Dagoberto Callegaro

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.

Evaluation of Inner Retinal Layers in Patients with Multiple Sclerosis or Neuromyelitis Optica Using Optical Coherence Tomography

PURPOSE To evaluate the thickness of the inner retinal layers in the macula using frequency-domain optical coherence tomography (fd-OCT) in patients with demyelinating diseases. DESIGN Cross-sectional study. PARTICIPANTS A total of 301 eyes of 176 subjects were evaluated. Subjects were divided in 5 different groups: controls, neuromyelitis optica (NMO), longitudinally extensive transverse myelitis (LETM), multiple sclerosis with a history of optic neuritis (MS-ON), and multiple sclerosis without a history of optic neuritis (MS non-ON). METHODS The individual layers from macular fd-OCT cube scans were segmented with an automated algorithm and then manually hand-corrected. For each scan, we determined the thickness of the retinal nerve fiber layer (RNFL), the combined retinal ganglion cell and inner plexiform layers (RGCL+), and the inner nuclear layer (INL). MAIN OUTCOME MEASURES Macular RNFL, RGCL+, and INL thickness. RESULTS The RNFL was significantly thinner than in controls for all patient groups (P ≤ 0.01). Macular RGCL+ thickness was significantly thinner than in controls for the NMO, MS-ON, and MS non-ON groups (P<0.001 for the 3 groups). The INL thickness was significantly thicker than in controls for the patients with NMO (P = 0.003) and LETM (P = 0.006) but not for those with MS-ON or MS non-ON. Although the RNFL and RGCL+ were not significantly different between the NMO and MS-ON groups, the patients with NMO had a significantly thicker INL than the patients with MS-ON (P = 0.02). CONCLUSIONS Macular RNFL and RGCL+ demonstrate axonal and neural loss in patients with MS, either with or without ON, and in patients with NMO. In addition, the INL thickening occurs in patients with NMO and patients with LETM, and study of this layer may hold promise for differentiating between NMO and MS.

The prevalence of multiple sclerosis in the city of São Paulo, Brazil, 1997.

July 1, 1997 was stipulated as the day for estimating the prevalence of multiple sclerosis within the city of São Paulo. The patients were identified via various sources, including associated universities and magnetic resonance services of the city of São Paulo. The area covered by the study has a population of 9,380,000, mainly white and of European origin, with a large number of immigrants from Spain and Portugal. The patients were classified in accordance with the criteria of Poser et al. (1983), and only those with defined multiple sclerosis were registered. The study gave a prevalence of 15.0/105 inhabitants, or three times the value obtained in a similar study in 1990. This increase reveals the larger number of cases encompassed by the study, and is attributed to the use of more detailed recording methods, improvements in diagnosis, and better conditions for treatment.

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.).

Prevalence of Multiple Sclerosis in the City of São Paulo, Brazil, in 1990

A case register of multiple sclerosis (MS) was set up in the city of São Paulo, Brazil, situated at a latitude of 23-24 degrees south. Cases were notified by neurologists, neuroradiologists and by an association of patients with MS. Prevalence rate was 4.27 x 10(-5) (men: 2.89 x 10(-5); women: 5.59 x 10(-5)), with a preponderance of young adults. We discuss here whether these rates are artifact due to poor health care facilities, to poor notification and deficiencies in diagnosis, or whether these rates are really low.

Fatigue in amyotrophic lateral sclerosis: Frequency and associated factors

We aimed to quantify fatigue frequency and evolution in amyotrophic lateral sclerosis (ALS), and to correlate fatigue with factors such as age, sex, educational level, disease duration, functionality, quality of life, dyspnoea, depression and sleepiness. Sixty ALS patients (test group: TG) selected by El Escorial criteria and 60 normal individuals (control group: CG) matched according to sex and age, were followed every three months, during 9 months, by means of self‐report scales: Fatigue Assessment Instrument (Fatigue Severity Scale plus three qualitative subscales); ALS Functional Rating Scale; McGill Quality of Life Questionnaire; dyspnoea analogical scale; Beck Depression Inventory and Epworth Sleepiness Scale. Fatigue was reported by 83% of TG (median: 3.6, interquartile range 1.5−5.4), compared with 20% of CG (median: 1, 1−1), and was significantly greater in the TG (p<0.001, Mann‐Whitney test). Fatigue severity increased by the ninth month of the study (p = 0.0008, Friedman, Müller‐Dunn post test). There was no correlation between fatigue and other parameters, except for an inverse correlation with age at disease onset (p = 0.0395, Spearman rank correlation). In conclusion, fatigue was frequent in ALS, greater in the youngest patients and worsened during follow‐up. Possibly, ALS related fatigue is an independent factor, which deserves individualized approach and treatment.

Amyotrophic lateral sclerosis in Brazil: 1998 national survey

OBJECTIVES To assess the epidemiologic characteristics of amyotrophic lateral sclerosis (ALS) in Brazil in 1998. METHOD Structured Clinical Report Forms (CRFs) sent to 2,505 Brazilian neurologists from January to September 1998 to be filled with demographic and clinical data regarding any ALS patient seen at any time during that year. RESULTS Five hundred and forty CRFs were returned by 168 neurologists. Data on 443 patients meeting the criteria of probable or definite ALS according to El Escorial definition were analysed: 63 probable (14.2%) and 380 definite (85. 8%). Two hundred and fifty-nine (58.5%) of the patients were male, mean age of onset was 52. Spinal onset occurred in 306 patients (69%); bulbar onset in 82 (18.5%), and both in 52 (11.7%). Twenty-six (5.9%) had a family history of ALS. Two hundred and fifty-nine (58.6%) were seen by private practitioners, and 178 (40. 2%) at a hospital clinic. Age-ajusted incidence shows a peak incidence at the 65-74 years old range. CONCLUSIONS The diseases characteristics are similar to those described in international studies, except for age of onset (Brazilian patients are younger). This difference is not confirmed when figures are age-adjusted.

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.

Pediatric multiple sclerosis report of 14 cases

We present clinical data from 14 multiple sclerosis (MS) patients who have been admitted to our hospital between January 1980 and May 1992, whose age of onset ranged from 2-15 years. Our patients could be classified as having a clinically definite form of the disease. Initial symptoms varied from minor, such as motor or sensory impairment, bladder dysfunction, to the worst clinical presentation, suggesting diffuse encephalopathy. All the patients had a relapsing-remitting course. We report the paraclinical and laboratory examinations that were done in these patients. Over the period 1980 to 1992 these patients had 39 attacks. CSF analysis was performed in the phase of activity of the disease on 23 occasions and was normal in 12. At least one brain CT scan was performed in 9 patients and showed white matter abnormalities in 6. Cranial magnetic resonance imaging was done in 6 patients and were abnormal in 5. Visual evoked potential (EP) was abnormal in 7 of 8 patients; brainstem acoustic EP was abnormal in 4 of 8 patients and somatosensory EP in 4 of 8. MS is not so rare in childhood and although its diagnosis is essentially a clinical one, paraclinical investigations are of great value in the identification of demyelinating disorders in childhood.

HTLV-I associated myelopathy in Brazil: a preliminary report

In this preliminary report the authors present the finding of a high prevalence (37.5%) of seropositivity of antibodies to HTLV-I tested by Western blotting in a sample of 16 Brazilian patients with chronic myelopathies of undetermined origin.