Cervical Spinal Segments Research Articles

Clinical presentation, imaging characteristics, and short‐term outcome of eight cats presented with suspected traumatic atlantoaxial hyperflexion

AbstractTraumatic atlantoaxial hyperflexion is considered rare in cats, and only a few case reports have been published. There are other conditions that can result in a peracute onset of neurological signs localized to the cervical spinal cord segments, including acute noncompressive nucleus pulposus extrusion, ischemic myelopathy, or vertebral fractures. Appropriate treatment for these conditions can only be initiated after an accurate diagnosis has been obtained. The aim of this observational, retrospective, single‐center, descriptive case series study was to describe the clinical presentation, imaging characteristics, and short‐term outcome of eight cats presented with suspected traumatic atlantoaxial hyperflexion. Young male healthy domestic shorthair cats were overrepresented (7/8) and typically presented with a peracute, nonprogressive, nonpainful, nonlateralizing C1–C5 myelopathy (tetraplegia or nonambulatory tetraparesis) following a road traffic accident or head trauma. All MRI studies demonstrated a solitary, focal, ill‐defined intramedullary lesion immediately dorsal to the dens of the axis, affecting both grey and white matter. All cats were treated medically. In 50% of the cats, the neurological grade improved at discharge or short‐term follow‐up, 25% of the cats recovered completely, one cat was static at short‐term follow‐up, and one cat was euthanized due to persistent forebrain signs and lack of neurological improvement.

Effects of exercise on autonomic cardiovascular control in individuals with chronic, motor-complete spinal cord injury: an exploratory randomised clinical trial.

Secondary analysis of a clinical trial. To assess the impact of 6 months of armcycle ergometry training (ACET), or body weight-supported treadmill training (BWSTT), on autonomic cardiovascular responses to a laboratory sit-up test (SUT) in individuals with chronic (≥1-year post-injury) spinal cord injury (SCI). Tertiary Rehabilitation Centre, Vancouver, Canada. Sixteen individuals with motor-complete (American Spinal Injury Association Impairment Scale A-B) SCI between the fourth cervical and sixth thoracic spinal cord segments, aged 39 ± 11 years, were assessed. Participants were randomized to receive 72 sessions of moderate-to-vigorous intensity ACET (n = 8) or passive BWSTT (n = 8). Changes in mean arterial pressure (finger plethysmography), hemodynamics (Modelflow® method), and heart rate/heart rate variability (HR/HRV; electrocardiography) were measured in response toa SUT before and after 6 months of exercise training. Spontaneous cardiovagal baroreflex sensitivity (cvBRS) was assessed using the sequence method. Neither ACET nor BWSTT impacted hemodynamic responses to SUT or the incidence of orthostatic hypotension (all P > 0.36). ACET increased HR (P < 0.01, ηp2 = 0.34) and high frequency (HF) power HRV responses (P < 0.01, ηp2 = 0.42) to SUT following 6 months of training while BWSTT did not. Consistent with this, cvBRS improved (P < 0.05, ηp2 = 0.16) only following ACET. Improvements in cvBRS were correlated with both the HR (r = 0.726, P < 0.0001) and HF power (r = -0.484, P < 0.01) responses to SUT. Six months of ACET, but not BWSTT, improved cardiovagal baroreflex control of HR but had no effect on BP responses to SUT in individuals with chronic, motor-complete SCI. Canadian Institutes of Health Research (CIHR) CLINICAL TRIAL REGISTRATION: NCT01718977.

ROLE OF FORELIMB MORPHOLOGY IN MUSCLE SENSORIMOTOR FUNCTIONS DURING LOCOMOTION IN THE CAT.

Previous studies established strong links between morphological characteristics of mammalian hindlimb muscles and their sensorimotor functions during locomotion. Less is known about the role of forelimb morphology in motor outputs and generation of sensory signals. Here, we measured morphological characteristics of 46 forelimb muscles from 6 cats. These characteristics included muscle attachments, physiological cross-sectional area (PCSA), fascicle length, etc. We also recorded full-body mechanics and EMG activity of forelimb muscles during level overground and treadmill locomotion in 7 and 16 adult cats of either sex, respectively. We computed forelimb muscle forces along with force- and length-dependent sensory signals mapped onto corresponding cervical spinal segments. We found that patterns of computed muscle forces and afferent activities were strongly affected by the muscle's moment arm, PCSA, and fascicle length. Morphology of the shoulder muscles suggests distinct roles of the forelimbs in lateral force production and movements. Patterns of length-dependent sensory activity of muscles with long fibers (brachioradialis, extensor carpi radialis) closely matched patterns of overall forelimb length, whereas the activity pattern of biceps brachii matched forelimb orientation. We conclude that cat forelimb muscle morphology contributes substantially to locomotor function, particularly to control lateral stability and turning, rather than propulsion.

Structural changes in spinal cord following optic neuritis: Insights from quantitative spinal MRI

ObjectivesPrevious studies have demonstrated that optic neuritis (ON) affects brain plasticity. However, whether ON affects the spinal cord remains unclear. We aimed to investigate the spinal cord changes in ON and their associations with disability. MethodsA total of 101 ON patients, and 41 healthy controls (HC) were retrospectively recruited. High-resolution imaging was conducted using a Magnetization Prepared Rapid Acquisition Gradient-Echo (MP-RAGE) sequence for T1-weighted images and an echo planar imaging (EPI) sequence for Diffusion Tensor Imaging (DTI) data collection. Additionally, patients' disability and cognitive impairment were evaluated using the Expanded Disability Status Scale (EDSS) and the Paced Auditory Serial Addition Test (PASAT), respectively. The quantitative spinal MRI was employed to examine the cross-sectional area (CSA) and diffusion indicators, with a specific focus on calculating the average values across the C2-C7 cervical spinal cord segments. CSA, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were compared between groups. Correlation analyses were performed between CSA, diffusion indicators, and clinical variables. ResultsNo significant differences were found in CSA between ON patients and HCs. MD (p = 0.007) and RD (p = 0.018) were increased in ON patients compared with HCs, and AD was decreased in ON (p = 0.013). The AD values of the ON patients were significantly positively correlated with PASAT scores (r = 0.37, p < 0.001). ConclusionsThis study provided imaging evidence for DTI abnormalities in patients with ON. Spinal cord DTI can improve our knowledge of the path physiology of ON, and clinical progression.

Impaired communication at the neuromotor axis during Degenerative Cervical Myelopathy.

Degenerative Cervical Myelopathy (DCM) is a progressive neurological condition characterized by structural alterations in the cervical spine, resulting in compression of the spinal cord. While clinical manifestations of DCM are well-documented, numerous unanswered questions persist at the molecular and cellular levels. In this study, we sought to investigate the neuromotor axis during DCM. We use a clinically relevant mouse model, where after 3 months of DCM induction, the sensorimotor tests revealed a significant reduction in both locomotor activity and muscle strength compared to the control group. Immunohistochemical analyses showed alterations in the gross anatomy of the cervical spinal cord segment after DCM. These changes were concomitant with the loss of motoneurons and a decrease in the number of excitatory synaptic inputs within the spinal cord. Additionally, the DCM group exhibited a reduction in the endplate surface, which correlated with diminished presynaptic axon endings in the supraspinous muscles. Furthermore, the biceps brachii (BB) muscle exhibited signs of atrophy and impaired regenerative capacity, which inversely correlated with the transversal area of remnants of muscle fibers. Additionally, metabolic assessments in BB muscle indicated an increased proportion of oxidative skeletal muscle fibers. In line with the link between neuromotor disorders and gut alterations, DCM mice displayed smaller mucin granules in the mucosa layer without damage to the epithelial barrier in the colon. Notably, a shift in the abundance of microbiota phylum profiles reveals an elevated Firmicutes-to-Bacteroidetes ratio-a consistent hallmark of dysbiosis that correlates with alterations in gut microbiota-derived metabolites. Additionally, treatment with short-chain fatty acids stimulated the differentiation of the motoneuron-like NSC34 cell line. These findings shed light on the multifaceted nature of DCM, resembling a synaptopathy that disrupts cellular communication within the neuromotor axis while concurrently exerting influence on other systems. Notably, the colon emerges as a focal point, experiencing substantial perturbations in both mucosal barrier integrity and the delicate balance of intestinal microbiota.

Facet joint involvement in the inflammatory rheumatic disease

BackgroundThe involvement of facet joints (FJ) in patients with inflammatory rheumatic disorders remains underexplored. This review aims to look at FJ disease from a rheumatologist's perspective, with the emphasis given to the clinical presentations and patterns of FJ engagement in axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), rheumatoid arthritis (RA), and crystal-related arthropathies, and discussion of challenges in studying FJ in rheumatic disease. MethodsA systematic PubMed search using the pertinent keywords was performed, relevant articles extracted, and the acquired data critically assessed, interpreted, and organized according to the authors’ experience and judgment. ResultsFJ involvement is common in patients with radiographic axSpA, occurs throughout the spine, but is more frequently seen in the thoracic segment. The existing data suggests that the FJ are primarily affected by the disease process, while altered spine biomechanics due to the presence of syndesmophytes at the same vertebral level contributes to the FJ fusion. Predominant involvement of FJ of the cervical spinal segment has been suggested in PsA; however, prevalence and clinical significance of FJ involvement in PsA is still markedly underexplored. RA-related FJ disease of the cervical spine in patients with poorly controlled RA is not uncommon and can be related to significant morbidity, while the burden of FJ involvement in the thoracic and lumbar spinal segments in RA is also underexplored. FJ disease is possible in the course of crystal-related arthropathies, but the high level of suspicion is a prerequisite for the timely diagnosis. ConclusionsThe involvement of FJ in the course of inflammatory rheumatic disease is not uncommon. Prospective studies are needed to understand the epidemiology and significance of FJ disease in inflammatory rheumatic conditions.

Finite Element Analysis of Head-Neck Kinematics in Rear-End Impact Conditions with Headrest.

A detailed three-dimensional (3D) head-neck (C0-C7) finite element (FE) model was developed and used to dictate the motions of each cervical spinal segment under static physiological loadings of flexion and extension with a magnitude of 1.0 Nm and rear-end impacts. In this dynamic study, a rear-end impact pulse was applied to C7 to create accelerations of 4.5 G and 8.5 G. The predicted segmental motions and displacements of the head were in agreement with published results under physiological loads of 1.0 Nm. Under rear-end impact conditions, the effects of peak pulse acceleration and headrest angles on the kinematic responses of the head-neck complex showed rates of increase/decrease in the rotational motion of various cervical spinal segments that were different in the first 200 ms. The peak flexion rotation of all segments was lower than the combined ROM of flexion and extension. The peak extension rotation of all segments showed variation compared to the combined ROM of flexion and extension depending on G and the headrest angle. A higher acceleration of C7 increased the peak extension angle of lower levels, but the absolute increase was restricted by the distance between the head and the headrest. A change in the headrest angle from 45° to 30° resulted in a change in extension rotation at the lower C5-C6 segments to flexion rotation, which further justified the effectiveness of having distance between the head and the headrest. This study shows that the existing C0-C7 FE model is efficient at defining the gross reactions of the human cervical spine under both physiological static and simulated whiplash circumstances. The fast rate of changes in flexion and extension rotation of various segments may result in associated soft tissues and bony structures experiencing tolerances beyond their material characteristic limits. It is suggested that a proper location and angle of the headrest could effectively prevent the cervical spine from injury in traumatic vehicular accidents.

Deep phenotyping the cervical spine: automatic characterization of cervical degenerative phenotypes based on T2-weighted MRI.

Radiological degenerative phenotypes provide insight into a patient's overall extent of disease and can be predictive for future pathological developments as well as surgical outcomes and complications. The objective of this study was to develop a reliable method for automatically classifying sagittal MRI image stacks of cervical spinal segments with respect to these degenerative phenotypes. We manually evaluated sagittal image data of the cervical spine of 873 patients (5182 motion segments) with respect to 5 radiological phenotypes. We then used this data set as ground truth for training a range of multi-class multi-label deep learning-based models to classify each motion segment automatically, on which we then performed hyper-parameter optimization. The ground truth evaluations turned out to be relatively balanced for the labels disc displacement posterior, osteophyte anterior superior, osteophyte posterior superior, and osteophyte posterior inferior. Although we could not identify a single model that worked equally well across all the labels, the 3D-convolutional approach turned out to be preferable for classifying all labels. Class imbalance in the training data and label noise made it difficult to achieve high predictive power for underrepresented classes. This shortcoming will be mitigated in the future versions by extending the training data set accordingly. Nevertheless, the classification performance rivals and in some cases surpasses that of human raters, while speeding up the evaluation process to only require a few seconds.

Role of MRI Diffusion Tensor Imaging in Early Diagnosis of Cervical Spondylotic Myelopathy (CSM)

Abstract Background and Purpose Cervical spondylotic myelopathy (CSM) is a common degenerative disorder of the cervical spine and is considered as the most common cause of spinal cord dysfunction in older individuals worldwide. Assessing the severity of the disease objectively remains a challenge and there is still remaining controversy in terms of the optimal timing and indications for surgical intervention. The conventional MRI is the gold standard for radiographic evaluation of the spinal cord; however, it cannot assess the underlying microstructural deficits of the spinal cord and it has a limited application in determining prognosis and recovery of the disease [1]. We sought to assess the utility of MR diffusion tensor imaging as an imaging technique in clinically suggested CSM patients by obtaining the microstructural parameters (Fractional anisotropy; FA and apparent diffusion coefficient; ADC) in the cervical spinal cord segments. Patient &amp; methods our study was a prospective cross-sectional study including 40 patients with clinical manifestations of cervical spondylotic myelopathy. The patients were sorted according to the European myelopathy score into three categories as follows: grade 1 (with mild symptoms), grade 2 (with moderate symptoms) and grade 3 (with severe symptoms). All the patients were investigated with a 1.5 T MRI unit acquiring conventional MRI and DTI sequences. FA and ADC values at each spinal segment from C2/C3 to C6/C7 were generated and measured using manual drawing of multiple ROIs within the cervical cord in the sagittal and axial combined anatomical and color-coded images. For each of these cases, the patient’s age, gender, DTI parameters at each spinal segment level, maximum compression level, conventional T2WI characteristics and EMS score were recorded, analyzed and compared. Results The study included 23 females (57.5%) and 17 males (42.5%). Their age ranged from 30 to 72 years with a mean age of 47.3 ± 9.79 years. The study revealed a significant difference in the mean FA and ADC values between stenotic and non-stenotic segments of the cervical spinal cord. There was a significant correlation between the European myelopathy score and DTI parameters (FA and ADC). FA and ADC values performed better in recognizing myelopathic changes in patients who were classified as grade 1 according to EMS compared to conventional MRI T2WI which performed very poorly in recognizing myelopathy changes in the same patients, therefore DTI indices were more sensitive in the detection of CSM patients compared to conventional MRI especially in early myelopathic stages. T2 weighted images were highly significant in recognizing myelopathy changes in patients who were classified as grade 3 according to EMS. The CSM patients had significant FA decrease and ADC increase at the most compressed part of the cervical spinal cord and there was a significant correlation between the number of patients who had myelopathic changes by DTI parameters and the severity of disease. The FA sensitivity and specificity in recognition of myelopathic changes were 73.5% and 83.3% respectively and the ADC sensitivity and specificity were 100% and 70.6% respectively. Conclusion In conclusion, diffusion tensor imaging enhances the efficacy and accuracy of MRI in the diagnosis of cervical spondylotic myelopathy. Therefore, it can be used as a non-invasive modality for detection of the spondylotic myelopathy changes in the early stages helping to decide the appropriate timing of decompression surgery before attaining the irreversible chronic changes. Abbreviations ADC: Apparent diffusion coefficient; CSM: Cervical spondylotic myelopathy; DTI: Diffusion tensor imaging; FA: Fractional Anisotropy; EMS: European myelopathy score

Targeted transcutaneous spinal cord stimulation promotes persistent recovery of upper limb strength and tactile sensation in spinal cord injury: a pilot study.

Long-term recovery of limb function is a significant unmet need in people with paralysis. Neuromodulation of the spinal cord through epidural stimulation, when paired with intense activity-based training, has shown promising results toward restoring volitional limb control in people with spinal cord injury. Non-invasive neuromodulation of the cervical spinal cord using transcutaneous spinal cord stimulation (tSCS) has shown similar improvements in upper-limb motor control rehabilitation. However, the motor and sensory rehabilitative effects of activating specific cervical spinal segments using tSCS have largely remained unexplored. We show in two individuals with motor-complete SCI that targeted stimulation of the cervical spinal cord resulted in up to a 1,136% increase in exerted force, with weekly activity-based training. Furthermore, this is the first study to document up to a 2-point improvement in clinical assessment of tactile sensation in SCI after receiving tSCS. Lastly, participant gains persisted after a one-month period void of stimulation, suggesting that targeted tSCS may lead to persistent recovery of motor and sensory function.

The Effect of Yoga Practice on Cervical Tactile Acuity and Body Awareness.

Body-mind-based holistic methods of relaxation and improved well-being, such as yoga and meditation, improve body awareness and have often been used to enhance quality of life and the ability to cope with pain. We aimed to compare tactile sensory acuity and body awareness in healthy sedentary individuals who practiced yoga regularly and in control participants who had not practiced yoga. Participants were 60 individuals, aged between 18 and 35years who were divided into two groups according to whether they had previously practiced yoga. We used the two-point discrimination (TPD) test to determine participants' tactile acuity, as measured with a digital calliper at the C7, C5, C3, C1 and T1 spinal segments and with the Body Awareness Questionnaire (BAQ). The TPD measurements of individuals who practiced yoga and meditation had a lower discriminatory threshold compared to those who had not practiced yoga (p < .001), and the self-reported BAQ score of yoga practitioners was higher than that of the controls (p < .001). We found a positive correlation between the length of the prior duration of yoga experience and self-reported body awareness (r = .567, p < .001). There was a significant negative correlation (r = -.379, p = .015) between the C5 segment and the TPD measurements, but not for the other cervical spinal segments (p > .05). There was a negative correlation between the length of prior yoga practice and the TPD measurements in all cervical segments (p < .001). The most negative correlation was found at the C7 segment (r = -.844, p < .001) and the least negative correlation was found at the C3 segment (r = -.669, p < .001). These data suggest that yoga and meditation practices may improve well-being and diminish pain by increasing body awareness and tactile sensory acuity in the cervical region.

DISTRIBUTION OF PARVALBUMIN-EXPRESSING NEURONAL POPULATIONS IN THE CAT CERVICAL AND LUMBAR SPINAL CORD GRAY MATTER

Parvalbumin is a classical marker of interneuronal populations in the central nervous system. Analyzing the cervical and lumbar spinal cord segments of cats (Felis catus), both individual cells and entire populations of neurons expressing parvalbumin were identified in most of the gray matter laminae. These populations have strict laminar and nuclear localization. Numerous neuronal clusters are located in the medial part of lamina V–VI and in laminae VII of cervical and lumbar enlargements. We believe that the first one located in segments C4–C8 and L4–L7 may participate in the modulatory mechanisms of locomotor activity via the convergence of cutaneous and proprioceptive afferentation from the limbs. Neuronal populations in lamina VII consist of Ia interneurons and Renshaw interneurons that participate in the motoneuron inhibition. Less numerous populations of parvalbumin-immunopositive cells found in laminae III possibly participated in the regulation of cutaneous sensitivity. Another population located in lamina VIII possibly forms commissural and propriospinal connections and participates in modulating the activity of motoneurons. Immunopositive interneurons also revealed in the precerebellar nuclei: central cervical nucleus and Clarke’s nucleus; unlike the general population of these nuclei, neurons revealed are interneurons. Scarce immunopositive cells are found in lamina I of L6–L7 segments, as well as in laminae II, IV, and X of all segments investigated.

Clinical Profile and Predictors of Early Outcome in Patients with Traumatic Spinal Cord Injury in Jos, North-Central Nigeria.

Spinal cord injury is a devastating condition and has been recognised so since antiquity with evolving pattern of presentation and outcome. This study aimed to review the clinical profile and determinants of early outcome in patients with traumatic spinal cord injury (TSCI) in Jos, Nigeria. This retrospective cohort study, reviewed the health records of all patients with TSCI that were managed, based on the neurosurgical unit protocol for the management of TSCI in our institution from 2011 to 2021. Relevant data were retrieved into a preformed pro forma, analysis was done for determinants of outcome using SPSS and presented in tables and figure. A total of 296 patients, aged 20-39 years, with male to female ratio of 5.2:1 were studied. The median time from injury to presentation was 96 h, and the cervical spine was the most (139, 47.0%) affected region. Most of the patients (183, 61.8%) had complete injury (ASIA A) at presentation, the average, first week mean arterial blood pressure (MAP) of 89.98 ± 8.86. Mortality was 73 (24.7%) at 6 weeks post injury and complete TSCI, cervical spinal cord segment and the average "first week" MAP were, independent predictors of mortality. The admission ASIA impairment scale (AIS) and injury to presentation interval were predictive of AIS improvement at 6 weeks and length of hospital stay (LOHs). We also found that AIS at admission, level of spinal cord affected and the average first week MAP were early predictors of mortality, while the injury to presentation interval and admission AIS, predicted improvement of AIS at 6 weeks. The LOHs was seen more in patients with severe AIS at admission and those who had delayed presentation.

Congenitally Fused Cervical Spine Is Associated With Adjacent-Level Degeneration in the Absence of Cervical Spine Surgery.

Cervical fusion surgery is associated with adjacent-level degeneration, but surgical and technical factors are difficult to dissociate from the mechanical effects of the fusion itself. To determine the effect of fusion on adjacent-level degeneration in unoperated patients using a cohort of patients with congenitally fused cervical vertebrae. We identified 96 patients with incidental single-level cervical congenital fusion on computed tomography imaging. We compared these patients to an age-matched control cohort of 80 patients without congenital fusion. We quantified adjacent-level degeneration through direct measurements of intervertebral disk parameters as well as the validated Kellgren & Lawrence classification scale for cervical disk degeneration. Ordinal logistic regression and 2-way analysis of variance testing were performed to correlate extent of degeneration with the congenitally fused segment. Nine hundred fifty-five motion segments were analyzed. The numbers of patients with C2-3, C3-4, C4-5, C5-6, and C6-7 congenitally fused segments were 47, 11, 11, 17, and 9, respectively. We found that patients with congenital fusion at C4-C5 and C5-C6 had a significantly greater extent of degeneration at adjacent levels compared with the degree of degeneration at the same levels in control patients and in patients with congenital fusion at other cervical levels, even while controlling for expected degeneration and age. Taken together, our data suggest that congenitally fused cervical spinal segments at C4-C5 and C5-C6 are associated with adjacent-level degeneration independent of fixation instrumentation. This study design removes surgical factors that might contribute to adjacent-level degeneration.

Atypical Heterotopic Bone Formation Rear to the Functioning Cervical Artificial Disc Prosthesis Causing Cervical Spondylotic Myelopathy

Although heterotopic ossification (HO) might occur in a substantial proportion of cervical disc arthroplasty-switched spinal segments, it is predominantly discovered at the anterior vertebral edges of the treated interspace. Herein, we present the case of a 63-year-old woman who presented with clinical signs of myelopathy almost 5 years after the implantation of a Mobi-C disc prosthesis for C6-7 soft disc herniation. As shown by magnetic resonance imaging and computed tomography, spinal cord compression and a consequent signal change inside the cord were attributed to bony spurs from HO posterior to the still-moving prosthesis. Initial full posterior decompression through C6-7 bilateral laminectomy added to posterior stabilization almost fully relieved the patient’s functional and sensory changes from myelopathy. However, the device, as well as the ectopic bone deposits, had to be removed, and switching to anterior arthrodesis was necessary due to the imminent aggravation and progression of cervical kyphotic curvature from the still-functioning device. To the authors’ knowledge, such extensive bone accumulation posterior to a functional Mobi-C cervical prosthesis causing myelopathy has not yet been reported in the literature. Conversion to solid fusion would be preferred to posterior decompression for the sake of maintaining cervical curvature.

Acute sleep deprivation aggravates nitroglycerin-evoked hyperalgesia in mice.

Sleep deprivation can trigger migraine, and migraineurs often choose to sleep to relieve headaches during acute migraine. This study aimed to explore the effect of acute sleep deprivation on hyperalgesia induced by nitroglycerin in mice. In part one, after either 6-h sleep deprivation or 6-h normal sleep, mice were intraperitoneally injected with nitroglycerin or saline. The mechanical pain threshold and withdrawal latency of the hindpaw were measured every 30min for 6h. Next, the same sleep deprivation and injection procedure was performed with new mice, and mice were sacrificed 4.5h after injection. The trigeminal nucleus caudalis and upper cervical spinal segments were taken for immunofluorescence Fos staining. In part two, after injection of saline or nitroglycerin, the mice were either deprived of sleep for 6h or allowed to sleep without interference. The mechanical and thermal pain threshold were measured after 6h. In part three, we compared the sleep time of mice after intraperitoneal injection of saline or nitroglycerin without interference. Sleep deprivation for 6h did not cause any changes in the baseline pain thresholds in mice. However, pretreatment with 6-h sleep deprivation significantly prolonged the duration of hyperalgesia induced by nitroglycerin. Additionally, the expression of Fos at 4.5h was significantly higher in the 6-h sleep deprivation and nitroglycerin group than in the other three groups. When intraperitoneal injection was given first, the mechanical pain threshold of the hind paw was significantly lower in the group that received nitroglycerin with 6-h sleep deprivation than in the other groups. Compared to the saline injection, one-time nitroglycerin injection would result in a significant increase in sleep latency and decrease in sleep duration for the normal mice. Acute sleep deprivation significantly aggravated the hyperalgesia induced by nitroglycerin in mice, which highlights the importance of sleep disorders for migraine.

A candidate protective factor in amyotrophic lateral sclerosis: heterogenous nuclear ribonucleoprotein G.

Heterogenous nuclear ribonucleoprotein G is down-regulated in the spinal cord of the Tg(SOD1*G93A)1Gur (TG) amyotrophic lateral sclerosis mouse model. However, most studies have only examined heterogenous nuclear ribonucleoprotein G expression in the amyotrophic lateral sclerosis model and heterogenous nuclear ribonucleoprotein G effects in amyotrophic lateral sclerosis pathogenesis such as in apoptosis are unknown. In this study, we studied the potential mechanism of heterogenous nuclear ribonucleoprotein G in neuronal death in the spinal cord of TG and wild-type mice and examined the mechanism by which heterogenous nuclear ribonucleoprotein G induces apoptosis. Heterogenous nuclear ribonucleoprotein G in spinal cord was analyzed using immunohistochemistry and western blotting, and cell proliferation and proteins (TAR DNA binding protein 43, superoxide dismutase 1, and Bax) were detected by the Cell Counting Kit-8 and western blot analysis in heterogenous nuclear ribonucleoprotein G siRNA-transfected PC12 cells. We analyzed heterogenous nuclear ribonucleoprotein G distribution in spinal cord in the amyotrophic lateral sclerosis model at various time points and the expressions of apoptosis and proliferation-related proteins. Heterogenous nuclear ribonucleoprotein G was mainly localized in neurons. Amyotrophic lateral sclerosis mice were examined at three stages: preonset (60-70 days), onset (90-100 days) and progression (120-130 days). The number of heterogenous nuclear ribonucleoprotein G-positive cells was significantly higher in the anterior horn of the lumbar spinal cord segment of TG mice at the preonset stage than that of control group but lower than that of the control group at the onset stage. The number of heterogenous nuclear ribonucleoprotein G-positive cells in both central canal and surrounding gray matter of the whole spinal cord of TG mice at the onset stage was significantly lower than that in the control group, whereas that of the lumbar spinal cord segment of TG mice was significantly higher than that in the control group at preonset stage and significantly lower than that in the control group at the progression stage. The numbers of heterogenous nuclear ribonucleoprotein G-positive cells in the posterior horn of cervical and thoracic segments of TG mice at preonset and progression stages were significantly lower than those in the control group. The expression of heterogenous nuclear ribonucleoprotein G in the cervical spinal cord segment of TG mice was significantly higher than that in the control group at the preonset stage but significantly lower at the progression stage. The expression of heterogenous nuclear ribonucleoprotein G in the thoracic spinal cord segment of TG mice was significantly increased at the preonset stage, significantly decreased at the onset stage, and significantly increased at the progression stage compared with the control group. heterogenous nuclear ribonucleoprotein G expression in the lumbar spinal cord segment of TG mice was significantly lower than that of the control group at the progression stage. After heterogenous nuclear ribonucleoprotein G gene silencing, PC12 cell survival was lower than that of control cells. Both TAR DNA binding protein 43 and Bax expressions were significantly increased in heterogenous nuclear ribonucleoprotein G-silenced cells compared with control cells. Our study suggests that abnormal distribution and expression of heterogenous nuclear ribonucleoprotein G might play a protective effect in amyotrophic lateral sclerosis development via preventing neuronal death by reducing abnormal TAR DNA binding protein 43 generation in the spinal cord.

Integrative transcriptomic analysis of the amyotrophic lateral sclerosis spinal cord implicates glial activation and suggests new risk genes.

Amyotrophic lateral sclerosis (ALS) is a progressively fatal neurodegenerative disease affecting motor neurons in the brain and spinal cord. In this study, we investigated gene expression changes in ALS via RNA sequencing in 380 postmortem samples from cervical, thoracic and lumbar spinal cord segments from 154 individuals with ALS and 49 control individuals. We observed an increase in microglia and astrocyte gene expression, accompanied by a decrease in oligodendrocyte gene expression. By creating a gene co-expression network in the ALS samples, we identified several activated microglia modules that negatively correlate with retrospective disease duration. We mapped molecular quantitative trait loci and found several potential ALS risk loci that may act through gene expression or splicing in the spinal cord and assign putative cell types for FNBP1, ACSL5, SH3RF1 and NFASC. Finally, we outline how common genetic variants associated with splicing of C9orf72 act as proxies for the well-known repeat expansion, and we use the same mechanism to suggest ATXN3 as a putative risk gene.

Targeting drug or gene delivery to the phrenic motoneuron pool.

Phrenic motoneurons (PhrMNs) innervate diaphragm myofibers. Located in the ventral gray matter (lamina IX), PhrMNs form a column extending from approximately the third to sixth cervical spinal segment. Phrenic motor output and diaphragm activation are impaired in many neuromuscular diseases, and targeted delivery of drugs and/or genetic material to PhrMNs may have therapeutic application. Studies of phrenic motor control and/or neuroplasticity mechanisms also typically require targeting of PhrMNs with drugs, viral vectors, or tracers. The location of the phrenic motoneuron pool, however, poses a challenge. Selective PhrMN targeting is possible with molecules that move retrogradely upon uptake into phrenic axons subsequent to diaphragm or phrenic nerve delivery. However, nonspecific approaches that use intrathecal or intravenous delivery have considerably advanced the understanding of PhrMN control. New opportunities for targeted PhrMN gene expression may be possible with intersectional genetic methods. This article provides an overview of methods for targeting the phrenic motoneuron pool for studies of PhrMNs in health and disease.

Nuclear countdown

Case: A 50-year-old woman presented with a 10-year history of progressive symptoms, beginning with right facial numbness. She developed dysgeusia, and dysphagia before the onset of dysarthria. She had progressive gait instability with frequent backwards falls. A gastrostomy was inserted for persistent weight loss. She required hospital admission for aspiration pneumonia and type 2 respiratory failure. On examina- tion she had a head drop and staring expression with reduced blink frequency and hypophonia. There was bilateral facial weakness with temporalis and tongue wasting. She had a supranuclear gaze palsy and her saccadic eye movements were almost absent in all directions. Limbs were hypotonic with distal weakness and reduced reflexes.InvestigationsNCS/EMG showed chronic widespread partial denervation in the facial, trigeminal (motor) and hypoglossal-innervated muscles. Blink reflexes were absent bilaterally. There were chronic denerva- tion changes in the cervical and lumbar spinal segments. MRI brain showed global atrophy particularly implicating the temporal lobes and brainstem.DiagnosisA diagnosis of Facial-Onset Sensory and Motor Neuronopathy (FOSMN) was made. Given the additional clinical features of supranuclear gaze palsy we believe this is the first case of FOSMN-PSP overlap syndrome.ConclusionWe report a unique FOSMN case with some overlap features of PSP, not previously described. daniel.rice-wilson@nhs.net23