Effects of different endurance exercise modalities on migraine days and cerebrovascular health in episodic migraineurs: A randomized controlled trial.

Aerobic exercise training is a promising complementary treatment option in migraine and can reduce migraine days and improve retinal microvascular function. Our aim was to elucidate whether different aerobic exercise programs at high vs moderate intensities distinctly affect migraine days as primary outcome and retinal vessel parameters as a secondary. In this randomized controlled trial, migraine days were recorded by a validated migraine diary in 45 migraineurs of which 36 (female: 28; age: 36 (SD:10)/BMI: 23.1 (5.3) completed the training period (dropout: 20%). Participants were assigned (Strata: age, gender, fitness and migraine symptomatology) to either high intensity interval training (HIT), moderate continuous training (MCT), or a control group (CON). Intervention groups trained twice a week over a 12-week intervention period. Static retinal vessel analysis, central retinal arteriolar (CRAE) and venular (CRVE) diameters, as well as the arteriolar-to-venular diameter ratio (AVR) were obtained for cerebrovascular health assessment. Incremental treadmill testing yielded maximal and submaximal fitness parameters. Overall, moderate migraine day reductions were observed (ηP2 = .12): HIT revealed 89% likely beneficial effects (SMD = 1.05) compared to MCT (SMD = 0.50) and CON (SMD = 0.59). Very large intervention effects on AVR improvement (ηP2 = 0.27), slightly favoring HIT (SMD=-0.43) over CON (SMD=0), were observed. HIT seems more effective for migraine day reduction and improvement of cerebrovascular health compared to MCT. Intermittent exercise programs of higher intensities may need to be considered as an additional treatment option in migraine patients.

Increased functional connectivity in the resting-state basal ganglia network after acute heroin substitution.

Reinforcement signals in the striatum are known to be crucial for mediating the subjective rewarding effects of acute drug intake. It is proposed that these effects may be more involved in early phases of drug addiction, whereas negative reinforcement effects may occur more in later stages of the illness. This study used resting-state functional magnetic resonance imaging to explore whether acute heroin substitution also induced positive reinforcement effects in striatal brain regions of protracted heroin-maintained patients. Using independent component analysis and a dual regression approach, we compared resting-state functional connectivity (rsFC) strengths within the basal ganglia/limbic network across a group of heroin-dependent patients receiving both an acute infusion of heroin and placebo and 20 healthy subjects who received placebo only. Subsequent correlation analyses were performed to test whether the rsFC strength under heroin exposure correlated with the subjective rewarding effect and with plasma concentrations of heroin and its main metabolites morphine. Relative to the placebo treatment in patients, heroin significantly increased rsFC of the left putamen within the basal ganglia/limbic network, the extent of which correlated positively with patients' feelings of rush and with the plasma level of morphine. Furthermore, healthy controls revealed increased rsFC of the posterior cingulate cortex/precuneus in this network relative to the placebo treatment in patients. Our results indicate that acute heroin substitution induces a subjective rewarding effect via increased striatal connectivity in heroin-dependent patients, suggesting that positive reinforcement effects in the striatum still occur after protracted maintenance therapy.

Genetic associations with brain cortical thickness in multiple sclerosis.

Multiple sclerosis (MS) is characterized by temporal and spatial dissemination of demyelinating lesions in the central nervous system. Associated neurodegenerative changes contributing to disability have been recognized even at early disease stages. Recent studies show the importance of gray matter damage for the accrual of clinical disability rather than white matter where demyelination is easily visualized by magnetic resonance imaging (MRI). The susceptibility to MS is influenced by genetic risk, but genetic factors associated with the disability are not known. We used MRI data to determine cortical thickness in 557 MS cases and 75 controls and in another cohort of 219 cases. We identified nine areas showing different thickness between cases and controls (regions of interest, ROI) (eight of them were negatively correlated with Kurtzke's expanded disability status scale, EDSS) and conducted genome-wide association studies (GWAS) in 464 and 211 cases available from the two data sets. No marker exceeded genome-wide significance in the discovery cohort. We next combined nominal statistical evidence of association with physical evidence of interaction from a curated human protein interaction network, and searched for subnetworks enriched with nominally associated genes and for commonalities between the two data sets. This network-based pathway analysis of GWAS detected gene sets involved in glutamate signaling, neural development and an adjustment of intracellular calcium concentration. We report here for the first time gene sets associated with cortical thinning of MS. These genes are potentially correlated with disability of MS.

No abnormalities of intrinsic brain connectivity in the interictal phase of migraine with aura.

BACKGROUND AND PURPOSE: Functional neuroimaging studies have shown hyperresponsiveness of cortical areas to visual stimuli in migraine patients with aura outside of attacks. This may be a key feature in the initiation of aura episodes and possibly also migraine headache attacks. It is unknown if cortical dysfunction is present at rest, i.e. in the absence of any external stimuli. Functional magnetic resonance imaging is a powerful technique for evaluating resting state functional connectivity, i.e. coherence of brain activity across cerebral areas. The objective of this study was to investigate resting-state functional brain connectivity in migraineurs with aura outside of attacks using functional magnetic resonance imaging. METHODS: Forty patients suffering from migraine with visual aura and 40 individually age and gender matched healthy controls with no history or family history of migraine were investigated. Following advanced denoising, the data were analyzed both in a hypothesis-driven fashion, testing for abnormalities involving 27 different brain areas of potential relevance to migraine with aura including the cortical visual areas, the amygdala and peri-aqueductal grey matter, and in a data-driven exploratory fashion (dual regression) in order to reveal any possible between-group differences of resting state networks. Age, gender, attack frequency and disease duration were included as nuisance variables. RESULTS: No differences of functional connectivity were found between patients and controls. CONCLUSIONS: The previously reported increased cortical hyperresponsivity in the interictal phase of migraine with aura is unlikely to be caused by abnormalities of intrinsic brain connectivity. The interictal migraine aura brain may be abnormally functioning only during exposure to external stimuli.

The Relationship of Hemoglobin Levels, Delirium and Cognitive Status in Hospitalized Geriatric Patients: Results from the CRIME Study.

OBJECTIVE: Delirium is a frequent clinical complication in geriatric patients admitted to the hospital, because of the simultaneous presence and synergistic effect of predisposing and precipitating factors. Also anaemia is a common concern in geriatric population. The aim of this study was to investigate the association between anaemia (precipitating factor) and delirium in a sample of Italian older hospitalized patients with different degree of cognitive impairment (predisposing factor). DESIGN, SETTING, PARTICIPANTS: Cross-sectional analysis of 1069 participants enrolled in the CRIME study, with assessment of hemoglobin levels at hospital admission. MEASUREMENTS: Delirium was assessed using DSM-IV criteria, whereas cognitive status was categorized as dementia, cognitive impairment or normal, according to clinical history, specific treatment and MMSE score. Anaemia was defined according to sex-specific WHO criteria. The association of hemoglobin levels and delirium was investigated with multivariable logistic regression models. RESULTS: Mean age of study participants was 81.4±7.2 years, 52.2% had prevalent anaemia, 6.1% had delirium. According to cognitive status 20.8% had dementia and 40.9% had cognitive impairment. Overall there was no association between anaemia and delirium. However, among patients with cognitive impairment (MMSE <24, no dementia) anaemia was significantly associated with the likelihood of delirium (p<0.006). Multivariate logistic regression analysis, adjusted for potential confounders, showed in these patients a graded increased risk of delirium according to anaemia severity with an almost six-fold increased risk of delirium in moderate-severe anaemia (OR 5.95, 95% CI:1.15-30.73). CONCLUSION: In older patients with cognitive impairment moderate-severe anaemia is independently associated with the likelihood of delirium. Further studies should investigate if anaemia correction would translate in delirium risk reduction.

Six-year follow-up of a case series with non-communicating syringomyelia in multiple sclerosis.

BACKGROUND: Non-communicating syringomyelia (NCS) has occasionally been described in case reports and small case series as an incidental finding of spinal cord (SC) pathology in patients with multiple sclerosis (MS), but only little is known on the clinical course and progression of NCS, and in more general terms on the prognosis of patients with MS and NCS. METHODS: Nine patients with MS with known NCS at baseline and a control group of 18 age-, sex- and disease course-matched patients with MS without NCS were recruited for a follow-up visit after 6 years. All 27 patients underwent clinical examination and brain magnetic resonance imaging (MRI), and 8/9 patients with NCS were additionally studied with MRI of the SC. MRI data were analysed for changes in length and maximal cross-sectional area of the NCS, lesion volumes of the brain and cord as well as for volumetric metrics of the whole brain (using SIENAX), the cerebellum and medulla oblongata (using ECCET). RESULTS: NCS did not significantly change in size when corrected for multiple comparisons. The clinical data (annual relapse rate, EDSS and disease duration) and MRI metrics (T2 and T1 lesion load; whole brain, cerebellar and medulla oblongata volumes as well as their percentage volume change per year) did not significantly differ between patients with MS with or without NCS. CONCLUSION: The stable findings regarding size and shape of the syrinx and lack of distinguishing MRI and clinical features support the assumption that NCS is not defining a prognostically or pathogenetically distinct subgroup of patients with MS.

Review of corpus callosum topography, analysis of diffusion values for the different callosal fibers and sex differences.

Conventional MRI shows the morphology of the corpus callosum (CC), but does not reveal cortical connectivity or structural information on the CC. Here, we applied diffusion tensor imaging (DTI) in conjunction with a tract-tracing algorithm to incorporate cortical connectivity information on the CC in 40 subjects and to detect the main area and sex structural differences. CC parcellation was based on trajectories to different cortical (prefrontal, frontal motor/premotor/supplementary motor connections, parieto-occipital, temporal) and sub-cortical areas (capsular/basal ganglia connections). In agreement with recent DTI studies, we found that motor fibers occupy a much larger portion of the CC than previously believed on the basis of anatomical data. Differences in anisotropy values were instead in agreement with previous morphological evidence of smaller fibers in the anterior and posterior portions of the CC. The main sex difference was observed in anisotropy values in frontal fibers that proved to be lower in females than in males. Statistically significant differences in the regional diffusion parameters and between sexes give rise to many important questions regarding fiber organization patterns, CC microstructure and the functional relevance of these differences and provide evidence for the role of DTI, which reaches beyond the information given by morphological analysis.