Objective.- To evaluate whether the same or different patients respond to triptans and telcagepant. Background.- Telcagepant is an oral calcitonin gene-related peptide receptor antagonist with... Show moreObjective.- To evaluate whether the same or different patients respond to triptans and telcagepant. Background.- Telcagepant is an oral calcitonin gene-related peptide receptor antagonist with acute antimigraine efficacy comparable to oral triptans. It is currently unknown whether migraine patients who cannot be adequately helped with triptans might benefit from treatment with telcagepant. Methods.- Post-hoc analysis of data from a randomized, controlled trial of telcagepant (150 mg, 300 mg) zolmitriptan 5 mg, or placebo for a moderate/severe migraine. Responder rates were analyzed according to patients' self-reported historical triptan response (HTR): (1) good HTR (N = 660): response in 75-100% of attacks; (2) intermediate HTR (N = 248): response in 25-74% of attacks; (3) poor HTR/no use (N = 407): response in < 25% of attacks, or patient did not take triptans. A limitation of the analysis is that the last subgroup comprised mainly (91%) patients who reported that they did not take triptans, but it was not known whether these patients were triptan-naive or had previously used triptans and stopped taking them. Results.- For zolmitriptan, 2-hour pain relief rates were higher in the good HTR subgroup (116/162, 72%) than in the intermediate (29/62, 47%) and poor/no use (44/111, 40%) HTR subgroups. The 2-hour pain relief rates were similar across HTR subgroups for telcagepant 150 mg (48-58%), 300 mg (52-58%), and placebo (26-31%). In the poor/no use HTR subgroup, more patients receiving telcagepant 300 mg (56/98, 57.1%) had 2-hour pain relief than those receiving zolmitriptan (44/111, 39.6%; odds ratio = 2.11 [95% CI: 1.20,3.71], P = .009); the percentage for telcagepant 150 mg (57/119, 47.9%) was not significantly different from zolmitriptan (odds ratio = 1.41 [95% CI: 0.82, 2.40], P = .211). Conclusions.- This suggests that different patients may respond to triptans or telcagepant 300 mg. Caution should be exercised in interpreting the results because of the post-hoc nature of the analysis (clinical trial registry: NCT00442936). Show less
Stam, A.H.; Louter, M.A.; Haan, J.; Vries, B. de; Maagdenberg, A.M.J.M. van den; Frants, R.R.; ... ; Terwindt, G.M. 2011
OBJECTIVE Our objective was to study the long-term prognosis of sporadic hemiplegic migraine (SHM). METHODS We performed a longitudinal follow-up study in 18 patients who were diagnosed with SHM... Show moreOBJECTIVE Our objective was to study the long-term prognosis of sporadic hemiplegic migraine (SHM). METHODS We performed a longitudinal follow-up study in 18 patients who were diagnosed with SHM between 1993 and 1996. Follow-up time between the first and second survey ranged from nine to 14 years. These patients were included as part of a genetic study in which we systematically analysed the role of the three known familial hemiplegic migraine (FHM) genes. RESULTS In 12 out of 18 patients the clinical diagnosis was unchanged. In two of the six remaining patients the attacks were no longer associated with hemiplegia; one of them had an ATP1A2 gene mutation (E120A). In the four other patients, the diagnosis changed into FHM, because a family member had developed hemiplegic migraine since the initial diagnosis was made. In two of the four patients a mutation was demonstrated (CACNA1A [R583Q] and ATP1A2 [R834X]). CONCLUSION This study shows that the diagnosis of SHM changes into FHM in a considerable percentage of patients (22% [4 of 18]), almost a decade after the initial diagnosis. This indicates that a careful follow-up of SHM patients and their families is advisable for optimal care and counseling. Diagnostic screening of FHM genes in SHM patients can be of value. Our genetic and clinical follow-up studies reinforce the evidence that FHM and SHM are part of the same spectrum of migraine. Show less
Stam, A.H.; Louter, M.A.; Haan, J.; Vries, B. de; Maagdenberg, A.M.J.M. van den; Frants, R.R.; ... ; Terwindt, G.M. 2011
BACKGROUND AND PURPOSE Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small vessel disease. Although postmortem studies have... Show moreBACKGROUND AND PURPOSE Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small vessel disease. Although postmortem studies have demonstrated mural thickening in leptomeningeal arteries and lenticulostriate perforating arteries, it is unclear whether this also leads to luminal narrowing. High-field MRI scanners enable in vivo imaging of the lumen of the lenticulostriate arteries. The aim of this study is to examine the luminal diameters of lenticulostriate arteries in living patients with CADASIL and to investigate whether luminal narrowing is correlated with the number of lacunar infarcts in the basal ganglia. METHODS Twenty-two NOTCH3 mutation carriers and 11 healthy control subjects were examined using high-resolution 3-dimensional time-of-flight MR angiography imaging on a 7-T MRI scanner. Scans were analyzed for the presence of focal stenotic segments. The total number, length, and total cross-sectional area of lenticulostriate arteries were measured and compared between mutation carriers and control subjects. These measurements were correlated with age, disease duration, and number of lacunar infarcts in the basal ganglia. RESULTS No stenotic segments were observed. No differences between mutation carriers and control subjects were found in total number of end branches (mutation carriers: mean, 14.6; control subjects: mean, 12.8), length of the lenticulostriate system, or total cross-sectional area of lenticulostriate artery lumina. Measurements of lenticulostriate artery lumina were not associated with lacunar infarct load in the basal ganglia area or with basal ganglia hyperintensities. CONCLUSIONS Three-dimensional time-of-flight MR angiographic on 7 T showed no differences in luminal diameters of lenticulostriate arteries between patients with CADASIL and control subjects. Show less
Liem, M.K.; Grond, J. van der; Versluis, M.J.; Haan, J.; Webb, A.G.; Ferrari, M.D.; ... ; Oberstein, S.A.J.L. 2010
Background and Purpose-Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small vessel disease. Although postmortem studies have... Show moreBackground and Purpose-Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small vessel disease. Although postmortem studies have demonstrated mural thickening in leptomeningeal arteries and lenticulostriate perforating arteries, it is unclear whether this also leads to luminal narrowing. High-field MRI scanners enable in vivo imaging of the lumen of the lenticulostriate arteries. The aim of this study is to examine the luminal diameters of lenticulostriate arteries in living patients with CADASIL and to investigate whether luminal narrowing is correlated with the number of lacunar infarcts in the basal ganglia. Methods-Twenty-two NOTCH3 mutation carriers and 11 healthy control subjects were examined using high-resolution 3-dimensional time-of-flight MR angiography imaging on a 7-T MRI scanner. Scans were analyzed for the presence of focal stenotic segments. The total number, length, and total cross-sectional area of lenticulostriate arteries were measured and compared between mutation carriers and control subjects. These measurements were correlated with age, disease duration, and number of lacunar infarcts in the basal ganglia. Results-No stenotic segments were observed. No differences between mutation carriers and control subjects were found in total number of end branches (mutation carriers: mean, 14.6; control subjects: mean, 12.8), length of the lenticulostriate system, or total cross-sectional area of lenticulostriate artery lumina. Measurements of lenticulostriate artery lumina were not associated with lacunar infarct load in the basal ganglia area or with basal ganglia hyperintensities. Conclusions-Three-dimensional time-of-flight MR angiographic on 7 T showed no differences in luminal diameters of lenticulostriate arteries between patients with CADASIL and control subjects. (Stroke. 2010;41:2812-2816.) Show less
We present a previously unreported early 18th-century description of cluster headache by the English antiquary Abraham de la Pryme (1671-1704) initially attributed to hydrophobia (rabies). We will... Show moreWe present a previously unreported early 18th-century description of cluster headache by the English antiquary Abraham de la Pryme (1671-1704) initially attributed to hydrophobia (rabies). We will also give a short overview of other descriptions of cluster and cluster-like headache in historical literature. Show less
Liem, M.K.; Oberstein, S.A.J.L.; Grond, J. van der; Ferrari, M.D.; Haan, J. 2010
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene and is clinically characterized by recurrent stroke,... Show moreCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene and is clinically characterized by recurrent stroke, cognitive decline, psychiatric disturbances and migraine. The prevalence of migraine in CADASIL is slightly higher than in the general population, and the proportion of migraine with aura is much higher. The pathophysiological mechanism that leads to increased aura prevalence in CADASIL is unknown. Possible mechanisms of the excess of migraine with aura are an increased susceptibility to cortical spreading depression (CSD) or a different expression of CSD. It is also possible that the brainstem migraine area is involved in CADASIL. Last, it is possible that the NOTCH3 mutation acts as a migraine aura susceptibility gene by itself. In this narrative review we summarize the literature about migraine in CADASIL, with a special focus on what CADASIL might teach us about the pathophysiology of migraine. Show less
Liem, M.K.; Oberstein, S.A.J.L.; Grond, J. van der; Ferrari, M.D.; Haan, J. 2010
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene and is clinically characterized by recurrent stroke,... Show moreCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene and is clinically characterized by recurrent stroke, cognitive decline, psychiatric disturbances and migraine. The prevalence of migraine in CADASIL is slightly higher than in the general population, and the proportion of migraine with aura is much higher. The pathophysiological mechanism that leads to increased aura prevalence in CADASIL is unknown. Possible mechanisms of the excess of migraine with aura are an increased susceptibility to cortical spreading depression (CSD) or a different expression of CSD. It is also possible that the brainstem migraine area is involved in CADASIL. Last, it is possible that the NOTCH3 mutation acts as a migraine aura susceptibility gene by itself. In this narrative review we summarize the literature about migraine in CADASIL, with a special focus on what CADASIL might teach us about the pathophysiology of migraine. Show less
Anttila, V.; Stefansson, H.; Kallela, M.; Todt, U.; Terwindt, G.M.; Calafato, M.S.; ... ; Int Headache Genetics Consortium 2010
Migraine is a common episodic neurological disorder, typically presenting with recurrent attacks of severe headache and autonomic dysfunction. Apart from rare monogenic subtypes, no genetic or... Show moreMigraine is a common episodic neurological disorder, typically presenting with recurrent attacks of severe headache and autonomic dysfunction. Apart from rare monogenic subtypes, no genetic or molecular markers for migraine have been convincingly established. We identified the minor allele of rs1835740 on chromosome 8q22.1 to be associated with migraine (P = 5.38 x 10(-9), odds ratio = 1.23, 95% CI 1.150-1.324) in a genome-wide association study of 2,731 migraine cases ascertained from three European headache clinics and 10,747 population-matched controls. The association was replicated in 3,202 cases and 40,062 controls for an overall meta-analysis P value of 1.69 x 10(-11) (odds ratio = 1.18, 95% CI 1.127-1.244). rs1835740 is located between MTDH (astrocyte elevated gene 1, also known as AEG-1) and PGCP (encoding plasma glutamate carboxypeptidase). In an expression quantitative trait study in lymphoblastoid cell lines, transcript levels of the MTDH were found to have a significant correlation to rs1835740 (P = 3.96 x 10(-5), permuted threshold for genome-wide significance 7.7 x 10(-5)). To our knowledge, our data establish rs1835740 as the first genetic risk factor for migraine. Show less
Introduction: Lasmiditan (COL-144; LY573144) is a novel, highly selective and potent agonist at 5-HTIF receptors that lacks vasoconstrictor activity. Preclinical and early clinical experiments... Show moreIntroduction: Lasmiditan (COL-144; LY573144) is a novel, highly selective and potent agonist at 5-HTIF receptors that lacks vasoconstrictor activity. Preclinical and early clinical experiments predict acute antimigraine efficacy of COL-144 that is mediated through a non-vascular, primarily neural, mechanism. Subjects and methods: In a randomised, multicentre, placebo-controlled, double-blind, group-sequential, adaptive treatment-assignment, proof-of-concept and dose-finding study, we treated 130 subjects in-hospital during a migraine attack. Subjects were allocated to an intravenous dose level of lasmiditan or placebo in small cohorts. The starting dose was 2.5 mg. Subsequent doses were adjusted, up or down, according to the safety and efficacy seen in the preceding cohort. The primary outcome measure was headache response defined as improvement from moderate or severe headache at baseline to mild or no headache at 2 h post-dose. The study was designed to explore the overall dose response relationship but was not powered to differentiate individual doses from placebo, nor to detect effect differences for other migraine symptoms. Results: Forty-two subjects received placebo and 88 received lasmiditan in doses of 2.5-45 mg. Subjects were observed in the clinic for 4 h after treatment and used a diary card to record symptoms and adverse events for up to 24 h. The study was terminated when the 20 mg dose met predefined efficacy stopping rules. Of subjects treated in the 10, 20, 30 and 45 mg lasmiditan dose groups, 54-75% showed a 2 h headache response, compared to 45% in the placebo group (P = 0.0126 for the linear association between response rates and dose levels). Patient global impression at 2 h and lack of need for rescue medication also showed statistically significant linear correlations with dose. Lasmiditan was generally well tolerated. Adverse events were reported by 65% of subjects on lasmiditan and by 43% on placebo and were generally mild. Dizziness, paresthesia and sensations of heaviness (usually limb) were more common on lasmiditan. Conclusions: At intravenous doses of 20 mg and higher, lasmiditan proved effective in the acute treatment of migraine. Further studies to assess the optimal oral dose and full efficacy and tolerability profile are under way. The non-vascular, neural mechanism of action of lasmiditan may offer an alternative means to treat migraine especially in patients who have contra-indications for agents with vasoconstrictor activity. The clinicaltrials.gov identifier for this study is NCT00384774. Show less
INTRODUCTION Lasmiditan (COL-144; LY573144) is a novel, highly selective and potent agonist at 5-HT(1F) receptors that lacks vasoconstrictor activity. Preclinical and early clinical experiments... Show moreINTRODUCTION Lasmiditan (COL-144; LY573144) is a novel, highly selective and potent agonist at 5-HT(1F) receptors that lacks vasoconstrictor activity. Preclinical and early clinical experiments predict acute antimigraine efficacy of COL-144 that is mediated through a non-vascular, primarily neural, mechanism. SUBJECTS AND METHODS In a randomised, multicentre, placebo-controlled, double-blind, group-sequential, adaptive treatment-assignment, proof-of-concept and dose-finding study, we treated 130 subjects in-hospital during a migraine attack. Subjects were allocated to an intravenous dose level of lasmiditan or placebo in small cohorts. The starting dose was 2.5 mg. Subsequent doses were adjusted, up or down, according to the safety and efficacy seen in the preceding cohort. The primary outcome measure was headache response defined as improvement from moderate or severe headache at baseline to mild or no headache at 2 h post-dose. The study was designed to explore the overall dose response relationship but was not powered to differentiate individual doses from placebo, nor to detect effect differences for other migraine symptoms. RESULTS Forty-two subjects received placebo and 88 received lasmiditan in doses of 2.5-45 mg. Subjects were observed in the clinic for 4 h after treatment and used a diary card to record symptoms and adverse events for up to 24 h. The study was terminated when the 20 mg dose met predefined efficacy stopping rules. Of subjects treated in the 10, 20, 30 and 45 mg lasmiditan dose groups, 54-75% showed a 2 h headache response, compared to 45% in the placebo group (P = 0.0126 for the linear association between response rates and dose levels). Patient global impression at 2 h and lack of need for rescue medication also showed statistically significant linear correlations with dose. Lasmiditan was generally well tolerated. Adverse events were reported by 65% of subjects on lasmiditan and by 43% on placebo and were generally mild. Dizziness, paresthesia and sensations of heaviness (usually limb) were more common on lasmiditan. CONCLUSIONS At intravenous doses of 20 mg and higher, lasmiditan proved effective in the acute treatment of migraine. Further studies to assess the optimal oral dose and full efficacy and tolerability profile are under way. The non-vascular, neural mechanism of action of lasmiditan may offer an alternative means to treat migraine especially in patients who have contra-indications for agents with vasoconstrictor activity. The clinicaltrials.gov identifier for this study is NCT00384774. Show less
