Cognitive-affective manifestations since premanifest phases of Spinocerebellar Ataxia Type 3/Machado-Joseph Disease.

BACKGROUND: Cognitive deficits were related to Spinocerebellar Ataxia type 3/Machado-Joseph Disease (SCA3/MJD), but the Cerebellar Cognitive Affective Syndrome (CCAS) needs further investigation in this disorder. We aimed to characterize cognitive-affective deficits in manifest and premanifest SCA3/MJD carriers. METHODS: Subjects at 50% risk, manifest carriers and unrelated controls were evaluated in-person or in virtual settings with CCAS Scale (CCAS-S), Stroop Color-Word Test (SCWT), Trail-Making Test (TMT), and Reading the Mind in the Eyes Test (RMET). Scale for Assessment and Rating of Ataxia (SARA) >2.5 or Friedreich Ataxia Rating Scale/Activities of Daily Living (FARS-adl) >4 divided carriers into manifest and premanifest. Time after onset or time left to gait ataxia onset (TimeToAfterOnset) were estimated. Differences between groups and correlations with TimeToAfterOnset, SARA and FARS-adl were checked. RESULTS: After random selection to balance groups, 23 manifest and 35 premanifest carriers, and 58 controls were included. CCAS-S, semantic fluency, phonemic fluency, category switching, affect, SCWT, and RMET showed significant differences between manifest carriers and controls; premanifest carriers mostly displayed intermediate values between controls and manifest carriers. These variables correlated with TimeToAfterOnset and SARA scores of the carriers. Correlations with SARA were stronger in the pre-ataxic group. CCAS-S had the strongest correlations with time and SARA. DISCUSSION: Cognitive-affective deficits in SCA3/MJD involve executive function, language, affect, and social cognition, which seem to be altered prior to the ataxia onset, and correlate with markers of motor progression. CCAS-S was the most promising biomarker and should be evaluated in longitudinal studies.

Genetic diagnosis in recently transfused patients.

Analysis of recently transfused patients is usually postponed to avoid spurious results because of contamination with donor's cells. However, little is known about the extent of this influence in routine molecular diagnostic tests. To elucidate this question, we tested a mix of blood samples from 2 α-1-antitrypsin-deficient patients diagnosed as Pi*Z homozygous with 1 normal donor at 1:1, 1:10, 1:20, and 1:30 proportions. Human identification panel and Pi*Z allele detection were used to establish the detection limit of a blood mixture. Mixtures of 1:1 and 1:10 were easily detected with both techniques, whereas for 1:30, it was necessary to change the equipment settings to identify the mixture. Moreover, the heterozygous pattern observed for the mixtures on Pi*Z genotyping was weaker at this level of mixture. We further evaluated the degree of mixture detectable in 20 transfused patients who received 1 blood unit (concentrate of irradiated or nonirradiated red blood cells) using the human identification panel. Two days after the transfusion, the presence of the donor's markers was not detected, suggesting that after this time point the levels of admixture are below 1:30. The methods applied in the present study showed adequate sensitivity to identify alleles of the so-called "smaller population" of cells up to 3%, approximately. The same result was obtained in a "diagnostic situation," in which the blood mixture was submitted to a PCR-RFLP protocol to detect a mutation.