Arzu Ceylan Has

Effect of clozapine on white matter integrity in patients with schizophrenia: A diffusion tensor imaging study

Several diffusion tensor imaging (DTI) studies have reported disturbed white matter integrity in various brain regions in patients with schizophrenia, whereas only a few studied the effect of antipsychotics on DTI measures. The aim of this study was to investigate the effect of 12 weeks of clozapine treatment on DTI findings in patients with schizophrenia, and to compare the findings with those in unaffected controls. The study included 16 patients with schizophrenia who were assessed with the Positive and Negative Syndrome Scale, a neurocognitive test battery, and DTI at baseline and 12 weeks after the initiation of clozapine treatment. Eight unaffected controls were assessed once with the neurocognitive test battery and DTI. Voxel-wise analysis of DTI data was performed via tract-based spatial statistics (TBSS). Compared with the control group, the patient group exhibited lower fractional anisotropy (FA) in 16 brain regions, including the bilateral superior longitudinal fasciculi, inferior fronto-occipital fasciculi, superior and inferior parietal lobules, cingulate bundles, cerebellum, middle cerebellar peduncles, and left inferior longitudinal fasciculus, whereas the patients had higher FA in six regions, including the right parahippocampus, left anterior thalamic radiation, and right posterior limb of the internal capsule before clozapine treatment. After 12 weeks of treatment with clozapine, white matter FA was increased in widespread brain regions. In two of the regions where FA had initially been lower in patients compared with controls (left inferior fronto-occipital fasciculus and superior parietal lobule), clozapine appeared to increase FA. An improvement in semantic fluency was correlated with the increase in FA value in the left inferior fronto-occipital fasciculus. An increase in FA following 12 weeks of treatment with clozapine suggests that this treatment alters white matter microstructural integrity in patients with schizophrenia previously treated with typical and/or atypical antipsychotics and, in some locations, reverses a previous deficit.

Ischemic Stroke Phenotype in Patients With Nonsustained Atrial Fibrillation

Background and Purpose— The widespread use of ambulatory cardiac monitoring has not only increased the detection of high-risk arrhythmias like persistent and paroxysmal atrial fibrillation (AF), but also made it possible to identify other aberrations such as short-lasting (<30 seconds) irregular runs of supraventricular tachycardia. Ischemic stroke phenotype might be helpful in understanding whether these nonsustained episodes play a similar role in stroke pathophysiology like their persistent and paroxysmal counterparts. Methods— In a consecutive series of patients with ischemic stroke, we retrospectively determined clinical and imaging features associated with nonsustained AF (n=126), defined as <30-second-lasting supraventricular tachyarrhythmias with irregular RR interval on 24-hour Holter monitoring, and compared them to patients with persistent/paroxysmal AF (n=239) and no AF (n=246). Results— Patients with persistent/paroxysmal AF significantly differed from patients with nonsustained AF by a higher prevalence of female sex (odds ratio [95% confidence interval], 1.8 [1.1–2.9]), coronary artery disease (1.9 [1.1–3.0]), and embolic imaging features (2.7 [1.1–6.5]), and lower frequency of smoking (0.4 [0.2–0.8]) and hyperlipidemia (0.5 [0.3–0.8]). In contrast, patients with no AF were younger (0.5 [0.4–0.6] per decade) and more likely to be male (1.7 [1.0–2.8]) in comparison with nonsustained AF population. The prevalence of nonsustained AF was similar among cryptogenic and noncryptogenic stroke patients (32% versus 29%). Voxel-wise comparison of lesion probability maps revealed no significant difference between cryptogenic stroke patients with and without nonsustained AF. Conclusions— Clinical features of patients with nonsustained AF exhibited an intermediary phenotype in between patients with persistent/paroxysmal AF and no AF. Furthermore, imaging features did not entirely resemble patterns observed in patients with longer durations of AF.

Default mode network connectivity is linked to cognitive functioning and CSF Aβ1–42 levels in Alzheimer’s disease

BACKGROUND Changes in the default mode network (DMN) activity are early features of Alzheimers disease (AD) and may be linked to AD-specific Aβ pathology. METHODS Cognitive profiles; DMN connectivity alterations; and cerebrospinal fluid (CSF) amyloid beta (Aβ)1-42, total tau, phosphorylated tau 181, and α-synuclein levels were studied in 21 patients with AD and 10 controls. RESULTS DMN activity is altered in AD. Posterior cingulate cortex (PCC) functional connectivity with other parts of DMN was related to cognitive function scores. The reduction of connectivity of the dorsal PCC with the retrosplenial cortex on the right side was closely related to decreased CSF Aβ1-42 levels in patients with AD. CONCLUSIONS The dorsal PCC and retrosplenial cortex may have special importance in the pathogenesis and cognitive findings of AD.

Tract-based spatial statistics of diffusion tensor imaging in hereditary spastic paraplegia with thin corpus callosum reveals widespread white matter changes.

PURPOSE We aimed to investigate white matter diffusivity abnormalities in hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) patients in relation with electrophysiological findings. MATERIALS AND METHODS Brain magnetic resonance imaging (MRI) and diffusion tensor imaging were performed on four HSP-TCC patients and 15 age-matched healthy subjects. Voxel-wise statistical analysis of fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity maps were carried out using tract-based spatial statistics, and significantly affected voxels were labeled using a human white matter atlas. Conventional nerve conduction studies, cortical and spinal-root motor evoked potentials, and somatosensory evoked potentials were examined in three patients. RESULTS On MRI, all patients had a thin corpus callosum with mild T2 hyperintensity in the periventricular white matter. Compared to control subjects, we detected widespread significant decreases in fractional anisotropy, and increases in axial diffusivity, radial diffusivity, and mean diffusivity in structures including in the corpus callosum, motor, and non-motor white matter tracts in HSP-TCC patients. Several different regions showed significant reduction in axial diffusivity. Electrophysiological studies revealed prolonged central motor conduction times and reduced cortical motor evoked potentials and somatosensory evoked potentials amplitudes in all patients. One patient had low sural sensory nerve action potential suggestive of axonal neuropathy. CONCLUSION Tract-based spatial statistics of diffusion tensor imaging revealed a more widespread involvement of white matter in HSP-TCC patients than has previously been detected by conventional MRI. This may explain the broad spectrum of electrophysiological and neurological abnormalities that complicate hereditary spastic paraplegia in these patients.

Effect of Patient Sex on White Matter Alterations in Unilateral Medial Temporal Lobe Epilepsy with Hippocampal Sclerosis Assessed by Diffusion Tensor Imaging

BACKGROUND AND PURPOSE: Studies shows ictal behavior and symptoms are affected by patient sex in temporal lobe epilepsy. The purpose of our study was to determine whether alterations in the WM as assessed by DTI display different patterns in male and female patients with unilateral HS. MATERIALS AND METHODS: Patients with unilateral HS were categorized as women with right HS (n=12), men with right HS (n=10), women with left HS (n=12), and men with left HS (n=10). DTI of the brain along 64 noncollinear directions was obtained from 44 patients and 37 sex-matched control participants. We used TBSS to analyze whole-brain WM. Regions with significant changes of FA and MD, and their mean FA, MD, total number of significant voxels, and asymmetry indices were determined for each group. RESULTS: All groups showed bilateral and extensive reductions of FA and elevated MD in the WM, more prominent ipsilateral to the affected hippocampus. The total number of voxels with decreased FA in patients compared with that of control participants was higher in women with right HS (24,727 vs 5,459) and in men with left HS (27,332 vs 14,013) than in their counterparts. Changes in MD associated with right HS were more extensive in both men and women (right vs left HS, women: 16,926 vs 5,458; men: 5,389 vs 4,764) than in those with left HS. In patients with right HS, the ipsilateral cingulum, uncinate fasciculus, internal and external capsules, and right acoustic radiation were involved extensively in women. CONCLUSIONS: Women and men showed different patterns in extent of WM alterations associated with HS.

Assessment of whole-brain white matter by DTI in autosomal recessive spastic ataxia of Charlevoix-Saguenay.

BACKGROUND AND PURPOSE: Extension and characteristics of WM involvement other than the brain stem remain inadequately investigated in ARSACS. The aim of this study was to investigate whole-brain WM alterations in patients with ARSACS. MATERIALS AND METHODS: Nine Turkish unrelated patients with ARSACS and 9 sex- and age-matched healthy control participants underwent neurologic examination, molecular studies, electrophysiologic studies, and DTI of the brain. TBSS was used for whole-brain voxelwise analysis of FA, AD, RD, mean diffusivity of WM. Tractographies for the CST and TPF were also computed. RESULTS: Molecular studies revealed 8 novel mutations (3 nonsense, 4 missense, and 1 frameshift insertion) and a missense variation in the SACS gene. Thick TPF displaced and compressed the CST in the pons. The TPF had increased FA, decreased RD, and increased AD, which may be attributed to hypertrophy and/or hypermyelination. Widespread decreased FA and increased RD, suggesting demyelination, was found in the limbic, commissural, and projection fibers. In addition to demyelination, CST coursing cranial and caudal to the pons also showed a marked decrease in AD, suggesting axonal degeneration. Electrophysiologic studies revealed findings that concur with demyelination and axonal involvement. CONCLUSIONS: In addition to developmental changes of the TPF and their effects on the CST in the brain stem, axonal degeneration mainly along the pyramidal tracts and widespread demyelination in WM also occur in patients with ARSACS. Widespread tissue damage may be associated with extensive loss of sacsin protein in the brain and may explain a wide range of progressive neurologic abnormalities in patients with ARSACS.

Structural brain alterations of Down's syndrome in early childhood evaluation by DTI and volumetric analyses.

AbstractObjectivesTo provide an initial assessment of white matter (WM) integrity with diffusion tensor imaging (DTI) and the accompanying volumetric changes in WM and grey matter (GM) through volumetric analyses of young children with Down’s syndrome (DS).MethodsTen children with DS and eight healthy control subjects were included in the study. Tract-based spatial statistics (TBSS) were used in the DTI study for whole-brain voxelwise analysis of fractional anisotropy (FA) and mean diffusivity (MD) of WM. Volumetric analyses were performed with an automated segmentation method to obtain regional measurements of cortical volumes.ResultsChildren with DS showed significantly reduced FA in association tracts of the fronto-temporo-occipital regions as well as the corpus callosum (CC) and anterior limb of the internal capsule (p < 0.05). Volumetric reductions included total cortical GM, cerebellar GM and WM volume, basal ganglia, thalamus, brainstem and CC in DS compared with controls (p < 0.05).ConclusionThese preliminary results suggest that DTI and volumetric analyses may reflect the earliest complementary changes of the neurodevelopmental delay in children with DS and can serve as surrogate biomarkers of the specific elements of WM and GM integrity for cognitive development.Key Points• DS is the most common genetic cause of intellectual disability. • WM and GM structural alterations represent the neurological features of DS. • DTI may identify the earliest aging process changes. • DTI-volumetric analyses can serve as surrogate biomarkers of neurodevelopment in DS.

The association of cognitive impairment with gray matter atrophy and cortical lesion load in clinically isolated syndrome

BACKGROUND Multiple sclerosis can impair cognition from the early stages and has been shown to be associated with gray matter damage in addition to white matter pathology. OBJECTIVES To investigate the profile of cognitive impairment in clinically isolated syndrome (CIS), and the contribution of cortical inflammation, cortical and deep gray matter atrophy, and white matter lesions to cognitive decline. METHODS Thirty patients with clinically isolated syndrome and twenty demographically- matched healthy controls underwent neuropsychologic assessment through the Rao Brief Repeatable Battery, and brain magnetic resonance imaging with double inversion recovery using a 3T scanner. RESULTS Patients with clinically isolated syndrome performed significantly worse than healthy controls on tests that evaluated verbal memory, visuospatial learning and memory, and verbal fluency. Significant deep gray matter atrophy was found in the patients but cortical volume was not lower than the controls. Visual memory tests correlated with the volume of the hippocampus, cerebral white matter and deep gray matter structures and with cerebellar cortical atrophy. Cortical or white matter lesion load did not affect cognitive test results. CONCLUSION In our patients with CIS, it was shown that cognitive impairment was mainly related to cerebral white matter, cerebellar cortical and deep gray matter atrophy, but not with cortical inflammation, at least in the early stage of disease.

White matter involvement beyond the optic nerves in CRION as assessed by diffusion tensor imaging.

Background: Chronic relapsing inflammatory optic neuropathy (CRION) is an inflammatory optic neuropathy, characterized by relapses and remissions in patients with normal brain and spinal magnetic resonance imaging (MRI). Discrepancy from other demyelinating diseases is important, and it is still uncertain whether CRION is restricted to the optic pathways or it affects other brain white matter (WM) structures. Objective: To assess WM structure in patients with CRION by using diffusion tensor imaging (DTI). Methods: DTI was performed in six CRION patients and six age- and sex-matched healthy controls on a 3 T scanner. Tract-based spatial statistics (TBSS) was used for voxelwise statistical analysis of DTI data. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) measures were obtained. Results: TBSS analysis revealed two different patterns of WM alterations in patients with CRION. The optic chiasm and connected structures had significantly higher FA and lower RD, AD and MD in the patients than in the healthy controls. On the other hand, anterior frontal bundles of inferior fronto-occipital tracts, left uncinate fascicule and internal capsule showed decreased FA and increased RD. No correlation was found between the clinical variables and diffusion measures. Conclusion: WM appearing normal on brain MRI shows widespread abnormalities in a cohort of CRION patients as assessed by DTI.

Assessment of the effect of cigarette smoking on regional brain volumes and lesion load in patients with clinically isolated syndrome

Purpose: Smoking has been associated with an increased risk of developing multiple sclerosis, disease progression and clinical disability. We detected the effects of smoking on regional brain volumes and lesion load in patients with clinically isolated syndrome using quantitative magnetic resonance imaging. Materials and Methods: Smoker patients (n = 16), smoker healthy controls (n = 13), non-smoker patients (n = 17) and non-smoker healthy controls (n = 14) underwent magnetic resonance imaging and neocortical volumes were measured. Lesion load was calculated in terms of number and volume of white matter hyperintensities. Results: Smoking was associated with increased gray matter volumes in several regions of the brain. A tendency towards greater lesion load in smoker patients was found. Smoking duration was significantly negatively correlated with intracranial volume and left hemisphere cortical gray matter volume. There was no relationship between regional brain volumes and clinical disability scores, lesion load duration of the disease and degree of smoking exposure. Conclusions: Clinically isolated syndrome related regional brain atrophy might vary in extent and severity with smoking. Despite increased lesion load, less cortical and deep gray matter damage with a possible neuroprotective effect occurs in smoking.