Onset Of Optic Neuritis Research Articles

Evaluation of the circulating CD34 + , CD309 + , and endothelial progenitor cells in patients with first attack of optic neuritis

Background:Endothelial progenitor cells (EPCs) are present in circulation and contribute to vasculogenesis in adults. The aim of the present study was to determine the number of circulating EPCs in patients with optic neuritis (ON).Materials and Methods:Fifty patients with ON were diagnosed by expert neurologist and optometrist at the Feiz Hospital, Isfahan, Iran (2012–2013). Blood samples were collected from ON patients in the first attack. The number of EPCs was measured by flow cytometry through the assessment of CD34+ and CD309+ in patients and healthy individuals.Results:With using flow cytometry, CD34+ and CD309+ cells detected in peripheral blood cells of patients (n = 50) with ON, and healthy individuals (n = 30). Patients with ON had (mean = 66.71 ± 17.82) CD34+ and CD309+ cells compared with healthy controls (mean = 28.72 ± 22.46). In addition, there was no significant difference in CD309+ cells in both groups.Conclusion:This study showed elevated CD34+ and CD309+ cells in the early stage of the disease. Regarded to EPC increment in neural repair, it expected the EPC level be increased in these patients, but no detectable differences were observed among both markers in healthy and patient with first attack.

Detecting Optic Atrophy in Multiple Sclerosis Patients Using New Colorimetric Analysis Software: From Idea to Application

Neuro-ophthalmologists typically observe a temporal pallor of the optic disc in patients with multiple sclerosis. Here, we describe the emergence of an idea to quantify these optic disc color changes in multiple sclerosis patients. We recruited 12 multiple sclerosis patients with previous optic neuritis attack and obtained photographs of their optic discs. The Laguna ONhE, a new colorimetric software using hemoglobin as the reference pigment in the papilla, was used for the analysis. The papilla of these multiple sclerosis patients showed greater pallor, especially in the temporal sector. The software detected the pallor and assigned hemoglobin percentages below normal reference values. Measurements of optic disc hemoglobin levels obtained with the Laguna ONhE software program had good ability to detect optic atrophy and, consequently, axonal loss in multiple sclerosis patients. This new technology is easy to implement in routine clinical practice.

P010 - Neuromyelitis optica: Case reports from Oman

Neuromyelitis optica (NMO), a multiple sclerosis mimic, is a rare disorder with a combination of optic neuritis and transverse myelitis. Only few cases were reported in Oman and were considered a diagnostic challenge. Most of them had an unusual presentation and were confused with multiple sclerosis. The neuromyelitis optica IgG test helped confirming the diagnosis. We present 4 cases of neuromyelitis optica from a tertiary referral hospital, Royal Hospital, Oman. The criterion of Wingerchuk et al. was used for the diagnosis. All patients had MRI brain and spine and neuromyelitis optica IgG test. First patient , a 29 years old female, was referred to outpatient clinic with a history of an attack of left optic neuritis. Subsequently had 3 recurrent attacks in Rt eye. After each attack she received IV methylprednisolone followed by a tapering dose of oral prednisolone. She had a partial recovery after each attack. Initial CSF oligoclonal bands and NMO IgG were −ve. MRI brain showed non-specific white matter changes. After the 4th attack of optic neuritis she was started on a monthly dose of cyclophosphamide. After the 7th dose she was changed to oral mycophenolate. After 9 months she had a new attack of optic neuritis and same treatment was continued. After 2 years free of relapses mycophenolate was stopped. After 4 months she developed acute paraplegia. MRI spine showed focal T2 hyperintensities from T3 to T5. Repeat NMO IgG was +ve. At this point a diagnosis of neuromyelitis optica was made and patient was planned for Rituximab therapy. Second patient is a 35 years old female, presented to neurology clinic with history of recurrent optic neuritis for which she was followed up by ophthalmologist. After 16 months she was admitted with acute transverse myelitis and optic neuritis. Initial NMO IgG was −ve. MRI brain showed nonspecific T2 hyperintensities. MRI spine showed diffuse T2 hyperintensties from C5 through T10. She was treated with IV methyl prednisolone, and because the response was not favorable, IV immunoglubulins was given, and maintained on prednisolone (tapering dose) and mycophenolate. On out patient follow up she continued to have mild residual weakness. After a year she developed another attack of paraplegia and optic neuritis; and was started on interferon. A repeat NMO IgG was +ve. After 2 months she developed another attack of paraplegia. And after 4 months it also recurred. She was offered treatment with Mitoxantrone but refused. Third patient is a 24 years old female, transferred to our hospital with 2 months H/O acute transverse myelitis and optic neuritis for which she was admitted to a local hospital and received IV methyl prednisolon. MRI brain showed multiple white matter T2 hyperintensities. MRI spine showed diffuse T2 hyperintensities C2 to T1 and T7–T12. Patient refused lumbar puncture. She was seen in neurology clinic after 2 months with 3 weeks H/O Lt optic neuritis and received IV methyl prednisolone. NMO IgG was +ve and was started on interferon. Seen again after 4 months. Doing well, ambulant without support. Patient lost to follow up. She subsequently deteriorated and was started on Rituximab. Fourth patient is a 46 years old female, admitted with urinary retention, generalized weakness, and altered sensorium. MRI brain : non-specific T2 white matter changes. MRI spine : extensive T2 hyperintensities from C2 to T1 and from T8 to T10 with contrast enhancement. Treated with methyl prednisolone. Had gradual progressive recovery. After 4 months had another attack of transverse myelitis. MRI spine : T2 hyperintensities from lower medulla to T10. Received IV methyl prednisolone. CSF oligoclonal bands was +ve. NMO IgG was +ve. ANCA-PR3 A6 was +ve. Cyclophosphamaide treatment was attempted but was not tolerated by patient and was stopped. Neuromyelitis optica should be suspected in any patient presenting with optic neuritis, transverse myelitis or both with an MRI brain not suggestive of multiple sclerosis. Neither a positive oligo clonal band in CSF, nor an initial negative NMO IgG test can exclude the diagnosis of NMO, as the former may be present in 35% of patients with NOM and the last can turn positive later on in the disease coarse. The diagnosis of NMO warrants early initiation of a disease specific therapy to prevent relapses.

P060 - Evaluation of circulating endothelial cell level in patients with optic neuritis attack

Objective Optic neuritis (ON) is inflammation of the optic nerve. In multiple sclerosis (MS) acute demyelization of optic nerve is a common cause of ON in some parts. Endothelial progenitor cells (EPCs) are present in circulation and contribute to vasculogenesis in adults. The aim of present study was to determine the number of circulating EPCs in MS patients with ON. Material and methods Blood samples were collected from 50 MS patients with ON and 40 healthy individuals (mean ages: 26±5). Together with the collection of demographic data, a sample of venous blood was drawn to assess a complete blood count with differential; circulating, VEGF2, CD31, CD144 and CD309 as ECs markers and CD34 as hematopoietic cell marker using flow cytometry. Data are expressed as mean±SD. Results were analyzed statistically, using the Independent sample T test. Values of p Results The median absolute percentage of circulating CD34+HPCs in the overall population of ON patients was 18±9.96. Against in the healthy was 26.31±14.33% ( p Conclusion Overall, data indicated EPCs circulate in peripheral blood of MS patients with an early phase of ON. It seems to increase of EPC relates to a good outcome. It may be that Heightened mobilization of EPCs represents an important role in prevention from BBB disruption or may be caused neoangiogenesis in MS patients with ON.

Opportunistic Infections of the Retina in Patients With Aquaporin-4 Antibody Disease

Patients with neuromyelitis optica who have aquaporin-4 antibodies are being identified and receiving immunosuppressant treatment earlier and more aggressively as a result of increasing awareness of the importance of preventing relapses responsible for the high morbidity and mortality associated with the disease. To our knowledge, opportunistic retinal infection in patients with aquaporin-4 antibodies who are receiving immunosuppressants has not been reported to date. We describe 2 patients with aquaporin-4 antibodies who were receiving conventional doses of first-line immunosuppressive therapy. Both patients presented with vision loss that was initially thought to be optic neuritis attacks. The subsequent diagnoses were ocular toxoplasmosis and cytomegalovirus retinitis. Retinal opportunistic infections can occur in patients with aquaporin-4 antibodies who are receiving relatively low levels of immunosuppression, may mimic optic neuritis, and are a potentially reversible cause of vision loss when treated promptly.

P057 - Remarkable response of seropositive neuromyelitis optica to rituximab therapy – First report from kingdom of Bahrain

Background Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system that causes severe optic neuritis and myelitis attacks. Humoral immunity seems to have a prominent role in the pathogenesis of the disease. Recently the nature and understanding of NMO have been revolutionized by two factors (1) the identification of both a NMO IgG as a sensitive and specific diagnostic marker and (2) the identification of both specific radiological and pathologic features of the disease. Also with the limited treatment options, recently positive results reported with the use of the anti-CD20 monoclonal antibody rituximab are promising. Objectives We present 2 cases, first to be reported in Kingdom of Bahrain, of NMO with positive NMO IgG and favorable response to Rituximab. Methods and results Case # 1: 56 year old female patient. She had on 2008 left optic neuritis with residual visual loss. On September 2011 she had right optic neuritis. For both she received Methylprednisolone plus therapy for 4 days with partial response and residual visual loss. On October 2011, she developed severe myelitis with severe spastic paraplegia (grade 0–1) and urinary retention. The patient became bed bound. Her initial MRI of brain showed few scattered lesions for which the patient was diagnosed as multiple sclerosis and maintained on Betaferon injection as a disease modifying therapy. The repeated MRI showed long segment lesion of the spinal cord and her blood test was positive to NMO IgG. The patient did not respond to steroid or IVIg therapy. However, she responded remarkably well to Rituximab injection. In 3 months she is fully independent in her movements with almost normal power and continent. Case # 2: 43 year old female patient. On 2009, she developed a right optic neuritis that responded well to steroid therapy. 2 years later she developed spastic Paraparesis due to myelitis, she responded partially to steroid therapy and was put on Avonex injection as her MRI brain showed changes was diagnosed as MS in private hospital. However, one year later, she developed another sever myelitis that made her wheelchair bound with bladder involvement. Her MRI showed fairly long segment involvement of spinal cord. Her serum test showed positive NMO IgG. I gave her Rituximab injection therapy on which she showed remarkable improvement. In 3 months she is able to walk by herself and she independent in her ADL and bladder continent. Conclusion The remarkable recovery of these 2 patients from their severe disability in this case report support other reports of the effectiveness of Rituximab in the treatment of NMO and the humoral immunity nature of the illness. These are the first cases of NMO with positive IgG to be reported from Bahrain. NMO is not often seen in Bahrain despite high prevalence of MS.

Axonal transport rate decreased at the onset of optic neuritis in EAE mice

Optic neuritis is frequently the first symptom of multiple sclerosis (MS), an inflammatory demyelinating neurodegenerative disease. Impaired axonal transport has been considered as an early event of neurodegenerative diseases. However, few studies have assessed the integrity of axonal transport in MS or its animal models. We hypothesize that axonal transport impairment occurs at the onset of optic neuritis in experimental autoimmune encephalomyelitis (EAE) mice. In this study, we employed manganese-enhanced MRI (MEMRI) to assess axonal transport in optic nerves in EAE mice at the onset of optic neuritis. Axonal transport was assessed as (a) optic nerve Mn2+ accumulation rate (in % signal change/h) by measuring the rate of increased total optic nerve signal enhancement, and (b) Mn2+ transport rate (in mm/h) by measuring the rate of change in optic nerve length enhanced by Mn2+. Compared to sham-treated healthy mice, Mn2+ accumulation rate was significantly decreased by 19% and 38% for EAE mice with moderate and severe optic neuritis, respectively. The axonal transport rate of Mn2+ was significantly decreased by 43% and 65% for EAE mice with moderate and severe optic neuritis, respectively. The degree of axonal transport deficit correlated with the extent of impaired visual function and diminished microtubule-associated tubulins, as well as the severity of inflammation, demyelination, and axonal injury at the onset of optic neuritis.

Optic neuritis in Hong Kong: a 1-year follow-up study.

To investigate the etiology and prevalence of optic neuritis in a Chinese population. This was a single centre prospective cohort study. Consecutive patients with either a first or recurrent attack of optic neuritis from November 2010 to December 2011 were recruited from a district hospital in Hong Kong Special Administrative Region, China. All patients underwent serology testing for NMO (neuromyelitis optica) IgG; oligoclonal bands from lumbar puncture; computer tomography and contrast magnetic resonance imaging (MRI) of the brain and orbit as well as visual field; and optical coherence tomography testing. Patients were followed up for 1 year after the initial attack. 30 optic neuritis subjects were recruited. 73.3 % (22/30) remain as clinical isolated syndrome (CIS) after 1-year follow-up. 10 % (3/30) patients developed multiple sclerosis. 10 % (3/30) were diagnosed with NMO and 6.7 % (2/30) with NMO-spectrum disorder. The majority of acute unilateral optic neuritis in Chinese was CIS in origin although a fraction does progress to develop MS or NMO-related disorders. Clinicians should be aware of the associations and offer appropriate systemic workups.

Teaching Neuro Images : MRI in advanced neuromyelitis optica

A 51-year-old woman was treated with multiple medications for relapsing-remitting multiple sclerosis (MS) over 20 years, including interferons and glatiramer, but continued to have recurrent attacks of optic neuritis and transverse myelitis, leading to bilateral blindness and triplegia. Even with MS-type lesions on MRI, neuromyelitis optica (NMO) was ultimately suspected and confirmed by detection of aquaporin-4 autoantibodies. MRI showed nonenhancing T2 linear hyperintensity around the ventricular system in areas known to highly express aquaporin-4 (figure).1 Profound spinal cord atrophy was evident, consistent with severe, chronic NMO. This case illustrates the lack of effectiveness and potential detriment when MS-directed immunomodulatory medications are aimed at NMO.2

Aquaporin 4 IgG Serostatus and Outcome in Recurrent Longitudinally Extensive Transverse Myelitis

Studies focused on recurrent longitudinally extensive transverse myelitis (rLETM) are lacking. To determine the aquaporin 4 (AQP4) IgG detection rate using recombinant human APQ4-based assays in sequential serum specimens collected from patients with rLETM categorized as negative by first-generation tissue-based indirect immunofluorescence (IIF) assay and to define the clinical characteristics and motor disability outcomes in AQP4-IgG-positive rLETM. A search of the Mayo Clinic computerized central diagnostic index (October 1, 2005, through November 30, 2011), cross-linked with the Neuroimmunology Laboratory database, identified 48 patients with rLETM, of whom 36 (75%) were positive and 12 (25%) negative for neuromyelitis optica (NMO) IgG (per IIF of serial serum specimens). Stored serum specimens from "seronegative" patients were retested with recombinant human AQP4-based assays, including enzyme-linked immunosorbent, transfected cell-based, and fluorescence-activated cell-sorting assays. Control patients included 140 AQP4-IgG-positive patients with NMO, of whom a subgroup of 20 initially presented with 2 attacks of transverse myelitis (rLETM-onset NMO). AQP4-IgG serostatus, clinical characteristics, and Expanded Disability Status Scale score. Six patients with negative IIF results were reclassified as AQP4-IgG positive, yielding an overall AQP4-IgG seropositivity rate of 89%. Fluorescence-activated cell-sorting, cell-based, and enzyme-linked immunosorbent assays improved the detection rate to 89%, 85%, and 81%, respectively. The female to male ratio was 2:3 for AQP4-IgG-negative rLETM and 5:1 for AQP4-IgG-positive patients. The AQP4-IgG-positive patients with rLETM or rLETM-onset NMO were similar in age at onset, sex ratio, attack severity, relapse rate, and motor disability. From Kaplan-Meier analyses, 36% of AQP4-IgG-positive patients with rLETM are anticipated to need a cane to walk within 5 years after onset. For patients with rLETM-onset NMO, the median time from onset to first optic neuritis attack (54 months) was similar to the median disease duration for AQP4-IgG-positive patients with rLETM (59 months). The median number of attacks was 3 for AQP4-IgG-positive patients with rLETM (range, 2-22), and the first optic neuritis attack for those with rLETM-onset NMO followed a median of 3 myelitis attacks (range, 2-19). Immunosuppressant therapy reduced the relapse rate in both AQP4-IgG-positive and AQP4-IgG-negative patients with rLETM. Recombinant antigen-based assays significantly increase AQP4-IgG detection in patients with rLETM, and AQP4-IgG-negative adults with rLETM are rare. Evolution to NMO can be anticipated in AQP4-IgG-positive patients. Early initiation of immunotherapy may result in a more favorable motor outcome.

The Pathology of an Autoimmune Astrocytopathy: Lessons Learned from Neuromyelitis Optica

Neuromyelitis optica (NMO) is a disabling autoimmune astrocytopathy characterized by typically severe and recurrent attacks of optic neuritis and longitudinally extensive myelitis. Until recently, NMO was considered an acute aggressive variant of multiple sclerosis (MS), despite the fact that early studies postulated that NMO and MS may be two distinct diseases with a common clinical picture. With the discovery of a highly specific serum autoantibody (NMO-IgG), Lennon and colleagues provided the first unequivocal evidence distinguishing NMO from MS and other central nervous system (CNS) inflammatory demyelinating disorders. The target antigen of NMO-IgG was confirmed to be aquaporin-4 (AQP4), the most abundant water channel protein in the CNS, mainly expressed on astrocytic foot processes at the blood-brain barrier, subpial and subependymal regions. Pathological studies demonstrated that astrocytes were selectively targeted in NMO as evidenced by the extensive loss of immunoreactivities for the astrocytic proteins, AQP4 and glial fibrillary acidic protein (GFAP), as well as perivascular deposition of immunoglobulins and activation of complement even within lesions with a relative preservation of myelin. In support of these pathological findings, GFAP levels in the cerebrospinal fluid (CSF) during acute NMO exacerbations were found to be remarkably elevated in contrast to MS where CSF-GFAP levels did not substantially differ from controls. Additionally, recent experimental studies showed that AQP4 antibody is pathogenic, resulting in selective astrocyte destruction and dysfunction in vitro, ex vivo and in vivo. These findings strongly suggest that NMO is an autoimmune astrocytopathy where damage to astrocytes exceeds both myelin and neuronal damage. This chapter will review recent neuropathological studies that have provided novel insights into the pathogenic mechanisms, cellular targets, as well as the spectrum of tissue damage in NMO.

Plasmablasts as Migratory IgG-Producing Cells in the Pathogenesis of Neuromyelitis Optica

Neuromyelitis optica (NMO) is an inflammatory disease characterized by recurrent attacks of optic neuritis and myelitis. It is generally accepted that autoantibodies against aquaporin 4 water channel protein play a pathogenic role in neuromyelitis optica. We have recently reported that plasmablasts are increased in the peripheral blood of this autoimmune disease, and are capable of producing autoantibodies against aquaporin 4. Here, we demonstrate that CD138+HLA-DR+ plasmablasts, a subset of IgG-producing cells, are increased in the peripheral blood and are enriched among the cerebrospinal fluid (CSF) lymphocytes during the relapse of neuromyelitis optica. Notably, these CD138+HLA-DR+ plasmablasts overexpress CXCR3, whose ligands are present in the cerebrospinal fluid during the relapse of neuromyelitis optica. These results led us to speculate that plasmablasts producing anti-aquaporin 4 autoantibodies might traffic toward the central nervous system (CNS). Furthermore, we performed single-cell sorting of plasmablasts from peripheral blood and CSF samples from NMO and sequenced the complementarity-determining regions (CDRs) of the IgG heavy chain expressed by the sorted plasmablast clones. There were high frequencies of mutations in the CDRs compared with framework regions, indicating that these plasmablast clones would represent a post-germinal center B-cell lineage. Consistent with the preceding results, the plasmablast clones from the peripheral blood shared the same CDR sequences with the clones from the CSF. These results indicate that IgG-producing plasmablasts, which are guided by helper T-cells, may migrate from the peripheral blood preferentially to the CSF. Since migratory plasmablasts could be involved in the inflammatory pathology of NMO, the B-cell subset and their migration might be an attractive therapeutic target.

Allogeneic Hematopoietic Stem Cell Transplantation For Severe Neuromyelitis Optica

BackgroundNeuromyelitis Optica (NMO), also known as Devic's disease, is a rare inflammatory and demyelinating disorder of the central nervous system characterized by recurrent attacks of optic neuritis (ON) and longitudinally extensive trasverse myelitis (LETM). Previously considered as a severe variant of multiple sclerosis, NMO has been recently recognized as a distinct disorder associated with peculiar pathogenic auto-antibodies to aquaporin-4 (AQP4). Despite transient control of disease activity, standard treatments are often followed by relapses with accumulating disability and ultimately a poor prognosis. Thus, new therapeutic strategies for NMO are warranted. Hematopoietic Stem Cell Transplantation (HSCT) can induce stable remissions in patients with severe treatment-refractory Autoimmune Diseases. Here we report our investigational experience on allogeneic HSCT in two patients with severe and refractory forms of the disease. MethodsBoth treated patients had aggressive forms of NMO and serum positivity for AQP4 antibodies. Upn#1 is a 30 yrs old male affected by severe relapsing LETM, with paraparesis and thoracic spinal cord lesion on magnetic resonance imaging (MRI). Upn#2 is a 28 yrs female with recurrent attacks of ON and LETM. Both had received several lines of treatment without benefit, including high-dose corticosteroids, cyclophosphamide, rituximab, natalizumab, alemtuzumab, plasma exchange, high-dose thiotepa/cyclophosphamide and/or BEAM with Anti-Thymocyte Globulin (ATG) and cyclosporine followed by autologous HSCT rescue. Before HSCT the two patients showed an Kurtzke Expanded Disability Status Score (EDSS) of 6 (assistance required to walk) and 8.5 (restricted to bed, paraplegia) respectively, while both of them presented active contrast enhancing lesions on MRI and positivity for the pathogenic AQP4 auto-antibodies. Upn#1 underwent allogeneic HSCT from his HLA-identical sibling, while Upn#2 from a matched unrelated donor. Conditioning regimen consisted of full-dose treosulfan and fludarabine. Graft versus host disease (GvHD) prophylaxis combined ATG-Fresenius with cyclosporine and a short course of methotrexate (Upn#1) or mycophenolate and rapamycin (Upn#2); B cell depletion of both patients and graft was obtained by rituximab. ResultsHematopoietic recovery occurred in both patients within day 30, and was accompanied by rapid achievement of full donor chimerism. Each patient experienced an episode of febrile neutropenia and one of them a CMV reactivation, both responsive to medical therapy; no serious adverse events were reported. None of the patients experienced neither acute nor chronic GvHD. MRI demonstrated the disappearance of the inflammatory lesions, without evidence of new ones. The immunological data obtained from the follow-up of these two patients suggest that allogeneic HSCT can alter the course of NMO through several concurring mechanisms: the eradication of autoreactive cell clones by high-dose chemotherapy and by the in vivo T and B cell depletion used for conditioning, the disappearance of the pathogenetic anti-AQP4 antibodies and achievement of a stable full-donor hematopoietic chimerism by donor T cell-mediated alloreactivity; the re-establishment of thymic central tolerance and renewal of the immune repertoire. Strikingly, these results correlated with a marked improvement of neurological functions in both treated patients. In UPN#1 EDSS dropped from 6 to 3.5 (fully ambulatory but with moderate disability in one functional neurological system), while in UPN#2 EDSS decreased from 8.5 to 7.5 (unable to take more than a few steps, restricted to wheelchair). At last follow-up (48 and 36 months after HSCT, respectively), both patients are alive, well and relapse-free. ConclusionsThese findings suggest that allogeneic HSCT may be beneficial in patients who have aggressive forms of NMO, by renewing the immune repertoire of T- and B-cells, thus reducing disease activity and arresting disability progression. The preliminary evidence of long-term disease control in these two refractory patients paves the way for further prospective phase I-II clinical trials to validate allogeneic HSCT as promising novel option for aggressive forms of NMO. Disclosures:Bonini:MolMed S.p.A: Consultancy.

Glycine receptor and myelin oligodendrocyte glycoprotein antibodies in Turkish patients with neuromyelitis optica

BackgroundSeronegative NMO is highly prevalent in non-Western countries implying the presence of as yet unknown antibodies (Ab). We investigated potential novel Ab in aquaporin-4 Ab (AQP-4-Ab) positive and negative NMO patients. MethodsSera of 20 NMO patients were examined for AQP-4, myelin oligodendrocyte glycoprotein (MOG) and glycine receptor (GlyR) Ab by cell-based assays. ResultsAQP-4-Ab was identified in 10 NMO patients, MOG-Ab was detected only in one AQP-4-Ab positive patient and GlyR-Ab was detected in two AQP-4-Ab negative patients. GlyR-Ab positive patients displayed simultaneous optic neuritis and transverse myelitis attacks and relatively low disability, whereas MOG and AQP-4-Ab double positive patient had a significantly increased disability. ConclusionThis study showed for the first time the presence of GlyR-Ab in Turkish NMO patients. In contrast with previous reports, MOG Ab does not appear to be a distinctive marker for Turkish AQP-4-Ab negative NMO patients.

A Chinese Lady with Combine Neuromyelitis Optica and Sjögren's Syndrome: A Case Report

Neuromyelitis optica (NMO) is an inflammatory demyelinating disorder of the central nervous system while Sjogren’s syn drome is a chronic systemic inflammatory disease. Co-existing NMO and Sjogren’s syndrome was reported as a rare asso ciation in the literature. We report a case of a middle-age Chinese woman presented with unilateral optic neuritis who was subsequently diagnosed with seropositive NMO and Sjogren’s syndrome with seropositivity for NMO-IgG and anti-Ro (SSA) antibodies respectively. Work up for other autoimmune disorders was negative. She was prescribed with oral azathioprine daily with no further attack of optic neuritis and longitudinal myelitis for 3 years. In view of high risk of relapse and signifi cant morbidity in most cases with NMO, rapid diagnosis and early initiation of aggressive immunosuppressive treatment are essential to minimize unfavorable outcomes.

Central nervous system inflammatory demyelinating disorders among Hong Kong Chinese

Classical multiple sclerosis (CMS) and neuromyelitis optica spectrum disorders (NMOSD) are distinct central nervous system inflammatory demyelinating disorders (CNS IDD). Early diagnosis of CNS IDD is important as appropriate immunotherapies to optimize prognosis. We studied the diagnoses of CNS IDD among Hong Kong Chinese in a hospital-based setting. Consecutive Chinese patients who presented to our hospital with clinically isolated syndrome and subsequently diagnosed to have CNS IDD from 1980 to 2010 were reviewed. Patients with known diagnosis of CNS IDD referred for further care were excluded. Serial sera were assayed for aquaporin-4 autoantibodies (AQP4 Ab), at least 3 assays within 2–5years. A total of 210 patients diagnosed to have CNS IDD with disease duration of at least 2years were studied. Among 198 patients with serial sera available, 40 (20.2%, 20 had NMO and 20 other NMOSD) were AQP4 Ab-positive. Four patients who were AQP4 Ab-negative on the initial assay converted to AQP4 Ab-positive on repeated assays. The diagnoses of 210 patients were CMS in 88 (41.9%), NMOSD 47 (22.4%, 27 NMO, 20 other NMOSD), single attack of myelitis 23 (11.0%), single attack of optic neuritis 21 (10.0%), relapsing myelitis 10 (4.8%), acute disseminated encephalomyelitis (ADEM) 9 (4.3%), relapsing optic neuritis in 6 (2.9%), opticospinal multiple sclerosis 3 (1.4%) and single attack of brainstem encephalitis 3 (1.4%). Compared to CMS, NMOSD patients had older onset age, lower frequencies of brain MRI abnormalities and CSF OCB, higher frequency of LETM, higher CNS inflammation attack frequency in the first 2years, worse clinical outcome with higher EDSS score and mortality rate. This hospital-based study suggests that CMS (41.9%) and NMOSD (22.4%) are the most common CNS IDD among Hong Kong Chinese. NMOSD has worse clinical outcome than CMS. Detection of AQP4 Ab facilitates early diagnosis and prompts immunotherapies of NMOSD.

Brain Tissue Volumes and Perfusion Change with the Number of Optic Neuritis Attacks in Relapsing Neuromyelitis Optica: A Voxel-Based Correlation Study

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 total attacks on the other side. For this purpose, high resolution T1-weighted MRI and perfusion SPECT imaging were obtained in 15 RNMO patients. The results showed negative regional correlations of WMV, GMV and perfusion with the number of ON attacks, involving important components of the visual system, which could be relevant for the comprehension of incremental visual disability in RNMO. We also found positive regional correlation of perfusion with the number of ON attacks, mostly overlapping the brain area where the WMV showed negative correlation. This provides evidence that brain microvasculature is an early disease target and suggests that perfusion alteration could be important in the development of brain structural abnormalities in RNMO.

Decreased Ocular Pulse Amplitude and Retinal Nerve Fibre Layer in Multiple Sclerosis

This study was conducted to assess ocular pulse amplitude and retinal nerve fibre layer in patients with multiple sclerosis and their correlation with disease duration and with severity. Retinal nerve fibre layer thickness was measured by Heidelberg Retinal Tomography II (HRT-II; Heidelberg Engineering, Dossenheim, Germany) and ocular pulse amplitude was measured by dynamic contour tonometry (Ziemer Ophthalmic Systems, Port, Switzerland) in 37 multiple sclerosis patients and 72 age- and gender-matched controls. Ocular pulse amplitude was significantly reduced and retinal nerve fibre layer was significantly thinner in temporal, superotemporal, and nasal sectors in patients with multiple sclerosis regardless of having an optic neuritis attack. The retinal nerve fibre layer was thinner in eyes with a previous optic neuritis attack compared with the eyes without an attack, but the difference was not significant. Ocular pulse amplitude showed a positive correlation with visual evoked potential amplitude and a negative correlation with visual evoked potential latency. Retinal nerve fibre layer thickness showed a significant negative correlation with the disease duration but not with visually evoked potential, disease severity, nor previous optic neuritis. These findings indicate that the process of degeneration starts in the early period of the disease, as our study group is composed of early–middle-stage multiple sclerosis patients, and is independent of relapses.

Predictive value of 1 month retinal nerve fiber layer thinning for deficits at 6 months after acute optic neuritis

Background: Retinal nerve fiber layer (RNFL) loss occurs with multiple sclerosis and after optic neuritis. Vision or RNFL changes at presentation of optic neuritis are not predictive of outcome, but vision loss at 1 month correlates with vision deficits at 6 months. We hypothesized that RFNL thinning at 1 month would predict RNFL loss at 6 months. Methods: We prospectively studied the RNFL by optical coherence tomography (OCT) and scanning laser polarimetry (SLP), and determined the threshold field mean deviation, in 25 subjects with acute optic neuritis over a 6-month period. RNFL values, including the amount of thinning at 1-month, were correlated with 6-month outcome. Results: Baseline visual performance and RNFL values were similar for eyes grouped by 1 month RNFL thinning. Eyes with 1 month RNFL thinning had greater and significant RNFL thinning at 6 months, for all quadrants by OCT and for the nasal and inferior quadrants by SLP. RNFL thinning by OCT and SLP at 1 month correlated with 6-month OCT (r = 0.58; p = 0.006) and SLP (r = 0.59; p = 0.002) RNFL thinning, respectively. Conclusion: Early RNFL loss at 1 month was predictive of the RNFL thinning at 6 months, which corroborated the importance of the 1-month time point for predicting the outcome of an optic neuritis attack.

Should we sequence everyone’s genome? Yes

<b>Background:</b> Neuromyelitis optica (NMO) is a disease of the CNS characterized by severe optic neuritis and longitudinally extended transverse myelitis. Recent studies suggest that anti-aquaporin-4 (AQP4) antibodies, NMO-specific biomarkers, are...