Hoffmann's sign in cervical spondylotic myelopathy patients: pathological insights from neuroimaging.

OBJECTIVE: Hoffmann's sign testing is a commonly used physical examination in clinical practice for patients with cervical spondylotic myelopathy (CSM). However, the pathophysiological mechanisms underlying its occurrence and development have not been thoroughly investigated. Therefore, the present study aimed to explore whether a positive Hoffmann's sign (PHS) in CSM patients is associated with spinal cord and brain remodeling and to identify potential neuroimaging biomarkers with diagnostic value. METHODS: Seventy-six patients with CSM and 40 sex- and age-matched healthy controls (HCs) underwent multimodal MRI. Based on the results of the Hoffmann's sign examination, patients were divided into two groups: those with a PHS (n = 38) and those with a negative Hoffmann's sign (NHS; n = 38). Quantification of spinal cord and brain structural and functional parameters of the participants was performed using various methods, including functional connectivity analysis, voxel-based morphometry, and atlas-based analysis based on functional MRI and structural MRI data. Furthermore, this study conducted a correlation analysis between neuroimaging metrics and neurological function and utilized a support vector machine (SVM) algorithm for the classification of PHS and NHS. RESULTS: In comparison with the NHS and HC groups, PHS patients exhibited significant reductions in the cross-sectional area and fractional anisotropy (FA) of the lateral corticospinal tract (CST), reticulospinal tract (RST), and fasciculus cuneatus, concomitant with bilateral reductions in the volume of the lateral pallidum. The functional connectivity analysis indicated a reduction in functional connectivity between the left lateral pallidum and the right angular gyrus in the PHS group. The correlation analysis indicated a significant positive association between the CST and RST FA and the volume of the left lateral pallidum in PHS patients. Furthermore, all three variables exhibited a positive correlation with the patients' motor function. Finally, using multimodal neuroimaging metrics in conjunction with the SVM algorithm, PHS and NHS were classified with an accuracy rate of 85.53%. CONCLUSIONS: This research revealed a correlation between structural damage to the pallidum and RST and the presence of Hoffmann's sign as well as the motor function in patients with CSM. Features based on neuroimaging indicators have the potential to serve as biomarkers for assessing the extent of neuronal damage in CSM patients.

Contribution of changes in the spinal cord and brain to the onset and progression of hand clumsiness symptoms in cervical spondylotic myelopathy.

OBJECTIVE: Cervical spondylotic myelopathy (CSM) stands as the most prevalent form of spinal cord injury, frequently prompting various changes in both the brain and spinal cord. However, the precise nature of these changes within the brains and spinal cords of CSM patients experiencing hand clumsiness (HCL) symptoms has remained elusive. The authors aimed to scrutinize these alterations and explore potential links between these changes and the onset of HCL symptoms. METHODS: Using the modified Japanese Orthopaedic Association (mJOA) scale, the authors classified CSM patients into two groups: those without HCL and those with HCL. The authors performed voxel-wise z-score transformation amplitude of low-frequency fluctuations (zALFF) and resting-state functional connectivity (FC) evaluations in the brain. Additionally, they used the Spinal Cord Toolbox to calculate the fractional anisotropy (FA) of spinal cord tracts. The analysis also encompassed an examination of the correlation of these measures with improvements in mJOA scores. RESULTS: Significant disparities in zALFF values surfaced in the right calcarine, right cuneus, right precuneus, right middle occipital gyrus (MOG), right superior occipital gyrus (SOG), and right superior parietal gyrus (SPG) between healthy controls (HC), patients without HCL, and patients with HCL, primarily within the visual cortex. In the patient group, patients with HCL displayed reduced FC between the right calcarine, right MOG, right SOG, right SPG, right SFG, bilateral MFG, and left median cingulate and paracingulate gyri when compared with patients without HCL. Moreover, significant differences in FA values of the corticospinal tract (CST) and reticulospinal tract (REST) at the C2 level emerged among HC, patients without HCL, and patients with HCL. Notably, zALFF, FC, and FA values in specific brain regions and spinal cord tracts exhibited correlations with mJOA upper-extremity scores. Additionally, FA values of the CST and REST correlated with zALFF values in the right calcarine, right MOG, right SOG, and right SPG. CONCLUSIONS: Alterations within brain regions associated with the visual cortex, the fronto-parietal-occipital attention network, and spinal cord pathways appear to play a substantial role in the emergence and progression of HCL symptoms. Furthermore, the existence of a potential connection between the spinal cord and the brain suggests that this link might be related to the clinical symptoms of CSM.

The enhanced connectivity between the frontoparietal, somatomotor network and thalamus as the most significant network changes of chronic low back pain.

The prolonged duration of chronic low back pain (cLBP) inevitably leads to changes in the cognitive, attentional, sensory and emotional processing brain regions. Currently, it remains unclear how these alterations are manifested in the interplay between brain functional and structural networks. This study aimed to predict the Oswestry Disability Index (ODI) in cLBP patients using multimodal brain magnetic resonance imaging (MRI) data and identified the most significant features within the multimodal networks to aid in distinguishing patients from healthy controls (HCs). We constructed dynamic functional connectivity (dFC) and structural connectivity (SC) networks for all participants (n = 112) and employed the Connectome-based Predictive Modeling (CPM) approach to predict ODI scores, utilizing various feature selection thresholds to identify the most significant network change features in dFC and SC outcomes. Subsequently, we utilized these significant features for optimal classifier selection and the integration of multimodal features. The results revealed enhanced connectivity among the frontoparietal network (FPN), somatomotor network (SMN) and thalamus in cLBP patients compared to HCs. The thalamus transmits pain-related sensations and emotions to the cortical areas through the dorsolateral prefrontal cortex (dlPFC) and primary somatosensory cortex (SI), leading to alterations in whole-brain network functionality and structure. Regarding the model selection for the classifier, we found that Support Vector Machine (SVM) best fit these significant network features. The combined model based on dFC and SC features significantly improved classification performance between cLBP patients and HCs (AUC=0.9772). Finally, the results from an external validation set support our hypotheses and provide insights into the potential applicability of the model in real-world scenarios. Our discovery of enhanced connectivity between the thalamus and both the dlPFC (FPN) and SI (SMN) provides a valuable supplement to prior research on cLBP.

Dysregulated neural activity between the thalamus and cerebral cortex mediates cortical reorganization in cervical spondylotic myelopathy.

Neuroimaging research has revealed significant changes in brain structure and function in patients with cervical spondylotic myelopathy(CSM). The thalamus plays a crucial role in this process, although its mechanisms of action remain incompletely understood. This study aimed to investigate whether spinal cord compression leads to alterations in the functional connectivity between the thalamus and the cerebral cortex, and to determine if such changes are associated with structural and functional remodeling of the brain in patients with CSM, and to identify potential neuroimaging biomarkers for classification. The study included 40 patients with CSM and 34 healthy controls(HCs) who underwent resting-state functional magnetic resonance imaging(fMRI) and structural MRI scans. Brain structural and functional metrics were quantified using functional connectivity(FC), fractional amplitude of low-frequency fluctuations(fALFF), surface-based morphometry(SBM), and independent component analysis(ICA) based on functional and structural MRI. Patients with CSM exhibited significantly reduced fALFF in the bilateral lateral lingual gyrus, bilateral calcarine fissure, left precentral gyrus and postcentral gyrus, left middle and superior occipital gyrus, left superior marginal gyrus, left inferior parietal gyrus, and right Rolandic operculum. ICA results revealed weakened functional connectivity between the sensorimotor network (SMN) and the left and right frontoparietal network(FPN), and lateral visual network (lVN), along with decreased connectivity between lVN and rFPN, and increased connectivity between lFPN and rFPN. Patients with CSM also had decreased sulcus depth in the bilateral insula, left precentral and postcentral gyrus, and right lingual gyrus and calcarine fissure. Furthermore, cervical spondylotic myelopathy patients showed decreased functional connectivity between the left ventral posterolateral nucleus (VPL) of the thalamus and the right middle occipital gyrus (MOG). Finally,multimodal neuroimaging with support vector machine(SVM) classified patients with CSM and healthy controls with 86.00% accuracy. Our study revealed that the decrease in functional connectivity between the thalamus and cortex mediated by spinal cord compression leads to structural and functional reorganization of the cortex. Features based on neuroimaging markers have the potential to become neuroimaging biomarkers for CSM.

Remodeling of the brain correlates with gait instability in cervical spondylotic myelopathy.

Introduction: Cervical spondylotic myelopathy (CSM) is a common form of non-traumatic spinal cord injury (SCI) and usually leads to remodeling of the brain and spinal cord. In CSM with gait instability, the remodeling of the brain and cervical spinal cord is unclear. We attempted to explore the remodeling of these patients' brains and spinal cords, as well as the relationship between the remodeling of the brain and spinal cord and gait instability. Methods: According to the CSM patients' gait, we divided patients into two groups: normal gait patients (nPT) and abnormal gait patients (aPT). Voxel-wise z-score transformation amplitude of low-frequency fluctuations (zALFF) and resting-state functional connectivity (rs-FC) were performed for estimating brain changes. Cross-sectional area (CSA) and fractional anisotropy (FA) of the spinal cord were computed by Spinal cord toolbox. Correlations of these measures and the modified Japanese Orthopedic Association (mJOA) score were analyzed. Results: We found that the zALFF of caudate nucleus in aPT was higher than that in healthy controls (HC) and lower than that in nPT. The zALFF of the right postcentral gyrus and paracentral lobule in HC was higher than those of aPT and nPT. Compared with the nPT, the aPT showed increased functional connectivity between the caudate nucleus and left angular gyrus, bilateral precuneus and bilateral posterior cingulate cortex (PCC), which constitute a vital section of the default mode network (DMN). No significantly different FA values or CSA of spinal tracts at the C2 level were observed between the HC, nPT and aPT groups. In CSM, the right paracentral lobule's zALFF was negatively correlated with the FA value of fasciculus gracilis (FCG), and the right caudate zALFF was positively correlated with the FA value of the fasciculus cuneatus (FCC). The results showed that the functional connectivity between the right caudate nucleus and DMN was negatively correlated with the CSA of the lateral corticospinal tract (CST). Discussion: The activation of the caudate nucleus and the strengthening functional connectivity between the caudate nucleus and DMN were associated with gait instability in CSM patients. Correlations between spinal cord and brain function might be related to the clinical symptoms in CSM.

Degeneration of the Sensorimotor Tract in Degenerative Cervical Myelopathy and Compensatory Structural Changes in the Brain.

Degenerative cervical myelopathy is a progressive neurodegenerative disease, that has become increasingly prevalent in the aging population worldwide. The current study determined the factors affecting degeneration in the sensorimotor tract with degenerative cervical myelopathy and its relationship with brain structure. We divided patients into hyperintensity (HS) and non-hyperintensity (nHS) groups and measured the fractional anisotropy and apparent diffusion coefficients of the lateral corticospinal tract (CST), fasciculus gracilis and fasciculus cuneatus (FGC). Voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) techniques were used to estimate brain structure changes. Correlation of the modified Japanese Orthopaedic Association (mJOA) score, light touch, pinprick, motor score, and fractional anisotropy (FA) ratios of the CST at different levels were analyzed. Compared to healthy controls, the FA ratios of CST in the HS and nHS groups were decreased at all levels, and the apparent diffusion coefficient (ADC) ratio was increased only at C4/5 levels in the HS group. The FA ratio of FGC was decreased at the C3/4 and C4/5 levels in the HS group and only decreased at the C4/5 level in the nHS group. The ADC ratio was decreased only at the C4/5 level in the HS group. VBM analysis revealed that the volume of the precentral gyrus, postcentral gyrus, and paracentral lobule increased in patients compared to controls. TBSS analysis found no statistical significance between the sensory and motor tracts in white matter. The volume of clusters in HS and nHS groups negatively correlated with the C1/2 FA ratio of the CST. The results showed that the degeneration distance of the CST was longer than the FGC, and the degeneration distance was related to the degree of compression and spinal cord damage. Structural compensation and the neurotrophin family may lead to enlargement of the brain.