Hai Chen

DYNAMIC FUNCTIONAL REORGANIZATION OF THE MOTOR EXECUTION NETWORK AFTER STROKE

Numerous studies argue that cortical reorganization may contribute to the restoration of motor function following stroke. However, the evolution of changes during the post-stroke reorganization has been little studied. This study sought to identify dynamic changes in the functional organization, particularly topological characteristics, of the motor execution network during the stroke recovery process. Ten patients (nine male and one female) with subcortical infarctions were assessed by neurological examination and scanned with resting-state functional magnetic resonance imaging across five consecutive time points in a single year. The motor execution network of each subject was constructed using a functional connectivity matrix between 21 brain regions and subsequently analysed using graph theoretical approaches. Dynamic changes in topological configuration of the network during the process of recovery were evaluated by a mixed model. We found that the motor execution network gradually shifted towards a random mode during the recovery process, which suggests that a less optimized reorganization is involved in regaining function in the affected limbs. Significantly increased regional centralities within the network were observed in the ipsilesional primary motor area and contralesional cerebellum, whereas the ipsilesional cerebellum showed decreased regional centrality. Functional connectivity to these brain regions demonstrated consistent alterations over time. Notably, these measures correlated with different clinical variables, which provided support that the findings may reflect the adaptive reorganization of the motor execution network in stroke patients. In conclusion, the study expands our understanding of the spectrum of changes occurring in the brain after stroke and provides a new avenue for investigating lesion-induced network plasticity.

A longitudinal diffusion tensor imaging study on Wallerian degeneration of corticospinal tract after motor pathway stroke

Wallerian degeneration of the corticospinal tract (CST) after motor pathway ischemic stroke can be characterized by diffusion tensor imaging (DTI). However, the dynamic evolution of the diffusion indices in the degenerated CST has not previously been completely identified. We investigated this dynamic evolution and the relationship between early changes of the diffusion indices in the degenerated CST and long-term clinical outcomes. DTI and neurological examinations were performed repeatedly in 9 patients with first-onset motor pathway subcortical infarction at 5 consecutive time points, i.e. within 1 week, at 2 weeks, 1 month, 3 months and 1 year. Using a region of interest method, we analyzed the ratios of the fractional anisotropy (rFA), mean diffusivity (rMD), primary eigenvalue (rlambda(1)) and transverse eigenvalue (rlambda(23)) between the affected and unaffected sides of the CSTs. We did not find any significant changes in the diffusion indices of the contralesional CSTs across time points. The rFA decreased monotonously during the first 3 months and then stabilized. The rMD increased after 2 weeks and stabilized after the third month. The rlambda(1) decreased during the first 2 weeks and then remained unchanged. The rlambda(23) increased during the first 3 months and then stabilized. We also found that the changes in the rFA between the first 2 time points were correlated with the NIHSS (P=0.00003) and the Motricity Indices (P=0.0004) after 1 year. Our results suggest that for patients with motor pathway stroke the diffusion indices in the degenerated CST stabilize within 3 months and that early changes in the rFA of the CST may predict long-term clinical outcomes.

Dynamic Brain Structural Changes After Left Hemisphere Subcortical Stroke

This study aimed to quantify dynamic structural changes in the brain after subcortical stroke and identify brain areas that contribute to motor recovery of affected limbs. High‐resolution structural MRI and neurological examinations were conducted at five consecutive time points during the year following stroke in 10 patients with left hemisphere subcortical infarctions involving motor pathways. Gray matter volume (GMV) was calculated using an optimized voxel‐based morphometry technique, and dynamic changes in GMV were evaluated using a mixed‐effects model. After stroke, GMV was decreased bilaterally in brain areas that directly or indirectly connected with lesions, which suggests the presence of regional damage in these “healthy” brain tissues in stroke patients. Moreover, the GMVs of these brain areas were not correlated with the Motricity Index (MI) scores when controlling for time intervals after stroke, which indicates that these structural changes may reflect an independent process (such as axonal degeneration) but cannot affect the improvement of motor function. In contrast, the GMV was increased in several brain areas associated with motor and cognitive functions after stroke. When controlling for time intervals after stroke, only the GMVs in the cognitive‐related brain areas (hippocampus and precuneus) were positively correlated with MI scores, which suggests that the structural reorganization in cognitive‐related brain areas may facilitate the recovery of motor function. However, considering the small sample size of this study, further studies are needed to clarify the exact relationships between structural changes and recovery of motor function in stroke patients. Hum Brain Mapp, 2013.

Contribution of the Resting-State Functional Connectivity of the Contralesional Primary Sensorimotor Cortex to Motor Recovery after Subcortical Stroke

It remains uncertain if the contralesional primary sensorimotor cortex (CL_PSMC) contributes to motor recovery after stroke. Here we investigated longitudinal changes in the resting-state functional connectivity (rsFC) of the CL_PSMC and their association with motor recovery. Thirteen patients who had experienced subcortical stroke underwent a series of resting-state fMRI and clinical assessments over a period of 1 year at 5 time points, i.e., within the first week, at 2 weeks, 1 month, 3 months, and 1 year after stroke onset. Thirteen age- and gender-matched healthy subjects were recruited as controls. The CL_PSMC was defined as a region centered at the voxel that had greatest activation during hand motion task. The dynamic changes in the rsFCs of the CL_PSMC within the whole brain were evaluated and correlated with the Motricity Index (MI) scores. Compared with healthy controls, the rsFCs of the CL_PSMC with the bilateral PSMC were initially decreased, then gradually increased, and finally restored to the normal level 1 year later. Moreover, the dynamic change in the inter-hemispheric rsFC between the bilateral PSMC in these patients was positively correlated with the MI scores. However, the intra-hemispheric rsFC of the CL_PSMC was not correlated with the MI scores. This study shows dynamic changes in the rsFCs of the CL_PSMC after stroke and suggests that the increased inter-hemispheric rsFC between the bilateral PSMC may facilitate motor recovery in stroke patients. However, generalization of our findings is limited by the small sample size of our study and needs to be confirmed.

Clinical isolated syndrome: a 3-year follow-up study in China.

OBJECTIVE To summarize the characteristics of Chinese clinically isolated syndrome (CIS) patients and their 3-year follow-up results. Investigate the relationship between CIS features and clinical outcomes. METHODS Forty-nine CIS patients were recruited and 42 of them were able to be followed up for a mean of 38 months (range 26-48 months). We recorded baseline features including patient demographics, site of CIS, presence or absence of cerebrospinal fluid (CSF) oligoclonal bands (OCB) and MRI lesions in brain and spinal cord. The incidence of conversion to clinically definite MS (CDMS) or neuromyelitis optica (NMO) after CIS was calculated, and the relationship between baseline features and CDMS was explored. All data were statistically processed with SPSS for Windows Version 11.5. RESULTS After a mean follow-up of 38 months, 10/42 patients had converted to CDMS (24%), and one patient had developed definite NMO. The other 31 patients remained in CIS status. A spinal cord syndrome was the initial CIS manifestation in 57% of patients. The conversion rates to MS were 22% (5/23) for patients presenting with a spinal cord syndrome and 27% (3/11) for multi-focal manifestations. The three-year CDMS conversion rates were 70% (7/10) for patients who fulfilled the MRI dissemination in space criteria (2005 revised McDonald) at onset of CIS, while only 9% (3/32) of patients who did not fulfill these criteria converted to CDMS. Females had significantly higher conversion rate than males. CONCLUSION A spinal cord syndrome was the most common initial presentation of our Chinese CIS group. After a mean follow-up of 38 months, the conversion rate to MS was approximately 25%. The 2005 revised McDonald MRI criteria for dissemination in space is a key prognostic factor for conversion to MS in CIS in Chinese patients.

Metabolic changes in normal-appearing white matter in patients with neuromyelitis optica and multiple sclerosis: a comparative magnetic resonance spectroscopy study

Background Previous studies with a small sample size have not reported metabolic changes in neuromyelitis optica (NMO). Metabolic changes, such as decreased N-acetylaspartate (NAA), are well-established in patients with multiple sclerosis (MS). It remains unknown whether different patterns of metabolic changes occur in NMO and MS. Purpose To investigate the metabolic changes in normal-appearing white matter (NAWM) in NMO, compared with MS patients and healthy controls (HC), and correlate these changes with clinical disability. Material and Methods We recruited 27 patients with NMO, 24 patients with MS, and 24 HC. Each participant underwent chemical shift imaging with a 1H-MR spectroscopy operating in a 1.5 T magnetic resonance imaging (MRI) scanner. The absolute concentrations of NAA, choline (Cho), creatine (Cr) as well as the metabolite ratios of NAA/Cr, Cho/Cr, and NAA/Cho were measured and compared among the groups. The correlations between the metabolic concentrations, disease duration, and clinical disability (Expanded Disability Status Scale, EDSS) were further explored. Results Compared with HC, a mild increase of Cho without significant NAA changes was observed in NMO patients, while both a significant reduction of NAA and an increase of Cho were observed in MS patients. The absolute concentration of NAA and NAA/Cho ratio were significantly decreased in MS patients in a direct comparison with NMO patients. In MS patients, the EDSS was correlated with the NAA/Cr and Cho/Cr ratios. Conclusion A reduction of NAA was not observed in NMO, implying axonal or neuronal damage may be absent in NAWM for NMO, which is different from MS. A mild increase in Cho was observed in NAWM of NMO patients, suggesting that subtle metabolic changes occur in NMO.

Clinical Features of Patients with Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders

Background: Neuromyelitis optica spectrum disorder (NMOSD) was long believed to be an aggressive form of multiple sclerosis (MS). This study aimed to describe the clinical features of patients with MS and NMOSD to assist in differential diagnoses in clinical practice. Methods: Data including the patients’ serum and cerebrospinal fluid (CSF) tests, image findings, and clinical information from 175 patients with MS or NMOSD at Xuanwu Hospital, Capital Medical University from November 2012 to May 2014 were collected and analyzed retrospectively. An enzyme-linked immunosorbent assay was performed to detect the myelin oligodendrocyte glycoprotein (MOG) autoantibodies in CSF and serum. Cell-based assays were used to detect aquaporin-4-antibody (AQP4-Ab). The Chi-square test was used to compare the categorical variables. Wilcoxon rank sum test was performed to analyze the continuous variables. Results: Totally 85 MS patients (49%) and 90 NMOSD patients (51%) were enrolled, including 124 (71%) women and 51 (29%) men. Fewer MS patients (6%) had autoimmune diseases compared to NMOSD (19%) (&khgr; 2 = 6.9, P < 0.01). Patients with NMOSD had higher Expanded Disability Status Scale scores (3.5 [3]) than MS group (2 [2]) (Z = −3.69, P < 0.01). The CSF levels of white cell count and protein in both two groups were slightly elevated than the normal range, without significant difference between each other. Positivity of serum AQP4-Ab in NMOSD patients was higher than that in MS patients (MS: 0, NMOSD: 67%; &khgr; 2 = 63.9, P < 0.01). Oligoclonal bands in CSF among NMOSD patients were remarkably lower than that among MS (MS: 59%, NMOSD: 20%; &khgr; 2 = 25.7, P < 0.01). No significant difference of MOG autoantibodies was found between the two groups. Conclusion: The different CSF features combined with clinical, magnetic resonance imaging, and serum characteristics between Chinese patients with MS and NMOSD could assist in the differential diagnosis.

White matter microstructural alterations in clinically isolated syndrome and multiple sclerosis

This study aims to determine whether and how diffusion alteration occurs in the earliest stage of multiple sclerosis (MS) and the differences in diffusion metrics between CIS and MS by using the tract-based spatial statistics (TBSS) method based on diffusion tensor imaging (DTI). Thirty-six CIS patients (mean age ± SD: 34.0 years ± 12.6), 36 relapsing-remitting multiple sclerosis (RRMS) patients (mean age ± SD: 35.0 years ± 9.4) and 36 age- and gender-matched normal controls (NCs) were included in this study. Voxel-wise analyses were performed with TBSS using multiple diffusion metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ1) and radial diffusivity (λ23). In the CIS patients, TBSS analyses revealed diffusion alterations in a few white matter (WM) regions including the anterior thalamic radiation, corticospinal tract, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, body and splenium of the corpus callosum, internal capsule, external capsule, and cerebral peduncle. MS patients showed more widespread diffusion changes (decreased FA, increased λ1, λ23 and MD) than CIS. Exploratory analyses also revealed the possible associations between WM diffusion metrics and clinical variables (Expanded Disability Status Scale and disease duration) in the patients. This study provided imaging evidence for DTI abnormalities in CIS and MS and suggested that DTI can improve our knowledge of the path physiology of CIS and MS and clinical progression.