Samira Apostolos-Pereira

Distinction between MOG antibody–positive and AQP4 antibody–positive NMO spectrum disorders

Objective: To evaluate clinical features among patients with neuromyelitis optica spectrum disorders (NMOSD) who have myelin oligodendrocyte glycoprotein (MOG) antibodies, aquaporin-4 (AQP4) antibodies, or seronegativity for both antibodies. Methods: Sera from patients diagnosed with NMOSD in 1 of 3 centers (2 sites in Brazil and 1 site in Japan) were tested for MOG and AQP4 antibodies using cell-based assays with live transfected cells. Results: Among the 215 patients with NMOSD, 7.4% (16/215) were positive for MOG antibodies and 64.7% (139/215) were positive for AQP4 antibodies. No patients were positive for both antibodies. Patients with MOG antibodies represented 21.1% (16/76) of the patients negative for AQP4 antibodies. Compared with patients with AQP4 antibodies or patients who were seronegative, patients with MOG antibodies were more frequently male, had a more restricted phenotype (optic nerve more than spinal cord), more frequently had bilateral simultaneous optic neuritis, more often had a single attack, had spinal cord lesions distributed in the lower portion of the spinal cord, and usually demonstrated better functional recovery after an attack. Conclusions: Patients with NMOSD with MOG antibodies have distinct clinical features, fewer attacks, and better recovery than patients with AQP4 antibodies or patients seronegative for both antibodies.

Quantification of retinal neural loss in patients with neuromyelitis optica and multiple sclerosis with or without optic neuritis using Fourier-domain optical coherence tomography.

PURPOSE We compared retinal nerve fiber layer (RNFL) and macular thickness measurements in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO) with or without a history of optic neuritis, and in controls using Fourier-domain (FD) optical coherence tomography (OCT). METHODS Patients with MS (n = 60), NMO (n = 33), longitudinal extensive transverse myelitis (LETM, n = 28) and healthy controls (n = 41) underwent ophthalmic examination, including automated perimetry, and FD-OCT RNFL and macular thickness measurements. Five groups of eyes were compared: MS with or without previous optic neuritis, NMO, LETM, and controls. Correlation between OCT and visual field (VF) findings was investigated. RESULTS With regard to most parameters, RNFL and macular thickness measurements were significantly smaller in eyes of each group of patients compared to controls. MS eyes with optic neuritis did not differ significantly from MS eyes without optic neuritis, but measurements were smaller in NMO eyes than in all other groups. RNFL (but not macular thickness) measurements were significantly smaller in LETM eyes than in controls. While OCT abnormalities were correlated significantly with VF loss in NMO/LETM and MS, the correlation was much stronger in the former. CONCLUSIONS Although FD-OCT RNFL and macular thickness measurements can reveal subclinical or optic neuritis-related abnormalities in NMO-spectrum and MS patients, abnormalities are predominant in the macula of MS patients and in RFNL measurements in NMO patients. The correlation between OCT and VF abnormalities was stronger in NMO than in MS, suggesting the two conditions differ regarding structural and functional damage. (ClinicalTrials.gov number, NCT01024985.).

Comparison of visual acuity and automated perimetry findings in patients with neuromyelitis optica or multiple sclerosis after single or multiple attacks of optic neuritis.

Objective: To review the clinical characteristics of patients with neuromyelitis optica (NMO) and to compare their visual outcome with those of patients with optic neuritis (ON) and multiple sclerosis (MS). Methods: Thirty-three patients with NMO underwent neuro-ophthalmic evaluation, including automated perimetry along with 30 patients with MS. Visual function in both groups was compared overall and specifically for eyes after a single episode of ON. Results: Visual function and average visual field (VF) mean deviation were significantly worse in eyes of patients with NMO. After a single episode of ON, the VF was normal in only 2 of 36 eyes of patients with NMO compared to 17 of 35 eyes with MS (P < 0.001). The statistical analysis indicated that after a single episode of ON, the odds ratio for having NMO was 6.0 (confidence interval [CI]: 1.6–21.9) when VF mean deviation was worse than -20.0 dB while the odds ratio for having MS was 16.0 (CI: 3.6–68.7) when better than -3.0 dB. Conclusion: Visual outcome was significantly worse in NMO than in MS. After a single episode of ON, suspicion of NMO should be raised in the presence of severe residual VF deficit with automated perimetry and lowered in the case of complete VF recovery.

Recurrent neuromyelitis optica in Brazilian patients: clinical, immunological, and neuroimaging characteristics

Neuromyelitis optica has not been thoroughly studied in Brazilian patients following the discovery of NMO-IgG and its specific antigen aquaporin-4. In this study we aimed to describe the clinical NMO-IgG immunological status and neuroimaging characteristics of recurrent neuromyelitis optica in a series Brazilian patients. We undertook a retrospective study of 28 patients with recurrent neuromyelitis optica, according to 1999 Wingerchuk’s diagnostic criteria. Data on NMO-IgG status, clinical features, and MRI findings were analyzed. Three men and 25 women were evaluated. Median age at onset of disease was 26 years (range 7—55); median time of follow-up was 7 years (range 2—14). The mean time elapsed between the first and the second attack was 17 months (median 8.5; range 2—88). NMO-IgG was detected in 18 patients (64.3%). Four patients died due to respiratory failure. Most patients presented with cervical (36%) and cervical-thoracic myelitis (46.4%). Holocord lesion was the most common pattern of involvement (50%) on the axial plane. We did not find a statistical association between myelitis extension and NMO-IgG result. Our series of Brazilian patients showed a younger age of onset than previously reported. In our series, in contrast to previous reports, there was no correlation between the extension of myelitis and NMO-IgG positivity.

Cerebrospinal fluid aquaporin‐4 antibody levels in neuromyelitis optica attacks

To elucidate immunopathogenetic roles of aquaporin‐4 antibodies in the cerebrospinal fluid (CSF) of neuromyelitis optica spectrum disorders (NMOSD), we analyzed aquaporin‐4 antibody titers, cellular and inflammatory markers in the CSF collected from 11 aquaporin‐4 antibody seropositive patients. The CSF aquaporin‐4 antibody levels during attacks (but not in sera) closely correlated with pleocytosis, inflammatory cytokines including interleukin‐6 that can regulate antibody‐producing plasmablasts, and glial fibrillary acidic protein levels in the CSF. The amount of aquaporin‐4 antibodies present in the central nervous system may have therapeutic implications, as it is associated with astrocyte injury and inflammatory responses during NMOSD attacks. Ann Neurol 2014;76:305–309

MOG-IgG-Associated Optic Neuritis, Encephalitis, and Myelitis: Lessons Learned From Neuromyelitis Optica Spectrum Disorder

Antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been found in some cases diagnosed as seronegative neuromyelitis optica spectrum disorder (NMOSD). MOG-IgG allowed the identification of a subgroup with a clinical course distinct from that of NMOSD patients who are seropositive for aquaporin-4-IgG antibodies. MOG-IgG is associated with a wider clinical phenotype, not limited to NMOSD, with the majority of cases presenting with optic neuritis (ON), encephalitis with brain demyelinating lesions, and/or myelitis. Therefore, we propose the term MOG-IgG-associated Optic Neuritis, Encephalitis, and Myelitis (MONEM). Depending on the clinical characteristics, these patients may currently be diagnosed with NMOSD, acute disseminated encephalomyelitis, pediatric multiple sclerosis, transverse myelitis, or ON. With specific cell-based assays, MOG-IgG is emerging as a potential biomarker of inflammatory disorders of the central nervous system. We review the growing body of evidence on MONEM, focusing on its clinical aspects.

Alternatives for reducing relapse rate when switching from natalizumab to fingolimod in multiple sclerosis

ABSTRACT Natalizumab is a therapeutic option for treating multiple sclerosis (MS) and is particularly efficacious for patients with highly active disease. A long washout period has been recommended between withdrawal of natalizumab and start of fingolimod (another option for treating MS). This long washout period has been associated with a significant increase in MS activity. In the present study, a group of 96 patients who were switched from natalizumab to fingolimod had short washout periods between drugs, or monthly corticosteroid pulse therapy if longer washout periods were recommended. This therapeutic approach led to the lowest reported relapse rate so far, among patients with MS switching from natalizumab to fingolimod (8.3%). No complications from short withdrawal were observed in this group of patients.

Voiding dysfunction in patients with neuromyelitis optica spectrum disorders.

We assessed the lower urinary tract symptoms (LUTS) and urodynamic findings in patients with neuromyelitis optica spectrum disorders (NMO‐SD), a recently defined neurological disease.

Anti-MOG (Myelin Oligodendrocyte Glycoprotein)–Positive Severe Optic Neuritis with Optic Disc Ischaemia and Macular Star

Abstract A 44-year-old man presented with severe right visual loss. The right fundus examination showed marked optic disc oedema associated with partial macular star. Serological blood tests for infectious agents were all negative. Serum aquaporin-4 antibody was negative but anti-MOG (myelin oligodendrocyte glycoprotein) was positive. Magnetic resonance revealed extensive lesion in right optic nerve. There was no visual improvement after intravenous therapy. Patient had no further attacks after follow-up. Optic disc oedema with macular star is found in several infectious and non-inflammatory disorders, but it has not been reported in optic neuritis (ON) associated with autoantibodies to myelin oligodendrocyte glycoprotein (anti-MOG).

Encephalomyelitis responsive to ganciclovir.

Department of Neurology and Institute of Radiology, Medical School, University of Sao Paulo, Sao Paulo SP, Brazil. A 19-year-old previously healthy boy was admitted with a ten-day history of rapidly progressive urinary retention, constipation, ascending hypoesthesia up to the thoracic level and gait instability. On physical examination, he presented fever, tetraparesis, brisk reflexes, multidirectional nystagmus, right-side Horner’s syndrome. CSF: 225 cells/mm (15% neutrophils), protein 142 mg/dl, glucose 46 mg/dl. MRI: Fig 1. Acute demyelinating encephalomyelitis was diagnosed and the patient was treated with high doses of corticosteroids for five days. Despite CSF improvement after corticosteroid treatment, clear signs of clinical worsening were observed. Anti-CMV (IgG and IgM) antibodies were detected in the CSF, and this justified empirical treatment with ganciclovir, starting one week after the corticosteroids. In one month, the patient was able to stand and walk with canes. MRI showed complete recovery (Fig 2).