Lower frequency of antibodies to MOG in Brazilian patients with demyelinating diseases: An ethnicity influence?

OBJECTIVE: Antibodies against Myelin Oligodendrocyte glycoprotein (MOG-Ab) have been investigated as potential biological marker for neuromyelitis optica (NMO) and high-risk syndromes (HR) negative for AQP4-Ab in populations with different ethnic background. We tested AQP4 and MOG antibodies in a Brazilian population with high African ethnic background. METHOD: The study population was composed of adult patients from Rio de Janeiro with inflammatory demyelinating diseases (new and old cases). Blood samples were sent blindly to test the AQP4 and MOG antibodies by CBA. The frequency of positive MOG-Ab was estimated in the NMOHR and the NMO spectrum disorders (NMOSD). A systematic review with meta-analysis assessed the frequency of MOG-Ab in Caucasians and non-Caucasians. RESULTS: 200 adult patients (52% Afro-Brazilian) 115 of them with NMOHR were tested. MOG antibodies were found in 5/68 negative cases of AQP4-Ab negative (7%). The criteria for NMOSD were fulfilled by 70 patients with NMOHR and none of them was positive for MOG-Ab. A low prevalence of MOG antibodies and a predominant phenotype of bilateral Optic Neuritis were found in most non-Caucasian patients. CONCLUSION: The low frequency of MOG Ab in patients from Rio de Janeiro and in other non-Caucasian populations suggests a racial/ancestral influence.

22q11.2q13 duplication including SOX10 causes sex-reversal and peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease.

Diagnosis of genetic syndromes may be difficult when specific components of a disorder manifest at a later age. We present a follow up of a previous report [Seeherunvong et al., (2004); AJMGA 127: 149-151], of an individual with 22q duplication and sex-reversal syndrome. The subject's phenotype evolved to include peripheral and central demyelination, Waardenburg syndrome type IV, and Hirschsprung disease (PCWH; MIM 609136). DNA microarray analysis defined the duplication at 22q11.2q13, including SOX10. Sequencing of the coding region of SOX10 did not reveal any mutations. Our data suggest that SOX10 duplication can cause disorders of sex development and PCWH, supporting the hypothesis that SOX10 toxic gain of function rather than dominant negative activity underlies PCWH.

Risk factors for convertion to clinically defined multiple sclerosis after clinically isolated syndrome in a racially mixed Brazilian cohort.

UNLABELLED: Clinically isolated syndrome may reflect the first symptom of Multiple Sclerosis. Though more prevalent in Caucasians, MS can also affect Afrodescendts. Modifying disease drugs can delay convertion to clinically defined multiple sclerosis, therefore, identify patients at a higher risk of convertion is important. However data of risk factors in racially mixed population are scarce. OBJECTIVES: To analyze predictor factors to the conversion from CIS to CDMS in a mixed race Brazilian cohort. PATIENTS AND METHODS: It is a prognostic observational retrospective study, in 122 patients from MS referential center at Hospital da Lagoa, Rio de Janeiro-Brazil. Demographic and clinical features, as well as MRI and cerebrospinal fluid data were analyzed. RESULTS: After five years follow-up 87.3% converted to CDMS. Regarding to median time of conversion, there was no difference between gender, race, age at onset, mono or polysymptomatic presentation. Cerebellar CIS significantly reduced time to second event; likewise sphincter impairment. Considering DMD, patients without treatment converted earlier. CONCLUSION: Ancestry did not influence conversion risk. Cerebellar and shpincter impairment as well as MRI criteria both Barkhof/Tintoré and Swanton were important predictors. In future studies it should be also analysed the risk factors of progression in mixed race populations.

An algorithm for genetic testing of Serbian patients with demyelinating Charcot-Marie-Tooth.

Charcot-Marie Tooth (CMT) is a clinically and genetically heterogeneous group of diseases with rough genotype-phenotype correlation, so the final diagnosis requires extensive clinical and electrophysiological examination, family data, and gene mutation analysis. Although there is a common pattern of genetic basis of CMT, there could be some population differences that should be taken into account to facilitate analyses. Here we present the algorithm for genetic testing in Serbian patients with demyelinating CMT, based on their genetic specificities: in cases of no PMP22 duplication, and if -X-linked CMT (CMTX) is not contraindicated by pattern of inheritance (male-to-male transmission), one should test for c.94A>G GJB founder mutation, first. Also, when a patient is of Romani ethnicity, or if there is an autosomal recessive inheritance in a family and unclear ethnicity, c.442C>T mutation in NDRG1 should be tested.

Incidence of acquired CNS demyelinating syndromes in a multiethnic cohort of children.

OBJECTIVE: To determine whether the incidence and clinical features of pediatric multiple sclerosis (MS) and other forms of pediatric acquired demyelinating syndromes (ADS) vary by race/ethnicity in a population-based cohort. METHODS: We used a combination of electronic database searches followed by complete medical records review to identify all children diagnosed with MS and ADS in the multiethnic membership of Kaiser Permanente Southern California from January 1, 2004, to December 31, 2009. Incidence rates were standardized to the US census by age and gender. RESULTS: We identified 81 incident cases of ADS from 4.87 million person-years of observation in children 0-18 years of age. The incidence rate of pediatric MS was 0.51 per 100,000 person-years (95% confidence interval [CI] 0.33-0.75) and incidence of other forms of ADS including optic neuritis, transverse myelitis, other forms of clinically isolated syndrome (CIS), and acute disseminated encephalomyelitis (ADEM) was 1.56 (95% CI 1.23-1.95) for an overall incidence of ADS of 1.66 per 100,000 person-years (95% CI 1.32-2.06). Incidence of ADS was higher in black (4.4 per 100,000 person-years, 95% CI 2.5-7.2, p < 0.001) and Asian/Pacific Islander (2.8, 95% CI 1.2-5.2, p = 0.02) than white (1.03, 95% CI 0.6-1.7) and Hispanic (1.5, 95% CI 1.1-2.1, per 100,000 person-years) children. Black children were also significantly more likely to have MS than white children (p = 0.001). Children who presented with ADEM were significantly younger than children with other types of ADS clinical presentations (mean age 5.6, range 0.7-17.6 years vs 14.6, range 2.7-18.5, respectively). CONCLUSIONS: The incidence of pediatric acquired demyelinating syndromes is 1.66 per 100,000 person-years in a population-based cohort of Southern Californian children. The incidence of ADS and MS is higher in black children compared with white and Hispanic children.

Evaluation of the 2005 McDonald MRI criteria for dissemination in space in Afro-Caribbean patients with clinically isolated syndromes.

BACKGROUND: In 2005, the McDonald MRI criteria for dissemination in space were revised to improve diagnosis of multiple sclerosis (MS) in non-Caucasians. METHODS: We included patients with a first clinically isolated syndrome (CIS) to assess their performance in the Afro-Caribbean population. Baseline brain and spine MRI examinations were available within 3 months after onset of CIS. The development of a second clinical event was used as the main outcome indicating clinically definite MS. RESULTS: A total of 66 patients (52F/14M) were included between January 1998 and January 2008 (mean age: 34.7; median follow-up: 34 months). CIS was classified as spinal cord (30.3%), optic neuritis (28.8%), brainstem (24.2%), multiregional (10.6%), hemispheric (4.5%), or undetermined (1.5%). Overall conversion rate was 42.4% (median: 11 months). The McDonald criteria revised for dissemination in space were fulfilled in 33.3% (sensitivity: 0.39 (+/-0.18); specificity: 0.66 (+/-0.15), positive predictive value: 0.46 (+/-0.20), negative predictive value: 0.60 (+/-0.15). CONCLUSION: The Afro-Caribbean population is characterized by a strong proportion of CIS in the spinal cord and a lower burden of disease on the baseline brain MRI. This may explain the low sensitivity of the 2005 McDonald criteria for dissemination in space. Further prospective studies emphasizing MRI spinal cord features are needed to improve diagnostic criteria in a population of African descent.