Systemic features of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations: a monogenic small vessel disease.

BACKGROUND: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a small vessel disease caused by C-terminal truncating TREX1 mutations. The disease is typically characterized by vascular retinopathy and focal and global brain dysfunction. Systemic manifestations have also been reported but not yet systematically investigated. METHODS: In a cross-sectional study, we compared the clinical characteristics of 33 TREX1 mutation carriers (MC+) from three Dutch RVCL-S families with those of 37 family members without TREX1 mutation (MC-). All participants were investigated using personal interviews, questionnaires, physical, neurological and neuropsychological examinations, blood and urine tests, and brain MRI. RESULTS: In MC+, vascular retinopathy and Raynaud's phenomenon were the earliest symptoms presenting from age 20 onwards. Kidney disease became manifest from around age 35, followed by liver disease, anaemia, markers of inflammation and, in some MC+, migraine and subclinical hypothyroidism, all from age 40. Cerebral deficits usually started mildly around age 50, associated with white matter and intracerebral mass lesions, and becoming severe around age 60-65. CONCLUSIONS: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations is a rare, but likely underdiagnosed, systemic small vessel disease typically starting with vascular retinopathy, followed by multiple internal organ disease, progressive brain dysfunction, and ultimately premature death.

Alcoholic beverages as trigger factor and the effect on alcohol consumption behavior in patients with migraine.

BACKGROUND AND PURPOSE: Alcoholic beverages are frequently reported migraine triggers. We aimed to assess self-reported alcohol consumption as a migraine attack trigger and to investigate the effect on alcohol consumption behavior in a large migraine cohort. METHODS: We conducted a cross-sectional, web-based, questionnaire study among 2197 patients with migraine from the well-defined Leiden University MIgraine Neuro-Analysis (LUMINA) study population. We assessed alcoholic beverage consumption and self-reported trigger potential, reasons behind alcohol abstinence and time between alcohol consumption and migraine attack onset. RESULTS: Alcoholic beverages were reported as a trigger by 35.6% of participants with migraine. In addition, over 25% of patients with migraine who had stopped consuming or never consumed alcoholic beverages did so because of presumed trigger effects. Wine, especially red wine (77.8% of participants), was recognized as the most common trigger among the alcoholic beverages. However, red wine consistently led to an attack in only 8.8% of participants. Time of onset was rapid (<3 h) in one-third of patients and almost 90% had an onset <10 h independent of beverage type. CONCLUSIONS: Alcoholic beverages, especially red wine, are recognized as a migraine trigger factor by patients with migraine and have a substantial effect on alcohol consumption behavior. Rapid onset of provoked migraine attacks in contrast to what is known about hangover headache might point to a different mechanism. The low consistency of provocation suggests that alcoholic beverages acting as a singular trigger is insufficient and may depend on a fluctuating trigger threshold.

Chronotypes and circadian timing in migraine.

Background It has been suggested that migraine attacks strike according to circadian patterns and that this might be related to individual chronotype. Here we evaluated and correlated individual chronotypes, stability of the circadian rhythm, and circadian attack timing in a large and well-characterised migraine population. Methods In 2875 migraine patients and 200 non-headache controls we assessed differences in: (i) distribution of chronotypes (Münich Chronotype Questionnaire); (ii) the circadian rhythm's amplitude and stability (Circadian Type Inventory); and (iii) circadian timing of migraine attacks. Data were analysed using multinomial and linear regression models adjusted for age, gender, sleep quality and depression. Results Migraineurs more often showed an early chronotype compared with controls (48.9% versus 38.6%; adjusted odds ratio [OR] = 2.42; 95% confidence interval [CI] = 1.58-3.69; p < 0.001); as well as a late chronotypes (37.7% versus 38.1%; adjusted OR = 1.69; 95% CI = 1.10-2.61; p = 0.016). Migraineurs, particularly those with high attack frequency, were more tired after changes in circadian rhythm (i.e. more languid; p < 0.001) and coped less well with being active at unusual hours (i.e. more rigid; p < 0.001) than controls. Of 2389 migraineurs, 961 (40.2%) reported early morning attack onset. Conclusion Migraine patients are less prone to be of a normal chronotype than controls. They are more languid and more rigid when changes in circadian rhythm occur. Most migraine attacks begin in the early morning. These data suggest that chronobiological mechanisms play a role in migraine pathophysiology.

Recurrent coma and fever in familial hemiplegic migraine type 2. A prospective 15-year follow-up of a large family with a novel ATP1A2 mutation.

Background Familial hemiplegic migraine (FHM) is a rare monogenic migraine subtype characterised by attacks associated with transient motor weakness. Clinical information is mainly based on reports of small families with only short follow-up. Here, we document a prospective 15-year follow-up of an extended family with FHM type 2. Patients and methods After diagnosing FHM in a patient with severe attacks associated with coma and fever, we identified eight more family members with FHM and one with possible FHM. All family members were prospectively followed for 15 years. In total 13 clinically affected and 21 clinically non-affected family members were genetically tested and repeatedly investigated. Results A novel p.Arg348Pro ATP1A2 mutation was found in 14 family members: 12 with clinical FHM, one with psychomotor retardation and possible FHM, and one without FHM features. In 9/12 (75%) family members with genetically confirmed FHM, attacks were severe, long-lasting, and often associated with impaired consciousness and fever. Such attacks were frequently misdiagnosed and treated as viral meningitis or stroke. Epilepsy was reported in three family members with FHM and in the one with psychomotor retardation and possible FHM. Ataxia was not observed. Conclusion FHM should be considered in patients with recurrent coma and fever.

Cardiac monitoring of high-dose verapamil in cluster headache: An international Delphi study.

BACKGROUND: In many patients, high-dose verapamil (HDV) is the only effective prophylactic treatment for cluster headache. Although cardiac adverse events and EKG abnormalities are relatively common, evidence-based guidelines for screening and monitoring patients on HDV are lacking. GOAL AND METHODS: Using the Delphi approach, we interviewed 22 international clinical experts in cardiac rhythm disorders to formulate EKG guidelines for the pretreatment screening and monitoring of cluster headache patients using HDV. RESULTS: The panel agreed only on performing pretreatment EKG to screen for pre-existing cardiac arrhythmia. Pretreatment EKG was deemed not necessary by most panel members for patients who did not have cardiac adverse events during a previous period of cluster headache attacks treated with HDV. Half the panel advised Holter EKG for patients on verapamil ≥ 480 mg/day. The highest recommended daily doses varied between 240 and 960 mg. Contraindications for use of verapamil largely followed FDA guidelines. DISCUSSION: Experts in cardiac rhythm disorders agreed on pretreatment EKG monitoring, but no consensus was reached on EKG monitoring during HDV treatment and around dose adjustments.

Evaluation of the new ICHD-III beta cluster headache criteria.

AIM: In the revised criteria of the International Classification of Headache Disorders (ICHD-III beta) the following items are added to the diagnostic criteria of cluster headache: ipsilateral sensation of fullness in the ear and ipsilateral forehead/facial flushing. We evaluated the possible additional value of these symptoms for diagnosing cluster headache. METHODS: In this cross-sectional cohort study of (potential) cluster headache patients we investigated these additional symptoms using a Web-based questionnaire. Patients not fulfilling the ICHD-II criteria for cluster headache but fulfilling the ICHD-III beta criteria were interviewed. RESULTS: Response rate was 916/1138 (80.5%). Of all 573 patients with cluster headache according to ICHD-II criteria, 192 (33.5%) reported ipsilateral ear fullness and 113 (19.7%) facial flushing during attacks. There was no difference in reporting ipsilateral ear fullness and facial flushing between patients who received a diagnosis of cluster headache and patients who did not. None of the patients who did not fulfill all ICHD-II criteria could be categorized as cluster headache according to the ICHD-III beta criteria. CONCLUSION: The results of this study do not support the addition of ear fullness and facial flushing to the new ICHD-III beta criteria.

Detoxification in medication-overuse headache, a retrospective controlled follow-up study: Does care by a headache nurse lead to cure?

AIM: J.A.P. and M.A.L. contributed equally to this manuscript.The aim of this article is to determine whether support by a headache nurse in the treatment of medication-overuse headache (MOH) increases successful withdrawal, and to study determinants of response to withdrawal therapy. METHODS: A retrospective, controlled follow-up study was performed with 416 MOH patients. All patients were treated with outpatient withdrawal therapy, with two treatment arms: with or without the support of a specialised headache nurse. The outcome measures were: i) successful withdrawal, defined as discontinuation of all headache medication according to the study protocol; and ii) the responder rate, defined as the percentage of patients with ≥ 50% reduction in headache days after successful withdrawal and iii) relative reduction in headache days after successful withdrawal. RESULTS: Successful withdrawal percentages were significantly higher in the group supported by the headache nurse than in the group without support (73.1% vs. 60.7%; p = 0.008), which was confirmed in multivariate analysis (OR 1.73, 95% CI 1.11-2.71, p = 0.016). Support by a headache nurse was not associated with response. The underlying primary headache diagnosis, determined after withdrawal, was significantly correlated with response. CONCLUSION: The support by a headache nurse results in an increased adherence to detoxification.

Restless legs syndrome in migraine patients: prevalence and severity.

BACKGROUND AND PURPOSE: Our aim was to study not only the prevalence but more importantly the severity and the correlation between sleep quality and restless legs syndrome (RLS) in a large population of well-defined migraine patients as poor sleep presumably triggers migraine attacks. METHODS: In a large cross-sectional and observational study, data on migraine and RLS were collected from 2385 migraine patients (according to the International Classification of Headache Disorders ICHD-IIIb) and 332 non-headache controls. RLS severity (International RLS Study Group severity scale) and sleep quality (Pittsburgh Sleep Quality Index) were assessed. Risk factors for RLS and RLS severity were calculated using multivariable-adjusted regression models. RESULTS: Restless legs syndrome prevalence in migraine was higher than in controls (16.9% vs. 8.7%; multivariable-adjusted odds ratio 1.83; 95% confidence interval 1.18-2.86; P = 0.008) and more severe (adjusted severity score 14.5 ± 0.5 vs. 12.0 ± 1.1; P = 0.036). Poor sleepers were overrepresented amongst migraineurs (50.1% vs. 25.6%; P < 0.001). Poorer sleep quality was independently associated with RLS occurrence (odds ratio 1.08; P < 0.001) and RLS severity (P < 0.001) in migraine patients. CONCLUSION: Restless legs syndrome is not only twice as prevalent but also more severe in migraine patients, and associated with decreased sleep quality.

Space headache on Earth: head-down-tilted bed rest studies simulating outer-space microgravity.

BACKGROUND: Headache is a common symptom during space travel, both isolated and as part of space motion syndrome. Head-down-tilted bed rest (HDTBR) studies are used to simulate outer space microgravity on Earth, and allow countermeasure interventions such as artificial gravity and training protocols, aimed at restoring microgravity-induced physiological changes. OBJECTIVES: The objectives of this article are to assess headache incidence and characteristics during HDTBR, and to evaluate the effects of countermeasures. METHODS: In a randomized cross-over design by the European Space Agency (ESA), 22 healthy male subjects, without primary headache history, underwent three periods of -6-degree HDTBR. In two of these episodes countermeasure protocols were added, with either centrifugation or aerobic exercise training protocols. Headache occurrence and characteristics were daily assessed using a specially designed questionnaire. RESULTS: In total 14/22 (63.6%) subjects reported a headache during ≥1 of the three HDTBR periods, in 12/14 (85.7%) non-specific, and two of 14 (14.4%) migraine. The occurrence of headache did not differ between HDTBR with and without countermeasures: 12/22 (54.5%) subjects vs. eight of 22 (36.4%) subjects; p = 0.20; 13/109 (11.9%) headache days vs. 36/213 (16.9%) headache days; p = 0.24). During countermeasures headaches were, however, more often mild (p = 0.03) and had fewer associated symptoms (p = 0.008). CONCLUSIONS: Simulated microgravity during HDTBR induces headache episodes, mostly on the first day. Countermeasures are useful in reducing headache severity and associated symptoms. Reversible, microgravity-induced cephalic fluid shift may cause headache, also on Earth. HDTBR can be used to study space headache on Earth.

A human capsaicin model to quantitatively assess salivary CGRP secretion.

BACKGROUND: Capsaicin induces the release of calcitonin gene-related peptide (CGRP) via the transient receptor potential channel V1 (TRPV1). The CGRP response after capsaicin application on the tongue might reflect the "activation state" of the trigeminal nerve, since trigeminal CGRP-containing vesicles are depleted on capsaicin application. We tested (i) the quantitative CGRP response after oral capsaicin application; (ii) the optimal concentration of red chili homogenate; and (iii) the day-to-day variability in this response. METHODS: Saliva was collected for two consecutive days after oral application of eight capsaicin dilutions (red chili homogenates) of increasing concentrations in 13 healthy individuals. Effects of homogenate concentration were assessed. Consecutively, saliva was sampled after application of vehicle and undiluted homogenates. RESULTS: CGRP secretion (pg/ml) increased dose-dependently with homogenate concentration (p < 0.001). CGRP levels were highest after application of nondiluted homogenate (vs. baseline: 13.3 (5.0) vs. 9.7 (2.9); p = 0.003, as was total CGRP secretion in five minutes (pg) with undiluted (vs. baseline): 89.2 (44.1) vs. 14.1 (2.8); p < 0.001. The dose-dependent response in CGRP was not affected by day (p = 0.14) or day*concentration (p = 0.60). Increase in CGRP (undiluted - baseline; pg/ml) did not differ between measurements on dose-finding (p = 0.67) and follow-up days (p = 0.46). CONCLUSION: Oral application of red chili homogenate is well tolerated and causes a dose-dependent CGRP release in saliva, without day-to-day effects in this response. This model could be used to noninvasively study the activation state of the trigeminal nerve innervating salivary glands.

Candidate-gene association study searching for genetic factors involved in migraine chronification.

INTRODUCTION: Chronic migraine (CM) is at the severe end of the clinical migraine spectrum, but its genetic background is unknown. Our study searched for evidence that genetic factors are involved in the chronification process. METHODS: We initially selected 144 single-nucleotide polymorphisms (SNPs) from 48 candidate genes, which we tested for association in two stages: The first stage encompassed 262 CM patients, the second investigated 226 patients with high-frequency migraine (HFM). Subsequently, SNPs with p values < 0.05 were forwarded to the replication stage containing 531 patients with CM or HFM. RESULTS: Eight SNPs were significantly associated with CM and HFM in the two-stage phase. None survived replication in the third stage. DISCUSSION: We present the first comprehensive genetic association study for migraine chronification. There were no significant findings. Future studies may benefit from larger, genome-wide data sets or should use other genetic approaches to identify genetic factors involved in migraine chronification.

The comorbid relationship between migraine and epilepsy: a systematic review and meta-analysis.

A number of studies have suggested a pathophysiologic link between migraine and epilepsy. Our aim was to examine the relative lifetime prevalence of migraine in people with epilepsy (PWE) as well that of epilepsy in migraineurs. We carried out a systematic review, searching five electronic databases, specified bibliographies and conference abstracts in order to identify population-based studies that measured the lifetime co-prevalence of migraine and epilepsy. Two reviewers independently screened all titles and abstracts, carried out a risk of bias assessment and extracted the data. Meta-analyses were carried out using random effects models. Of the 3640 abstracts and titles screened, we identified 10 eligible studies encompassing a total of 1,548,967 subjects. Few of the studies used validated case ascertainment tools and there were inconsistent attempts to control for confounding. There was an overall 52% increase in the prevalence of migraine among PWE versus those without epilepsy [PR: 1.52 (95% CI: 1.29, 1.79)]. There was an overall 79% increase in the prevalence of epilepsy among migraineurs versus those without migraine [PR: 1.79 (95% CI: 1.43, 2.25)]. Subgroup analyses revealed that the method of ascertaining the epilepsy or migraine status of subjects was an important source of inter-study heterogeneity. Additional high quality primary studies are required, ones that use validated and accurate methods of case ascertainment as well as control for potential confounders.

Acute predictors for mortality after severe TBI in Spain: Gender differences and clinical data.

OBJECTIVE: The main objective of this study is to determine whether gender affects global mortality and functional outcome after severe traumatic brain injury (TBI). METHODS: This retrospective cohort study included 629 patients with severe TBI (14.9% female) admitted to the ICU of a university hospital. Patients were split into gender groups to study potential differences in global mortality and functional outcome at ICU discharge and 6 months post-trauma using the GOS. The following variables were analysed: age, intracranial injury, injury mechanism, injury severity, factors contributing to secondary brain injury, monitoring level, treatment, complications, length of stay in the ICU and cause of death. RESULTS: No differences were found between gender groups in neuromonitoring level or surgical procedures. Women had higher APACHE II scores, a higher incidence of pre-hospital hypotension, anaemia and transfusion and higher mortality rates in the ICU (OR = 1.74; 95% CI = 1.09-2.77) and 6 months post-trauma (OR = 1.65; 95% CI = 1.02-2.67). There were no significant differences in functional outcome at ICU discharge or 6 months post-injury. The multivariate analysis did not show gender as an independent predictive factor in mortality after severe TBI. CONCLUSION: In this study, gender was not found to be an independent predictor for poorer outcome after severe TBI.

European Headache Federation consensus on technical investigation for primary headache disorders.

The diagnosis of primary headache disorders is clinical and based on the diagnostic criteria of the International Headache Society (ICHD-3-beta). However several brain conditions may mimic primary headache disorders and laboratory investigation may be needed. This necessity occurs when the treating physician doubts for the primary origin of headache. Features that represent a warning for a possible underlying disorder causing the headache are new onset headache, change in previously stable headache pattern, headache that abruptly reaches the peak level, headache that changes with posture, headache awakening the patient, or precipitated by physical activity or Valsalva manoeuvre, first onset of headache ≥50 years of age, neurological symptoms or signs, trauma, fever, seizures, history of malignancy, history of HIV or active infections, and prior history of stroke or intracranial bleeding. All national headache societies and the European Headache Alliance invited to review and comment the consensus before the final draft. The consensus recommends brain MRI for the case of migraine with aura that persists on one side or in brainstem aura. Persistent aura without infarction and migrainous infarction require brain MRI, MRA and MRV. Brain MRI with detailed study of the pituitary area and cavernous sinus, is recommended for all TACs. For primary cough headache, exercise headache, headache associated with sexual activity, thunderclap headache and hypnic headache apart from brain MRI additional tests may be required. Because there is little and no good evidence the committee constructed a consensus based on the opinion of experts, and should be treated as imperfect.

Allodynia is associated with a higher prevalence of depression in migraine patients.

INTRODUCTION: There is a strong association between migraine and depression. The aim of this study is to identify migraine-specific factors involved in this association. METHODS: We conducted a cross-sectional study in a large, well-defined cohort of migraine patients (n=2533). We assessed lifetime depression using validated questionnaires, and diagnosed migraine based on the International Classification of Headache Disorders III-beta criteria. Multivariate regression analyses were conducted. RESULTS: Of the 2533 migraineurs that were eligible, 1137 (45%) suffered from lifetime depression. The following independent factors were associated with an increased depression prevalence: i) migraine-specific risk factors: high migraine attack frequency and the presence of allodynia, ii) general factors: being a bad sleeper, female gender, high BMI, being single, smoking, and a low alcohol consumption. CONCLUSION: This study identified allodynia, in addition to high migraine attack frequency, as a new migraine-specific factor associated with depression.

Biochemical changes in the brain of hemiplegic migraine patients measured with 7 tesla 1H-MRS.

AIM: The aim of this study was to assess biochemical changes in the brain of patients with hemiplegic migraine in between attacks. METHODS: Eighteen patients with hemiplegic migraine (M:F, 7:11; age 38 ± 14 years) of whom eight had a known familial hemiplegic migraine (FHM) mutation (five in the CACNA1A gene (FHM1), three in the ATP1A2 gene (FHM2)) and 19 age- and sex-matched healthy controls (M:F, 7:12; mean age 38 ± 12 years) were studied. We used single-voxel 7 tesla (1)H-MRS (STEAM, TR/TM/TE = 2000/19/21 ms) to investigate four brain regions in between attacks: cerebellum, hypothalamus, occipital lobe, and pons. RESULTS: Patients with hemiplegic migraine showed a significantly lower total N-acetylaspartate/total creatine ratio (tNAA/tCre) in the cerebellum (median 0.73, range 0.59-1.03) than healthy controls (median 0.79, range (0.67-0.95); p = 0.02). In FHM1 patients with a CACNA1A mutation, the tNAA/tCre was lowest. DISCUSSION: We found a decreased cerebellar tNAA/tCre ratio that might serve as an early biomarker for neuronal dysfunction and/or loss. This is the first high-spectral resolution 7 tesla (1)H-MRS study of interictal biochemical brain changes in hemiplegic migraine patients.

Preventive treatment for migraine in primary care, a population-based study in the Netherlands.

BACKGROUND: Preventive treatment of migraine contributes to reducing the impact of migraine but its extent of use in routine care is unknown. OBJECTIVE: The objective of this article is to assess current use, previous use, duration and course of preventive treatment of migraine in Dutch general practice. METHODS: We conducted a retrospective cohort study, for the period between 1997 and 2007, in the Interdisciplinary Processing of Clinical Information (IPCI) database, a GP research database in the Netherlands (source population of more than half a million subjects). All prevalent and incident migraine patients ( N = 7367) were included. RESULTS: About 13% of all migraine patients currently use preventive therapy and almost half of migraine patients have prior use. Of those starting with preventive treatment, 56% (95% CI: 54.3-64.7) still used it after nine months. There was a long delay between migraine diagnosis and preventive treatment start. Forty-four percent (95% CI 43.0-45.7) started preventive therapy in the study period. CONCLUSION: This large primary-care database study shows that a limited number of patients are current users of preventive treatment, but many patients have prior use. After diagnosis there is often an extended time before preventive treatment is applied. Also there is often only one attempt. The continuation in time seems appropriate. Preventive therapy in migraine still deserves focus.

Aortic root pathology in Marfan syndrome increases the risk of migraine with aura.

AIM: To assess the lifetime prevalence of migraine in patients with Marfan syndrome (MFS) and to investigate a history of aortic root replacement (AR) as a possible risk factor. METHODS: In a multicentre study 123 MFS patients (n = 52 with AR, n = 71 without AR), 82 age- and sex-matched controls and 51 patients with AR but without MFS, were interviewed using a semi-structured headache questionnaire. A multinomial logistic regression model was used to investigate risk factors for migraine with and without aura, adjusting for age and gender. RESULTS: Lifetime migraine prevalence was increased in female MFS patients (51%) compared to healthy female controls (29%), p = 0.017. In males lifetime migraine prevalence among MFS patients was only numerically increased. Lifetime prevalence of migraine with aura was increased among MFS patients compared to healthy controls both in males (19% vs. 3%, p = 0.048) and females (30% vs. 14%, p = 0.049). A history of AR, independently from MFS, gender and age, increased the lifetime prevalence of migraine with aura (OR 3.1 [1.2-8.0]). In all but one patient migraine started before the AR. CONCLUSIONS: The lifetime prevalence of migraine with aura, but not migraine without aura, is increased in patients with MFS. This association is driven by a history of AR. The replacement procedure itself is unlikely to be causally associated with migraine as in nearly all subjects, migraine started before the procedure. However this study adds to the evidence that underlying vessel wall pathology may be involved in migraine with aura.

[Emergency transcranial doppler ultrasound: predictive value for the development of symptomatic vasospasm in spontaneous subarachnoid hemorrhage in patients in good neurological condition]. / Ultrasonografía doppler transcraneal urgente: utilidad predictiva del vasoespasmo sintomático en la hemorragia subaracnoidea espontánea en pacientes con buena situación neurológica.

PURPOSE: To examine the predictive value of an early transcranial Doppler ultrasound (TCD) study performed in the emergency department in patients with spontaneous subarachoniod hemorrhage (SAH) in good neurological condition, in order to know which patients are at high risk of developing delayed cerebral ischemia (DCI). DESIGN: A descriptive observational study was carried out involving a period of 3 years. SETTING: Critical Care and Emergency Department. PATIENTS: The study consecutively included patients with SAH of grade I-III on the Hunt and Hess scale. VARIABLES OF INTEREST: DCI (decrease of 2 points in GCS or focal deficit), Mean Velocity (MV) of middle cerebral arteries (MCA), Lindegaard Index (IL). Sonographic vasospasm pattern (SVP) was considered if MCA-MV>120cm/sc and IL>3. RESULTS: The mean age of the 122 patients was 54.1±13.7 years; 57.3% were women. SVP was detected in 24 patients (19.7%), although high velocities patterns (HVP) were present in 38 patients (31.1%). DCI developed in 21 patients (MV183+/-49cm/sc), all with previous SVP. In this group MV increased 22+/-5cm/sc/day during the first 3 days. The group without HVP (84 patients/MV of 67+/-16.6cm/sc), compared with DCI group, showed differences in highest MV (p<0.001), and also ΔMV/day (8.30+/-4,5cm/sc Vs 22+/-5cm/sc) during the first 3 days (p=0.009). In our series, ROC analysis selected the best cut-off value for ΔMV/day as 21cm/sc (p<0.001). CONCLUSION: During the first 3 days, an increase of 21cm/s/24h in MCA-MV was associated with the development of symptomatic vasospasm. TCD is a useful tool for the early detection of patients at risk of DCI after SAH.

Triptan overuse in the Dutch general population: a nationwide pharmaco-epidemiology database analysis in 6.7 million people.

INTRODUCTION: A population-based observational study was used to assess the prevalence, demographics, risk factors, and costs of triptan overuse, defined as more than 30 (International Headache Society criteria) or 54 (stringent criteria) defined daily doses per 3 months. METHODS: Analysis of the Dutch Health Care Insurance Board Database for 2005, which included prescriptions for 6.7 million people (46% of the total Dutch population). RESULTS: Triptans were used by 85,172 (1.3%) people; of these, 8,844 (10.4%; 95% CI 10.2-10.6) were overusers by International Headache Society and 2,787 (3.3%; 95% CI 3.2-3.4) were overusers by stringent criteria. The triptan-specific odds ratios for the rate of International Headache Society overuse compared with sumatriptan were: 0.26 (95% CI 0.19-0.36) for frovatriptan; 0.34 (95% CI 0.32-0.37) for rizatriptan; 0.76 95% CI 0.68-0.85) for naratriptan; 0.86 (95% CI 0.72-1.02) for eletriptan; 0.97 (95% CI 0.88-1.06) for zolmitriptan; and 1.49 (95% CI 1.31-1.72) for almotriptan. Costs for overuse were 29.7 million euros; for the International Headache Society criteria this was 46% of total costs and for stringent criteria it was 23%. DISCUSSION: In the Dutch general population, 1.3% used a triptan in 2005, of which 10.3% were overusers and accounted for half of the total costs of triptans. Users of frovatriptan, rizatriptan and naratriptan had a lower level of overuse.