to those in the original investigation., Results: Both endpoint and completer analyses revealed significant improvement on all measures studied-headache days per month, analgesic consumption, and MIDAS scores (Total, Headache Frequency, and Headache Intensity)-with some loss of benefits over time for the pain indices. MIDAS total scores, however, were lower at 36 months than at 6 months. Comparisons of those who completed the 3-year follow-up to those who did not revealed few differences at baseline. All of this suggests attrition did not have a bearing on outcome., Discussion: High levels of maintenance were revealed at 3 years. Even though reports of pain revealed some lessening of effects, this was not accompanied by reports of deterioration in functioning. This suggests that patients have learned to adapt and adjust to headaches in their daily lives.

Background: The 4-item Migraine-ACT questionnaire is an assessment tool for use by primary care physicians to identify patients who require a change in their current acute migraine treatment. It has been shown to be easy to use, and to be reliable and accurate in its assessments., Objectives: To further analyze the Migraine-ACT study database, providing additional information on the reliability, validity, and potential clinical utility of the questionnaire., Methods: Reliability was assessed by recording the distribution of Migraine-ACT scores recorded at baseline and 1 week later (test-retest reliability). Analyses of consistency of Migraine-ACT scores were conducted on the total sample of patients and for the separate centers, using Pearson and Spearman correlations. Validity was assessed by comparing the t-discrimination values for clinically relevant questions within domains of the original 27-item questionnaire. Reliability and validity were also assessed by constructing an "alternative" (Form B) Migraine-ACT questionnaire, derived from an analysis of the second-best items in each domain in the original study data. Clinical utility was assessed using Pearson pairwise correlations to compare Migraine-ACT scores with clinically defined criteria as analyzed by the SF-36 Quality of Life questionnaire, the Migraine Disability Assessment (MIDAS) questionnaire, and the Migraine Therapy Assessment (MTAQ) questionnaire., Results: The distribution of Migraine-ACT scores between the 2 completions of the questionnaire was consistent for the total sample (test-retest reliability, r= .81) and between the individual countries (r= .61 to .92). In this study, the validity (assessed as t-discrimination) of the Migraine-ACT "impact" and "global assessment of relief" questions were markedly higher than those of other endpoints used in migraine clinical studies. The Form B Migraine-ACT questionnaire was almost as reliable and accurate as the original Form A questionnaire. The distribution of Migraine-ACT scores was: 0 = 12.6%, 1 = 13.7%, 2 = 14.7%, 3 = 20.5%, and 4 = 38.4%. The change in Migraine-ACT score correlated with, and had a linear relationship with changes in SF-36, MIDAS, and MTAQ scores, and indicated that a Migraine-ACT score of

Celiac disease is sometimes associated with neurological complications. Only one case of celiac disease associated with migraine and cerebral calcifications has been reported. We present a patient with migraine (with and without aura) in whom neuroimaging revealed cerebral calcifications in the occipital and parietal regions bilaterally. Visual examination showed bilateral double scotoma, and further investigations revealed celiac disease. Migraine may on occasion be a sentinel symptom of mild celiac disease.

Objectives: To assess headache-related disability in chronic migraine with medication overuse (CMO), as defined by Silberstein and Lipton (1996, 2001) in comparison to that caused by migraine without aura, investigating similarities and differences in disability patterns in these two conditions., Background: It is well known that migraine has a marked impact on daily activities. Less information is available on the functional consequences of chronic migraine., Methods: This was a prospective study on 247 patients with CMO and 264 with migraine without aura. All completed the validated Italian version of the Migraine Disability Assessment questionnaire (MIDAS). The MIDAS total score and scores of each question (investigating total or partial inability to perform different daily activities) were evaluated, and compared in the two groups using the Mann-Whitney rank sum test. We also evaluated the number of missed days (question 1) and days with significantly reduced effectiveness at work (question 2) and in nonwork activities (questions 3, 4, and 5), using descriptive statistics., Results: MIDAS total score in the CMO group was rather high (mean 84.1, median 70) and significantly higher than in the migraine group (mean 23.4, median 19). CMO patients also reported higher scores than migraine patients in MIDAS questions investigating disability in different domains, the differences being highly significant for questions 3, 4, and 5. In both CMO and migraine the number of days with total or significant disability in nonwork activities was higher than the number of days with total or significant disability in work activities, and days spent at work with significantly reduced effectiveness were more than work days missed., Conclusions: Our findings show that CMO has a profound effect on patients' daily functioning. They suggest that differences between CMO and migraine are mainly quantitative, while the two groups are similar in terms of disability pattern. These results are consistent with the fact that CMO may be an evolution of episodic migraine, characterized by increase in headache frequency and more evident disability in performing different daily duties.

Objective: To determine (1) the clinical course of a sample of chronic migraine patients with drug overuse 6 and 12 months following in-patient treatment and (2) whether functional impairment, assessed by the Migraine Disability Assessment (MIDAS) questionnaire, improved upon treatment., Background: Patients with chronic migraine and medication overuse are particularly difficult to treat (prophylactic medications that otherwise are effective become ineffective; discontinuation of the offending medication can lead to withdrawal headache; physical and emotional dependence can be present, as well as increased psychological involvement; initial treatment gains can be difficult to maintain)., Methods: Of the 106 patients meeting criteria for chronic migraine with medication overuse, 84 went on to complete a structured in-patient treatment, consisting of medication withdrawal and then prophylactic treatment., Results: As a group, the patients were improved at both 6- and 12-month follow-up, with respect to two headache parameters (frequency and medication use) and three measures of functional impact extracted from the MIDAS questionnaire (Total Score, Headache Frequency, and Headache Intensity)., Conclusion: Chronic migraine accompanied with medication overuse led to the considerable disability prior to treatment. However, notable improvement occurred coincident with the treatment. This suggests that successful treatment has more wide-ranging positive benefits beyond mere symptom reduction. To our knowledge, this is the first investigation where the MIDAS questionnaire has been used prospectively as an outcome measure in patients with chronic migraine and medication overuse to assess disability subsequent to a semi-standardized treatment program.

Objective: To determine whether combined treatment using medication and biofeedback would be more effective than drug treatment alone for treating transformed migraine complicated by analgesic overuse., Background: Headaches that are chronic, daily, and aggravated by medication overuse are particularly difficult to treat., Methods: Sixty-one consecutive patients with transformed migraine and analgesic overuse were treated with inpatient pharmacologic therapy alone or with inpatient pharmacologic therapy combined with biofeedback-assisted relaxation. All patients then were followed prospectively for 3 years., Results: Both treatment groups exhibited similar levels of improvement immediately following treatment and for 1 year thereafter. At year 3, participants receiving combined treatment showed greater sustained improvement on two of three outcome measures assessed (ie, fewer days of headache and reduced consumption of analgesic medication). In addition, a greater number of patients assigned to pharmacologic treatment alone relapsed (ie, resumed overuse of analgesics) compared to patients receiving combined treatment., Conclusions: These results suggest that a combination of pharmacologic and behavioral treatment is more effective than drug therapy alone in the long-term management of transformed migraine with analgesic overuse. Confirmation of these findings, as well as extension to other forms of behavioral and cognitive-behavioral treatment, is required.

Transdermal clonidine has recently been reported to be efficacious in the prophylaxis of cluster headache. A 2-week course of transdermal clonidine (5 mg the first week, 7.5 mg the second week) preceded by a 5-day run-in period, was administered to 16 patients with episodic cluster headache in an active cluster period. In 5 patients, the painful attacks disappeared after the seventh day of treatment. For the group as a whole, no significant variations in headache frequency, pain intensity, or attack duration were observed between the run-in period and the first and second weeks of treatment (ANOVA). Further studies are necessary to clarify the effectiveness of transdermal clonidine in the prophylaxis of episodic cluster headache.

We conducted an open study on the efficacy of 50 mg of sumatriptan as an acute treatment for migraine without aura. We recruited 200 consecutive patients, with an established history of migraine without aura, presenting at a headache center. The patients were instructed to take half a 100-mg sumatriptan tablet for their next migraine attack, and to record details of their headache in a diary. The primary outcome of the study was headache relief from one migraine attack. Attacks were moderately intense (46%), moderate to severe (7%), or severe (47%). Total or partial benefit at 2 hours from the 50-mg dose was reported by 140 of 200 patients (70%). Thirty-six patients received no benefit from half a tablet, and 24 did not take sumatriptan, preferring their habitual medication. Side effects were few, mild, and short lasting. We conclude that the 50-mg oral dose is generally effective for migraine without aura attacks of both moderate and severe intensity and recommend this dose for all such patients. If, however, sumatriptan is ineffective at that dose it can be increased to a maximum of 100 mg.

We report on 10 patients suffering from two types of primary headache, migraine and cluster, diagnosed according to IHS criteria, and selected from headache patients attending two Italian headache centers. We briefly review the literature on coexisting migraine and cluster headache, considering the time relationships between these two headaches. The present series seems not to confirm the hypothesis that migraine transforms into cluster headache since both headaches persist together in the patients. The series is of clinical interest particularly with regard to diagnosis and to treatment strategies. Furthermore, while migraine and cluster headache comorbidity must be confirmed by population-based epidemiological studies, the possibility arises that the two conditions may be linked pathophysiologically: common genetic factors or functional alterations in the same central neurological circuits may play a role in the pathogenesis of both disorders.

We report on three families in which cluster headache is present in more than one member. In one of these families a boy, his father, and paternal grandfather were affected. In the other two families, a father and son and mother and daughter were the affected members. Diagnoses were based on IHS criteria, after examining and taking the history directly from the patient in all but one of the seven cases; the seventh patient was deceased and the diagnosis was based on reports from the affected son. Considered in the light of other recent reports of familial cluster headache, these cases suggest that cluster headache can have a genetic component.

According to Sjaastad, the pain in cervicogenic headache, a form not recognized by the IHS, is long lasting and always side-locked unilateral. The frequency of side-locked unilateral pain (defined here as no change in side from onset) and other characteristics of cervicogenic headache were investigated in 300 outpatients using information collected on standard forms in structured interviews. Three hundred seventy-four headaches diagnosed according to IHS criteria were identified. Three hundred forty-eight of these headaches were long-lasting (duration of more than 4 hours); migraine (65%) followed by tension-type headache (25%) were the commonest forms. Side-locked unilaterality was present in 29% (101 of 348), and occurred most frequently in migrainous disorders not fulfilling the criteria (25 of 56, 44.6%). This group differed significantly from the other migraine conditions for longer pain duration (P < 0.02) and less frequent nausea, vomiting, photophobia, phonophobia (P < 0.0001), and aggravation by physical activity (P < 0.02). With these characteristics, this group resembled cervicogenic headache. However, in none of these patients was pain triggered by head or neck movements, and the frequency of head or neck trauma did not differ from other headaches. A more precise definition of clinical criteria for cervicogenic headache vs migraine is, therefore, required.

Side-locked unilaterality and specific localization of pain are not as well-defined clinical characteristics in long-lasting headaches (duration more than 4 hours) as they are in short-lasting forms. We examined side-locked unilaterality and pain distribution at onset and at peak headache in 74 patients with different forms of long-lasting headache: migraine and tension-type headache (IHS) and cervicogenic headache (according to Sjaastad et al). Side-locked unilaterality of pain was found in all forms, but to differing extents - 20.8% in migraine, 12.5% in tension-type headache, while it was a mandatory criterion for cervicogenic headache. The pain tended to localize anteriorly, particularly at onset, in migraine; was more diffuse in tension-type headache; and always began in the occipitonuchal region in cervicogenic headache. Our results may contribute to a better clinical definition of long-lasting headaches.

The relevance of side-locked unilateral pain (with no side shift) in diagnosing and differentiating primary long-lasting cephalgias such as tension headache and migraine is not clear. In the present study we have retrospectively examined the frequency of side-locked unilaterality in 1169 primary headache outpatients, whose pain duration was more than four hours. The cases were migraine (66%), tension-type headache (21%) and non-classifiable headache and atypical facial pain (not well defined headaches) (13%). The occurrence of side-locked unilateral pain was more frequent in migraine (17%) than tension headache (4%). However side-locked pain was found to be more frequent in patients with not-well-defined head pain (28%). Of the 1169 patients, 181 (15%) had side-locked unilateral pain: 70% of the 181 had migraine, 25% were not-well-defined head pain cases and 5% were tension-type headache cases. The high percentage of migraine cases in the side-locked unilateral group reflects the high proportion of migraine patients in the studied population.

The shift reagents thulium(III) 1,4,7,10-tetraazacyclododecane N,N',N",N"'tetramethylenephosphonate (TmDOTP5-), and dysprosium(III)triethylenetetramine-hexaacetate (DyTTHA3-) are compared in this work for their uses in sodium chemical shift imaging (NaCSI). In a series of experiments using phantoms we evaluated the relative contributions of bulk magnetic susceptibility (BMS) effects and hyperfine shifts to the induced 23Na chemical shift for these two shift reagents. The ratios of BMS effects to hyperfine shifts suggest that TmDOTP5- should be a more effective shift reagent than DyTTHA3- for 23Na NMR spectroscopy as well as NaCSI. The dependence on pH and free Ca2+ concentration of the 23Na NMR frequency shift induced by TmDOTP5- was evaluated. It was found that TmDOTP5- produces good spectral resolution under physiologic conditions. Examples presented from in vivo NaCSI experiments using TmDOTP5- to study diffusion in the posterior chamber of the rabbit eye and to monitor the rate of clearance of aqueous fluid from the anterior chamber demonstrate the effectiveness of this new shift reagent and of the NaCSI technique for in vivo studies.

A 69 year old man complaining of a cluster-like headache is reported. CT scan showed a median intracranial calcified lesion. Two main considerations are: 1) the importance of searching for an underlying structural lesion in patients with an "atypical" cluster headache; 2) the possible significance of a lesion localized close to the midline structures in the pathogenesis of cluster headache.