Assessing the spatial distribution of cervical spinal cord activity during tactile stimulation of the upper extremity in humans with functional magnetic resonance imaging.

Dermatomal maps are a mainstay of clinical practice and provide information on the spatial distribution of the cutaneous innervation of spinal nerves. Dermatomal deficits can help isolate the level of spinal nerve root involvement in spinal conditions and guide clinicians in diagnosis and treatment. Dermatomal maps, however, have limitations, and the spatial distribution of spinal cord sensory activity in humans remains to be quantitatively assessed. Here we used spinal cord functional MRI to map and quantitatively compare the spatial distribution of sensory spinal cord activity during tactile stimulation of the left and right lateral shoulders (i.e. C5 dermatome) and dorsal third digits of the hands (i.e., C7 dermatome) in healthy humans (n â€‹= â€‹24, age â€‹= â€‹36.8 â€‹± â€‹11.8 years). Based on the central sites for processing of innocuous tactile sensory information, we hypothesized that the activity would be localized more to the ipsilateral dorsal spinal cord with the lateral shoulder stimulation activity being localized more superiorly than the dorsal third digit. The findings demonstrate lateralization of the activity with the left- and right-sided stimuli having more activation in the ipsilateral hemicord. Contradictory to our hypotheses, the activity for both stimulation sites was spread across the dorsal and ventral hemicords and did not demonstrate a clear superior-inferior localization. Instead, the activity for both stimuli had a broader than expected distribution, extending across the C5, C6, and C7 spinal cord segments. We highlight the complexity of the human spinal cord neuroanatomy and several sources of variability that may explain the observed patterns of activity. While the findings were not completely consistent with our a priori hypotheses, this study provides a foundation for continued work and is an important step towards developing normative quantitative spinal cord measures of sensory function, which may become useful objective MRI-based biomarkers of neurological injury and improve the management of spinal disorders.

Isolating Neurologic Deficits in Cervical Spondylotic Myelopathy: A Case-Controlled Study, Using the NIH Toolbox Motor Battery.

Background and Objectives: Patients with cervical spondylotic myelopathy (CSM) have motor impairments, including weakness, imbalance, and loss of dexterity. The reliable assessment of these symptoms is critical for treatment decisions. This study aimed to determine, for the first time, the use of the NIH Toolbox motor battery (NIHTBm) in the objective assessment of motor deficits in patients with CSM. Methods: Patients with symptoms and MRI evidence of CSM and age-matched healthy controls (HC), with no evidence of spinal disorder or surgery were included in this case-control study based on our inclusion and exclusion criteria. We performed motor tests, dexterity, gait speed, grip strength, and balance tests, using the NIHTBm in patients with CSM and HCs. Motor impairment rates were determined in patients with CSM based on the NIHTBm scores. We determined the association between NIHTBm scores and patient-reported outcome scores; patient-reported outcome measures (the modified Japanese Orthopedic Association [mJOA] and Nurick grade) to determine the association. One-way analysis of variance was used to analyze group differences and the Spearman rank correlation to determine the relationship between assessment scores. Results: We enrolled 24 patients with CSM with a mean age (SD) of 57.96 (10.61) years and 24 age-matched HCs with a mean age (SD) of 53.17 (6.04) years in this study. Overall, we observed a significant decrease in the motor function T-scores mean (SD): dexterity 31.54 (14.82) vs 51.54 (9.72), grip strength 32.00 (17.47) vs 56.79 (8.46), balance 27.58 (16.65) vs 40.21 (6.35), and gait speed 0.64 (0.18) vs 0.99 (0.17) m/s, in patients with CSM compared with that in HCs. The lower extremity dysfunction scores on the NIHTBm, balance (ρ = -0.67) and gait speed (ρ = -0.62), were associated with higher Nurick grades. We observed a similar but weaker association with the Nurick grades and NIHTBm tests: dexterity (ρ = -0.49) and grip strength (ρ = -0.31) scores. The total motor mJOA showed a positive but weak association with NIHTBm scores, gait speed (ρ = 0.38), balance (ρ = 0.49), grip strength (ρ = 0.41), and dexterity (ρ = 0.45). Discussion: Patients with CSM had significantly lower NIHTBm scores compared with HCs. The results from the NIHTBm are consistent with the clinical presentation of CSM showing patients have motor impairments in both upper and lower extremities. As a neurologic-specific scale, NIHTBm should be used in the evaluation and clinical management of patients with CSM.

Fatty infiltration in cervical flexors and extensors in patients with degenerative cervical myelopathy using a multi-muscle segmentation model.

BACKGROUND: In patients with degenerative cervical myelopathy (DCM) that have spinal cord compression and sensorimotor deficits, surgical decompression is often performed. However, there is heterogeneity in clinical presentation and post-surgical functional recovery. OBJECTIVES: Primary: a) to assess differences in muscle fat infiltration (MFI) in patients with DCM versus controls, b) to assess association between MFI and clinical disability. Secondary: to assess association between MFI pre-surgery and post-surgical functional recovery. STUDY DESIGN: Cross-sectional case control study. METHODS: Eighteen patients with DCM (58.6 ± 14.2 years, 10 M/8F) and 25 controls (52.6 ± 11.8 years, 13M/12 F) underwent 3D Dixon fat-water imaging. A convolutional neural network (CNN) was used to segment cervical muscles (MFSS- multifidus and semispinalis cervicis, LC- longus capitis/colli) and quantify MFI. Modified Japanese Orthopedic Association (mJOA) and Nurick were collected. RESULTS: Patients with DCM had significantly higher MFI in MFSS (20.63 ± 5.43 vs 17.04 ± 5.24, p = 0.043) and LC (18.74 ± 6.7 vs 13.66 ± 4.91, p = 0.021) than controls. Patients with increased MFI in LC and MFSS had higher disability (LC: Nurick (Spearman's ρ = 0.436, p = 0.003) and mJOA (ρ = -0.399, p = 0.008)). Increased MFI in LC pre-surgery was associated with post-surgical improvement in Nurick (ρ = -0.664, p = 0.026) and mJOA (ρ = -0.603, p = 0.049). CONCLUSION: In DCM, increased muscle adiposity is significantly associated with sensorimotor deficits, clinical disability, and functional recovery after surgery. Accurate and time efficient evaluation of fat infiltration in cervical muscles may be conducted through implementation of CNN models.

Magnetic Resonance Imaging Atlas-Based Volumetric Mapping of the Cervical Cord Gray Matter in Cervical Canal Stenosis.

BACKGROUND: White matter volume loss may be an anatomic driver in the development of clinical symptoms in cervical spondylotic myelopathy (CSM). Considerably less attention has been devoted to gray matter (GM) injury. Newly developed atlas-based mapping techniques may allow evaluation of GM cord volume alterations in CSM. METHODS: There were 29 subjects evaluated: 15 patients with CSM (61.1 ± 8.7 years old) and 14 age-matched control subjects (56.1 ± 5.3 years old). All subjects underwent 3T magnetic resonance imaging of the cervical spine. Post-processing with the Spinal Cord Toolbox (v3.0) provided GM volumetric analysis. Clinical scores collected included modified Japanese Orthopaedic Association, neck and arm numeric rating scales, Nurick Scale, and Neck Disability Index. All volumes were normalized to account for anatomic variability. RESULTS: Normalized mean ventral GM volume in the compression region was significantly lower in patients compared with control subjects (1.103 ± 0.21 vs. 1.35 ± 0.32, P = 0.027). Normalized mean dorsal volume in the compression region was decreased in patients compared with control subjects (0.90 ± 0.17 vs. 1.04 ± 0.15, P = 0.049). GM volumes were associated with clinical scores, including Neck Disability Index, arm numeric rating scale, modified Japanese Orthopaedic Association, and Nurick Scale scores (P = 0.022, P = 0.004, P = 0.027, and P = 0.016). CONCLUSIONS: GM volume loss may be evaluated through atlas-based post-processing techniques and may correlate with clinical symptoms in CSM.

Macromolecular changes in spinal cord white matter characterize whiplash outcome at 1-year post motor vehicle collision.

Each year, whiplash injuries from motor vehicle collisions (MVC) affect millions worldwide, with no strong evidence of pathology. While the majority recover soon after the injury, the same is not true for roughly 20% reporting higher levels of pain and distress, without diagnostic options. This study used magnetization transfer (MT) imaging to quantify white matter integrity in 78 subjects with varying levels of pain, 1 year after MVC. MT images of the cervical spinal cord were collected parallel to the intervertebral disks. MT ratios (MTR) were calculated in select white matter tracts along with MTR homogeneity (MTRh) at each level. Significant differences were observed between clinical outcome groups in the left and right spinothalamic tracts (p = 0.003 and 0.020) and MTRh (p = 0.009). MTRh was elevated in females with poor recovery versus females reporting recovery (p < 0.001) or milder symptoms (p < 0.001), and in males reporting recovery (p = 0.007) or no recovery (p < 0.001). There was a significant interaction between recovery status and sex (p = 0.015). MT imaging identified tract specific and regional changes in white matter integrity suggesting potential insults to the cord. Additionally, significant MTRh differences between sexes were observed, characterizing the heterogeneity of whiplash recovery and worse outcomes in females.

Magnetization Transfer Ratio and Morphometrics of the Spinal Cord Associates with Surgical Recovery in Patients with Degenerative Cervical Myelopathy.

OBJECTIVES: We assessed the prognostic value of the preoperative magnetization transfer ratio (MTR) and morphometrics of the spinal cord in patients with degenerative cervical myelopathy (DCM) in a longitudinal cohort study. METHODS: Thirteen subjects with DCM underwent 3T magnetization transfer imaging. The MTR was calculated for the spinal cord regions and specific white matter tracts. Morphometric measures were extracted. Clinical (modified Japanese Orthopaedics Association [mJOA] and Nurick scale scores) and health-related quality of life scores were assessed before and after cervical decompression surgery. The association between the magnetic resonance imaging (MRI) metrics and postoperative recovery was assessed (Spearman's correlation). Receiver operating characteristics were used to assess the accuracy of MRI metrics in identifying ≥50% recovery in function. RESULTS: Preoperative anterior cord MTRs were associated with recovery in mJOA scores (ρ = 0.608; P = 0.036; area under the curve [AUC], 0.66). Preoperative lateral cord MTR correlated with the neck disability index (ρ = 0.699; P = 0.011) and pain interference scale (ρ = 0.732; P = 0.007). Preoperative rubrospinal tract MTR was associated with mJOA score recovery (ρ = 0.573; P = 0.041; AUC, 0.86). Preoperative corticospinal tract and reticulospinal MTRs were related to recovery in pain interference scores (ρ = 0.591; P = 0.033; and ρ = 0.583; P = 0.035, respectively). Eccentricity of the cord was associated with Nurick scores (ρ = 0.606; P = 0.028) and mJOA scores (ρ = 0.651; P = 0.025; AUC, 0.92). CONCLUSIONS: Preoperative MTR and eccentricity measurements of the spinal cord have prognostic value in assessing the response to surgery and recovery in patients with DCM. Advanced MRI and atlas-based postprocessing techniques can inform interventions and advance the healthcare received by patients with DCM.

Machine Learning for the Prediction of Cervical Spondylotic Myelopathy: A Post Hoc Pilot Study of 28 Participants.

BACKGROUND: Cervical spondylotic myelopathy (CSM) severity and presence of symptoms are often difficult to predict based simply on clinical imaging alone. Similarly, improved machine learning techniques provide new tools with immense clinical potential. METHODS: A total of 14 patients with CSM and 14 controls underwent imaging of the cervical spine. Two different artificial neural network models were trained; 1) to predict CSM diagnosis; and 2) to predict CSM severity. Model 1 consisted of 6 inputs including 3 common imaging scales for the evaluation of cord compression, alongside 3 objective magnetic resonance imaging measurements. The outcome for model 1 was binary to predict CSM diagnosis. Model 2 consisted of 23 input variables derived from probabilistic volume mapping measurements of white matter tracts in the region of compression. The outcome of model 2 was linear, to predict the modified Japanese Orthopedic Association (mJOA) score. RESULTS: Model 1 was used in predicting CSM. The mean cross-validated accuracy of the trained model was 86.50% (95% confidence interval, 85.16%-87.83%) with a median accuracy of 90.00%. Area under the curve (AUC) was calculated for each repetition. Average AUC for each repetition was 0.947 with a median AUC of 1.0. Average sensitivity, specificity, positive predictive value, and negative predictive value were 90.25%, 85.05%, 81.58%, and 91.94%, respectively. Model 2 was used in modeling mJOA. The mJOA model predicted scores, with a mean and median error of -0.29 mJOA points and -0.08 mJOA points, respectively, mean error per batch was 0.714 mJOA points. CONCLUSIONS: Machine learning provides a promising method for prediction, diagnosis, and even prognosis in patients with CSM.

Assessing hand dysfunction in cervical spondylotic myelopathy.

METHODS: Twenty patients with CSM and 17 controls were recruited. Clinical scores of modified Japanese Orthopedic Association (mJOA) and Nurick were collected. MRI based compression grades such as cord distortion were assessed. Hand dysfunction was tested using a custom motorized apparatus. Subject's forearm was placed in a cast and positioned such that their metacarpophalangeal (MCP) joint was vertically aligned with the motor shaft. Surface electromyographic sensors were placed on flexor digitorum superficialis (FDS) and extensor digitorum communis muscles. Hyperreflexia was measured as the FDS muscle activation during reflex when the MCP joint was moved from flexion to extension at 300°/sec. Proprioception was quantified as the angle of detection in absence of visual or auditory cues (subjects were blindfolded and given noise-cancelling headphones). Strength was measured as the maximum isometric force at the MCP joint. 2-sample t-test (p<0.05) were performed to assess significant differences in reflexes, proprioception and strength among patients and controls (SPSS software version 24). RESULTS: Patients reported higher Nurick (1.90±1.0 vs 0±0, p<0.001) and lower mJOA scores (14.3±1.9 vs 18.0±0, p<0.001) as compared to controls. Similarly, patients with CSM had increased reflexes (peak FDS EMG) (0.073±0.096 vs. 0.014±0.010, p = 0.019). Patient proprioception was significantly worse; mean angle of detection was greater than twice as high in patients (9.6± 9.43°) compared to controls (4.0± 2.3°), p = 0.022. MRI based compression ratio (CR) was a significant predictor of hyperreflexia, CR<0.44 resulted in steep increase in reflex activity. Fifteen of the 20 patients who completed follow up testing at 6 months after surgery show substantial clinical improvement in reflexes and proprioceptive angle, while repeated testing in controls were unchanged. CONCLUSION: In conclusion, hyperreflexia and decline in proprioception are the main drivers of hand disability in patients with CSM. Of multiple scales, only a select few MRI scales (such as compression ratio) were predictive of increased reflexes. The study describes a pre-clinical testing apparatus to quantitatively and objectively assess primary presenting symptoms in CSM. This pilot apparatus has the potential to evaluate treatment efficacy through repeated testing. Objective testing of hand dysfunction can help inform the design of clinically feasible devices, guide MRI biomarker analysis, and improve our understanding of the progression of neurological injury in this patient population.

Tract-Specific Volume Loss on 3T MRI in Patients With Cervical Spondylotic Myelopathy.

STUDY DESIGN: Case-control. OBJECTIVE: The aim of this study was to understand the role of high-resolution magnetic resonance (MR) in identifying regional cord volume loss in cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA: Preliminary studies suggest that compression of the ventral region of the cord may contribute disproportionately to CSM symptomology; however, tract-specific data are lacking in the CSM population. The current study is the first to use 3T MR imaging (MRI) images of CSM patients to determine specific volume loss at the level of detail of individual descending white matter tracts. METHODS: Twelve patients with CSM and 14 age-matched were enrolled prospectively and underwent 3-Tesla MRI of the cervical spine. Using the high-resolution images of the spinal cord, straightening and alignment with a template was performed and specific spinal cord tract volumes were measured using Spinal Cord Tool-box version 3.0.7. Modified Japanese orthopedic association (mJOA) and Nurick disability scores were collected in a prospective manner and were analyzed in relation to descending spinal tract volumes. RESULTS: Having CSM was predicted by anterior/posterior diameter, eccentricity of the cord [odds ratio (OR) 0.000000621, P = 0.004], ventral reticulospinal tract volume (OR 1.167, P = 0.063), lateral corticospinal tract volume (OR 1.034, P = 0.046), rubrospinal tract volume (OR 1.072, P = 0.011), and ventrolateral reticulospinal tract volume (OR 1.474, P = 0.005) on single variable logistic regression. Single variable linear regression showed decreases in anterior/posterior spinal cord diameter (P = 0.022), ventral reticulospinal tract volumes (P = 0.007), and ventrolateral reticulospinal tract volumes (P = 0.017) to significantly predict worsening mJOA scores. Similarly, decreases in ventral reticulospinal tract volumes significantly predicted increasing Nurick scores (P = 0.039). CONCLUSION: High-resolution 3T MRI can detect tract-specific volume loss in descending spinal cord tracts in CSM patients. Anterior/posterior spinal cord diameter, ventral reticulospinal tract, ventrolateral reticulospinal tract, lateral corticospinal tract, and rubrospinal tract volume loss are associated with CSM symptoms. LEVEL OF EVIDENCE: 2.

Fatty infiltration of the cervical multifidus musculature and their clinical correlates in spondylotic myelopathy.

Cervical spondylotic myelopathy (CSM) is among the most common spinal cord disorders of the elderly. Muscle fat infiltration (MFI), a potential pathological sign of muscle adiposity, may contribute to or be associated with pain/disability/impairments in patients with CSM. We examined the relationship between MFI and CSM's clinical manifestations by enrolling nine CSM patients and five aged-matched controls to undergo MRI imaging of the cervical spine with MFI. A blinded investigator calculated MFI for each of the bilateral multifidii muscles from C3 to C7 on the MRI images. Nurick scores, Neck Disability Index, and modified Japanese Orthopedic Association scores were collected for all patients. CSM patients and controls were equivalent with respect to age, height, weight, gender, race, smoking status, and employment status. MFI was higher in patients with CSM than in controls (31.7% v. 24.6%, respectively, p = 0.0178). Higher MFI was associated with increased disability on the Nurick scale (p = 0.0371). MJOA scores correlated linearly with MFI (R = 0.542, p = 0.0453), but not NDI (p = 0.3125). Increased MFI of the multifidus muscles is associated with cervical myelopathy and a clinically significant decline in sensorimotor function as measured by mJOA and Nurick scores. Spinal injury in CSM may lead to secondary muscle loss and muscle fat infiltration.