White matter microstructure shows sex differences in late childhood: Evidence from 6,797 children

Sex differences in white matter microstructure have been robustly demonstrated in the adult brain using both conventional and advanced diffusion-weighted magnetic resonance imaging (dMRI) approaches. However, the effect of sex on white matter microstructure prior to adulthood remains poorly understood, with previous developmental work focusing on conventional microstructure metrics and yielding mixed results. Here we thoroughly and rigorously characterized sex differences in white matter microstructure among over 6,000 children from the Adolescent Brain Cognitive Development (ABCD) Study who were between 9 and 10 years old. Microstructure was quantified using both the conventional model - diffusion tensor imaging (DTI) - and an advanced model, restriction spectrum imaging (RSI). DTI metrics included fractional anisotropy (FA) and mean, axial, and radial diffusivity (MD, AD, RD). RSI metrics included normalized isotropic, directional, and total intracellular diffusion (N0, ND, NT). We found significant and replicable sex differences in DTI or RSI microstructure metrics in every white matter region examined across the brain. The impact of sex on FA was regionally specific. Across white matter regions, boys exhibited greater MD, AD, and RD than girls, on average. Girls displayed increased N0, ND, and NT compared to boys, on average, suggesting greater cell and neurite density in girls. Together, these robust and replicable findings provide an important foundation for understanding sex differences in health and disease.

Deep brain stimulation modulates hypothalamic-brainstem fibers in cluster headache: case report

Hypothalamic deep brain stimulation (DBS) has been used for more than a decade to treat cluster headache (CH) but its mechanisms remain poorly understood. The authors have successfully treated a patient with CH using hypothalamic DBS and found that the contact used for chronic stimulation was located in a white matter region posterior to the mammillary bodies. Fiber tracts crossing that region were the medial forebrain bundle and those interconnecting the hypothalamus and brainstem, including the dorsal longitudinal fasciculus. Because the stimulation of axons is an important mechanism of DBS, some of its clinical effects in CH may be related to the stimulation of fibers interconnecting the hypothalamus and brainstem.

Abstract TP67: Safety of Intravenous Alteplase in Chronic Intracranial Hemorrhage: a Five Year Multicenter Study

Introduction: Although, the recently updated tPA label removed a history of intracranial hemorrhage (ICH) as a contraindication, there is very limited data on the safety of intravenous thrombolysis in chronic ICH. The purpose of this study is to evaluate the safety of intravenous tPA among patient with chronic ICH. Methods: We analyzed consecutive patients who received intravenous tPA for stroke symptoms at three tertiary stroke centers in a five-year period. Patients without imaging confirmation of the old hemorrhage were excluded from the study. Outcome measures in our study were occurrences of symptomatic ICH and were defined according to European Cooperative Acute Stroke Study (ECASS)-III criteria combined with clinical deterioration of ≥4 points on NIHSS or death. Results: Out of 1212 post tPA patients evaluated in this study, seven patients (age 72 ± 11, four men, median NIHSS 5, IQR [2-8], volume ICH 1-21 cm3) had a history and neuroimaging findings consistent with an old ICH. Patients with old ICH did not differ in terms of rates of symptomatic ICH (0%, 95%CI (0-32%) by the adjusted Wald method versus 3.6%, p=0.61) and in-hospital mortality (0% versus 6.0%, p=0.5) when compared with the rest of patients. There was no significance difference between two groups in terms of age and admission NIHSS. Out of seven patients, five patients had ICH in basal ganglia and two patients had ICH in pre-ventricular white matter region. Discussion: Our study indicates that administration of intravenous tPA is safe among patients with a history of chronic ICH. More studies are needed to define chronic in such a setting.

Maturation of White Matter is Associated with the Development of Cognitive Functions during Childhood

In the human brain, myelination of axons continues until early adulthood and is thought to be important for the development of cognitive functions during childhood. We used diffusion tensor MR imaging and calculated fractional anisotropy, an indicator of myelination and axonal thickness, in children aged between 8 and 18 years. Development of working memory capacity was positively correlated with fractional anisotropy in two regions in the left frontal lobe, including a region between the superior frontal and parietal cortices. Reading ability, on the other hand, was only correlated with fractional anisotropy in the left temporal lobe, in the same white matter region where adults with reading disability are known to have lower fractional anisotropy. Both the temporal and the frontal regions were also correlated with age. These results show that maturation of white matter is an important part of brain maturation during childhood, and that maturation of relatively restricted regions of white matter is correlated with development of specific cognitive functions.

Metabolic differences between multiple sclerosis subtypes measured by quantitative MR spectroscopy

We used quantitative magnetic resonance (MR) spectroscopic imaging with T1-based image segmentation to evaluate the subtypes of multiple sclerosis (MS) (eight patients each group of relapsing-remitting [RR], secondary progressive [SP] and primary progressive [PP]). There was no significant difference in age between the PP group with the RR, SP or control group. We found that the metabolite ratio of choline/NA from the periventricular white matter region was not significantly different between the RR and SP groups. Using an ANOVA, the ratios of periventricular choline/NA or creatine/NA of these combined groups were significantly higher than the PP and control groups. Quantification of these data suggest that the major cause of the elevation of these parameters is due to an increase in choline and creatine in the RR group while NA is decreased in the SP group. Thus, early PP disease appears to be relatively intact with respect to neuronal loss.