Longitudinal assessment of cervical spinal cord compartments in multiple sclerosis.

BACKGROUND: Although cervical spinal cord (cSC) area is an established biomarker in MS, there is currently a lack of longitudinal assessments of cSC gray and white matter areas. OBJECTIVE: We conducted an explorative analysis of longitudinal changes of cSC gray and white matter areas in MS patients. METHODS: 65 MS patients (33 relapsing-remitting; 20 secondary progressive and 12 primary progressive) and 20 healthy controls (HC) received clinical and upper cSC MRI assessments over 1.10±0.28 years. cSC compartments were quantified on MRI using the novel averaged magnetization inversion recovery acquisitions sequence (in-plane resolution=0.67 × 0.67mm2), and in-house developed post-processing methods. Patients were stratified regarding clinical progression. RESULTS: Patients with clinical progression showed faster reduction of cSC areas over time at the level of cSC enlargement (approximate vertebral level C4-C5) compared to stable patients (p<0.05). In addition, when compared to the rostral-cSC (approximate vertebral level C2-C3), a preferential reduction of cSC and white matter areas over time at the level of cSC enlargement (p<0.05 and p<0.01, respectively) was demonstrated only in patients with clinical progression, but not in stable MS patients and HC. Compared to HC, MS patients showed comparable changes over time in all cSC compartments. CONCLUSIONS: MS patients with clinical disease progression demonstrate subtle signs of a more pronounced tissue loss at the level of cSC enlargement. Future studies should consider larger sample sizes and more extended observation periods.

Protective Effects of Lovastatin in a Population-Based ALS Study and Mouse Model.

OBJECTIVE: The objective of this study was to use a novel combined pharmacoepidemiologic and amyotrophic lateral sclerosis (ALS) mouse model approach to identify potential motor neuron protective medications. METHODS: We constructed a large, population-based case-control study to investigate motor neuron disease (MND) among US Medicare beneficiaries aged 66 to 90 in 2009. We included 1,128 incident MND cases and 56,400 age, sex, race, and ethnicity matched controls. We calculated MND relative risk for >1,000 active ingredients represented in Part D (pharmacy) claims in 2006 to 2007 (>1 year before diagnosis/reference). We then applied a comprehensive screening approach to select medications for testing in SOD1G93A mice: sulfasalazine, telmisartan, and lovastatin. We treated mice with the human dose equivalent of the medication or vehicle via subcutaneous osmotic pump before onset of weakness. We then assessed weight, gait, and survival. In additional mice, we conducted histological studies. RESULTS: We observed previously established medical associations for MND and an inverse dose-response association between lovastatin and MND, with 28% reduced risk at 40 mg/day. In SOD1G93A mouse studies, sulfasalazine and telmisartan conferred no benefit, whereas lovastatin treatment delayed onset and prolonged survival. Lovastatin treated mice also had less microgliosis, misfolded SOD1, and spinal motor neuron loss in the ventral horn. INTERPRETATION: Lovastatin reduced the risk of ALS in humans, which was confirmed in an ALS mouse model by delayed symptom onset, prolonged survival, and preservation of motor neurons. Although further studies to understand the mechanism are required, lovastatin may represent a potential neuroprotective therapy for patients with ALS. These data demonstrate the utility of a combined pharmacoepidemiologic and mouse model approach. ANN NEUROL 2023;93:881-892.

Non-invasive near-infrared spectroscopy assessment of the spinal neurovascular response in a patient with transverse myelitis: a case report.

BACKGROUND: Transverse myelitis (TM) is characterized by acute development of motor, sensory and autonomic dysfunctions due to horizontally diffused inflammation in one or more segments of the spinal cord in the absence of a compressive lesion. The not well-known inflammation process induces demyelination resulting in neurological dysfunction. CASE PRESENTATION: In this case report we used a functional Near-Infrared Spectroscopy (fNIRS) technique to evaluate changes in the peri-spinal vascular response induced by a peripheral median nerve electrical stimulation in a patient with chronic transverse myelitis (TM). fNIRS showed drastically reduced signal amplitude in the peri-spinal vascular response, compared to that obtained from a healthy control group throughout most of the C7-T1 and T10-L2 spinal cord segments. CONCLUSION: The potential use of this relatively non-invasive fNIRS technology support the potential clinical application of this method for functional test of the spinal cord through the assessment of the spinal neurovascular response.

Assessment of cervical spinal cord volume in pediatric-onset multiple sclerosis.

PURPOSE: Several studies of adult-onset multiple sclerosis (AOMS) patients have demonstrated that spinal cord volume loss is associated with disease progression and clinical disability. However, complementary studies of young patients with pediatric-onset multiple sclerosis (POMS) are lacking. Our retrospective study aimed to assess spinal cord volume in POMS patients compared with that in healthy controls. METHODS: Cervical spinal cord magnetic resonance images were evaluated for 20 POMS patients and 20 age- and sex-matched controls. Cross-sectional areas (CSAs) were measured at C2 and C7, along with the spinal cord average segmental area (CASA). The POMS group was further subdivided based on the presence or absence of spinal cord lesions, specifically C2 lesions. Pairwise area and volume comparisons were made across the different groups. RESULTS: No significant difference was found in CASA and CSA at C2 and C7 between POMS patients and comparative controls. However, CASA, CSA at C7, and estimated spinal cord volume were significantly lower in a small subset of POMS patients with C2 lesions (3 patients) than in controls (P = 0.001, 0.02, and 0.001, respectively). CONCLUSION: No significant difference was found in spinal cord areas and volumes between POMS patients and controls. This finding contrasts with spinal cord volume measurements in AOMS patients.

Assessment of acute traumatic cervical spinal cord injury using conventional magnetic resonance imaging in combination with diffusion tensor imaging-tractography: a retrospective comparative study.

PURPOSE: The application of conventional magnetic resonance imaging (MRI) in combination with diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) to diagnose acute traumatic cervical SCI has not been studied. This study explores the role of MRI with DTI-DTT in the diagnosis of acute traumatic cervical spinal cord injury (SCI). METHODS: Thirty patients with acute traumatic cervical SCI underwent conventional MRI and DTI-DTT. Conventional MRI was used to detect the intramedullary lesion length (IMLL) and intramedullary hemorrhage length (IMHL). DTI was used to detect the spinal cord's fractional anisotropy (FA) and apparent diffusion coefficient value, and DTT detected the imaginary white matter fiber volume and the connection rates of fiber tractography (CRFT). Patients' neurological outcome was determined using the American Spinal Injury Association (ASIA) Impairment Scale (AIS) grades. RESULTS: Patients were divided into group A (without AIS grade conversion) and group B (with AIS grade conversion). The IMLL and IMHL of group A were significantly higher than those of group B. The FA and CRFT of group A were significantly lower than those of group B. The final AIS grade was negatively correlated with the IMLL and IMHL, and positively correlated with the FA and CRFT. According to imaging features based on conventional MRI and DTI-DTT, we propose a novel classification and diagnostic procedure. CONCLUSIONS: The combination of conventional MRI with DTI-DTT is a valid diagnostic approach for SCI. Lower IMLL and IMHL, and higher FA value and CRFT are linked to better neurological outcomes.

Simultaneous assessment of regional distributions of atrophy across the neuraxis in MS patients.

BACKGROUND: The ability to assess brain and cord atrophy simultaneously would improve the efficiency of MRI to track disease evolution. OBJECTIVE: To test a promising tool to simultaneously map the regional distribution of atrophy in multiple sclerosis (MS) patients across the brain and cord. METHODS: Voxel-based morphometry combined with a statistical parametric mapping probabilistic brain-spinal cord (SPM-BSC) template was applied to standard T1-weighted magnetic resonance imaging (MRI) scans covering the brain and cervical cord from 37 MS patients and 20 healthy controls (HC). We also measured the cord area at C2-C3 with a semi-automatic segmentation method using (i) the same T1-weighted acquisitions used for the new voxel-based analysis and (ii) dedicated spinal cord phase sensitive inversion recovery (PSIR) acquisitions. Cervical cord findings derived from the three approaches were compared to each other and the goodness to fit to clinical scores was assessed by regression analyses. RESULTS: The SPM-BSC approach revealed a severity-dependent pattern of atrophy across the cervical cord and thalamus in MS patients when compared to HCs. The magnitude of cord atrophy was confirmed by the semi-automatic extraction approach at C2-C3 using both standard brain T1-weighted and advanced cord dedicated acquisitions. Associations between atrophy of cord and thalamus with disability and cognition were demonstrated. CONCLUSION: Atrophy in the brain and cervical cord of MS patients can be identified simultaneously and rapidly at the voxel-level. The SPM-BSC approach yields similar results as available standard processing tools with the added advantage of performing the analysis simultaneously and faster.

Improved Assessment of Longitudinal Spinal Cord Atrophy in Multiple Sclerosis Using a Registration-Based Approach: Relevance for Clinical Studies.

BACKGROUND: Reliable measurements of cervical cord atrophy progression may be useful for monitoring neurodegeneration in multiple sclerosis (MS). PURPOSE: To compare a new, registration-based (Reg) method with two existing methods (active surface [AS] and propagation segmentation [PropSeg]) to measure cord atrophy changes over time in MS. STUDY TYPE: Retrospective. SUBJECTS: Cohort I: Eight healthy controls (HC) and 28 MS patients enrolled at a single institution, and cohort II: 25 HC and 63 MS patients enrolled at three European sites. FIELD STRENGTH/SEQUENCE: 3D T1-weighted gradient echo sequence, acquired at 1.5 T (cohort I) and 3.0 T (cohort II). ASSESSMENT: Percentage cord area changes (PCACs) between baseline and follow-up (cohort I: 2.34 years [interquartile range = 2.00-2.55 years], cohort II: 1.05 years [interquartile range = 1.01-1.18 years]) were evaluated for all subjects using Reg, AS, and PropSeg. Reg included an accurate registration of baseline and follow-up straightened cord images, followed by AS-based optimized cord segmentation. A subset of studies was analyzed twice by two observers. STATISTICAL TESTS: Linear regression models were used to estimate annualized PCAC, and effect sizes expressed as the ratio between the estimated differences and HC error term (P < 0.05). Reproducibility was assessed by linear mixed-effect models. Annualized PCACs were used for sample size calculations (significance: α = 0.05, power: 1 - ß = 0.80). RESULTS: Annualized PCACs and related standard errors (SEs) were lower with Reg than with other methods: PCAC in MS patients at 1.5 T was -1.12% (SE = 0.22) with Reg, -1.32% (SE = 0.30) with AS, and -1.40% (SE = 0.33) with PropSeg, while at 3.0 T PCAC was -0.83% (SE = 0.25) with Reg, -0.92% (SE = 0.32) with AS, and -1.18 (SE = 0.53) with PropSeg. This was reflected in larger effect sizes and lower sample sizes. Intra- and inter-observer agreement range was 0.72-0.91 with AS, and it was >0.96 with Reg. DATA CONCLUSION: The results support the use of the registration method to measure cervical cord atrophy progression in future MS clinical studies. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Potential of intraoperative ultrasonographic assessment of the spinal cord central echo complex in predicting postoperative neurological recovery of degenerative cervical myelopathy.

BACKGROUND AND PURPOSE: The spinal cord central echo complex (SCCEC) is a special ultrasonography-based intramedullary structure, but its clinical significance in degenerative cervical myelopathy (DCM) is undefined. This study aimed to explore the potential of the SCCEC in predicting postoperative neurological recovery in DCM. METHODS: Thirty-two DCM patients who underwent intraoperative ultrasonography-guided French-door laminoplasty were prospectively enrolled. The modified Japanese Orthopaedic Association (mJOA) score was evaluated preoperatively and 12 months postoperatively. SCCEC width (SCCEC-W), and anteroposterior diameter (APD) and transverse diameter (TD) of the spinal cord were measured on transverse ultrasonographic images, while the tissue widths from anterior and posterior borders of the spinal cord to the SCCEC were measured on sagittal ultrasonographic images. The APD of the spinal cord and occupying rate of the spinal canal were measured on preoperative magnetic resonance imaging (MRI). RESULTS: All patients achieved improvements in mJOA scores, with an average recovery rate (RR) of 68.69 ± 20.22%. Spearman correlation analysis revealed that SCCEC-W, and ratios between the SCCEC-W and APD/TD based on ultrasonography, correlated moderately with mJOA score RR, with coefficients of -0.527, -0.605 and -0.514, respectively. The ratio between SCCEC-W and ultrasonographic TD correlated moderately with preoperative APD of the spinal cord. The MRI measurements and ultrasonography-based tissue widths showed no significant correlation with mJOA score RR. CONCLUSIONS: The SCCEC may have predictive potential as an intraoperative indicator of neurological recovery in treating DCM. SCCEC-W may be related to spinal cord compression in DCM.

Intravital Assessment of Cells Responses to Conducting Polymer-Coated Carbon Microfibres for Bridging Spinal Cord Injury.

The extension of the lesion following spinal cord injury (SCI) poses a major challenge for regenerating axons, which must grow across several centimetres of damaged tissue in the absence of ordered guidance cues. Biofunctionalized electroconducting microfibres (MFs) that provide biochemical signals, as well as electrical and mechanical cues, offer a promising therapeutic approach to help axons overcome this blind journey. We used poly(3,4-ethylenedioxythiophene)-coated carbon MFs functionalized with cell adhesion molecules and growth factors to bridge the spinal cord after a partial unilateral dorsal quadrant lesion (PUDQL) in mice and followed cellular responses by intravital two-photon (2P) imaging through a spinal glass window. Thy1-CFP//LysM-EGFP//CD11c-EYFP triple transgenic reporter animals allowed real time simultaneous monitoring of axons, myeloid cells and microglial cells in the vicinity of the implanted MFs. MF biocompatibility was confirmed by the absence of inflammatory storm after implantation. We found that the sprouting of sensory axons was significantly accelerated by the implantation of functionalized MFs after PUDQL. Their implantation produced better axon alignment compared to random and misrouted axon regeneration that occurred in the absence of MF, with a most striking effect occurring two months after injury. Importantly, we observed differences in the intensity and composition of the innate immune response in comparison to PUDQL-only animals. A significant decrease of immune cell density was found in MF-implanted mice one month after lesion along with a higher ratio of monocyte-derived dendritic cells whose differentiation was accelerated. Therefore, functionalized carbon MFs promote the beneficial immune responses required for neural tissue repair, providing an encouraging strategy for SCI management.

A validated quantitative method for the assessment of neuroprotective barrier impairment in neurodegenerative disease models.

The blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) are highly specialized structures that limit molecule entry from the blood and maintain homeostasis within the central nervous system (CNS). BBB and BSCB breakdown are associated with multiple neurodegenerative diseases. Given the key role of neuroprotective barrier impairment in neurodegeneration, it is important to identify an effective quantitative method to assess barrier integrity in animal models. In this study, we developed and validated a quantitative method for assessing BBB and BSCB integrity using sodium fluorescein, a compound that outperformed other fluorescent dyes. We demonstrated using this method that multiple CNS regions progressively increase in permeability in models of Huntington's disease and amyotrophic lateral sclerosis, whereas biphasic disruption occurred in a mouse model of Alzheimer's disease with disease progression. Collectively, we report a quantitative fluorometric marker with validated reproducible experimental methods that allows the effective assessment of BBB and BSCB integrity in animal models. This method could be useful to further the understanding of the contribution of these neuroprotective barriers to neurodegeneration processes.

Real-Time Assessment of Spinal Cord Microperfusion in a Porcine Model of Ischemia/Reperfusion.

Spinal cord injury is a devastating complication of aortic repair. Despite developments for the prevention and treatment of spinal cord injury, its incidence is still considerably high and therefore, influences patient outcome. Microcirculation plays a key role in tissue perfusion and oxygen supply and is often dissociated from macrohemodynamics. Thus, direct evaluation of spinal cord microcirculation is essential for the development of microcirculation-targeted therapies and the evaluation of existing approaches in regard to spinal cord microcirculation. However, most of the methods do not provide real-time assessment of spinal cord microcirculation. The aim of this study is to describe a standardized protocol for real-time spinal cord microcirculatory evaluation using laser-Doppler needle probes directly inserted in the spinal cord. We used a porcine model of ischemia/reperfusion to induce deterioration of the spinal cord microcirculation. In addition, a fluorescent microsphere injection technique was used. Initially, animals were anesthetized and mechanically ventilated. Thereafter, laser-Doppler needle probe insertion was performed, followed by the placement of cerebrospinal fluid drainage. A median sternotomy was performed for exposure of the descending aorta to perform aortic cross-clamping. Ischemia/reperfusion was induced by supra-celiac aortic cross-clamping for a total of 48 min, followed by reperfusion and hemodynamic stabilization. Laser-Doppler Flux was performed in parallel with macrohemodynamic evaluation. In addition, automated cerebrospinal fluid drainage was used to maintain a stable cerebrospinal pressure. After completion of the protocol, animals were sacrificed, and the spinal cord was harvested for histopathological and microsphere analysis. The protocol reveals the feasibility of spinal cord microperfusion measurements using laser-Doppler probes and shows a marked decrease during ischemia as well as recovery after reperfusion. Results showed comparable behavior to fluorescent microsphere evaluation. In conclusion, this new protocol might provide a useful large animal model for future studies using real-time spinal cord microperfusion assessment in ischemia/reperfusion conditions.

Longitudinal assessment of recovery after spinal cord injury with behavioral measures and diffusion, quantitative magnetization transfer and functional magnetic resonance imaging.

Spinal cord injuries (SCIs) are a leading cause of disability and can severely impact the quality of life. However, to date, the processes of spontaneous repair of damaged spinal cord remain incompletely understood, partly due to a lack of appropriate longitudinal tracking methods. Noninvasive, multiparametric magnetic resonance imaging (MRI) provides potential biomarkers for the comprehensive evaluation of spontaneous repair after SCI. In this study in rats, a clinically relevant contusion injury was introduced at the lumbar level that impairs both hindlimb motor and sensory functions. Quantitative MRI measurements were acquired at baseline and serially post-SCI for up to 2 wk. The progressions of injury and spontaneous recovery in both white and gray matter were tracked longitudinally using pool-size ratio (PSR) measurements derived from quantitative magnetization transfer (qMT) methods, measurements of water diffusion parameters using diffusion tensor imaging (DTI) and intrasegment functional connectivity derived from resting state functional MRI. Changes in these quantitative imaging measurements were correlated with behavioral readouts. We found (a) a progressive decrease in PSR values within 2 wk post-SCI, indicating a progressive demyelination at the center of the injury that was validated with histological staining, (b) PSR correlated closely with fractional anisotropy and transverse relaxation of free water, but did not show significant correlations with behavioral recovery, and (c) preliminary evidence that SCI induced a decrease in functional connectivity between dorsal horns below the injury site at 24 h. Findings from this study not only confirm the value of qMT and DTI methods for assessing the myelination state of injured spinal cord but indicate that they may also have further implications on whether therapies targeted towards remyelination may be appropriate. Additionally, a better understanding of changes after SCI provides valuable information to guide and assess interventions.

Establishment of Neurobehavioral Assessment System in Tree Shrew SCT Model.

Tree shrews, possessing higher developed motor function than rats, were more suitable to study neurological behavior after spinal cord injury (SCI). Here, we established a feasible behavioral assessment method to detect the degree of ethology recovery in tree shrew subjected to spinal cord transection (SCT). Tree shrews were divided into normal group, sham group, and SCT group. The tree shrew in sham group was subjected to laminectomy without SCI, while the tree shrews in the SCT group were subjected to a complete SCT in thoracic 10 (T10). A novel neurobehavior assessment scale was established, in which, the behavior index including slow advancement, fast advancement, standing, shaking head, voluntary jump, lateral movement, and tail status, was determined, respectively. Meanwhile, magnetic resonance imaging (MRI) was applied to observe the structure of the spinal cord, and diffusion tensor imaging (DTI)-based white matter mapping was used to show the fibers of the spinal cord. As a result, a marked decrease in locomotor function and consciousness was seen in tree shrews with SCT, and the detection of MRI showed the collapsing of nerve fibers after SCT is completely cut and there is corresponding to the behavior change. Together, the present study provided a novel and feasible method that can be used to assess the neurobehavior in SCT model from tree shrews, which may be useful to the SCI translational study in future preclinic trial.

Generalised boundary shift integral for longitudinal assessment of spinal cord atrophy.

Spinal cord atrophy measurements obtained from structural magnetic resonance imaging (MRI) are associated with disability in many neurological diseases and serve as in vivo biomarkers of neurodegeneration. Longitudinal spinal cord atrophy rate is commonly determined from the numerical difference between two volumes (based on 3D surface fitting) or two cross-sectional areas (CSA, based on 2D edge detection) obtained at different time-points. Being an indirect measure, atrophy rates are susceptible to variable segmentation errors at the edge of the spinal cord. To overcome those limitations, we developed a new registration-based pipeline that measures atrophy rates directly. We based our approach on the generalised boundary shift integral (GBSI) method, which registers 2 scans and uses a probabilistic XOR mask over the edge of the spinal cord, thereby measuring atrophy more accurately than segmentation-based techniques. Using a large cohort of longitudinal spinal cord images (610 subjects with multiple sclerosis from a multi-centre trial and 52 healthy controls), we demonstrated that GBSI is a sensitive, quantitative and objective measure of longitudinal spinal cord volume change. The GBSI pipeline is repeatable, reproducible, and provides more precise measurements of longitudinal spinal cord atrophy than segmentation-based methods in longitudinal spinal cord atrophy studies.

Diffusion Tensor Imaging Assessment of Regional White Matter Changes in the Cervical and Thoracic Spinal Cord in Pediatric Subjects.

There are no studies to date,describing changes in the diffusion tensor imaging (DTI) metrics of the white matter (WM) regions of the entire cervical and thoracic spinal cord (SC) remote from the lesion in pediatric spinal cord injury (SCI) subjects. The purpose of this study was to determine whether DTI at sites cephalad and caudal to a lesion provides measures of cord abnormalities in children with chronic SCI. A retrospective study included 10 typically developing subjects (TD) and 10 subjects with chronic SCI who underwent SC imaging in 2014-2017. Axial diffusion tensor images using an inner field of view DTI sequence were acquired to cover the entire cervical and thoracic SC. Regions of interest were drawn on the SC WM: right and left lateral (motor), ventral (motor), and dorsal (sensory) tracts. To detect differences in DTI metrics between TD and SCI of the cord, a one way analysis of variance with pooled t test was performed. A stepwise regression analysis was performed to assess the correlation between DTI metrics and clinical scores. In motor and sensory tracts, fractional anisotropy (FA) and axial diffusivity (AD) were significantly decreased in the proximal segments of the caudal cord. In motor tracts cephalad to the lesion, FA was significantly decreased whereas AD was significantly increased in the proximal segment; however, AD was decreased in the distal and middle segments. International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) total score was significantly correlated with FA and AD of the motor and sensory tracts cephalad to the lesion. This study demonstrates that FA and AD have the potential to be sensitive biomarkers of the full extent of cord injury and might be useful in detecting remote injuries to the SC and in guiding new treatments.

Non-invasive assessment of disease progression and neuroprotective effects of dietary coconut oil supplementation in the ALS SOD1G93A mouse model: A 1H-magnetic resonance spectroscopic study.

Amyotrophic Lateral Sclerosis (ALS) is an incurable neurodegenerative disease primarily characterized by progressive degeneration of motor neurons in the motor cortex, brainstem and spinal cord. Due to relatively fast progression of ALS, early diagnosis is essential for possible therapeutic intervention and disease management. To identify potential diagnostic markers, we investigated age-dependent effects of disease onset and progression on regional neurochemistry in the SOD1G93A ALS mouse model using localized in vivo magnetic resonance spectroscopy (MRS). We focused mainly on the brainstem region since brainstem motor nuclei are the primarily affected regions in SOD1G93A mice and ALS patients. In addition, metabolite profiles of the motor cortex were also assessed. In the brainstem, a gradual decrease in creatine levels were detected starting from the pre-symptomatic age of 70 days postpartum. During the early symptomatic phase (day 90), a significant increase in the levels of the inhibitory neurotransmitter γ- aminobutyric acid (GABA) was measured. At later time points, alterations in the form of decreased NAA, glutamate, glutamine and increased myo-inositol were observed. Also, decreased glutamate, NAA and increased taurine levels were seen at late stages in the motor cortex. A proof-of-concept (PoC) study was conducted to assess the effects of coconut oil supplementation in SODG93A mice. The PoC revealed that the coconut oil supplementation together with the regular diet delayed disease symptoms, enhanced motor performance, and prolonged survival in the SOD1G93A mouse model. Furthermore, MRS data showed stable metabolic profile at day 120 in the coconut oil diet group compared to the group receiving a standard diet without coconut oil supplementation. In addition, a positive correlation between survival and the neuronal marker NAA was found. To the best of our knowledge, this is the first study that reports metabolic changes in the brainstem using in vivo MRS and effects of coconut oil supplementation as a prophylactic treatment in SOD1G93A mice.

Assessment of the corticospinal fiber integrity in mirror movement disorder.

Mirror movements are unintended movements occurring on one side of the body that mirror the contralateral voluntary ones. It has been proposed that mirror movements occur due to abnormal decussation of the corticospinal pathways. Using detailed multidisciplinary approach, we aimed to enlighten the detailed mechanism underlying the mirror movements in a case subject who is diagnosed with mirror movements of the hands and we compared the findings with the unaffected control subjects. To evaluate the characteristics of mirror movements, we used several techniques including whole exome sequencing, computed tomography, diffusion tensor imaging and transcranial magnetic stimulation. Computed tomography showed the absence of a spinous process of C5, fusion of the body of C5-C6 vertebrae, hypoplastic dens and platybasia of the posterior cranial fossa. A syrinx cavity was present between levels C3-C4 of the spinal cord. Diffusion tensor imaging of the corticospinal fibers showed disorganization and minimal decussations at the lower medulla oblongata. Transcranial magnetic stimulation showed that motor commands were distributed to the motor neuron pools on the left and right sides of the spinal cord via fast-conducting corticospinal tract fibers. Moreover, a heterozygous missense variation in the deleted in colorectal carcinoma gene has been observed. Developmental absence of the axonal guidance molecules or their receptors may result in abnormalities in the leading of the corticospinal fibers. Clinical evaluations and basic neuroscience techniques, in this case, provide information for this rare disease and contribute to our understanding of the normal physiology of bimanual coordination.

Brain Motor Control Assessment Post Early Intensive Hand Rehabilitation After Spinal Cord Injury.

Background: The Brain Motor Control Assessment (BMCA) is a surface electromyography (sEMG)-based measure of motor output from the central nervous system during a variety of reflex and voluntary motor tasks. Objective: The aim of this study was to assess the pattern of voluntary movements in patients with spinal cord injury (SCI) to investigate whether BMCA could add more resolution to clinical assessments and the recovery path of these patients. Method: Ten participants were recruited from the Royal Talbot Rehabilitation Centre as part of a multicenter randomized controlled trial. Four participants received usual care while the other 3 participants received usual care plus an intensive task-specific hand training program in conjunction with functional electrical stimulation for 8 weeks. BMCA assessments were completed for 7 participants at this center 4 times over a period of 1 year. Results: Generalized linear model analysis showed a significant main effect of task (p < .001) and assessment time (p = .003) on the Similarity Index. However, there were no significant interactions among the factors (p > .05). Based on ARAT or summed upper limb strength scores, some participants showed significant improvement after 8 weeks of rehabilitation, however this improvement was not reflected in the pattern of muscle activation that was captured by BMCA. Conclusion: The quantifiable features of BMCA through surface EMG may increase the resolution of SCI characterization by adding subclinical details to the clinical picture of lesion severity and progression during rehabilitation.

Assessment of Neurological Toxicity of Hydroxyethyl Starch 130/0.4 Injected in the Intrathecal Space in Rats.

Objective: Epidural blood patch is the procedure of choice to relieve postdural puncture headache. Hydroxyethyl-starch (HES) has been proposed as a patch in some circumstances such as in the case of hematological disease due to the theoretical risk of neoplastic seeding to the central nervous system. Acute neurological HES toxicity has been excluded by a previous animal study, but the long-term neurological toxicity has not been evaluated. Methods: Rats were randomly assigned to one of three groups: no intrathecal injection, 20 µL of intrathecal saline, or a 20-µL intrathecal HES (6% hydroxyethyl starch 130/0.4) administered via a cervical puncture. Clinical daily rat activity was measured before and after dural puncture by actinometry. The rats were killed at day 28, and the spinal cord was surgically removed and stained with hematoxylin-phloxine-saffron for gross and microscopic examination. Results: Eleven rats underwent dural puncture without injection, 11 were injected with normal saline, and 12 received intrathecal HES. No clinical or actimetric changes (total distance traveled, number of direction changes, and number of rearings) were observed up to one month after injection. Nonspecific histopathological changes were equally observed in all groups. Conclusions: The results of the current study indicate that intrathecal injection of HES in rats does not induce any clinical or histopathological evidence of long-term neuronal toxicity. Further safety studies in animals are warranted before HES might be considered a safe alternative to the classic epidural blood patch.