Severe Optic Neuritis Research Articles

Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype

To report an association of myelin-oligodendrocyte glycoprotein (MOG) antibodies with aquaporin-4 (AQP4) antibody-seronegative neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder (NMOSD) in adults. We describe the clinical and serologic features of 4 adult patients with an NMO/NMOSD phenotype who had antibodies to MOG. Twenty-seven adult AQP4-seronegative NMO/NMOSD patients were tested for MOG antibodies. Four patients (3 male, 1 female) with severe optic neuritis and/or longitudinally extensive transverse myelitis were positive. All 4 made good recoveries with steroids or plasma exchange. Two patients experienced recurrence of symptoms when corticosteroids were withdrawn quickly but none have experienced further relapses over a mean follow-up of 12 months, although 3 patients remain on treatment. Imaging abnormalities resolved fully following clinical recovery and MOG antibody titers fell in all 4 patients. MOG antibodies were not found in 44 AQP4 antibody-positive NMO/NMOSD patients, 75 adult patients with multiple sclerosis, or 47 healthy individuals. MOG antibody-associated NMO/NMOSD could account for some cases thought previously to be AQP4-seronegative NMO/NMOSD. Our 4 patients appear to have more favorable clinical outcomes than those with typical AQP4 antibody-mediated disease. However, further studies of NMO/NMOSD and other demyelinating conditions are required to help clarify the diagnostic and prognostic relevance of MOG antibodies.

A practical guide to the treatment of neuromyelitis optica

Neuromyelitis optica (NMO) is a relapsing demyelinating disorder with a predilection for the optic nerves and spinal cord, associated with autoantibodies to aquaporin-4 (AQP4) water channels in most cases. It...

Neuromyelitis optica should be classified as an astrocytopathic disease rather than a demyelinating disease

AbstractNeuromyelitis optica (NMO) is characterized by severe optic neuritis and transverse myelitis. The relationship of NMO to multiple sclerosis (MS) has long been debated, but NMO has been classified as a demyelinating disease. Since the discovery of an NMO‐specific autoantibody to aquaporin 4 (AQP4), a dominant water channel in the central nervous system densely expressed on end‐feet of astrocytes, the clinical, magnetic resonance imaging and laboratory findings to distinguish NMO from MS have been clarified. Furthermore, pathological studies showed an extensive loss of immunoreactivities to astrocytic proteins, AQP4 and glial fibrillary acidic protein (GFAP), and perivascular deposition of immunoglobulins and activated complements with a relative preservation of the staining of myelin basic protein (MBP) in acute NMO lesions, but not in MS. In support of these pathological findings, the GFAP levels in the cerebrospinal fluid (CSF) during acute exacerbation of NMO are remarkably elevated compared with MBP and neurofilament, whereas the CSF‐GFAP in MS is not different from those in controls. Additionally, recent experimental studies have convincingly shown that AQP4 antibody is pathogenic in causing astorocytic destruction and dysfunction in vitro, ex vivo and in vivo. These findings strongly suggest that damage of astrocytes is far more severe than those of myelin and neurons, and that autoimmune astrocytopathy is the primary pathology in NMO. Based on these accumulated data, we propose that NMO should be classified as an astrocytopathic disease rather than a demyelinating disease.

124 When “the drugs don't work”: think NMO!

We present a 21-year-old Caucasian female with antibody positive NMO, mis-diagnosed as MS for a period of 5 years. The diagnosis became evident only when bilateral severe optic neuritis occurred...

Rituximab dosing and monitoring strategies in neuromyelitis optica patients: creating strategies for therapeutic success

Background: Neuromyelitis optica (NMO) is an autoimmune condition that predominantly causes severe optic neuritis and transverse myelitis. Rituximab therapy has dramatically improved patient care, but standardized dosing regimens and guidelines are lacking. Objectives: The objective of this study was to define a rituximab dosing strategy for NMO patients that achieves the lowest rate of relapses. Methods: This was a retrospective chart review of patients treated with various doses of rituximab. Results: Combining data from the NMO and multiple sclerosis (MS) patients, identified that the mean number of days after a 100 mg dose of rituximab until the CD19 population was greater than 2% was 99 days (standard deviation 36, range 43–172). When allowed to rise, the mean number of days after a 1000 mg dose of rituximab until the CD19 population was greater than 2% was 184 (standard deviation 72, range 52–288). The median number of days until a CD19 percentage of 2% was achieved was 133 days in the 100 mg dosing arm and 259 days in the 1000 mg dosing arm. Analysis of the survival curves via both the Mantel–Cox log-rank test and the Wilcoxon test determined that the difference between medial survival for 100 and 1000 mg doses was statistically significant with p-values <0.0001. Conclusions: Low doses of rituximab have a high rate of early B-cell repopulation. Any NMO patient treated with rituximab should be followed with monthly CD19 counts in order to identify the rare, but clinically significant, early repopulators.

Treatment of Neuromyelitis Optica

Neuromyelitis optica (NMO) or Devic's disease is an inflammatory neurologic disease characterized by severe optic neuritis and transverse myelitis. Other features of NMO include female preponderance, higher onset age, severe functional disability, longitudinally extensive spinal cord lesions (longer than 3 vertebral segments), and oligoclonal IgG bands negativity. Brain lesions are not uncommon in NMO. The relation between NMO and multiple sclerosis (MS) has long been a matter of controversy, but since the discovery of anti-aquaporin 4 (AQP4) antibody (NMO-IgG), an NMO-specific autoantibody, the clinical, MRI, and laboratory features that distinguish NMO from MS have been clarified. Anti-AQP4 antibody binds to the extracellular domain of AQP4, which is highly expressed in endfeet of astrocytes. Recent neuropathological studies, analysis of CSF-GFAP levels during relapse and experimental studies strongly suggest that NMO is an anti-AQP4 antibody-mediated astrocytopathic disease and that T cell-mediated CNS inflammation is necessary to develop NMO. Also, IL-6 is remarkably elevated in the CSF and appears to regulate plasmablasts to produce anti-AQP4 antibody. Therefore, from the therapeutic point of view, depletion of anti-AQP4 antibody, suppression of T cell response to trigger relapse and anti-IL-6 therapy seem to be pivotal. High-dose intravenous methylprednisolone is the first-line therapy for acute exacerbations of NMO. But plasma exchange should be started soon if corticosteroid is not efficacious. If untreated, AQP4 antibody-positive patients are highly likely to experience relapses within a year. Thus, immunosuppressive therapy (corticosteroids, immunosuppressants, rituximab) should be initiated without delay. Preliminary results suggest that eculizumab, an anti-C5 monoclonal antibody, can also prevent relapse in NMO, Meanwhile, interferon-beta, a first-line disease modifying drug of MS, is not effective in NMO. Symptomatic therapy for pain, paresthesia, spasticity, dysuria and constipation which commonly occur in the chronic stage of NMO is also important to improve patients' quality of life.

Treatment of neuromyelitis optica: an evidence based review

Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system characterized by severe optic neuritis and transverse myelitis, usually with a relapsing course. Aquaporin-4 antibody is positive in a high percentage of NMO patients and it is directed against this water channel richly expressed on foot processes of astrocytes. Due to the severity of NMO attacks and the high risk for disability, treatment should be instituted as soon as the diagnosis is confirmed. There is increasing evidence that NMO patients respond differently from patients with multiple sclerosis (MS), and, therefore, treatments for MS may not be suitable for NMO. Acute NMO attacks usually are treated with high dose intravenous corticosteroid pulse and plasmapheresis. Maintenance therapy is also required to avoid further attacks and it is based on low-dose oral corticosteroids and non-specific immunosuppressant drugs, like azathioprine and mycophenolate mofetil. New therapy strategies using monoclonal antibodies like rituximab have been tested in NMO, with positive results in open label studies. However, there is no controlled randomized trial to confirm the safety and efficacy for the drugs currently used in NMO.

Neuromyelitis optica and astrocytic damage in its pathogenesis

Neuromyelitis optica (NMO) is characterized by severe optic neuritis and longitudinally extended, transverse myelitis. There have been long controversial whether NMO is a variant of multiple sclerosis (MS) or a different disease. However, since the discovery of an NMO-specific autoantibody to aquaporin 4 (AQP4), a dominant water channel in the central nervous system densely expressed on foot processes of astrocytes, the clinical distinction between NMO and MS has become clear, and now AQP4 antibody status is critically important for neurologists in deciding on treatment strategy. Moreover, pathological studies demonstrated an extensive loss of immunoreactivities to AQP4 and glial fibrillary acidic protein (GFAP) with relative preservation of the staining of myelin basic protein in acute NMO lesions, which is not seen in MS. In fact, the GFAP levels in the cerebrospinal fluid during acute exacerbation of NMO are remarkably elevated, while the values in MS are not different from those in controls. In addition, recent experimental studies conducted in vitro and in vivo have shown that AQP4 antibody is pathogenic. These findings strongly suggest that AQP4 antibody has diagnostic, therapeutic and pathogenetic implications, and that severe astrocytic damage mediated by AQP4 antibody distinguishes NMO from MS.

Neuromyelitis Optica Antibodies in Patients With Severe Optic Neuritis in China

Severe visual loss is seen in both multiple sclerosis-associated optic neuritis (ON) and neuromyelitis optica (NMO)-associated ON. NMO (aquaporin 4) antibodies have been reported to have diagnostic and prognostic value for visual and neurological outcomes of recurrent ON. We performed this study to investigate the frequency of NMO antibodies and its prognostic value for visual and neurological outcomes in Chinese patients with severe ON. Single-center prospective cohort study. Detection of NMO antibodies was by indirect immunofluorescence method using human aquaporin 4-transfected cells. Severe ON was defined as visual acuity of 20/200 or worse in at least 1 eye at the nadir of the patients' course. Clinical features at baseline, visual outcome, and sequential neurological events were compared between seropositive and seronegative groups. NMO antibodies were detected in 11 of 34 patients (32.4%) with severe ON. Five seropositive patients with recurrent ON had significantly higher titers (range: 1:512 to 1:65,536; median: 1:512) than those of 6 seropositive patients with only 1 episode (range: 1:16 to 1:512; median: 1:32) (P=0.021). Female to male ratio (10:1) and antinuclear autoantibody positivity in seropositive patients (3 of 9, 33.3%) were statistically higher than those of the seronegative group (12:11; 0 of 19; P=0.026). The seropositive patients had significantly poorer visual outcomes than seronegative patients (P=0.025). During the averaged 32-month follow-up, 2 of 11 seropositive patients (18.2%) developed clinically incomplete transverse myelitis, while no similar symptoms were reported in the seronegative group. NMO antibody positivity is relatively high in Chinese patients with severe ON and suggests a poorer visual outcome, probably higher risk of developing spinal cord lesions and a closer association with systemic autoimmune disorders.

Therapeutic Efficacy of Interferon .BETA.-1b in Japanese Patients with Optic-Spinal Multiple Sclerosis

Optic neuritis and myelitis are manifestations in both multiple sclerosis (MS) and neuromyelitis optica (NMO). But unlike MS, NMO is characterized by severe optic neuritis, longitudinally extensive and transverse myelitis, and the presence of aquaporin-4 antibody. Since patients with optic neuritis and myelitis have often been diagnosed with "optic-spinal MS (OSMS)" in Asia, it was obscure whether "OSMS" is synonymous with NMO or includes both NMO and MS. Interferon β (IFNβ)-1a and -1b are used as the first-line disease-modifying therapy for MS. However, some neurologists have been reluctant to use IFNβ to treat patients with optic-spinal symptoms, because IFNβ therapy is not efficacious in NMO. To evaluate the therapeutic effect of IFNβ in patients with "genuine" OSMS, we retrospectively evaluated Japanese MS patients who fulfilled the following six criteria: 1) Relapsing-remitting MS with optic-spinal presentation alone (no brain symptoms), 2) With or without asymptomatic brain MRI lesions, 3) Oligoclonal IgG band-positive, 4) aquaporin-4 antibody seronegativity, 5) No myelitis extending longitudinally over ≥ 3 vertebral segments, and 6) Duration of IFNβ-1b therapy ≥ 2 years. Among 157 patients with MS, six (four women and two men, age 43.8 ± 8.5 years old) met all the criteria. Their Expanded Disability Status Scale scores were lowered (4.1 ± 2.4 → 3.1 ± 2.8) (P = 0.033) and annualized relapse rate was decreased (0.59 ± 0.34 → 0.13 ± 0.15) (P = 0.027) after IFNβ-1b therapy. These results suggest that IFNβ is therapeutically effective in inhibiting functional worsening and reducing relapse rate in "genuine" OSMS.

Neuromyelitis optica preceded by hyperCKemia episode

Background: Neuromyelitis optica (NMO) is a disease of the CNS characterized by severe optic neuritis and longitudinally extended transverse myelitis. Recent studies suggest that anti-aquaporin-4 (AQP4) antibodies, NMO-specific biomarkers, are pathogenic and target AQP4-expressing astrocytes in NMO, although an additional event (T-cell response or infection) should occur for anti-AQP4 antibodies and complements to pass through the blood–brain barrier and cause the CNS lesions. AQP4 is the major water channel in the CNS, but it is also expressed in fast-twitch skeletal muscle fibers. However, muscle diseases have not been described in NMO. Methods: We retrospectively examined the serologic database of 733 cases of NMO with anti-AQP4 antibody at the Department of Neurology, Tohoku University School of Medicine. The serum samples were sent to our laboratory for testing anti-AQP4 antibody from around the country during the period from 2006 to 2009. Results: We found 3 anti-AQP4 antibody-positive female patients (7, 34, and 67 years old) with NMO who had episodes of prominent hyperCKemia (12,520, 19,415, and 59,660 IU/L) with general fatigue some weeks before the onset of optic neuritis. HyperCKemia was transient without any treatment in all patients, but recurred once in one of them. Conclusions: These cases suggest that hyperCKemia may be involved in the pathogenesis of neuromyelitis optica (NMO) in a fraction of patients. The causes of transient hyperCKemia are unknown. Further studies are needed to know the frequency of hyperCKemia in NMO and clarify its pathogenic role.

Neuromyelitis optica preceded by hyperCKemia episode

Neuromyelitis optica (NMO) is a disease of the CNS characterized by severe optic neuritis and longitudinally extended transverse myelitis. Recent studies suggest that anti-aquaporin-4 (AQP4) antibodies, NMO-specific biomarkers, are pathogenic and target AQP4-expressing astrocytes in NMO, although an additional event (T-cell response or infection) should occur for anti-AQP4 antibodies and complements to pass through the blood-brain barrier and cause the CNS lesions. AQP4 is the major water channel in the CNS, but it is also expressed in fast-twitch skeletal muscle fibers. However, muscle diseases have not been described in NMO. We retrospectively examined the serologic database of 733 cases of NMO with anti-AQP4 antibody at the Department of Neurology, Tohoku University School of Medicine. The serum samples were sent to our laboratory for testing anti-AQP4 antibody from around the country during the period from 2006 to 2009. We found 3 anti-AQP4 antibody-positive female patients (7, 34, and 67 years old) with NMO who had episodes of prominent hyperCKemia (12,520, 19,415, and 59,660 IU/L) with general fatigue some weeks before the onset of optic neuritis. HyperCKemia was transient without any treatment in all patients, but recurred once in one of them. These cases suggest that hyperCKemia may be involved in the pathogenesis of neuromyelitis optica (NMO) in a fraction of patients. The causes of transient hyperCKemia are unknown. Further studies are needed to know the frequency of hyperCKemia in NMO and clarify its pathogenic role.

Early high-dose intravenous methylprednisolone is effective in preserving retinal nerve fiber layer thickness in patients with neuromyelitis optica

Neuromyelitis optica (NMO) is a recurring inflammatory neurological disease characterized by severe optic neuritis and myelitis. The purpose of this study was to determine whether the retinal nerve fiber layer thickness (RNFLT) is correlated with the clinical presentations in patients with NMO and to determine the clinical factors that lead to poor visual outcomes. Thirty-five eyes of 18 patients with the NMO spectrum and 28 eyes of 14 patients with multiple sclerosis (MS) were studied. All of the patients had at least one episode of optic neuritis (ON) >6 months before being studied. The eyes were classified into four groups based on an episode of ON: NMO-ON, NMO eyes with at least one episode of ON; NMO-nonON, NMO eyes without an episode of ON; MS-ON, MS eyes with at least one episode of ON; and MS-nonON, MS eyes without an episode of ON. The RNFLT was measured by optical coherence tomography (OCT). The correlations between the RNFLT and the clinical data were determined. The overall RNFL was thinner in patients in the NMO-ON group than in the MS-ON group (63.84 µm vs. 84.28 µm; p = 0.0006) especially in the superior and inferior quadrants. The overall RNFLT was significantly correlated with the best-corrected visual acuity (BCVA) in both the NMO groups (r = 0.67; p < 0.0001) and the MS groups (r = 0.62; p = 0.0097). The overall RNFLT was negatively correlated with the number of relapses in the NMO group. A receiver operating characteristic (ROC) analysis showed that the cut-off value for a decrease in visual acuity to <20/20 was 71.41 µm of the overall RNFLT in the NMO group. The frequency of the ON relapses and the time for beginning the treatment with high-dose intravenous methylprednisolone (HIMP) significantly affected the preservation of the RNFLT. The overall thinner RNFL in eyes with NMO than in eyes with MS indicates a greater loss of optic nerve axons in eyes with NMO. An early intervention with HIMP and preventing recurrences in NMO are critical for minimizing the axonal loss. Our findings indicate that OCT is an important method of evaluating loss of optic nerve axons in eyes with NMO and MS.

Differential Regulation of IgG-NMO Autoantibodies on S100Beta Protein and Disability in Relapsing Neuromyelitis Optica

Neuromyelitis optica (NMO), an uncommon central nervous system (CNS) demyelinating disease, produces transverse myelitis and severe optic neuritis. IgG-NMO autoantibody, a specific immunoglobulin binding aquaporin-4 water channel protein, confirms that NMO is a different entity to multiple sclerosis. Parallel to cytokine down-regulations found in serum of relapsing-NMO (rNMO) patients, it has been reported that IgG-NMO may also confer a worse course of the disease in r-NMO Caribbean patients. In this study, we were interested in exploring the influence of IgG-NMO autoantibody on S100β levels and clinical parameters from serum of r-NMO patients. Serum samples from 24 rNMO patients and 10 controls were evaluated. The reduction of S100β observed in r-NMO patients was not significant compared to controls; and no differences were present regarding IgG-NMO immunoreactivity. At the same time, a significant correlation was also observed between IgG-NMO autoantibody serum detection and EDSS (Expanded Disability Status Scale) in rNMO. These results corroborate a differential regulation of IgG-NMO autoantibodies on the S100β glial marker and on the disability present in rNMO patients.

Patient with neuromyelitis optica and inflammatory demyelinating lesions comprising whole spinal cord from C2 level till conus: case report

BackgroundNeuromyelitis optica (NMO) is an idiopathic, severe, inflammatory demyelinating disease of the central nervous system, that causes severe optic neuritis and myelitis attacks. Early discrimination between multiple sclerosis (MS) and NMO is important, as optimum treatment for both diseases may differ considerably.Case PresentationWe report a case of a patient who initially presented as longitudinally extensive transverse myelitis (LETM), having spastic upper extremities diparesis and spastic paraplegia, C2/C3 sensory level and urinary incontinence, as well as extensive inflammatory spinal cord lesions from C2 level to conus. After 5 months the patient had another attack of transverse myelitis, had electrophysiological findings consistent with optic neuritis, was seropositive for NMO-IgG (aquaporin-4 IgG) and thus fulfilled NMO diagnostic criteria. Following treatment of disease attacks with pulse corticosteroid therapy and intravenous immunoglobulins, we included oral azathioprine in a combination with oral prednisone in the therapy. Since there was no significant clinical improvement, we decided to use cyclophosphamide therapy, which resulted in good clinical improvement and gradual decrease of cord swelling.ConclusionIn this NMO case report we wanted to emphasize the extensiveness of inflammatory spinal cord changes in our patient, from C2 level to conus. In the conclusion it is important to say that accurate, early diagnosis and distinction from MS is critical to facilitate initiation of immunosuppressive therapy for attack prevention.

Rezidivierende bilaterale Optikusneuritis bei schubförmiger MS und Verlauf unter Interferon β-1b

A 40-years-old female with recurrent bilateral severe optic neuritis (ON) was diagnosed having relapsing-remitting multiple sclerosis (MS). The low cerebral lesion load in MRI and non-responsiveness to steroid treatment lead to the differential diagnoses of isolated recurrent ON, incomplete neuromyelitis optica and Leber hereditary optic neuropathy (LHON). None of these MS-mimicks could be confirmed later on. The MS-typical CSF pattern and the positive response to plasma exchange were suggestive of an atypical course of MS, possibly a special subtype. Further support for this assumption comes from the stable disease course under interferon β-1b treatment and the reoccurrence of a relapse after termination of this treatment.

Effect of geranylgeranylacetone on optic neuritis in experimental autoimmune encephalomyelitis

Optic neuritis is an acute inflammatory demyelinating syndrome of the central nervous system (CNS) that often occurs in multiple sclerosis (MS). Since it can cause irreversible visual loss, especially in the optic-spinal form of MS or neuromyelitis optica (NMO), the present study was conducted to assess the effects of geranylgeranylacetone (GGA) on optic neuritis in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Myelin oligodendrocyte glycoprotein-induced EAE mice received oral administration of GGA at 500mg/kg or vehicle once daily for 22 days. The effects of GGA on the severity of optic neuritis were examined by morphological analysis on day 22. Visual functions were measured by the multifocal electroretinograms (mfERG). In addition, the effects of GGA on severity of myelitis were monitored both on clinical signs and morphological aspects. The visual function, as assessed by the second-kernel of mfERG, was significantly improved in GGA-treated mice compared with vehicle-treated mice. GGA treatment decreased the number of degenerating axons in the optic nerve and prevented cell loss in the retinal ganglion cell layer. However, the severity of demyelination in the spinal cord remained unaffected with the treatment of GGA. These results suggest that oral GGA administration has beneficial effect on the treatment for optic neuritis in the EAE mouse model of MS.

Role of n‐type voltage‐dependent calcium channels in autoimmune optic neuritis

The aim of this study was to investigate the role of voltage-dependent calcium channels (VDCCs) in axon degeneration during autoimmune optic neuritis. Calcium ion (Ca(2+)) influx into the optic nerve (ON) through VDCCs was investigated in a rat model of optic neuritis using manganese-enhanced magnetic resonance imaging and in vivo calcium imaging. After having identified the most relevant channel subtype (N-type VDCCs), we correlated immunohistochemistry of channel expression with ON histopathology. In the confirmatory part of this work, we performed a treatment study using omega-conotoxin GVIA, an N-type specific blocker. We observed that pathological Ca(2+) influx into ONs during optic neuritis is mediated via N-type VDCCs. By analyzing the expression of VDCCs in the inflamed ONs, we detected an upregulation of alpha(1B), the pore-forming subunit of N-type VDCCs, in demyelinated axons. However, high expression levels were also found on macrophages/activated microglia, and lower levels were detected on astrocytes. The relevance of N-type VDCCs for inflammation-induced axonal degeneration and the severity of optic neuritis was corroborated by treatment with omega-conotoxin GVIA. This blocker led to decreased axon and myelin degeneration in the ONs together with a reduced number of macrophages/activated microglia. These protective effects were confirmed by analyzing the spinal cords of the same animals. We conclude that N-type VDCCs play an important role in inflammation-induced axon degeneration via two mechanisms: First, they directly mediate toxic Ca(2+) influx into the axons; and second, they contribute to macrophage/microglia function, thereby promoting secondary axonal damage. Ann Neurol 2009;66:81-93.

A case of NMO seropositive for aquaporin-4 antibody more than 10 years before onset

Neuromyelitis optica (NMO) is characterized by severe optic neuritis and longitudinally extended transverse myelitis (LETM). The clinical and laboratory features of NMO are different from multiple sclerosis (MS).1 An autoantibody to aquaporin-4 (AQP4) has been detected exclusively in the NMO sera.1 Moreover, we demonstrated an extensive loss of AQP4 and glial fibrillary acidic protein immunoreactivities in the perivascular regions with complement and immunoglobulin deposition in NMO that suggests astrocytic impairment. However, when AQP4 antibody is produced in patients with NMO is unknown, and thus it remains unresolved whether there are long-term asymptomatic AQP4 antibody–positive carriers, whether AQP4 antibody alone can be pathogenic, and whether AQP4 antibody is produced secondarily as a result of tissue destruction in attacks of NMO. We herein report a case of NMO in which AQP4 antibody was detected years before the NMO onset. ### Case report. A 34-year-old healthy woman without previous history of inflammatory or neurologic diseases noticed temporary skin eruptions on her chest and shoulders in June 2007. A dermatologist made the diagnosis of eczema. Three weeks later, when the skin eruptions subsided, she noted progressive paresthesia in the chest and toes. Within a few days, she could not walk well due to right leg weakness, and then she was hospitalized. Neurologic examination on …

Prevalence of neuromyelitis optica spectrum disorder and phenotype distribution

Neuromyelitis optica spectrum disorder (NMOsd) is a group of demyelinating disorders recently redefined and associated with NMO-IgG/anti-aquaporin 4 antibodies. Because NMOsd is of unknown prevalence worldwide, we conducted a retrospective, cross-sectional study of 850 patients with demyelinating disorders hospitalized in North East Tuscany from 1998 to 2006 to examine the prevalence of NMO and related disorders among unselected consecutive neurological patients with inflammatory CNS diseases and to evaluate the clinical phenotype spectrum of identified cases. Clinical data were updated after at least 2 years of follow-up. An immunofluorescence technique was used to detect NMO-IgG on rat brain tissue. Sera from other 828 neurological patients, 65 non-neurological patients and 50 healthy donors served as controls. The prevalence of NMOsd was 1.5%, with a MS:NMOsd ratio of 42.7. Among 13 NMOsd patients, 77% had long spinal cord lesions, 38% had severe optic neuritis and 23% had brain or brainstem lesions. Only 56% had clinically definite NMO at follow-up. The final EDSS score ranged from 1 to 10, mainly depending on brainstem involvement occurrence. Our findings confirm a low prevalence of NMO and related disorders among demyelinating inflammatory diseases in a Caucasian population. Moreover, this study demonstrates an unexpectedly high prevalence of limited and atypical variants of this disease, not previously documented.