Spinocerebellar ataxia in a cohort of patients from Rio de Janeiro.

OBJECTIVE: The objective of this study is to describe the first series of spinocerebellar ataxia (SCA) in Rio de Janeiro, whose population has a high proportion of mixed Portuguese and African ancestry. METHODS: We reviewed the medical records of patients with progressive ataxia evaluated at the Sarah Network of Rehabilitation Hospitals (Rio de Janeiro). Clinical course, genetic tests for hereditary ataxia, brain MRI, and electroneuromyography were analyzed. RESULTS: SCA was confirmed in 128 individuals, one-third of African descendants. SCA3 predominated (83.6%), followed by SCA7 (7%); SCA2 (3.9%); SCA1, SCA6, and SCA8 (1.6% each); and SCA10 (0.8%). Dysphagia, pyramidal signs, and neurogenic bladder occurred frequently. Oculomotor disorders occurred with SCA3, SCA7, SCA2, and SCA1; peripheral neuropathies with SCA3 and SCA1; extrapyramidal syndromes with SCA3, SCA7, and SCA2; bilateral visual impairment with SCA7; and epilepsy with SCA10. Mobility assistance was required in 75% after 11 years and wheelchair in 25%. The Scale for the Assessment and Rating of Ataxia scores at the last follow-up varied from 2 to 37 (median = 14.50) and correlated positively with duration of the disease. In SCA3, a higher CAG repeats correlated with a lower age at onset. African ethnicity was associated with earlier onset, regardless of CAG repeats. The main brain MRI abnormality was cerebellar atrophy, isolated or associated with brainstem atrophy, "hot cross bun" sign, or brain atrophy. Linear T2 hyperintensity along the medial margin of the globus pallidus occurred in SCA3, SCA2, SCA1, and SCA7. ENMG confirmed peripheral neuropathy in SCA3 and SCA1. CONCLUSION: Machado Joseph disease/SCA3 was the most frequent inherited dominant ataxia in Rio de Janeiro. This study revealed new aspects of ethnic influence in the clinical course and new MRI findings.

Neuromyelitis optica is an HLA associated disease different from Multiple Sclerosis: a systematic review with meta-analysis.

Neuromyelitis Optica and Multiple Sclerosis are idiopathic inflammatory demyelinating diseases of the central nervous system that currently are considered distinct autoimmune diseases, so differences in genetic susceptibility would be expected. This study aimed to investigate the HLA association with Neuromyelitis Optica by a systematic review with meta-analysis. The STROBE instrument guided research paper assessments. Thirteen papers published between 2009 and 2020 were eligible. 568 Neuromyelitis Optica patients, 41.4% Asians, 32.4% Latin Americans and 26.2% Europeans were analyzed. Only alleles of the DRB1 locus were genotyped in all studies. Neuromyelitis Optica patients have 2.46 more chances of having the DRB1*03 allelic group than controls. Ethnicity can influence genetic susceptibility. The main HLA association with Neuromyelitis Optica was the DRB1*03:01 allele in Western populations and with the DPB1*05:01 allele in Asia. Differences in the Multiple Sclerosis and Neuromyelitis Optica genetic susceptibility was confirmed in Afro descendants. The DRB1*03 allelic group associated with Neuromyelitis Optica has also been described in other systemic autoimmune diseases.

Central Nervous System Idiopathic Inflammatory Demyelinating Disorders in South Americans: A Descriptive, Multicenter, Cross-Sectional Study.

The idiopathic inflammatory demyelinating disease (IIDD) spectrum has been investigated among different populations, and the results have indicated a low relative frequency of neuromyelitis optica (NMO) among multiple sclerosis (MS) cases in whites (1.2%-1.5%), increasing in Mestizos (8%) and Africans (15.4%-27.5%) living in areas of low MS prevalence. South America (SA) was colonized by Europeans from the Iberian Peninsula, and their miscegenation with natives and Africans slaves resulted in significant racial mixing. The current study analyzed the IIDD spectrum in SA after accounting for the ethnic heterogeneity of its population. A cross-sectional multicenter study was performed. Only individuals followed in 2011 with a confirmed diagnosis of IIDD using new diagnostic criteria were considered eligible. Patients' demographic, clinical and laboratory data were collected. In all, 1,917 individuals from 22 MS centers were included (73.7% female, 63.0% white, 28.0% African, 7.0% Mestizo, and 0.2% Asian). The main disease categories and their associated frequencies were MS (76.9%), NMO (11.8%), other NMO syndromes (6.5%), CIS (3.5%), ADEM (1.0%), and acute encephalopathy (0.4%). Females predominated in all main categories. The white ethnicity also predominated, except in NMO. Except in ADEM, the disease onset occurred between 20 and 39 years old, early onset in 8.2% of all cases, and late onset occurred in 8.9%. The long-term morbidity after a mean disease time of 9.28±7.7 years was characterized by mild disability in all categories except in NMO, which was scored as moderate. Disease time among those with MS was positively correlated with the expanded disability status scale (EDSS) score (r=0.374; p=<0.001). This correlation was not observed in people with NMO or those with other NMO spectrum disorders (NMOSDs). Among patients with NMO, 83.2% showed a relapsing-remitting course, and 16.8% showed a monophasic course. The NMO-IgG antibody tested using indirect immunofluorescence (IIF) with a composite substrate of mouse tissues in 200 NMOSD cases was positive in people with NMO (95/162; 58.6%), longitudinally extensive transverse myelitis (10/30; 33.3%) and bilateral or recurrent optic neuritis (8/8; 100%). No association of NMO-IgG antibody positivity was found with gender, age at onset, ethnicity, early or late onset forms, disease course, or long-term severe disability. The relative frequency of NMO among relapsing-remitting MS (RRMS) + NMO cases in SA was 14.0%. Despite the high degree of miscegenation found in SA, MS affects three quarters of all patients with IIDD, mainly white young women who share similar clinical characteristics to those in Western populations in the northern hemisphere, with the exception of ethnicity; approximately one-third of all cases occur among non-white individuals. At the last assessment, the majority of RRMS patients showed mild disability, and the risk for secondary progression was significantly superior among those of African ethnicity. NMO comprises 11.8% of all IIDD cases in SA, affecting mostly young African-Brazilian women, evolving with a recurrent course and causing moderate or severe disability in both ethnic groups. The South-North gradient with increasing NMO and non-white individuals from Argentina, Paraguay, Brazil and Venezuela confirmed previous studies showing a higher frequency of NMO among non-white populations.

A cluster of transverse myelitis following dengue virus infection in the brazilian Amazon region.

BACKGROUND AND PURPOSE: During the last two decades, clinical reports have begun to place increasing emphasis on the possible neurological complications related to dengue. However, reports of cases with myelitis post dengue are rare. This study describes an unprecedented cluster of transverse myelitis following a dengue virus infection. METHODS: 51 possible cases of neurological complications related to dengue were identified by the epidemiological surveillance of the State of Rondônia, Brazil and submitted to serial neurological examination, electromyography, vertebral MR and laboratory investigation to confirm the dengue diagnosis and rule out other arboviruses. RESULTS: The diagnosis of acute transverse myelitis post-dengue was established in 26 patients, the majority were women, young and white. Antibodies against virus IgM were present in all cases and DEN 3 virus was isolated by PCR in one patient. Treatment with IV steroids was useful. CONCLUSIONS: The cluster of transverse myelitis post-dengue with favorable clinical outcome here reported suggests an immune mediated mechanism for the spinal cord involvement. Whereas dengue epidemics are frequent in tropical and subtropical countries, the dengue fever should be part in the differential diagnosis of the infectious and post-infectious myelitis.

Anti-AQP(4) antibody in idiopathic acute transverse myelitis with recurrent clinical course: frequency of positivity and influence in prognosis.

BACKGROUND: The anti-aquaporin4 (anti-AQP4) antibody is specific for neuromyelitis optica (NMO), but is also found in limited forms. The presence of this antibody in acute transverse myelitis (ATM) has been associated with recurrence and conversion to NMO, but the influence on disability has not yet been described. OBJECTIVE: To describe the frequency of anti-AQP4 in ATM and analyze the influence in long-term prognosis. DESIGN: Cross-sectional and retrospective study. METHODS: Consecutive ATM cases in a multiple sclerosis center in Rio de Janeiro, Brazil, from 2000 through 2009 were reviewed. Recurrent cases tested for anti-AQP4 were selected. ATM with magnetic resonance imaging spinal cord lesions extending over three or more vertebral segments was classified as longitudinally extensive transverse myelitis (LETM); Kurtzke scale was applied at last evaluation. OUTCOME MEASURES: Frequency of anti-AQP4; severity of spinal cord dysfunction at last follow-up. RESULTS: Twenty six patients (21 female:5 male; 17 white:9 African descent) were studied. The first ATM occurred at 38.04 ± 12.7 years. The interval between the first and the second ATM was eight months (1-150) and the number of ATM varied from two to seven. After 40.5 months (12-192) of disease, the median Expanded Disability Status Scale (EDSS) score was three (0-9). Anti-AQP4 antibody was positive in 26.9%. LETM was found in 65.4%. LETM presented later onset, higher disability and higher positivity to anti-AQP4 (LETM 41.2% versus no-LETM 0%, P = 0.024). Dysfunction at long-term follow-up was similar in anti-AQP4 positive and negative cases. CONCLUSION: The frequency of anti-AQP4 in recurrent ATM was 26.9%, increasing to 41.2% among LETM. Presence of the antibody had no influence on morbidity.

The clinical course of idiopathic acute transverse myelitis in patients from Rio de Janeiro.

The aim of this study was to describe the demographic, clinical and laboratory features of idiopathic acute transverse myelitis (IATM). Patients with non-compressive ATM receiving care at Hospital da Lagoa, Rio de Janeiro (Brazil) between 2000 and 2008 were selected. Of the 70 cases of acute myelopathies, the idiopathic form was identified in 41 following exclusion of the cases associated with systemic lupus erythematosus (n = 1), Sjogren's syndrome (n = 1), herpes zoster (n = 1), cytomegalovirus in an HIV-positive patient (n = 1), Schistosoma mansoni (n = 1), actinic myelitis (n = 1), infectious myelitis of unknown etiology (n = 2) and those that, following the first attack of myelitis, converted to NMO (n = 19) or to clinically defined MS (n = 2). Of the 41 cases of IATM, the majority of patients were female (68.3%) and white (65.9%). Median age at first myelitis was 37.0 +/- 11.8 years. Over a median observation time of 36 months, 39.0% of patients remained monophasic, while recurrences occurred in 61.0% of cases. The number of ATM/patient ranged from one to seven. Among the recurrent cases the median time between the first and the second ATM was 12 months (range 1-150 months).The first myelitis was characterized mainly by partial myelitis with motor and sensorial dysfunction (63.4%). Complete and severe myelitis occurred more frequently among monophasic patients and partial myelitis with moderate dysfunction at onset in recurrent cases; however, over the long-term, dysfunction and disability were mild in both groups. Serial spine MRI confirmed spinal cord inflammation in 92.0% of cases and extensive spinal cord lesion was identified in 61.0%. Brain MRI was normal or not suggestive of MS in 94.4% of cases. CSF showed pleocytosis in 41.2%, increased IgG index in 24.0% and oligoclonal bands in 38.0% of 34 patients tested. Abnormal visual evoked potentials occurred in 11.5% of 26 patients. Positivity for anti-AQP4 was found in 23.5% of the 17 cases tested, suggesting limited forms of NMO. This study suggests some new aspects of the clinical course of IATM such as the high conversion rate to NMO, the predominance of women and a higher frequency of recurrent forms.