Retinal Thickness Predicts the Risk of Cognitive Decline in Parkinson Disease.

OBJECTIVE: This study was undertaken to analyze longitudinal changes of retinal thickness and their predictive value as biomarkers of disease progression in idiopathic Parkinson's disease (iPD). METHODS: Patients with Lewy body diseases were enrolled and prospectively evaluated at 3 years, including patients with iPD (n = 42), dementia with Lewy bodies (n = 4), E46K-SNCA mutation carriers (n = 4), and controls (n = 17). All participants underwent Spectralis retinal optical coherence tomography and Montreal Cognitive Assessment, and Unified Parkinson's Disease Rating Scale score was obtained in patients. Macular ganglion cell-inner plexiform layer complex (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) thickness reduction rates were estimated with linear mixed models. Risk ratios were calculated to evaluate the association between baseline GCIPL and pRNFL thicknesses and the risk of subsequent cognitive and motor worsening, using clinically meaningful cutoffs. RESULTS: GCIPL thickness in the parafoveal region (1- to 3-mm ring) presented the largest reduction rate. The annualized atrophy rate was 0.63µm in iPD patients and 0.23µm in controls (p < 0.0001). iPD patients with lower parafoveal GCIPL and pRNFL thickness at baseline presented an increased risk of cognitive decline at 3 years (relative risk [RR] = 3.49, 95% confidence interval [CI] = 1.10-11.1, p = 0.03 and RR = 3.28, 95% CI = 1.03-10.45, p = 0.045, respectively). We did not identify significant associations between retinal thickness and motor deterioration. INTERPRETATION: Our results provide evidence of the potential use of optical coherence tomography-measured parafoveal GCIPL thickness to monitor neurodegeneration and to predict the risk of cognitive worsening over time in iPD. ANN NEUROL 2021;89:165-176.

Foveal Pit Morphology Characterization: A Quantitative Analysis of the Key Methodological Steps.

Disentangling the cellular anatomy that gives rise to human visual perception is one of the main challenges of ophthalmology. Of particular interest is the foveal pit, a concave depression located at the center of the retina that captures light from the gaze center. In recent years, there has been a growing interest in studying the morphology of the foveal pit by extracting geometrical features from optical coherence tomography (OCT) images. Despite this, research has devoted little attention to comparing existing approaches for two key methodological steps: the location of the foveal center and the mathematical modelling of the foveal pit. Building upon a dataset of 185 healthy subjects imaged twice, in the present paper the image alignment accuracy of four different foveal center location methods is studied in the first place. Secondly, state-of-the-art foveal pit mathematical models are compared in terms of fitting error, repeatability, and bias. The results indicate the importance of using a robust foveal center location method to align images. Moreover, we show that foveal pit models can improve the agreement between different acquisition protocols. Nevertheless, they can also introduce important biases in the parameter estimates that should be considered.

Myocardial MIBG scintigraphy in genetic Parkinson's disease as a model for Lewy body disorders.

PURPOSE: To identify myocardial sympathetic denervation patterns suggestive of Lewy body (LB) pathology in patients with genetic and idiopathic parkinsonisms by 123I-metaiodobenzylguanidine (MIBG) scintigraphy. METHODS: We retrospectively analysed myocardial MIBG images acquired with a dual-head gamma camera and low-energy high-resolution collimator (LEHR) in 194 patients with suspected synucleinopathy or atypical parkinsonism, including 34 with genetic Parkinson's disease (PD; 4 PARK1, 8 PARK2 and 22 PARK8), 85 with idiopathic PD (iPD), 6 with idiopathic REM sleep behaviour disorder (iRBD), 17 with dementia with LB (DLB), 40 with multiple system atrophy (MSA) and 12 with progressive supranuclear palsy (PSP), and in 45 healthy controls. We calculated heart-to-mediastinum MIBG uptake ratios (HMR) at 15 min and 4 h (HMR4H) for the LEHR and standardized medium-energy collimators, to obtain classification accuracies and optimal cut-off values for HMR using supervised classification and ROC analyses. RESULTS: While patients with LB disorders had markedly lower HMR4HLEHR than controls (controls 1.86 ± 0.26, iPD 1.38 ± 0.29, iRBD 1.23 ± 0.09, PARK1 1.20 ± 0.09, DLB 1.17 ± 0.11; p < 0.05), for the remaining patient categories differences were smaller (PARK8 1.51 ± 0.32; p < 0.05) or not significant (MSA 1.82 ± 0.37, PSP 1.59 ± 0.23, PARK2 1.51 ± 0.30; p > 0.05). The diagnostic accuracy of HMR4HLEHR was highest in patients with LB disorders (PARK1, iPD, DLB, iRBD; 89% to 97%) and lowest in those with PARK2, PARK8, PSP and MSA (65% to 76%), with an optimal HMR4HLEHR cut-off value of 1.72 for discriminating most patients with LB disorders including iPD and 1.40 for discriminating those with aggressive LB spectrum phenotypes (DLB, PARK1 and iRBD). CONCLUSION: Our study including patients with a wide spectrum of genetic and idiopathic parkinsonisms with different degrees of LB pathology further supports myocardial MIBG scintigraphy as an accurate tool for discriminating patients with LB spectrum disorders.

Parafoveal thinning of inner retina is associated with visual dysfunction in Lewy body diseases.

BACKGROUND: Retinal optical coherence tomography findings in Lewy body diseases and their implications for visual outcomes remain controversial. We investigated whether region-specific thickness analysis of retinal layers could improve the detection of macular atrophy and unravel its association with visual disability in Parkinson's disease. METHODS: Patients with idiopathic Parkinson's disease (n = 63), dementia with Lewy bodies (n = 8), and E46K mutation carriers in the α-synuclein gene (E46K-SNCA) (n = 4) and 34 controls underwent Spectralis optical coherence tomography macular scans and a comprehensive battery of visual function and cognition tests. We computed mean retinal layer thicknesses of both eyes within 1-, 2-, 3-, and 6-mm diameter macular discs and in concentric parafoveal (1- to 2-mm, 2- to 3-mm, 1- to 3-mm) and perifoveal (3- to 6-mm) rings. Group differences in imaging parameters and their relationship with visual outcomes were analyzed. A multivariate logistic model was developed to predict visual impairment from optical coherence tomography measurements in Parkinson's disease, and cutoff values were determined with receiver operating characteristic analysis. RESULTS: When compared with controls, patients with dementia with Lewy bodies had significant thinning of the ganglion cell-inner plexiform layer complex within the central 3-mm disc mainly because of differences in 1- to 3-mm parafoveal thickness. This parameter was strongly correlated in patients, but not in controls, with low contrast visual acuity and visual cognition outcomes (P < .05, False Discovery Rate), achieving 88% of accuracy in predicting visual impairment in Parkinson's disease. CONCLUSION: Our findings support that parafoveal thinning of ganglion cell-inner plexiform complex is a sensitive and clinically relevant imaging biomarker for Lewy body diseases, specifically for Parkinson's disease. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Rehabilitation, the Great Absentee of Virtual Coaching in Medical Care: Scoping Review.

BACKGROUND: In the last few years, several studies have focused on describing and understanding how virtual coaches (ie, coaching program or smart device aiming to provide coaching support through a variety of application contexts) could be key drivers for health promotion in home care settings. As there has been enormous technological progress in the field of artificial intelligence and data processing in the past decade, the use of virtual coaches gains an augmented attention in the considerations of medical innovations. OBJECTIVE: This scoping review aimed at providing an overview of the applications of a virtual coach in the clinical field. In particular, the review focused on the papers that provide tangible information for coaching activities with an active implication for engaging and guiding patients who have an ongoing plan of care. METHODS: We aimed to investigate the use of the term virtual coach in the clinical field performing a methodical review of the relevant literature indexed on PubMed, Scopus, and Embase databases to find virtual coach papers focused on specific activities dealing with clinical or medical contexts, excluding those aimed at surgical settings or electronic learning purposes. RESULTS: After a careful revision of the inclusion and exclusion criteria, 46 records were selected for the full-text review. Most of the identified articles directly or indirectly addressed the topic of physical activity. Some papers were focused on the use of virtual coaching (VC) to manage overweight or nutritional issues. Other papers dealt with technological interfaces to facilitate interactions with patients suffering from different chronic clinical conditions such as heart failure, chronic obstructive pulmonary disease, depression, and chronic pain. CONCLUSIONS: Although physical activity is a healthy practice that is most encouraged by a virtual coach system, in the current scenario, rehabilitation is the great absentee. This paper gives an overview of the tangible applications of this tool in the medical field and may inspire new ideas for future research on VC.

Structure-function multi-scale connectomics reveals a major role of the fronto-striato-thalamic circuit in brain aging.

Physiological aging affects brain structure and function impacting morphology, connectivity, and performance. However, whether some brain connectivity metrics might reflect the age of an individual is still unclear. Here, we collected brain images from healthy participants (N = 155) ranging from 10 to 80 years to build functional (resting state) and structural (tractography) connectivity matrices, both data sets combined to obtain different connectivity features. We then calculated the brain connectome age-an age estimator resulting from a multi-scale methodology applied to the structure-function connectome, and compared it to the chronological age (ChA). Our results were twofold. First, we found that aging widely affects the connectivity of multiple structures, such as anterior cingulate and medial prefrontal cortices, basal ganglia, thalamus, insula, cingulum, hippocampus, parahippocampus, occipital cortex, fusiform, precuneus, and temporal pole. Second, we found that the connectivity between basal ganglia and thalamus to frontal areas, also known as the fronto-striato-thalamic (FST) circuit, makes the major contribution to age estimation. In conclusion, our results highlight the key role played by the FST circuit in the process of healthy aging. Notably, the same methodology can be generally applied to identify the structural-functional connectivity patterns correlating to other biomarkers than ChA.

Progressive multifocal leukoencephalopathy 11 years after liver transplantation: a case report.

Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection of the central nervous system caused by JC virus. Only ten cases of PML have been reported so far in liver transplant recipients. We present a case of liver posttransplantation PML with characteristic clinical and brain MRI findings, but with an atypical late onset, developed 11 years after transplantation and after single-drug, long-term (8 years), and low-dose (750 mg twice a day) immunosuppression with mycophenolate mofetil (MMF). This is the latest onset of PML associated to liver transplant reported. The present case should help physicians to be aware of PML after transplantation, even in the long term and even under low doses of immunosuppressants, especially MMF.

The influence of posterior visual pathway damage on visual information processing speed in multiple sclerosis.

BACKGROUND: The injury of visual pathway and abnormalities of visual processing speed (VPS) are frequent in MS, but their association remains unexplored. OBJECTIVE: To evaluate the impact of posterior visual pathway structural and functional integrity on VPS of MS patients. METHODS: Cross-sectional study of 30 MS patients and 28 controls, evaluating the association of a VPS tests composite (Salthouse Perceptual Comparison test, Trail Making Test A and Symbol Digit Modalities Test) with 3T MRI visual cortex thickness, optic radiations (OR) diffusion tensor imaging indexes, and medial visual component (MVC) functional connectivity (FC) (MVC-MVC FC (iFC) and MVC-brain FC (eFC)) by linear regression, removing the effect of premorbid IQ, fatigue, and depression. RESULTS: V2 atrophy, lower OR fractional anisotropy (FA) and MVC FC significantly influenced VPS in MS (at none or lesser extent in controls), even after removing the effect of Expanded Disability Status Scale and previous optic neuritis (V2 ( r2 = 0.210): ß = +0.366, p = 0.046; OR FA ( r2 = 0.243): ß = +0.378, p = 0.034; MVC iFC, for example, left cuneus ( r2 = 0.450): ß = -0.613, p < 0.001; MVC eFC, for example, right precuneus-postcentral gyrus ( r2 = 0.368): ß = -0.466, p = 0.002). CONCLUSION: Posterior visual pathway integrity, structural (V2 thickness and OR FA) and functional (MVC FC), may explain respectively up to 24% and 45% of VPS variability in MS.

Dynamics of retinal injury after acute optic neuritis.

OBJECTIVE: We set out to assess the dynamics of retinal injury after acute optic neuritis (ON) and their association with clinical visual outcomes. METHODS: Thirty-one consecutive patients with acute ON were prospectively analyzed over a 6-month follow-up period. Each month, we used optical coherence tomography (OCT) to assess the thickness of peripapillary retinal nerve fiber layer (pRNFL) and segmented macular layers, as well as high-contrast visual acuity, low-contrast visual acuity (LCVA), color visual acuity (CVA), and visual fields (VF). RESULTS: In this prospective study, we found that 6 months after clinical onset, ON eyes suffered a reduction in pRNFL (-45.3 µm) and macular thickness (-17.3 µm). Macular atrophy was due to the decrease of macular RNFL thickness (-7.8 µm) and that of the ganglion cell layer and inner plexiform layer (GCIP, -11.3 µm), whereas the thickness of the outer retinal layers increased slightly. The macular RNFL and GCIP thickness decreased in parallel, yet it always occurred more rapidly and more severely for the GCIP. The change in the GCIP thickness in the first month predicted the visual impairment by month 6; a decrease ≥ of 4.5 µm predicted poor LCVA (sensitivity of 93% and specificity of 88%), and a decrease of ≥ 7 µm predicted poor VF and CVA (sensitivity of 78% and 100% and specificity of 63% and 66%, respectively). INTERPRETATION: Retinal axonal and neuronal damage develops quickly after ON onset. Assessment of ganglion cell layer thickness by OCT after ON onset can be used as an imaging marker of persistent visual disability.

Trans-synaptic axonal degeneration in the visual pathway in multiple sclerosis.

OBJECTIVE: To evaluate the association between the damage to the anterior and posterior visual pathway as evidence of the presence of retrograde and anterograde trans-synaptic degeneration in multiple sclerosis (MS). METHODS: We performed a longitudinal evaluation on a cohort of 100 patients with MS, acquiring retinal optical coherence tomography to measure anterior visual pathway damage (peripapillary retinal nerve fiber layer [RNFL] thickness and macular volume) and 3T brain magnetic resonance imaging (MRI) for posterior visual pathway damage (volumetry and spectroscopy of visual cortex, lesion volume within optic radiations) at inclusion and after 1 year. Freesurfer and SPM8 software was used for MRI analysis. We evaluated the relationships between the damage in the anterior and posterior visual pathway by voxel-based morphometry (VBM), multiple linear regressions, and general linear models. RESULTS: VBM analysis showed that RNFL thinning was specifically associated with atrophy of the visual cortex and with lesions in optic radiations at study inclusion (p < 0.05). Visual cortex volume (ß = +0.601, 95% confidence interval [CI] = +0.04 to +1.16), N-acetyl aspartate in visual cortex (ß = +1.075, 95% CI = +0.190 to +1.961), and lesion volume within optic radiations (ß = -2.551, 95% CI = -3.910 to -1.192) significantly influenced average RNFL thinning at study inclusion independently of other confounders, especially optic neuritis (ON). The model indicates that a decrease of 1cm(3) in visual cortex volume predicts a reduction of 0.6µm in RNFL thickness. This association was also observed after 1 year of follow-up. Patients with severe prior ON (adjusted difference = -3.01, 95% CI = -5.08 to -0.95) and mild prior ON (adjusted difference = -1.03, 95% CI = -3.02 to +0.95) had a lower adjusted mean visual cortex volume than patients without ON. INTERPRETATION: Our results suggest the presence of trans-synaptic degeneration as a contributor to chronic axon damage in MS.

Colour vision impairment is associated with disease severity in multiple sclerosis.

BACKGROUND: Colour vision assessment correlates with damage of the visual pathway and might be informative of overall brain damage in multiple sclerosis (MS). OBJECTIVE: The objective of this paper is to investigate the association between impaired colour vision and disease severity. METHODS: We performed neurological and ophthalmic examinations, as well as magnetic resonance imaging (MRI) and optical coherence tomography (OCT) analyses, on 108 MS patients, both at baseline and after a follow-up of one year. Colour vision was evaluated by Hardy, Rand and Rittler plates. Dyschromatopsia was defined if colour vision was impaired in either eye, except for participants with optic neuritis (ON), for whom only the unaffected eye was considered. We used general linear models adjusted for sex, age, disease duration and MS treatment for comparing presence of dyschromatopsia and disease severity. RESULTS: Impaired colour vision in non-ON eyes was detected in 21 out of 108 patients at baseline. At baseline, patients with dyschromatopsia had lower Multiple Sclerosis Functional Composite (MSFC) scores and Brief Repeatable Battery-Neuropsychology executive function scores than those participants with normal colour vision. In addition, these patients had thinner retinal nerve fiber layer (RNFL), and smaller macular volume, normalized brain volume and normalized gray matter volume (NGMV) at baseline. Moreover, participants with incident dyschromatopsia after one-year follow-up had a greater disability measured by the Expanded Disability Status Scale and MSFC-20 and a greater decrease in NGMV than participants with normal colour vision. CONCLUSIONS: Colour vision impairment is associated with greater MS severity.

Cognitive functions in multiple sclerosis: impact of gray matter integrity.

OBJECTIVES: Our aim was to investigate the impact of gray matter (GM) integrity on cognitive performance in multiple sclerosis (MS), and its relationship with white matter (WM) integrity and presence of lesions. METHODS: Sixty-seven patients with MS and 26 healthy controls underwent voxel-based analysis of diffusion tensor images (DTI) in GM and tract-based spatial statistics (TBSS) from WM to identify the regional correlations between cognitive functions and integrity. Lesion probability mapping (LPM) was generated for correlation analysis with cognition. Multiple linear regression analyses were used to identify the imaging measures associated with cognitive scores. RESULTS: Compared with controls, patients showed abnormal DTI indices in several GM regions and in most WM tracts. Impairment in DTI indices in specific GM regions was associated with worse performance of distinct cognitive functions. Those regions showed anatomical correspondence with cognitively relevant tracts in TBSS and LPM. The combination of regional GM and WM DTI and lesion volume accounted for 36-51% of the variance of memory and attention scores. Regional GM DTI explained less than 5% of that variance. CONCLUSION: GM and WM integrity of specific networks influences cognitive performance in MS. However, GM damage assessed by DTI only adds a small increment to the explained variance by WM in predicting cognitive functioning.

Understanding the olfactory role in post-COVID cognitive and neuropsychiatric manifestations.

Introduction: Olfactory dysfunction (OD) is frequent after SARS-CoV-2 infection. The aim of this study was to examine if long-term OD is common in post-COVID condition, and the relationship between olfaction, cognition, neuropsychiatric symptoms, and disease duration in these patients. Methods: This study included 121 participants with post-COVID condition and 51 healthy controls (HC). A comprehensive neuropsychological and neuropsychiatric assessment was conducted, encompassing various domains, including general cognition, processing speed, verbal fluency, attention, verbal memory, visual memory, visuoconstructive ability, visuospatial ability, abstraction, executive functions, anxious-depressive symptoms, general health perception, fatigue level, sleep quality, and olfaction. Statistical analyses were carried out to understand the relationship of OD with cognition, and its role as moderator variable. Results: In total, 25% of the post-covid patients had a reduced smell capacity, while only 9.3% of HC presented OD. Post-COVID patients had statistically significantly worse cognitive performance and clinical status than HC. Verbal fluency (AUC = 0.85, p < 0.001), and attention (AUC = 0.82, p < 0.001) were the variables that best discriminate between groups. OD seemed to be a moderator between fatigue and cognition, and between disease duration and attention (ß = -0.04; p = 0.014). Discussion: The study highlights marked cognitive and neuropsychiatric sequelae in individuals post-COVID relative to HC. Olfactory impairment exhibits correlations with both cognitive performance and general health. Olfaction emerges as a potential prognostic marker owing to its moderating influence on disease severity indicators.

Association of retinal neurodegeneration with the progression of cognitive decline in Parkinson's disease.

Retinal thickness may serve as a biomarker in Parkinson's disease (PD). In this prospective longitudinal study, we aimed to determine if PD patients present accelerated thinning rate in the parafoveal ganglion cell-inner plexiform layer (pfGCIPL) and peripapillary retinal nerve fiber layer (pRNFL) compared to controls. Additionally, we evaluated the relationship between retinal neurodegeneration and clinical progression in PD. A cohort of 156 PD patients and 72 controls underwent retinal optical coherence tomography, visual, and cognitive assessments between February 2015 and December 2021 in two Spanish tertiary hospitals. The pfGCIPL thinning rate was twice as high in PD (ß [SE] = -0.58 [0.06]) than in controls (ß [SE] = -0.29 [0.06], p < 0.001). In PD, the progression pattern of pfGCIPL atrophy depended on baseline thickness, with slower thinning rates observed in PD patients with pfGCIPL below 89.8 µm. This result was validated with an external dataset from Moorfields Eye Hospital NHS Foundation Trust (AlzEye study). Slow pfGCIPL progressors, characterized by older at baseline, longer disease duration, and worse cognitive and disease stage scores, showed a threefold increase in the rate of cognitive decline (ß [SE] = -0.45 [0.19] points/year, p = 0.021) compared to faster progressors. Furthermore, temporal sector pRNFL thinning was accelerated in PD (ßtime x group [SE] = -0.67 [0.26] µm/year, p = 0.009), demonstrating a close association with cognitive score changes (ß [SE] = 0.11 [0.05], p = 0.052). This study suggests that a slower pattern of pfGCIPL tissue loss in PD is linked to more rapid cognitive decline, whereas changes in temporal pRNFL could track cognitive deterioration.

Pediatric anti-N-methyl-D-aspartate receptor encephalitis-clinical analysis and novel findings in a series of 20 patients.

OBJECTIVE: To report the clinical features of 20 pediatric patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. STUDY DESIGN: Review of clinical data, long-term follow-up, and immunologic studies performed in a single center in Spain in the last 4 years. RESULTS: The median age of the patients was 13 years (range, 8 months-18 years), 70% were female. In 12 patients (60%), the initial symptoms were neurologic, usually dyskinesias or seizures, and in the other 40% psychiatric. One month into the disease, all patients had involuntary movements and alterations of behavior and speech. All patients received steroids, intravenous immunoglobulin or plasma exchange, and 7 rituximab or cyclophosphamide. With a median follow up of 17.5 months, 85% had substantial recovery, 10% moderate or severe deficits, and 1 died. Three patients had previous episodes compatible with anti-NMDAR encephalitis, 2 of them with additional relapses after the diagnosis of the disorder. Ovarian teratoma was identified in 2 patients, 1 at onset of encephalitis and the other 1 year later. Two novel observations (1 patient each) include, the identification of an electroencephalographic pattern ("extreme delta brush") considered characteristic of this disorder, and the development of anti-NMDAR encephalitis as post herpes simplex encephalitis choreoathetosis. CONCLUSIONS: The initial symptoms of pediatric anti-NMDAR encephalitis vary from those of the adults (more neurologic and less psychiatric in children), the development of a mono-symptomatic illness is extremely rare (except in relapses), and most patients respond to treatment. Our study suggests a link between post herpes simplex encephalitis choreoathetosis and anti-NMDAR encephalitis.

Analysis of prognostic factors associated with longitudinally extensive transverse myelitis.

OBJECTIVE: The aim of this study is to report the clinical profile and outcome of longitudinally extensive transverse myelitis (LETM). METHODS: We prospectively studied adult patients who presented with LETM from January 2008 to December 2011. Information on demographic, clinical course, magnetic resonance imaging (MRI) and outcome was collected. HLA-DRB1 genotype was compared with those of 225 normal controls and patients with MS (228) and neuromyelitis optica (NMO) (22). RESULTS: In total, 23 patients (16 female) with a median age of 44.5 years (range: 20-77 years) were included. Most (74%) had moderate-severe disability at nadir (48% non-ambulatory), normal/non-multiple sclerosis (MS) brain MRI (96%) and a median MRI cord lesion of 5 vertebral segments (range: 3-19). Laboratory analysis showed cerebrospinal fluid pleocytosis (45%), NMO-IgG (9%), antinuclear antibodies (70%), and genotype HLA-DRB1*13 (57%). The frequency of DRB1*13 genotype was higher compared with controls (p=0.002), MS (p=0.001) and NMO (p=0.003) patients. After a median follow-up of 32 months, one patient converted to MS, two had relapsing LETM with NMO-IgG, and 20 remained as idiopathic with recurrences in four (20%). Twelve (52%) patients recovered with minimal disability (Expanded Disability Status Scale (EDSS) ≤2.5) and three (13%) remained wheelchair dependent. Disability at nadir was associated with the final outcome and extension of the spinal cord lesion with risk of recurrence. Recurrence was not associated with worse outcome. CONCLUSIONS: Inflammatory LETM is mostly idiopathic with a good outcome. It includes a relatively homogenous group of patients with an overrepresentation of the HLA-DRB1*13 genotype. EDSS at nadir is a predictor of the final outcome and extension of the myelitis of the recurrence risk.

Brain Degeneration in Synucleinopathies Based on Analysis of Cognition and Other Nonmotor Features: A Multimodal Imaging Study.

BACKGROUND: We aimed to characterize subtypes of synucleinopathies using a clustering approach based on cognitive and other nonmotor data and to explore structural and functional magnetic resonance imaging (MRI) brain differences between identified clusters. METHODS: Sixty-two patients (n = 6 E46K-SNCA, n = 8 dementia with Lewy bodies (DLB) and n = 48 idiopathic Parkinson's disease (PD)) and 37 normal controls underwent nonmotor evaluation with extensive cognitive assessment. Hierarchical cluster analysis (HCA) was performed on patients' samples based on nonmotor variables. T1, diffusion-weighted, and resting-state functional MRI data were acquired. Whole-brain comparisons were performed. RESULTS: HCA revealed two subtypes, the mild subtype (n = 29) and the severe subtype (n = 33). The mild subtype patients were slightly impaired in some nonmotor domains (fatigue, depression, olfaction, and orthostatic hypotension) with no detectable cognitive impairment; the severe subtype patients (PD patients, all DLB, and the symptomatic E46K-SNCA carriers) were severely impaired in motor and nonmotor domains with marked cognitive, visual and bradykinesia alterations. Multimodal MRI analyses suggested that the severe subtype exhibits widespread brain alterations in both structure and function, whereas the mild subtype shows relatively mild disruptions in occipital brain structure and function. CONCLUSIONS: These findings support the potential value of incorporating an extensive nonmotor evaluation to characterize specific clinical patterns and brain degeneration patterns of synucleinopathies.

Multimodal visual system analysis as a biomarker of visual hallucinations in Parkinson's disease.

Visual hallucinations (VH) are present in up to 75% of Parkinson's disease (PD) patients. However, their neural bases and participation of the visual system in VH are not well-understood in PD. Seventy-four participants, 12 PD with VH (PDVH), 35 PD without VH (PDnoVH) and 27 controls underwent a battery of primary visual function and visual cognition tests, retinal optical coherence tomography and structural and resting-state functional brain MRI. We quantified cortical thickness with Freesurfer and functional connectivity (FC) of Visual (VIS), Fronto-Parietal (FP), Ventral Attention (VAN) and Dorsal Attention (DAN) networks with CONN toolbox. Group comparisons were performed with MANCOVA. Area Under the Curve (AUC) was computed to assess the ability of visual variables to differentiate PDVH and PDnoVH. There were no significant PDVH vs PDnoVH differences in disease duration, motor manifestations, general cognition or dopamine agonist therapy (DA) use. Compared to PDnoVH and HC, and regardless of DA use, PDVH showed significantly reduced contrast sensitivity, visuoperceptive and visuospatial abilities, increased retina photoreceptor layer thickness, reduced cortical thickness mostly in right visual associative areas, decreased between-network VIS-VAN and VAN-DAN connectivity and increased within-network DAN connectivity. The combination of clinical and imaging variables that best discriminated PDVH and PDnoVH (highest AUC), where within-network DAN FC, photoreceptor layer thickness and cube analysis test from Visual Object and Space Perception Battery (accuracy of 81.8%). Compared to PDnoVH, PDVH have specific functional and structural abnormalities within the visual system, which can be quantified non-invasively and could potentially constitute biomarkers for VH in PD.

Retinal thickness as a biomarker of cognitive impairment in manifest Huntington's disease.

BACKGROUND: Cognitive decline has been reported in premanifest and manifest Huntington's disease but reliable biomarkers are lacking. Inner retinal layer thickness seems to be a good biomarker of cognition in other neurodegenerative diseases. OBJECTIVE: To explore the relationship between optical coherence tomography-derived metrics and global cognition in Huntington's Disease. METHODS: Thirty-six patients with Huntington's disease (16 premanifest and 20 manifest) and 36 controls matched by age, sex, smoking status, and hypertension status underwent macular volumetric and peripapillary optical coherence tomography scans. Disease duration, motor status, global cognition and CAG repeats were recorded in patients. Group differences in imaging parameters and their association with clinical outcomes were analyzed using linear mixed-effect models. RESULTS: Premanifest and manifest Huntington's disease patients presented thinner retinal external limiting membrane-Bruch's membrane complex, and manifest patients had thinner temporal peripapillary retinal nerve fiber layer compared to controls. In manifest Huntington's disease, macular thickness was significantly associated with MoCA scores, inner nuclear layer showing the largest regression coefficients. This relationship was consistent after adjusting for age, sex, and education and p-value correction with False Discovery Rate. None of the retinal variables were related to Unified Huntington's Disease Rating Scale score, disease duration, or disease burden. Premanifest patients did not show a significant association between OCT-derived parameters and clinical outcomes in corrected models. CONCLUSIONS: In line with other neurodegenerative diseases, OCT is a potential biomarker of cognitive status in manifest HD. Future prospective studies are needed to evaluate OCT as a potential surrogate marker of cognitive decline in HD.