Faculty Bibliography

BACKGROUND:Optical coherence tomography (OCT) studies have demonstrated differences between people with schizophrenia and controls. Many questions remain including the agreement between scanners. The current study seeks to determine inter-device agreement of OCT data in schizophrenia compared to controls and to explore the relations between OCT and visual function measures. METHODS:Participants in this pilot study were 12 individuals with schizophrenia spectrum disorders and 12 age- and sex-matched controls. Spectralis and Cirrus OCT machines were used to obtain retinal nerve fiber layer (RNFL) thickness and macular volume. Cirrus was used to obtain ganglion cell layer + inner plexiform layer (GCL + IPL) thickness. Visual function was assessed with low-contrast visual acuity and the King-Devick test of rapid number naming. RESULTS:There was excellent relative agreement in OCT measurements between the two machines, but poor absolute agreement, for both patients and controls. On both machines, people with schizophrenia showed decreased macular volume but no difference in RNFL thickness compared to controls. No between-group difference in GCL + IPL thickness was found on Cirrus. Controls showed significant associations between King-Devick performance and RNFL thickness and macular volume, and between low-contrast visual acuity and GCL + IPL thickness. Patients did not show significant associations between OCT measurements and visual function. CONCLUSIONS:Good relative agreement suggests that the offset between machines remains constant and should not affect comparisons between groups. Decreased macular volume in individuals with schizophrenia on both machines supports findings of prior studies and provides further evidence that similar results may be found irrespective of OCT device.

OBJECTIVE:The Mobile Universal Lexicon Evaluation System (MULES) is a test of rapid picture naming that captures extensive brain networks, including cognitive, language and afferent/efferent visual pathways. MULES performance is slower in concussion and multiple sclerosis, conditions in which vision dysfunction is common. Visual aspects captured by the MULES may be impaired in Parkinson's disease (PD) including color discrimination, object recognition, visual processing speed, and convergence. The purpose of this study was to compare MULES time scores for a cohort of PD patients with those for a control group of participants of similar age. We also sought to examine learning effects for the MULES by comparing scores for two consecutive trials within the patient and control groups. METHODS:MULES consists of 54 colored pictures (fruits, animals, random objects). The test was administered in a cohort of PD patients and in a group of similar aged controls. Wilcoxon rank-sum tests were used to determine statistical significance for differences in MULES time scores between PD patients and controls. Spearman rank-correlation coefficients were calculated to examine the relation between MULES time scores and PD motor symptom severity (UPDRS). Learning effects were assessed using Wilcoxon rank-sum tests. RESULTS: = 0.37, P = .02). Learning effects were greater among patients with PD (median improvement of 14.8 s between two MULES trials) compared to controls (median 7.4 s, P = .004). CONCLUSION/CONCLUSIONS:The MULES is a complex test of rapid picture naming that captures numerous brain pathways including an extensive visual network. MULES performance is slower in patients with PD and our study suggests an association with the degree of motor impairment. Future studies will determine the relation of MULES time scores to other modalities that test visual function and structure in PD.

Introduction: Natalizumab treatment in patients with early relapsing-remitting multiple sclerosis (RRMS) may improve clinical outcomes. STRIVE is a completed, 4-year, multicentre, observational, open-label, single-arm study of anti-JC virus antibody negative patients starting natalizumab < 3 years after RRMS diagnosis.
Objective(s): To examine 4-year, end-of-study no evidence of disease activity (NEDA) status, disability worsening and improvement, and cognitive performance of natalizumab-treated patients with early RRMS.
Method(s): Clinical NEDA, the primary endpoint, was defined as no relapses or Expanded Disability Status Scale (EDSS) worsening (score increase of >=1.5 from a baseline [BL] of 0.0, >=1.0 from a BL of 1.0-5.5, or >=0.5 from a BL >=6.0, confirmed over 24 weeks). MRI NEDA was defined as no gadolinium-enhancing or new/enlarging T2-hyperintense lesions. Overall NEDA encompassed both clinical and MRI NEDA. Annualised relapse rates (ARRs) were analysed with a negative binomial regression model. The Kaplan-Meier method estimated time to 24-week-confirmed EDSS worsening or improvement (score decrease of >=1.0 from a BL >=2.0). The Symbol Digit Modalities Test (SDMT) change from BL to year 4 was analysed via a Wilcoxon signed-rank test.
Result(s): At BL (N=222), patients had active disease, a mean (standard deviation [SD]) of 1.4 (1.2) relapses in the prior year, and a mean (SD) EDSS score of 2.04 (1.13). At study end, 100 of 169 patients (59.2%) achieved cumulative clinical NEDA, and 72 of 143 (50.4%) and 45 of 163 (27.6%) had MRI and overall NEDA, respectively. In year 4, 101 of 134 patients (75.4%) had overall NEDA. ARRs decreased by 90.2%, from 1.43 in the year before natalizumab to 0.14 on natalizumab (P< 0.0001). Cumulative probabilities of EDSS worsening and improvement over 4 years were 19.3% and 43.9%, respectively. At study end, the mean (SD) EDSS score was 1.77 (1.55). From BL to year 4, patients had significant improvement in SDMT score (n=174; mean change from BL: 4.6 [95% confidence interval: 2.9-6.2]; P< 0.0001). Serious adverse events were reported in 25 of 222 patients (11.3%), with no cases of progressive multifocal leukoencephalopathy.
Conclusion(s): Natalizumab treatment over 4 years was associated with NEDA achievement, a 43.9% probability of disability improvement, a 19.3% probability of disability worsening, and significantly improved cognitive performance. These results support natalizumab's long-term effectiveness in early RRMS patients

OBJECTIVE:We report analyses of a pooled database by the Multiple Sclerosis Outcome Assessments Consortium to evaluate 4 proposed components of a multidimensional test battery. METHODS:Standardized data on 12,776 participants, comprising demographics, multiple sclerosis disease characteristics, Expanded Disability Status Scale (EDSS) score, performance measures, and Short Form-36 Physical Component Summary (SF-36 PCS), were pooled from control and treatment arms of 14 clinical trials. Analyses of Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), Low Contrast Letter Acuity (LCLA), and Symbol Digit Modalities Test (SDMT) included measurement properties; construct, convergent, and known group validity; and longitudinal performance of the measures individually and when combined into a multidimensional test battery relative to the EDSS and SF-36 to determine sensitivity and clinical meaningfulness. RESULTS:The performance measures had excellent test-retest reliability and showed expected differences between subgroups based on disease duration and EDSS level. Progression rates in detecting time to 3-month confirmed worsening were lower for T25FW and 9HPT compared to EDSS, while progression rates for LCLA and SDMT were similar to EDSS. When the 4 measures were analyzed as a multidimensional measure rather than as individual measures, progression on any one performance measure was more sensitive than the EDSS. Worsening on the performance measures analyzed individually or as a multidimensional test battery was associated with clinically meaningful SF-36 PCS score worsening, supporting clinical meaningfulness of designated performance test score worsening. CONCLUSION/CONCLUSIONS:These results support the use of the 4 proposed performance measures, individually or combined into a multidimensional test battery as study outcome measures.

Background/UNASSIGNED:The association of peripapillary retinal nerve fibre layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness with neurodegeneration in multiple sclerosis (MS) is well established. The relationship of the adjoining inner nuclear layer (INL) with inflammatory disease activity is less well understood. Objective/UNASSIGNED:In this longitudinal, multi-centre study, optical coherence tomography (OCT) and clinical data (disability status, relapses and MS optic neuritis (MSON)) were collected in 785 patients with MS (68.3% female) and 92 healthy controls (63.4% female) from 11 MS centres between 2010 and 2017 and pooled retrospectively. Data on pRNFL, GCIPL and INL were obtained at each centre. Results/UNASSIGNED: = .474). Conclusion/UNASSIGNED:Our data demonstrate that an increase in INL volume is associated with MSON and the occurrence of clinical relapses. Therefore, INL volume changes may be useful as an outcome marker for inflammatory disease activity in MSON and MS treatment trials.