Treatment of MOG antibody associated disorders: results of an international survey.

INTRODUCTION: While monophasic and relapsing forms of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) are increasingly diagnosed world-wide, consensus on management is yet to be developed. OBJECTIVE: To survey the current global clinical practice of clinicians treating MOGAD. METHOD: Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February-April 2019). RESULTS: Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for ≥ 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after ≥ 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). In children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT. CONCLUSION: Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials.

Longitudinal changes in 18 F-THK5351 positron emission tomography in corticobasal syndrome.

BACKGROUND AND PURPOSE: Corticobasal syndrome (CBS) is pathologically characterized by tau deposits in neuronal and glial cells and by reactive astrogliosis. In several neurodegenerative disorders, 18 F-THK5351 has been observed to bind to reactive astrocytes expressing monoamine oxidase B. In this study, the aim was to investigate the progression of disease-related pathology in the brains of patients with CBS using positron emission tomography with 18 F-THK5351. METHODS: Baseline and 1-year follow-up imaging were acquired using magnetic resonance imaging and positron emission tomography with 18 F-THK5351 in 10 subjects: five patients with CBS and five age-matched normal controls (NCs). RESULTS: The 1-year follow-up scan images revealed that 18 F-THK5351 retention had significantly increased in the superior parietal gyrus of the patients with CBS compared with the NCs. The median increases in 18 F-THK5351 accumulation in the patients with CBS were 6.53% in the superior parietal gyrus, 4.34% in the precentral gyrus and 4.33% in the postcentral gyrus. In contrast, there was no significant increase in the regional 18 F-THK5351 retention in the NCs. CONCLUSIONS: Longitudinal increases in 18 F-THK5351 binding can be detected over a short interval in the cortical sites of patients with CBS. A monoamine oxidase B binding radiotracer could be useful in monitoring the progression of astrogliosis in CBS.

Complement-dependent and -independent aquaporin 4-antibody-mediated cytotoxicity in human astrocytes: Pathogenetic implications in neuromyelitis optica.

BACKGROUND: Neuromyelitis optica (NMO) is an inflammatory disease caused by the aquaporin (AQP)-4-antibody. Pathological studies on NMO have revealed extensive astrocytic damage, as evidenced by the loss of AQP4 and glial fibrillary acidic protein (GFAP), specifically in perivascular regions with immunoglobulin and complement depositions, although other pathological patterns, such as a loss of AQP4 without astrocyte destruction and clasmatodendrosis, have also been observed. Previous studies have shown that complement-dependent antibody-mediated astrocyte lysis is likely a major pathomechanism in NMO. However, there are also data to suggest antibody-mediated astrocyte dysfunction in the absence of complement. Thus, the importance of complement inhibitory proteins in complement-dependent AQP4-antibody-mediated astrocyte lysis in NMO is unclear. In most of the previous studies, the complement and target cells (astrocytes or AQP4-transfected cells) were derived from different species; however, the complement inhibitory proteins that are expressed on the cell surface cannot protect themselves against complement-dependent cytolysis unless the complements and complement inhibitory proteins are from the same species. To resolve these issues, we studied human astrocytes in primary culture treated with AQP4-antibody in the presence or absence of human complement and examined the effect of complement inhibitory proteins using small interfering RNA (siRNA). METHODS: Purified IgG (10 mg/mL) was obtained from 5 patients with AQP4-antibody-positive NMO, 3 patients with multiple sclerosis (MS), and 3 healthy controls. Confluent human astrocytes transfected with Venus-M1-AQP4-cDNA were incubated with IgG (5% volume). After washing, we cultured the cells with human complements with or without heat inactivation. We observed time-lapse morphological and immunohistochemical changes using a fluorescence microscope. We also evaluated cytotoxicity using a propidium iodide (PI) kit and the lactate dehydrogenase (LDH) assay. RESULT: AQP4-antibody alone caused clustering and degradation followed by endocytosis of membraneous AQP4, thereby resulting in decreased cellular adherence and the shrinkage of astrocytic processes. However, these changes were partially reversed by the removal of IgG in culture. In contrast, following the application of AQP4-antibody and non-heated human complements, the cell bodies and nuclei started to swell. At 3 h, most of the astrocytes had lost mobility and adherence and were eventually destroyed or had swollen and were then destroyed. In addition, the remaining adherent cells were mostly PI-positive, indicating necrosis. Astrocyte lysis caused by rabbit complement occurred much faster than did cell lysis with human complement. However, the cell lysis was significantly enhanced by the transfection of astrocytes with siRNA against human CD55 and CD59, which are major complement inhibitory proteins on the astrocyte membrane. AQP4-antibody-negative IgG in MS or control did not induce such changes. CONCLUSION: Taken together, these findings suggest that both complement-dependent and complement-independent AQP4-antibody-mediated astrocytopathies may operate in NMO, potentially contributing to diverse pathological patterns. Our results also suggest that the effect of complement inhibitory proteins should be considered when evaluating AQP4-antibody-mediated cytotoxicity in AQP4-expressing cells.

Multiple sclerosis in Japan appears to be a milder disease compared to the UK.

Multiple sclerosis (MS) is relatively common in the West, but rare in Japan. In the literature, there are few comparative data regarding disease severity throughout the world. The objective of this study was to compare disability in patients from a UK and a Japanese MS cohort. We retrospectively analysed the clinical features of patients with MS from a UK and Japanese MS centre. The Multiple Sclerosis Severity Score (MSSS), which adjusts the Expanded Disability Status Scale score according to disease duration, was used as a marker of disease severity. One thousand one hundred forty-eight UK patients and 104 Japanese patient were identified representing the relative national prevalence. Demographics and disease duration did not differ between the groups. Median MSSS was significantly different between the two groups (Japan 3.34 vs. UK 5.87, p < 0.001). Primary progressive MS was more common in the UK (12.9%) than in the Japanese cohort (3%, p = 0.044). The majority of Japanese patients (83.7% vs. UK 17%) had been exposed to disease modifying treatments (DMTs). Exposure to DMTs did not show a significant effect on disability. In conclusion, this study suggests that MS in Japan may be associated with less disability than in UK. More Japanese patients were treated with DMTs. Differences in treatments do not seem to explain the disparity in disability severity. This suggests either genetic or environmental influences on disease severity.

Features of anti-aquaporin 4 antibody-seronegative Thai patients with neuromyelitis optica spectrum disorders: a comparison with seropositive cases.

OBJECTIVE: The aim of this study is to investigate the unique features of seronegative neuromyelitis optica spectrum disorders (NMOSD) in Thailand. BACKGROUND: It remains unknown whether seronegative NMOSD patients possess clinical and paraclinical features that are distinct from those with seropositivity. METHODS: In a Thai cohort of idiopathic inflammatory CNS disorders (n=122), 52 patients fulfilled the Wingerchuk 2007 criteria for NMOSD. We determined anti-AQP4 antibody statuses using three different assays (an in-house cell-based assay [CBA], a commercially available CBA and a tissue-based indirect immunofluorescence [IIF] assay). RESULTS: Among the NMOSD patients, the percentage of seropositive cases was 54.5% based on the in-house and commercial CBAs and 30.8% based on the IIF assay. Using the in-house CBA, seronegative NMOSD patients exhibited distinct features compared with seropositive patients, such as a lack of female preponderance (F/M=1.2 vs. 6.0), frequent simultaneous bilateral optic involvement (33.3% vs. 0.04%), a lower annual relapse rate (0.4 ± 0.3 vs. 0.7 ± 0.6), fewer spinal cord lesions (1.0 ± 4.3 vs. 1.4 ± 0.6), and lower CSF cell counts (20 ± 72 vs. 80 ± 285). Use of the commercial CBA yielded essentially similar results, but some of these differences were not significant using IIF. CONCLUSIONS: Sensitive anti-AQP4 antibody assays reveal features of seronegative NMOSD patients that differ from those of seropositive patients from Thailand.

Brainstem manifestations in neuromyelitis optica: a multicenter study of 258 patients.

BACKGROUND: Neuromyelitis optica (NMO) is a severe autoimmune disease of the central nervous system characterized by spinal cord and optic nerve involvement. Brainstem manifestations have recently been described. OBJECTIVE: To evaluate the time of occurrence, the frequency and the characteristics of brainstem symptoms in a cohort of patients with NMO according to the ethnic background and the serologic status for anti-aquaporin-4 antibodies (AQP4-abs). METHODS: We performed a multicenter study of 258 patients with NMO according to the 2006 Wingerchuk criteria and we evaluated prospectively the frequency, the date of onset and the duration of various brainstem signs in this population. RESULTS: Brainstem signs were observed in 81 patients (31.4%). The most frequently observed signs were vomiting (33.1%), hiccups (22.3%), oculomotor dysfunction (19.8%), pruritus (12.4%), followed by hearing loss (2.5%), facial palsy (2.5%), vertigo or vestibular ataxia (1.7%), trigeminal neuralgia (2.5%) and other cranial nerve signs (3.3%). They were inaugural in 44 patients (54.3%). The prevalence was higher in the non-Caucasian population (36.6%) than in the Caucasian population (26%) (p<0.05) and was higher in AQP4-ab-seropositive patients (32.7%) than in seronegative patients (26%) (not significant). CONCLUSIONS: This study confirms the high frequency of brainstem symptoms in NMO with a majority of vomiting and hiccups. The prevalence of these manifestations was higher in the non Caucasian population.

Myasthenia gravis and neuromyelitis optica spectrum disorder: a multicenter study of 16 patients.

OBJECTIVE: To describe 16 patients with a coincidence of 2 rare diseases: aquaporin-4 antibody (AQP4-Ab)-mediated neuromyelitis optica spectrum disorder (AQP4-NMOSD) and acetylcholine receptor antibody (AChR-Ab)-mediated myasthenia gravis (AChR-MG). METHODS: The clinical details and antibody results of 16 patients with AChR-MG and AQP4-NMOSD were analyzed retrospectively. RESULTS: All had early-onset AChR-MG, the majority with mild generalized disease, and a high proportion achieved remission. Fifteen were female; 11 were Caucasian. In 14/16, the MG preceded NMOSD (median interval: 16 years) and 11 of these had had a thymectomy although 1 only after NMOSD onset. In 4/5 patients tested, AQP4-Abs were detectable between 4 and 16 years prior to disease onset, including 2 patients with detectable AQP4-Abs prior to thymectomy. AChR-Abs decreased and the AQP4-Ab levels increased over time in concordance with the relevant disease. AChR-Abs were detectable at NMOSD onset in the one sample available from 1 of the 2 patients with NMOSD before MG. CONCLUSIONS: Although both conditions are rare, the association of MG and NMOSD occurs much more frequently than by chance and the MG appears to follow a benign course. AChR-Abs or AQP4-Abs may be present years before onset of the relevant disease and the antibody titers against AQP4 and AChR tend to change in opposite directions. Although most cases had MG prior to NMOSD onset, and had undergone thymectomy, NMOSD can occur first and in patients who have not had their thymus removed.

Influence of pregnancy on neuromyelitis optica spectrum disorder.

OBJECTIVE: To investigate the influence of pregnancy on patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: A total of 190 women with NMOSD were enrolled from 7 referral hospitals in 4 countries. We reviewed medical records and used a structured questionnaire to investigate gravidity, parity, and the number of relapses during the 2 years before pregnancy, during each trimester of pregnancy, during the first and second trimesters after delivery, and for 6 months thereafter. The annualized relapse rate (ARR) was calculated for each period. RESULTS: Of the 190 women with NMOSD, 40 patients experienced 54 informative pregnancies, and all of them were seropositive for aquaporin-4 antibody. Fourteen patients developed the first symptoms of NMOSD either during the pregnancy (3 patients) or within a year after delivery or abortion (8 and 3 patients, respectively). Twenty-six patients experienced 40 pregnancies after the onset of NMOSD (26 deliveries and 14 abortions [1 spontaneous and 13 elective]). There was one preterm delivery with birth defects and no stillbirths. The ARR during pregnancy did not differ from that before pregnancy, but it increased significantly during the first and second trimesters after delivery (5.3 and 3.7 times, respectively). Moreover, 77% of the deliveries were associated with postpartum relapses. CONCLUSION: The significantly increased relapse rate and numerous cases of NMOSD onset after pregnancy suggest that delivery adversely affects the course of NMOSD. Prospective studies are needed to confirm our findings.

Pain in neuromyelitis optica and its effect on quality of life: a cross-sectional study.

OBJECTIVE: To assess the features of pain and its impact on the health-related quality of life (HRQOL) in neuromyelitis optica (NMO). METHODS: We analyzed 37 patients with NMO or NMO spectrum disorders seen at the Department of Neurology, Tohoku University Hospital, Sendai, Japan, during the period from November 2008 to February 2009. A total of 35 of them were aquaporin-4 antibody-positive. We used Short Form Brief Pain Inventory (BPI) to assess pain and Short Form 36-item (SF-36) health survey to evaluate the HRQOL. Fifty-one patients with multiple sclerosis (MS) were also studied for comparison. RESULTS: Pain in NMO (83.8%) was far more common than in MS (47.1%). The Pain Severity Index score in BPI was significantly higher in NMO than in MS, and patients' daily life assessed by BPI was highly interfered by pain in NMO as compared with MS. Pain involving the trunk and both legs was much more frequent in NMO than in MS. SF-36 scores in NMO were lower than MS, especially in bodily pain. CONCLUSION: Our study showed that pain in NMO is more frequent and severe than in MS and that pain has a grave impact on NMO patients' daily life and HRQOL. Therapy to relieve pain is expected to improve their HRQOL.

AQP4 antibody-positive Thai cases: clinical features and diagnostic problems.

OBJECTIVE: To evaluate the prevalence of aquaporin-4 (AQP4) antibody in Thai patients with idiopathic inflammatory demyelinating CNS diseases (IIDCDs) and to analyze the significance of the autoantibody to distinguish neuromyelitis optica (NMO) and other NMO spectrum disorders (ONMOSDs) from other IIDCDs, especially multiple sclerosis (MS). METHODS: We retrospectively evaluated 135 consecutive patients with IIDCDs seen at the MS clinic at Siriraj Hospital, Bangkok, Thailand, and classified them into NMO, ONMOSDs, optic-spinal MS (OSMS), classic MS (CMS), and clinically isolated syndrome (CIS) groups in this order with accepted diagnostic criteria. The patients' coded sera were tested separately for AQP4 antibody. Then the relations between the clinical diagnosis and the AQP4 antibody serologic status were analyzed. RESULTS: Among the 135 patients, 53 (39.3%) were AQP4 antibody-positive. Although the AQP4 antibody-positive group had features of NMO, such as female predominance, long cord lesions (>3 vertebral bodies), and CSF pleocytosis, only 18 patients (33% of 54) fully met Wingerchuk 2006 criteria except for AQP4 antibody-seropositive status. We also detected some AQP4 antibody-positive patients in the OSMS (4 of 7), CMS (11 of 46), and CIS (1 of 16) groups. These patients had been misdiagnosed with MS because they often had brain lesions and never underwent spinal cord MRI examination or lacked long cord lesions. CONCLUSIONS: AQP4 antibody was highly prevalent (almost 40%) in Thai patients with IIDCDs. Moreover, only one-third of AQP4 antibody-positive patients fully met Wingerchuk 2006 criteria, and many were misdiagnosed with MS. A sensitive AQP4 antibody assay is required in this region because the therapy for NMO is different from that for MS.

Occurrence of acute large and edematous callosal lesions in neuromyelitis optica.

BACKGROUND: The corpus callosum is commonly involved in multiple sclerosis (MS), but the characteristics of callosal lesions in neuromyelitis optica (NMO) are unknown.ObjectiveTo reveal the features of callosal lesions in NMO in comparison to MS. METHODS: We retrospectively reviewed the medical records and the brain magnetic resonance imaging films of 56 patients with MS and 22 patients with NMO. RESULTS: In MS, 36 (64.3%) of 56 patients had callosal lesions, but only four patients had acute lesions. All such acute lesions were small, isolated and non-edematous, and the intensity was homotonic. Chronic lesions were observed in 34 patients with MS, and 32 (94%) of them presented small lesions located at the callosal lower margin ("hemi-oval pattern"). Meanwhile, four (18.2%) patients with NMO had callosal lesions, and three of them had acute lesions. Those acute lesions were multiple, large edematous ones with heterogeneous intensity ("marbled pattern"). In the chronic stage, the lesions shrank or disappeared. CONCLUSIONS: Acute large, edematous callosal lesions occasionally occur in NMO. Similar to longitudinally extensive transverse myelitis, such callosal lesions may reflect severe edematous inflammation in NMO, and may provide additional evidence that the pathogenesis in NMO is different from that in MS.

Intractable hiccup and nausea in neuromyelitis optica with anti-aquaporin-4 antibody: a herald of acute exacerbations.

BACKGROUND: Intractable hiccup and nausea (IHN) are unique symptoms in neuromyelitis optica (NMO). Recent studies have strongly suggested that the pathogenesis of NMO is closely associated with anti-aquaporin-4 (AQP4) antibody. However, clinical implications of IHN and the relationship with anti-AQP4 antibody remain unknown. METHODS: The past medical records of 35 patients with seropositivity for anti-AQP4 antibody were reviewed. We also followed the titres of anti-AQP4 antibody in a patient with NMO, who had newly developed IHN. RESULTS: Of the 35 patients, 15 patients (43%) had episodes of IHN. There was a total of 35 episodes of IHN in these 15 patients and, of the 35 episodes, hiccup was seen in 23 episodes (66%) and nausea was seen in 28 episodes (80%). The IHN frequently preceded (54%) or accompanied (29%) myelitis or optic neuritis. The IHN was often preceded by an episode of viral infection. The titres of anti-AQP4 antibody were remarkably increased when the intractable hiccup appeared in a case. CONCLUSIONS: IHN could be a clinical marker for the early phase of an exacerbation. Careful observation may be needed when INH is seen in patients with NMO, and the early initiation of the treatment could prevent subsequent neurological damage.

Preferential spinal central gray matter involvement in neuromyelitis optica. An MRI study.

OBJECTIVE: To delineate the MRI features that distinguish neuromyelitis optica (NMO) from multiple sclerosis (MS). METHODS: We compared the distribution of the spinal cord lesions by analyzing 1) lesion area, 2) lesion density (by superimposing the lesions onto the standard sections of the cervical and thoracic cord with appropriate transparencies using computer software), and 3) T1-hypointensity in axial sections of MRI in NMO and MS. RESULTS: In NMO, 60-70% of the cervical and thoracic cord MRI lesions occupied more than half of the cord area and mainly involved the central gray matter in the acute stage. In the chronic stage, half or more of the lesions were localized at the central gray matter region. The lesion superimposition analysis also revealed much higher densities in the central gray matter region than in the peripheral white matter regions. Two patients with NMO had T1-hypointense lesions in the central region. In contrast, over 80% of the lesions in MS were localized in the lateral and posterior white matter regions of the cord in the chronic as well as acute stage. Lesion densities were much higher in the lateral and posterior white matter regions than in the central gray matter region. None of the lesions in MS were T1-hypointense. CONCLUSIONS: These MRI findings strongly suggest a preferential involvement in the spinal central gray matter in NMO which is distinct from MS.

Modulation of dendritic cell development by immunoglobulin G in control subjects and multiple sclerosis patients.

Intravenous immunoglobulin (IVIg) preparations are reportedly effective in inhibiting the relapse of multiple sclerosis (MS), but few reports have investigated the effect of IVIg on dendritic cells (DCs), which are thought to be involved in such relapses. In the system that uses monokines to differentiate DCs from peripheral blood monocytes (Mo-DCs), we investigated the effect of immunoglobulin G (IgG) on these antigen-presenting cells. Using monocytes derived from healthy volunteers, IgG partially inhibited the expression of CD1a, a marker of immature DCs (imDCs), and CD40 and CD80, which are markers associated with T cell activation. In contrast, IgG enhanced the expression of CD83, a marker of mature DCs (mDCs). Furthermore, IgG markedly inhibited the expression of CD49d [very late activation antigen (VLA)-4 alpha4-integrin], the adhesion molecule required for mDCs to cross the blood-brain barrier. We obtained similar results on all the aforementioned cell surface molecules investigated in both healthy controls and MS patients. In addition, IgG treatment of cells from both healthy controls and MS patients inhibited the production of interleukin (IL)-12, a cytokine associated with mDC differentiation, but did not inhibit the production of IL-10. These results suggested the possibility that IgG treatment, apart from its known ability to regulate inflammation, may help to prevent relapses of MS by controlling DC maturation, consequently inhibiting invasion of immune cells into the central nervous system and affecting the cytokine profile.

Low-dose corticosteroids reduce relapses in neuromyelitis optica: a retrospective analysis.

Neuromyelitis optica (NMO) is a relapsing neurologic disease characterized by severe optic neuritis and transverse myelitis. A disease-modifying therapy for NMO has not been established. We retrospectively analysed the effect of low-dose corticosteroid (CS) monotherapy on the annual relapse rate in nine patients with NMO. We divided the clinical course in each patient into two periods; the CS Period in which CS was administered, and the No CS Period in which CS was not administered. Periods related to other immunological therapies, such as high-dose methylprednisolone, immunosuppressants, interferon-beta, and plasma exchange, were excluded. As a result, the annual relapse rate during the CS Periods [median, 0.49 (range, 0-1.31)] was found to be significantly lower than that during the No CS Periods [1.48 (0.65-5.54)]. As for the dose of CS, relapses occurred significantly more frequently with ;10 mg/day or less' than with ;over 10 mg/day' (odds ratio: 8.75). The results of the present study suggest a beneficial effect of low-dose CS monotherapy in reducing relapses in NMO.

Loss of aquaporin 4 in lesions of neuromyelitis optica: distinction from multiple sclerosis.

Neuromyelitis optica (NMO) is an inflammatory and necrotizing disease clinically characterized by selective involvement of the optic nerves and spinal cord. There has been a long controversy as to whether NMO is a variant of multiple sclerosis (MS) or a distinct disease. Recently, an NMO-specific antibody (NMO-IgG) was found in the sera from patients with NMO, and its target antigen was identified as aquaporin 4 (AQP4) water channel protein, mainly expressed in astroglial foot processes. However, the pathogenetic role of the AQP4 in NMO remains unknown. We did an immunohistopathological study on the distribution of AQP4, glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), activated complement C9neo and immunoglobulins in the spinal cord lesions and medulla oblongata of NMO (n = 12), MS (n = 6), brain and spinal infarction (n = 7) and normal control (n = 8). The most striking finding was that AQP4 immunoreactivity was lost in 60 out of a total of 67 acute and chronic NMO lesions (90%), but not in MS plaques. The extensive loss of AQP4 accompanied by decreased GFAP staining was evident, especially in the active perivascular lesions, where immunoglobulins and activated complements were deposited. Interestingly, in those NMO lesions, MBP-stained myelinated fibres were relatively preserved despite the loss of AQP4 and GFAP staining. The areas surrounding the lesions in NMO had enhanced expression of AQP4 and GFAP, which reflected reactive gliosis. In contrast, AQP4 immunoreactivity was well preserved and rather strongly stained in the demyelinating MS plaques, and infarcts were also stained for AQP4 from the very acute phase of necrosis to the chronic stage of astrogliosis. In normal controls, AQP4 was diffusely expressed in the entire tissue sections, but the staining in the spinal cord was stronger in the central grey matter than in the white matter. The present study demonstrated that the immunoreactivities of AQP4 and GFAP were consistently lost from the early stage of the lesions in NMO, notably in the perivascular regions with complement and immunoglobulin deposition. These features in NMO were distinct from those of MS and infarction as well as normal controls, and suggest that astrocytic impairment associated with the loss of AQP4 and humoral immunity may be important in the pathogenesis of NMO lesions.

Clinical and laboratory features of neuromyelitis optica with oligoclonal IgG bands.

Of 23 neuromyelitis optica (NMO) cases, we found two cases with oligoclonal IgG bands (OBs). Both patients were positive for NMO-IgG. Their common features were long disease duration and co-existing autoimmune diseases (myasthenia gravis and sicca syndrome). Although OBs are mostly negative in NMO, which distinguishes it from multiple sclerosis (MS), they can be positive by long-standing autoimmunity, which may not be directly related to NMO.

High CSF neurofilament heavy chain levels in neuromyelitis optica.

The neurofilament heavy chain (NfHSMI35), a biomarker of axonal damage in the CSF, was measured in patients with neuromyelitis optica (NMO) and multiple sclerosis (MS). Significantly high CSF NfHSMI35 levels (>0.73 ng/mL) were found in 6 of 24 (25%) of the patients with NMO but none of the patients with MS (0/24). This finding suggests that axonal damage is more severe in NMO than in MS.