Cortical thickness, surface area and volume measures in Parkinson's disease, multiple system atrophy and progressive supranuclear palsy

OBJECTIVE Parkinson's disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) are neurodegenerative diseases that can be difficult to distinguish clinically. The objective of the current study was to use surface-based analysis techniques to assess cortical thickness, surface area and grey matter volume to identify unique morphological patterns of cortical atrophy in PD, MSA and PSP and to relate these patterns of change to disease duration and clinical features. METHODS High resolution 3D T1-weighted MRI volumes were acquired from 14 PD patients, 18 MSA, 14 PSP and 19 healthy control participants. Cortical thickness, surface area and volume analyses were carried out using the automated surface-based analysis package FreeSurfer (version 5.1.0). Measures of disease severity and duration were assessed for correlation with cortical morphometric changes in each clinical group. RESULTS Results show that in PSP, widespread cortical thinning and volume loss occurs within the frontal lobe, particularly the superior frontal gyrus. In addition, PSP patients also displayed increased surface area in the pericalcarine. In comparison, PD and MSA did not display significant changes in cortical morphology. CONCLUSION These results demonstrate that patients with clinically established PSP exhibit distinct patterns of cortical atrophy, particularly affecting the frontal lobe. These results could be used in the future to develop a useful clinical application of MRI to distinguish PSP patients from PD and MSA patients

Diffusion tensor imaging of Parkinson's disease, multiple system atrophy and progressive supranuclear palsy: a tract-based spatial statistics study

Although often clinically indistinguishable in the early stages, Parkinson's disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) have distinct neuropathological changes. The aim of the current study was to identify white matter tract neurodegeneration characteristic of each of the three syndromes. Tract-based spatial statistics (TBSS) was used to perform a whole-brain automated analysis of diffusion tensor imaging (DTI) data to compare differences in fractional anisotropy (FA) and mean diffusivity (MD) between the three clinical groups and healthy control subjects. Further analyses were conducted to assess the relationship between these putative indices of white matter microstructure and clinical measures of disease severity and symptoms. In PSP, relative to controls, changes in DTI indices consistent with white matter tract degeneration were identified in the corpus callosum, corona radiata, corticospinal tract, superior longitudinal fasciculus, anterior thalamic radiation, superior cerebellar peduncle, medial lemniscus, retrolenticular and anterior limb of the internal capsule, cerebral peduncle and external capsule bilaterally, as well as the left posterior limb of the internal capsule and the right posterior thalamic radiation. MSA patients also displayed differences in the body of the corpus callosum corticospinal tract, cerebellar peduncle, medial lemniscus, anterior and superior corona radiata, posterior limb of the internal capsule external capsule and cerebral peduncle bilaterally, as well as the left anterior limb of the internal capsule and the left anterior thalamic radiation. No significant white matter abnormalities were observed in the PD group. Across groups, MD correlated positively with disease severity in all major white matter tracts. These results show widespread changes in white matter tracts in both PSP and MSA patients, even at a mid-point in the disease process, which are not found in patients with PD

Safety and Clinical Outcome of Thrombolysis in Ischaemic Stroke Using a Perfusion CT Mismatch between 3 and 6 Hours

It may be possible to thrombolyse ischaemic stroke (IS) patients up to 6 h by using penumbral imaging. We investigated whether a perfusion CT (CTP) mismatch can help to select patients for thrombolysis up to 6 h.A cohort of 254 thrombolysed IS patients was studied. 174 (69%) were thrombolysed at 0-3 h by using non-contrast CT (NCCT), and 80 (31%) at 3-6 h (35 at 3-4.5 h and 45 at 4.5-6 h) by using CTP mismatch criteria. Symptomatic intracerebral haemorrhage (SICH), the mortality and the modified Rankin Score (mRS) were assessed at 3 months. Independent determinants of outcome in patients thrombolysed between 3 and 6 h were identified.The baseline characteristics were comparable in the two groups. There were no differences in SICH (3% v 4%, p = 0.71), any ICH (7% v 9%, p = 0.61), or mortality (16% v 9%, p = 0.15) or mRS 0-2 at 3 months (55% v 54%, p = 0.96) between patients thrombolysed at 0-3 h (NCCT only) or at 3-6 h (CTP mismatch). There were no significant differences in outcome between patients thrombolysed at 3-4.5 h or 4.5-6 h. The NIHSS score was the only independent determinant of a mRS of 0-2 at 3 months (OR 0.89, 95% CI 0.82-0.97, p = 0.007) in patients treated using CTP mismatch criteria beyond 3 h.The use of a CTP mismatch model may help to guide thrombolysis decisions up to 6 h after IS onset

A case-controlled comparison of thrombolysis outcomes between wake-up and known time of onset ischemic stroke patients

Background and Purpose— Wake-up ischemic stroke (WUIS) patients are not thrombolysed even if they meet other criteria for treatment. We hypothesized that patients with WUIS showing no or early ischemic changes on brain imaging will have thrombolysis outcomes comparable with those with known time of symptom onset. Methods— Consecutive sampling of a prospective registry of patients with stroke between January 2009 and December 2010 identified 394 thrombolysed patients meeting predefined inclusion criteria, 326 presenting within 0 to 4.5 hours of symptom onset (Reference Group) and 68 WUIS patients. Inclusion criteria were last seen normal &lt;12 hours or &gt;4.5 hours (WUIS) or presented &lt;4.5 hours (Reference Group), had National Institutes of Health Stroke Scale score ≥5, and no or early ischemic changes on imaging at presentation. The primary outcome measure was the modified Rankin Scale of 0 to 2 at 90 days measured by trained assessors blinded to patient grouping. Other outcome measures were symptomatic intracerebral hemorrhage, modified Rankin Scale 0 to 1, and mortality at 90 days. Results— The groups were comparable for mean age (72.8 versus 73.9 years; P =0.58) and baseline median National Institutes of Health Stroke Scale score (median 13 versus 12; P =0.34). The proportions of patients with modified Rankin Scale 0 to 2 (38% versus 37%; P =0.89) and modified Rankin Scale 0 to 1 (24% versus 16%; P =0.18) at 90 days, any ICH (20% versus 22%; P =0.42) and symptomatic intracerebral hemorrhage (3.4% versus 2.9%; P =1.0) were comparable after adjusting for age, stroke severity, and imaging changes. Only 9/394 (2%) patients were lost to follow-up. Conclusions— Thrombolysis in selected patients with WUIS is feasible, and its outcomes are comparable with those thrombolysed with 0 to 4.5 hours. </jats:sec

An Observational Study of Thrombolysis Outcomes in Wake-Up Ischemic Stroke Patients

Background and Purpose— Wake-up ischemic stroke (WUIS) patients are not eligible for thrombolysis; the a priori hypothesis was that thrombolysis of selected WUIS patients who meet clinical and imaging criteria for treatment is associated with better outcomes. Methods— The sample consisted of consecutive WUIS patients who fulfilled predefined criteria: (1) were last seen normal &gt;4.5 hours and &lt;12 hours before presentation; (2) National Institute of Health Stroke Scale score ≥5; (3) No or early ischemic changes &lt;1/3 middle cerebral artery territory on computed tomography imaging; (4) No absolute contraindications to thrombolysis. The primary outcome measure was the modified Rankin Scale of 0 to 2 at 90 days. Other outcome measures were mortality and symptomatic intracerebral hemorrhage. Results— WUIS patients constituted 10.5% (193/1836) of all stroke admissions. Inclusion criteria were fulfilled by 122 (63%) patients, of whom 68 (56%) were thrombolysed. Thrombolysed and nonthrombolysed patients were comparable for baseline characteristics, but the median baseline National Institute of Health Stroke Scale score was higher in thrombolysed patients (9 versus 11.5; P =0.034). There was no difference in modified Rankin Scale 0 to 2 (25 [37%] versus 14 [26%]; P =0.346), death (10 [15%] versus 14 [26%]; P =0.122), and symptomatic intracerebral hemorrhage (2 versus 0; P =0.204) between thrombolysed and nonthrombolysed patients. After adjusting for age, sex, and baseline National Institute of Health Stroke Scale score thrombolysis was associated with odds ratio of 5.2 (95% confidence interval 1.3–20.3), P =0.017 for modified Rankin Scale 0 to 2 at 90 days and odds ratio of 0.09 (95% confidence interval 0.02–0.44), P =0.003 for death. Conclusions— Thrombolysis in selected WUIS patients is feasible and may have potential of benefit. </jats:sec

Reproducibility of MRI-based white matter tract estimation using multi-fiber probabilistic tractography:effect of user-defined parameters and regions

OBJECTIVE: There is a pressing need to assess user-dependent reproducibility of multi-fibre probabilistic tractography in order to encourage clinical implementation of these advanced and relevant approaches. The goal of this study was to evaluate both intrinsic and inter-user reproducibility of corticospinal tract estimation. MATERIALS AND METHODS: Six clinical datasets including motor functional and diffusion MRI were used. Three users performed an independent tractography analysis following identical instructions. Dice indices were calculated to quantify the reproducibility of seed region, fMRI-based end region, and streamline maps. RESULTS: The inter-user reproducibility ranged 41–93%, 29–94%, and 50–92%, for seed regions, end regions, and streamline maps, respectively. Differences in streamline maps correlated with differences in seed and end regions. Good inter-user agreement in seed and end regions, yielded inter-user reproducibility close to the intrinsic reproducibility (92–97%) and in most cases higher than 80%. DISCUSSION: Uncertainties related to user-dependent decisions and the probabilistic nature of the analysis should be considered when interpreting probabilistic tractography data. The standardization of the methods used to define seed and end regions is a necessary step to improve the accuracy and robustness of multi-fiber probabilistic tractography in a clinical setting. Clinical users should choose a feasible compromise between reproducibility and analysis duration

Implementation of clinically relevant and robust fMRI-based language lateralization: Choosing the laterality index calculation method.

The assessment of language lateralization has become widely used when planning neurosurgery close to language areas, due to individual specificities and potential influence of brain pathology. Functional magnetic resonance imaging (fMRI) allows non-invasive and quantitative assessment of language lateralization for presurgical planning using a laterality index (LI). However, the conventional method is limited by the dependence of the LI on the chosen activation threshold. To overcome this limitation, different threshold-independent LI calculations have been reported. The purpose of this study was to propose a simplified approach to threshold-independent LI calculation and compare it with three previously reported methods on the same cohort of subjects. Fifteen healthy subjects, who performed picture naming, verb generation, and word fluency tasks, were scanned. LI values were calculated for all subjects using four methods, and considering either the whole hemisphere or an atlas-defined language area. For each method, the subjects were ranked according to the calculated LI values, and the obtained rankings were compared. All LI calculation methods agreed in differentiating strong from weak lateralization on both hemispheric and regional scales (Spearman's correlation coefficients 0.59-1.00). In general, a more lateralized activation was found in the language area than in the whole hemisphere. The new method is well suited for application in the clinical practice as it is simple to implement, fast, and robust. The good agreement between LI calculation methods suggests that the choice of method is not key. Nevertheless, it should be consistent to allow a relative comparison of language lateralization between subjects