Regions Of Cord Research Articles

Distribution of Lewy-related pathology in the brain, spinal cord, and periphery: the population-based Vantaa 85 + study

Evolving evidence has supported the existence of two anatomically distinct Lewy-related pathology (LRP) types. Investigation of spinal cord and peripheral LRP can elucidate mechanisms of Lewy body disorders and origins of synuclein accumulation. Still, very few unselected studies have focused on LRP in these regions. Here we analysed LRP in spinal cord, dorsal root ganglion, and adrenal gland in the population-based Vantaa 85 + study, including every ≥ 85 years old citizen living in the city of Vantaa in 1991 (n = 601). Samples from spinal cord (C6-7, TH3-4, L3-4, S1-2) were available from 303, lumbar dorsal root ganglion from 219, and adrenal gland from 164 subjects. Semiquantitative scores of LRP were determined from immunohistochemically stained sections (anti-alpha-synuclein antibody 5G4). LRP in the ventral and dorsal horns of spinal cord, thoracic intermediolateral column, dorsal root ganglion and adrenal gland were compared with brain LRP, previously determined according to DLB Consortium criteria and by caudo-rostral versus amygdala-based LRP classification. Spinal LRP was found in 28% of the total population and in 61% of those who had LRP in the brain. Spinal cord LRP was found only in those subjects with LRP in the brain, and the quantity of spinal cord LRP was associated with the severity of brain LRP (p < 0.001). Unsupervised K-means analysis identified two cluster types of spinal and brain LRP corresponding to caudo-rostral and amygdala-based LRP types. The caudo-rostral LRP type exhibited more frequent and severe pathology in spinal cord, dorsal root ganglion and adrenal gland than the amygdala-based LRP type. Analysis of specific spinal cord regions showed that thoracic intermediolateral column and sacral dorsal horn were the most frequently affected regions in both LRP types. This population-based study on brain, spinal and peripheral LRP provides support to the concept of at least two distinct LRP types.

Selective vulnerability of brainstem and cervical spinal cord regions in people with non-progressive multiple sclerosis of Black or African American and European ancestry

Background: We evaluated imaging features suggestive of neurodegeneration within the brainstem and upper cervical spinal cord (UCSC) in non-progressive multiple sclerosis (MS). Methods: Standardized 3-Tesla three-dimensional brain magnetic resonance imaging (MRI) studies were prospectively acquired. Rates of change in volume, surface texture, curvature were quantified at the pons and medulla-UCSC. Whole and regional brain volumes and T2-weighted lesion volumes were also quantified. Independent regression models were constructed to evaluate differences between those of Black or African ancestry (B/AA) and European ancestry (EA) with non-progressive MS. Results: 209 people with MS (pwMS) having at least two MRI studies, 29% possessing 3–6 timepoints, resulted in 487 scans for analysis. Median follow-up time between MRI timepoints was 1.33 (25th–75th percentile: 0.51–1.98) years. Of 183 non-progressive pwMS, 88 and 95 self-reported being B/AA and EA, respectively. Non-progressive pwMS demonstrated greater rates of decline in pontine volume (p < 0.0001) in B/AA and in medulla-UCSC volume (p < 0.0001) for EA pwMS. Longitudinal surface texture and curvature changes suggesting reduced tissue integrity were observed at the ventral medulla-UCSC (p < 0.001), dorsal pons (p < 0.0001) and dorsal medulla (p < 0.0001) but not the ventral pons (p = 0.92) between groups. Conclusions: Selectively vulnerable regions within the brainstem-UCSC may allow for more personalized approaches to disease surveillance and management.

Cervical Epidural Electrical Stimulation Increases Respiratory Activity through Somatostatin-Expressing Neurons in the Dorsal Cervical Spinal Cord in Rats.

We tested the hypothesis that dorsal cervical epidural electrical stimulation (CEES) increases respiratory activity in male and female anesthetized rats. Respiratory frequency and minute ventilation were significantly increased when CEES was applied dorsally to the C2-C6 region of the cervical spinal cord. By injecting pseudorabies virus into the diaphragm and using c-Fos activity to identify neurons activated during CEES, we found neurons in the dorsal horn of the cervical spinal cord in which c-Fos and pseudorabies were co-localized, and these neurons expressed somatostatin (SST). Using dual viral infection to express the inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADD), hM4D(Gi), selectively in SST-positive cells, we inhibited SST-expressing neurons by administering Clozapine N-oxide (CNO). During CNO-mediated inhibition of SST-expressing cervical spinal neurons, the respiratory excitation elicited by CEES was diminished. Thus, dorsal cervical epidural stimulation activated SST-expressing neurons in the cervical spinal cord, likely interneurons, that communicated with the respiratory pattern generating network to effect changes in ventilation.SIGNIFICANCE STATEMENT A network of pontomedullary neurons within the brainstem generates respiratory behaviors that are susceptible to modulation by a variety of inputs; spinal sensory and motor circuits modulate and adapt this output to meet the demands placed on the respiratory system. We explored dorsal cervical epidural electrical stimulation (CEES) excitation of spinal circuits to increase ventilation in rats. We identified dorsal somatostatin (SST)-expressing neurons in the cervical spinal cord that were activated (c-Fos-positive) by CEES. CEES no longer stimulated ventilation during inhibition of SST-expressing spinal neuronal activity, thereby demonstrating that spinal SST neurons participate in the activation of respiratory circuits affected by CEES. This work establishes a mechanistic foundation to repurpose a clinically accessible neuromodulatory therapy to activate respiratory circuits and stimulate ventilation.

Circular RNA Expression and Interaction Patterns Are Perturbed in Amyotrophic Lateral Sclerosis

Circular RNAs (circRNAs) are a type of long noncoding RNA that are highly abundant and highly conserved throughout evolution and exhibit differential expression patterns in various tissue types in multiple diseases, including amyotrophic lateral sclerosis (ALS). The most well-known function of circRNAs is their ability to act as microRNA (miRNA) sponges. This entails circRNA binding to miRNA, which would otherwise target and degrade messenger RNA, thus affecting gene expression. This study analyzed ALS patient samples from three spinal cord regions to investigate circular transcriptome perturbation and circular RNA-microRNA-mRNA interactions. Using stringent statistical parameters, we identified 92 differentially expressed circRNAs across the spinal cord tissues with the aim of identifying specific circRNAs with biomarker potential. We also found evidence for differential expression of 37 linear RNAs possibly due to miRNA sequestration by circRNAs, thus revealing their potential as novel biomarkers and therapeutic candidates for ALS.

Recognition of necrotic regions in MRI images of chronic spinal cord injury based on superpixel

Background and objectiveThe cystic cavity and its surrounding dense glial scar formed in chronic spinal cord injury (SCI) hinder the regeneration of nerve axons. Accurate location of the necrotic regions formed by the scar and the cavity is conducive to eliminate the re-growth obstacles and promote SCI treatment. This work aims to realize the accurate and automatic location of necrotic regions in the chronic SCI magnetic resonance imaging (MRI). MethodsIn this study, a method based on superpixel is proposed to identify the necrotic regions of spinal cord in chronic SCI MRI. Superpixels were obtained by a simple linear iterative clustering algorithm, and feature sets were constructed from intensity statistical features, gray level co-occurrence matrix features, Gabor texture features, local binary pattern features and superpixel areas. Subsequently, the recognition effects of support vector machine (SVM) and random forest (RF) classification model on necrotic regions were compared from accuracy (ACC), positive predictive value (PPV), sensitivity (SE), specificity (SP), Dice coefficient and algorithm running time. ResultsThe method is evaluated on T1- and T2-weighted MRI spinal cord images of 24 adult female Wistar rats. And an automatic recognition method for spinal cord necrosis regions was established based on the SVM classification model finally. The recognition results were 1.00±0.00 (ACC), 0.89±0.09 (PPV), 0.88±0.12 (SE), 1.00±0.00 (SP) and 0.88±0.07 (Dice), respectively. ConclusionsThe proposed method can accurately and noninvasively identify the necrotic regions in MRI, which is helpful for the pre-intervention assessment and post-intervention evaluation of chronic SCI research and treatments, and promoting the clinical transformation of chronic SCI research.

Variations in the origin of the anterior spinal artery in a Colombian population sample.

Based on most neuroanatomical descriptions, the anterior spinal artery (ASA) originates from two small vessels of the vertebral arteries, which are anastomosed just before forming the basilar artery. This study aimed to determine and quantify the possible variants of the origin of the ASA and its trajectory in samples of human brain stems. Male brain stems with the superior portion of the spinal cord until myelomera C3 of 23 adult human, and no evident morphological alterations were selected. The brain stems were collected for three years and fixed in a 10% formalin solution at the Anatomy Laboratory of the Universidad de Caldas (Colombia). Five samples (21.7%) had variations in the origin and trajectory of the anterior spinal artery. The variations in the origin of the ASA could generate morphofunctional advantages instead of leading to complications. That is the case when there are two anterior spinal arteries since it would increase tissue perfusion, thus protecting part of the spinal cord from ischemic pathologies. It is essential to consider the variations that may exist in the supply of the anterior region of the spinal cord for clinical and surgical assessments due to variations in its supplied territory.

Optic Neuritis and Macular Edema in a Patient With NMOSD

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system caused by antibodies preferably to the optic nerve, spinal cord, and certain brain regions. Symptoms may occur at the same time or vary over a period of time. The best prognostic factor of conversion from optic neuritis to clinical definite NMO is the presence of a serum antibody to aquaporin-4 called NMO-IgG. Suspicion of NMO should be high in patients who present with simultaneous bilateral optic neuritis or recurrent attacks and in those with vision of light perception or worse or who are with acuity of 20/50 or worse after optic neuritis.

Positive Allosteric Modulators of Glycine Receptors and Their Potential Use in Pain Therapies.

Glycine receptors are ligand-gated ion channels that mediate synaptic inhibition throughout the mammalian spinal cord, brainstem, and higher brain regions. They have recently emerged as promising targets for novel pain therapies due to their ability to produce antinociception by inhibiting nociceptive signals within the dorsal horn of the spinal cord. This has greatly enhanced the interest in developing positive allosteric modulators of glycine receptors. Several pharmaceutical companies and research facilities have attempted to identify new therapeutic leads by conducting large-scale screens of compound libraries, screening new derivatives from natural sources, or synthesizing novel compounds that mimic endogenous compounds with antinociceptive activity. Advances in structural techniques have also led to the publication of multiple high-resolution structures of the receptor, highlighting novel allosteric binding sites and providing additional information for previously identified binding sites. This has greatly enhanced our understanding of the functional properties of glycine receptors and expanded the structure activity relationships of novel pharmacophores. Despite this, glycine receptors are yet to be used as drug targets due to the difficulties in obtaining potent, selective modulators with favorable pharmacokinetic profiles that are devoid of side effects. This review presents a summary of the structural basis for how current compounds cause positive allosteric modulation of glycine receptors and discusses their therapeutic potential as analgesics. SIGNIFICANCE STATEMENT: Chronic pain is a major cause of disability, and in Western societies, this will only increase as the population ages. Despite the high level of prevalence and enormous socioeconomic burden incurred, treatment of chronic pain remains limited as it is often refractory to current analgesics, such as opioids. The National Institute for Drug Abuse has set finding effective, safe, nonaddictive strategies to manage chronic pain as their top priority. Positive allosteric modulators of glycine receptors may provide a therapeutic option.

Fibrocartilaginous embolism: a rare cause leading to spinal cord infarction?

Fibrocartilaginous nucleus pulposus components herniation and embolism rarely causes acute ischaemic events involving the spinal cord. Few reports have suggested this as a mechanism leading to anterior spinal artery syndrome. The purpose of this study was to evaluate the topography and pattern of this rare myelopathy by MRI. A retrospective observational case series of patients, admitted to our Institute between 2008 and 2021, with a diagnosis of fibrocartilaginous embolism based on typical clinical and radiological features. Five patients were identified (2 men and 3 women; range 13-38years). No one had pre-existing vascular risk factors. All referred potential precipitating event in the 24h prior to symptom onset. MRI findings showed increased signal intensity of the spinal cord on T2-weighted images in all cases and degenerative disc changes opposite to it in four of them. The outcome was poor: three showed only partial sensitivity and motor improvement (mRs 4, 3, and 2, respectively); one completely recovered except for isolated hand paresis (mRs 1); and one remained severely neurologically affected (mRs 5). Fibrocartilaginous embolism must be a differential diagnosis in case of otherwise unexplained spinal cord infarction in adult and paediatric low risk population. Neuroradiological findings such as abnormal spinal cord signal intensity and degenerative disc changes can aid in early diagnosis of this rare myelopathy. The prevalent myelopathy location was thoracic. All signal alterations were detected in the anterior region of the spinal cord in the territories of the anterior spinal artery.

Silicone plastination of spinal cord of cat: as an alternative specimen for neuroanatomy education

Plastination is a technique that aims to preserve biological materials for education, training, and research. Plastinated models increase knowledge and skill, make students easily understand the complex anatomical parts of the central nervous system, meanwhile can reduce the use of animals in research and education. The study aimed to produce a silicone plastinated model of the spinal cord of a cat for practical teaching of neuroanatomy. The spinal cord of a stray cat that died of natural causes was plastinated using silicone plastination method. The cervical spinal nerves (1-8) and brachial plexus were demonstrated. The thoracic region of the spinal cord was also well preserved, but the demonstration of thoracic spinal nerves became very difficult because of too much thinness of the nerves. The lumbosacral plexus was preserved well. In this region cranial iliohypogastric nerve, caudal iliohypogastric nerve, ilioinguinal nerve, femoral nerve, gluteal nerve, ischiadic nerve, obturator nerve, pudendal nerve and cauda equina were visible. The spinal cord of cats prepared by silicone plastination methods can be used as an alternative sample to formalin preserved specimens.

Dbx1 controls the development of astrocytes of the intermediate spinal cord by modulating Notch signaling.

Significant progress has been made in elucidating the basic principles that govern neuronal specification in the developing central nervous system. In contrast, much less is known about the origin of astrocytic diversity. Here, we demonstrate that a restricted pool of progenitors in the mouse spinal cord, expressing the transcription factor Dbx1, produces a subset of astrocytes, in addition to interneurons. Ventral p0-derived astrocytes (vA0 cells) exclusively populate intermediate regions of spinal cord with extraordinary precision. The postnatal vA0 population comprises gray matter protoplasmic and white matter fibrous astrocytes and a group of cells with strict radial morphology contacting the pia. We identified that vA0 cells in the lateral funiculus are distinguished by the expression of reelin and Kcnmb4. We show that Dbx1 mutants have an increased number of vA0 cells at the expense of p0-derived interneurons. Manipulation of the Notch pathway, together with the alteration in their ligands seen in Dbx1 knockouts, suggest that Dbx1 controls neuron-glial balance by modulating Notch-dependent cell interactions. In summary, this study highlights that restricted progenitors in the dorsal-ventral neural tube produce region-specific astrocytic subgroups and that progenitor transcriptional programs highly influence glial fate and are instrumental in creating astrocyte diversity.

Divergent complement system activation in two clinically distinct murine models of multiple sclerosis.

Multiple sclerosis (MS) is a neurological disease featuring neuroinflammation and neurodegeneration in young adults. So far, most research has focused on the peripheral immune system, which appears to be the driver of acute relapses. Concurrently, the mechanisms underlying neurodegeneration in the progressive forms of the disease remain unclear. The complement system, a molecular component of the innate immunity, has been recently implicated in several neurological disorders, including MS. However, it is still unknown if the complement proteins detected in the central nervous system (CNS) are actively involved in perpetuating chronic inflammation and neurodegeneration. To address this knowledge gap, we compared two clinically distinct mouse models of MS: 1) proteolipid protein (PLP)-induced experimental autoimmune encephalomyelitis (rEAE) resembling a relapsing-remitting disease course, and 2) Theiler’s murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) resembling a progressive disease. Real-time PCR was performed in the spinal cord of rEAE mice, TMEV-IDD mice and age-matched sham controls to quantify gene expression for a broad range of complement components. In both experimental models, we found significantly increased expression of complement factors, such as C1q, C3, CfB, and C3aR. We showed that the complement system, specifically the classical complement pathway, was associated with TMEV-IDD pathogenesis, as the expression of C1q, C3 and C3aR1 were all significantly correlated to a worse disease outcome (all P≤0.0168). In line with this finding, C1q and C3 deposition was observed in the spinal cord of TMEV-IDD mice. Furthermore, C1q deposition was detected in spinal cord regions characterized by inflammation, demyelination, and axonal damage. Conversely, activation of the classical complement cascade seemed to result in protection from rEAE (C1q: P=0.0307). Interestingly, the alternative pathway related to a worse disease outcome in rEAE (CFb: P=0.0006). Overall, these results indicate potential divergent roles for the complement system in MS. The chronic-progressive disease form is more reliant on the activation of the classic complement pathway, while protecting from acute relapses. Conversely, relapsing MS appears more likely affected by the alternative pathway. Understanding the functions of the complement system in MS is critical and can lead to better, more targeted therapies in the future.

Effect of daily treadmill running exercise on masseter muscle nociception associated with social defeat stress in mice.

We investigated the effects of social defeat stress (SDS) and treadmill running on masseter muscle nociception, which was quantified by the orofacial formalin test and c-Fos and FosB immunoreactivities in the upper cervical spinal cord (C1/C2) region in male mice. After daily SDS or non-SDS conditioning for 10 days, SDS-conditioned mice were categorized into SDS-susceptible versus resilient mice. Several mice, including non-SDS-conditioned, SDS-susceptible, and resilient mice, were selected to assess masseter muscle nociception on Day11. SDS conditioning for 10 days increased masseter muscle-evoked nocifensive behaviors and c-Fos and FosB expression in SDS-susceptible compared to non-SDS and resilient mice. The remaining SDS-susceptible and non-SDS mice were subjected to an additional 10 days of SDS plus treadmill running or sedentary sessions before assessing masseter muscle nociception on Day21. Daily treadmill running sessions reduced enhanced masseter muscle nociception in SDS-susceptible mice but not in non-SDS mice. The preventive effects of daily treadmill running immediately after each SDS conditioning for 10 days on orofacial nocifensive behaviors were assessed on Day11. Treadmill running conducted immediately after daily SDS inhibited enhanced orofacial nocifensive behaviors. These findings indicate that repeated SDS increases masseter muscle nociception, which could be prevented by daily treadmill running exercise.

Incidental Dural Tears in Lumbar Decompressive Surgery: Incidence, Causes, Treatment, Results

Durotomy (Incidental dural tears or ID) is a very rarely occurring disorder when decompressive surgery (spinal surgery) of the patients takes place. This disorder has severe effects on patients. During different surgeries of the spinal cord, the chances of this durotomy vary greatly. Objective: The main objective of this research work is to evaluate the main reasons for the incidence of this durotomy disease. During different surgeries of the spinal cord surgeries (decompressive and compressive) within the different regions, many factors play their role in the initiation of this durotomy disease. It is the target of this work to find the initiation factors of the disease so that effective methods of treatment can also find out. Methods: It was a retrospective study with a statistical approach. This study was conducted in Neurosurgery unit, Mardan medical complex / Bacha khan medical college, Mardan for the Duration of one year August 2020 to July 2021. To proceed with this study, 30 patients were selected with posterolateral and posterior compressive and decompressive surgeries within the different regions of the spinal cord. The patients were randomly selected from December 2020 to December 2021. Results: The incidence of this durotomy disease was investigated within all groups and the probability of this disease was only 12.65%. The occurrence of this disease also depends upon the type of surgery. Patients suffering from spinal trauma, stenosis of the spinal, different tumors, and vertebral disc herniation had exaggerating role in the incidence of durotomy in patients having some spinal surgery. Conclusion: The durotomy disease should be considered a serious issue with a number of other complications. For the treatment of this disease, prevention is the best method and to know about the complications is important because all of the factors involved in the incidence of durotomy should be considered while performing any kind of surgery

Theoretical model of external spinal cord stimulation

In this paper, a simple theoretical model of the excitation of action potentials of multiple motor pools by stimulating current pulses over the lumbosacral regions of the spinal cord is presented. The present model is consistent with known experimental data.

Intubation biomechanics: Computational modeling to identify methods to minimize cervical spine motion and spinal cord strain during laryngoscopy and tracheal intubation in an intact cervical spine

Study objectiveTo minimize the risk of cervical spinal cord injury in patients who have cervical spine pathology, minimizing cervical spine motion during laryngoscopy and tracheal intubation is commonly recommended. However, clinicians may better aim to reduce cervical spinal cord strain during airway management of their patients. The aim of this study was to predict laryngoscope force characteristics (location, magnitude, and direction) that would minimize cervical spine motions and cord strains. DesignWe utilized a computational model of the adult human cervical spine and spinal cord to predict intervertebral motions (rotation [flexion/extension] and translation [subluxation]) and cord strains (stretch and compression) during laryngoscopy. InterventionsRoutine direct (Macintosh) laryngoscopy conditions were defined by a specific force application location (mid-C3 vertebral body), magnitude (48.8 N), and direction (70 degrees). Sixty laryngoscope force conditions were simulated using 4 force locations (cephalad and caudad of routine), 5 magnitudes (25–200% of routine), and 3 directions (50, 70, 90 degrees). Main resultsUnder all conditions, extension at Oc-C1 and C1-C2 were greater than in all other cervical segments. Decreasing force magnitude to values reported for indirect laryngoscopes (8–17 N) decreased cervical extension to ~50% of routine values. The cervical cord was most likely to experience potentially injurious compressive strain at C3, but force magnitudes ≤50% of routine (≤24.4 N) decreased strain in C3 and all other cord regions to non-injurious values. Changing laryngoscope force locations and directions had minor effects on motion and strain. ConclusionsThe model predicts clinicians can most effectively minimize cervical spine motion and cord strain during laryngoscopy by decreasing laryngoscope force magnitude. Very low force magnitudes (<5 N, ~10% of routine) are necessary to decrease overall cervical extension to <50% of routine values. Force magnitudes ≤24.4 N (≤50% of routine) are predicted to help prevent potentially injurious compressive cord strain.

Diffuse noxious inhibitory controls and conditioned pain modulation: a shared neurobiology within the descending pain inhibitory system?

Diffuse noxious inhibitory controls and conditioned pain modulation: a shared neurobiology within the descending pain inhibitory system?

Identification of injury type using somatosensory and motor evoked potentials in a rat spinal cord injury model.

The spinal cord is at risk of injury during spinal surgery. If intraoperative spinal cord injury is identified early, irreversible impairment or loss of neurological function can be prevented. Different types of spinal cord injury result in damage to different spinal cord regions, which may cause different somatosensory and motor evoked potential signal responses. In this study, we examined electrophysiological and histopathological changes between contusion, distraction, and dislocation spinal cord injuries in a rat model. We found that contusion led to the most severe dorsal white matter injury and caused considerable attenuation of both somatosensory and motor evoked potentials. Dislocation resulted in loss of myelinated axons in the lateral region of the injured spinal cord along the rostrocaudal axis. The amplitude of attenuation in motor evoked potential responses caused by dislocation was greater than that caused by contusion. After distraction injury, extracellular spaces were slightly but not significantly enlarged; somatosensory evoked potential responses slightly decreased and motor evoked potential responses were lost. Correlation analysis showed that histological and electrophysiological findings were significantly correlated and related to injury type. Intraoperative monitoring of both somatosensory and motor evoked potentials has the potential to identify iatrogenic spinal cord injury type during surgery.

066 Clinical and imaging findings in MOG antibody positive patients presenting to Kings College Hospital

We identified all patients testing positive for MOG antibodies at KCH and reviewed their clinical phenotype and imaging findings. 22 patients tested positive for MOG antibodies between Jan 2015 and Aug 2019 (11 female, mean age 39 (SD 18)). The majority of patients 15/22 presented with optic neuritis, 3 patients bilateral, 2 bilateral sequential. Other presentations included LETM (2), ADEM(2), brain stem syndrome (1), lower cord/conus syndrome (1) seizures (1). Mean logMar visual acuity at nadir in patients present- ing with an optic neuritis was 0.69 (SD 0.58). Mean logMar visual acuity at recovery was logMAR 0.1 (SD 0.54), 12/15 eyes had documented optic disc swelling. MRI brain was performed in 20 patients and was normal in 10, 6 had non-specific white matter changes the remainder had inflammatory brainstem and ADEM –like changes. MRI orbits was performed in 13 patients, 4 had bilateral optic nerve involvement and 5 had longitudinally extensive optic nerve lesions. Spinal cord imaging was performed in 9 patients, 2 had a LETM, 1 multifocal signal change and the remainder normal imaging. The cervical cord was the most frequently involved region of the spinal cord. 5 patients developed relapses (all optic neuritis), 3 relapses occurred off treatment.r.raftopoulos@ucl.ac.uk

Neuromyelitis Optica and Differential Diagnosis (mimics)

Neuromyelitis Optica is an inflammatory neurodegenerative demyelinating autoimmune channelopathy affecting brain and spinal cord, for which Aquaporin-4(AQP4) water channels are the main target. Discovery of the AQP4 immunoglobulin (IGG) antibody in 2004 was a major step for understanding the disease which helped to distinguish from multiple sclerosis and other demyelinating diseases. Aquaporin -4 (AQP4) is a water channel protein expressed in two major isoforms which includes a short isoform M1 and a isoform M23 , AQP4 is expressed heavily on astrocyte endfeet end process at blood brain barrier, nodes of Ranvier and neuronal synapses processes in spinal cord, optic nerves , brain stem, thalamus ,hypothalamus, dorsal medulla at area postrema, diencephalon, subcortical white matter, gray and white matter in spinal cord, periaqueductal and periventricular region.