Definite Neuromyelitis Optica Research Articles

Retinal segmented layers with strong aquaporin-4 expression suffered more injuries in neuromyelitis optica spectrum disorders compared with optic neuritis with aquaporin-4 antibody seronegativity detected by optical coherence tomography

PurposeTo evaluate retinal segmented layer alterations in optic neuritis (ON) in an AQP4-Ab seropositive (AQP4-Ab+/ON) cohort and in neuromyelitis optica (NMO) with ON eyes (NMO-ON) compared with an AQP4-Ab seronegative...

Accuracy of the Fluorescence-Activated Cell Sorting Assay for the Aquaporin-4 Antibody (AQP4-Ab): Comparison with the Commercial AQP4-Ab Assay Kit.

BackgroundThe aquaporin-4 antibody (AQP4-Ab) is a disease-specific autoantibody to neuromyelitis optica (NMO). We aimed to evaluate the accuracy of the FACS assay in detecting the AQP4-Ab compared with the commercial cell-based assay (C-CBA) kit.MethodsHuman embryonic kidney-293 cells were transfected with human aquaporin-4 (M23) cDNA. The optimal cut off values of FACS assay was tested using 1123 serum samples from patients with clinically definite NMO, those at high risk for NMO, patients with multiple sclerosis, patients with other idiopathic inflammatory demyelinating diseases, and negative controls. The accuracy of FACS assay and C-CBA were compared in consecutive 225 samples that were collected between January 2014 and June 2014.ResultsWith a cut-off value of MFIi of 3.5 and MFIr of 2.0, the receiver operating characteristic curve for the FACS assay showed an area under the curve of 0.876. Among 225 consecutive sera, the FACS assay and C-CBA had a sensitivity of 77.3% and 69.7%, respectively, in differentiating the sera of definite NMO patients from sera of controls without IDD or of MS. Both assay had a good specificity of 100% in it. The overall positivity of the C-CBA among FACS-positive sera was 81.5%; moreover, its positivity was low as 50% among FACS-positive sera with relatively low MFIis.ConclusionsBoth the FACS assay and C-CBA are sensitive and highly specific assays in detecting AQP4-Ab. However, in some sera with relatively low antibody titer, FACS-assay can be a more sensitive assay option. In real practice, complementary use of FACS assay and C-CBA will benefit the diagnosis of NMO patients, because the former can be more sensitive among low titer sera and the latter are easier to use therefore can be widely used.

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.

How long does it take to diagnose patients with neuromyelitis optica (NMO) using the 2006 diagnostic criteria?

Background and purposeA few reports studied the time use to diagnose patient with neuromyelitis optica (NMO). The Aim of the study is to evaluate the interval from disease onset to the time when patients fulfilled the NMO diagnostic criteria 2006 in Thai. Method: A retrospective study of the NMO patients visiting the MS clinic and related disorders at Siriraj hospital was reviewed. Results: There were 42 definite NMO. All were female. The most common first presentations were optic neuritis (ON) (45.2%), transverse myelitis (TM) (35.7%), ON and TM (9.5%) and brainstem symptoms (9.5%), respectively. The mean age at onset of their ON and TM attack was 33.4 and 38.4 years, respectively. Anti-AQP4 antibody was presented in 82% using cell based assay. For those presented with ON, 7.1% reported painful eye movements and 33.3% had bilateral involvement. Brain MRI not compatible with MS was found in 94.87%. In who presented with TM, 87.8% revealed long extensive transverse myelitis (LETM) in spinal MRI. The presence of CSF-oligoclonal band (CSF-OCB) was found in 14.6%. Our NMO patients had the average number of the attack of 1.5 times before the diagnosis could be made. Nearly fifty-five percent of NMO patients fulfilled the NMO diagnostic criteria 2006 within 1 year after disease onset and 90.5% within 5 years Conclusion: About half of Thai patients with definite NMO were diagnosed within 1 year and approximately 90% within 5 years from their disease onset.

The correlation factor analysis for conversion of clinically isolated syndrome to multiple sclerosis and neuromyelitis optica

To analyze the features of patients who converted from clinically isolated syndrome (CIS) to multiple sclerosis (MS) and neuromyelitis optica (NMO) and explore the correlated factors. A total of 151 patients admitted in our unit as CIS from January 2009 to December 2014 were enrolled in the study. All patients were divided into the following four groups by locations of the initial lesion, which were the spinal cord, the optic nerve, the brain stem and the multifocal lesions. Data were collected at the baseline including demographics, expanded disability status scale (EDSS) score, site of CIS, presence or absence of cerebrospinal fluid (CSF) oligoclonal bands (OB) and serum aquaporin-4 antibody (AQP4-Ab), evoked potential (EP) and MRI lesions. The conversion rates from CIS to clinically definite MS or NMO were calculated and the correlated factors were explored. With a mean follow-up period of (44.11±17.62)months, 46/151(30.5%) patients converted to MS, 28/151 (18.5%) to definite NMO and 66/151 patients(43.7%)remained as CIS. Other patients were converted to optic neuritis(4/151), one-time transverse myelitis(3/151), acute disseminated encephalomyelitis (1/151) and Balo concentric sclerosis(3/151) . The EDSS score was significantly higher in patients converted to NMO than those converted to MS (P=0.003). The initial manifestation of optic neuritis significantly correlated with the conversion to NMO (P=0.000), while the initial manifestation of CIS with multifocal lesions significantly correlated with the conversion to MS (P=0.000). Neither the isolated BAEP (P=0.703), VEP (P=0.076), SEP (P=0.915) nor the combination of two (P=0.546)or three (P=1.000) of the above parameters could help to distinguish the conversion to MS or NMO. More patients with positive CSF-OB converted to MS (P=0.001), while more patients with positive serum AQP4-Ab converted to NMO (P=0.001). More patients were serum AQP4-Ab positive in those converted to NMO than those converted to MS (P=0.000). Lesions longer than three vertebral segments were dominant in patients converted to NMO (P=0.000). The logistic regression analysis revealed that factors correlated with conversion from CIS to MS were the initial CIS manifestation of multifocal lesions (OR=4.775, P=0.002), positive CSF-OB (OR=7.794, P=0.002) and VEP abnormality (OR=7.251, P=0.001). Factors correlated with conversion from CIS to NMO were female in gender (OR=12.536, P=0.019), positive serum AQP4-Ab (OR=36.410, P=0.002), lesions longer than three vertebral segments (OR=93.602, P=0.001), abnormal VEP and SEP (OR=18.448, P=0.002; OR=12.731, P=0.016). Factors correlated with the conversion from CIS to MS are initial CIS manifestation of multifocal lesions, positive CSF-OB and abnormal VEP, while those correlated with the conversion from CIS to NMO are female in gender, positive serum AQP4-Ab, initial CIS manifestation with optic nerve, lesions involved more than three vertebral segments and abnormal VEP and SEP.

T-cell responses to distinct AQP4 peptides in patients with neuromyelitis optica (NMO)

BackgroundAlthough antibodies to aquaporin-4(AQP4) are strongly associated with Neuromyelitis optica (NMO), the sole transfer of these antibodies is not sufficient to induce an NMO-like disease in experimental animals and T-cells and complement are also needed. Initial data indicating the presence of T-cell responses to AQP4 in patients with NMO, have beeen recently reported. ObjectiveTo evaluate the T-cell responses to specific AQP4 peptides/epitopes in patients with NMO and multiple sclerosis (MS). MethodsPeripheral blood mononuclear cells (PBMCs) were obtained from 14 patients fulfilling the criteria for definite NMO and the proliferation responses to one of 15 distinct pentadecapeptides of AQP4, spanning the whole protein (except of its transmembrane parts) were tested by a standard [H3]-thymidine uptake assay and compared with those of 9 healthy controls and 7 MS patients. A cytometric bead array assay (CBA) and flow cytometry were used to evaluate cytokine (IFNγ, IL17, IL2, IL4, IL5, IL10 and TNFα) and chemokine (CXCL8, CCL5, CXCL10, CXCL9, CCL2) secretion by PHA-stimulated PBMCs and AQP4-specific T-cell lines. ResultsFour main immunodominant epitopes of the AQP4 protein (p137–151, p222–236, p217–231 and the p269–283) were identified in the NMO group. The first two epitopes (assigned as peptides 3 and 9) showed the highest sensitivity (~60% positivity), whereas the latter two (assigned as peptides 8 and 11), the higher specificity. Longitudinal follow up of 5 patients revealed changes in the epitope-specificities during the course of NMO. T-cell lines specific for the AQP4 peptides, produced from NMO patients (but not healthy donors) secreted mainly IL-17 and IL-10 and less IFNγ. ConclusionsOur findings indicate that T-cells bearing characteristics of both Th1 and Th17 T-cells and targeting specific immunodominant epitopes of the AQP4 protein might be involved in the pathogenesis of NMO.

Antibodies to MOG in adults with inflammatory demyelinating disease of the CNS.

Objective:To evaluate the clinical relevance of myelin oligodendrocyte glycoprotein antibody (MOG-Ab) in a cohort of adults with inflammatory demyelinating disease (IDD) of the CNS.Methods:Live cell-based assays for MOG-Ab (IgG1 subset) and antibody to aquaporin-4 (AQP4-Ab) were performed in a cohort of 270 adult patients with IDD and 72 controls. Patients were first grouped by positive antibody result as MOG-Ab or AQP4-Ab, and the remainder were grouped by published diagnostic criteria.Results:Seventeen patients with IDD (6.3%) had MOG-Abs and 49 patients (18.1%) had AQP4-Abs; none had both antibodies. The MOG-Ab patients predominantly manifested with isolated symptoms of optic neuritis (83%). One-third of these patients experienced relapses, which involved only the optic nerve, and all relapsed within 1 year of disease onset. At onset, MRI in the MOG-Ab group uniquely demonstrated perineural enhancement, extending to the soft tissues around the optic nerves (33%). Although about 30% of MOG-Ab patients had brain MRI lesions, they had fewer periventricular lesions than the 26 patients with relapsing-remitting multiple sclerosis (MS); none of these lesions were ovoid or perpendicular to the ventricle. Moreover, MOG-Ab patients did not meet the diagnostic criteria for definite neuromyelitis optica (NMO) and had less spinal cord involvement than the AQP4-Ab group. Four patients (23.5%) had poor visual outcomes (<0.2) or paraplegia.Conclusions:MOG-Abs may be a disease-specific biomarker in adult patients with IDD who have a disease distinct from NMO or MS. The radiologic as well as clinical manifestations of MOG-Ab patients can be useful in their differential diagnosis.

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.

Neuromyelitis optica phenotype associated with therapy-responsive acute peripheral neuropathy.

A 51-year-old Hispanic woman with a history of Churg-Strauss syndrome (in remission for 20 years)–associated mesangial glomerulonephritis and end-stage renal disease with a recent renal transplant and previously cured cytomegalovirus (CMV) infection who was on a tapering dose of tacrolimus presented with sudden onset of lower extremity numbness. Symptoms progressed to complete paraplegia and sensory loss over 24 hours. The following day, ascending paresis extended to bilateral upper extremities, with high thoracic sensory level and complete blindness. Initial MRI revealed contrast enhancement of bilateral prechiasmatic optic nerve as well as T2 hyperintensities involving the central gray matter of the entire spinal cord with associated edema. CSF analysis documented neutrophilic pleocytosis (182 neutrophils per mm3) and increased total protein level (142 mg/dL) without oligoclonal banding. Bacterial, fungal, and mycobacterial cultures from the CSF were negative, as was PCR for CMV, Epstein-Barr virus, herpes simplex virus, human herpesvirus 6, and varicella-zoster virus. Serologic autoimmune assessment, including onconeuronal, anti-neutrophil cytoplasmic antibody, and other rheumatologic, Lyme, and aquaporin-4 (AQP4) antibody testing, was negative. Moreover, testing for sarcoidosis and HIV antibody was unrevealing. Nerve conduction studies (NCS) performed 2 weeks after symptom onset documented severe reduction in compound motor action potential amplitudes (worse in the lower extremities), <10% slowing of distal latencies but not conduction velocities, and mildly slowed upper extremity f-wave latencies. Sensory nerve action potentials were pathologically reduced in the lower extremities (table). Needle examination (EMG) showed active, severe denervation changes in lower extremity muscles and less severe changes in upper extremity muscles. Subsequent GM1, GM2, GD1a, GD1b, and GQ1b ganglioside antibody testing was negative. The patient was diagnosed with concurrent clinically definite neuromyelitis optica (NMO) phenotype1 and acute axonal polyradiculoneuropathy with primarily axonal features.

Neuromielitis óptica: asociación con espasmos tónicos paroxísticos dolorosos

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.

Therapy of NMO spectrum disorders.

Neuromyelitis optica (NMO) is an autoimmune demyelinating condition of the central nervous system often associated with aquaporin-4 (AQP4) autoantibodies manifesting as severe optic neuritis and long segment myelitis with tendency to relapse. Seronegative patients and who do not meet the NMO criteria are classified as having NMO Spectrum Disorder (NMOSD), but are treated identically to clinically definite NMO. Acute relapse is treated with intravenous methylprednisolone for 5 days with or without subsequent treatment with plasma exchange (PE). This must be followed by oral steroid to prevent rebound worsening and further relapse. For relapse prevention, immunosuppressive agents that have been found to be effective are azathioprine, rituximab, mycophenolate mofetil, methotrexate, and mitoxantrone; although none of which have been validated in randomized, controlled trial. Some patients do relapse with monotherapy, and switching to more effective agent or use of combination therapy is beneficial in such situation. There is no consensus about the duration of preventive therapy, but generally 2-3 years of relapse-free period is considered the minimum, taking into account the risks of long-term toxicity of these agents.

Characterization of the spectrum of Korean inflammatory demyelinating diseases according to the diagnostic criteria and AQP4-Ab status.

BackgroundThe relative frequencies of demyelinating diseases among Korean patients with idiopathic inflammatory demyelinating disease of the central nervous system (IIDD) have not been sufficiently studied. We therefore describe a cohort of 203 patients with IIDD from three centers in Korea whose syndromes were identified precisely according to international clinical criteria and autoantibody to aquaporin 4 (AQP4-Ab) status.MethodsIn total, 260 consecutive patients were screened and 203 were included from three hospitals in Korea. All were tested for AQP4-Ab by using a cell-based assay. Patients who met the criteria for definite neuromyelitis optica (NMO) or had a positive AQP4-Ab test result were defined as the NMO group. Among the others, patients were assessed if they had acute disseminated encephalomyelitis, multiple sclerosis (MS), acute transverse myelitis, optic neuritis, or other demyelinating disease as a clinically isolated syndrome of the brain.ResultsEighteen percent of patients were classified as the NMO group, 2% as acute disseminated encephalomyelitis, 18% as MS, 41% as acute transverse myelitis, 11% as optic neuritis, and 8% as other clinically isolated syndrome of the brain. AQP4-Ab was positive in 18% of patients and the relative frequency of NMO to MS (NMO/MS ratio) was 1.06. The mean duration of follow up in our patients was 64 months.ConclusionsAmong Korean patients with idiopathic inflammatory demyelinating diseases, the incidence of NMO may be similar to that of MS, and the overall positivity of AQP4-Ab could be lower than previously reported. In addition, acute transverse myelitis that is not associated with MS or NMO can be relatively common in these patients. Further population-based studies with AQP4-Ab are needed to determine the exact incidence of NMO and other idiopathic inflammatory demyelinating diseases in Korea.

An Optimized Immunohistochemistry Technique Improves NMO-IgG Detection: Study Comparison with Cell-Based Assays

Cell-based assays (CBA) have increased the sensitivity of the neuromyelitis optica (NMO)-IgG/aquaporin-4-antibody detection compared to classical tissue-based indirect assays. We describe the sensitivity of an optimized immunohistochemistry (IHC-o) to detect NMO-IgG/aquaporin-4-antibody in comparison with that of two CBA: an in-house (CBA-ih) and a commercial (CBA-c) assay (Euroimmun, Germany). Coded serum from 103 patients with definite NMO and 122 inflammatory controls were studied by IHC-o, CBA-ih, and CBA-c. IHC-o used the same protocol described to detect antibodies against cell surface antigens. CBA-ih used live cells transfected with the aquaporin-4-M23-isoform. The sensitivity of the IHC-o was 74.8% (95% confidence interval [CI] 65-83) and was similar to that of the CBA-ih 75.7% (95% CI 66-84) and the CBA-c 73.8% (95% CI 64-82). The specificity of the three assays was 100% (95% CI 97-100). Interassay concordance was high, 100 of 103 samples were coincident in all techniques. The optimized immunohistochemistry proves to be as sensitive and specific as the cell-based assays. This assay extends the available tools for NMO-IgG/aquaporin-4-antibody detection.

Visual evoked potentials in neuromyelitis optica and its spectrum disorders

Optic neuritis (ON) is a key feature of neuromyelitis optica (NMO). Recently, NMO patients of predominantly Afro-Brazilian origin were evaluated by visual evoked potentials (VEPs) and showed marked amplitude reductions. Here, we analyzed VEPs in a predominantly Caucasian cohort, consisting of 43 patients with definite NMO, 18 with anti-aquaporin (AQP) 4 antibody-seropositive NMO spectrum disorders and 61 matched healthy controls. We found reduced amplitudes in only 12.3%, prolonged latencies in 41.9% and a lack of response in 14.0% of NMO eyes. Delayed P100 latencies in eyes without prior ON suggested this was a subclinical affection. The data indicate heterogenous patterns in NMO, warranting further investigation.

Anti-Aquaporin-4 Antibody Positivity in Neuromyelitis Optica Is Associated with Lesion Activity

Aims: To assess the demographic, clinical and spinal cord MRI characteristics of clinically definite neuromyelitis optica (NMO) patients for association with anti-aquaporin-4 (AQP4) antibody positivity in Chinese patients. Methods: We recruited 72 consecutive patients with NMO. The clinical assessments, sera and spinal MRI scans were obtained within 1 week after the onset of symptoms of acute myelitis. The statistical significance of potential differences in demographic, clinical and spinal MRI lesion characteristics between the two groups (anti-AQP4 antibody positive vs. negative) was determined using the two-sample t test or Fisher's exact test. Results: Forty-nine patients (49/72, 68.1%) were anti-AQP4 antibody positive and 23 patients (23/72, 31.9%) were anti-AQP4 antibody negative. The only characteristic that was significantly different between the groups was the presence of an enhancing spinal cord lesion (p < 0.001). Conclusion: We found a strong association between serum anti-AQP4 antibody positivity and lesional gadolinium enhancement in patients with clinically definite NMO. These findings support prior evidence that anti-AQP4 antibody could be pathogenic in NMO lesion development.

Modifications of longitudinally extensive transverse myelitis and brainstem lesions in the course of neuromyelitis optica (NMO): a population-based, descriptive study

BackgroundNeuromyelitis optica (NMO) includes transverse myelitis, optic neuritis and brain lesions. Recent studies have indicated that the brainstem is an important site of attack in NMO. Longitudinally extensive transverse myelitis (LETM) is an important component of the clinical diagnosis of NMO. The frequency of brainstem and LETM lesions, changes over time of LETM and the clinical consequences in the course of NMO have only been sparsely studied.MethodsThe study was a population-based retrospective case series with clinical and magnetic resonance imaging (MRI) follow-up of 35 patients with definite NMO and a relapsing-remitting course.ResultsBrainstem lesions were observed in 25 patients, 18 in medulla oblongata (11 in area postrema). Lesions in the pons, mesencephalon and diencephalon occurred in 10, 7 and 7 patients, respectively. Lesions were symptomatic in medulla oblongata and pons, asymptomatic in mesencephalon and diencephalon. Brainstem lesions were observed significantly more often in anti-aquaporin-4 (AQP-4) antibody positive than in seronegative patients (p < 0.002).LETM was demonstrated by MRI of the spinal cord in 30/36 patients, 23/30 of whom had follow-up MRI of the spinal cord. Recurrent LETM was observed in five patients. In nine patients the LETM changed into multiple lesions during remission or treatment. Spinal cord atrophy was observed in 12/23 (52%) patients, correlating to Expanded Disability Status Scale (r = 0.88, p < 0.001).ConclusionsNMO patients had frequent occurrence of brainstem lesions and LETM. Brainstem lesions were associated with anti-AQP4 antibody positivity. LETM lesions differentiated over time and the outcome included relapses, fragmentation and atrophy. Correlation was observed between spinal cord atrophy and neurological disability.

Two patients with neuromyelitis optica but contrasting clinical courses

Neuromyelitis optica (NMO) is an idiopathic, relapsing, demyelinating disease of the central nervous system that preferentially affects the optic nerve and spinal cord. Diagnostic criteria for definite NMO require optic neuritis, myelitis, and at least two of three supportive criteria: onset brain MRI non-diagnostic of MS; spinal cord lesion extending over 3 or more vertebral segments; or seropositive for NMO-IgG. We report two Sri Lankan patients who fulfil the above diagnostic criteria but have contrasting clinical courses over a 4-year follow-up period. The NMOIgG seropositive patient demonstrated a more severe, relapsing disease course whilst the seronegative patient did not relapse despite not being on long-term immunosuppressive therapy. Given that para-infectious NMO is often monophasic and seronegative, discerning guidelines in recommending maintenance immunosuppression in NMO is required particularly in settings where incriminatory infections are prevalent.

Persisting myelin oligodendrocyte glycoprotein antibodies in aquaporin-4 antibody negative pediatric neuromyelitis optica

Background: Recently we showed that antibodies to myelin oligodendrocyte glycoprotein (MOG) can be found in aquaporin-4 (AQP4)-immunoglobulin (IgG) seronegative pediatric and adult patients with definite and high-risk neuromyelitis optica (NMO). Objective: The purpose of this study was to describe the clinical characteristics and temporal dynamics of MOG-IgG in AQP4-IgG seronegative pediatric patients presenting with definite NMO. Methods: Children with definite NMO who were referred for further testing of serum antibodies for AQP4 and MOG with a cell-based assay were included in this study. Clinical disease course, cerebrospinal fluid and magnetic resonance imaging (MRI) studies of these patients were reviewed. Results: Between 2008 and 2012 eight children who fulfilled the diagnostic criteria of definite NMO were recruited. Two children with definite NMO tested positive for AQP4-IgG but were negative for MOG-IgG antibodies. Three children had an absence of AQP4-IgG and MOG-IgG antibodies. Three children with definite NMO had high titers of serum MOG-IgG antibodies (≥1: 160), but no AQP4-directed humoral immune response. Longitudinal analysis of serum samples of the latter three children showed persisting high MOG-IgG titers over time. Conclusion: Pediatric patients presenting with clinical symptoms and MRI findings highly suggestive of NMO but with high and persisting MOG-IgG antibody titers are most likely to represent a distinct subgroup of acute demyelinating diseases with important clinical and therapeutic implications.

Painful Tonic Spasm in Neuromyelitis Optica

To evaluate the diagnostic utility and clinical characteristics of painful tonic spasm (PTS) in neuromyelitis optica (NMO). Retrospective study. Two referral hospitals. Forty patients who had NMO spectrum disorder with anti-aquaporin 4 autoantibody or met the revised diagnostic criteria for definite NMO; 35 patients with multiple sclerosis; and 41 patients with idiopathic acute transverse myelitis without anti-aquaporin 4 antibody. The incidence and clinical characteristics of PTS in the different groups, diagnostic value of PTS in identifying patients with NMO, and predictors of PTS in NMO. The incidence of PTS was significantly higher in the patients with NMO (10 patients [25.0%]) than in those with multiple sclerosis (1 patient [2.9%]) or idiopathic acute transverse myelitis without anti-aquaporin 4 antibody (1 patient [2.4%]). Most PTS episodes (in 8 of 10 patients [80.0%]) in the NMO group occurred after a mean interval of 48.13 days from the onset of the first myelitis episode and were not accompanied by another demyelinating episode with its onset. Painful tonic spasm associated with myelitis had a specificity of 98.7% for identifying the NMO group. Myelitis at disease onset was a predictor of PTS in the NMO group (odds ratio = 6.545, presence vs absence). Painful tonic spasm is a common symptom in NMO. When associated with myelitis, it is relatively specific to patients with NMO and is most commonly observed during recovery from the first myelitis episode. Patients with NMO presenting with myelitis at disease onset appear to be at higher risk for developing PTS compared with other patients with NMO.

Neuromyelitis Optica

Neuromyelitis optica (NMO) is a disabling inflammatory condition that targets astrocytes in the optic nerves and spinal cord. Neuro-ophthalmologists must be particularly aware of this disorder because about half of patients present as isolated unilateral optic neuritis months or years before a disease-defining and often crippling bout of myelitis. NMO is easily confused with multiple sclerosis because it is characterized by relapses that lead to stepwise accrual of deficits. The best predictor of conversion from optic neuritis to clinical definite NMO is the presence of a serum antibody to aquaporin-4 called NMO-IgG. However, this test is currently only about 75% sensitive. Suspicion of NMO should be high in patients who present with vision of light perception or worse or who are left with acuity of 20/50 or worse after optic neuritis and in those with simultaneous bilateral optic neuritis or recurrent attacks. Acute NMO relapses are generally treated with high-dose intravenous steroids, with plasma exchange often used as a rescue therapy for those who do not respond. Preventative strategies against relapses currently use broad-spectrum or selective B-lymphocyte immune suppression, but their use is based on small, generally uncontrolled studies. Hopefully, the future will bring more sensitive tools for defining risk and predicting outcome, as well as more targeted and effective forms of therapy.