Inge H. Palm-Meinders

Structural Brain Changes in Migraine

CONTEXT A previous cross-sectional study showed an association of migraine with a higher prevalence of magnetic resonance imaging (MRI)-measured ischemic lesions in the brain. OBJECTIVE To determine whether women or men with migraine (with and without aura) have a higher incidence of brain lesions 9 years after initial MRI, whether migraine frequency was associated with progression of brain lesions, and whether progression of brain lesions was associated with cognitive decline. DESIGN, SETTING, AND PARTICIPANTS In a follow-up of the 2000 Cerebral Abnormalities in Migraine, an Epidemiological Risk Analysis cohort, a prospective population-based observational study of Dutch participants with migraine and an age- and sex-matched control group, 203 of the 295 baseline participants in the migraine group and 83 of 140 in the control group underwent MRI scan in 2009 to identify progression of MRI-measured brain lesions. Comparisons were adjusted for age, sex, hypertension, diabetes, and educational level. The participants in the migraine group were a mean 57 years (range, 43-72 years), and 71% were women. Those in the control group were a mean 55 years (range, 44-71 years), and 69% were women. MAIN OUTCOME MEASURES Progression of MRI-measured cerebral deep white matter hyperintensities, infratentorial hyperintensities, and posterior circulation territory infarctlike lesions. Change in cognition was also measured. RESULTS Of the 145 women in the migraine group, 112 (77%) vs 33 of 55 women (60%) in the control group had progression of deep white matter hyperintensities (adjusted odds ratio [OR], 2.1; 95%CI, 1.0-4.1; P = .04). There were no significant associations of migraine with progression of infratentorial hyperintensities: 21 participants (15%) in the migraine group and 1 of 57 participants (2%) in the control group showed progression (adjusted OR, 7.7; 95% CI, 1.0-59.5; P = .05) or new posterior circulation territory infarctlike lesions: 10 of 203 participants (5%) in the migraine group but none of 83 in the control group (P = .07). There was no association of number or frequency of migraine headaches with progression of lesions. There was no significant association of high vs nonhigh deep white matter hyperintensity load with change in cognitive scores (-3.7 in the migraine group vs 1.4 in the control group; 95% CI, -4.4 to 0.2; adjusted P = .07). CONCLUSIONS In a community-based cohort followed up after 9 years, women with migraine had a higher incidence of deep white matter hyperintensities but did not have significantly higher progression of other MRI-measured brain changes. There was no association of migraine with progression of any MRI-measured brain lesions in men.

Hypoxic-Ischemic Encephalopathy: Diagnostic Value of Conventional MR Imaging Pulse Sequences in Term-born Neonates

PURPOSE To retrospectively compare different magnetic resonance (MR) imaging techniques and pulse sequences for the depiction of brain injury in neonatal hypoxic-ischemic encephalopathy. MATERIALS AND METHODS The institutional review board approved this retrospective study and waived informed consent. Term-born neonates underwent MR imaging within 10 days after birth because of perinatal asphyxia. Two investigators separately and retrospectively evaluated T1-weighted, T2-weighted, fluid-attenuated inversion recovery (FLAIR), diffusion-weighted, and T1-weighted contrast material-enhanced MR images for presence of hypoxic-ischemic injury patterns. Interobserver agreement between the raters for visualizing abnormalities on images obtained with the individual pulse sequences was analyzed. Individual assessments were compared with the consensus reading (reference standard) to determine which techniques were best for visualizing hypoxic-ischemic damage. Last, which combination of pulse sequences had the best performance for visualizing certain injury patterns was evaluated. All analyses were repeated for infants imaged within 4 days after birth and those imaged between 4 and 10 days after birth. RESULTS Forty term-born neonates (22 boys; gestational age, 37 weeks to 42 weeks 2 days) were included. Interobserver agreement was moderate for all pulse sequences (intraclass correlation coefficient [ICC], 0.52-0.73). As compared with the reference standard, T1-weighted imaging performed best in both groups (infants imaged < or = 4 days and those imaged > 4 days after birth) for lesions in the basal ganglia, thalamus, and posterior limb of the internal capsule (ICC, 0.93), as well as for punctate white matter lesions (ICC, 0.88). For infarction, diffusion-weighted images were scored best in both groups (ICC, 0.86). For nonpunctate white matter lesions, T2-weighted images were scored as good in both groups (ICC, 0.59). Adding FLAIR and contrast-enhanced imaging to the combination of T1- and T2-weighted imaging and diffusion-weighted imaging did not contribute to detection of hypoxic-ischemic brain damage. CONCLUSION The combination of T1- and T2-weighted MR imaging and diffusion-weighted imaging is best for detecting hypoxic-ischemic brain lesions in the early neonatal period in term-born infants.

Pravastatin Decreases Wall Shear Stress and Blood Velocity in the Internal Carotid Artery Without Affecting Flow Volume Results From the PROSPER MRI Study

Background and Purpose— Despite speculations, it is unknown whether statins affect wall shear stress (WSS). Therefore, the effect of pravastatin on WSS was investigated. Methods— In 355 elderly individuals participating in the PROSPER study (follow up after 3 years), the effect of 40 mg pravastatin on WSS was assessed in the internal carotid artery using magnetic resonance imaging. Results— WSS and blood velocity decreased both in the pravastatin group and in the placebo group but decreased faster in the pravastatin group (P<0.04, P<0.02). Blood volume flow did not differ between the groups. Conclusions— In elderly subjects, the WSS and blood velocity of the internal carotid artery declines significantly over time and this decline is more pronounced in subjects treated with 40 mg pravastatin compared with the placebo group.

Reproducibility of wall shear stress assessment with the paraboloid method in the internal carotid artery with velocity encoded MRI in healthy young individuals.

To verify whether wall shear stress (WSS) can be assessed in a reproducible manner using automatic model‐based segmentation of phase‐contrast MR images by determination of flow volume and maximum flow velocity (Vmax) in cross‐sections of these vessels.

The impact of a migraine attack and its after-effects on perceptual organization, attention, and working memory

Introduction: Many migraine patients report cognitive complaints during the first hours or days following a migraine attack. The aim of this study was to assess whether and which cognitive (perceptual, attentional, or memory) processes are impaired during the first 48 hours after a migraine attack. Methods: Three different cognitive tasks (global-local task, the attentional network task, and N-back task) were administered to 16 migraine patients (13 migraine without aura; mean age 58 years, 15 female) and 18 controls (59 years, 15 female), matched on age, gender, and educational level. Tasks were administered at three time points; during the first headache free day following a migraine attack (first session), 24 hours later (second session), and 12 days after the attack (third session). Results: The attentional network and N-back tasks showed no significant differences between migraineurs and controls. In the global-local task, controls showed faster reaction times to global than to local stimuli, which is the standard global-precedence effect. This effect was absent in the migraineurs in all three sessions, especially if they used prophylaxis. Conclusion: Migraineurs had no impaired attentional or working-memory functioning in the 2 days after an attack. They did show impairments in the processing of global visual features compared with controls, both between and immediately after an attack.

Diastolic Wall Shear Stress in the Internal Carotid Artery Is Associated with Different Cardiovascular Risk Factors than Systolic Wall Shear Stress

Background and Purpose: Wall shear stress (WSS) is the frictional force exerted by the circulating blood on the endothelium. Low systolic WSS is identified as an atherosclerotic risk factor. Recently, also the importance of diastolic WSS has been described. Still, it is unknown whether diastolic WSS carries similar cardiovascular risk factors compared to systolic WSS. Methods: Of 379 subjects (70–82 years, 56% male) diastolic and systolic WSS in the internal carotid arteries was determined. Results: After adjustment for age and gender, diastolic blood pressure was associated with systolic WSS (p = 0.02). Body mass index was associated with diastolic WSS (p = 0.04). Smoking was associated with diastolic WSS (p = 0.05). Myocardial infarction was associated with both systolic WSS (p = 0.04) and diastolic WSS (p < 0.01). No associations between cholesterol, HDL, LDL, triglycerides, history of diabetes, hypertension, angina pectoris, claudication, stroke, or any vascular disease were found with systolic or diastolic WSS. Conclusions: Our data indicates different cardiovascular risk factors for diastolic WSS compared to systolic WSS.

Systemic right-to-left shunts, ischemic brain lesions, and persistent migraine activity

Objective: To assess whether migraine in the general population is associated with increased risk of systemic right-to-left shunts (RLS) and whether RLS are associated with increased prevalence of brain infarcts and persistent recurrence of migraine attacks at older age. Methods: Brain MRI and transcranial Doppler with air contrast in 166 unselected migraineurs (mean age ± SD 56 ± 7.7 years; 70% women; n = 96 migraine with aura) and 69 controls (mean age ± SD 55 ± 7.6 years; 65% women) from the general population. Results: Participants with migraine with aura more frequently had Valsalva-induced RLS (60%), in particular large-sized, compared to controls (42%; odds ratio [OR] 2.1; 95% confidence interval [CI] 1.1–3.9; p = 0.02) and participants with migraine without aura (40%; OR 2.3; 95% CI 1.2–4.3; p = 0.01). They also more frequently had spontaneous RLS (35%) than participants with migraine without aura (17%; OR 2.6; 95% CI 1.3–5.6; p = 0.01) but not compared to controls (26%; OR 1.6; 95% CI 0.8–3.1; p = 0.2). Participants with migraine with aura and spontaneous RLS more frequently had persistent migraine activity (85%) than participants with migraine without spontaneous RLS (63%; OR 3.4; 95% CI 1.2–10.1; p = 0.03). Nine percent of participants with RLS had silent posterior circulation infarcts compared to 3% of participants without RLS (OR 2.8; 95% CI 0.9–9.3; p = 0.08), independent of migraine status. RLS were not associated with white matter lesions. Conclusions: RLS are more prevalent in migraineurs with aura but do not explain the increased prevalence of silent posterior circulation infarcts or white matter lesions in migraineurs. Spontaneous RLS are associated with persistent migraine.

Volumetric brain changes in migraineurs from the general population

Objective: To assess volumetric brain changes in migraineurs from the general population compared with controls. Methods: Structural brain changes in migraineurs from the general population-based MRI Cerebral Abnormalities in Migraine, an Epidemiologic Risk Analysis (CAMERA)-2 observational cohort study were assessed by state-of-the-art voxel-based morphometry. T1-weighted MRIs of 84 migraineurs (52 with aura, 32 without aura) and 35 headache-free controls were evaluated. Regional volumes were compared voxelwise, corrected for age, sex, and total intracranial volume, with region-of-interest and whole-brain analyses. Results: In region-of-interest analyses, migraineurs showed decreased gray matter volume in the visual areas V3 and V5 of the right occipital cortex compared to controls (p < 0.05, familywise error correction). Post hoc analyses revealed that similar changes were present regardless of migraine aura status, disease activity (>1 year attack-free [inactive] vs ≥1 attack within the last year [active] and attack frequency [≤1 (low) vs ≥1 attack per month [high]). In exploratory whole-brain analyses (p < 0.001, uncorrected for multiple comparisons), we identified additional structural differences in migraineurs in other cortical and subcortical areas, including white matter tracts, that are particularly involved in visual processing. Conclusions: Migraineurs from the general population showed small volumetric brain changes, mainly in cortical areas involved in visual motion processing, compared to controls. The presence of morphologic changes regardless of the presence of migraine aura or disease activity suggests that migraines with and without aura share common pathophysiologic pathways and suggests that these changes are (partially) irreversible or might have been present throughout life.

Cerebellar function and ischemic brain lesions in migraine patients from the general population

Objective The objective of this article is to obtain detailed quantitative assessment of cerebellar function and structure in unselected migraine patients and controls from the general population. Methods A total of 282 clinically well-defined participants (migraine with aura n = 111; migraine without aura n = 89; non-migraine controls n = 82; age range 43–72; 72% female) from a population-based study were subjected to a range of sensitive and validated cerebellar tests that cover functions of all main parts of the cerebellar cortex, including cerebrocerebellum, spinocerebellum, and vestibulocerebellum. In addition, all participants underwent magnetic resonance imaging (MRI) of the brain to screen for cerebellar lesions. As a positive control, the same cerebellar tests were conducted in 13 patients with familial hemiplegic migraine type 1 (FHM1; age range 19–64; 69% female) all carrying a CACNA1A mutation known to affect cerebellar function. Results MRI revealed cerebellar ischemic lesions in 17/196 (8.5%) migraine patients and 3/79 (4%) controls, which were always located in the posterior lobe except for one control. With regard to the cerebellar tests, there were no differences between migraine patients with aura, migraine patients without aura, and controls for the: (i) Purdue-pegboard test for fine motor skills (assembly scores p = 0.1); (ii) block-design test for visuospatial ability (mean scaled scores p = 0.2); (iii) prism-adaptation task for limb learning (shift scores p = 0.8); (iv) eyeblink-conditioning task for learning-dependent timing (peak-time p = 0.1); and (v) body-sway test for balance capabilities (pitch velocity score under two-legs stance condition p = 0.5). Among migraine patients, those with cerebellar ischaemic lesions performed worse than those without lesions on the assembly scores of the pegboard task (p < 0.005), but not on the primary outcome measures of the other tasks. Compared with controls and non-hemiplegic migraine patients, FHM1 patients showed substantially more deficits on all primary outcomes, including Purdue-peg assembly (p < 0.05), block-design scaled score (p < 0.001), shift in prism-adaptation (p < 0.001), peak-time of conditioned eyeblink responses (p < 0.05) and pitch-velocity score during stance-sway test (p < 0.001). Conclusions Unselected migraine patients from the general population show normal cerebellar functions despite having increased prevalence of ischaemic lesions in the cerebellar posterior lobe. Except for an impaired pegboard test revealing deficits in fine motor skills, these lesions appear to have little functional impact. In contrast, all cerebellar functions were significantly impaired in participants with FHM1.

Postural sway in migraine patients and controls, results from a population based CAMERA-2 study

Methods Trunk sway in the medio-lateral (roll) and anterior-posterior (pitch) plane was measured using two digital angular velocity transducers attached to the lower back. Subjects completed three different trials. All tests were done interictally and investigators were blinded for all participant characteristics. Outcomes are given as trunksway angles and angular velocity in both the roll and pitch plane.