Diagnosis Of Neuromyelitis Optica Research Articles

Therapeutic efficacy of plasma exchange in neuromyelitis optica

Background:Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that selectively affects the optic nerves and spinal cord and generally follows a relapsing course. Therapeutic plasma exchange (TPE) appears to be effective in patients with central nervous system inflammatory demyelinating disease who do not respond to first-line corticosteroid treatment.Objective:We represent a retrospective review of the use of TPE in the treatment of an acute attack of NMO in five patients who failed to respond to initial immunomodulatory treatment.Materials and Methods:We evaluated the effect of TPE on the degree of recovery from NMO. It was performed using a single volume plasma exchange with intermittent cell separator (Hemonetics Mobile Collection System plus) by femoral or central line access and scheduled preferably on alternate-day intervals from 8 to 10 days. Both subjective and objective clinical response to TPE was estimated, and final assessment of response was made at the time of the last TPE in the series.Results:All patients were severely disabled before the initiation of TPE and they were female; with the mean age of these patients was 52.5 years (range = 36-69 years), the median age of NMO diagnosis was 49.4 years (range = 35–65 years), and the median duration of disease was 2.6 years (range = 0–5 years). Out of five patients, three had a history of bilateral optic neuritis, and all patients were anti-against protein aquaporin-4antibody positive. Totally 24 TPE procedures were performed on five patients, the mean time of start of TPE in the acute attack was 18.6 days. Patients were severely disabled at the initiation of TPE (range = expanded disability status scale 6.5–9), and improvement was observed early in the course of TPE treatment in most patients.Conclusion:The present study provides clinical support for the importance of TPE in refractory acute attack in NMO. However, with new diagnostic technologies and increasing clinical awareness, we may see a more improved ways of TPE in these patients in the future; hence, TPE is more effective modality of treatment as it also removed the antibodies.

The 2015 NMOSD diagnostic criteria - are they an improvement?

Revision to the widely accepted Wingerchuk 2006 criteria for diagnosis of neuromyelitis optica (NMO) was necessary for several reasons: 1. The spectrum of the disease was determined to be broader than previously recognized and to include certain brainstem, hypothalamic and cerebral syndromes; 2. The advent of a specific biomarker, aquaporin-4 IgG (AQP4-IgG), enabled a confident NMO diagnosis at first presentation; 3. Whether AQP4-IgG seronegative patients with symptoms compatible with NMO could be diagnosed with this condition needed to be clarified. The criteria proposed by the International Panel on NMO Diagnosis (IPND) subsumed all NMO-associated syndromes under the term “NMO spectrum disorders (NMOSD).” A diagnosis in AQP4-IgG seropositive patients requires only a single compatible syndrome and neither optic neuritis nor myelitis. For AQP4-IgG seronegative patients, dissemination in space is necessary in addition to certain MRI requirements to increase stringency and reliability. Retrospective studies from Korea and the U.K. have documented 75-85% increased sensitivity of the new IPND criteria, especially for seropositive cases. However, the specificity of the IPND criteria and ability to discriminate NMOSD from a growing number of mimic conditions remains to be established. It seems likely that a new form of NMOSD associated with myelin oligodendrocyte glycoprotein IgG antibodies will be considered a distinct form of NMOSD with an overlapping but somewhat distinct prognosis and possibly similar requirement for immunosuppression rather than MS-directed immunomodulatory treatment. Although the IPND criteria represent an incremental improvement, diagnostic criteria for NMOSD will likely evolve especially based on discovery of novel pathogenic autoantibody biomarkers.

Complexity and wide range of neuromyelitis optica spectrum disorders: more than typical manifestations.

Neuromyelitis optica (NMO), considered to be mediated by autoantibodies, often cause severely disabling disorders of the central nervous system, and predominantly cause optic nerve damage and longitudinally extensive transverse myelitis. Remarkable progress has been made in deciphering NMO pathogenesis during the past decade. In 2015, the International Panel for NMO Diagnosis proposed the unifying term “NMO spectrum disorders” (NMOSD) and the updated NMOSD criteria reflects a wide range of disease and maintains reasonable specificity. Moreover, cumulative findings have indicated that NMOSD are frequently associated with multiple autoimmune diseases, thereby presenting complex clinical symptoms that make this disease more difficult to recognize. Notably, most neurologists do not heed these symptoms or comorbid conditions in patients with NMOSD. Whereas previous reviews have focused on pathogenesis, treatment, and prognosis in NMOSD, we summarize the present knowledge with particular emphasis on atypical manifestations and autoimmune comorbidities in patients with NMOSD. Furthermore, we emphasized the identification of these atypical characteristics to enable a broader and better understanding of NMOSD, and improve early accurate diagnosis and therapeutic decision making.

Neuromyelitis optica spectrum disorders: An experience from tertiary care hospital of North–West India

Abstract Introduction N ew criteria given by International Panel for NMO Diagnosis (IPND) for Neuromyelitis optica (NMO) & widespread availability of neuroimaging and diagnostic facilities, have changed the concepts of NMOSD. Objectives To study the clinico- radiological profile of patients of NMOSDs & categorize them into specific groups according to current diagnostic criteria. Materials and Methods This was a prospective study of 54 cases of NMOSDs admitted to the Department of Neurology of SMS Medical College, Jaipur, Rajasthan,from August 2014 to March 2017. Results Of the 54 cases, Female to Male ratio was 3.8:1 and mean age of the study population was 34.1 years. NMOSD with AQP4-IgG group constituted 42.5%(n = 23), NMOSD without AQP4-IgG group constituted 35.2% (n = 19), NMOSD with unknown AQP4-IgG status group constituted 22.2% (n = 12). Most common clinical presentation was myelitis (70.3%) followed by optic neuritis (48.12%), area postrema syndrome (29.6%), brainstem syndrome (24.07%), cerebral syndrome (9.25%) and diencephalic syndrome (1.8%). MRI brain & spine were abnormal in respectively 41.1% & 71.7% cases. Conclusion Revised diagnostic criteria for NMOSD enables them to diagnose early & classify even in absence of AQP4-IgG positivity. They have varied clinical presentation and neuro-imaging plays an important diagnostic role in defining these syndromes.

Headache in Neuromyelitis Optica.

Neuromyelitis optica (NMO) classically features a clinical presentation that includes longitudinally extensive transverse myelitis and optic neuritis. However, many other pathognomonic phenomena have more recently been described in patients diagnosed with NMO, including intractable hiccups, vomiting, and painful tonic spasms, but less has been reported regarding the relationship between NMO and headache. Though headache is well established as both a symptom and comorbidity of multiple sclerosis (MS), it has been much less described thus far in the NMO literature and warrants more careful evaluation. Many questions remain unanswered about the relationship between NMO and headache, including headache prevalence in certain groups, distribution of primary and symptomatic headache disorders that are seen most frequently and the specific neuroimaging findings that are associated with an increased risk of headache. Various types of headache, such as cervicogenic headache and trigeminal autonomic cephalalgia-like headache, have been reported as the initial clinical presentation of NMO. Other publications have emphasized the association of NMO and other etiologies of headache, such as trigeminal neuralgia, PRES, and preeclampsia. Certain MR imaging findings such as medullary lesions in patients with NMO have also been associated with headache. The link between headache and NMO is evident not only in limited case reports and clinical studies but also with both MR imaging and even with some potential common underlying biomarkers such as pentraxin-3 and interleukin-6. Developing a further understanding in the association between these two diseases may lead to better management of headache in patients with NMO and potentially lead to earlier diagnosis of NMO in whom headache may serve as an initial presenting symptom and may even herald a disease exacerbation.

Interleukin-6 analysis of 572 consecutive CSF samples from neurological disorders: A special focus on neuromyelitis optica

BackgroundElevation of cerebrospinal fluid (CSF) interleukin (IL)-6 has been reported in various neurological disorders but has never been systematically analyzed. Our main objectives are to compare the CSF IL-6 levels among various neurological disorders and to evaluate the significance of CSF IL-6 measurements for the diagnosis of neuromyelitis optica (NMO). MethodsWe retrospectively investigated the IL-6 levels of 572 consecutive CSF samples in patients with various neurological disorders. Additionally, the associations between clinical manifestations in NMO patients and CSF IL-6 levels were closely investigated. ResultsAmong the neurological disorders, patients with NMO had the highest CSF IL-6 level. Receiver operating characteristic analysis found the optimal cutoff CSF IL-6 value for diagnosing NMO as 7.8pg/ml, and the sensitivity and specificity were 0.7317 and 0.7694, respectively. In NMO, CSF IL-6 levels were correlated with the length of the spinal cord lesion and anti-aquaporin-4 antibody-positivity and decreased after treatment. ConclusionCSF IL-6 can be high in various inflammatory and non-inflammatory CNS disorders, but its upregulation appears to be the most remarkable in NMO.

Neuromyelitis optica: phenotypic characteristics in a Brazilian case series

To describe the characteristics of 34 Brazilian NMO patients. To evaluate the contribution of the 2015 criteria to the diagnosis of NMO spectrum disorders (NMOSD) in 40 patients with longitudinal extensive transverse myelitis (LEMT). This is a retrospective, descriptive and analytic study. Among NMO patients, there was a predominance of women, with onset in the fourth decade of life, and AQP4-IgG seropositivity in 73.5%. The diagnosis of NMOSD was established in 37.5% of LETM patients according to AQP4-IgG positivity and in 5% of LETM patients if the AQP4-IgG result was unknown. The characteristics of this series are similar to those of other Western populations. The AQP4-IgG testing assists in the diagnosis of NMOSD.

Neuromyelitis optica: Association with paroxysmal painful tonic spasms

IntroductionParoxysmal painful tonic spasms (PPTS) were initially described in multiple sclerosis (MS) but they are more frequent in neuromyelitis optica (NMO). The objective is to report their presence in a series of cases of NMO and NMO spectrum disorders (NMOSD), as well as to determine their frequency and clinical features. Patients and methodsWe conducted a retrospective assessment of medical histories of NMO/NMOSD patients treated in 2 hospitals in Buenos Aires (Hospital Durand and Hospital Álvarez) between 2009 and 2013. ResultsOut of 15 patients with NMOSD (7 with definite NMO and 8 with limited NMO), 4 presented PPTS (26.66%). PPTS frequency in the definite NMO group was 57.14% (4/7). Of the 9 patients with longitudinally extensive transverse myelitis (LETM), 44.44% (9/15) presented PPTS. Mean age was 35 years (range, 22-38 years) and all patients were women. Mean time between NMO diagnosis and PPTS onset was 7 months (range, 1-29 months) and mean time from last relapse of LETM was 30 days (range 23-40 days). LETM (75% cervicothoracic and 25% thoracic) was observed by magnetic resonance imaging (MRI) in all patients. Control over spasms and pain was achieved in all patients with carbamazepine (associated with gabapentin in one case). No favourable responses to pregabalin, gabapentin, or phenytoin were reported. ConclusionsPPTS are frequent in NMO. Mean time of PPTS onset is approximately one month after an LETM relapse, with extensive cervicothoracic lesions appearing on the MRI scan. They show an excellent response to carbamazepine but little or no response to pregabalin and gabapentin. Prospective studies with larger numbers of patients are necessary in order to confirm these results.

Pediatric acquired CNS demyelinating syndromes: Features associated with multiple sclerosis.

Approximately one-third of children with an acquired demyelinating syndrome (ADS) will be diagnosed with multiple sclerosis (MS), either at onset according to the 2010 McDonald criteria, or on the basis of clinical or MRI evidence of relapsing disease, in the majority of patients within 2-4 years. ADS in adolescents, female patients, and patients with polyfocal deficits is associated with the highest likelihood of MS, while children with acute disseminated encephalomyelitis, those with documented preceding infection, and ADS presentation in young children more commonly portends a monophasic outcome. While pediatric MS associates with similar genetic risk alleles as have been documented in adult-onset MS, such associations are not diagnostically valuable at the individual level. The presence of antibodies directed against aquaporin-4 strongly supports a diagnosis of neuromyelitis optica, and should be assayed in children manifesting with severe optic neuritis, longitudinally extensive myelitis, or brainstem/hypothalamic syndromes. Further research will determine whether other antibody signatures are indicative of relapsing demyelination distinct from MS.

Espectro de neuromielitis óptica en Colombia, primera caracterización clínico imagenológica en tres centros de Bogotá

Introducción: La neuromielitis óptica, es un síndrome clínico caracterizado por la asociación de mielitis transversa y neuritis óptica, hoy en día es reconocida como una enfermedad cuya fisiopatología, clínica, hallazgos en imágenes diagnósticas de laboratorio y tratamiento son específicos.
 Objetivo: describir las características clínicas, métodos diagnósticos y tratamiento de los pacientes con neuromielitis óptica (NMO) en tres centros asistenciales de cuarto nivel de la ciudad de Bogotá.
 Materiales y métodos: Diseño: se realizó un estudio de tipo serie de casos. Participantes: se incluyeron casos consecutivos de pacientes de cualquier género, entre los 19 y los 48 años, clasificados en dos grupos según los criterios del Consenso Internacional para el Diagnóstico de Neuromielitis óptica 2015, NMOSD con AQP4-IgG positivos, y NMOSD con AQP4-IgG negativos. Los pacientes fueron reclutados en tres centros hospitalarios, desde junio de 2013 a mayo de 2015. Análisis estadístico: la descripción de las variables se realizó por frecuencias absolutas y relativas, los análisis se realizaron en el paquete estadístico STATA 13®.
 Resultados: participaron 22 pacientes, con una edad mediana de 36 años, la mayoría mujeres, la mediana de inicio de síntomas fue de 31 años (RIC 24-39). La técnica para el diagnóstico más utilizada fue IFI, la clínica más frecuente del evento inicial fue mielitis y de neuritis óptica en las recaídas posteriores, la mitad de los pacientes presentaron dos o menos eventos, ningún paciente cumplió criterios para otra enfermedad sistémica. Se observaron escalas de discapacidad mas altas en el grupo con AQP4 positivos, y mas bajas en los que recibieron corticoide al inicio.
 Discusión y conclusiones: esta caracterización constituye la primera descripción de esta enfermedad en Colombia, nuestros hallazgos son similares a los obtenidos en otras poblaciones, algunos datos relevantes requieren más estudios.

Structural Alterations of Segmented Macular Inner Layers in Aquaporin4-Antibody-Positive Optic Neuritis Patients in a Chinese Population.

ObjectivesThis study aimed to analyse the structural injury of the peripapillary retinal nerve fibre layer (pRNFL) and segmented macular layers in optic neuritis (ON) in aquaporin4-antibody (AQP4-Ab) seropositivity(AQP4-Ab-positiveON) patients and in AQP4-Ab seronegativity (AQP4-Ab-negative ON) patients in order to evaluate their correlations with the best-corrected visual acuity (BCVA) and the value of the early diagnosis of neuromyelitis optica (NMO).DesignThis is a retrospective, cross-sectional and control observational study.MethodsIn total, 213 ON patients (291 eyes) and 50 healthy controls (HC) (100 eyes) were recruited in this study. According to a serum AQP4-Ab assay, 98 ON patients (132 eyes) were grouped as AQP4-Ab-positive ON and 115 ON patients (159 eyes) were grouped as AQP4-Ab-negative ON cohorts. All subjects underwent scanning with spectralis optical coherence tomography (OCT) and BCVA tests. pRNFL and segmented macular layer measurements were analysed.ResultsThe pRNFL thickness in AQP4-Ab-positive ON eyes showed a more serious loss during 0–2 months (-27.61μm versus -14.47 μm) and ≥6 months (-57.91μm versus -47.19μm) when compared with AQP4-Ab-negative ON eyes. AQP4-Ab-positive ON preferentially damaged the nasal lateral pRNFL. The alterations in the macular ganglion cell layer plus the inner plexiform layer (GCIP) in AQP4-Ab-positive ON eyes were similar to those in AQP4-Ab-negative ON eyes. AQP4-Ab-positive ON eyes had entirely different injury patterns in the inner nuclear layer (INL) compared with AQP4-Ab-negative ON eyes during the first 6 months after the initial ON attack. These differences were as follows: the INL volume of AQP4-Ab-positive ON eyes had a gradual growing trend compared with AQP4-Ab-negative ON eyes, and it increased rapidly during 0–2 months, reached its peak during 2–4 months, and then decreased gradually. The pRNFL and GCIP in AQP4-Ab-positive ON eyes had positive correlations with BCVA. When the pRNFL thickness decreased to 95%CI (50.77μmto 60.85μm) or when the GCIP volume decreased to 95%CI (1.288 mm3to 1.399 mm3), BCVA began to be irreversibly damaged.ConclusionThe structural alterations of pRNFL and GCIP could indicate the resulting visual damage. In addition, the injury pattern of INL could be a potential structural marker to predict the conversion of ON to NMO.

Longitudinally extensive transverse myelitis: A retrospective analysis of sixty-four patients at tertiary care center of North-West India

ObjectivesTo evaluate the demographic profile, clinical presentations, laboratory parameters and etiologies of longitudinally extensive transverse myelitis (LETM) patients in Indian population. Patients and methodsLETM is characterized by contiguous inflammatory lesions of spinal cord extending to three or more vertebral segments. Neuromyelitis optica (NMO) is the most common cause of LETM. In clinical practice, both LETM and NMO are thought to be synonymous with each other because of their very frequent association. Other causes of LETM are infective, neoplastic, autoimmune diseases and connective tissue disorders. All other causes should be ruled out before making the diagnosis of NMO in LETM patients. We conducted a retrospective study from August 2010 to February 2016 and analyzed various demographic profile, clinical presentations, laboratory parameters and etiologies in sixty-four patients of LETM. ResultsIn our series, majority of the patients presented with acute bladder dysfunction and paraparesis. Twenty-one patients (32.81%) were clinically diagnosed as NMO, out of which thirteen patients were found to have positive serum NMO antibody. Other etiologies of LETM in our series were multiple sclerosis [9 patients], acute disseminated encephalomyelitis (ADEM) [6 patients], postinfectious [5 patient], subacute combined degeneration (SCD) [4 patient], tuberculous myelitis [4 patients], spinal arteriovenous malformation (AVM) [3 patient] and systemic lupus erythematosus (SLE) [3 patient], respectively. In nine patients, cause could not be ascribed despite thorough investigations. ConclusionLETM is a heterogeneous disorder with a varied clinical feature, etiologies and outcome. Even the LETM patients who presented with optic neuritis do not necessarily have NMO. Therefore, the diagnosis of NMO should be made only after excluding other causes of LETM. The presence of NMO-Ab (Aquaporin 4-Ab) predicts the increased risk of recurrence of LETM or conversion to NMO.

Intractable Hiccups and Nausea as a Principal Symptom of Neuromyelitis Optica in a Patient with a Prior History of Miller‐Fisher Syndrome

Nausea is a common symptom and usually suggests a gastrointestinal disease rather than rare and severe neurological disorders such as neuromyelitis optica (NMO). A 69‐year‐old female with a prior history of Miller–Fisher syndrome presented with unremitting vomiting and hiccups. She was diagnosed with gastroenteritis over multiple visits to our hospital. However, she developed right‐sided vision loss and bilateral lower extremity weakness. Magnetic resonance imaging of her spinal cord showed a lesion extending from T4 to L4, indicating transverse myelitis, and another lesion in the right ophthalmic nerve. Aquaporin‐4 antibody testing was positive. A definitive diagnosis of NMO was made 23 days after the manifestation of her initial symptom however treatment produced only partial recovery of muscle weakness, and no recovery of her vision. It is important to make a timely diagnosis of NMO since specific treatment may be effective if provided at an earlier stage of the disease.

Pediatric familial neuromyelitis optica in two sisters with long term follow-up

Neuromyelitis optica causes bilateral optic neuritis and longitudinal extensive transverse myelitis. Although usually sporadic, 3% of cases of neuromyelitis optica are familial. The interval over which attacks continue and the long term prognosis for pediatric-onset neuromyelitis optica are not well defined. We describe two patients with pediatric familial neuromyelitis optica with the longest clinical follow-up of a pediatric case reported in the literature to our knowledge. One woman developed blindness with bilateral eye involvement within a few weeks at age 3. This was followed by transverse myelitis with paraparesis at age 19 leading to diagnosis of neuromyelitis optica. Her serum anti-aquaporin 4 antibody was later found to be positive. She continued with sporadic myelitis-related relapses but remained ambulant until age 40 when she had a more severe relapse. There was evidence of longitudinal extensive T2 hyperintensity in the thoracic spinal cord. Her sister also developed blindness at age 3.5 followed by myelitis 1year later with multiple relapses of gait impairment until her death from pneumonia at age 21. These patients represent the rare occurrence of neuromyelitis optica in children within the same family and show that this disease can have prolonged periods of remission but a continued tendency to relapse, supporting the need for lifelong immunosuppression.

Linear lesions may assist early diagnosis of neuromyelitis optica and longitudinally extensive transverse myelitis, two subtypes of NMOSD

Purpose: To investigate the relationship between linear lesions (LL) and the development of longitudinally extensive spinal cord lesions (LESCL) in Chinese patients with neuromyelitis optica or longitudinally extensive transverse myelitis.Method: The clinical records of 143 patients with these conditions were reviewed. Forty-one patients with LL were divided into three groups according to the order of appearance of LL and LESCL (simultaneously [n=10], LL first [n=26], or LESCL first [n=5]). The remaining 102 patients without LL were used as a control group.Results: Patients who developed LL first demonstrated a lower annualized relapse rate than those in the simultaneous group (1.00 [0.23–10.00] vs. 4.38 [0.60–6.67], p=0.017) and the control group (1.00 [0.23–10.00] vs. 2.00 [0.24–10.00], p=0.007). Among all patients with LL, there were significantly more who developed them before LESCL than those who developed them after LESCL (p<0.001) or at the same time (p=0.008). The mean time before the appearance of LESCL was 9.0months (2–35months) in the ‘LL-first’ group, which was shorter than that in the control group (12months [1–60months], p=0.010). The rate of positivity for anti-aquaporin 4 IgG antibodies was higher in patients with LL compared with controls (90.24% vs. 64.71%, p=0.002).Conclusion: LL may be a precursor to LESCL and assist early diagnosis of neuromyelitis optica and longitudinally extensive transverse myelitis.

Detection of aquaporin-4 antibody using aquaporin-4 extracellular loop-based carbon nanotube biosensor for the diagnosis of neuromyelitis optica

Here we propose a carbon nanotube (CNT) field-effect transistor (FET) functionalized with aquaporin-4 (AQP4) extracellular loop peptides for the rapid detection of AQP4 antibody without pretreatment. Neuromyelitis optica (NMO) is a rare disease of the central nerve system that affects the optic nerves and the spinal cord. NMO-IgG, a serum antibody in patients, is highly specific for NMO and targets AQP4. We synthesized AQP4 extracellular loop peptides, known as primary autoimmune target in NMO, and immobilized them onto CNT-FET. The sensor showed p-type FET characteristics after the functionalization of peptides. The sensor was able to detect antibody with a detection limit of 1ngl−1. Moreover, AQP4 antibody in human serum was detected without any pretreatment. These results indicate that the biosensor can be used for rapid and simple detection of NMO antibody.

Treatment of neuromyelitis optica.

Neuromyelitis optica (NMO) is an antibody-mediated inflammatory disease of the central nervous system with a predilection for the optic nerves, spinal cord and certain brain regions. It has a distinct pathogenesis relating to aquaporin-4 autoimmunity and complement-mediated injury. This knowledge has translated into targeted efforts to develop novel, disease-specific treatments. In this review, we discuss evidence supporting the use of currently available treatments for acute exacerbations and for long-term disease modification. We also discuss the risks and benefits of available and emerging immunotherapies. Early, accurate diagnosis of NMO with appropriate acute and long-term immunosuppressive treatment is of prime importance for the prevention of disability associated with this disease. Standard measures for the management of acute exacerbations include intravenous methylprednisolone and plasmapheresis. First-line, long-term immunotherapies for NMO include azathioprine, mycophenolate mofetil and rituximab. Three randomized controlled treatment trials evaluating these agents are currently being conducted. In addition, there are numerous emerging therapies that are based upon current understanding of the disease immunopathogenesis. NMO is an autoimmune disease that is separate from multiple sclerosis. Better understanding of its antibody and complement-dependent pathophysiology has proven to be critical for the formulation of current and future treatment strategies.

Update on biomarkers in neuromyelitis optica.

Neuromyelitis optica (NMO) (and NMO spectrum disorder) is an autoimmune inflammatory disease of the CNS primarily affecting spinal cord and optic nerves. Reliable and sensitive biomarkers for onset, relapse, and progression in NMO are urgently needed because of the heterogeneous clinical presentation, severity of neurologic disability following relapses, and variability of therapeutic response. Detecting aquaporin-4 (AQP4) antibodies (AQP4-IgG or NMO-IgG) in serum supports the diagnosis of seropositive NMO. However, whether AQP4-IgG levels correlate with disease activity, severity, response to therapy, or long-term outcomes is unclear. Moreover, biomarkers for patients with seronegative NMO have yet to be defined and validated. Collaborative international studies hold great promise for establishing and validating biomarkers that are useful in therapeutic trials and clinical management. In this review, we discuss known and potential biomarkers for NMO.

International consensus diagnostic criteria for neuromyelitis optica spectrum disorders

Neuromyelitis optica (NMO) is an inflammatory CNS syndrome distinct from multiple sclerosis (MS) that is associated with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). Prior NMO diagnostic criteria required optic nerve and spinal cord involvement but more restricted or more extensive CNS involvement may occur. The International Panel for NMO Diagnosis (IPND) was convened to develop revised diagnostic criteria using systematic literature reviews and electronic surveys to facilitate consensus. The new nomenclature defines the unifying term NMO spectrum disorders (NMOSD), which is stratified further by serologic testing (NMOSD with or without AQP4-IgG). The core clinical characteristics required for patients with NMOSD with AQP4-IgG include clinical syndromes or MRI findings related to optic nerve, spinal cord, area postrema, other brainstem, diencephalic, or cerebral presentations. More stringent clinical criteria, with additional neuroimaging findings, are required for diagnosis of NMOSD without AQP4-IgG or when serologic testing is unavailable. The IPND also proposed validation strategies and achieved consensus on pediatric NMOSD diagnosis and the concepts of monophasic NMOSD and opticospinal MS.

Longitudinally extensive transverse myelitis in neuromyelitis optica: a prospective study of 13 Caucasian patients and literature review.

Neuromyelitis optica (NMO) is a homogenous disease that can be diagnosed by an association of clinical, neuroimaging and serological aspects. We analysed our 4 years NMO series with longitudinally extensive transverse myelitis (LETM) during the disease course. We included consecutive adult Caucasian patients who were diagnosed with definite NMO, or cases of NMO-IgG seropositive LETM considered as limited forms of NMO. Patients included were negative for other diseases (autoimmune, infectious, etc.). We report the Expanded Disability Status Scale (EDSS), brain and spine MRI, CSF, NMO-IgG, treatment, motor and visual outcome. Thirteen cases fulfilled the inclusion criteria, and the mean follow-up period was 3.74 ± 1.8 years. The initial motor deficit was severe with the mean value of motor functional parameter of 4.46 ± 1 and improved at discharge to 2.53 ± 1.4 (p < 0.001). With treatment, the outcome after LETM attack was good in 10 patients, with a significant improvement of the EDSS mainly upon motor deficit, while visual function had a very slight amelioration. The CSF analysis was normal in 8 cases; spinal MRI showed evidence of LETM in all patients while brain MRI was normal in 7. NMO-IgG is a biomarker for NMO that is of diagnostic value in cases of isolated LETM. LETM has a better outcome than ON in NMO Caucasians. Spinal MRI is essential for NMO diagnosis in the presence of LETM and the absence of multiple brain MRI lesions. Maintenance immunosuppressive therapy reduces the frequency of attacks.