ABSTRACT
Spinocerebellar ataxia type 8 (SCA8) is a progressive neurological disorder caused by the expanded repeat CTA/CTG of two overlapping genes, ATXN8OS and ATXN8, expressed bidirectionally. Normal alleles have 15-50 repeats, and pathogenic alleles range from 71 to 1300 repeats. The disorder is relatively rare, accounting for about 2%-5% of the autosomal dominant forms of hereditary ataxia worldwide. However, the prevalence of disease-causing ATXN8OS/ATXN8 expansions is higher than the disease because of the reduced penetrance of the expanded allele. The aim of this study was to describe the first fully penetrant SCA8 family showing mixed Brazilian African and Amerindian origin. Eight members of this family were evaluated-the mother and seven offspring-through a complete neurological examination conducted at the Neurogenetics Clinic, HCFMRP-USP in Brazil. The number of CTA/CTG repeats was obtained after polymerase chain reaction (PCR) and fragment analysis. The haplotype analysis was conducted using a microsatellite marker, D13S1296, and four single nucleotide polymorphisms (SNPs), rs1831189, rs8002227, rs11841483, and rs72284461, all spanning a 70.1 Mb region on chromosome 13q21.3. The molecular analysis showed that the expansions ranged from 104 to 109 CTA/CTG repeats in the six affected individuals and were absent in two asymptomatic daughters (aged 53 and 40 years). Three SNPs cosegregate with the expanded alleles, confirming the connection between expansion and disease in this family. As the SCA8 diagnosis demands careful interpretation, we suggest the use of linkage analysis to observe segregation of the mutation, making more accurate its genotyping.
Subject(s)
Nerve Tissue Proteins/genetics , Penetrance , Polymorphism, Single Nucleotide , Spinocerebellar Ataxias/genetics , Adult , Aged , Brazil , Female , Haplotypes , Humans , Male , Middle Aged , Spinocerebellar Ataxias/pathology , Trinucleotide Repeat ExpansionABSTRACT
Intraoperative brain mapping has the goal of aiding with maximal surgical resection of brain tumors while minimizing functional sequelae. Retrospective randomized studies on large populations have shown that this technique can optimize the surgical approach while reducing postoperative morbidity. During direct electrical stimulation of the language areas adjacent to the tumor, the patient should be collaborative and be able to speak to participate in language testing. Different anesthesiological protocols have been proposed to allow intraoperative brain mapping, which range from local anesthesia to conscious sedation or general anesthesia, with or without airway instrumentation. The most common intraoperative complications are seizure, respiratory depression, and patients' stress and discomfort. Since awake craniotomy carries both benefits and potential risks, the following factors are crucial in the management of patients: 1) careful selection of the patients and 2) communication between the anesthesiological and surgical teams. To date, there remains no consensus about the optimal anesthesiological regimen to use. Only prospective, multicentre randomized studies focused on evaluating the role of different anesthesiological techniques on intraoperative monitoring, postoperative deficits, and intraoperative complications can answer the question of which anesthesiological approach should be chosen when intraoperative brain mapping is requested.
