Predictors of manual dexterity at 3 and 6 months after stroke: integration of clinical, neurophysiological, and neuroimaging factors.

This retrospective study aimed to predict dexterity at 3 and 6 months post-stroke by integrating clinical, neurophysiological, and neuroimaging factors. We included 126 patients with first-ever, unilateral, and supratentorial stroke. Demographic, stroke characteristics, and initial clinical assessment variables [Mini-mental state examination and Fugl-Meyer Assessment Upper Extremity (FMA-UE)] were evaluated 2 weeks after stroke. Dexterity, measured using the Manual Function Test (MFT) hand subscore, was the primary outcome. The neurophysiological variables, upper limb somatosensory evoked potential (SEP) and motor evoked potential (MEP), were assessed 2 weeks post-stroke. The neuroimaging variable, fractional anisotropy (FA) of the corticospinal tract (CST), was assessed 3 weeks post-stroke. Multiple regression analysis revealed significant predictors for improved dexterity at 3 and 6 months post-stroke, including younger age, higher FMA-UE score, presence of waveforms in the SEP and MEP, and higher FA values in the CST (adjusted R 2  = 0.776, P  < 0.001 at 3 months; adjusted R 2  = 0.668, P  < 0.001 at 6 months; where MEP, SEP, and FA accounted together for an additional 0.079 and 0.166 of variance beyond age and FMA-UE, respectively). Subgroup analysis was conducted by categorizing the participants based on their initial hand function: those with no hand function (MFT hand subscore = 0) (N = 60) and those with a score >0 (N = 51). Initial FMA-UE was a primary predictive factor regardless of the time point or initial severity, whereas the presence of MEP was a significant predictor only in the group with no initial hand dexterity.

The Quinazoline Otaplimastat (SP-8203) Reduces the Hemorrhagic Transformation and Mortality Aggravated after Delayed rtPA-Induced Thrombolysis in Cerebral Ischemia.

Acute ischemic stroke is the leading cause of morbidity and mortality worldwide. Recombinant tissue plasminogen activator (rtPA) is the only agent clinically approved by FDA for patients with acute ischemic stroke. However, delayed treatment of rtPA (e.g., more than 3 h after stroke onset) exacerbates ischemic brain damage by causing intracerebral hemorrhage and increasing neurotoxicity. In the present study, we investigated whether the neuroprotant otaplimastat reduced delayed rtPA treatment-evoked neurotoxicity in male Sprague Dawley rats subjected to embolic middle cerebral artery occlusion (eMCAO). Otaplimastat reduced cerebral infarct size and edema and improved neurobehavioral deficits. In particular, otaplimastat markedly reduced intracerebral hemorrhagic transformation and mortality triggered by delayed rtPA treatment, consequently extending the therapeutic time window of rtPA. We further found that ischemia-evoked extracellular matrix metalloproteases (MMPs) expression was closely correlated with cerebral hemorrhagic transformation and brain damage. In ischemic conditions, delayed rtPA treatment further increased brain injury via synergistic expression of MMPs in vascular endothelial cells. In oxygen-glucose-deprived endothelial cells, otaplimastat suppressed the activity rather than protein expression of MMPs by restoring the level of tissue inhibitor of metalloproteinase (TIMP) suppressed in ischemia, and consequently reduced vascular permeation. This paper shows that otaplimastat under clinical trials is a new drug which can inhibit stroke on its own and extend the therapeutic time window of rtPA, especially when administered in combination with rtPA.

Effects of aging on brain networks during swallowing: general linear model and independent component analyses.

Swallowing disorders occur more frequently in older adults. However, the effects of the aging process on neural activation when swallowing are unclear. We aimed to identify neural regions activated during swallowing and evaluate changes in neural activation and neural networks with aging. Using a general linear model (GLM) and independent component (IC) analyses, blood oxygen level-dependent (BOLD) signals were observed in the lateral precentral gyrus, postcentral gyrus, anterior insular cortices, supramarginal gyri, and medial frontal gyrus during swallowing. The right thalamus and anterior cingulate gyri were found to be active areas by GLM and IC analyses, respectively. In the correlational analyses, age was negatively correlated with BOLD signals of the lateral precentral gyri, postcentral gyri, and insular cortices in swallowing tasks. Additionally, correlation analyses between ICs of all participants and age revealed negative correlations in the right supramarginal gyrus, both anterior cingulate cortices, putamen, and cerebellum. In the network analysis, the BOLD signal positively correlated with age in the default mode network (DMN), and was negatively correlated in the lateral precentral gyri, postcentral gyri, and insular cortices. The amplitude of low-frequency fluctuations was significantly decreased in the DMN and increased in swallowing-related areas during swallowing tasks. These results suggest that aging has negative effects on the activation of swallowing-related regions and task-induced deactivation of the DMN. These changes may be used to detect early functional decline during swallowing.

Shape and Volumetric Differences in the Corpus Callosum between Patients with Major Depressive Disorder and Healthy Controls.

OBJECTIVE: This study aimed to investigate the morphometric differences in the corpus callosum between patients with major depressive disorder (MDD) and healthy controls and analyze their relationship to gray matter changes. METHODS: Twenty female MDD patients and 21 healthy controls (HCs) were included in the study. To identify the difference in the regional gray matter concentration (GMC), VBM was performed with T1 magnetic resonance imaging. The shape analysis of the corpus callosum was processed. Diffusion tensor imaging (DTI) fiber-tracking was performed to identify the regional tract pathways in the damaged corpus callosal areas. RESULTS: In the shape analysis, regional shape contractions in the rostrum and splenium were found in the MDD patients. VBM analysis showed a significantly lower white matter concentration in the genu and splenium, and a significantly lower GMC in the frontal, limbic, insular, and temporal regions of the MDD patients compared to the HCs. In DTI fiber-tracking, the fibers crossing the damaged areas of the genu, rostrum, and splenium were anatomically connected to the areas of lower GMC in MDD patients. CONCLUSION: These findings support that major depressive disorder may be due to disturbances in multiple neuronal circuits, especially those associated with the corpus callosum.

Clinical and neuroimaging factors associated with aphasia severity in stroke patients: diffusion tensor imaging study.

This study investigated factors associated with aphasia severity at both 2 weeks and 3 months after stroke using demographic and clinical variables, brain diffusion tensor imaging (DTI) parameters, and lesion volume measurements. Patients with left hemisphere stroke were assessed at 2 weeks (n = 68) and at 3 months (n = 20) after stroke. Demographic, clinical, and neuroimaging data were collected; language functions were assessed using the Western Aphasia Battery. For neuroimaging, DTI parameters, including the laterality index (LI) of fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity, mean diffusivity and fibre density (FD) of the arcuate fasciculus (AF), and lesion volume, were measured. Lesion volume, cortical involvement, and the National Institutes of Health Stroke Scale score significantly predicted aphasia severity at 2 weeks after stroke, whereas the aphasia quotient and presence of depression during the early subacute stage were significant predictors at 3 months after stroke. According to Pearson correlation, LI-AD and LI-FD were significantly correlated with the aphasia quotient 2 weeks after ischaemic stroke, and the LI-FA was significantly correlated with the aphasia quotient 2 weeks after haemorrhagic stroke, suggesting that the extent and mechanism of AF injuries differ between ischaemic and haemorrhagic strokes. These differences may contribute to aphasia severity.

Reduced axial diffusivity and increased mode and T2 signals in cerebral white matter of chronic obstructive pulmonary disease using tract-based spatial statistics.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is considered to be a multi-systemic disease involving pathological changes in the brain. This study investigated how diffusion tensor imaging (DTI) parameters in patients with non-hypoxemic COPD differ from those in controls. Moreover, we tried to examine whether the mode of anisotropy (MO) reflects early changes in white matter (WM) integrity in COPD. METHODS: DT images were obtained from 13 male COPD patients and 13 age- and sex-matched healthy controls. Raw DT images were processed using an automated tract-based spatial statistics (TBSS) pipeline. DTI scalars of fractional anisotropy (FA); axial, radial, and mean diffusivities (AD, RD, and MD, respectively); MO; and raw T2 signal (S0) were statistically compared between COPD patients and controls. TBSS methods were used for analysis. RESULTS: In patients with COPD, decreased AD was observed in the temporal stem (TS), corticospinal tract (CST), thalamus, subiculum, crus cerebri, and midbrain. Increased MO values were found in the corpus callosum, CST, internal capsule, cerebellar peduncle (CP), and medial lemniscus (ML). Additionally, increased S0 was found in the TS, CP, pons, and cerebellar tonsil (threshold-free cluster enhancement to a family-wise error rate of p < 0.05). CONCLUSION: The results revealed decreased AD and increased MO scalars in COPD patients compared with the controls, although there were no differences in FA, RD, and MD scalars. Decreased AD and increased MO scalars may reflect early changes in WM integrity in COPD patients.

Neuroanatomical Mechanism of Cerebellar Mutism After Stroke.

Cerebellar mutism (CM) is a rare neurological condition characterized by lack of speech due to cerebellar lesions. CM is often reported in children. We describe a rare case of CM after spontaneous cerebellar hemorrhage. The patient showed mutism, irritability, decreased spontaneous movements and oropharyngeal apraxia. Diffusion tensor imaging revealed significant volume reduction of medial frontal projection fibers from the corpus callosum. In Tracts Constrained by UnderLying Anatomy (TRACULA) analysis, forceps major and minor and bilateral cingulum-angular bundles were not visualized. Cerebello-frontal pathway reconstructed from the FMRIB Software Library showed continuity of fibers, with decreased number of fibers on qualitative analysis. These results suggest that cerebello-frontal disconnection may be a neuroanatomical mechanism of CM. Damage of brain network between occipital lobe, cingulate and cerebellum caused by hemorrhage may also have role in the mechanism of CM in our case.