Retinal nerve fibre layer thickness correlates with brain white matter damage in multiple sclerosis: a combined optical coherence tomography and diffusion tensor imaging study.

We investigated the association of retinal nerve fibre layer thickness (RNFL) with white matter damage assessed by diffusion tensor imaging (DTI). Forty-four MS patients and 30 healthy subjects underwent optical coherence tomography. DTI was analysed with a voxel-based whole brain and region-based analysis of optic radiation, corpus callosum and further white matter. Correlations between RNFL, fractional anisotropy (FA) and other DTI-based parameters were assessed in patients and controls. RNFL correlated with optic radiation FA, but also with corpus callosum and remaining white matter FA. Our findings demonstrate that RNFL changes indicate white matter damage exceeding the visual pathway.

Functional and structural brain changes in anti-N-methyl-D-aspartate receptor encephalitis.

OBJECTIVE: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune encephalitis with a characteristic neuropsychiatric syndrome and severe and prolonged clinical courses. In contrast, standard clinical magnetic resonance imaging (MRI) remains normal in the majority of patients. Here, we investigated structural and functional brain changes in a cohort of patients with anti-NMDAR encephalitis. METHODS: Twenty-four patients with established diagnosis of anti-NMDAR encephalitis and age- and gender-matched controls underwent neuropsychological testing and multimodal MRI, including T1w/T2w structural imaging, analysis of resting state functional connectivity, analysis of white matter using diffusion tensor imaging, and analysis of gray matter using voxel-based morphometry. RESULTS: Patients showed significantly reduced functional connectivity of the left and right hippocampus with the anterior default mode network. Connectivity of both hippocampi predicted memory performance in patients. Diffusion tensor imaging revealed extensive white matter changes, which were most prominent in the cingulum and which correlated with disease severity. In contrast, no differences in T1w/T2w structural imaging and gray matter morphology were observed between patients and controls. INTERPRETATION: Anti-NMDAR encephalitis is associated with characteristic alterations of functional connectivity and widespread changes of white matter integrity despite normal findings in routine clinical MRI. These results may help to explain the clinicoradiological paradox in anti-NMDAR encephalitis and advance the pathophysiological understanding of the disease. Correlation of imaging abnormalities with disease symptoms and severity suggests that these changes play an important role in the symptomatology of anti-NMDAR encephalitis.

Angiotensin II type 2 receptor mediates sex differences in mice renal interlobar arteries response to angiotensin II.

OBJECTIVE: Functional sex differences are described in several vascular beds. In the case of renal vessels, sex differences could influence processes like regulation of blood pressure and ion balance. Angiotensin II and nitric oxide are important regulators of renal vascular tone. Females have higher nitric oxide synthase expression, nitric oxide bioavailability and ratio of angiotensin II type 2/type 1 receptors. Thus, our objective was to examine whether renal interlobar arteries present sex differences in their response to angiotensin II, and whether angiotensin II type 2 receptors play a role in such differences. METHODS: We investigated the isometric contraction and relaxation of interlobar arteries from female and male mice under blockade of nitric oxide synthases and angiotensin II type 2 receptors. We also investigated the expression of angiotensin II receptors (type 1 and 2) and endothelial nitric oxide synthase. RESULTS: Significantly less intense contraction to angiotensin II were seen in arteries from females in comparison to male mice. Inhibition of nitric oxide synthases and endothelial removal abolished this difference. Angiotensin II type 2 receptors blockade enhanced contraction to angiotensin II in females, but not in males. Endothelial-dependent vasodilation was more dependent on nitric oxide in females than in males. Expression of angiotensin II type 1 and type 2 receptors was similar between sexes. Expression of endothelial nitric oxide synthase was higher in females. CONCLUSION: A sex-specific, nitric oxide-mediated effect via angiotensin II type 2 receptors underlies the sex differences in the response of interlobar arteries to angiotensin II. Our findings may help understanding sex differences in renal hemodynamics and blood pressure control.

Dynamics of saccade parameters in multiple sclerosis patients with fatigue.

Fatigue is one of the most frequent and disabling symptoms in multiple sclerosis (MS). Its pathophysiology remains poorly understood and objective measures to quantify fatigue are unavailable to date. To investigate whether analysis of ocular motor movements can provide diagnostic information in MS patients with fatigue, 37 MS patients (21 female, age 44 ± 9 years) and 20 age- and gender-matched healthy controls were prospectively recruited. Fatigue was assessed with the fatigue severity scale (FSS). Twenty-five MS patients were fatigued (defined as FSS ≥ 4) and 12 MS patients were not. Subjects performed a saccadic fatigue task that required execution of uniform saccades over a period of 10 min. Saccadic amplitude, latency and peak velocities during the task were analysed and selected parameters were tested in a receiver operating characteristic (ROC) analysis. Fatigued patients showed a significantly larger decrease of saccadic peak velocity and amplitude when compared to patients without fatigue and healthy controls. Furthermore, fatigued patients showed significantly longer latencies compared to non-fatigued patients and healthy controls. Peak velocity change over time and latencies correlated with FSS scores. The best parameter to discriminate between fatigued and non-fatigued patients was peak velocity change over time (ROC; area under the curve = 0.857). Assessment of peak velocity, amplitude and latency in a saccade fatigue task is a promising approach for quantifying fatigue in MS patients.