CIRH1A augments the proliferation of RKO colorectal cancer cells.

Accumulating evidence suggests that ribosomal proteins may have extraribosomal functions in various physiological and pathological processes, including cancer. We analyzed the expression of the CIRH1A ribosomal protein in colorectal carcinoma and para-carcinoma samples by bioinformatics analyses of data extracted from The Cancer Genome Atlas and in colorectal cancer cell lines in vitro by qPCR. CIRH1A was highly expressed in carcinoma samples and colorectal cancer cells. We also transduced the RKO colorectal cancer (CRC) cell line with lentivirus-mediated small interfering RNAs (siRNAs) and studied the impact that this knockdown of CIRH1A expression had on cell growth. RNA interference (RNAi)-mediated inhibition of CIRH1A expression significantly suppressed proliferation and increased apoptosis of transduced cells, and tended to arrest them in G1 phase. Our data suggest that CIRH1A plays a critical role in the proliferation, cell cycle distribution, and apoptosis of human malignant colorectal cells, and might therefore be a potential target for therapeutic strategies.

Gene mutation profiling of primary glioblastoma through multiple tumor biopsy guided by 1H-magnetic resonance spectroscopy.

Genetic mutation has served as the biomarkers for the diagnosis and treatment of glioblastoma multiforme (GBM). However, intra-tumor heterogeneity may interfere with personalized treatment strategies based on mutation analysis. This study aimed to characterize somatic mutation profiling of GBM. We collected 33 samples from 7 patients with the primary GBM associated with different Choline (Cho) to N-acetylaspartate (NAA) index (CNI) through the frameless proton magnetic resonance spectroscopy (1H-MRS) guided biopsies and investigated multiple somatic mutations profiling using the AmpliSeq cancer hotspot panel V2. We identified 53 missense or nonsense mutations in 27 genes including some novel mutations such as APC and IDH2. The mutations in EGFR, TP53, PTEN, PIK3CA genes were presented with different frequency and the majority of the mutated gene was only shared by 1-2 samples from one patient. Moreover, we found the association of CNI with histological grade, but there was no significant change of CNI in the presence of TP53, EGFR and PTEN mutations. These data suggest that gene mutations constitute a heterogeneous marker for primary GBM which may be independent of intra-tumor morphological phenotypes of GBM; therefore, gene mutation markers could not be determined from a small number of needle biopsies or only confined to the high-grade region.

rs17501976 polymorphism of CLDN1 gene is associated with decreased risk of colorectal cancer in a Chinese population.

The purpose of this study was to determine the relationship between polymorphisms in Claudin-1 (CLDN1) and the risk of colorectal cancer in a Chinese population. In this study, a case-control study was conducted in which polymorphisms in CLDN1 were analyzed in 50 patients with colorectal cancer (CRC) and 50 healthy individuals as controls. No rs16865344 and rs17429833 polymorphism were found among all analyzed samples. For the rs17501976 polymorphism, the TC genotype (OR = 0. 41, 95% CI = 0.18-0.91, and P = 0.045) was closely associated with the risk of colorectal cancer compared with the more common TT genotype. And the TC + CC genotypes (OR = 0.41, 95% CI = 0.18-0.91, and P = 0.045) were also significantly associated with the risk of CRC compared with the TT genotype. However, a C > T change of the rs17501976 polymorphism did not show a difference in transcription factor binding to the promoter region of CLDN1. For rs12696600 polymorphism, no significant difference was found in colorectal cancer risk between cases and controls in corresponding genotypes. Collectively, our data suggest that rs17501976 polymorphism significantly associated with a decreased susceptibility to CRC in a Chinese population.

Recurrent gain-of-function USP8 mutations in Cushing's disease.

Cushing's disease, also known as adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (PAs) that cause excess cortisol production, accounts for up to 85% of corticotrophin-dependent Cushing's syndrome cases. However, the genetic alterations in this disease are unclear. Here, we performed whole-exome sequencing of DNA derived from 12 ACTH-secreting PAs and matched blood samples, which revealed three types of somatic mutations in a candidate gene, USP8 (encoding ubiquitin-specific protease 8), exclusively in exon 14 in 8 of 12 ACTH-secreting PAs. We further evaluated somatic USP8 mutations in additional 258 PAs by Sanger sequencing. Targeted sequencing further identified a total of 17 types of USP8 variants in 67 of 108 ACTH-secreting PAs (62.04%). However, none of these mutations was detected in other types of PAs (n = 150). These mutations aggregate within the 14-3-3 binding motif of USP8 and disrupt the interaction between USP8 and 14-3-3 protein, resulting in an elevated capacity to protect EGFR from lysosomal degradation. Accordingly, PAs with mutated USP8 display a higher incidence of EGFR expression, elevated EGFR protein abundance and mRNA expression levels of POMC, which encodes the precursor of ACTH. PAs with mutated USP8 are significantly smaller in size and have higher ACTH production than wild-type PAs. In surgically resected primary USP8-mutated tumor cells, USP8 knockdown or blocking EGFR effectively attenuates ACTH secretion. Taken together, somatic gain-of-function USP8 mutations are common and contribute to ACTH overproduction in Cushing's disease. Inhibition of USP8 or EGFR is promising for treating USP8-mutated corticotrophin adenoma. Our study highlights the potentially functional mutated gene in Cushing's disease and provides insights into the therapeutics of this disease.

Localizing hand motor area using resting-state fMRI: validated with direct cortical stimulation.

BACKGROUND: Resting-state functional magnetic resonance imaging (R-fMRI) is a promising tool in clinical application, especially in presurgical mapping for neurosurgery. This study aimed to investigate the sensitivity and specificity of R-fMRI in the localization of hand motor area in patients with brain tumors validated by direct cortical stimulation (DCS). We also compared this technique to task-based blood oxygenation level-dependent (BOLD) fMRI (T-fMRI). METHODS: R-fMRI and T-fMRI were acquired from 17 patients with brain tumors. The cortex sites of the hand motor area were recorded by DCS. Site-by-site comparisons between R-fMRI/T-fMRI and DCS were performed to calculate R-fMRI and T-fMRI sensitivity and specificity using DCS as a "gold standard". R-fMRI and T-fMRI performances were compared statistically RESULTS: A total of 609 cortex sites were tested with DCS and compared with R-fMRI findings in 17 patients. For hand motor area localization, R-fMRI sensitivity and specificity were 90.91 and 89.41 %, respectively. Given that two subjects could not comply with T-fMRI, 520 DCS sites were compared with T-fMRI findings in 15 patients. The sensitivity and specificity of T-fMRI were 78.57 and 84.76 %, respectively. In the 15 patients who successfully underwent both R-fMRI and T-fMRI, there was no statistical difference in sensitivity or specificity between the two methods (p = 0.3198 and p = 0.1431, respectively) CONCLUSIONS: R-fMRI sensitivity and specificity are high for localizing hand motor area and even equivalent or slightly higher compared with T-fMRI. Given its convenience for patients, R-fMRI is a promising substitute for T-fMRI for presurgical mapping.

Diffusion tensor magnetic resonance imaging for predicting the consistency of intracranial meningiomas.

BACKGROUND: The ability of preoperative MRI-sequences to predict the consistency of intracranial meningiomas has not yet been clearly defined. We aim to demonstrate that diffusion tensor imaging (DTI) improves the prediction of intracranial meningiomas consistency. METHODS: We prospectively studied 110 meningioma patients operated on in a single center from March 1st to the 25th of May 2012. Demographic data, location and size of the tumor, peritumoral edema, T1WI, T2WI, proton density weighted (PDWI), fluid-attenuated inversion recover (FLAIR) sequences, and arterial spin labeling (ASL) perfusion were studied and compared with the gray matter signal to predict meningioma consistency. Diffusion tensor imaging (DTI) with fractional anisotropy (FA) and mean diffusivity (MD) maps were included in the preoperative MRI. Meningioma consistency was evaluated by the operating surgeon who was unaware of the neuroradiological findings. RESULTS: In univariate analysis, meningioma size (diameter > 2 cm) and supratentorial or sphenoidal wing location were more frequently associated with hard-consistency meningiomas (p < 0.05). In addition, isointense signal on MD maps (p = 0.009), hyperintense signal on FA maps, and FA value > 0.3 (p = 0.00001) were associated with hard-consistency tumors. Age and sex, T1WI, T2WI, PDWI, FLAIR, or ASL perfusion sequences and peritumoral edema were not significantly associated with meningioma consistency. In logistic regression analysis, the most accurate model (AUC: 0.9459) for predicting a hard-consistency meningioma shows that an isointense signal in MD-maps, a hyperintense signal in FA-maps, and an FA value of more than 0.3 have a significant predictive value. CONCLUSIONS: FA value and MD and FA maps are useful for prediction of meningioma consistency and, therefore, may be considered in the preoperative routine MRI examination of all patients with intracranial meningiomas.

Sensorimotor cortical changes assessed with resting-state fMRI following total brachial plexus root avulsion.

OBJECTIVE: Peripheral nerve injury can induce immediate and long-standing remodelling of the brain cortex, which may affect outcomes of nerve repair. This study examined changes of corresponding cortical representations in patients with brachial plexus injuries. METHODS: Resting-state fMRI was acquired for 13 adult patients with total brachial plexus root avulsion, three of whom underwent second scans 7 or 8 months later. The time of examination ranged from 1 to 16 months after injuries. Nine healthy adults were enrolled as control. Seed-based functional connectivity was performed for all subjects. RESULTS: For nine patients whose first fMRI was performed from 1 to 4 months after brachial plexus injuries, images showed that their cortical maps of sensorimotor areas corresponding to the hand and arm in the hemisphere contralateral to the injured side had much weaker correlation with the supplementary motor area (SMA) than those ipsilateral to the injured side. Symmetrical maps of bilateral cortical sensorimotor areas corresponding to the hand and arm were observed in other four cases with fMRI tested from 7 to 16 months after injuries. For three of the nine patients with asymmetrical cortical representations, second scans indicated symmetric results or even stronger correlation with SMA in the cerebral cortex contralateral to the injured side. CONCLUSIONS: Total brachial plexus root avulsion causes cortical representations of the brachial plexus to undergo a change from an inactive to an active state. This implies that peripheral deafferentation after brachial plexus injuries will induce corresponding cortical representations to be occupied by adjacent non-deafferented cortical territories.

Clinical application of motor pathway mapping using diffusion tensor imaging tractography and intraoperative direct subcortical stimulation in cerebral glioma surgery: a prospective cohort study.

BACKGROUND: Glioma surgery in eloquent areas remains a challenge because of the risk of postoperative motor deficits. OBJECTIVE: To prospectively evaluate the efficiency of using a combination of diffusion tensor imaging (DTI) tractography functional neuronavigation and direct subcortical stimulation (DsCS) to yield a maximally safe resection of cerebral glioma in eloquent areas. METHODS: A prospective cohort study was conducted in 58 subjects with an initial diagnosis of primary cerebral glioma within or adjacent to the pyramidal tract (PT). The white matter beneath the resection cavity was stimulated along the PT, which was visualized with DTI tractography. The intercept between the PT border and DsCS site was measured. The sensitivity and specificity of DTI tractography for PT mapping were evaluated. The efficiency of the combined use of both techniques on motor function preservation was assessed. RESULTS: Postoperative analysis showed gross total resection in 40 patients (69.0%). Seventeen patients (29.3%) experienced postoperative worsening; 1-month motor deficit was observed in 6 subjects (10.3%). DsCS verified a high concordance rate with DTI tractography for PT mapping. The sensitivity and specificity of DTI were 92.6% and 93.2%, respectively. The intercepts between positive DsCS sites and imaged PTs were 2.0 to 14.7 mm (5.2 ± 2.2 mm). The 6-month Karnofsky performance scale scores in 50 postoperative subjects were significantly increased compared with their preoperative scores. CONCLUSION: DTI tractography is effective but not completely reliable in delineating the descending motor pathways. Integration of DTI and DsCS favors patient-specific surgery for cerebral glioma in eloquent areas.

Preoperative surgical planning for intracranial meningioma resection by virtual reality.

BACKGROUND: The Dextroscope system by Volume Interactions (Singapore) had been applied to minimally invasive neurosurgery in many units. This system enables the neurosurgeon to interact intuitively with the three-dimensional graphics in a direct manner resembling the way one communicates with the real objects. In the paper, we explored its values in pre-operation surgical planning for intracranial meningiomas resection. METHODS: Brain computed tomography (CT), magnetic resonance imaging (MRI), and magnetic resonance venography (MRV) were performed on 10 patients with parasagittal and falcine meningiomas located on central groove area; brain CT, MRI and magnetic resonance angiography (MRA) were performed on 10 patients with anterior skull base meningiomas and 10 patients with sphenoid ridge meningiomas. All these data were transferred to Dextroscope virtual reality system, and reconstructed. Then meningiomas, skull base, brain tissue, drainage vein and cerebral arteries were displayed within the system, and their anatomic relationships were evaluated. Also, the simulation operations were performed. RESULTS: For parasagittal and falcine meningiomas, the relationships of tumor with drainage vein and superior sagittal sinus were clearly displayed in the Dextroscope system. For anterior skull base and sphenoid ridge meningiomas, the relationships of tumor with bilateral internal carotid arteries, anterior cerebral arteries, middle cerebral arteries and skull base were vividly displayed within the virtual reality system. Surgical planning and simulation operation of all cases were performed as well. The real operations of all patients were conducted according to the simulation with well outcomes. CONCLUSIONS: According to the virtual reality planning, neurosurgeons could get more anatomic information about meningioma and its surrounding structures, especially important vessels, and choose the best approach for tumor resection, which would lead to better prognosis for patients.

Virtual reality presurgical planning for cerebral gliomas adjacent to motor pathways in an integrated 3-D stereoscopic visualization of structural MRI and DTI tractography.

OBJECTIVE: Resection of gliomas invading primary motor cortex and subcortical motor pathway is difficult in both surgical decision-making and functional outcome prediction. In this study, magnetic resonance (MR) diffusion tensor imaging (DTI) data were used to perform tractography to visualize pyramidal tract (PT) along its whole length in a stereoscopic virtual reality (VR) environment. The potential value of its clinical application was evaluated. METHODS: Both three-dimensional (3-D) magnetic resonance imaging (MRI) and DTI datasets were obtained from 45 eligible patients with suspected cerebral gliomas and then transferred to the VR system (Dextroscope; Volume Interactions Pte. Ltd., Singapore). The cortex and tumor were segmented and reconstructed via MRI, respectively, while the tractographic PTs were reconstructed via DTI. All those were presented in a stereoscopic 3-D display synchronously, for the purpose of patient-specific presurgical planning and surgical simulation in each case. The relationship between increasing amplitude of the number of effective fibers of PT (EPT) at affected sides and the patients' Karnofsky Performance Scale (KPS) at 6 months was addressed out. RESULTS: In VR presurgical planning for gliomas, surgery was aided by stereoscopic 3-D visualizing the relative position of the PTs and a tumor. There was no significant difference between pre- and postsurgical EPT in this population. A positive relationship was proved between EPT increasing amplitude and 6-month KPS. CONCLUSIONS: 3-D stereoscopic visualization of tractography in this VR environment enhances the operators to well understand the anatomic information of intra-axial tumor contours and adjacent PT, results in surgical trajectory optimization initially, and maximal safe tumor resection finally. In accordance to the EPT increasing amplitude, surgeon can predict the long-term motor functional outcome.

Preoperative evaluation of neurovascular relationships for microvascular decompression in the cerebellopontine angle in a virtual reality environment.

OBJECT: In this paper the authors' goal was to evaluate the feasibility and efficacy of a virtual reality (VR) system in preoperative planning for microvascular decompression (MVD) procedures treating idiopathic trigeminal neuralgia and hemifacial spasm. The system's role in surgical simulation and training was also assessed. METHODS: Between May 2008 and April 2009, the authors used the Dextroscope system to visualize the neurovascular complex and simulate MVD in the cerebellopontine angle in a VR environment in 16 patients (6 patients had trigeminal neuralgia and 10 had hemifacial spasm). Reconstructions were carried out 2-3 days before MVD. Images were printed in a red-blue stereoscopic format for teaching and discussion and were brought into the operating room to be compared with real-time intraoperative findings. RESULTS: The VR environment was a powerful aid for spatial understanding of the neurovascular relationship in MVD for operating surgeons and trainees. Through an initial series of comparison/confirmation experiences, the senior neurosurgeon became accustomed to the system. He could predict intraoperative problems and simulate surgical maneuvering, which increased his confidence in performing the procedure. CONCLUSIONS: The Dextroscope system is an easy and rapid method to create a stereoscopic neurovascular model for MVD that is highly concordant with intraoperative findings. It effectively shortens the learning curve and adds to the surgeon's confidence.

[Association between clinical ischemic events and carotid calcification evaluated by 64 slices CT angiography].

OBJECTIVE: To explore the relationship between clinical ischemic events and carotid calcification detected by 64 slices CT angiography. METHODS: We retrospectively analyzed the carotid calcified plaques in 116 patients underwent the 64 slices CT angiography. The relationship between the carotid calcification and the clinical ischemic events was analyzed. RESULTS: A total of 377 plaques were detected and the incidence of carotid plaque calcification was 63.40%. Incidence of plaque calcification was significantly lower in patients with ages < 50 years than that in patients with ages 51 - 59 years, 60 - 69 years and higher than 70 years (P = 0.003, P = 0.002, P = 0.000, respectively). The incidence of plaque calcification in the common carotid artery was significantly lower than the carotid bifurcation (P = 0.000) and the internal carotid artery (P = 0.000). The incidences of calcification in the mild, moderate and severe degree of stenosis and occlusion were 46.54%, 33.33%, 26.67% and 0% respectively. The distribution of intraplaque calcium was similar between patients with ischemic event and non-ischemic event group. However, the incidence of calcification was significantly lower patients with ischemic event than that in patients without ischemic event (30.34% vs. 43.10%, P = 0.013). Calcified plaque was negatively associated with ischemic event (beta = -0.688, P = 0.006). CONCLUSION: 64 slices CT angiography can analyze the characterization of carotid plaque calcium.

Clinical evaluation and follow-up outcome of diffusion tensor imaging-based functional neuronavigation: a prospective, controlled study in patients with gliomas involving pyramidal tracts.

OBJECTIVE: To evaluate diffusion tensor imaging (DTI)-based functional neuronavigation in surgery of cerebral gliomas with pyramidal tract (PT) involvement with respect to both perioperative assessment and follow-up outcome. METHODS: A prospective, randomized controlled study was conducted between 2001 and 2005. A consecutive series of 238 eligible patients with initial imaging diagnosis of cerebral gliomas involving PTs were randomized into study (n = 118) and control (n = 120) groups. The study cases underwent DTI and three-dimensional magnetic resonance imaging scans. The maps of fractional anisotropy were calculated for PT mapping. Both three-dimensional magnetic resonance imaging data sets and fractional anisotropy maps were integrated by rigid registration, after which the tumor and adjacent PT were segmented and reconstructed for presurgical planning and intraoperative guidance. The control cases were operated on using routine neuronavigation. RESULTS: There was a trend for high-grade gliomas (HGGs) in the study group to be more likely to achieve gross total resection (74.4 versus 33.3%, P < 0.001). There was no significant difference of low-grade gliomas resection between the two groups. Postoperative motor deterioration occurred in 32.8% of control cases, whereas it occurred in only 15.3% of the study cases (P < 0.001). The 6-month Karnofsky Performance Scale score of study cases was significantly higher than that of control cases (86 +/- 20 versus 74 +/- 28 overall, P < 0.001; 93 +/- 10 versus 86 +/- 17 for low-grade gliomas, P = 0.013; and 77 +/- 27 versus 53 +/- 32 for HGGs, P = 0.001). For 81 HGGs, the median survival of study cases was 21.2 months (95% confidence interval, 14.1-28.3 mo) compared with 14.0 months (95% confidence interval, 10.2-17.8 mo) of control cases (P = 0.048). The estimated hazard ratio for the effect of DTI-based functional neuronavigation was 0.570, representing a 43.0% reduction in the risk of death. CONCLUSION: DTI-based functional neuronavigation contributes to maximal safe resection of cerebral gliomas with PT involvement, thereby decreasing postoperative motor deficits for both HGGs and low-grade gliomas while increasing high-quality survival for HGGs.

Neuronal specificity of needling acupoints at same meridian: a control functional magnetic resonance imaging study with electroacupuncture.

The purpose of this study was to investigate the neuronal specificity of needling acupoints at same meridian by functional Magnetic Resonance Imaging (fMRI). The selected acupoints GB34 (Yanglinquan) and GB39 (Xuanzhong) were at the same gallbladder meridian based on traditional Chinese medicine. In our study we devise three distinct EA (electroacupuncture) manipulations: real EA (deep needling at acupoints), sham EA (deep needling at no-meridian points) and shallow EA (subcutaneous needling at acupoints). Twelve healthy volunteers with right-handiness were enrolled and received three different EA manipulations in counter-balanced orders. DeQi scores were used to evaluate the degree of needling sensation. We found real EA can induce significant stronger needling sensation than sham EA and shallow EA. Multisubjects group mean analysis showed that pain-related cortex including primary and secondary somatosensory cortex (SI and S II), anterior cingulated cortex (ACC), insula were involved in three EA stimulation. Bilateral activation of prefrontal gyrus and occipital cortex were exclusively found in real EA. Deactivation over the rostral segment of ACC was also shown in real and shallow EA. Further paired two difference analysis indicated that real EA induced higher activation than sham EA over bilateral prefrontal gyrus, right-side occipital gyrus and deactivation over the rostral segment of ACC. In the comparing with real EA versus shallow EA, there was right-side activation over the SI, S II, motor cortex, ACC, insula, thalamus, hippocampus, occipital cortex, and cerebellum; also activation over bilateral prefrontal gyrus, caudate and pons. Although no significant activation was found over periaqueductal gray (PAG), further analysis showed the mean and maximal signal changes were different under three EA manipulations. We concluded that EA at analgesic acupoints of same meridian maybe involved the pain-related neuromatrix especially the hypothalamus-limbic system; deep EA at meridian points could elicit stronger needling sensation and modulate the pain-related neuromatrix more effectively than EA at nonmeridian points or shallow EA at meridian points.

Epigallocatechin gallate preserves endothelial function by reducing the endogenous nitric oxide synthase inhibitor level.

Asymmetric dimethylarginine (ADMA), the endogenous nitric oxide synthase inhibitor, is thought to be a key factor contributing to endothelial dysfunction. Tea catechins can cause an endothelium-dependent vasorelaxation. The present study examined the effect of epigallocatechin gallate (EGCG), the major component of tea catechins, on endothelial dysfunction induced by native low density lipoprotein (LDL) in rats and oxidized LDL (ox-LDL) in cultured endothelial cells, and whether the protective effect of EGCG is related to reduction of ADMA level. A single injection of LDL (4 mg x kg(-1), i.v.) markedly reduced endothelium-dependent relaxation and the serum nitrite/nitrate (NO) level, and increased serum concentrations of ADMA, malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-alpha). EGCG (10 or 50 mg x kg(-1), i.p.) significantly attenuated the inhibition of vasodilator response to acetylcholine and the decreased serum nitrite/nitrate level, and reduced the elevated levels of ADMA, MDA, and TNF-alpha. Exposure of endothelial cells to ox-LDL (100 microg x mL(-1)) for 24 h markedly increased the medium levels of lactate dehydrogenase (LDH), ADMA, TNF-alpha, and MDA, and decreased the level of nitrite/nitrate in the medium and the activity of dimethylarginine dimethylaminohydrolase (DDAH) in the endothelial cells. EGCG (10 and 100 microg x mL(-1)) significantly decreased the levels of LDH, ADMA, TNF-alpha, and MDA, and increased the level of nitrite/nitrate and the activity of DDAH. These results suggest that EGCG protects endothelial dysfunction induced by native LDL in vivo or by ox-LDL in endothelial cells, and the protective effect of EGCG on the endothelium is related to decrease in ADMA level via increasing of DDAH activity.

[Regional modulation of primary motor cortex after peripheral nerve injury: a functional magnetic resonance imaging study].

OBJECTIVE: To map dynamic changes of primary motor cortex after total brachial plexus traction injury by using functional magnetic resonance imaging, and to explore underlying probable mechanisms. METHODS: Five patients with total traumatic root avulsions of the brachial plexus underwent varied kinds of nerve transfer to restore partially shoulder or elbow function. Four of them (cases 1, 3, 4, 5) accepted the first fMRI examination prior to surgery treatment, and four of them (cases 2, 3, 4, 5) accepted second or third or fourth fMRI follow-up re-examinations after surgery treatment. Maps of neuronal activation within the motor cortex were generated for both hands in each patient by using BOLD-fMRI and the cluster size and position were recorded. The motor tasks consisted of simple hand grasping of both hands respectively. Patients with paralytic hand were asked to complete task under "virtual" condition. The cluster size and intensity as well as location of motor activation within the primary motor cortex of the affected hand generated were compared with those of unaffected hand generated as reference in single subject, and the resultant maps of follow-up re-examinations were also compared with those of the prior examinations. RESULTS: All patients' unaffected hand movement generated strong signal change within the contralateral primary motor cortex. In contrast, the clusters generated by affected hand showed very small and lower intensity than usual (2 cases) or could not be induced (2 case) in the first examination that prior to surgery treatment and seemed larger gradually in the following re-examination with time increasing. CONCLUSION: Peripheral nerve injury can produced significant changes in the motor cortex of human brain. fMRI is a valuable tool to evaluate neural plasticity in motor cortex after peripheral nerve injury.