Spinal Cord Gray Matter Research Articles

Serum response factor promotes axon regeneration following spinal cord transection injury.

Studies have shown that serum response factor is beneficial for axonal regeneration of peripheral nerves. However, its role after central nervous system injury remains unclear. In this study, we established a rat model of T9-T10 spinal cord transection injury. We found that the expression of serum response factor in injured spinal cord gray matter neurons gradually increased with time, reached its peak on the 7th day, and then gradually decreased. To investigate the role of serum response factor, we used lentivirus vectors to overexpress and silence serum response factor in spinal cord tissue. We found that overexpression of serum response factor promoted motor function recovery in rats with spinal cord injury. Qualitative observation of biotinylated dextran amine anterograde tracing showed that overexpression of serum response factor increased nerve fibers in the injured spinal cord. Additionally, transmission electron microscopy showed that axon and myelin sheath morphology was restored. Silencing serum response factor had the opposite effects of overexpression. These findings suggest that serum response factor plays a role in the recovery of motor function after spinal cord injury. The underlying mechanism may be related to the regulation of axonal regeneration.

Association of daily physical activity with brain volumes and cervical spinal cord areas in multiple sclerosis

Background: Remote activity monitoring has the potential to evaluate real-world, motor function, and disability at home. The relationships of daily physical activity with spinal cord white matter and gray matter (GM) areas, multiple sclerosis (MS) disability and leg function, are unknown. Objective: Evaluate the association of structural central nervous system pathology with ambulatory disability. Methods: Fifty adults with progressive or relapsing MS with motor disability who could walk >2 minutes were assessed using clinician-evaluated, patient-reported outcomes, and quantitative brain and spinal cord magnetic resonance imaging (MRI) measures. Fitbit Flex2, worn on the non-dominant wrist, remotely assessed activity over 30 days. Univariate and multivariate analyses were performed to assess correlations between physical activity and other disability metrics. Results: Mean age was 53.3 years and median Expanded Disability Status Scale (EDSS) was 4.0. Average daily step counts (STEPS) were highly correlated with EDSS and walking measures. Greater STEPS were significantly correlated with greater C2-C3 spinal cord GM areas (ρ = 0.39, p = 0.04), total cord area (TCA; ρ = 0.35, p = 0.04), and cortical GM volume (ρ = 0.32, p = 0.04). Conclusion These results provide preliminary evidence that spinal cord GM area is a neuroanatomical substrate associated with STEPS. STEPS could serve as a proxy to alert clinicians and researchers to possible changes in structural nervous system pathology.

Anterior horn atrophy in the cervical spinal cord: A new biomarker in progressive multiple sclerosis

Background: Spinal cord (SC) gray and white matter pathology plays a central role in multiple sclerosis (MS). Objective: We aimed to investigate the extent, pattern, and clinical relevance of SC gray and white matter atrophy in vivo. Methods: 39 relapsing–remitting patients (RRMS), 40 progressive MS patients (PMS), and 24 healthy controls (HC) were imaged at 3T using the averaged magnetization inversion recovery acquisitions sequence. Total and lesional cervical gray and white matter, and posterior (SCPH) and anterior horn (SCAH) areas were automatically quantified. Clinical assessment included the expanded disability status scale, timed 25-foot walk test, nine-hole peg test, and the 12-item MS walking scale. Results: PMS patients had significantly reduced cervical SCAH — but not SCPH — areas compared with HC and RRMS (both p < 0.001). In RRMS and PMS, the cervical SCAH areas increased significantly less in the region of cervical SC enlargement compared with HC (all p < 0.001). This reduction was more pronounced in PMS compared with RRMS (both p < 0.001). In PMS, a lower cervical SCAH area was the most important magnetic resonance imaging (MRI)-variable for higher disability scores. Conclusion: MS patients show clinically relevant cervical SCAH atrophy, which is more pronounced in PMS and at the level of cervical SC enlargement.

Spinal Central Canal Dilation in MOG Antibody-Associated Disease Versus Other CNS Demyelinating Disorders

Objective To assess the frequency of spinal cord central canal dilation on magnetic resonance imaging (MRI) in patients with myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) myelitis compared to myelitis patients with aquaporin-4-positive-neuromyelitis optic spectrum disorder (AQP4+NMOSD) and multiple sclerosis (MS). Background In MOGAD myelitis, a sagittal T2-hyperintense line accompanied by axial T2-signal restricted to the spinal cord gray matter forming an H-sign have been recognized and occur more frequently than in AQP4+NMOSD and MS myelitis. Pseudo-dilation of the ependymal canal has also been highlighted in cases of MOGAD myelitis, but detailed studies of this are lacking. Design/Methods The spinal cord MRIs of myelitis patients with MOGAD (n = 63), AQP4+NMOSD (n = 37), and MS (n = 26) were evaluated for central canal dilation, defined as T2-hyperintensity with similar consistency to cerebrospinal fluid within a myelitis T2-lesion. Clinical data were collected from the medical record for MOGAD patients. The expanded disability status scale (EDSS) was used to quantify disability at nadir. Results The median EDSS score at nadir for the MOGAD myelitis patients was 6 (range: 0-8). MOGAD patients experienced weakness (55/63[87%]), urinary retention/incontinence (50/63[79%]), numbness/paresthesias (48/63[76%]), and stool incontinence/constipation (36/63[57%]). Central canal dilation was more frequent in patients with MOGAD (23/63[37%]) than MS (0/26[0%]); p &lt; 0.001) but did not differ from AQP4+NMOSD (14/37[38%]; p = 0.89). Spinal canal dilation resolved on follow-up axial MRI for most MOGAD (29/34[85%]) and AQP4+NMOSD (13/14[93%]) patients. Conclusions Central canal dilation is a common radiologic accompaniment of acute MOGAD and AQP4+NMOSD myelitis, but not MS myelitis. The resolution of central canal dilation on follow-up MRI in most patients suggests it is transient and related to the acute inflammatory edema. Central canal dilation may differentiate MOGAD and AQP4+NMOSD from MS. Its recognition could facilitate earlier testing for MOG-IgG and AQP4-IgG, accurate diagnosis, and treatment.

The Impact of Activity-Based Interventions on Neuropathic Pain in Experimental Spinal Cord Injury.

Physical activity-based rehabilitative interventions represent the main treatment concept for people suffering from spinal cord injury (SCI). The role such interventions play in the relief of neuropathic pain (NP) states is emerging, along with underlying mechanisms resulting in SCI-induced NP (SCI-NP). Animal models have been used to investigate the benefits of activity-based interventions (ABI), such as treadmill training, wheel running, walking, swimming, and bipedal standing. These activity-based paradigms have been shown to modulate inflammatory-related alterations as well as induce functional and structural changes in the spinal cord gray matter circuitry correlated with pain behaviors. Thus far, the research available provides an incomplete picture of the cellular and molecular pathways involved in this beneficial effect. Continued research is essential for understanding how such interventions benefit SCI patients suffering from NP and allow the development of individualized rehabilitative therapies. This article reviews preclinical studies on this specific topic, goes over mechanisms involved in SCI-NP in relation to ABI, and then discusses the effectiveness of different activity-based paradigms as they relate to different forms, intensity, initiation times, and duration of ABI. This article also summarizes the mechanisms of respective interventions to ameliorate NP after SCI and provides suggestions for future research directions.

MobileUNetV3—A Combined UNet and MobileNetV3 Architecture for Spinal Cord Gray Matter Segmentation

The inspection of gray matter (GM) tissue of the human spinal cord is a valuable tool for the diagnosis of a wide range of neurological disorders. Thus, the detection and segmentation of GM regions in magnetic resonance images (MRIs) is an important task when studying the spinal cord and its related medical conditions. This work proposes a new method for the segmentation of GM tissue in spinal cord MRIs based on deep convolutional neural network (CNN) techniques. Our proposed method, called MobileUNetV3, has a UNet-like architecture, with the MobileNetV3 model being used as a pre-trained encoder. MobileNetV3 is light-weight and yields high accuracy compared with many other CNN architectures of similar size. It is composed of a series of blocks, which produce feature maps optimized using residual connections and squeeze-and-excitation modules. We carefully added a set of upsampling layers and skip connections to MobileNetV3 in order to build an effective UNet-like model for image segmentation. To illustrate the capabilities of the proposed method, we tested it on the spinal cord gray matter segmentation challenge dataset and compared it to a number of recent state-of-the-art methods. We obtained results that outperformed seven methods with respect to five evaluation metrics comprising the dice similarity coefficient (0.87), Jaccard index (0.78), sensitivity (87.20%), specificity (99.90%), and precision (87.96%). Based on these highly competitive results, MobileUNetV3 is an effective deep-learning model for the segmentation of GM MRIs in the spinal cord.

Delayed administration of elezanumab, a human anti-RGMa neutralizing monoclonal antibody, promotes recovery following cervical spinal cord injury

Spinal cord injury (SCI) elicits a cascade of degenerative events including cell death, axonal degeneration, and the upregulation of inhibitory molecules which limit repair. Repulsive guidance molecule A (RGMa) is an axon growth inhibitor which is also involved in neuronal cell death and differentiation. SCI causes upregulation of RGMa in the injured rodent, non-human primate, and human spinal cord. Recently, we showed that delayed administration of elezanumab, a high affinity human RGMa-specific monoclonal antibody, promoted neuroprotective and regenerative effects following thoracic SCI. Since most human traumatic SCI is at the cervical level, and level-dependent anatomical and molecular differences may influence pathophysiological responses to injury and treatment, we examined the efficacy of elezanumab and its therapeutic time window of administration in a clinically relevant rat model of cervical impact-compression SCI. Pharmacokinetic analysis of plasma and spinal cord tissue lysate showed comparable levels of RGMa antibodies with delayed administration following cervical SCI. At 12w after SCI, elezanumab promoted long term benefits including perilesional sparing of motoneurons and increased neuroplasticity of key descending pathways involved in locomotion and fine motor function. Elezanumab also promoted growth of corticospinal axons into spinal cord gray matter and enhanced serotonergic innervation of the ventral horn to form synaptic connections caudal to the cervical lesion. Significant recovery in grip and trunk/core strength, locomotion and gait, and spontaneous voiding ability was found in rats treated with elezanumab either immediately post-injury or at 3 h post-SCI, and improvements in specific gait parameters were found when elezanumab was delayed to 24 h post-injury. We also developed a new locomotor score, the Cervical Locomotor Score, a simple and sensitive measure of trunk/core and limb strength and stability during dynamic locomotion.

Clinical presentation, electrodiagnostic findings and outcomes of acute flaccid myelitis: A brief review and case series.

Acute flaccid myelitis (AFM) is an acute condition occurring mostly in children. Although affected patients can show a broad spectrum of symptoms, it is mainly characterized by the progressive onset of focal limb weakness, presenting over a period of hours to a week, with or without pain, and spinal cord gray matter involvement on magnetic resonance imaging (MRI). There is compelling evidence to support the role of viruses, in particular enteroviruses. Studies describing electrodiagnostic (EDX) abnormalities and long-term outcomes in AFM are limited. In this report, the clinical presentation, EDX and MRI findings, and long-term outcomes in three children with AFM who presented with progressive and asymmetric weakness of the limbs are described. MRI showed a long segment cervicothoracic lesion with vertical expansion in all three cases. Patients do recover in time, but many continue to have permanent muscle weakness in the worst affected part(s), and complete recovery is rare. Follow-up of these three cases at 18 months demonstrated a partial recovery in the motor system.

Altered SOD1 maturation and post-translational modification in amyotrophic lateral sclerosis spinal cord.

Aberrant self-assembly and toxicity of wild-type and mutant superoxide dismutase 1 (SOD1) has been widely examined in silico, in vitro and in transgenic animal models of amyotrophic lateral sclerosis. Detailed examination of the protein in disease-affected tissues from amyotrophic lateral sclerosis patients, however, remains scarce.We used histological, biochemical and analytical techniques to profile alterations to SOD1 protein deposition, subcellular localization, maturation and post-translational modification in post-mortem spinal cord tissues from amyotrophic lateral sclerosis cases and controls. Tissues were dissected into ventral and dorsal spinal cord grey matter to assess the specificity of alterations within regions of motor neuron degeneration.We provide evidence of the mislocalization and accumulation of structurally disordered, immature SOD1 protein conformers in spinal cord motor neurons of SOD1-linked and non-SOD1-linked familial amyotrophic lateral sclerosis cases, and sporadic amyotrophic lateral sclerosis cases, compared with control motor neurons. These changes were collectively associated with instability and mismetallation of enzymatically active SOD1 dimers, as well as alterations to SOD1 post-translational modifications and molecular chaperones governing SOD1 maturation. Atypical changes to SOD1 protein were largely restricted to regions of neurodegeneration in amyotrophic lateral sclerosis cases, and clearly differentiated all forms of amyotrophic lateral sclerosis from controls. Substantial heterogeneity in the presence of these changes was also observed between amyotrophic lateral sclerosis cases.Our data demonstrate that varying forms of SOD1 proteinopathy are a common feature of all forms of amyotrophic lateral sclerosis, and support the presence of one or more convergent biochemical pathways leading to SOD1 proteinopathy in amyotrophic lateral sclerosis. Most of these alterations are specific to regions of neurodegeneration, and may therefore constitute valid targets for therapeutic development.

Ameliorative effect of vitamin E and selenium against bisphenol A-induced toxicity in spinal cord and submandibular salivary glands of adult male albino rats

ABSTRACT Bisphenol A (BPA) used in plastic industry. This study evaluate ameliorative effect of vitamin E and selenium in combating BPA toxicity in spinal cord (SC) and submandibular glands (SMGs). Thirty rats divided into three groups [Group I, controls; Group II, BPA orally (25 mg/kg) three times a week, 60 days; Group III, BPA (25 mg/kg) plus vitamin E and selenium in water (1 ml/L/day)]. By histopathological, immunohistochemical, and biochemical investigations. Bisphenol A group showed degenerative alterations. SC gray matter showed pyknotic nuclei and white matter revealed neuropil degeneration. Myelinated fibers showed dispersed myelin. SMGs, exhibited vacuolated cytoplasm in acinar cells. Intense glial fibrillary acidic protein in SC and strong proliferating cell nuclear antigen in acinar and ductal cell nuclei of SMGs. Malondialdehyde elevated in SC and catalase decreased in SMG. Group III, SC and SMG revealed partial recovery. Vitamin E and selenium displayed protective effects against BPA toxicity in SC and SMGs.

Spinal cord grey matter atrophy in Multiple Sclerosis clinical practice

PurposeSeveral studies have indicated the relevance of spinal cord grey matter atrophy for Multiple Sclerosis (MS) related disability. This work aimed at evaluating feasibility and clinical relevance of MRI-derived estimations of spinal cord grey matter atrophy in clinical practice. MethodsA convenience sample of MS patients (n=48) and healthy controls (HC, n=11) was scanned using brain sagittal 3D T1w (MPRAGE) and transverse T2w-FLAIR, and transverse single-slice spinal cord 2D heavily T1w (PSIR: phase-sensitive inversion recovery) sequences. An experienced technician with neuroradiological supervision used a semiautomated thresholding method implemented in JIM software on PSIR sequences to obtain cross-sectional area (CSA) of the spinal canal (CSAcanal), whole cord (CSAcord), grey (CSAgm) and white matter (CSAwm) at C2-C3. MPRAGE and T2w-FLAIR sequences were used to obtain brain parenchymal, grey and white matter fractions (BPF, GMF and WMF) using the Statistical Parametric Mapping software. Appropriate statistical tests were used before and after age and sex adjustment. ResultsCSAgm and CSAwm could be obtained in all HC, but only 18 patients (37.5%) due to presence of lesions at C2-C3. Significant univariate associations between EDSS and BPF (rho =−0.376, p=0.015), GMF (rho =−0.287, p=0.069), CSAcanal (rho =−0.310, p=0.049), CSAcord (rho =−0.533 p<0.001) and CSAgm (rho =−0.511, p=0.062) were detected. After age/sex adjustment trends were observed for CSAcanal and CSAcord. ConclusionIn a clinical practice setting, relevance of spinal cord grey matter is confirmed, but cervical cord lesions could greatly hamper its application. Clinical associations with disability have been observed and seem stronger for spinal cord than for brain atrophy measures.

Activity dependent stimulation increases synaptic efficacy in spared pathways in an anesthetized rat model of spinal cord contusion injury.

Background:Closed-loop neuromodulation systems have received increased attention in recent years as potential therapeutic approaches for treating neurological injury and disease.Objective:The purpose of this study was to assess the ability of intraspinal microstimulation (ISMS), triggered by action potentials (spikes) recorded in motor cortex, to alter synaptic efficacy in descending motor pathways in an anesthetized rat model of spinal cord injury (SCI).Methods:Experiments were carried out in adult, male, Sprague Dawley rats with a moderate contusion injury at T8. For activity-dependent stimulation (ADS) sessions, a recording microelectrode was used to detect neuronal spikes in motor cortex that triggered ISMS in the spinal cord grey matter. SCI rats were randomly assigned to one of four experimental groups differing by: a) cortical spike-ISMS stimulus delay (10 or 25 ms) and b) number of ISMS pulses (1 or 3). Four weeks after SCI, ADS sessions were conducted in three consecutive 1-hour conditioning bouts for a total of 3 hours. At the end of each conditioning bout, changes in synaptic efficacy were assessed using intracortical microstimulation (ICMS) to examine the number of spikes evoked in spinal cord neurons during 5-minute test bouts. A multichannel microelectrode recording array was used to record cortically-evoked spike activity from multiple layers of the spinal cord.Results:The results showed that ADS resulted in an increase in cortically-evoked spikes in spinal cord neurons at specific combinations of spike-ISMS delays and numbers of pulses. Efficacy in descending motor pathways was increased throughout all dorsoventral depths of the hindlimb spinal cord.Conclusions:These results show that after an SCI, ADS can increase synaptic efficacy in spared pathways between motor cortex and spinal cord. This study provides further support for the potential of ADS therapy as an effective method for enhancing descending motor control after SCI.

Decoding Bilateral Hindlimb Kinematics From Cat Spinal Signals Using Three-Dimensional Convolutional Neural Network.

To date, decoding limb kinematic information mostly relies on neural signals recorded from the peripheral nerve, dorsal root ganglia (DRG), ventral roots, spinal cord gray matter, and the sensorimotor cortex. In the current study, we demonstrated that the neural signals recorded from the lateral and dorsal columns within the spinal cord have the potential to decode hindlimb kinematics during locomotion. Experiments were conducted using intact cats. The cats were trained to walk on a moving belt in a hindlimb-only condition, while their forelimbs were kept on the front body of the treadmill. The bilateral hindlimb joint angles were decoded using local field potential signals recorded using a microelectrode array implanted in the dorsal and lateral columns of both the left and right sides of the cat spinal cord. The results show that contralateral hindlimb kinematics can be decoded as accurately as ipsilateral kinematics. Interestingly, hindlimb kinematics of both legs can be accurately decoded from the lateral columns within one side of the spinal cord during hindlimb-only locomotion. The results indicated that there was no significant difference between the decoding performances obtained using neural signals recorded from the dorsal and lateral columns. The results of the time-frequency analysis show that event-related synchronization (ERS) and event-related desynchronization (ERD) patterns in all frequency bands could reveal the dynamics of the neural signals during movement. The onset and offset of the movement can be clearly identified by the ERD/ERS patterns. The results of the mutual information (MI) analysis showed that the theta frequency band contained significantly more limb kinematics information than the other frequency bands. Moreover, the theta power increased with a higher locomotion speed.

GABAB receptors constrain glutamate presynaptic release and postsynaptic actions in substantia gelatinosa of rat spinal cord.

The substantia gelatinosa (SG, lamina II of spinal cord gray matter) is pivotal for modulating nociceptive information from the peripheral to the central nervous system. γ-Aminobutyric acid type B receptors (GABABRs), the metabotropic GABA receptor subtype, are widely expressed in pre- and postsynaptic structures of the SG. Activation of GABABRs by exogenous agonists induces both pre- and postsynaptic inhibition. However, the actions of endogenous GABA via presynaptic GABABRs on glutamatergic synapses, and the postsynaptic GABABRs interaction with glutamate, remain elusive. In the present study, first, using in vitro whole-cell recordings and taking minimal stimulation strategies, we found that in rat spinal cord glutamatergic synapses, blockade of presynaptic GABABRs switched "silent" synapses into active ones and increased the probability of glutamate release onto SG neurons; increasing ambient GABA concentration mimicked GABABRs activation on glutamatergic terminals. Next, using holographic photostimulation to uncage glutamate on postsynaptic SG neurons, we found that postsynaptic GABABRs modified glutamate-induced postsynaptic potentials. Taken together, our data identify that endogenous GABA heterosynaptically constrains glutamate release via persistently activating presynaptic GABABRs; and postsynaptically, GABABRs modulate glutamate responses. The results give new clues for endogenous GABA in modulating the nociception circuit of the spinal dorsal horn and shed fresh light on the postsynaptic interaction of glutamate and GABA.

Spinal cord gray matter atrophy is associated with functional decline in post-polio syndrome.

ObjectiveTo determine if patients with post‐polio syndrome (PPS) show spinal cord gray matter (SCGM) atrophy and to assess associations between SCGM atrophy, muscle strength and patient‐reported functional decline.MethodsTwenty patients diagnosed with PPS (March of Dimes criteria) and 20 age‐ and sex‐matched healthy controls (HC) underwent 3T axial 2D‐rAMIRA magnetic resonance imaging at the intervertebral disc levels C2/C3–C6/C7, T9/T10 and the lumbar enlargement level (T max) (0.5 × 0.5 mm2 in‐plane resolution). SCGM areas were segmented manually by two independent raters. Muscle strength, self‐reported fatigue, depression and pain measures were assessed.ResultsPost‐polio syndrome patients showed significantly and preferentially reduced SCGM areas at C2/C3 (p = 0.048), C3/C4 (p = 0.001), C4/C5 (p < 0.001), C5/C6 (p = 0.004) and T max (p = 0.041) compared to HC. SCGM areas were significantly associated with muscle strength in corresponding myotomes even after adjustment for fatigue, pain and depression. SCGM areaTmax together with age and sex explained 68% of ankle dorsiflexion strength variance. No associations were found with age at or time since infection. Patients reporting PPS‐related decline in arm function showed significant cervical SCGM atrophy compared to stable patients adjusted for initial disease severity.ConclusionsPatients with PPS show significant SCGM atrophy that correlates with muscle strength and is associated with PPS‐related functional decline. Our findings suggest a secondary neurodegenerative process underlying SCGM atrophy in PPS that is not explained by aging or residua of the initial infection alone. Confirmation by longitudinal studies is needed. The described imaging methodology is promising for developing novel imaging surrogates for SCGM diseases.

Multiscale Computer Model of the Spinal Dorsal Horn Reveals Changes in Network Processing Associated with Chronic Pain.

Pain-related sensory input is processed in the spinal dorsal horn (SDH) before being relayed to the brain. That processing profoundly influences whether stimuli are correctly or incorrectly perceived as painful. Significant advances have been made in identifying the types of excitatory and inhibitory neurons that comprise the SDH, and there is some information about how neuron types are connected, but it remains unclear how the overall circuit processes sensory input or how that processing is disrupted under chronic pain conditions. To explore SDH function, we developed a computational model of the circuit that is tightly constrained by experimental data. Our model comprises conductance-based neuron models that reproduce the characteristic firing patterns of spinal neurons. Excitatory and inhibitory neuron populations, defined by their expression of genetic markers, spiking pattern, or morphology, were synaptically connected according to available qualitative data. Using a genetic algorithm, synaptic weights were tuned to reproduce projection neuron firing rates (model output) based on primary afferent firing rates (model input) across a range of mechanical stimulus intensities. Disparate synaptic weight combinations could produce equivalent circuit function, revealing degeneracy that may underlie heterogeneous responses of different circuits to perturbations or pathologic insults. To validate our model, we verified that it responded to the reduction of inhibition (i.e., disinhibition) and ablation of specific neuron types in a manner consistent with experiments. Thus validated, our model offers a valuable resource for interpreting experimental results and testing hypotheses in silico to plan experiments for examining normal and pathologic SDH circuit function.SIGNIFICANCE STATEMENT We developed a multiscale computer model of the posterior part of spinal cord gray matter (spinal dorsal horn), which is involved in perceiving touch and pain. The model reproduces several experimental observations and makes predictions about how specific types of spinal neurons and synapses influence projection neurons that send information to the brain. Misfiring of these projection neurons can produce anomalous sensations associated with chronic pain. Our computer model will not only assist in planning future experiments, but will also be useful for developing new pharmacotherapy for chronic pain disorders, connecting the effect of drugs acting at the molecular scale with emergent properties of neurons and circuits that shape the pain experience.

Lower motor neuron involvement in patients with neuromyelitis optica spectrum disorders

BackgroundInvolvement of the central gray matter of spinal cord is a characteristic magnetic resonance imaging (MRI) feature of aquaporin-4-immunoglobulin G antibodies (AQP4-IgG) positive neuromyelitis optica spectrum disorders (NMOSD). However, there has been no systemic electrophysiological study investigating the frequency of lower motor neuron involvement in NMOSD patients. MethodsWe retrospectively reviewed a cohort of 59 NMOSD patients with results of concentric needle electromyography (EMG) and nerve conduction studies (NCS) that were admitted to the Department of Neurology of Chinese PLA General Hospital between January 2016 and December 2019. ResultsAcute and/or chronic denervation was found in 22.0% (13/59) of the NMOSD patients by EMG. Peripheral or cranial neuropathy indicated by abnormal NCS changes was found in 11.9% (7/59) of the NMOSD patients. Denervation indicated by EMG that can be accounted for by abnormal NCS was found in 6.8% (4/59) of the NMOSD patients, while 3.4% (2/59) of the NMOSD patients had NCS abnormality without denervation indicated by EMG. Accordingly, 9 of the 59 NMOSD patients (15.3%) had lower motor neuron involvement, and moreover, 6.8% (4/59) of the NMOSD patients had corresponding spinal cord or brainstem lesions on MRI. ConclusionNot uncommon lower motor neuron involvement exists in NMOSD patients, so needle EMG and NCS studies should be performed in NMOSD patients with suspected lower motor neuron involvement.

Spinal cord representation of motor cortex plasticity reflects corticospinal tract LTP

Although it is well known that activity-dependent motor cortex (MCX) plasticity produces long-term potentiation (LTP) of local cortical circuits, leading to enhanced muscle function, the effects on the corticospinal projection to spinal neurons has not yet been thoroughly studied. Here, we investigate a spinal locus for corticospinal tract (CST) plasticity in anesthetized rats using multichannel recording of motor-evoked, intraspinal local field potentials (LFPs) at the sixth cervical spinal cord segment. We produced LTP by intermittent theta burst electrical stimulation (iTBS) of the wrist area of MCX. Approximately 3 min of MCX iTBS potentiated the monosynaptic excitatory LFP recorded within the CST termination field in the dorsal horn and intermediate zone for at least 15 min after stimulation. Ventrolaterally, in the spinal cord gray matter, which is outside the CST termination field in rats, iTBS potentiated an oligosynaptic negative LFP that was localized to the wrist muscle motor pool. Spinal LTP remained robust, despite pharmacological blockade of iTBS-induced LTP within MCX using MK801, showing that activity-dependent spinal plasticity can be induced without concurrent MCX LTP. Pyramidal tract iTBS, which preferentially activates the CST, also produced significant spinal LTP, indicating the capacity for plasticity at the CST-spinal interneuron synapse. Our findings show CST monosynaptic LTP in spinal interneurons and demonstrate that spinal premotor circuits are capable of further modifying descending MCX control signals in an activity-dependent manner.

Does acute flaccid myelitis cause respiratory failure in children?

Acute flaccid myelitis (AFM) is a rare disease that affects spinal cord gray matter, results in acute flaccid weakness of one or more limbs and predominantly involves the cervical spinal cord, which places patients at higher risk for respiratory failure. Our study aims to describe respiratory failure in pediatric AFM patients with emphasis on the need for assisted ventilation and respiratory nerve involvement from an acute and long-term perspective. We reviewed the medical records of patients diagnosed with AFM seen in a multidisciplinary clinic for persistent limb weakness between 2016 and 2020. We studied 54 patients, 35% were female. The median age of patients at illness onset was 5 years (range 7 months-19 years). The median age of patients at the time of study was 8.5 years (range 2-20 years). Eleven patients (20%) required assisted ventilation for acute respiratory failure. Of those that experienced acute respiratory failure, 81% developed chronic respiratory failure. Fifty-six percent of patients with chronic respiratory failure were able to wean off assisted ventilation by 1year. All patients that experienced unilateral diaphragm impairment with AFM onset experienced acute and chronic respiratory failure. Many patients with AFM may experience respiratory compromise and develop chronic respiratory failure. However, most of these patients can be weaned off ventilatory support by 1 year from illness onset. Most children with unilateral diaphragm impairment can sustain adequate ventilation without the need for long-term ventilatory support.

S-CUDA: Self-cleansing unsupervised domain adaptation for medical image segmentation.

Medical image segmentation tasks hitherto have achieved excellent progresses with large-scale datasets, which empowers us to train potent deep convolutional neural networks (DCNNs). However, labeling such large-scale datasets is laborious and error-prone, which leads the noisy (or incorrect) labels to be an ubiquitous problem in the real-world scenarios. In addition, data collected from different sites usually exhibit significant data distribution shift (or domain shift). As a result, noisy label and domain shift become two common problems in medical imaging application scenarios, especially in medical image segmentation, which degrade the performance of deep learning models significantly. In this paper, we identify a novel problem hidden in medical image segmentation, which is unsupervised domain adaptation on noisy labeled data, and propose a novel algorithm named "Self-Cleansing Unsupervised Domain Adaptation" (S-CDUA) to address such issue. S-CUDA sets up a realistic scenario to solve the above problems simultaneously where training data (i.e., source domain) not only shows domain shift w.r.t. unsupervised test data (i.e., target domain) but also contains noisy labels. The key idea of S-CUDA is to learn noise-excluding and domain invariant knowledge from noisy supervised data, which will be applied on the highly corrupted data for label cleansing and further data-recycling, as well as on the test data with domain shift for supervised propagation. To this end, we propose a novel framework leveraging noisy-label learning and domain adaptation techniques to cleanse the noisy labels and learn from trustable clean samples, thus enabling robust adaptation and prediction on the target domain. Specifically, we train two peer adversarial networks to identify high-confidence clean data and exchange them in companions to eliminate the error accumulation problem and narrow the domain gap simultaneously. In the meantime, the high-confidence noisy data are detected and cleansed in order to reuse the contaminated training data. Therefore, our proposed method can not only cleanse the noisy labels in the training set but also take full advantage of the existing noisy data to update the parameters of the network. For evaluation, we conduct experiments on two popular datasets (REFUGE and Drishti-GS) for optic disc (OD) and optic cup (OC) segmentation, and on another public multi-vendor dataset for spinal cord gray matter (SCGM) segmentation. Experimental results show that our proposed method can cleanse noisy labels efficiently and obtain a model with better generalization performance at the same time, which outperforms previous state-of-the-art methods by large margin. Our code can be found at https://github.com/zzdxjtu/S-cuda.