Underdiagnosis and undertreatment of migraine in Italy: a survey of patients attending for the first time 10 headache centres.

The aim of this study was to asses the clinical features, pattern of healthcare and drug utilization of migraine patients attending 10 Italian headache centres (HC). Migraine is underdiagnosed and undertreated everywhere throughout the world, despite its considerable burden. Migraine sufferers often deal with their problem alone using self-prescribing drugs, whereas triptans are used by a small proportion of patients. All patients attending for the first time 10 Italian HCs over a 3-month period were screened for migraine. Migraine patients underwent a structured direct interview about previous migraine diagnosis, comorbidity, headache treatments and their side-effects and healthcare utilization for migraine. Patient satisfaction with their usual therapy for the migraine attack was evaluated with the Migraine-Assessment of Current Therapy (ACT) questionnaire. The quality of life of migraine patients was assessed by mean of Short Form (SF)-12 and Migraine-Specific Quality of life (MSQ) version 2.1 questionnaires. Of the 2675 patients who attended HCs for the first time during the study period, 71% received a diagnosis of migraine and the first 953 subjects completed the study out of 1025 patients enrolled. Only 26.8% of migraine patients had a previous diagnosis of migraine; 62.4% of them visited their general practitioner (GP) in the last year, 38.2% saw a specialist for headache, 23% attended an Emergency Department and 4.5% were admitted to hospital for migraine; 82.8% of patients used non-specific drugs for migraine attacks, whereas 17.2% used triptans and only 4.8% used a preventive migraine medication. Triptans were used by 46.4% of patients with a previous diagnosis of migraine. About 80% of migraine patients took over-the-counter medications. The Migraine-ACT revealed that 60% of patients needed a change in their treatment of migraine attacks, 85% of whom took non-specific drugs. Both the MSQ version 2.1 and the SF-12 questionnaires indicated a poor quality of life of most patients. Migraine represents the prevalent headache diagnosis in Italian HCs. Migraine is still underdiagnosed in Italy and migraine patients receive a suboptimal medical approach in our country, despite the healthcare utilization of migraine subjects being noteworthy. A cooperative network involving GPs, neurologists and headache specialists is strongly desirable in order to improve long-term migraine management in Italy.

Psychiatric comorbidity and psychosocial stress in patients with tension-type headache from headache centers in Italy. The Italian Collaborative Group for the Study of Psychopathological Factors in Primary Headaches.

A multicenter study was carried out in 10 Italian Headache Centers to investigate the prevalence of psychosocial stress and psychiatric disorders listed by the IHS classification as the "most likely causative factors" of tension-type headache (TTH). Two hundred and seventeen TTH adult outpatients consecutively recruited underwent a structured psychiatric interview (CIDI-c). The assessment of psychosocial stress events was carried out using an ad hoc questionnaire. The psychiatric disorders that we included in the three psychiatric items of the fourth digit of the IHS classification were depressive disorders for the item depression, anxiety disorders for the item anxiety, and somatoform disorders for the item headache as a delusion or an idea. Diagnoses were made according to DSM-III-R criteria. At least one psychosocial stress event or a psychiatric disorder was detected in 84.8% of the patients. Prevalence of psychiatric comorbidity was 52.5% for anxiety, 36.4% for depression, and 21.7% for headache as a delusion or an idea. Psychosocial stress was found in 29.5% of the patients and did not differ between patients with and without psychiatric comorbidity. Generalized anxiety disorder (83.3%) and dysthymia (45.6%) were the most frequent disorders within their respective psychiatric group. The high prevalence of psychiatric disorders observed in this wide sample of patients emphasizes the need for a systematic investigation of psychiatric comorbidity aimed at a more comprehensive and appropriate clinical management of TTH patients.

Stress, mood disorders and memory in headache.

Comorbidity between headache and other disorders such as psychological or memory problems is a topic of increasing scientific interest both for us diagnostic and therapeutic implications but also for pathogenetic advances. A central neurogenic mechanism such as a dysregulation of some neurotransmitter system might underlie not only headache but also other coexistent disorders; findings highlight the role of serotonin pathways.

Clinical pharmacodynamics of acetyl-L-carnitine in patients with Parkinson's disease.

Two groups of 10 patients with Parkinson's disease received doses of either 1g acetyl-L-carnitine (ALC) per day for seven days or 2g. The effects of this drug on intermittent luminous stimulation and on nocturnal sleep patterns were studied. In both cases with either dose of ALC the effect was an improvement of the H response, sleep stages and spindling activity. However a further study of the complexity of action of acetyl-L-carnitine is necessary.

Somatosensory evoked potentials in migraine.

Twenty-six patients suffering from migraine with aura and without aura were examined using somatosensory evoked potentials (SEPs) during the intercritical phase. The mean amplitude of the prerolandic component was significantly reduced in migraine patients with and without aura on the right hemisphere; the ratio between the parietal N20/P25 and the prerolandic P22/N30 was significantly enhanced in migraine groups over the left and the right hemisphere. A significant interside asymmetry of the N30 amplitude was observed in the migraine with aura group in comparison with control subjects. The occurrence of SEP abnormalities was not correlated with the age of the patients, with illness duration or with the frequency of migraine attacks. SEP abnormalities observed in migraine with and without aura may have an underlying primary neural disorder probably based on a chronic dopaminergic dysfunction.

Quality of life in shift work syndrome.

Air Force radar controllers represent an excellent example of night shift workers, as they are obliged to demonstrate perfect alertness during working hours. We set out: a) to assess the quality of life in these shift workers; b) to identify those with shift work syndrome and c) to evaluate the possible effects of triazolam both on their quality of life and sleep. The results reveal an impairment of the quality of life in shift workers, independently of the presence of a circadian rhythm sleep disorder. Quality of life was more severely impaired in subjects with circadian rhythm sleep disorder. Hypnotic therapy brought about an improvement both in the sleep disorder and in the quality of life of subjects affected by shift work syndrome. Selective alertness tests failed to demonstrate any "sedative carry-over" in the treated patients.

Efficacy of dosing and re-dosing of two oral fixed combinations of indomethacin, prochlorperazine and caffeine compared with oral sumatriptan in the acute treatment of multiple migraine attacks: a double-blind, double-dummy, randomised, parallel group, multicentre study.

AIMS AND METHODS: In this double-blind, double-dummy, randomised, parallel group, multicentre study, the efficacy of dosing and re-dosing of a fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) was compared with encapsulated sumatriptan in the acute treatment of two migraine attacks. Additionally, in the group taking Indoprocaf, two different oral formulations were tested: effervescent tablets and encapsulated coated tablets. RESULTS: Of 297 patients randomised (150 assigned to Indoprocaf and 147 to sumatriptan), 281 were included in the intention-to-treat efficacy analysis. The initial dosing of Indoprocaf and sumatriptan was similarly effective with pain-free rates higher than 30% (95% CI of odds-ratio: 0.57-1.28) and headache relief rates of about 60% (95% CI of odds-ratio: 0.82-1.84) with both the drugs. The efficacy of re-dosing of Indoprocaf as rescue medication was more effective than that of sumatriptan with pain-free values of 47% vs. 27% in the total attacks with a statistically significant difference in the first migraine attack in favour of Indoprocaf. The efficacy of re-dosing to treat a recurrence/relapse was very high without differences between the drugs (pain-free: 60% with Indoprocaf and 50% with sumatriptan in the total attacks). Indoprocaf and sumatriptan were well-tolerated. CONCLUSION: The study demonstrated that the efficacy of the initial dosing of Indoprocaf was not higher than that of sumatriptan, but that the strategy to use the lowest effective dose as soon as the headache occurred, followed by a second dose if the headache has not relieved or to treat a relapse, was very effective, especially with Indoprocaf.

Headache and anxiety-depressive disorder comorbidity: the HADAS study.

Psychiatric comorbidity (prevalence and types) was tested in a naturalistic sample of adult patients with pure migraine without aura, and in two control groups of patients, one experiencing pure tension-type headache and the other combined migraine and tension-type headaches. The study population included 374 patients (158, 110 and 106) from nine Italian secondary and tertiary centres. Psychiatric comorbidity was recorded through structured interview and also screened with the Mini International Neuropsychiatry Interview (MINI). Only anxiety and depression were investigated. Psychiatric disorders were reported by 49 patients (14.6%; 10.9% of patients with migraine, 12.8% of those with tension-type headache and 21.4% of those with combined migraine and tension-type headaches). The MINI interview detected a depressive episode in 59.9% of patients with migraine, 68.3% of patients with tension-type headache and 69.6% of patients with combined migraine and tension-type headaches. Depression subtypes were significantly different across groups (p=0.03). Anxiety (mostly generalised) was reported by 18.4% of patients with migraine, 19.3% of patients with tension-type headache, and 18.4% of patients with combined migraine and tension-type headaches. The values for panic disturbance were 12.7, 5.5 and 14.2, and those for obsessive-compulsive disorders were 2.3, 1.1 and 9.4% (p=0.009). Based on these results, psychopathology of primary headache can be a reflection of the burden of the disease rather than a hallmark of a specific headache category.

Effects of amitriptyline and intra-oral device appliance on clinical and laser-evoked potentials features in chronic tension-type headache.

In the present study, we examined clinical and laser-evoked potentials (LEP) features in two groups of chronic tension-type headache (CTTH) patients treated with two different approaches: intra-oral appliance of prosthesis, aiming to reduce muscular tenderness, and 10 mg daily amitriptyline. Eighteen patients suffering from CTTH (IHS, 2004) participated in the study. We performed a basal evaluation of clinical features and LEPs in all patients (T0) vs. 12 age- and sex-matched controls; successively, patients were randomly assigned to a two-month treatment by amitriptyline or intra-oral device appliance. The later LEPs, especially the P2 component, were significantly increased in amplitude in the CTTH group. Both the intra-oral prosthesis and amitriptyline significantly reduced headache frequency. Total Tenderness Score was significantly reduced in the group treated by the prosthesis. The amplitude of P2 response elicited by stimulation of pericranial zones showed a reduction after amitriptyline treatment. The results of this study may confirm that pericranial tenderness is primarily a phenomenon initiating a self-perpetuating circuit, favoured by central sensitisation at the level of the cortical nociceptive areas devoted to the attentive and emotive compounds of pain. Both the interventions at the peripheral and central levels may interrupt this reverberating circuit, improving the outcome of headache.

Workplace disability in migraine: an Italian experience.

Workplace disability due to migraine has not been extensively researched in non-English speaking countries. We assessed the repercussions of headache, and particularly of migraine, on work in a sample of employees from an Italian company (Bulgari). Information was obtained through a self-answering questionnaire in "all headaches" sufferers, and through direct interview in migraine sufferers (diagnosis according to IHS criteria). Headache frequency, pain intensity and headache-related disability were higher in migraineurs than in "all headaches" sufferers. About a quarter of migraineurs missed at least one day in the three months prior to the interview due to headache, and around 10% lost two or more days over the same period. Moore than 50% of migraineurs reported 1-7 days per month at work with headache, with reduction in productivity level by 50% or more in 15% of respondents. Our data confirmed that headaches, and particularly migraine, cause a considerable reduction in workplace productivity. Workplace interventions to effectively manage migraine are needed.

Topographic analysis of steady-state visual evoked potentials (SVEPs) in the medium frequency range in migraine with and without aura.

Topographic analysis of SVEPs in the medium frequencies range was performed in 30 migraineurs without aura, 20 migraineurs with aura and in 20 control subjects. The mean absolute power values of the fundamental component F1, the subharmonic F1/2 and the first harmonic F2, corrected by logarithmic transformation, were computed in each group and then compared using Student's t-test. The interhemispheric coherence of the F1 component was also evaluated. The 18, 21, and 27 Hz F1 components were increased in both migraineurs with and without aura, particularly in the temporo-parietal regions. The 24 Hz F1 component was augmented only in migraineurs without aura in the parieto-occipital regions in comparison with migraineurs with aura and controls. Migraine with aura patients had a reduced interhemispheric coherence mostly of 12 Hz and 15 Hz F1 components in frontal and temporo-parietal regions. Results of the study confirm abnormalities of SVEPs in migraineurs with and without aura. These consist of widespread increases of F1 components in the medium frequency range over the temporo-parietal regions.

EEG features in juvenile migraine: topographic analysis of spontaneous and visual evoked brain electrical activity: a comparison with adult migraine.

Topographic analysis of spontaneous and steady-state visual evoked brain electrical activity was carried out between attacks in 82 migraine patients (40 youths and 42 adults). In adult migraine with aura a significant increase of delta rhythm percentage power was observed compared with migraine without aura and age-matched controls. Children suffering from migraine both with aura and without aura had an increased theta rhythm compared to normal controls. The presence of alpha interhemispheric asymmetry discriminated between migraine with aura and without aura, just as in adults. An increased amplitude of the SVEP F1 component with a tendency to the spread of visual reactivity was observed in juvenile migraine with and without aura; this pattern was not dissimilar from the one previously observed in adult migraine with and without aura. Abnormal photic driving in migraine is independent of age and type of migraine.

Psychologic factors in chronic headache: assessment by means of the SCL-90-R inventory.

A survey of the psychologic profile of 540 chronic headache cases, including migraine, tension, and mixed headache, has been carried out with the symptom check list (SCL)-90-R inventory. The results obtained were viewed in relation to sex, age, illness onset, and illness duration. Females showed a positive correlation of somatization with present age and with age at onset of illness and a negative correlation of interpersonal sensitivity, hostility, and paranoid ideation with present age and age at onset of illness. Men showed a negative correlation of obsessive-compulsive and paranoid scores with age and a positive correlation between onset of illness and somatization. Data were also analyzed by cluster analysis, which showed underpopulation with peculiar patterns of symptom profile. A prospective, long-term epidemiologic study could provide more conclusive results.

[Sleep in chronic chorea patients after therapy with sodium valproate]. / Il sonno di coreici cronici dopo terapia con valproato di sodio.

In previous researches spontaneous nocturnal sleep in chronic chorea showed short total sleep time, prolonged sleep latency, several awakenings, reduction of REM sleep time, decrease in slow waves sleep, strong increase in sleep spindles. Some of these alterations improved after therapy with lithium, haloperidol and lithium, pimozide. Since the concentration of GABA has been found to be reduced in patients with Huntington's chorea, we studied the effect of sodium valproate, a drug that enhances GABA inhibition in cerebral cortex, on nocturnal sleep of six patients with chronic chorea, aged 35 to 60 years (mean 47,3). Nocturnal polygraphic records (EEG, EOG, EMG of chin muscles) were carried out after two consecutive adjustative nights, both before therapy and after sixty days of treatment with sodium valproate (800-2000 mg four times a day, orally). Moreover, chorea, finger dexterity and gait were each rated once a week by three members of the research team and by one independent observer, using a five points rating scale from 0 (normal) to 4 (very severely abnormal). Before therapy the sleep parameters were in accordance with our previous results in chronic choreic patients. After two months therapy we observed a statistically significant (P less than 0.05) reduction of awakenings and of wake time. Sodium valproate produced no objective change in any of the parameters of motor function studied. If singularly examined, however, a reduction of chorea was obtained only in a patient, whose favourable response to therapy was also demonstrated by the normalization of other sleep parameters. These data stress the importance of sleep study in extrapyramidal disorders and suggest a different involvement of GABA-mediated transmission in various patients with chronic chorea.

Homovanillic acid and 5-hydroxyindoleacetic acid in lumbar cerebrospinal fluid after total and REM sleep deprivation in humans.

Lumbar CSF HVA and 5-HIAA levels were assayed in 3 groups each of 10 subjects, which were respectively deprived of sleep for 30 h, deprived of REM sleep and disturbed with several awakenings during SW sleep for two consecutive nights. HVA levels after total sleep (39 +/- 20 ng/ml) or REM (35 +/- 11 ng/ml) deprivation as well as after SW sleep awakenings (32 +/- 26 ng/ml) were not different from controls (42 +/- 14 ng/ml). 5-HIAA levels after REM deprivation (32 +/- 15 ng/ml) appeared increased when compared with controls (21 +/- 7 ng/ml), total sleep-deprived subjects (21 +/- 10 ng/ml) or subjects with SW sleep awakenings (27 +/- 13 ng/ml). Possible increase in 5-HT turnover after REM deprivation and possible 5-HT role in REM sleep regulation in humans are discussed.

The Migraine Disability Assessment (MIDAS) questionnaire: translation and reliability of the Italian version.

We have developed and tested an Italian version of the Migraine Disability Assessment (MIDAS) questionnaire, an established instrument for assessing headache-related disability. A multistep process was used to translate and adapt the questionnaire into Italian, which was then tested on 109 Italian migraine without aura patients, 86 (78.9%) of whom completed the form a second time 21 days later. Overall MIDAS score had good test-retest reliability (Spearman's correlation 0.77), closely similar to that found in English-speaking migraineurs, and individual responses were also satisfactorily reliable. Internal consistency was good (Cronbach's alpha 0.7). These findings support the use of the MIDAS questionnaire as a clinical and research tool with Italian patients.