Lower Motor Neuron Abnormality in Chronic Cervical Spinal Cord Injury: Implications for Nerve Transfer Surgery.

Nerve transfer surgery (NT) constitutes an exciting option to improve upper limb functions in chronic spinal cord injury (SCI), but requires intact sublesional lower motor neuron (LMN) health. The purpose of this study was to characterize patterns of LMN abnormality in nerve-muscle groups that are the potential recipients of NT, using a standardized electrodiagnostic examination, in individuals with chronic SCI (injury duration >2 years, injury levels C4-T1). The LMN abnormality was determined using a semihierarchical approach, combining the amplitude compound muscle action potential (CMAP) and abnormal spontaneous activity on needle electromyography (EMG). Ten participants (46 potential recipient muscles) were included (median age, 42.5 years; six males and four females; median duration from injury, 15.5 years). A high frequency of LMN abnormality was observed (87%), although there was substantial variation within and between individuals. No statistically significant discordance was observed between LMN abnormality on CMAP and EMG (p = 0.24), however, 50% of muscles with normal CMAP demonstrated abnormal spontaneous activity. The high frequency of LMN abnormality in recipient nerve-muscle groups has implications to candidate selection for NT surgery in chronic SCI and supports the important role of the pre-operative electrodiagnostic examination. Our results further support the inclusion of both CMAP and needle EMG parameters for characterization of LMN health. Although the number of nerve-muscle groups with normal LMN health was small (13%), this underscores the neurophysiological potential of some patients with chronic injuries to benefit from NT surgery.

Autonomic dysreflexia associated with cervical spinal cord gliofibroma: case report.

BACKGROUND: Autonomic dysreflexia (AD) is an abnormal reflex of the autonomic nervous system normally observed in patients with spinal cord injury from the sixth thoracic vertebra and above. AD causes various symptoms including paroxysmal hypertension due to stimulus. Here, we report a case of recurrent AD associated with cervical spinal cord tumor. CASE PRESENTATION: The patient was a 57-year-old man. Magnetic resonance imaging revealed an intramedullary lesion in the C2, C6, and high Th12 levels. During the course of treatment, sudden loss of consciousness occurred together with abnormal paroxysmal hypertension, marked facial sweating, left upward conjugate gaze deviation, ankylosis of both upper and lower extremities, and mydriasis. Seizures repeatedly occurred, with symptoms disappearing after approximately 30 min. AD associated with cervical spinal cord tumor was diagnosed. Histological examination by tumor biopsy confirmed the diagnosis of gliofibroma. Radiotherapy was performed targeting the entire brain and spinal cord. The patient died approximately 3 months after treatment was started. CONCLUSIONS: AD is rarely associated with spinal cord tumor, and this is the first case associated with cervical spinal cord gliofibroma. AD is important to recognize, since immediate and appropriate response is required.

The prediction of intraoperative cervical cord function changes by different motor evoked potentials phenotypes in cervical myelopathy patients.

BACKGROUND: Surgery is usually the treatment of choice for patients with cervical compressive myelopathy (CCM). Motor evoked potential (MEP) has proved to be helpful tool in evaluating intraoperative cervical spinal cord function change of those patients. This study aims to describe and evaluate different MEP baseline phenotypes for predicting MEP changes during CCM surgery. METHODS: A total of 105 consecutive CCM patients underwent posterior cervical spine decompression were prospectively collected between December 2012 and November 2016. All intraoperative MEP baselines recorded before spinal cord decompression were classified into 5 types (I to V) that were carefully designed according to the different MEP parameters. The postoperative neurologic status of each patient was assessed immediately after surgery. RESULTS: The mean intraoperative MEP changes range were 10.2% ± 5.8, 14.7% ± 9.2, 54.8% ± 31.9, 74.1% ± 24.3, and 110% ± 40 in Type I, II, III, IV, and V, respectively. There was a significant correlation of the intraoperative MEP change rate with different MEP baseline phenotypes (r = 0.84, P < 0.01). Postoperative transient new spinal deficits were found 0/31 case in Type I, 0/21 in Type II, 1/14 in Type III, 2/24 in Type IV, and 4/15 in Type V. No permanent neurological injury was found in our cases series. CONCLUSIONS: The MEP baselines categories for predicting intraoperative cervical cord function change is proposed through this work. The more serious the MEP baseline abnormality, the higher the probability of intraoperative MEP changes, which is beneficial to early warning for the cervical cord injury.

Grip force control during object manipulation in cervical myelopathy.

STUDY DESIGN: Cross-sectional research. OBJECTIVES: To objectively evaluate grip force (GF) control while holding a freely movable object in individuals with cervical myelopathy (CM). SETTING: Harunaso Hospital, Takasaki, Japan. METHODS: We studied 52 hands from 26 individuals with CM. Participants performed a grip-and-lift task by pulp pinch using the thumb and index finger before surgery. We monitored individual finger GF (N) during the first 3 s while lifting and holding an object. Correlations between the GF and other clinical tests were evaluated. A multiple stepwise regression analysis was used to examine the contribution of the GF to the severity of clinical symptoms. RESULTS: Thumb GF was negatively correlated with the 10-s test (rs = -0.32), and index finger GF was positively correlated with its cutaneous pressure threshold (rs = 0.34). Multiple regression for the severity of upper extremity symptoms revealed that the model including the GF had a larger adjusted R2 and a lower AIC value than that of conventionally used clinical tests. CONCLUSIONS: These results suggested that the assessment of individual finger GF control could provide an indicator of the clinical severity of upper extremity in individuals with CM.

Cord compression defined by MRI is the driving factor behind the decision to operate in Degenerative Cervical Myelopathy despite poor correlation with disease severity.

OBJECTIVES: The mainstay treatment for Degenerative Cervical Myelopathy (DCM) is surgical decompression. Not all cases, however, are suitable for surgery. Recent international guidelines advise surgery for moderate to severe disease as well as progressive mild disease. The goal of this study was to examine the factors in current practice that drive the decision to operate in DCM. STUDY DESIGN: Retrospective cohort study. METHODS: 1 year of cervical spine MRI scans (N = 1123) were reviewed to identify patients with DCM with sufficient clinical documentation (N = 39). Variables at surgical assessment were recorded: age, sex, clinical signs and symptoms of DCM, disease severity, and quantitative MRI measures of cord compression. Bivariate correlations were used to compare each variable with the decision to offer the patient an operation. Subsequent multivariable analysis incorporated all significant bivariate correlations. RESULTS: Of the 39 patients identified, 25 (64%) were offered an operation. The decision to operate was significantly associated with narrower non-pathological canal and cord diameters as well as cord compression ratio, explaining 50% of the variance. In a multivariable model, only cord compression ratio was significant (p = 0.017). Examination findings, symptoms, functional disability, disease severity, disease progression, and demographic factors were all non-significant. CONCLUSIONS: Cord compression emerged as the main factor in surgical decision-making prior to the publication of recent guidelines. Newly identified predictors of post-operative outcome were not significantly associated with decision to operate.

Sleep disordered breathing induced by cervical spinal cord injury and effect of adenosine A1 receptors modulation in rats.

Sleep-disordered breathing (SDB) is very common after spinal cord injury (SCI). The present study was designed to evaluate the therapeutic efficacy of adenosine A1 receptor blockade (8-cyclopentyl-1,3-dipropylxanthine, DPCPX) on SDB in a rodent model of SCI. We hypothesized that SCI induced via left hemisection of the second cervical segment (C2Hx) results in SDB. We further hypothesized that blockade of adenosine A1 receptors following C2Hx would reduce the severity of SDB. In the first experiment, adult male rats underwent left C2Hx or sham (laminectomy) surgery. Unrestrained whole body plethysmography (WBP) and implanted wireless electroencephalogram (EEG) were used for assessment of breathing during spontaneous sleep and for the scoring of respiratory events at the acute (~1 wk), and chronic (~6 wk) time points following C2Hx. During the second experiment, the effect of oral administration of adenosine A1 receptor antagonist (DPCPX, 3 times a day for 4 days) on SCI induced SDB was assessed. C2Hx animals exhibited a higher apnea-hypopnea index (AHI) compared with the sham group, respectively (35.5 ± 12.6 vs. 19.1 ± 2.1 events/h, P < 0.001). AHI was elevated 6 wk following C2Hx (week 6, 32.0 ± 5.0 vs. week 1, 42.6 ± 11.8 events/h, respectively, P = 0.12). In contrast to placebo, oral administration of DPCPX significantly decreased AHI 4 days after the treatment (159.8 ± 26.7 vs. 69.5 ± 8.9%, P < 0.05). Cervical SCI is associated with the development of SDB in spontaneously breathing rats. Adenosine A1 blockade can serve as a therapeutic target for SDB induced by SCI.NEW & NOTEWORTHY The two key novel findings of our study included that 1) induced cervical spinal cord injury results in sleep-disordered breathing in adult rats, and 2) oral therapy with an adenosine A1 receptor blockade using DPCPX is sufficient to significantly reduce apnea-hypopnea index following induced cervical spinal cord injury.

Tissue bridges predict recovery after traumatic and ischemic thoracic spinal cord injury.

OBJECTIVE: To investigate the spatiotemporal evolution and predictive properties of intramedullary damage and midsagittal tissue bridges at the epicenter of a thoracic spinal cord injury (SCI) using MRI. METHODS: We retrospectively assessed midsagittal T2-weighted scans from 25 patients with thoracic SCI (14 traumatic, 11 ischemic) at 1 month post-SCI. In 12 patients with SCI, linear mixed-effects models on serial MRI explored temporal trajectories of quantifiable lesion markers (area, length, and width) and tissue bridges. Using partial correlation analysis, we assessed associations between structural lesion characteristics at 1 month post-SCI and recovery at 1 year postinjury, adjusting for baseline clinical status, age, and sex. RESULTS: Lesion area decreased by 5.68 mm2 (p = 0.005), lesion length by 2.14 mm (p = 0.004), and lesion width by 0.13 mm (p = 0.004) per month. Width of tissue bridges increased by 0.06 mm (p = 0.019) per month, being similar in traumatic and ischemic SCI (p = 0.576). Smaller lesion area, length, width, and wider tissue bridges at 1 month post-SCI predicted better recovery at 1-year follow-up. CONCLUSIONS: Over time, the immediate area of cord damage shrunk while the cystic cavity became demarcated. Adjacent to the cyst, midsagittal tissue bridges became visible. The width of tissue bridges at 1 month post-SCI predicted recovery at 1 year follow-up. Measures of lesion area and tissue bridges early after traumatic and ischemic thoracic SCI therefore allow characterizing the evolution of focal cord damage and are predictive of recovery in thoracic SCI. Thus, lesion extent and tissue bridges hold potential to improve diagnosis and patient stratification in interventional trials.

Adjusting Assistance Commensurates with Patient Effort During Robot-Assisted Upper Limb Training for a Patient with Spasticity After Cervical Spinal Cord Injury: A Case Report.

Limited evidence is available on optimal patient effort and degree of assistance to achieve preferable changes during robot-assisted training (RAT) for spinal cord injury (SCI) patients with spasticity. To investigate the relationship between patient effort and robotic assistance, we performed training using an electromyography-based robotic assistance device (HAL-SJ) in an SCI patient at multiple settings adjusted to patient effort. In this exploratory study, we report immediate change in muscle contraction patterns, patient effort, and spasticity in a 64-year-old man, diagnosed with cervical SCI and with American Spinal Injury Association Impairment Scale C level and C4 neurological level, who underwent RAT using HAL-SJ from post-injury day 403. Three patient effort conditions (comfortable, somewhat hard, and no-effort) by adjusting HAL-SJ's assists were set for each training session. Degree of effort during flexion and extension exercise was assessed by visual analog scale, muscle contraction pattern by electromyography, modified Ashworth scale, and maximum elbow extension and flexion torques, immediately before and after each training session, without HAL-SJ. The amount of effort during training with the HAL-SJ at each session was evaluated. The degree of effort during training can be set to three effort conditions as we intended by adjusting HAL-SJ. In sessions other than the no-effort setting, spasticity improved, and the level of effort was reduced immediately after training. Spasticity did not decrease in the training session using HAL-SJ with the no-effort setting, but co-contraction further increased during extension after training. Extension torque was unchanged in all sessions, and flexion torque decreased in all sessions. When performing upper-limb training with HAL-SJ in this SCI patient, the level of assistance with some effort may reduce spasticity and too strong assistance may increase co-contraction. Sometimes, a patient's effort may be seemingly unmeasurable; hence, the degree of patient effort should be further measured.

Independent replication of motor cortex and cervical spinal cord electrical stimulation to promote forelimb motor function after spinal cord injury in rats.

Cervical spinal cord injury (SCI) impairs arm and hand function largely by interrupting descending tracts. Most SCI spare some axons at the lesion, including the corticospinal tract (CST), which is critical for voluntary movement. We targeted descending motor connections with paired electrical stimulation of motor cortex and cervical spinal cord in the rat. We sought to replicate the previously published effects of intermittent theta burst stimulation of forelimb motor cortex combined with trans-spinal direct current stimulation placed on the skin over the neck to target the cervical enlargement. We hypothesized that paired stimulation would improve performance in skilled walking and food manipulation (IBB) tasks. Rats received a moderate C4 spinal cord contusion injury (200 kDynes), which ablates the main CST. They were randomized to receive paired stimulation for 10 consecutive days starting 11 days after injury, or no stimulation. Behavior was assessed weekly from weeks 4-7 after injury, and then CST axons were traced. Rats with paired cortical and spinal stimulation achieved significantly better forelimb motor function recovery, as measured by fewer stepping errors on the horizontal ladder task (34 ±â€¯9% in stimulation group vs. 51 ±â€¯18% in control, p = .013) and higher scores on the food manipulation task (IBB, 0-9 score; 7.2 ±â€¯0.8 in stimulated rats vs. 5.2 ±â€¯2.6 in controls, p = .025). The effect size for both tasks was large (Cohen's d = 1.0 and 0.92, respectively). The CST axon length in the cervical spinal cord did not differ significantly between the groups, but there was denser and broader ipsilateral axons distribution distal to the spinal cord injury. The large behavioral effect and replication in an independent laboratory validate this approach, which will be trialed in cats before being tested in people using non-invasive methods.

Altered Cervical Spinal Cord Resting-State Activity in Fibromyalgia.

OBJECTIVE: Altered afferent input and central neural modulation are thought to contribute to fibromyalgia symptoms, and these processes converge within the spinal cord. We undertook this study to investigate the hypothesis that, using resting-state functional magnetic resonance imaging (rs-fMRI) of the cervical spinal cord, we would observe altered frequency-dependent activity in fibromyalgia. METHODS: Cervical spinal cord rs-fMRI was conducted in fibromyalgia patients (n = 16) and healthy controls (n = 17). We analyzed the amplitude of low-frequency fluctuations (ALFF), a measure of low-frequency oscillatory power, for frequencies of 0.01-0.198 Hz and frequency sub-bands to determine regional and frequency-specific alterations in fibromyalgia. Functional connectivity and graph metrics were also analyzed. RESULTS: As compared to healthy controls (n = 14), greater ventral and lesser dorsal mean ALFF of the cervical spinal cord was observed in fibromyalgia patients ( n = 15) (uncorrected P < 0.05) for frequencies of 0.01-0.198 Hz and all sub-bands. Additionally, lesser mean ALFF within the right dorsal quadrant (corrected P < 0.05) for frequencies of 0.01-0.198 Hz and sub-band frequencies of 0.073-0.198 Hz was observed in fibromyalgia. Regional mean ALFF was not correlated with pain; however, regional lesser mean ALFF was correlated with fatigue in patients (r = 0.763, P = 0.001). Functional connectivity and graph metrics were similar between groups. CONCLUSION: Our results indicate unbalanced activity between the ventral and dorsal cervical spinal cord in fibromyalgia. Increased ventral neural processes and decreased dorsal neural processes may reflect the presence of central sensitization and contribute to fatigue and other bodily symptoms in fibromyalgia.

The Impact of Cervical Spinal Cord Contusion on the Laryngeal Resistance in the Rat.

The present study was designed to investigate laryngeal function responses to chemoreceptor activation after unilateral high-cervical spinal cord contusion in rats. Adult male Sprague-Dawley rats received laminectomy or unilateral contusion at the C2 spinal cord. Both respiratory airflow and subglottal pressure were measured in spontaneously breathing rats at three days, two weeks, or six weeks after spinal surgery. Laryngeal closure responses were evoked via intrajugular capsaicin (1.5 µg/kg) administration and hypoxia (12.5% O2, 3 min) to activate bronchopulmonary C-fibers and chemoreceptors, respectively. High cervical contusion resulted in long-term reductions in tidal volume without changes in laryngeal resistance at baseline. Alternatively, capsaicin-induced increased subglottal pressure was significantly attenuated in contused rats at three days post-injury. Contused rats regained the ability to increase laryngeal resistance after capsaicin treatment at two and six weeks post-injury, whereas this recovered response remained weaker than uninjured animals. Notably, hypoxia-induced laryngeal closure was not altered during the acute injured stage, but instead was blunted at six weeks post-injury. These data suggest that cervical spinal cord injury not only influences the breathing pattern, but it also impacts upper airway function through modulation of laryngeal resistance. An attenuated laryngeal closure response may negatively impact the ability to prevent irritant inhalation and maintenance of the functional residual capacity. This may contribute to the provocation of pulmonary disease after cervical spinal cord injury.

A neurophysiological approach to nerve transfer to restore upper limb function in cervical spinal cord injury.

A successful nerve transfer surgery can provide a wealth of benefits to a patient with cervical spinal cord injury. The process of surgical decision making ideally uses all pertinent information to produce the best functional outcome. Reliance on clinical examination and imaging studies alone can miss valuable information on the state of spinal cord health. In this regard, neurophysiological evaluation has the potential to effectively gauge the neurological status of even select pools of anterior horn cells and their axons to small nerve branches in question to determine the potential efficacy of their use in a transfer. If available preoperatively, knowledge gained from such an evaluation could significantly alter the reconstructive surgical plan and avoid poor results. The authors describe their institution's approach to the assessment of patients with cervical spinal cord injury who are being considered for nerve transfer surgery in both the acute and chronic setting and broadly review the neurophysiological techniques used.

Relevance of early cervical cord volume loss in the disease evolution of clinically isolated syndrome and early multiple sclerosis: a 2-year follow-up study.

Upper cervical cord area (UCCA) atrophy is a prognostic marker for clinical progression in longstanding multiple sclerosis (MS). The objectives of the study were to quantify UCCA atrophy and evaluate its impact in clinically isolated syndrome (CIS) and relapsing-remitting MS (RRMS); to compare converting CIS patients with stable CIS, and to study changes of UCCA and brain white matter (WM) and grey matter (GM) at 2-year follow-up. 110 therapy-naive patients including 53 CIS [6 ± 6 months after symptom onset (SO)] and 57 early RRMS (SO: 12 ± 9 months) underwent sagittal 3D-T1w brain MR (3T). Mean UCCA (C1-C3 level), WM and GM, disability status (EDSS), pyramidal and sensory functional scores, motoric fatigue were assessed at baseline (BL), 12 and 24 months. Volumes were compared with 34 age- and gender-matched healthy controls to assess atrophy. RRMS (78.1 ± 8.7 mm2, p = 0.011) and converting CIS (77.3 ± 8.0 mm2, p = 0.046) presented with baseline UCCA atrophy, when compared with controls (82.7 ± 5.2 mm2), but not stable CIS (82.6 ± 7.4 mm2, p = 0.998). Baseline WM was reduced in RRMS (509.3 ± 25.7 ml vs. CONTROLS: 528.4 ± 24.1 ml, p = 0.032). Baseline UCCA correlated negative with muscular weakness and fatigability in all patients and RRMS. EDSS exceeding 3 was associated with lower baseline UCCA. Longitudinal atrophy rates were higher in UCCA than in brain volumes. Early cervical cord atrophy in CIS and RRMS was confirmed and may represent a potential new risk marker for conversion from CIS to MS. Baseline atrophy and atrophy change rates were higher in UCCA compared to WM and GM, suggesting that cervical cord volumetry might become an additional MRI marker relevant in future clinical studies in CIS and early MS.

Can the acute magnetic resonance imaging features reflect neurologic prognosis in patients with cervical spinal cord injury?

BACKGROUND CONTEXT: Several prognostic studies looked for an association between the degree of spinal cord injury (SCI), as depicted by primary magnetic resonance imaging (MRI) within 72 hours of injury, and neurologic outcome. It was not clearly demonstrated whether the MRI at any time correlates with neurologic prognosis. PURPOSE: The purpose of the present study was to investigate the relationship between acute MRI features and neurologic prognosis, especially walking ability of patients with cervical spinal cord injury (CSCI). Moreover, at any point, MRI was clearly correlated with the patient's prognosis. STUDY DESIGN: Retrospective image study. PATIENT SAMPLE: From January 2010 to October 2015, 102 patients with CSCI were treated in our hospital. Patients who were admitted to our hospital within 3 days after injury were included in this study. The diagnosis was 78 patients for CSCI with no or minor bony injury and 24 patients for CSCI with fracture or dislocation. A total of 88 men and 14 women were recruited, and the mean patient age was 62.6 years (range, 16-86 years). Paralysis at the time of admission was graded as A in 32, B in 15, C in 42, and D in 13 patients on the basis of the American Spinal Injury Association (ASIA) impairment scale. Patients with CSCI with fracture or dislocation were treated with fixation surgery and those with CSCI with no or minor bony injury were treated conservatively. Patients were followed up for an average of 168 days (range, 25-496 days). OUTCOME MEASURES: Neurologic evaluation was performed using the ASIA motor score and the modified Frankel grade at the time of admission and discharge. METHODS: Magnetic resonance imaging was performed for all patients at admission. Using the MRI sagittal images, we measured the vertical diameter of intramedullary high-intensity changed area with T2-weighted images at the injured segment. We studied separately the patients divided into two groups: 0-1 day admission after injury, and 2-3 days admission after injury. We evaluated the relationship between the vertical diameter of T2 high-intensity changed area in MR images and neurologic outcome in these two groups. This study does not contain any conflict of interest. RESULTS: In the group admitted at 0-1 day after injury, there was a relationship between the vertical diameter of T2 high-intensity area in MR image and the ASIA motor score at admission and at discharge, but correlation coefficient was low (0.3766 at admission and 0.4239 at discharge). On the other hand, in the group admitted at 2-3 days after injury, there was a significant relationship between the vertical diameter of T2 high-intensity area in MR image and the ASIA motor score at admission and at discharge, and correlation coefficient was very high (0.6840 at admission and 0.5293 at discharge). In the group admitted at 2-3 days after injury, a total of 17 patients (68%) recovered to walk with or without a cane. Receiver operating characteristic (ROC) curve analysis demonstrated that the optimal vertical diameter of T2 high-intensity area cutoffvalue for patients who were able to walk at discharge was 45.8 mm. If the vertical diameter of T2 high-intensity area cutoff value was 45 mm, there was a significant positive correlation with being able to walk at discharge (p<.0001). CONCLUSIONS: From our study, 2-3 days after injury, a significant relationship was observed between the vertical diameter of T2 high-intensity area and the neurologic prognosis at discharge. Zero to 1 day after injury, the relationship between the vertical diameter of T2 high-intensity area and the neurologic prognosis at discharge was weak. Neurologic prognosis is more correlated with MRI after 2-3 days after the injury. If the vertical diameter of T2 high-intensity area was <45 mm, the patients were able to walk with or without a cane at discharge. T2 high-intensity changed area can reflect the neurologic prognosis in patients with CSCI.

Mild Acute Intermittent Hypoxia Improves Respiratory Function in Unanesthetized Rats With Midcervical Contusion.

BACKGROUND: Mild intermittent hypoxia has been considered a potential approach to induce respiratory neuroplasticity. OBJECTIVE: The purpose of the present study was to investigate whether mild acute intermittent hypoxia can improve breathing function in a clinically relevant spinal cord injury animal model. METHODS: Adult male rats received laminectomy or unilateral contusion at the C3-C4 spinal cord using a MASCIS Impactor (height: 6.25 or 12.5 mm). At 4 weeks postinjury, the breathing patterns of unanesthetized rats were measured by whole body plethysmography before, during and after 10 episodes of 5 minutes of hypoxia (10% O2, 4% CO2, balance N2) with 5 minutes of normoxia intervals. RESULTS: The results demonstrated that cervical contusion resulted in reduction in breathing capacity and number of phrenic motoneurons. Acute hypoxia induced significant increases in frequency and tidal volume in sham surgery and contused animals. In addition, there was a progressive decline in the magnitude of hypoxic ventilatory response during intermittent hypoxia. Further, the tidal volume was significantly enhanced in contused but not sham surgery rats at 15 and 30 minutes postintermittent hypoxia, suggesting intermittent hypoxia can bring about long-term facilitation of tidal volume following cervical spinal contusion. CONCLUSIONS: These results suggest that mild acute intermittent hypoxia can elicit differential forms of respiratory plasticity in sham surgery versus contused animals, and may be a promising neurorehabilitation approach to improve respiratory function after cervical spinal cord injury.

Self-assembling peptides optimize the post-traumatic milieu and synergistically enhance the effects of neural stem cell therapy after cervical spinal cord injury.

INTRODUCTION: The hostile environment after spinal cord injury (SCI) can compromise effects of regenerative therapies. We hypothesized that optimizing the post-traumatic environment with QL6 self-assembling peptides (SAPs) before neural precursor cell (NPC) transplantation would improve cell survival, differentiation and functional recovery. METHODS: A total of 90 Wistar rats received a clip-compression SCI at C7. Within each of two study arms, animals were randomized into 5 groups (NPC, SAP, NPC+SAP, vehicle, and sham). SAPs and NPCs were injected into the spinal cord 1day and 14days post-injury, respectively. Animals received growth factors over 7days and were immunosuppressed. Rats were sacrificed at 4weeks and sections of the cervical spinal cord prepared for immunohistochemistry (first study arm). Neurological function was assessed weekly for 8weeks using a battery of behavioral tests. Nine weeks post-SCI, the corticospinal tract was assessed using fiber-tracking (second arm). RESULTS: SAP-treated animals had significantly more surviving NPCs which showed increased differentiation to neurons and oligodendrocytes compared to controls. SAPs alone or in combination with NPCs resulted in smaller intramedullary cysts and larger volume of preserved tissue compared to other groups. The combined treatment group showed reduced astrogliosis and chondroitin sulfate proteoglycan deposition. Synaptic connectivity was increased in the NPC and combined treatment groups. Corticospinal tract preservation and behavioral outcomes improved with combinatorial treatment. CONCLUSION: Injecting SAPs after SCI enhances subsequent NPC survival, integration and differentiation and improves functional recovery. STATEMENT OF SIGNIFICANCE: The hostile environment after spinal cord injury (SCI) can compromise effects of regenerative therapies. We hypothesized that improving this environment with self-assembling peptides (SAPs) before neural precursor cell (NPC) transplantation would support their beneficial effects. SAPs assemble once injected, providing a supportive scaffold for repair and regeneration. We investigated this in a rat model of spinal cord injury. More NPCs survived in SAP-treated animals and these showed increased differentiation compared to controls. SAPS alone or in combination with NPCs resulted in smaller cysts and larger volume of preserved tissue with the combined treatment also reducing scarring and improving behavioral outcomes. Overall, injection of SAPs was shown to improve the efficacy of NPC treatment, a promising finding for those with SCIs.

Cervical cord compression in mucopolysaccharidosis VI (MPS VI): Findings from the MPS VI Clinical Surveillance Program (CSP).

OBJECTIVES: To gain insight into the frequency, age of onset, and management of cervical cord compression in mucopolysaccharidosis VI (MPS VI). METHODS: Cervical spine magnetic resonance imaging (MRI) data and/or cervical decompression surgery data collected between 30 June 2005 and 1 September 2015 were analyzed from subjects enrolled in the MPS VI Clinical Surveillance Program (CSP) (ClinicalTrials.gov: NCT00214773), an ongoing multicenter, observational, retrospective and prospective registry. RESULTS: Of 213 subjects enrolled in the CSP, 134 (62.9%) had at least one documented cervical spine MRI assessment. An additional four subjects were identified through surgery records alone to yield a study population comprising 138 subjects (mean age at enrollment =15.1years; age range=0.80-65.0years). Cervical cord compression was documented in 101 (75.4%) of the 134 subjects with ≥1 MRI assessment, the majority (95.0%) by the time of the first recorded MRI. In general, subjects with cervical cord compression had significantly lower height Z-scores compared to those without cervical cord compression (p<0.0001); nevertheless, a few subjects of taller stature had documented cervical cord compression at a young age. Most subjects >20years of age (31/33, 93.9%) presented with cervical cord compression. There was an insufficient number of subjects with both pre- and post-enzyme replacement therapy (ERT) MRI data to determine any association between ERT and cervical cord compression. Surgical decompression was performed on 58 subjects (42.0%), with mean age at first surgery of 13.1years. Decompression plus stabilization procedures accounted for 12.1% of surgeries. Eight subjects (13.8%) underwent reoperation. Complications during or following surgery were reported in 3 subjects, with anesthesia-related complications resulting in two deaths. CONCLUSIONS: All individuals with MPS VI are at high risk of developing cervical cord compression at an early age. Routine MRI assessments should be initiated from the time of MPS VI diagnosis. The perioperative management of MPS VI patients can be challenging. This study contributes to the understanding of the natural history of MPS VI.

Cervical spine surgery in professional athletes: a systematic review.

Cervical surgery is one of the most common surgical spinal procedures performed around the world. The authors performed a systematic review of the literature reporting the outcomes of cervical spine surgery in high-level athletes in order to better understand the nuances of cervical spine pathology in this population. A search of the MEDLINE database using the search terms "cervical spine" AND "surgery" AND "athletes" yielded 54 abstracts. After exclusion of publications that did not meet the criteria for inclusion, a total of 8 papers reporting the outcome of cervical spine surgery in professional or elite athletes treated for symptoms secondary to cervical spine pathology (focusing in degenerative conditions) remained for analysis. Five of these involved the management of cervical disc herniation, 3 were specifically about traumatic neurapraxia. The majority of the patients included in this review were American football players. Anterior cervical discectomy and fusion (ACDF) was commonly performed in high-level athletes for the treatment of cervical disc herniation. Most of the studies suggested that return to play is safe for athletes who are asymptomatic after ACDF for cervical radiculopathy due to disc herniation. Surgical treatment may provide a higher rate of return to play for these athletes than nonsurgical treatment. Return to play after cervical spinal cord contusion may be possible in asymptomatic patients. Cervical cord signal changes on MRI may not be an absolute contraindication for return to play in neurologically intact patients, according to some authors. Cervical contusions secondary to cervical stenosis may be associated with a worse outcome and a higher recurrence rate than those those secondary to disc herniation. The evidence is low (Level IV) and individualized treatment must be recommended.