Homeostasis of the central nervous system (CNS) microenvironment is essential for its normal function and is maintained by the blood-brain barrier (BBB). The BBB proper is made up of endothelial cells (ECs) interconnected by tight junctions (TJs) that reveal a unique morphology and biochemical composition of the bodys vasculature. In this article, we focus on developmental aspects of the BBB and describe morphological as well as molecular special features of the neuro-vascular unit (NVU) involved in barrier induction. Recently, we and others identified the Wnt/b-catenin pathway as crucial for brain angiogenesis, TJ and BBB formation. Based on these findings we discuss other pathways and molecular interactions for BBB establishment and maintenance. At the morphological level, our concept favors a major role for polarized astrocytes (ACs) therein. Orthogonal arrays of particles (OAPs) that are the morphological correlate of the water channel protein aquaporin-4 (AQP4) are specifically formed in the
Anti-Aquaporin 2 (254-271) Rabbit pAb Anti-Aquaporin 2 (254-271), rabbit polyclonal, recognizes the ~40 and ~29 kDa forms of aquaporin-2 in rat kidney membrane. Supplied with a control peptide. It is validated for WB, IHC, and IP. - Find MSDS or SDS, a COA, data sheets and more information.
Recovery from neuronal activation requires rapid clearance of potassium ions (K+) and restoration of osmotic equilibrium. The predominant water channel protein in brain, aquaporin-4 (AQP4), is concentrated in the astrocyte end-feet membranes adjacent to blood vessels in neocortex and cerebellum by association with alpha-syntrophin protein. Although AQP4 has been implicated in the pathogenesis of brain edema, its functions in normal brain physiology are uncertain. In this study, we used immunogold electron microscopy to compare hippocampus of WT and alpha-syntrophin-null mice (alpha-Syn-/-). We found that ,10% of AQP4 immunogold labeling is retained in the perivascular astrocyte end-feet membranes of the alpha-Syn-/- mice, whereas labeling of the inwardly rectifying K+ channel, Kir4.1, is largely unchanged. Activity-dependent changes in K+ clearance were studied in hippocampal slices to test whether AQP4 and K+ channels work in concert to achieve isosmotic clearance of K+ after neuronal ...
Aquaporin-4 (AQP4) is the major water channel in the central nervous system and plays an important role in the brains water balance, including edema formation and clearance. There are 6 splice variants; the shorter ones assemble into functional, tetrameric square arrays; the longer is palmitoylated on N-terminal cysteyl residues) (Suzuki et al., 2008). The longest, Aqp4e, has a novel N-terminal domain and forms a water channel in the plasma membrane although various shorter variants dont (Moe et al., 2008). AQP4, like AQP0 (1.A.8.8.2), forms water channels but also forms adhesive junctions (Engel et al., 2008) (causes cytotoxic brain swelling in mice (Yang et al., 2008)) Mice lacking Aqp4 have impaired olfactions (Lu et al., 2008). Aqp4 is down regulated in skeletal muscle in muscular dystrophy (Au et al. 2008). The crystal structure is known to 2.8 Å resolution (Tani et al., 2009). The structure reveals 8 water molecules in each of the four channels, supporting a hydrogen-bond isolation ...
Aquaporin 10 antibody, C-term (aquaporin 10) for WB. Anti-Aquaporin 10 pAb (GTX45889) is tested in Human samples. 100% Ab-Assurance.
Anti-Aquaporin 3 Antibody (#AQP-003) from Alomone Labs is a highly specific rabbit polyclonal Ab directed against an epitope of rat AQP3. Applications: IFC, IHC, IP, WB. Free samples available. Control antigen included. Lyophilized. Global shipping at room temperature. Your top supplier for aquaporin research!
Order monoclonal and polyclonal Aquaporin 5 antibodies for many applications. Selected quality suppliers for anti-Aquaporin 5 antibodies.
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Polyclonal antibody for AQUAPORIN 3/AQP3 detection. Host: Rabbit.Size: 100μg/vial. Tested applications: IHC-P. Reactive species: Human. AQUAPORIN 3/AQP3 information: Molecular Weight: 31544 MW; Subcellular Localization: Basolateral cell membrane; Multi-pa
Rabbit polyclonal Aquaporin 3 antibody. Validated in WB, ELISA, IHC and tested in Rat. Cited in 1 publication(s). Independently reviewed in 2 review(s). Immunogen corresponding to synthetic peptide.
Rabbit polyclonal Aquaporin 0 antibody validated for WB and tested in Human, Mouse and Rat. Immunogen corresponding to synthetic peptide
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Polyclonal antibody for AQP5 detection. Host: Rabbit.Size: 100μg/vial. Tested applications: WB. Reactive species: Human. AQP5 information: Molecular Weight: 28292 MW; Subcellular Localization: Membrane; Multi-pass membrane protein.
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Neuromyelitis optica spectrum disorder is uncommon in children, and often seronegative for aquaporin-4 immunoglobulin G (AQP4-IgG). We conducted a retrospective study of 67 children presenting to a single Australian center with acquired demyelinating syndromes over a 7-year period. All patients were tested for AQP4-IgG. Five children (7.5%) had neuromyelitis optica spectrum disorder. One child was seropositive for AQP4-IgG (1.5%) and had a relapsing disease course with mild residual deficits. She also had a concomitant motor axonal neuropathy that improved with immunosuppressive therapy. Of the remaining 4 children, 3 had a monophasic course and 1 a relapsing course. Two were tested for anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibody and both were seropositive. This study confirms that neuromyelitis optica spectrum disorder is uncommon in children, and that AQP4-IgG seropositivity is rare. Anti-MOG antibodies should be tested in children with neuromyelitis optica spectrum disorder ...
TY - JOUR. T1 - Neuromyelitis Optica Spectrum Disorder Coinciding with Spinocerebellar Ataxia Type 31. AU - Takahashi, Yoshiaki. AU - Manabe, Yasuhiro. AU - Morihara, Ryuta. AU - Narai, Hisashi. AU - Yamashita, Toru. AU - Abe, Koji. N1 - Publisher Copyright: © 2017 The Author(s). Published by S. Karger AG, Basel. PY - 2017/5/17. Y1 - 2017/5/17. N2 - We report the unusual case of a 63-year-old man with spinocerebellar ataxia (SCA) type 31 who developed neuromyelitis optica spectrum disorder (NMOSD) 14 years after the onset of cerebellar symptoms. In addition to cerebellar atrophy, magnetic resonance imaging showed multiple high-intensity areas in the brain and a long thoracic cord lesion from Th1/2 to Th11. The combination of NMOSD and SCA31 is accidental. However, our case suggests that inflammatory processes could be involved in the pathogenesis of NMOSD and SCA31.. AB - We report the unusual case of a 63-year-old man with spinocerebellar ataxia (SCA) type 31 who developed neuromyelitis optica ...
Neuromyelitis optica (NMO) is an autoimmune inflammatory condition of the central nervous system that is characterized by circulating anti-aquaporin-4 antibodies, transverse myelitis and optic neuritis. NMO spectrum disorders are rarely reported in patients with active pulmonary tuberculosis (TB). We report a fatal case of anti-aquaporin-4 antibody positive NMO spectrum disorder in a patient who was receiving treatment for pulmonary tuberculosis. A previously healthy 42-year-old Chinese man was diagnosed with smear positive pulmonary tuberculosis. After one month of anti-tuberculosis treatment, he presented with acute generalized weakness and rapid neurological deterioration. Spinal imaging and anti-aquaporin-4 antibody positivity established a diagnosis of neuromyelitis optica spectrum disorder. This is the first reported case of anti-aquaporin-4 antibody-positive NMO spectrum disorder in a patient with active tuberculosis. It shows the usefulness of testing for anti-aquaporin-4 antibodies while
In NMOSD, the likelihood of recurrence of disease activity is greater than 90%. Attacks in NMOSD can be devastating. Prior to the expansion of diagnoses about 50% of those diagnosed with NMOSD and untreated were dependent on a wheelchair and/or functionally blind by 5 years. With the advent of the antibody test we have recognized a wide variety of outcomes, but the condition is still considered potentially devastating. Therefore, it is generally thought that ongoing treatment with medications that suppress the immune system is necessary. There are two FDA-approved medications for maintenance in NMOSD, but anything else that is prescribed is done off-label. Soliris®️ (eculizumab) was the first FDA-approved complement inhibitor indicated for the treatment of adults with anti-aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD). Uplizna™ (inebilizumab-cdon) has also been granted approval from the U.S. Food and Drug Administration (FDA) for the treatment of ...
AstraZeneca and its global biologics research and development arm, MedImmune, today announced that the European Medicines Agency (EMA) has granted orphan designation to inebilizumab (formerly MEDI-551) for the treatment of neuromyelitis optica spectrum disorder (NMOSD). Developed by MedImmune, inebilizumab is currently in Phase IIb clinical development for NMOSD.. NMOSD is a rare, life-threatening autoimmune disease of the central nervous system in which the bodys immune system attacks healthy cells, most commonly in the optic nerves and spinal cord, resulting in severe damage. NMOSD may cause severe muscle weakness and paralysis, loss of vision, respiratory failure, problems with bowel and bladder function and neuropathic pain.1 There is currently no cure or approved medicine for NMOSD, which affects about five in 100,000 people.. Bing Yao, Senior Vice President, R&D and Head of the Respiratory, Inflammation and Autoimmunity Innovative Medicines unit, MedImmune, said: The EMAs orphan ...
Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that data from SAkuraSky, a pivotal phase III study of the investigational medicine satralizumab for the treatment of neuromyelitis optica spectrum disorder (NMOSD), were published in the 27 November 2019 online issue of the New England Journal of Medicine (NEJM).. The positive results from the pivotal SAkuraSky study of satralizumab support the hypothesis that IL-6 plays a key role in NMOSD, which is a debilitating and potentially fatal condition, said Levi Garraway, M.D., Ph.D., Roches Chief Medical Officer and Head of Global Product Development. Satralizumab has shown robust efficacy sustained for 144 weeks across a broad patient population in two phase III studies, whether given as a monotherapy or in combination with baseline therapy. Were encouraged that satralizumab may soon provide a new treatment option for people living with NMOSD.. People with NMOSD experience unpredictable, severe relapses that directly cause cumulative, ...
Irreversible disability in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) is largely attributed to neuronal and axonal degeneration, which, along with inflammation, is one of the major pathological hallmarks of these diseases. Optical coherence tomography (OCT) is a non-invasive imaging tool that has been used in MS, NMOSD, and other diseases to quantify damage to the retina, including the ganglion cells and their axons. The fact that these are the only unmyelinated axons within the central nervous system (CNS) renders the afferent visual pathway an ideal model for studying axonal and neuronal degeneration in neurodegenerative diseases. Structural magnetic resonance imaging (MRI) can be used to obtain anatomical information about the CNS and to quantify evolving pathology in MS and NMOSD, both globally and in specific regions of the visual pathway including the optic nerve, optic radiations and visual cortex. Therefore, correlations between brain or optic nerve ...
Neuromyelitis optica spectrum disorders (NMOSD) comprises a group of central nervous system disorders of inflammatory autoimmune origin that mainly affect the optic nerves and the spinal cord and can cause severe visual and general disability. The clinical signs are similar to those of multiple sclerosis (MS), with the result that it is often difficult to differentiate between the two, thus leading to misdiagnosis. As the treatment and prognosis of NMOSD and MS are different, it is important to make an accurate and early diagnosis of NMOSD. Optical coherence tomography (OCT) is a non-invasive technique that enables a quantitative study of the changes that the optic nerve and the macula undergo in several neurodegenerative diseases. Many studies have shown that some of these changes, such as retinal nerve fiber layer thinning or microcystic macular edema, can be related to alterations in the brain due to neurodegenerative disorders. The purpose of this mini-review is to show how OCT can be useful for the
The redefining of neuromyelitis optica spectrum disorder (NMOSD) in 2006 has revealed cases with unique and previously unrecognised presentations. We describe a case of an NMOSD relapse in which seizures were the main clinical feature.. A twenty three year old female first presented in 2006, then thirteen with hyponatraemia and bilateral, severe optic neuritis, in the context of hypothalamic and optic chiasm lesions on MRI brain. Central pontine myelinosis was initially diagnosed but this was revised to an acute disseminated encephalomyelitis (ADEM) in 2013. She remained well for nine years albeit with residual neurological disabilities, including mild spastic paraparesis, global hyperreflexia and bilateral extensor plantar responses. She had almost complete loss of vision in both eyes with peripheral sparing evidenced by bilateral optic atrophy. In September 2015 she presented with generalised seizures. MRI brain showed contrast enhancement in the right cingulate gyrus (DWI negative). ...
Neuromyelitis optica spectrum disorder is an autoimmune disease. Learn about the hereditary and environmental factors, and lifestyle causes and risks.
Conditions: Multiple Sclerosis; Neuromyelitis Optica Spectrum Disorder Attack; Neuromyelitis Optica Spectrum Disorder Relapse; Neuromyelitis Optica Spectrum Disorder Progression; Optic Neuritis Intervention: Diagnostic Test: Reflex (Brightlamp Inc., Purdue University) Sponsor: University of ...
Background: Neuromyelitis optica (NMO) is a severe autoimmune inflammatory disorder associated with considerable relapse-related disability. Immunosuppression is the mainstay of treatment but many patients do not tolerate first-line immunosuppressive agents, or experience ongoing relapses. Objective: To evaluate the effectiveness and tolerability of methotrexate in aquaporin-4 antibody seropositive NMO spectrum disorders. Methods: Retrospective observational case series of 14 aquaporin-4 antibody positive NMO and NMO spectrum disorder patients treated with methotrexate at two specialist centres within the UK. Annualised relapse rates, Expanded Disability Status Scale scores and tolerability were evaluated. Results: Median duration of treatment with methotrexate was 21.5 months (range 6-28 months) and only three patients were prescribed it first line. Median annualised relapse rate signi ficantly decreased following treatment (0.18 during methotrexate therapy vs 1.39 premethotrexate; p | 0.005). On
Neuromyelitis optica spectrum disorders (NMOSD) are demyelinating autoimmune diseases in the central nervous system (CNS) that are characterized by a high relapse rate and the presence of anti-aquaporin 4 antibodies (AQP4-IgG) in the serum. Azathioprine (AZA) is a first-line immunomodulatory drug that is widely used for the treatment of patients with NMOSD. However, the efficacy and safety of AZA vary in different individuals. Thirty-two patients with NMOSD who regularly took AZA were enrolled in the study at Beijing Tiantan Hospital, Capital Medical University. The efficacy of AZA was evaluated using the expanded disability status scale (EDSS) and the annual relapse rate (ARR). The erythrocyte concentrations of AZA metabolites were detected using an LC-MS/MS method. The erythrocyte concentrations of 6-thioguanine nucleotides (6-TGNs) and 6-methylmercaptopurine nucleotides (6-MMPNs) were 202.03 ± 63.35 pmol/8*108 RBC and 1618.90 ± 1607.06 pmol/8*108 RBC, respectively. After the patients had received
An increasing interest in the role of monocytes in the immune response has yielded findings that monocyte dysregulation is deeply involved in autoimmune diseases such as MS, SLE, and RA. For example, MS monocytes have been reported to be easily activated [30] and to have increased levels of inflammatory cytokine transcription and translation [31] and cell-surface molecule expression [32]. In this study, we hypothesized that NMOSD monocytes are dysregulated in much the same way that MS monocytes are. The data presented here demonstrate that NMOSD monocytes are readily activated and show increased production of inflammatory cytokines, decreased production of IL-10, increased expression of inflammatory surface molecules, and increased frequencies of a non-classical monocyte subset compared to HC monocytes. Interestingly, NMOSD monocytes have an even more inflammatory characteristic in some measures than MS monocytes, which are well-known to be highly inflammatory.. To examine monocyte cytokine ...
Natalizumab, rituximab, and fingolimod usage is associated with reactivation of John Cunningham virus and progressive multifocal leukoencephalopathy in patients with MS.5 Side effects for newer therapies such as eculizumab, inebilizumab, satralizumab, and tocilizumab in NMOSD are unclear, partly because of the relatively short duration and small numbers of patients exposure to these medications. Because these DMDs interfere with multiple arms of the immune system, altered immune functions in these patients are expected. Despite this anticipated risk, we did not observe an escalated rate of COVID-19 infection, even at the epicenter of the outbreak in Wuhan. SARS-CoV-2 has spread to all the provinces of China from the Wuhan epicenter since January 2020. The overall incidence of COVID-19 infection in China is estimated at 6/105 subjects comparable with the estimated incidence of NMOSD in China. These results from China are consistent with observations in some MS centers from Korea, Japan, and ...
Conclusions: Effectiveness of subcutaneous TCZ in NMOSD appears to be similar to that reported for the IV formulation and has an advantage of at-home administration. Prospective, comparative studies of subcutaneous TCZ for NMOSD are warranted....
Jueves 26 Julio. 08:00 - 08:30 Differential diagnosis and evaluation in pediatric inflammatory demyelinating disorders. Prof. Brenda Banwell. 08:30 - 09:00 Neuromyelitis optica spectrum disorders in children and adolescents. Prof. Silvia Tenembaum. 09:00 - 09:10 Q & A. 09:10 - 09:40 Consensus definitions for pediatric MS and other demyelielinating disorders in childhood. Prof. Silvia Tenembaum. 09:40 - 10:10 Update in MS therapy in children and adolescents. Prof. Brenda Banwell. 10:10 - 10:15 Q & A. 10:15 - 10:40 Coffee. 10:40 - 11:40 Simposio Satélite Biogen Spinal Muscular Atrophy treatment prospects, real-life data with antisense oligonucleotide technology. Prof. Samuel Ignacio Pascual-Pascual. 11:40 - 12:10 Diagnostic approach to Multiple Sclerosis. Prof. Friedemann. 12:10 - 13:10 Simposio Merck Effect of SIRT therapy on cerebral atrophy. Prof. Nicola De Stefano. 13:10 - 13:35 Lunch. 13:35 - 14:20 Neuromyelitis optica spectrum disorder (NMOSD) & MOG antibody-associated inflammatory ...
Dean M. Wingerchuk, Brenda Banwell, Jeffrey L. Bennett, Philippe Cabre, William Carroll, Tanuja Chitnis, Jérôme De Seze, Kazuo Fujihara, Benjamin Greenberg, Anu Jacob, Sven Jarius, Marco Lana-Peixoto, Michael Levy, Jack H. Simon, Silvia Tenembaum, Anthony L. Traboulsee, Patrick Waters, Kay E. Wellik, Brian G. Weinshenker ...
ABSTRACTCentral nervous system is the most complex and largest part of the nervous system. It plays a crucial role in aligning the activities of all body parts and ...
A 4-year-old boy presented with a 3-week history of rapidly progressive weakness involving the lower limbs followed by upper limbs and bilateral painless visual loss, preceded by a self-limiting febrile illness. Annals of Indian Academy of Neurology ¦ Volume 22 ¦ Issue 4 ¦ October-December 2019 541 Sir, A 4-year-old boy presented with a 3-week history of rapidly progressive weakness involving the lower limbs followed by upper limbs and bilateral painless visual loss. His symptoms had begun 8 months ago when he had fever followed by acute-onset hearing loss. He was treated with high-dose steroids, resulting in partial recovery. Five months later, he had fever followed by acute ataxia. He was again treated with intravenous steroids, resulting in complete recovery. His current hospitalization was for increasing unsteadiness, clumsiness while walking, slurring of speech, and irritability. He had become bed-bound. The current episode was preceded by a self-limiting febrile illness.
Results Median annualized relapse rate (ARR) was not significantly different between these groups. Pooled analysis of all fixed dosing (n=31, median duration 25 months) versus all variable dosing (n=36, median duration 38 months) showed median and mean ARRs of 0.00 and 0.10 in both groups. Patients on fixed dosing received a median 3.9 infusions/year; those on variable doing received only 1.5 infusions/year. ...
BACKGROUND AND OBJECTIVES: Optic neuritis or longitudinally extensive myelitis in Sjogren syndrome (SS) suggests a neuromyelitis optica spectrum disorder (NMOSD). However, brain abnormalities of SS remain to be elucidated for the association with neuromyelitis optica (NMO). METHODS: Twelve primary SS patients (all women, 42 +/- 13.2 years) who had recurrent central nervous system (CNS) manifestations with brain involvement were retrospectively identified. Brain MRI, and neurologic and serologic findings were analyzed with the measurement of anti-aquaporin-4 antibody (AQP4-Ab). RESULTS: All patients showed brain lesions characteristic of NMO as follows: 1) the involved sites adjacent to the third and fourth ventricles and in the posterior limb of the internal capsule, 2) unique configurations, such as the longitudinal course from the internal capsule to the midbrain, large cerebral or cerebellar lesions over 3 cm, and cavity-like formations. AQP4-Ab was positive in six of eight patients tested, and all
Background: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. Objective: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients AQP4-Ab serostatus. Methods: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%). Results: Seropositive patients were found to be predominantly female (p | 0.0003), to more often have signs of co-existing autoimmunity (p | 0.00001), and to experience more severe clinical attacks. A visual acuity of |= 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p | 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse,
Background: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. Objective: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients AQP4-Ab serostatus. Methods: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%). Results: Seropositive patients were found to be predominantly female (p , 0.0003), to more often have signs of co-existing autoimmunity (p , 0.00001), and to experience more severe clinical attacks. A visual acuity of ≤ 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p , 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse, ...
Background: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. Objective: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients AQP4-Ab serostatus. Methods: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%). Results: Seropositive patients were found to be predominantly female (p , 0.0003), to more often have signs of co-existing autoimmunity (p , 0.00001), and to experience more severe clinical attacks. A visual acuity of ≤ 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p , 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse, ...
RATIONALE: The conception that multiple sclerosis may be challenging to distinguish from demyelinating manifestations of Sj grens syndrome (SS) was introduced more than 30 years ago. However, it is now recognized that the neuromyelitis optica spectrum disorder (NMOSD) may occur more frequently in SS as opposed to multiple sclerosis. Characteristic NMOSD features can include severe attacks of optic neuritis, myelitis which is frequently longitudinally-extensive (spanning at least three vertebral segments on magnetic resonance imaging [MRI]), and an association with anti-aquaporin-4 antibodies. In addition, whereas NMOSD was initially thought to spare the brain, it is now recognized that brain lesions occur in a majority of NMOSD patients. Therefore, it is important for the multi-disciplinary team of physicians who care for SS patients to understand this widening spectrum of NMOSD as encompassing brain lesions. In this case-report we describe clinical features, radiographic findings, and ...
Brain. 2019 Jun 1;142(6):1598-1615. doi: 10.1093/brain/awz106.. Cotzomi E1,2, Stathopoulos P1,2, Lee CS1,2, Ritchie AM3, Soltys JN3, Delmotte FR2, Oe T2, Sng J2, Jiang R2, Ma AK4, Vander Heiden JA1, Kleinstein SH2,4,5, Levy M6, Bennett JL3, Meffre E2, OConnor KC1,2.. Neuromyelitis optica spectrum disorders (NMOSD) constitute rare autoimmune disorders of the CNS that are primarily characterized by severe inflammation of the spinal cord and optic nerve. Approximately 75% of NMOSD patients harbour circulating pathogenic autoantibodies targeting the aquaporin-4 water channel (AQP4). The source of these autoantibodies remains unclear, but parallels between NMOSD and other autoantibody-mediated diseases posit compromised B cell tolerance checkpoints as common underlying and contributing factors. Using a well established assay, we assessed tolerance fidelity by creating recombinant antibodies from B cell populations directly downstream of each checkpoint and testing them for polyreactivity and ...
Understanding neuromyelitis optica spectrum disorder (NMOSD) and the role of interleukin-6 in the inflammation that occurs in people with NMOSD.
We present recent clinical and diagnostic advances in spinal cord imaging. Because of the overlap of different pathologic entities, good knowledge of clinical information is necessary. Degenerative diseases of the spine can sometimes be misleading when the question of a possible tumor rises. The essentials of spinal cord tumors are discussed.. In patients with suspicion of demyelinating disease, the following considerations are of importance: multiple sclerosis (MS) should be differentiated from neuromyelitis optica spectrum disorder (NMOSD), and AQP4 and MOG-antibodies should be searched for. There is a growing body of evidence that there is an overlap between NMOSD and acute demyelinating encephalomyelitis (ADEM).. Acute transverse myelitis is often a diagnosis of exclusion after viral myelitis or autoimmune causes have been excluded. The involvement of specific areas can give an indication for the diagnosis, e.g., area postrema or conus medullaris. New MRI equipment enables more robust ...
Antibody-associated central nervous system (CNS) autoimmune diseases account for an important part in neuroimmunology. Early studies mainly focused on paraneoplastic onconeural antibodies with a target on intracellular antigens (such as Hu, Yo, Ri, etc.). The past decade has witnessed a surge of discovery of novel neural antibodies, along with a series of new CNS disorders mediated by those antibodies, such as autoimmune encephalitis represented by anti-N-methyl-D-aspartate receptor encephalitis, aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated disease, and autoimmune glial fibillary acidic protein astrocytopathy.With a surge of antibody-associated CNS disorders, clinicians are faced with emerging challenges, including (1) the clinical significance and diagnostic value of antibodies; (2) the diagnostic dilemma in circumstances of
Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system that is associated with autoantibodies to aquaporin-4. Treatment options for prevention of clinical relapses of NMO include immunosuppressive medications. Plasma exchange (PLEX) is commonly used as a rescue therapy for NMO relapses but ongoing, regular PLEX procedures (maintenance PLEX) is sometimes used to prevent relapses. This observational registry will record feasibility, tolerability, safety, and preliminary efficacy data regarding maintenance PLEX for participants with NMO, NMO spectrum disorders, and recurrent idiopathic longitudinally extensive transverse myelitis ...
BACKGROUND: Neuromyelitis optica (NMO) is an idiopathic, severe, inflammatory demyelinating disease of the central nervous system, that causes severe optic neuritis and myelitis attacks. Early discrimination between multiple sclerosis (MS) and NMO is important, as optimum treatment for both diseases may differ considerably. ----- CASE PRESENTATION: We report a case of a patient who initially presented as longitudinally extensive transverse myelitis (LETM), having spastic upper extremities diparesis and spastic paraplegia, C2/C3 sensory level and urinary incontinence, as well as extensive inflammatory spinal cord lesions from C2 level to conus. After 5 months the patient had another attack of transverse myelitis, had electrophysiological findings consistent with optic neuritis, was seropositive for NMO-IgG (aquaporin-4 IgG) and thus fulfilled NMO diagnostic criteria. Following treatment of disease attacks with pulse corticosteroid therapy and intravenous immunoglobulins, we included oral ...
The characteristic symptoms of neuromyelitis optica are either optic neuritis or myelitis; either may occur as the first symptom. Optic neuritis is inflammation, of the optic nerve (optic neuritis) leading to pain inside the eye which rapidly is followed by loss of clear vision (acuity). Usually, only one eye is affected (unilateral) although both eyes may be involved simultaneously (bilateral). Neuromyelitis optica may or may not be preceded by a prodromal upper respiratory infection.. The other cardinal syndrome is inflammation of the spinal cord, a condition known as transverse myelitis because the symptoms tend to affect all motor, sensory and autonomic functions (bladder and bowel) below a certain level on the body. Affected individuals may experience pain in the spine or limbs, and mild to severe paralysis (paraparesis to paraplegia) of the lower limbs, and loss of bowel and bladder control. Deep tendon reflexes may be diminished or absent initially and later become exaggerated. A variable ...
Recent neuroimaging studies show that brain abnormalities in neuromyelitis optica (NMO) are more frequent than earlier described. Yet, more research considering multiple aspects of NMO is necessary to better understand these abnormalities. A clinical feature of relapsing NMO (RNMO) is that the incremental disability is attack-related. Therefore, association between the attack-related process and neuroimaging might be expected. On the other hand, the immunopathological analysis of NMO lesions has suggested that CNS microvasculature could be an early disease target, which could alter brain perfusion. Brain tissue volume changes accompanying perfusion alteration could also be expected throughout the attack-related process. The aim of this study was to investigate in RNMO patients, by voxel-based correlation analysis, the assumed associations between regional brain white (WMV) and grey matter volumes (GMV) and/or perfusion on one side, and the number of optic neuritis (ON) attacks, myelitis attacks and/or
It has been shown in some scientific studies that the the antibody marker specific for neuromyelitis optica (NMO), known as NMO-Immunoglobulin G (IgG), causes inflammation in brain tissues by activating a substance called complement. Complement can greatly increase the immune attack in the optic nerves (causing optic neuritis (ON)), spinal cords (causing transverse myelitis (TM)) and brains of patients with NMO. Eculizumab has already been shown to be effective in a rare blood disorder known as paroxysmal nocturnal hemoglobinuria (PNH). Attacks of PNH are also mediated through complement. Therefore, the investigators of this study are investigating whether by turning off complement in NMO, further attacks of NMO can be prevented.. The primary (most important) objectives of this study are to determine:. Whether Eculizumab reduces relapse frequency in patients with relapsing NMO. The number of attacks during the one year treatment period will be compared to the number of attacks that occurred ...
Neuromyelitis optica is an autoimmune disorder that affects the nerves of the eyes and the central nervous system, which includes the brain and spinal cord. Autoimmune disorders occur when the immune system malfunctions and attacks the bodys own tissues and organs. In neuromyelitis optica, the autoimmune attack causes inflammation of the nerves, and the resulting damage leads to the signs and symptoms of the condition.Neuromyelitis optica is characterized by optic neuritis, which is inflammation of the nerve that carries information from the eye to the brain (optic nerve). Optic neuritis causes eye pain and vision loss, which can occur in one or both eyes.Neuromyelitis optica is also characterized by transverse myelitis, which is inflammation of the spinal cord. The inflammation associated with transverse myelitis damages the spinal cord, causing a lesion that often extends the length of three or more bones of the spine (vertebrae). In addition, myelin, which is the covering that protects ...
Neuromyelitis optica (NMO) may be a unique central nervous system demyelinating disease with distinct clinical and MRI manifestations, as well as different immune and pathological characteristics as compared to multiple sclerosis (MS).
Neuromyelitis optica (NMO) is an autoimmune CNS disorder mediated by pathogenic aquaporin-4 (AQP4) water channel autoantibodies (AQP4-IgG). Although AQP4-IgG-driven complement-dependent cytotoxicity (CDC) is critical for the formation of NMO lesions, the molecular mechanisms governing optimal classical pathway activation are unknown. We investigated the molecular determinants driving CDC in NMO using recombinant AQP4-specific autoantibodies (AQP4 rAbs) derived from affected patients. We identified a group of AQP4 rAbs targeting a distinct extracellular loop C epitope that demonstrated enhanced CDC on target cells. Targeted mutations of AQP4 rAb Fc domains that enhance or diminish C1q binding or antibody Fc-Fc interactions showed that optimal CDC was driven by the assembly of multimeric rAb platforms that increase multivalent C1q binding and facilitate C1q activation. A peptide that blocks antibody Fc-Fc interaction inhibited CDC induced by AQP4 rAbs and polyclonal NMO patient sera. ...
Neuromyelitis optica (NMO) is an autoimmune CNS disorder mediated by pathogenic aquaporin-4 (AQP4) water channel autoantibodies (AQP4-IgG). Although AQP4-IgG-driven complement-dependent cytotoxicity (CDC) is critical for the formation of NMO lesions, the molecular mechanisms governing optimal classical pathway activation are unknown. We investigated the molecular determinants driving CDC in NMO using recombinant AQP4-specific autoantibodies (AQP4 rAbs) derived from affected patients. We identified a group of AQP4 rAbs targeting a distinct extracellular loop C epitope that demonstrated enhanced CDC on target cells. Targeted mutations of AQP4 rAb Fc domains that enhance or diminish C1q binding or antibody Fc-Fc interactions showed that optimal CDC was driven by the assembly of multimeric rAb platforms that increase multivalent C1q binding and facilitate C1q activation. A peptide that blocks antibody Fc-Fc interaction inhibited CDC induced by AQP4 rAbs and polyclonal NMO patient sera. ...
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Plasma Exchange (PLEX) if no improvement occurs with corticosteroids. The goal of PLEX is to lower the level of NMO-IgG in the blood.PLEX involves removing blood from the body through a needle and tubing. Through a series of steps, the plasma (the liquid part of the blood) is separated from blood cells and replaced with an artificial plasma substitute; the plasma substitute and blood cells are combined and returned to the body through an intravenous line. The procedure lasts several hours and may be repeated multiple times over a number of days ...
This case study presents a patient living in a suburban/rural community who received appropriate referral to secondary and tertiary care for nausea and vomiting, accompanied by waxing and waning neurological symptoms, yet proved difficult to diagnose. This patient is presented to draw attention to a rare neurological disorder which should be included in the differential diagnosis of nausea and vomiting with some key neurological complaints, even in the absence of physical findings.
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Neuromyelitis optica (NMO) is an autoimmune disorder of the central nervous system, which is characterized by autoantibodies directed against the water channel aquaporin-4 (AQP4). As one of the main water regulators in the central nervous system, APQ4 is supposed to be involved in the dynamics of brain edema. Cerebral edema seriously affects clinical outcome after ischemic stroke; we therefore aimed to investigate whether NMO-antibodies may exert the same functional effects as an AQP4-inhibitor in-vivo in acute ischemic stroke. Sixteen male Wistar rats were randomized into two groups twice receiving either purified NMO-IgG or immune globulin from healthy controls, 24 hours and 30 minutes before middle cerebral artery occlusion (MCAO) was performed. T2-weighted MRI was carried out 24 hours after MCAO. MRI-examination showed a significant increase of infarct size in relation to the cerebral hemisphere volume with NMO-IgG treated animals (27.1% ± 11.1% vs. 14.3% ± 7.2%; p < 0.05) when corrected for the
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MRI red flags proposed over a decade ago by the European Magnetic Resonance Network in MS (MAGNIMS) have guided clinicians in the diagnosis of multiple sclerosis (MS). However, the past 10 years have seen increased recognition that vascular disease can coexist and possibly interact with MS, improvements in the reliability of ways to differentiate MS from novel antibody-mediated CNS disorders (such as anti-aquaporin-4 antibody and myelin-oligodendrocyte glycoprotein antibody-associated diseases) and advances in MRI techniques. In this Review, MAGNIMS updates the imaging features that differentiate the most common mimics of MS, particularly age-related cerebrovascular disease and neuromyelitis optica, from MS itself. We also provide a pragmatic summary of the clinically useful MRI features that distinguish MS from its mimics and discuss the future of nonconventional techniques that have identified promising disease-specific features. ...
I was diagnosed with Neuromyelitis optica (NMO) also known as Devics disease (similar to MS) last month after my MRI scans showed optic neuritis and brain lesions - and its completely shattered me.. Seven years ago, I experienced the same heartbreak in a cold office when the doctor told me I had systemic lupus. No matter how long youve lived with chronic pain, youre never quite prepared for the next invasion of torment. The pain from NMO fused with the suffering of lupus are unbearable at times. I feel ambushed. Walking is a joke as my knees have turned to brick. The pain is unreal. All I want to do is curl up in a blanket, take pain medicine, and sleep all the time (if I could sleep). At least when Im sleeping, Im not crying from the unbearable waves of pain or feeling the sting of missing the things I could once do normally.. Living with chronic disease wrecks you emotionally and it devastates all parts of your life. Im a teacher, and Ive missed sixteen days of work and its barely ...
Results A total of 173 patients were included in the cohort. Fifty patients (28.9%) were AQP4-Ab-positive and diagnosed with NMOSD-ON. Of 123 patients with seronegative AQP4-Ab, 37 (30.1%) patients had atypical ON, with male predominance (25, 67.6%). The atypical ON group (compared with the typical ON and NMOSD-ON groups) had a significantly lower female:male ratio (1:2.1 vs 1.8:1 and 9:1, respectively, p=0.001 and p,0.001), an older mean age of onset (44.8, 13-71 years vs 36.9, 13-73 years and 36.2, 13-66 years, p=0.003 and p=0.004), a lower rate of good (≥0.5) visual recovery (6.7% vs 79.8% and 30.9%, p,0.001 and p,0.001) and (compared with the NMOSD-ON group) a lower recurrence rate during a 2-year follow-up (29.3% vs 60%, p=0.009). However, none developed to multiple sclerosis or neuromyelitis optica in the atypical ON group. ...
Shuangren-Anshen capsule (SAC) is a traditional Chinese herb that was improved in our laboratory. An orthogonal experiment [L9(3)4] was used to optimize the extraction conditions. In vivo, a hemorrhage mouse model was established and the hemoglobin contents of normal control, model control, and treated mice were measured. Additionally, the sedative and hypnotic effects of SACs were assessed based on pharmacological parameters such as changes in locomotive activity, forelimb raising, sleep latency, sleep duration, and number of mice that fell asleep.
Q: What is Devics disease? Is it a kind of multiple sclerosis?A: Doctors Devic and Gault first described Devics disease (now called neuromyelitis optica or NMO) in 1894 from their experience with 16 patients. NMO is a rare disease of the central nervous system, affecting about 4000 Americans every year. It can affect anyone, but is much more common in women than men, with a mean age of onset of about 40.NMO is an autoimmune disease (the bodys own antibodies attack normal
Lawrence Steinman is the author of this article in the Journal of Visualized Experiments: Induction of Paralysis and Visual System Injury in Mice by T Cells Specific for Neuromyelitis Optica Autoantigen Aquaporin-4
Cells, Disease, Encephalomyelitis, Experimental Autoimmune Encephalomyelitis, Granulocyte, Multiple Sclerosis, Neuromyelitis Optica, Optic Nerve, Pathology, Sclerosis, Spinal Cord, Th17 Cells, Treatment
The early diagnosis of certain types of cancer, as well as nervous system diseases such as multiple sclerosis and neuromyelitis optica, may soon be facilitated by the use of a nanometric sensor capable of identifying biomarkers of these pathological conditions.
The Circulatory, Respiratory, Digestive, and Excretory Systems.Circulatory system diseases. Lessons. Coronary artery disease.The human excretory system functions to remove waste from the human body. The result is excessive urination and a disease called diabetes insipidus.. Just Passing Through Kidney. or excretory, system in the human body. When the kidney fails due to disease or accident,.From asthma to ulcers, this section is loaded with articles about diseases and conditions that can affect teens.Answers from specialists on diseases that affect the excretory system.Human Excretory System. Protection from Disease - The intact skin prevents invasion of micro-organisms and dust into the body.Malfunctioning of kidneys can lead to accumulation of urea in blood, a condition called uremia, which is.. In this resource from CK-12 we look at some common kidney diseases and dialysis.The classics are clearly Multiple Sclerosis, and far less common, Neuromyelitis Optica, yet, some cases of immune ...
Hoffmann, Frank; Kraft, Andrea; Heigl, Franz; Mauch, Erich; Koehler, Jürgen; Harms, Lutz; Kuempfel, Tania; Koehler, Wolfgang; Ehrlich, Sven; Bayas, Antonios; Weinmann-Menke, Julia; Beuker, Carolin; Henn, Karl-Heinz; Ayzenberg, Ilya; Ellrichmann, Gisa; Hellwig, Kerstin; Klingel, Reinhard; Fassbender, Cordula Marie; Fritz, Harald; Slowinski, Torsten; Weihprecht, Horst; Brand, Marcus; Stiegler, Thomas; Galle, Jan; Schimrigk, Sebastian (2018): Tryptophan immunoadsorption during pregnancy and breastfeeding in patients with acute relapse of multiple sclerosis and neuromyelitis optica. In: Therapeutic Advances in Neurological Disorders, Vol. 11 [PDF, 241kB] ...
Evaluation of new immunological targets in neuromyelitis optica.(2013) Chanson JB, Paolini I, Collongues N, Alcaro MC, Blanc F, Barbetti F, Fleury M, Peroni E, Rovero P, Rudolf G, Lolli F, Trifilieff É, Papini AM, de Seze J. J Pept Sci. 19(1):25-32. ,doi: 10.1002/psc.2470 ...
The Priority Programme for Drinking Water Supply and Irrigation 2020-2027 has recently been launched in Morocco. It will make it possible to allocate 115 billion Moroccan dirhams (€10.7 billion) to water infrastructure.
Aquaporin 8 (AQP8) is a water channel protein. Aquaporins are a family of small integral membrane proteins related to the major intrinsic protein (MIP or AQP0). Aquaporin 8 mRNA is found in pancreas and colon but not other tissues. [provided by RefSeq, Jul 2008 ...
Peptides , Phosphopeptides , Aquaporin-2 (254-267), pSER261, human; This peptide is a fragment of the human aquaporin-2 (AQP2) phosphorylated at Ser261. Protein phosphorylation plays a key role in vasopressin signaling in renal-collecting duct. Phosphorylation at several AQP2 residues including Ser256 and Ser261, is altered in response to vasopressin. It is possible that both sites are involved in vasopressin-dependent AQP2 trafficking.; RQSVELH-pS-PQSLPR; H-Arg-Gln-Ser-Val-Glu-Leu-His-pSer-Pro-Gln- Ser-Leu-Pro-Arg-OH
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A major water main break floods the University of California, Los Angeles campus and strands motorists. Vanessa Johnston reports.\rVideo provided by Reuters
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The proposed pipeline will cross the Mni Wiconi water pipeline twice. The Mni Wiconi is a major water source for Rosebud, Pine Ridge and Lower Brule reservations, and officials on those reservations have said they are concerned about the safety of the crossings. Read more: http://rapidcityjournal.com/news/celebrity-activist-protests-pipeline-at-pine-ridge/article_b86b55c0-0119-11e1-a2a7-001cc4c03286.html#ixzz1c5VMAIAd
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Two previous articles in this series on aquaporins have discussed their history, mechanism and stimulation. The current article describes the role of AQP3 in regulating skin cell growth.
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