Classification of Individual Finger Movements Using Intracortical Recordings in Human Motor Cortex

Neurosurgery, Volume 87, Issue 4, 1 October 2020, Pages 630–638

Intracortical microelectrode arrays have enabled people with tetraplegia to use a brain–computer interface for reaching and grasping. In order to restore dexterous movements, it will be necessary to control individual fingers.

OBJECTIVE: To predict which finger a participant with hand paralysis was attempting to move using intracortical data recorded from the motor cortex.

METHODS: A 31-yr-old man with a C5/6 ASIA B spinal cord injury was implanted with 2 88- channel microelectrode arrays in left motor cortex. Across 3 d, the participant observed a virtual hand flex in each finger while neural firing rates were recorded. A 6-class linear discriminant analysis (LDA) classifier, with 10 × 10-fold cross-validation, was used to predict which fingermovement was being performed (flexion/extension of all 5 digits and adduction/abduction of the thumb).

RESULTS: Themean overall classification accuracywas 67% (range: 65%-76%, chance: 17%), whichoccurredat anaverageof 560ms (range:420-780ms) aftermovementonset. Individually, thumb flexion and thumb adduction were classified with the highest accuracies at 92% and 93%, respectively. The index, middle, ring, and little achieved an accuracy of 65%, 59%, 43%, and 56%, respectively, and, when incorrectly classified, were typically marked as an adjacent finger. The classification accuracies were reflected in a low-dimensional projection of the neural data into LDA space, where the thumb-related movements were most separable from the finger movements.

CONCLUSION: Classification of intention to move individual fingers was accurately predicted by intracortical recordings from a human participant with the thumb being particularly independent.

Ultra-Early (<12 Hours) Surgery Correlates With Higher Rate of American Spinal Injury Association Impairment Scale Conversion After Cervical Spinal Cord Injury

Neurosurgery, Volume 85, Issue 2, August 2019, Pages 199–203

Cervical spinal cord injury (SCI) is a devastating condition with very few treatment options. It remains unclear if early surgery correlated with conversion of American Spinal Injury Association Impairment Scale (AIS) grade A injuries to higher grades.

OBJECTIVE: To determine the optimal time to surgery after cervical SCI through retrospective analysis.

METHODS: We collected data from 48 patients with cervical SCI. Based on the time from Emergency Department (ED) presentation to surgical decompression, we grouped patients into ultra-early (decompression within 12 h of presentation), early (within 12- 24 h), and late groups (>24 h).We compared the improvement in AIS grade fromadmission to discharge, controlling for confounding factors such as AIS grade on admission, injury severity, and age. The mean time from injury to ED for this group of patients was 17 min.

RESULTS: Patients who received surgery within 12 h after presentation had a relative improvement in AIS grade from admission to discharge: the ultra-early group improved on average 1.3. AIS grades compared to 0.5 in the early group (P = .02). In addition, 88.8% of patients with an AIS grade A converted to a higher grade (AIS B or better) in the ultraearly group, compared to 38.4% in the early and late groups (P= .054).

CONCLUSION: These data suggest that surgical decompression after SCI that takes place within 12 hmay lead to a relative improved neurological recovery compared to surgery that takes place after 12 h.

 

Correlation of magnetic resonance diffusion tensor imaging parameters with American Spinal Injury Association score for prognostication and long-term outcomes

Neurosurg Focus 46 (3):E2, 2019

Conventional MRI is routinely used to demonstrate the anatomical site of spinal cord injury (SCI). However, quantitative and qualitative imaging parameters have limited use in predicting neurological outcomes. Currently, there are no reliable neuroimaging biomarkers to predict short- and long-term outcome after SCI.

METHODS A prospective cohort of 23 patients with SCI (19 with cervical SCI [CSCI] and 4 with thoracic SCI [TSCI]) treated between 2007 and 2014 was included in the study. The American Spinal Injury Association (ASIA) score was determined at the time of arrival and at 1-year follow-up. Only 15 patients (12 with CSCI and 3 with TSCI) had 1-year follow-up. Whole-cord fractional anisotropy (FA) was determined at C1–2, following which C1–2 was divided into upper, middle, and lower segments and the corresponding FA value at each of these segments was calculated. Correlation analysis was performed between FA and ASIA score at time of arrival and 1-year follow-up.

RESULTS Correlation analysis showed a positive but nonsignificant correlation (p = 0.095) between FA and ASIA score for all patients (CSCI and TCSI) at the time of arrival. Additional regression analysis consisting of only patients with CSCI showed a significant correlation (p = 0.008) between FA and ASIA score at time of arrival as well as at 1-year follow-up (p = 0.025). Furthermore, in case of patients with CSCI, a significant correlation between FA value at each of the segments (upper, middle, and lower) of C1–2 and ASIA score at time of arrival was found (p = 0.017, p = 0.015, and p = 0.002, respectively).

CONCLUSIONS In patients with CSCI, the measurement of diffusion anisotropy of the high cervical cord (C1–2) correlates significantly with injury severity and long-term follow-up. However, this correlation is not seen in patients with TSCI. Therefore, FA can be used as an imaging biomarker for evaluating neural injury and monitoring recovery in patients with CSCI.

 

The role of diffusion tensor imaging in the diagnosis, prognosis, and assessment of recovery and treatment of spinal cord injury: a systematic review

Neurosurg Focus 46 (3):E7, 2019

Diffusion tensor imaging (DTI) is an MRI tool that provides an objective, noninvasive, in vivo assessment of spinal cord injury (SCI). DTI is significantly better at visualizing microstructures than standard MRI sequences. In this imaging modality, the direction and amplitude of the diffusion of water molecules inside tissues is measured, and this diffusion can be measured using a variety of parameters. As a result, the potential clinical application of DTI has been studied in several spinal cord pathologies, including SCI. The aim of this study was to describe the current state of the potential clinical utility of DTI in patients with SCI and the challenges to its use as a tool in clinical practice.

METHODS A search in the PubMed database was conducted for articles relating to the use of DTI in SCI. The citations of relevant articles were also searched for additional articles.

RESULTS Among the most common DTI metrics are fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. Changes in these metrics reflect changes in tissue integrity. Several DTI metrics and combinations thereof have demonstrated significant correlations with clinical function both in model species and in humans. Its applications encompass the full spectrum of the clinical assessment of SCI including diagnosis, prognosis, recovery, and efficacy of treatments in both the spinal cord and potentially the brain.

CONCLUSIONS DTI and its metrics have great potential to become a powerful clinical tool in SCI. However, the current limitations of DTI preclude its use beyond research and into clinical practice. Further studies are needed to significantly improve and resolve these limitations as well as to determine reliable time-specific changes in multiple DTI metrics for this tool to be used accurately and reliably in the clinical setting.

 

First Human Implantation of a Bioresorbable Polymer Scaffold for Acute Traumatic Spinal Cord Injury

First Human Implantation of a Bioresorbable Polymer Scaffold for Acute Traumatic Spinal Cord Injury

Neurosurgery 79:E305–E312, 2016

A porous bioresorbable polymer scaffold has previously been tested in preclinical animal models of spinal cord contusion injury to promote appositional healing, spare white matter, decrease posttraumatic cysts, and normalize intraparenchymal tissue pressure. This is the first report of its human implantation in a spinal cord injury patient during a pilot study testing the safety and feasibility of this technique (ClinicalTrials.gov Identifier: NCT02138110).

CLINICAL PRESENTATION: A 25-year-old man had a T11-12 fracture dislocation sustained in a motocross accident that resulted in a T11 American Spinal Injury Association Impairment Scale (AIS) grade A traumatic spinal cord injury. He was treated with acute surgical decompression and spinal fixation with fusion, and enrolled in the spinal scaffold study. A 2 x 10 mm bioresorbable scaffold was placed in the spinal cord parenchyma at T12. The scaffold was implanted directly into the traumatic cavity within the spinal cord through a dorsal root entry zone myelotomy at the caudal extent of the contused area. By 3 months, his neurological examination improved to an L1 AIS grade C incomplete injury. At 6-month postoperative follow-up, there were no procedural complications or apparent safety issues related to the scaffold implantation.

CONCLUSION: Although longer-term follow-up and investigation are required, this case demonstrates that a polymer scaffold can be safely implanted into an acutely contused spinal cord. This is the first human surgical implantation, and future outcomes of other patients in this clinical trial will better elucidate the safety and possible efficacy profile of the scaffold.

Autologous Mesenchymal Stem Cell Therapy for Spinal Cord Injury

A Phase III Clinical Trial Showing Limited Efficacy of Autologous Mesenchymal Stem Cell Therapy for Spinal Cord Injury

Neurosurgery 78:436–447, 2016

In our previous report, 3 of 10 patients with spinal cord injury who were injected with autologous mesenchymal stem cells (MSCs) showed motor improvement in the upper extremities and in activities of daily living.

OBJECTIVE: To report on the results of a phase III clinical trial of autologous MSCs therapy.

METHODS: Patients were selected based on the following criteria: chronic American Spinal Injury Association B status patients who had more than 12 months of cervical injury, and no neurological changes during the recent 3 months of vigorous rehabilitation. We injected 1.6 x10(7) autologous MSCs into the intramedullary area at the injured level and 3.2 x 10(7) autologous MSCs into the subdural space. Outcome data were collected over 6 months regarding neurological examination, magnetic resonance imaging with diffusion tensor imaging, and electrophysiological analyses.

RESULTS: Among the 16 patients, only 2 showed improvement in neurological status (unilateral right C8 segment from grade 1 to grade 3 in 1 patient and bilateral C6 from grade 3 to grade 4 and unilateral right C8 from grade 0 to grade 1 in 1 patient). Both patients with neurological improvement showed the appearance of continuity in the spinal cord tract by diffusion tensor imaging. There were no adverse effects associated with MSCs injection.

CONCLUSION: Single MSCs application to intramedullary and intradural space is safe, but has a very weak therapeutic effect compared with multiple MSCs injection. Further clinical trials to enhance the effect of MSCs injection are necessary.

Diffusion Tensor Imaging of the Spinal Cord

Diffusion_Tensor_Imaging_of_the_Spinal_Cord__

Neurosurgery 74:1–8, 2014

Diffusion tensor imaging (DTI) provides a measure of the directional diffusion of water molecules in tissues. The measurement of DTI indexes within the spinal cord provides a quantitative assessment of neural damage in various spinal cord pathologies.

DTI studies in animal models of spinal cord injury indicate that DTI is a reliable imaging technique with important histological and functional correlates. These studies demonstrate that DTI is a noninvasive marker of microstructural change within the spinal cord.

In human studies, spinal cord DTI shows definite changes in subjects with acute and chronic spinal cord injury, as well as cervical spondylotic myelopathy. Interestingly, changes in DTI indexes are visualized in regions of the cord, which appear normal on conventional magnetic resonance imaging and are remote from the site of cord compression.

Spinal cord DTI provides data that can help us understand underlying microstructural changes within the cord and assist in prognostication and planning of therapies. In this article, we review the use of DTI to investigate spinal cord pathology in animals and humans and describe advances in this technique that establish DTI as a promising biomarker for spinal cord disorders.

Transplantation of mesenchymal stem cells after spinal cord injury

Neurosurgery 70:1238–1247, 2012

DOI: 10.1227/NEU.0b013e31824387f9

Although the transplantation of mesenchymal stem cells (MSCs) after spinal cord injury (SCI) has shown promising results in animals, less is known about the effects of autologous MSCs in human SCI.

OBJECTIVE: To describe the long-term results of 10 patients who underwent intramedullary direct MSCs transplantation into injured spinal cords.

METHODS: Autologous MSCs were harvested from the iliac bone of each patient and expanded by culturing for 4 weeks. MSCs (8 · 106) were directly injected into the spinal cord, and 4 x 10(7) cells were injected into the intradural space of 10 patients with American Spinal Injury Association class A or B injury caused by traumatic cervical SCI. After 4 and 8 weeks, an additional 5 x 10(7) MSCs were injected into each patient through lumbar tapping. Outcome assessments included changes in the motor power grade of the extremities, magnetic resonance imaging, and electrophysiological recordings.

RESULTS: Although 6 of the 10 patients showed motor power improvement of the upper extremities at 6-month follow-up, 3 showed gradual improvement in activities of daily living, and changes on magnetic resonance imaging such as decreases in cavity size and the appearance of fiber-like low signal intensity streaks. They also showed electrophysiological improvement. All 10 patients did not experience any permanent complication associated with MSC transplantation.

CONCLUSION: Three of the 10 patients with SCI who were directly injected with autologous MSCs showed improvement in the motor power of the upper extremities and in activities of daily living, as well as significant magnetic resonance imaging and electrophysiological changes during long-term follow-up.

Acidic fibroblast growth factor for repair of human spinal cord injury: a clinical trial

J Neurosurg Spine 15:216–227, 2011. DOI: 10.3171/2011.4.SPINE10404

The study aimed to verify the safety and feasibility of applying acidic fibroblast growth factor (aFGF) with fibrin glue in combination with surgical neurolysis for nonacute spinal cord injury.

Methods. This open-label, prospective, uncontrolled human clinical trial recruited 60 patients with spinal cord injuries (30 cervical and 30 thoracolumbar). The mean patient age was 36.5 ± 15.33 (mean ± SD) years, and the male/ female ratio was 3:1. The mean time from injury to treatment was 25.7 ± 26.58 months, and the cause of injury included motor vehicle accident (26 patients [43.3%]), fall from a height (17 patients [28.3%]), sports (4 patients [6.7%]), and other (13 patients [21.7%]). Application of aFGF with fibrin glue and duraplasty was performed via laminectomy, and an adjuvant booster of combined aFGF and fibrin glue (2 ml) was given at 3 and 6 months postsurgery via lumbar puncture. Outcome measurements included the American Spinal Injury Association (ASIA) motor scores, sensory scores, impairment scales, and neurological levels. Examination of functional independence measures, visual analog scale, MR imaging, electrophysiological and urodynamic studies, hematology and biochemistry tests, tumor markers, and serum inflammatory cytokines were all conducted. All adverse events were monitored and reported. Exclusions were based on refusal, unrelated adverse events, or failure to participate in the planned rehabilitation.

Results. Forty-nine patients (26 with cervical and 23 with thoracolumbar injuries) completed the 24-month trial. Compared with preoperative conditions, the 24-month postoperative ASIA motor scores improved significantly in the cervical group (from 27.6 ± 15.55 to 37.0 ± 19.93, p < 0.001) and thoracolumbar group (from 56.8 ± 9.21 to 60.7 ± 10.10, p < 0.001). The ASIA sensory scores also demonstrated significant improvement in light touch and pinprick in both groups: from 55.8 ± 24.89 to 59.8 ± 26.47 (p = 0.049) and 56.3 ± 23.36 to 62.3 ± 24.87 (p = 0.003), respectively, in the cervical group and from 75.7 ± 15.65 to 79.2 ± 15.81 (p < 0.001) and 78.2 ± 14.72 to 82.7 ± 16.60 (p < 0.001), respectively, in the thoracolumbar group. At 24-month follow-up, the ASIA impairment scale improved significantly in both groups (30% cervical [p = 0.011] and 30% thoracolumbar [p = 0.003]). There was also significant improvement in neurological level in the cervical (from 5.17 ± 1.60 to 6.27 ± 3.27, p = 0.022) and thoracolumbar (from 18.03 ± 4.19 to 18.67 ± 3.96, p = 0.001) groups. The average sum of motor items in functional independence measure also had significant improvement in both groups (p < 0.05). The walking/wheelchair locomotion subscale showed increased percentages of patients who were ambulatory (from 3.4% to 13.8% and from 17.9% to 35.7% in the cervical and thoracolumbar groups, respectively). There were no related adverse events.

Conclusions. The use of aFGF for spinal cord injury was safe and feasible in the present trial. There were significant improvements in ASIA motor and sensory scale scores, ASIA impairment scales, neurological levels, and functional independence measure at 24 months after treatment. Further large-scale, randomized, and controlled investigations are warranted to evaluate the efficacy and long-term results.