Viral expression of constitutively active AKT3 induces CST axonal sprouting and regeneration, but also promotes seizures.

Increasing the intrinsic growth potential of neurons after injury has repeatedly been shown to promote some level of axonal regeneration in rodent models. One of the most studied pathways involves the activation of the PI3K/AKT/mTOR pathways, primarily by reducing the levels of PTEN, a negative regulator of PI3K. Likewise, activation of signal transducer and activator of transcription 3 (STAT3) has previously been shown to boost axonal regeneration and sprouting within the injured nervous system. Here, we examined the regeneration of the corticospinal tract (CST) after cortical expression of constitutively active (ca) Akt3 and STAT3, both separately and in combination. Overexpression of caAkt3 induced regeneration of CST axons past the injury site independent of caSTAT3 overexpression. STAT3 demonstrated improved axon sprouting compared to controls and contributed to a synergistic improvement in effects when combined with Akt3 but failed to promote axonal regeneration as an individual therapy. Despite showing impressive axonal regeneration, animals expressing Akt3 failed to show any functional improvement and deteriorated with time. During this period, we observed progressive Akt3 dose-dependent increase in behavioral seizures. Histology revealed increased phosphorylation of ribosomal S6 protein within the unilateral cortex, increased neuronal size, microglia activation and hemispheric enlargement (hemimegalencephaly).

Laplacian-Regularized Mean Apparent Propagator-MRI in Evaluating Corticospinal Tract Injury in Patients with Brain Glioma.

OBJECTIVE: To evaluate the application of laplacian-regularized mean apparent propagator (MAPL)-MRI to brain glioma-induced corticospinal tract (CST) injury. MATERIALS AND METHODS: This study included 20 patients with glioma adjacent to the CST pathway who had undergone structural and diffusion MRI. The entire CSTs of the affected and healthy sides were reconstructed, and the peritumoral CSTs were manually segmented. The morphological characteristics of the CST (track number, average length, volume, displacement of the affected CST) were examined and the diffusion parameter values, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), mean squared displacement (MSD), q-space inverse variance (QIV), return-to-origin probability (RTOP), return-to-axis probabilities (RTAP), and return-to-plane probabilities (RTPP) along the entire and peritumoral CSTs, were calculated. The entire and peritumoral CST characteristics of the affected and healthy sides as well as those relative CST characteristics of the patients with motor weakness and normal motor function were compared. RESULTS: The track number, volume, MD, RD, MSD, QIV, RTAP, RTOP, and RTPP of the entire and peritumoral CSTs changed significantly for the affected side, whereas the AD and FA changed significantly only in the peritumoral CST (p < 0.05). In patients with motor weakness, the relative MSD of the entire CST, QIV of the entire and peritumoral CSTs, and the AD, MD, RD of the peritumoral CST were significantly higher, whereas the RTPP of the entire and peritumoral CSTs and the RTOP of the peritumoral CST were significantly lower than those in patients with normal motor function (p < 0.05 for all). In contrast, no significant changes were found in the CST morphological characteristics, FA, or RTAP (p > 0.05 for all). CONCLUSION: MAPL-MRI is an effective approach for evaluating microstructural changes after CST injury. Its sensitivity may improve when using the peritumoral CST features.

A preliminary study on the application of DTI in the treatment of brain tumors in motor function areas with gamma knife.

OBJECTIVES: The treatment safety and efficiency as well as the life quality of patients are still main concerns in gamma knife radiosurgery. In this study, the feasibility of applying diffusion tensor imaging (DTI) in gamma knife radiosurgery for the treatment of brain tumor in motor function areas was investigated, which aims to provide protection on the pyramidal tract and preserve the motor function in patients. PATIENTS AND METHODS: Total 74 patients with solid brain tumor were enrolled and divided into DTI group and control group. The tumor control rate was assessed at 3 months after surgery. The muscle strength of affected limb, KPS scores, ZEW scores and complications were evaluated at 3 and 6 months after gamma knife radiosurgery. RESULTS: Our results indicated that the tumor control rate, complication rate, the muscle strength of affected limb and KPS scores were not significantly different between the two groups at 3 months after surgery. At 6 months after gamma knife radiosurgery, the complication rate (0% vs 50 %, P = 0.044), KPS scores (64.9 % vs 37.8 %, P = 0.036) and ZEW scores (78.4 % vs 54.1 %, P = 0.044) of DTI group were better than the control group. Furthermore, the stability of muscle strength in patients with limb dysfunction was significantly improved in DTI group (86.4 % vs 50 %, P = 0.028). CONCLUSION: In summary, the application of DTI in gamma knife radiosurgery for the treatment of brain tumors in motor function areas can precisely define the tumor edge from pyramidal tract, which will support on designing individual treatment plan, reducing the incidence of complications, and improving long-term life quality in patients.

[Quantitative characterization of risk of iatrogenic damage to pyramidal tracts based on data of intraoperative neuromonitoring during surgical correction of spinal deformities]. / Kolichestvennaia kharakteristika riska iatrogennykh povrezhdenii piramidnykh putei po dannym intraoperatsionnogo neiromonitoringa pri khirurgicheskoi korrektsii deformatsii pozvonochnika.

OBJECTIVE: Development of a quantitative indicator for the risk level of intraoperative iatrogenic motor disorders in the process of surgical correction of spinal deformity based on current neurophysiological monitoring data. MATERIAL AND METHODS: 288 patients 12.6±0.35 y.o. underwent surgical correction of spinal deformities under the control of intraoperative neuromonitoring. The nature of changes in motor evoked potentials was assessed according to the earlier proposed ranking scale. The incidence of different variants of changes in the rank values of the state of the pyramidal system during the operation and the resulting postoperative motor disturbances was calculated. RESULTS: By comparing probabilities of various changes in the conduction properties of pyramidal tracts during surgery with the incidence of the observed motor deficiencies we quantitatively assessed the possible correlation between these phenomena. We propose a method for calculating the risk index for postoperative motor disorders depending on the maximum rank of the pyramidal system's response to surgical aggression. CONCLUSION: The developed system of ranking evaluation of changes in motor evoked potentials during surgical correction of spinal deformity makes it possible to quantify the risk of postoperative motor disorders and, accordingly, to monitor the level of anxiety for a neurosurgeon during individual stages of surgical intervention.

Automated Forelimb Tasks for Rodents: Current Advantages and Limitations, and Future Promise.

Rodent tests of function have advanced our understanding of movement, largely through the human training and testing and manual assessment. Tools such as reaching and grasping of a food pellet have been widely adopted because they are effective and simple to use. However, these tools are time-consuming, subjective, and often qualitative. Automation of training, testing, and assessment has the potential to increase efficiency while ensuring tasks are objective and quantitative. We detail new methods for automating rodent forelimb tests, including the use of pellet dispensers, sensors, computer vision, and home cage systems. We argue that limitations in existing forelimb tasks are driving the innovations in automated systems. We further argue that automated tasks partially address these limitations, and we outline necessary precautions and remaining challenges when adopting these types of tasks. Finally, we suggest attributes of future automated rodent assessment tools that can enable widespread adoption and help us better understand forelimb function in health and disease.

Surgical strategy to avoid ischemic complications of the pyramidal tract in resective epilepsy surgery of the insula: technical case report.

Surgical treatment of the insula is notorious for its high probability of motor complications, particularly when resecting the superoposterior part. Ischemic damage to the pyramidal tract in the corona radiata has been regarded as the cause of these complications, resulting from occlusion of the perforating arteries to the pyramidal tract through the insular cortex. The authors describe a strategy in which a small piece of gray matter is spared at the bottom of the periinsular sulcus, where the perforating arteries pass en route to the pyramidal tract, in order to avoid these complications. This method was successfully applied in 3 patients harboring focal cortical dysplasia in the posterior insula and frontoparietal operculum surrounding the periinsular sulcus. None of the patients developed permanent postoperative motor deficits, and seizure control was achieved in all 3 cases. The method described in this paper can be adopted for functional preservation of the pyramidal tract in the corona radiata when resecting epileptogenic pathologies involving insular and opercular regions.

Optimal Factors of Diffusion Tensor Imaging Predicting Corticospinal Tract Injury in Patients with Brain Tumors.

OBJECTIVE: To identify the optimal factors in diffusion tensor imaging for predicting corticospinal tract (CST) injury caused by brain tumors. MATERIALS AND METHODS: This prospective study included 33 patients with motor weakness and 64 patients with normal motor function. The movement of the CST, minimum distance between the CST and the tumor, and relative fractional anisotropy (rFA) of the CST on diffusion tensor imaging, were compared between patients with motor weakness and normal function. Logistic regression analysis was used to obtain the optimal factor predicting motor weakness. RESULTS: In patients with motor weakness, the displacement (8.44 ± 6.64 mm) of the CST (p = 0.009), minimum distance (3.98 ± 7.49 mm) between the CST and tumor (p < 0.001), and rFA (0.83 ± 0.11) of the CST (p < 0.001) were significantly different from those of the normal group (4.64 ± 6.65 mm, 14.87 ± 12.04 mm, and 0.98 ± 0.05, respectively) (p = 0.009, p < 0.001, and p < 0.001). The frequencies of patients with the CST passing through the tumor (6%, p = 0.002), CST close to the tumor (23%, p < 0.001), CST close to a malignant tumor (high grade glioma, metastasis, or lymphoma) (19%, p < 0.001), and CST passing through infiltrating edema (19%, p < 0.001) in the motor weakness group, were significantly different from those of the patients with normal motor function (0, 8, 1, and 10%, respectively). Logistic regression analysis showed that decreased rFA and CST close to a malignant tumor were effective variables related to motor weakness. CONCLUSION: Decreased fractional anisotropy, combined with closeness of a malignant tumor to the CST, is the optimal factor in predicting CST injury caused by a brain tumor.

Thermal injury to corticospinal tracts and postoperative motor deficits after laser interstitial thermal therapy.

OBJECTIVE Laser interstitial thermal therapy (LITT) has been increasingly used to treat deep-seated tumors. Despite its being minimally invasive, there is a risk of LITT damaging adjacent critical structures, including corticospinal tracts (CSTs). In this study, the authors investigated the predictive value of overlap between the hyperthermic field and CSTs in determining postoperative motor deficit (PMDs). METHODS More than 140 patients underwent an LITT procedure in our institution between April 2011 and June 2015. Because of the tumor's proximity to critical structures, 80 of them underwent preoperative diffusion tensor imaging and were included in this study. Extent of the hyperthermic field was delineated by the software as thermal-damage-threshold (TDT) lines (yellow [43°C for 2 minutes], blue [43°C for 10 minutes], and white [43°C for 60 minutes]). The maximum volume and the surface area of overlaps between motor fibers and the TDT lines were calculated and compared with the PMDs. RESULTS High-grade glioma (n = 46) was the most common indication for LITT. Postoperative motor deficits (partial or complete) were seen in 14 patients (11 with permanent and 3 with temporary PMDs). The median overlap volumes between CSTs with yellow, blue, and white TDT lines in patients with any PMD (temporary or permanent) were 1.15, 0.68, and 0.41 cm3, respectively. The overlap volumes and surface areas revealed significant differences in those with PMDs and those with no deficits (p = 0.0019 and 0.003, 0.012 and 0.0012, and 0.001 and 0.005 for the yellow, blue, and white TDT lines, respectively). The receiver operating characteristic was used to select the optimal cutoff point of the overlapped volumes and areas. Cutoff points for overlap volumes and areas based on optimal sensitivity (92%-100%) and specificity (80%-90%) were 0.103, 0.068, and 0.046 cm3 and 0.15, 0.07, and 0.11 mm2 for the yellow, blue, and white TDT lines, respectively. CONCLUSIONS Even a minimal overlap between the TDT lines and CSTs can cause a PMD after LITT. Precise planning and avoidance of critical structures and important white matter fibers should be considered when treating deep-seated tumors.

Intramuscular Neurotrophin-3 normalizes low threshold spinal reflexes, reduces spasms and improves mobility after bilateral corticospinal tract injury in rats.

Brain and spinal injury reduce mobility and often impair sensorimotor processing in the spinal cord leading to spasticity. Here, we establish that complete transection of corticospinal pathways in the pyramids impairs locomotion and leads to increased spasms and excessive mono- and polysynaptic low threshold spinal reflexes in rats. Treatment of affected forelimb muscles with an adeno-associated viral vector (AAV) encoding human Neurotrophin-3 at a clinically-feasible time-point after injury reduced spasticity. Neurotrophin-3 normalized the short latency Hoffmann reflex to a treated hand muscle as well as low threshold polysynaptic spinal reflexes involving afferents from other treated muscles. Neurotrophin-3 also enhanced locomotor recovery. Furthermore, the balance of inhibitory and excitatory boutons in the spinal cord and the level of an ion co-transporter in motor neuron membranes required for normal reflexes were normalized. Our findings pave the way for Neurotrophin-3 as a therapy that treats the underlying causes of spasticity and not only its symptoms.

Functional Repair of Rat Corticospinal Tract Lesions Does Not Require Permanent Survival of an Immunoincompatible Transplant.

Cell transplantation is one of the most promising strategies for repair of human spinal cord injuries. Animal studies from a number of laboratories have shown that transplantation of olfactory ensheathing cells cultured from biopsies of the olfactory bulb mediate axonal regeneration and remyelination and restore lost functions in spinal cord injuries. For translation from small laboratory experimental injuries to the large spinal cord injuries encountered in human patients the numbers of cells that can be obtained from a patient's own olfactory bulb becomes a serious limiting factor. Furthermore, removal of an olfactory bulb requires invasive surgery and risks unilateral anosmia. We here report that xenografted mouse bulbar olfactory ensheathing cells immunoprotected by daily cyclosporine restore directed forepaw reaching function in rats with chronic C1/2 unilateral corticospinal tract lesions. Once function had been established for 10 days, cyclosporine was withdrawn. Thirteen out of 13 rats continued to increase directed forepaw reaching. Immunohistochemistry shows that in all cases neurofilament-positive axons were present in the lesion, but that the grafted cells had been totally rejected. This implies that once grafted cells have acted as bridges for axon regeneration across the lesion site their continued presence is no longer necessary for maintaining the restored function. This raises the possibility that in the future a protocol of temporary immunoprotection might allow for the use of the larger available numbers of immunoincompatible allografted cells or cell lines, which would avoid the need for removing a patient's olfactory bulb.

Restoration of skilled locomotion by sprouting corticospinal axons induced by co-deletion of PTEN and SOCS3.

The limited rewiring of the corticospinal tract (CST) only partially compensates the lost functions after stroke, brain trauma and spinal cord injury. Therefore it is important to develop new therapies to enhance the compensatory circuitry mediated by spared CST axons. Here by using a unilateral pyramidotomy model, we find that deletion of cortical suppressor of cytokine signaling 3 (SOCS3), a negative regulator of cytokine-activated pathway, promotes sprouting of uninjured CST axons to the denervated spinal cord. A likely trigger of such sprouting is ciliary neurotrophic factor (CNTF) expressed in local spinal neurons. Such sprouting can be further enhanced by deletion of phosphatase and tensin homolog (PTEN), a mechanistic target of rapamycin (mTOR) negative regulator, resulting in significant recovery of skilled locomotion. Ablation of the corticospinal neurons with sprouting axons abolishes the improved behavioural performance. Furthermore, by optogenetics-based specific CST stimulation, we show a direct limb motor control by sprouting CST axons, providing direct evidence for the reformation of a functional circuit.

A Single Bolus of Docosahexaenoic Acid Promotes Neuroplastic Changes in the Innervation of Spinal Cord Interneurons and Motor Neurons and Improves Functional Recovery after Spinal Cord Injury.

Docosahexaenoic acid (DHA) is an ω-3 polyunsaturated fatty acid that is essential in brain development and has structural and signaling roles. Acute DHA administration is neuroprotective and promotes functional recovery in animal models of adult spinal cord injury (SCI). However, the mechanisms underlying this recovery have not been fully characterized. Here we investigated the effects of an acute intravenous bolus of DHA delivered after SCI and characterized DHA-induced neuroplasticity within the adult injured spinal cord. We found robust sprouting of uninjured corticospinal and serotonergic fibers in a rat cervical hemisection SCI model. A mouse pyramidotomy model was used to confirm that this robust sprouting was not species or injury model specific. Furthermore, we demonstrated that corticospinal fibers sprouting to the denervated side of the cord following pyramidotomy contact V2a interneurons. We also demonstrated increased serotonin fibers and synaptophysin in direct contact with motor neurons. DHA also increased synaptophysin in rat cortical cell cultures. A reduction in phosphatase and tensin homolog (PTEN) has been shown to be involved in axonal regeneration and synaptic plasticity. We showed that DHA significantly upregulates miR-21 and downregulates PTEN in corticospinal neurons. Downregulation of PTEN and upregulation of phosphorylated AKT by DHA were also seen in primary cortical neuron cultures and were accompanied by increased neurite outgrowth. In summary, acute DHA induces anatomical and synaptic plasticity in adult injured spinal cord. This study shows that DHA has therapeutic potential in cervical SCI and provides evidence that DHA could exert its beneficial effects in SCI via enhancement of neuroplasticity. SIGNIFICANCE STATEMENT: In this study, we show that an acute intravenous injection of docosahexaenoic acid (DHA) 30 min after spinal cord injury induces neuroplasticity. We found robust sprouting of uninjured corticospinal and serotonergic fibers in a rat hemisection spinal cord injury model. A mouse pyramidotomy model was used to confirm that the robust sprouting involved V2a interneurons. We show that DHA significantly upregulates miR-21 and phosphorylated AKT, and downregulates phosphatase and tensin homolog (PTEN), which is involved in suppressing anatomical plasticity, in corticospinal neurons and in primary cortical neuron cultures. We conclude that acute DHA can induce anatomical and synaptic plasticity. This provides direct evidence that DHA could exert its beneficial effects in spinal cord injury via neuroplasticity enhancement.

Reciprocal interareal connections to corticospinal neurons in mouse M1 and S2.

Primary motor (M1) and secondary somatosensory (S2) cortices, although anatomically and functionally distinct, share an intriguing cellular component: corticospinal neurons (CSP) in layer 5B. Here, we investigated the long-range circuits of CSPs in mouse forelimb-M1 and S2. We found that interareal projections (S2 → M1 and M1 → S2) monosynaptically excited pyramidal neurons across multiple layers, including CSPs. Area-specific differences were observed in the relative strengths of inputs to subsets of CSPs and other cell types, but the general patterns were similar. Furthermore, subcellular mapping of the dendritic distributions of these corticocortical excitatory synapses onto CSPs in both areas also showed similar patterns. Because layer 5B is particularly thick in M1, but not S2, we studied M1-CSPs at different cortical depths, quantifying their dendritic morphology and mapping inputs from additional cortical (M2, contralateral M1, and local layer 2/3) and thalamic (VL nucleus) sources. These results indicated that CSPs exhibit area-specific modifications on an otherwise conserved synaptic organization, and that different afferents innervate M1-CSP dendritic domains in a source-specific manner. In the cervical spinal cord, CSP axons from S2 and M1 partly converged on middle layers, but S2-CSP axons extended further dorsally, and M1-CSP axons ventrally. Thus, our findings identify many shared features in the circuits of M1 and S2 and show that these areas communicate via mutual projections that give each area monosynaptic access to the other area's CSPs. These interareally yoked CSP circuits may enable M1 and S2 to operate in a coordinated yet differentiated manner in the service of sensorimotor integration.

Mammalian target of rapamycin's distinct roles and effectiveness in promoting compensatory axonal sprouting in the injured CNS.

Mammalian target of rapamycin (mTOR) functions as a master sensor of nutrients and energy, and controls protein translation and cell growth. Deletion of phosphatase and tensin homolog (PTEN) in adult CNS neurons promotes regeneration of injured axons in an mTOR-dependent manner. However, others have demonstrated mTOR-independent axon regeneration in different cell types, raising the question of how broadly mTOR regulates axonal regrowth across different systems. Here we define the role of mTOR in promoting collateral sprouting of spared axons, a key axonal remodeling mechanism by which functions are recovered after CNS injury. Using pharmacological inhibition, we demonstrate that mTOR is dispensable for the robust spontaneous sprouting of corticospinal tract axons seen after pyramidotomy in postnatal mice. In contrast, moderate spontaneous axonal sprouting and induced-sprouting seen under different conditions in young adult mice (i.e., PTEN deletion or degradation of chondroitin proteoglycans; CSPGs) are both reduced upon mTOR inhibition. In addition, to further determine the potency of mTOR in promoting sprouting responses, we coinactivate PTEN and CSPGs, and demonstrate that this combination leads to an additive increase in axonal sprouting compared with single treatments. Our findings reveal a developmental switch in mTOR dependency for inducing axonal sprouting, and indicate that PTEN deletion in adult neurons neither recapitulates the regrowth program of postnatal animals, nor is sufficient to completely overcome an inhibitory environment. Accordingly, exploiting mTOR levels by targeting PTEN combined with CSPG degradation represents a promising strategy to promote extensive axonal plasticity in adult mammals.

Corticospinal tract insult alters GABAergic circuitry in the mammalian spinal cord.

During perinatal development, corticospinal tract (CST) projections into the spinal cord help refine spinal circuitry. Although the normal developmental processes that are controlled by the arrival of corticospinal input are becoming clear, little is known about how perinatal cortical damage impacts specific aspects of spinal circuit development, particularly the inhibitory microcircuitry that regulates spinal reflex circuits. In this study, we sought to determine how ischemic cortical damage impacts the synaptic attributes of a well-characterized population of inhibitory, GABAergic interneurons, called GABApre neurons, which modulates the efficiency of proprioceptive sensory terminals in the sensorimotor reflex circuit. We found that putative GABApre interneurons receive CST input and, using an established mouse model of perinatal stroke, that cortical ischemic injury results in a reduction of CST density within the intermediate region of the spinal cord, where these interneurons reside. Importantly, CST alterations were restricted to the side contralateral to the injury. Within the synaptic terminals of the GABApre interneurons, we observed a dramatic upregulation of the 65-isoform of the GABA synthetic enzyme glutamic acid decarboxylase (GAD65). In accordance with the CST density reduction, GAD65 was elevated on the side of the spinal cord contralateral to cortical injury. This effect was not seen for other GABApre synaptic markers or in animals that received sham surgery. Our data reveal a novel effect of perinatal stroke that involves severe deficits in the architecture of a descending spinal pathway, which in turn appear to promote molecular alterations in a specific spinal GABAergic circuit.

Corticospinal tract sprouting in the injured rat spinal cord stimulated by Schwann cell preconditioning of the motor cortex.

UNLABELLED: Peripheral nerve preconditioning lesions have been shown to consistently enhance sensory nerve regeneration in the injured spinal cord. OBJECTIVE: The aim of this study was to determine if the rat motor cortex could be preconditioned through the implantation of Schwann cells (SC), thereby stimulating sprouting and regeneration of the corticospinal tract (CST). METHODS: Schwann cells (cultured in vitro) were injected into the motor cortex and seven days post-surgery rats underwent a dorsal spinal hemisection injury. Eight weeks following spinal injury animals were perfused and the CST visualised by Avidin-peroxidase histochemistry for dextran-biotin. RESULTS: Results demonstrate substantially enhanced CST collateral sprouting in both the rostral grey and white matter of the injured spinal cord in animals with SC implanted into the motor cortex compared to control animals with and without cortical vehicle injections. Corticospinal tract peri-wound regenerative sprouting was also enhanced in animals implanted with cortical SC compared to controls, however, only a small degree of CST axonal regeneration was present in the grey matter beneath the injury site. In all groups, CST peri-lesional regenerative sprouting occurred in close proximity to macrophages. Complicated and intimate relationships between CST fibres and these cells were evident. DISCUSSION: Overall, our data demonstrates that preconditioning the motor cortex with SC prior to spinal injury results in greatly enhanced CST sprouting and that CST peri-wound sprouting takes place in juxtaposition to macrophages.

Suppression of SHP-1 promotes corticospinal tract sprouting and functional recovery after brain injury.

Reorganization of spared neural network connections is one of the most important processes for restoring impaired function after brain injury. However, plasticity is quite limited in the adult brain due to the presence of inhibitory molecules and a lack of intrinsic neuronal signals for axonal growth. Src homology 2-containing phosphatase (SHP)-1 has been shown to have a role in axon growth inhibition. Here, we tested the hypothesis that SHP-1 negatively affects axonal reorganization. We observed that unilateral motor cortex injury led to increased expression and activity of SHP-1 in the contralesional cortex. In this model, corticospinal axons originating from the contralesional cortex sprouted into the denervated side of the cervical spinal cord after injury. We observed that the number of sprouting fibers was increased in SHP-1-deficient heterozygous viable motheaten (+/me(v)) mice, which show reduced SHP-1 activity, and in wild-type mice treated with an SHP inhibitor. Motor function recovery of impaired forelimb was enhanced in +/me(v) mice. Collectively, our results indicate that downregulation of SHP-1 activity promotes corticospinal tract sprouting and functional recovery after brain injury.

Usefulness of diffusion tensor imaging in patients who showed sustained unexplainable clinical symptom of torticollis.

To investigate corticospinal tract (CST) status using diffusion tensor imaging (DTI) in patients who had clinical symptom of torticollis but no definite cause of sustained symptom of torticollis. We evaluated 10 patients with sustained torticollis and 12 age-matched control subjects. All patients showed no specific fibromatosis coli findings on neck sonography. Even after intensive manual therapy, there was no improvement of clinical symptom of torticollis. DTI was performed using 1.5 T with a synergy-L Sensitivity Encoding (SENSE) head coil. Fractional anisotropy and apparent diffusion coefficient were measured using the region of interest method, and diffusion tensor tractography was conducted. We estimated the asymmetric anisotropic index (AA) and asymmetric mean diffusivity index (AD) to evaluate the asymmetry between right and left CSTs. All patients showed only torticollis symptom but no definite hemiplegic pattern on their extremities at initial evaluation. DTT, which was performed to reveal the reason of sustained asymmetric postural symptom showed hemiplegic pattern. The results of DTT corresponded to the delayed hemiplegic symptoms, which were found in the patients at second evaluation. AA and AD values between patients and control group were significantly different. Torticollis is usually caused by fibromatosis coli, but may be one of the symptoms of hemiplegia. DTI may be an additional technique for the early detection of hemiplegia in patients with sustained symptoms of unexplainable postural torticollis.