Cluster Headache is Associated With the Alcohol Dehydrogenase 4 (ADH4) Gene

(Headache 2010;50:92‐98) Background/Objectives.— Alcohol is a well‐known trigger factor for cluster headache attacks during the active phases of the disease. The alcohol dehydrogenase (ADH) pathway, which converts alcohol to the toxic substance acetaldehyde, is responsible for most of the alcohol breakdown in the liver. Humans have 7 ADH genes, tightly clustered on chromosome 4q21‐q25, that encode different ADH isoforms. The ADH4 gene encodes the class II ADH4 pi subunit, which contributes, in addition to alcohol, to the metabolization of a wide variety of substrates, including retinol, other aliphatic alcohols, hydroxysteroids, and biogenic amines. The purpose of this study was to investigate the association of genetic variants within the ADH4 gene with cluster headache susceptibility and phenotype. Methods.— A total of 110 consecutive unrelated cluster headache patients and 203 age‐ and sex‐matched healthy controls of Caucasian origin were involved in the study. Patients and controls were genotyped for 2 bi‐allelic single nucleotide polymorphisms (SNPs) of the ADH4 gene: SNP1 – rs1800759 and SNP2 – rs1126671. Allele, genotype, and haplotype frequencies of the examined polymorphisms were compared between cases and controls. Results.— Genotype frequencies of the rs1126671 polymorphism resulted significantly different between cluster headache patients and controls (χ² = 10.269, P = .006). The carriage of the AA genotype, in comparison with remaining genotypes, was associated with a significantly increased disease risk (OR = 2.33, 95% CI: 1.25‐4.37). Haplotype analysis confirmed the association between the ADH4 gene and the disease. No association between different clinical characteristics of cluster headache and the examined polymorphisms was found. Conclusion.— Our data suggest that cluster headache is associated with the ADH4 gene or a linked locus. Additional studies are warranted to elucidate the role of this gene in the etiopathogenesis of the disease.     

MTHFR 677C>T polymorphism and cluster headache

(Headache 2011;51:201‐207) Background.— An association between the 677C>T polymorphism (rs1801133) in the methylenetetrahydrofolate reductase gene (MTHFR) and cluster headache is plausible, but has not been investigated. Objective.— To investigate this association among Caucasians. Methods.— Case–control study among 147 cluster headache patients and 599 population‐based age‐ and gender‐matched controls. Cluster headache was diagnosed according to the criteria of the International Headache Society. Genotypes of the MTHFR 677C>T polymorphism were detected by restriction fragment length polymorphism analysis. We used logistic regression analysis to investigate the association between cluster headache and genotypes with additive, dominant, and recessive models. We considered a Bonferroni‐corrected P value <.004 as significant. Results.— Mean age at study entry among patients was 44.9 years (SD 11.4), of whom 76.2% were men. The genotype distribution among controls and patients was in Hardy–Weinberg equilibrium. The genotype and allele distribution did not differ between patients with any cluster headache and controls. We also did not find an association when assuming additive, dominant or recessive genetic models. When we looked at subgroups, the effect estimates suggested an increased risk for chronic cluster headache (dominant model: odds ratio = 2.82; 99.6% confidence interval = 0.72‐11.07; P = .03). Conclusions.— Data from our case–control study do not indicate an association between genotypes of the MTHFR 677C>T polymorphism and cluster headache overall. Subgroup analyses suggested that carriers of the MTHFR 677T allele may have an increased risk for chronic cluster headache. This may be regarded as hypothesis‐generating and should be further investigated in independent studies.     

基于脑表面形态学分析在特发性全面性癫痫的应用

目的 应用基于脑表面形态学的分析,探讨特发性全面性癫痫(IGE)脑皮层的结构改变。方法 收集IGE患者16例(IGE组)和健康志愿者16名(对照组),均行常规序列和高分辨率3D-T1WI结构像采集。利用FreeSurer软件测量脑皮层厚度、表面积及灰质体积,并分析形态学异常脑区与病程的相关性。结果 与对照组比较,IGE组右颞中回皮层变薄(P=0.010 9),左颞中回表面积减小(P=0.000 3),左额下回中部(P=0.000 2)、左外侧枕叶(P=0.043 6)、右岛叶(P=0.000 7)表面积增大;左颞上回体积减小(P=0.011 9)。皮层厚度、脑表面面积、脑灰质体积与病程、发病起始年龄均无相关性(P均>0.05);右颞中回皮层厚度与病程呈负相关(r=-0.48,P<0.05)。结论 IGE存在多个脑区微观结构的形态学异常。基于脑表面形态学分析可为IGE提供一定的影像学依据。     

Patterns of cortical thickness and surface area in early Parkinson's disease

Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder diagnosed on the basis of motor symptoms, but that also includes cognitive and visuo-spatial deficits. Though PD is known to initially affect subcortical regions, the cortex also exhibits neuronal loss in the course of the disease as post mortem studies have shown. So far, PD-related pattern of cortical damage remains unclear, because of disease-caused heterogeneity, and also in part because of methodological issues such as the limitations of Voxel Based Morphometry. Here corticometry was used, a technique that decouples local surface from thickness, to obtain a better picture of PD corticomorphometric patterns. We acquired MRI volumes for 33 healthy controls (HC) and 49 PD patients, extracted local cortical thickness and surface area and modeled both of them as a function of group and age for each participant. Cortical thickness averaged on the whole cortex did not differ between the two groups while mean surface area was significantly larger in the PD group. The bilateral parietal lobule, the right superior frontal gyrus, the left cingulate cortex and the left insular cortex exhibited larger local surface area in the PD group. The right precuneus exhibited cortical thinning associated with age in the PD group and not in the HC group. Furthermore, cortical thinning was observed in the PD group compared with the control group in the left medial supplementary motor area (SMA) and in the right dorsal pre-SMA. Finally, we found the left temporal pole thickness to correlate with disease duration, as well as the bilateral occipital cortex and Broca's area. These results suggest that PD etiology is associated with specific cortical alterations, which could account for cognitive deficits that arise as the disease evolves. Finally, our results observed in the occipital cortex as a function of disease duration may indicate the increase in PD-related visuo-spatial deficits, which can sometimes result in hallucinations later on in the disease. In the future, MRI-generated corticometry, combined with additional behavioral markers, may prove to be a useful diagnosis tool to characterize the evolution of motor and cognitive deficits in PD.     

经典三叉神经痛患者脑局部自发活动的静息态功能MRI

目的 观察经典三叉神经痛（CTN）患者静息状态下脑局部自发活动的改变。方法 对27例CTN患者（CTN组）和27名健康对照者（对照组）行静息态脑功能MRI数据采集,采用局部一致性（ReHo）数据分析方法获得CTN组ReHo差异脑区,并对组间差异脑区ReHo值分别与患者视觉模拟评分（VAS）和病程行相关性分析。结果 与对照组比较（P<0.05,高斯随机场校正）,CTN患者双侧初级感觉运动皮层,右侧辅助运动区、颞下皮层和小脑,左侧丘脑、边缘叶/海马旁回和颞上/中皮层ReHo值增高;双侧前额皮层/眶额皮层和脑岛,右侧额内侧皮层和颞上皮层,左侧前扣带回、缘上回和小脑ReHo值减低。右额内侧皮层ReHo值与病程呈负相关（r=-0.45,P=0.03）;左侧初级感觉运动皮层ReHo值与VAS评分（r=0.46,P=0.02）呈正相关。结论 CTN患者存在疼痛相关功能脑区自发功能活动一致性的异常,有助于对CTN发生机制的理解。     

Contribution of chronic pain and neuroticism to abnormal forebrain gray matter in patients with temporomandibular disorder

Cortical plasticity is thought to occur following continuous barrage of nociceptive afferent signals to the brain. Hence, chronic pain is presumed to induce anatomical and physiological changes in the brain over time. Inherent factors, some pre-dating the onset of chronic pain, may also contribute to brain abnormalities present in patients. In this study we used structural MRI to examine whether patients with chronic temporomandibular (TMD) pain have abnormalities in gray matter (GM) within brain areas implicated in pain, modulation and sensorimotor function. We found that patients with TMD have cortical thickening in the primary somatosensory cortex (S1), frontal polar and the ventrolateral prefrontal cortex (PFC). These findings provide a structural basis for previous findings of TMD pain and cognitive sluggishness in TMD. We then examined the contribution of TMD characteristics to GM abnormalities. We found that 1) GM in the sensory thalamus positively correlated to TMD duration, 2) cortical thickness in the primary motor (M1) and the anterior mid-cingulate cortices (aMCC) were negatively correlated to pain intensity, and 3) pain unpleasantness was negatively correlated to cortical thickness in the orbitofrontal cortex (OFC). These findings suggest that an individual's TMD pain history contributes to GM in the brain. Lastly, we examined the contribution of a potential pre-existing vulnerability due to neuroticism. In the TMD patients, we found that there was an abnormal positive correlation between neuroticism and OFC thickness, in contrast to the negative correlation found in the healthy controls. Therefore, neuroticism may contribute to TMD pathophysiology. In sum, our data suggest that GM in the brain of patients with chronic TMD pain can be shaped by both personality and pain characteristics.     

慢性应激与抑郁症患者脑影像学改变及预后的关系

  目的  探索慢性应激与抑郁症患者脑影像学改变及预后的关系。  方法  选取2019年2月~2021年2月120例抑郁症患者,采用生活事件量表（LES）评估患者慢性应激状态,根据评分结果分为慢性应激组（n=78）和非慢性应激组（n=42）,另选取同期30例健康志愿者作为对照组。受试者均行头颅MRI扫描,采集得到的3DT1数据采用FreeSurfer自动化处理,计算并比较全脑脑区皮层厚度,并采用17项汉密尔顿抑郁量表（HAMD-17）评估抑郁症状,分别比较慢性应激组、非慢性应激组、对照组全脑皮层厚度及HAMD-17评分,并采用Pearson相关系数分析LES评分与全脑皮层厚度、HAMD-17评分的相关性;抑郁症患者出院后随访6~12月,比较慢性应激组、非慢性应激组抑郁症发作时间及6月内临床治愈率。  结果  对照组、非慢性应激组、慢性应激组左侧额叶三角部、双侧额上回、左侧额缘、双侧楔前叶、双侧颞中回、左侧顶下缘上回、左侧扣带回、右侧额叶岛盖部、右侧额下回及皮层平均厚度均呈下降趋势,组间差异均有统计学意义（P<0.05）,未见皮层厚度增加脑区;对照组、非慢性应激组、慢性应激组HAMD-17评分呈升高趋势,组间差异均有统计学意义（P<0.05）;Pearson相关性分析显示,LES评分与大脑皮层平均厚度呈负相关关系（P<0.05）,与HAMD-17评分呈正相关关系（P<0.05）;慢性应激组6月临床治愈低于非慢性应激组（P<0.05）,抑郁发作时间长于非慢性应激组（P<0.05）。  结论  慢性应激可加剧抑郁症患者大脑皮层萎缩,且与患者病情程度及预后密切相关。      

Chronic Migraine With Medication Overuse Pre–Post Withdrawal of Symptomatic Medication: Clinical Results and fMRI Correlations

(Headache 2010;50:998‐1004) Background.— Chronic migraine with symptomatic medication overuse (CMwMO) is a common and often debilitating clinical condition. Withdrawal of the offending drug(s) is considered the first step in management. Functional magnetic resonance imaging (fMRI) may be a useful technique for obtaining information on particular neuronal changes in the pain network involved in this condition. Objective.— To identify specific fMRI patterns in patients suffering from CMwMO before and after withdrawal intervention. Methods.— We collected fMRI data from a group of patients suffering from CMwMO, evaluating those patients prior to and 6 months following withdrawal. We applied stimuli at sites far removed from where the headaches were experienced. Moreover, pre‐intervention fMRI data from the headache patients were compared with those obtained from headache‐free and otherwise healthy controls. Results.— Before withdrawal, the right supramarginal gyrus, the right inferior and superior parietal cortex were hypoactive. Activity recovered to almost normal 6 months after withdrawal of the offending medications. Conclusions.— The hypoactivation we detected in the lateral pain system indicate that there exists a modification of the pain network in CMwMO and that these changes are reversible with therapy.     

Evidence for abnormalities of cortical development in adolescent-onset schizophrenia

Voxel-Based Morphometry (VBM) identifies differences in grey matter brain structure in patients with schizophrenia relative to healthy controls, with particularly prominent differences found in patients with the more severe, adolescent-onset form of the disease. However, as VBM is sensitive to a combination of changes in grey matter thickness, intensity and folding, specific neuropathological interpretations are not possible. Here, we attempt to more precisely define cortical changes in 25 adolescent-onset schizophrenic patients and 25 age- and sex-matched healthy volunteers using Surface-Based Morphometry (SBM) to disambiguate the relative contributions of cortical thickness and surface area differences to changes in regional grey matter (GM) density measured with VBM. Cortical changes in schizophrenia were widespread, including particularly the prefrontal cortex and superior temporal gyrus. Nine regions of apparent reduction in GM density in patients relative to healthy matched controls were found using VBM that were not found with SBM-derived cortical thickness measures. In Regions of Interest (ROIs) derived from the VBM group results, we confirmed that local surface area differences accounted for these VBM changes. Our results emphasize widespread, but focally distinct cortical pathology in adolescent-onset schizophrenia. Evidence for changes in local surface area (as opposed to simply cortical thinning) is consistent with a neurodevelopmental contribution to the underlying neuropathology of the disease.     

Warfarin for refractory chronic cluster headache: a randomized pilot study

(Headache 2011;51:713‐725) Objective.— To investigate the effect of low‐intensity anticoagulation with warfarin on chronic cluster headache refractory to pharmacological management. Background.— Isolated case reports on induction of remission in patients with intractable chronic cluster headache upon institution of oral anticoagulant therapy do exist. Nonetheless, evidence from randomized controlled trials on the role of oral anticoagulants in cluster headache is lacking. Methods.— Thirty‐four patients with refractory chronic cluster headache were randomized to receive warfarin or placebo for 12 weeks. Warfarin was administered to achieve an international normalized ratio between 1.5 and 1.9. After a washout period of 2 weeks, patients were crossed over from 1 treatment to the other. Status of cluster headache was assessed during both treatment periods. The primary outcome measure was the occurrence of remission lasting ≥4 weeks. Results.— Seventeen (50%) patients underwent remission for ≥4 weeks during the warfarin period vs 4 (11.8%) patients during the placebo period (P = .004). This was associated with absolute risk reduction of 0.38 (95% CI = 0.18‐0.58), and number needed to treat of 2.6 (95% CI = 1.7‐5.5). The Kaplan–Meier curves for occurrence of remission had a hazard ratio of 5.26 (95% CI = 2.13‐13.03, P = .0003). Frequency, duration, and intensity of cluster attacks were all significantly lower during treatment with warfarin (P < .01). Conclusion.— In patients with refractory chronic cluster headache, low‐intensity anticoagulation with warfarin was associated with significantly higher incidence of remission and less impact of headache on patients' lives compared with placebo.     

内嗅皮质萎缩评价糖尿病患者认知功能

目的 探讨2型糖尿病（T2DM）伴轻度认知功能损害（MCI）患者与单纯T2DM患者、健康对照者间各脑区皮质体积的差异,并分析其与认知下降的关联程度。方法 收集30例单纯T2DM患者、30例T2DM伴MCI患者和30名健康对照者,通过高分辨率MR T1WI采集大脑结构像数据,应用FreeSurfer软件处理获得各脑区体积参数。3组间各脑区体积的比较采用方差分析,对差异有统计学意义的脑区与心理学量表进行相关分析。结果 T2DM与T2DM伴MCI患者的听觉词语学习测验、复杂图形20 min回忆测验、数字符号编码测验、连线测验A、连线测验B、蒙特利尔认知评估量表分数差异有统计学意义（P均<0.05）。与T2DM患者比较,T2DM伴MCI患者的左侧内嗅皮质、左侧外侧眶额皮层、左侧后扣带回皮质、右侧外侧眶额皮质、右侧眶部皮质、右侧岛叶皮质体积均降低（P均<0.05）;T2DM伴MCI患者的左侧内嗅皮质体积与听觉词语学习测验评分（即刻）呈正相关（r=0.452,P=0.018）。结论 T2DM伴MCI患者出现多个脑区皮质体积降低,其中左侧内嗅皮质体积可作为诊断和衡量T2DM伴MCI的潜在生物学指标。     

Nighttime blood pressure in cluster headache

Background.— It has been proposed that desaturation of oxygen during an apnea event is the trigger for cluster headache. Obstructive sleep apnea has been associated with a higher than normal cardiovascular morbidity and mortality. Some obstructive sleep apnea syndrome patients lack the sleep‐related, nocturnal decrease, or “dip” in blood pressure, which is seen in normal individuals. Objective.— The aim of this study is to assess whether this non‐dipper pattern is present in cluster headache patients. Design and Methods.— A total of 30 normotensive cluster headache patients underwent an ambulatory blood pressure monitoring. “Non dippers” were defined as patients with a nighttime mean blood pressure fall <10%. Results.— Fifteen cluster headache patients (50%) were non‐dippers, a frequency higher than expected. The pattern of nocturnal non‐dipping is associated with a higher body mass index. Non‐dipper patients displayed higher mean nighttime systolic and diastolic blood pressure. No significant difference was observed in the mean 24‐hour and daytime blood pressure. Conclusions.— The high incidence (50%) of non‐dipper pattern in both processes, cluster headache and obstructive sleep apnea syndrome, provides support for the hypothesis of a relationship between theses 2 disorders.     

Iron deposition in pain-regulatory nuclei in episodic migraine and chronic daily headache by MRI

Background.— Progression of migraine toward a more disabling chronic form of at least 15 days/month is linked with frequency of attacks. Magnetic resonance imaging (MRI) findings of iron accumulation in the brain, especially in periaqueductal gray and red nucleus, have been correlated with both duration of illness and frequency of attacks. Methods.— This study therefore evaluated iron deposition as measured with MRI in basal ganglia and pain regulatory nuclei in neurologically healthy control volunteers and in patients with various migraine subtypes: episodic migraine (n = 10) with (n = 4) or without aura (n = 6), and chronic daily headache (n = 11), including medication overuse headache (MOH, n = 8), chronic tension‐type headache (n = 1), and primary chronic migraine (n = 2). The goal was to assess differences in iron deposition among migraine subtypes and controls in the hopes of linking the by‐products of frequent attacks or long duration of illness with these changes. Results.— The study sought to evaluate the tradeoff between sensitivity and specificity in T2 imaging of patients with migraine, and found that only T2 imaging in the globus pallidus was able to distinguish between episodic and chronic migraine, suggesting that this technique may be the most appropriate to assess migraine frequency. Patients with MOH did not demonstrate T2′ shortening. Conclusions.— Because iron accumulation should cause shortening of both T2 and T2′, although the lack of significance in observed T2′ difference could be due to increased variance in T2′ the measurement, these results suggest that a mechanism other than increased iron deposition may play a role in the genesis or pathophysiology of MOH.     

fMRI investigation of unexpected somatosensory feedback perturbation during speech

Somatosensory feedback plays a critical role in the coordination of articulator movements for speech production. In response to unexpected resistance to lip or jaw movements during speech, fluent speakers can use the difference between the somatosensory expectations of a speech sound and the actual somatosensory feedback to adjust the trajectories of functionally relevant but unimpeded articulators. In an effort to investigate the neural substrates underlying the somatosensory feedback control of speech, we used an event-related sparse sampling functional magnetic resonance imaging paradigm and a novel pneumatic device that unpredictably blocked subjects' jaw movements. In comparison to speech, perturbed speech, in which jaw perturbation prompted the generation of compensatory speech motor commands, demonstrated increased effects in bilateral ventral motor cortex, right-lateralized anterior supramarginal gyrus, inferior frontal gyrus pars triangularis and ventral premotor cortex, and bilateral inferior posterior cerebellum (lobule VIII). Structural equation modeling revealed a significant increased influence from left anterior supramarginal gyrus to right anterior supramarginal gyrus and from left anterior supramarginal gyrus to right ventral premotor cortex as well as a significant increased reciprocal influence between right ventral premotor cortex and right ventral motor cortex and right anterior supramarginal gyrus and right inferior frontal gyrus pars triangularis for perturbed speech relative to speech. These results suggest that bilateral anterior supramarginal gyrus, right inferior frontal gyrus pars triangularis, right ventral premotor and motor cortices are functionally coupled and influence speech motor output when somatosensory feedback is unexpectedly perturbed during speech production.     

Regional cerebral blood flow as predictor of response to occipital nerve block in cluster headache

BackgroundCluster headache is an excruciating disorder with no cure. Greater occipital nerve blockades can transiently suppress attacks in approximately 50% of patients, however, its mechanism of action remains uncertain, and there are no reliable predictors of treatment response. To address this, we investigated the effect of occipital nerve blockade on regional cerebral blood flow (rCBF), an index of brain activity, and differences between treatment responders and non-responders. Finally, we compared baseline perfusion maps from patients to a matched group of healthy controls.Methods21 male, treatment-naive patients were recruited while in a cluster headache bout. During a pain-free phase between headaches, patients underwent pseudo-continuous arterial spin labelled MRI assessments to provide quantitative indices of rCBF. MRIs were performed prior to and 7-to-21 days following treatment. Patients also recorded the frequency of their headache attacks in a daily paper diary. Neuropsychological assessment including anxiety, depression and quality of life measures was performed in a first, scanning free session for each patient.ResultsFollowing treatment, patients demonstrated relative rCBF reductions in posterior temporal gyrus, cerebellum and caudate, and rCBF increases in occipital cortex. Responders demonstrated relative rCBF increases, compared to non-responders, in medial prefrontal cortex and lateral occipital cortex at baseline, but relative reductions in cingulate and middle temporal cortices. rCBF was increased in patients compared to healthy controls in cerebellum and hippocampus, but reduced in orbitofrontal cortex, insula and middle temporal gyrus.ConclusionsWe provide new mechanistic insights regarding the aetiology of cluster headache, the mechanisms of action of occipital nerve blockades and potential predictors of treatment response. Future investigation should determine whether observed effects are reproducible and extend to other headache disorders.     

MRI观察极高海拔攀登者大脑皮质结构改变

目的 采用MRI观察短暂极高海拔探险所致大脑皮质结构改变。方法 对28名健康青年在极高海拔登山前、后及1个月后随访进行常规T2W及全脑高分辨率三维T1W结构成像扫描,观察显著改变的脑区面积及其厚度,并应用Freesurfer软件进行统计学分析。结果 登山前、后及1个月T2WI均未发现异常;左、右侧大脑半球皮层总萎缩面积（平均萎缩率）分别为（3795.14±35.23）mm² [（9.33±3.19）%]和（2175.42±26.15）mm² [（6.49±2.76）%];左侧舌回皮层萎缩率与进入极高海拔持续时间呈弱相关,其余脑区则呈显著相关。结论 攀登极高海拔可引起大脑皮质萎缩,以优势半球明显,主要见于前额叶。     

Cortical thickness is associated with gait disturbances in cerebral small vessel disease

Although gait disturbances are present in a substantial portion of patients with cerebral small vessel disease (SVD), their pathogenesis has not been clarified as they are not entirely explained by the white matter lesions (WMLs) and lacunar infarcts. The role of cortical thickness in these patients remains largely unknown. We aimed to assess the regions of cortical thickness associated with distinct gait parameters in patients with SVD, and whether these associations were dependent on WMLs and lacunar infarcts. MRI data were obtained from 415 subjects with SVD, aged between 50 and 85 years. We assessed cortical thickness using surface-based cortical thickness analysis, and gait performance using the GAITRite system. Cortical thickness of predominantly the orbitofrontal and ventrolateral prefrontal cortex, the inferior parietal lobe, cingulate areas and visual association cortices was positively related to stride length. Thickness of the primary and supplementary motor cortices and the cingulate cortex was positively related to cadence, while thickness of the orbitofrontal and ventrolateral prefrontal cortex, anterior cingulate cortex and especially the inferior parietal lobe and superior temporal gyrus was negatively related to stride width. The associations with stride length and width were partially explained by the subcortical WMLs and lacunar infarcts. Cortical thickness may therefore be important in gait disturbances in individuals with SVD, with different cortical patterns for specific gait parameters. We suggest that cortical atrophy is part of the disease processes in patients with SVD.     

Regional changes of cortical mean diffusivities with aging after correction of partial volume effects

Accurately measuring the cortical mean diffusivity (MD) derived from diffusion tensor imaging (DTI) at the comprehensive lobe, gyral and voxel level of young, elderly healthy brains and those with Alzheimer's disease (AD) may provide insights on heterogeneous cortical microstructural changes caused by aging and AD. Due to partial volume effects (PVE), the measurement of cortical MD is overestimated with contamination of cerebrospinal fluid (CSF). The bias is especially severe for aging and AD brains because of significant cortical thinning of these brains. In this study, we aimed to quantitatively characterize the unbiased regional cortical MD changes due to aging and AD and delineate the effects of cortical thinning of elderly healthy and AD groups on MD measurements. DTI and T1-weighted images of 14 young, 15 elderly healthy subjects and 17 AD patients were acquired. With the parcellated cortical gyri and lobes from T1 weighted image transformed to DTI, regional cortical MD of all subjects before and after PVE correction were measured. CSF contamination model was used to correct bias of MD caused by PVE. Compared to cortical MD of young group, significant increases of corrected MD for elderly healthy and AD groups were found only in frontal and limbic regions, respectively, while there were significant increases of uncorrected MD all over the cortex. Uncorrected MD are significantly higher in limbic and temporal gyri in AD group, compared to those in elderly healthy group but higher MD only remained in limbic gyri after PVE correction. Cortical thickness was also measured for all groups. The correlation slopes between cortical MD and thickness for elderly healthy and AD groups were significantly decreased after PVE correction compared to before correction while no significant change of correlation slope was detected for young group. It suggests that the cortical thinning in elderly healthy and AD groups is a significant contributor to the bias of uncorrected cortical MD measurement. The established comprehensive unbiased cortical MD profiles of young, elderly healthy subjects and AD patients at the lobe, gyral and voxel level may serve as clinical references for cortical microstructure.     

Headache among patients with HIV disease: prevalence, characteristics, and associations

Background.— Headache is one of the most common medical complaints reported by individuals suffering from human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), but limited and conflicting data exist regarding their prevalence, prototypical characteristics, and relationship to HIV disease variables in the current era of highly active antiretroviral therapy (HAART). Objectives.— The aims of the present cross‐sectional study were to characterize headache symptoms among patients with HIV/AIDS and to assess relations between headache and HIV/AIDS disease variables. Methods.— Two hundred HIV/AIDS patients (49% female; mean age = 43.22 ± 12.30 years; 74% African American) from an internal medicine clinic and an AIDS outreach clinic were administered a structured headache diagnostic interview to assess headache characteristics and features consistent with International Classification of Headache Disorders (ICHD)‐II diagnostic semiologies. They also completed 2 measures of headache‐related disability. Prescribed medications, most recent cluster of differentiation (CD4) cell count, date of HIV diagnosis, possible causes of secondary headache, and other relevant medical history were obtained via review of patient medical records. Results.— One hundred seven patients (53.5%) reported headache symptoms, the large majority of which were consistent with characteristics of primary headache disorders after excluding 4 cases attributable to secondary causes. Among those who met criteria for a primary headache disorder, 88 (85.44%) met criteria for migraine, most of which fulfilled ICHD‐II appendix diagnostic criteria for chronic migraine. Fifteen patients (14.56%) met criteria for episodic or chronic tension‐type headache. Severity of HIV (as indicated by CD4 cell counts), but not duration of HIV or number of prescribed antiretroviral medications, was strongly associated with headache severity, frequency, and disability and also distinguished migraine from TTH. Conclusions.— Problematic headache is highly prevalent among patients with HIV/AIDS, most of which conform to the semiology of chronic migraine, although with some atypical features such as bilateral location and pressing/tightening quality. A low frequency of identifiable secondary causes is likely attributable to reduced frequency of opportunistic infections in the current era of HAART. Disease severity is strongly predictive of headache, highlighting the importance of physician attention to headache symptoms and of patient adherence to treatment. (Headache 2012;52:455‐466)