Performance validity in outpatients with multiple sclerosis and cognitive complaints.

BACKGROUND: Suboptimal performance during neuropsychological assessment renders cognitive test results invalid. However, suboptimal performance has rarely been investigated in multiple sclerosis (MS). OBJECTIVES: To investigate potential underlying mechanisms of suboptimal performance in MS. METHODS: Performance validity testing, neuropsychological assessments, neuroimaging, and questionnaires were analyzed in 99 MS outpatients with cognitive complaints. Based on performance validity testing patients were classified as valid or invalid performers, and based on neuropsychological test results as cognitively impaired or preserved. Group comparisons and correlational analyses were performed on demographics, patient-reported, and disease-related outcomes. RESULTS: Twenty percent displayed invalid performance. Invalid and valid performers did not differ regarding demographic, patient-reported, and disease-related outcomes. Disease severity of invalid and valid performers with cognitive impairment was comparable, but worse than cognitively preserved valid performers. Lower performance validity scores related to lower cognitive functioning, lower education, being male, and higher disability levels (p < 0.05). CONCLUSION: Suboptimal performance frequently occurs in patients with MS and cognitive complaints. In both clinical practice and in cognitive research, suboptimal performance should be considered in the interpretation of cognitive outcomes. Identification of factors that differentiate between suboptimal and optimal performers with cognitive impairment needs further exploration.

Impaired saccadic eye movements in multiple sclerosis are related to altered functional connectivity of the oculomotor brain network.

BACKGROUND: Impaired eye movements in multiple sclerosis (MS) are common and could represent a non-invasive and accurate measure of (dys)functioning of interconnected areas within the complex brain network. The aim of this study was to test whether altered saccadic eye movements are related to changes in functional connectivity (FC) in patients with MS. METHODS: Cross-sectional eye movement (pro-saccades and anti-saccades) and magnetoencephalography (MEG) data from the Amsterdam MS cohort were included from 176 MS patients and 33 healthy controls. FC was calculated between all regions of the Brainnetome atlas in six conventional frequency bands. Cognitive function and disability were evaluated by previously validated measures. The relationships between saccadic parameters and both FC and clinical scores in MS patients were analysed using multivariate linear regression models. RESULTS: In MS pro- and anti-saccades were abnormal compared to healthy controls A relationship of saccadic eye movements was found with FC of the oculomotor network, which was stronger for regional than global FC. In general, abnormal eye movements were related to higher delta and theta FC but lower beta FC. Strongest associations were found for pro-saccadic latency and FC of the precuneus (beta band ß = -0.23, p = .006), peak velocity and FC of the parietal eye field (theta band ß = -0.25, p = .005) and gain and FC of the inferior frontal eye field (theta band ß = -0.25, p = .003). Pro-saccadic latency was also strongly associated with disability scores and cognitive dysfunction. CONCLUSIONS: Impaired saccadic eye movements were related to functional connectivity of the oculomotor network and clinical performance in MS. This study also showed that, in addition to global network connectivity, studying regional changes in MEG studies could yield stronger correlations.

Immunoblot analysis of the antibody response to ovine lentivirus infections.

The antibody response of sheep to maedi-visna virus (MVV) infection was studied, using an immunoblotting technique that identified the four major viral structural proteins: the envelope glycoprotein gp135, and internal proteins p25, p16 and p14. In sequential serum samples of two inoculated sheep, antibodies to p25 appeared first, soon followed by antibodies to p16. In two sheep with natural infections, which were sampled with longer intervals, antibodies to p25 and p16 appeared simultaneously. Antibody response to p14, which was weak and inconsistent in most cases, appeared after the p16 response. Antibodies to gp135 were detected in only one sheep and appeared 7 weeks after those to p25. Antibodies to p25 were particularly persistent. Antibody recognition patterns of 21 necropsied sheep with naturally occurring infections were compared. Sheep with lesions lacked antibodies to p14 and p16 and sometimes even p25, although these antibodies had been present in earlier stages of infection. Since the time of onset of lesions was unknown, we could not determine whether this decline in antibody activity occurred before, together with, or after the onset of lesion development.

Genomic heterogeneity of small ruminant lentiviruses detected by PCR.

In order to detect a large spectrum of small ruminant lentiviruses, primers for PCR were chosen in conserved parts of the LTR and GAG genes of Icelandic Visna virus 1514 and of the POL gene of caprine arthritis-encephalitis virus. This set of primers was tested in six different caprine arthritis-encephalitis virus (CAEV)- and Maedi-Visna virus isolates of Dutch, American and Swiss origin. The LTR primers allowed the detection of the corresponding fragments of all isolates. The GAG primers allowed amplification of the corresponding fragments of all but the Swiss Maedi-Visna virus strain OLV. Using the POL primers, one Maedi-Visna- and two caprine arthritis-encephalitis virus strains were detected after one round of amplification. Sequencing of the GAG and POL amplification products and comparison to Icelandic Visna virus and CAEV strain CO revealed total heterogeneity of 38% for the GAG- and 28% for the POL fragment. The virus strains studied fall into two groups which are more closely related to one another than to Icelandic Visna virus.

-PCR for the detection of lentiviruses from small ruminants-. / Die PCR fäur den Nachweis von Lentiviren der kleinen Wiederküer.

The polymerase chain reaction has all attributes of a promising diagnostic technique. It is rapid, simple to perform and extremely sensitive. In a PCR developed for the detection of small ruminant lentiviruses (SRLV), we found under ideal conditions a detection on sensitivity up to less than 10 template DNA copies. The diagnostic application of PCR was not fully satisfying, even when the technique was refined by the use of a panel of suitable primer pairs. The reliability of PCR in blood and milk samples was much lower than that of antibody detection using ELISA. Interestingly, a positive PCR result was also recorded in 50% of the samples of seronegative animals. Seronegative lentivirus carriers due to delayed seroconversion have been described previously (Rimstad et al., 1993). Due to sporadic occurrence of false positive reactions in spite of contamination control, this result must be interpreted with caution unless the specificity of the fragments can be confirmed by sequencing. Using published sequences of SRLV, we show that sequencing of PCR products, followed by phylogenetic analysis should allow to study molecular epidemiology of field strains.

LAV/HTLV-III gag gene product p24 shares antigenic determinants with equine infectious anemia virus but not with visna virus or caprine arthritis encephalitis virus.

Antigenic cross-reactivity of the human acquired immunodeficiency disease syndrome virus LAV/HTLV-III with the lentiviruses visna virus, caprine arthritis encephalitis virus (CAEV), and equine infectious anemia virus (EIAV) was determined with indirect enzyme-linked immunosorbent assays, immunoblot analysis, and virus-specific polyclonal antisera. Nonreciprocal cross-reactivity was seen between the gag gene products p24 of LAV/HTLV-III and p28 of EIAV. Reciprocal cross-reactivity was seen between the gag gene product p28 of visna virus and CAEV. No cross-reactivity was detected between visna virus (or CAEV) and EIAV (or LAV/HTLV-III). This suggests a closer relationship of LAV/HTLV-III with EIAV than with visna virus or CAEV.

Expression in Escherichia coli and sequencing of the coding region for the capsid protein of Dutch maedi-visna virus strain ZZV 1050: application of recombinant protein in enzyme-linked immunosorbent assay for the detection of caprine and ovine lentiviruses.

Maedi-visna in sheep and caprine arthritis-encephalitis in goats are caused by two closely related and widespread lentiviruses. The infections are characterized by life-long virus persistence and slow induction of antiviral antibodies. The diagnosis is based on the detection of antiviral antibodies. We have used the polymerase chain reaction (PCR) to amplify a part of the gag gene coding for the entire capsid protein and for parts of the matrix and nucleocapsid proteins. Sequencing of the PCR fragment of the Dutch maedi-visna virus strain ZZV 1050 revealed 85 and 92% homology to the DNA and deduced amino acid sequences, respectively, of the distantly related Icelandic visna virus strain 1514. The respective homologies with caprine arthritis-encephalitis virus strain CO were 76 and 80%. The PCR fragment was cloned into pGEX-2T and expressed as a glutathione S-transferase fusion protein. The recombinant protein could be detected on immunoblots by using a monoclonal antibody and polyclonal antisera and was further purified by glutathione-based affinity chromatography. Enzyme-linked immunosorbent assay with purified recombinant fusion protein is shown to be a sensitive and specific diagnostic tool for the detection of lentiviral infection in goats and sheep.