Neuropsychiatric symptoms with focus on apathy and irritability in sporadic and hereditary cerebral amyloid angiopathy.

BACKGROUND: Neuropsychiatric symptoms (NPS) may affect cognition, but their burden in cerebral amyloid angiopathy (CAA), one of the main causes of intracerebral hemorrhage (ICH) and dementia in the elderly, remains unclear. We investigated NPS, with emphasis on apathy and irritability in sporadic (sCAA) and Dutch-type hereditary (D-)CAA. METHODS: We included patients with sCAA and (pre)symptomatic D-CAA, and controls from four prospective cohort studies. We assessed NPS per group, stratified for history of ICH, using the informant-based Neuropsychiatric Inventory (NPI-Q), Starkstein Apathy scale (SAS), and Irritability Scale. We modeled the association of NPS with disease status, executive function, processing speed, and CAA-burden score on MRI and investigated sex-differences. RESULTS: We included 181 participants: 82 with sCAA (mean[SD] age 72[6] years, 44% women, 28% previous ICH), 56 with D-CAA (52[11] years, 54% women, n = 31[55%] presymptomatic), and 43 controls (69[9] years, 44% women). The NPI-Q NPS-count differed between patients and controls (sCAA-ICH+:adj.ß = 1.4[95%CI:0.6-2.3]; sCAA-ICH-:1.3[0.6-2.0]; symptomatic D-CAA:2.0[1.1-2.9]; presymptomatic D-CAA:1.2[0.1-2.2], control median:0[IQR:0-3]), but not between the different CAA-subgroups. Apathy and irritability were reported most frequently: n = 12[31%] sCAA, 19[37%] D-CAA had a high SAS-score; n = 12[29%] sCAA, 14[27%] D-CAA had a high Irritability Scale score. NPS-count was associated with decreased processing speed (adj.ß=-0.6[95%CI:-0.8;-0.4]) and executive function (adj.ß=-0.4[95%CI:-0.6;-0.1]), but not with radiological CAA-burden. Men had NPS more often than women. DISCUSSION: According to informants, one third to half of patients with CAA have NPS, mostly apathy, even in presymptomatic D-CAA and possibly with increased susceptibility in men. Neurologists should inform patients and caregivers of these disease consequences and treat or refer patients with NPS appropriately.

Predicting Motor Outcome and Quality of Life After Subthalamic Deep Brain Stimulation for Parkinson's Disease: The Role of Standard Screening Measures and Wearable-Data.

BACKGROUND: Standardized screening for subthalamic deep brain stimulation (STN DBS) in Parkinson's disease (PD) patients is crucial to determine eligibility, but its utility to predict postoperative outcomes in eligible patients is inconclusive. It is unknown whether wearable data can contribute to this aim. OBJECTIVE: To evaluate the utility of universal components incorporated in the DBS screening, complemented by a wearable sensor, to predict motor outcomes and Quality of life (QoL) one year after STN DBS surgery. METHODS: Consecutive patients were included in the OPTIMIST cohort study from two DBS centers. Standardized assessments included a preoperative Levodopa Challenge Test (LCT), and questionnaires on QoL and non-motor symptoms including cognition, psychiatric symptoms, impulsiveness, autonomic symptoms, and sleeping problems. Moreover, an ambulatory wearable sensor (Parkinson Kinetigraph (PKG)) was used. Postoperative assessments were similar and also included a Stimulation Challenge Test to determine DBS effects on motor function. RESULTS: Eighty-three patients were included (median (interquartile range) age 63 (56-68) years, 36% female). Med-OFF (Stim-OFF) motor severity deteriorated indicating disease progression, but patients significantly improved in terms of Med-ON (Stim-ON) motor function, motor fluctuations, QoL, and most non-motor domains. Motor outcomes were not predicted by preoperative tests, including covariates of either LCT or PKG. Postoperative QoL was predicted by better preoperative QoL, lower age, and more preoperative impulsiveness scores in multivariate models. CONCLUSION: Data from the DBS screening including wearable data do not predict postoperative motor outcome at one year. Post-DBS QoL appears primarily driven by non-motor symptoms, rather than by motor improvement.

Clinical outcome in patients with suspected inflammatory neuropsychiatric lupus treated with immunosuppression: an observational cohort study.

BACKGROUND: The short-term and long-term outcome of inflammatory neuropsychiatric SLE (NPSLE) with immunosuppressive treatment is largely unknown. We used clinical data from our tertiary referral centre for NPSLE to investigate the type of inflammatory NPSLE manifestations, type of immunosuppressive treatment prescribed for these manifestations and clinical outcomes. METHODS: All patients with SLE visiting the Leiden University Medical Centre NPSLE clinic between 2007 and 2021 receiving immunosuppressive therapy for neuropsychiatric symptoms were included. Clinical, immunological and radiological information was collected in as standardised way during a 1-day multidisciplinary assessment. In a multidisciplinary consensus meeting, the presence of NPSLE and the type of NPSLE manifestations and treatment were determined. For this study, short-term (0-6 months) and long-term outcomes (7-24 months) of the NP symptoms were assessed by two independent readers and scored on a 7-point Likert scale, ranging from death to resolved. RESULTS: In total, 95 out of 398 (24%) patients visiting the NPSLE clinic between 2007 and 2021 received any form of immunosuppressive treatment for 101 separate NPSLE events. The most common NP manifestation was cognitive dysfunction (50%) as identified by formal cognitive assessment, often present in combination with other NPSLE manifestations. Treatment modalities were induction (24%), induction and maintenance (73%) and other therapy (3%). The treatments mostly consisted of (combinations of) prednisone (97%), methylprednisolone (53%), azathioprine (generally 2 mg/kg daily) (49%) and cyclophosphamide (generally induction 750 mg/m2 every 4 weeks for 24 weeks or 500mg biweekly for 12 weeks) (42%). Short-term outcome showed improvement on the Likert scale in 73% (improved: 22%, much improved: 29%, resolved: 22%), no change in 21% and worsening in 6% of patients. Long-term outcome was available for 78 out of 101 events and showed improvement in 70% (improved: 14%, much improved: 28%, resolved: 28%), no change in 17%, worsening in 10% and death in 3% of patients (none directly NPSLE-related). CONCLUSION: The outcome of inflammatory NPSLE after immunosuppressive treatment is generally good, with improvement of neuropsychiatric symptoms occuring in approximately 70% of events.

High Prevalence but Low Impact of Cognitive Dysfunction on Quality of Life in Patients With Lupus and Neuropsychiatric Symptoms.

OBJECTIVE: To evaluate the prevalence and impact of cognitive impairment on health-related-quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE) and neuropsychiatric (NP) symptoms. METHODS: Patients with SLE and NP symptoms referred to the Leiden NPSLE clinic (2007-2019) were included. In a multidisciplinary evaluation, NP symptoms were attributed to SLE (NPSLE: inflammatory, ischemic, or both combined) or other causes. Four cognitive domains were determined: global cognitive function (score 0-30), learning and memory, executive function and complex attention, and psychomotor speed (all T scores). HRQoL was determined using the mental component score and physical component score of the Short Form 36 health survey. The associations between cognition and NPSLE phenotype and cognition and HRQoL were assessed with multiple regression analyses and linear mixed models corrected for confounding and expressed in SDs. RESULTS: A total of 357 patients (86% female, mean age 44 years) were included. Of those 357 patients, 169 had a follow-up visit (median follow-up 11 months). Impairment in global cognitive function was present in 8% of patients, and in all other cognitive domains in ±50%. The most severe impairment (all domains) was seen in patients with a combined NPSLE phenotype. Diffuse cognitive impairment (learning and memory, executive function and complex attention, and psychomotor speed) was most common and was present more often in patients with an inflammatory phenotype. A weak association between cognition and HRQoL was found both cross-sectionally and longitudinally. In general, 1 SD lower scores on the cognitive domains were associated with at most one-fifth SD lower HRQoL. CONCLUSION: Objective cognitive impairment is common in SLE patients with NP symptoms, but may have a limited influence on HRQoL.

Patient-Related Factors Influencing Caregiver Burden in Parkinson's Disease Patients: Comparison of Effects Before and After Deep Brain Stimulation.

BACKGROUND: Caregivers of Parkinson's disease (PD) patients provide important support during the pre- and postoperative phase of deep brain stimulation (DBS). High levels of caregiver burden have been reported after DBS. However, a comparison between preoperative and postoperative burden and associated factors has been insufficiently studied. OBJECTIVE: To investigate the influence of DBS on caregiver burden, and to identify the differential impact of patient-related factors on caregiver burden before and after DBS. METHODS: Consecutive patients referred for DBS eligibility screening or during one-year follow-up assessments were included. Caregiver burden was measured with the short Zarit Burden Interview (ZBI-12). Inverse Probability Weighting (IPW) was used to compare caregiver burden between preoperative and postoperative assessments. RESULTS: We included 47 patients (24 screening, 23 follow-up) (median age 65 years, 29.4% female sex). DBS did not impact caregiver burden (screening: median ZBI-12 9.5 (IQR 3.25, 16.75); follow-up median ZBI-12 6 (IQR 4, 14); IPW-coefficient 0.57 (95% CI -2.75, 3.89)). Worse caregiver burden during DBS screening was associated with worse patient-related scores on depressive symptoms, anxiety, QoL, and impulsiveness. Worse scores on depressive symptoms, anxiety, apathy, postural-instability-gait-disorder, and QoL were associated with worse caregiver burden at one-year follow-up. CONCLUSION: DBS appears not associated with changes in caregiver burden. Various symptoms are valued differently between screening and follow-up assessments in terms of caregiver burden. Early recognition of caregivers "at risk" may improve guidance of patient-caregiver dyads throughout the DBS process.

Self-reported work productivity in people with multiple sclerosis and its association with mental and physical health.

PURPOSE: This study aimed to identify mental health, physical health, demographic and disease characteristics relating to work productivity in people with multiple sclerosis (MS). METHODS: In this cross-sectional study, 236 employed people with MS (median age = 42 years, 78.8% female) underwent neurological and neuropsychological assessments. Additionally, they completed questionnaires inquiring about work productivity (presenteeism: reduced productivity while working, and absenteeism: loss of productivity due to absence from work), mental and physical health, demographic and disease characteristics. Multiple linear and logistic regression analyses were performed with presenteeism and absenteeism as dependent variables, respectively. RESULTS: A model with mental and physical health factors significantly predicted presenteeism F(11,202) = 11.33, p < 0.001, R2 = 0.38; a higher cognitive (p < 0.001) and physical impact (p = 0.042) of fatigue were associated with more presenteeism. A model with only mental health factors significantly predicted absenteeism; χ2(11)=37.72, p < 0.001, with R2 = 0.27 (Nagelkerke) and R2 = 0.16 (Cox and Snell). Specifically, we observed that more symptoms of depression (p = 0.041) and a higher cognitive impact of fatigue (p = 0.011) were significantly associated with more absenteeism. CONCLUSIONS: In people with MS, both cognitive and physical impact of fatigue are positively related to presenteeism, while symptoms of depression and cognitive impact of fatigue are positively related to absenteeism.Implications for rehabilitationMultiple sclerosis (MS) affects people of working age, significantly interfering with work productivity.Higher cognitive and physical impact of fatigue were associated with more presenteeism in workers with MS.A higher cognitive impact of fatigue and more depressive symptoms were associated with absenteeism in workers with MS.Occupational and healthcare professionals should be aware of the impact of both physical and mental health on work productivity in workers with MS.

Cross-cohort generalizability of deep and conventional machine learning for MRI-based diagnosis and prediction of Alzheimer's disease.

This work validates the generalizability of MRI-based classification of Alzheimer's disease (AD) patients and controls (CN) to an external data set and to the task of prediction of conversion to AD in individuals with mild cognitive impairment (MCI). We used a conventional support vector machine (SVM) and a deep convolutional neural network (CNN) approach based on structural MRI scans that underwent either minimal pre-processing or more extensive pre-processing into modulated gray matter (GM) maps. Classifiers were optimized and evaluated using cross-validation in the Alzheimer's Disease Neuroimaging Initiative (ADNI; 334 AD, 520 CN). Trained classifiers were subsequently applied to predict conversion to AD in ADNI MCI patients (231 converters, 628 non-converters) and in the independent Health-RI Parelsnoer Neurodegenerative Diseases Biobank data set. From this multi-center study representing a tertiary memory clinic population, we included 199 AD patients, 139 participants with subjective cognitive decline, 48 MCI patients converting to dementia, and 91 MCI patients who did not convert to dementia. AD-CN classification based on modulated GM maps resulted in a similar area-under-the-curve (AUC) for SVM (0.940; 95%CI: 0.924-0.955) and CNN (0.933; 95%CI: 0.918-0.948). Application to conversion prediction in MCI yielded significantly higher performance for SVM (AUC = 0.756; 95%CI: 0.720-0.788) than for CNN (AUC = 0.742; 95%CI: 0.709-0.776) (p<0.01 for McNemar's test). In external validation, performance was slightly decreased. For AD-CN, it again gave similar AUCs for SVM (0.896; 95%CI: 0.855-0.932) and CNN (0.876; 95%CI: 0.836-0.913). For prediction in MCI, performances decreased for both SVM (AUC = 0.665; 95%CI: 0.576-0.760) and CNN (AUC = 0.702; 95%CI: 0.624-0.786). Both with SVM and CNN, classification based on modulated GM maps significantly outperformed classification based on minimally processed images (p=0.01). Deep and conventional classifiers performed equally well for AD classification and their performance decreased only slightly when applied to the external cohort. We expect that this work on external validation contributes towards translation of machine learning to clinical practice.

Preoperative Electroencephalography-Based Machine Learning Predicts Cognitive Deterioration After Subthalamic Deep Brain Stimulation.

BACKGROUND: Subthalamic deep brain stimulation (STN DBS) may relieve refractory motor complications in Parkinson's disease (PD) patients. Despite careful screening, it remains difficult to determine severity of alpha-synucleinopathy involvement which influences the risk of postoperative complications including cognitive deterioration. Quantitative electroencephalography (qEEG) reflects cognitive dysfunction in PD and may provide biomarkers of postoperative cognitive decline. OBJECTIVE: To develop an automated machine learning model based on preoperative EEG data to predict cognitive deterioration 1 year after STN DBS. METHODS: Sixty DBS candidates were included; 42 patients had available preoperative EEGs to compute a fully automated machine learning model. Movement Disorder Society criteria classified patients as cognitively stable or deteriorated at 1-year follow-up. A total of 16,674 EEG-features were extracted per patient; a Boruta algorithm selected EEG-features to reflect representative neurophysiological signatures for each class. A random forest classifier with 10-fold cross-validation with Bayesian optimization provided class-differentiation. RESULTS: Tweny-five patients were classified as cognitively stable and 17 patients demonstrated cognitive decline. The model differentiated classes with a mean (SD) accuracy of 0.88 (0.05), with a positive predictive value of 91.4% (95% CI 82.9, 95.9) and negative predictive value of 85.0% (95% CI 81.9, 91.4). Predicted probabilities between classes were highly differential (hazard ratio 11.14 [95% CI 7.25, 17.12]); the risk of cognitive decline in patients with high probabilities of being prognosticated as cognitively stable (>0.5) was very limited. CONCLUSIONS: Preoperative EEGs can predict cognitive deterioration after STN DBS with high accuracy. Cortical neurophysiological alterations may indicate future cognitive decline and can be used as biomarkers during the DBS screening. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Vigilance: discussion of related concepts and proposal for a definition.

We reviewed current definitions of vigilance to propose a definition, applicable in sleep medicine. As previous definitions contained terms such as attention, alertness, and arousal, we addressed these concepts too. We defined alertness as a quantitative measure of the mind state governing sensitivity to stimuli. Arousal comprises a stimulus-induced upward change in alertness, irrespective of the subsequent duration of the increased level of alertness. Vigilance is defined as the capability to be sensitive to potential changes in one's environment, ie the capability to reach a level of alertness above a threshold for a certain period of time rather than the state of alertness itself. It has quantitative and temporal dimensions. Attention adds direction towards a stimulus to alertness, requiring cognitive control: it involves being prepared to process stimuli coming from an expected direction. Sustained attention corresponds to a state in which some level of attention is purposefully maintained, adding a time factor to the definition of attention. Vigilance differs from sustained attention in that the latter in addition implies a direction to which attention is cognitively directed as well as a specification of duration. Attempts to measure vigilance, however, are often in fact measurements of sustained attention.

Effect of deep brain stimulation on caregivers of patients with Parkinson's disease: A systematic review.

BACKGROUND: Caregivers of patients with Parkinson's Disease (PD) often provide important support in the pre- and postoperative phase of Deep Brain Stimulation (DBS). DBS-associated changes of patient-functioning may affect caregiver wellbeing and impact the support system. Factors influencing caregiver-wellbeing under these circumstances are incompletely known. OBJECTIVE: to systematically review studies of sufficient methodological quality on the impact of DBS on caregivers of PD patients. METHODS: using PRISMA guidelines, major databases were searched up to May 2020. Five subcategories were identified: Caregiver burden, Caregiver cognitive and psychiatric functioning, Caregiver Quality of Life (QoL), Marital Satisfaction/Conflicts, and Caregiver Satisfaction. Quality was assessed using an in-house checklist. RESULTS: 293 studies were identified; 12 were ultimately included. Caregiver burden, psychiatric and cognitive functioning and QoL remained relatively unchanged. Results on marital satisfaction/conflicts were contrasting: an increase in marital conflicts despite improved relationship quality scores DBS. Caregiver satisfaction with surgery was low with 50-58% of caregivers being disappointed with DBS outcomes. Concerning caregiver related factors: a higher preoperative caregiver QoL, younger age, lower scores on psychiatric rating scales, and more favourable preoperative relationship quality scores, were associated with better caregiver wellbeing. A favourable patient-profile includes younger age and age-at-onset, shorter disease duration, lower medication requirements, and lower scores on psychiatric rating scales. CONCLUSION: Although most patient- and caregiver-related subdomains remained unchanged after DBS, dissatisfaction among caregivers and marital problems may constitute a large risk for a well-functioning patient-caregiver dyad. Early recognition of potential problem situations may improve post-DBS care for both patients and caregivers.

Mortality in patients with systemic lupus erythematosus and neuropsychiatric involvement: A retrospective analysis from a tertiary referral center in the Netherlands.

OBJECTIVE: We aimed to evaluate all-cause and cause-specific mortality in patients with systemic lupus erythematosus (SLE) and neuropsychiatric (NP) symptoms in the Netherlands between 2007-2018. METHODS: Patients visiting the tertiary referral NPSLE clinic of the Leiden University Medical Center were included. NP symptoms were attributed to SLE requiring treatment (major NPSLE) or to other and mild causes (minor/non-NPSLE). Municipal registries were checked for current status (alive/deceased). Standardized mortality ratios (SMRs) and 95% confidence intervals (CI) were calculated using data from the Dutch population. Rate ratio (RR) and 95% CI were calculated using direct standardization to compare mortality between major NPSLE and minor/non-NPSLE. RESULTS: 351 patients were included and 149 patients were classified as major NPSLE (42.5%). Compared with the general population, mortality was increased in major NPSLE (SMR 5.0 (95% CI: 2.6-8.5)) and minor/non-NPSLE patients (SMR 3.7 (95% CI: 2.2-6.0)). Compared with minor/non-NPSLE, mortality was similar in major NPSLE patients (RR: 1.0 (95% CI: 0.5-2.0)). Cause-specific mortality rates demonstrated an increased risk of death due to infections in both groups, whereas death due to cardiovascular disease was only increased in minor/non-NPSLE patients. CONCLUSION: Mortality was increased in both major NPSLE and minor/non-NPSLE patients in comparison with the general population. There was no difference in mortality between major NPSLE and minor/non-NPSLE patients.

The Association Between Biomarkers and Neuropsychiatric Symptoms Across the Alzheimer's Disease Spectrum.

OBJECTIVE: To investigate the relationship between Alzheimer's disease biomarkers and neuropsychiatric symptoms. METHODS: Data from two large cohort studies, the Dutch Parelsnoer Institute - Neurodegenerative Diseases and the Alzheimer's Disease Neuroimaging Initiative was used, including subjects with subjective cognitive decline (N = 650), mild cognitive impairment (N = 887), and Alzheimer's disease dementia (N = 626). Cerebrospinal fluid (CSF) levels of Aß42, t-tau, p-tau, and hippocampal volume were associated with neuropsychiatric symptoms (measured with the Neuropsychiatric Inventory) using multiple logistic regression analyses. The effect of the Mini-Mental State Examination (as proxy for cognitive functioning) on these relationships was assessed with mediation analyses. RESULTS: Alzheimer's disease biomarkers were not associated with depression, agitation, irritability, and sleep disturbances. Lower levels of CSF Aß42, higher levels of t- and p-tau were associated with presence of anxiety. Lower levels of CSF Aß42 and smaller hippocampal volumes were associated with presence of apathy. All associations were mediated by cognitive functioning. CONCLUSION: The association between Alzheimer's disease pathology and anxiety and apathy is partly due to impairment in cognitive functioning.

Cognitive functioning as a predictor of employment status in relapsing-remitting multiple sclerosis: a 2-year longitudinal study.

BACKGROUND: Cognitive functioning has been linked to employment outcomes in multiple sclerosis (MS) in cross-sectional studies. Longitudinal studies are however lacking and previous studies did not extensively examine executive functioning. OBJECTIVES: We examined whether baseline cognitive functioning predicts a change in employment status after 2 years, while taking into account mood, fatigue and disability level. METHODS: A total of 124 patients with relapsing-remitting MS (pwMS) and 60 healthy controls were included. They underwent neurological and neuropsychological examinations and completed online questionnaires. PwMS were divided into a stable and deteriorated employment status group (SES and DES), based on employment status 2 years after baseline. We first examined baseline differences between the SES and DES groups in cognitive functioning, mood, fatigue and disability level. A logistic regression analysis was performed, with change in employment status (SES/DES) as dependent variable. RESULTS: The DES group included 22% pwMS. Group differences were found in complex attention, executive functioning, self-reported cognitive functioning, fatigue and physical disability. More physical disability (OR = 1.90, p = 0.01) and lower executive functioning (OR = 0.30, p = 0.03) were retained as independent predictors of DES (R2 = 0.22, p ≤ 0.001). CONCLUSIONS: Baseline physical disability and executive functioning, but none of the other variables, moderately predicted a deterioration in employment status 2 years later. TRIAL REGISTRATION: This observational study is registered under NL43098.008.12: 'Voorspellers van arbeidsparticipatie bij mensen met relapsing-remitting Multiple Sclerose'. This study is registered at the Dutch CCMO register (https://www.toetsingonline.nl).

Incidence and Clinical Significance of Cerebral Embolism During Atrial Fibrillation Ablation With Duty-Cycled Phased-Radiofrequency Versus Cooled-Radiofrequency: A Randomized Controlled Trial.

OBJECTIVES: The purpose of this study was to randomly compare the incidence of asymptomatic cerebral embolism (ACE) between the second-generation pulmonary vein ablation catheter (PVAC Gold) and the irrigated Thermocool catheter. BACKGROUND: Pulmonary vein isolation (PVI) with the PVAC is associated with ACE. The PVAC Gold was designed to avoid this complication. METHODS: Patients with paroxysmal atrial fibrillation were randomized 1:1 to PVI with the PVAC Gold or Thermocool catheter. Cerebral magnetic resonance imaging was performed in the days before and after ablation and repeated after 3 months in case of a new lesion. Monitoring for microembolic signals (MES) was performed by using transcranial Doppler ultrasonography. Parameters of coagulation were determined before, during, and after ablation. Neuropsychological tests and questionnaires were applied 10 days before and 3 months after ablation. RESULTS: Seventy patients were included in the study (mean age 61 ± 9 years; 43 male subjects; CHA2DS2-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65 to 74 years, sex category] score 1.6 ± 1.2; international normalized ratio 2.7 ± 0.5; activated clotting time 374 ± 24 s; p > 0.05 for all parameters). Procedural duration was shorter in the PVAC Gold group (140 ± 34 vs. 207 ± 44 min; p < 0.001). Eight (23%; 7 infarcts) patients in the PVAC Gold group exhibited a new ACE, compared with 2 (6%; no infarcts) patients in the Thermocool group (p = 0.042). Median number of MES was higher in the PVAC Gold group (1,111 [interquartile range, 715-2,234] vs. 787 [interquartile range, 532-1,053]; p < 0.001). There were no differences between groups regarding coagulation and neuropsychological outcomes. CONCLUSIONS: PVI with the new PVAC Gold was associated with a higher incidence of ACE/cerebral infarcts and number of MES. Both catheters induced a comparable procoagulant state. Because there were no measurable differences in neuropsychological status, the clinical significance of ACE remains unclear. (Cerebral Embolism [CE] in Catheter Ablation of Atrial Fibrillation [AF] [CE-AF]; NCT01361295).

Visual Object Perception in Premanifest and Early Manifest Huntington's Disease.

OBJECTIVE: In Huntington's disease (HD), a hereditary neurodegenerative disorder, cognitive impairment in early disease stages mainly involves executive dysfunction. However, visual cognitive deficits have additionally been reported and are of clinical relevance given their influence on daily life and overall cognitive performance. This study aimed to assess visual perceptual skills in HD gene carriers. METHODS: Subtasks of the Visual Object and Space Perception battery and Groningen Intelligence Test were administered in 62 participants (18 healthy controls, 22 participants with a genetic confirmation of HD without symptoms, i.e., premanifest HD, and 22 participants with a genetic confirmation of HD with symptoms, i.e., manifest HD). Group differences in task performance were measured using analysis of covariance with and without correction for age. Receiver Operating Characteristics (ROC) analysis was performed to examine which task best discriminated between groups and cut-off scores were provided. RESULTS: Manifest HD performed significantly worse compared to both controls and premanifest HD on all visual perceptional tasks. Premanifest HD did not differ in task performance from controls. Besides the Shape Detection, all tasks were robust in discriminating between groups. The Animal Silhouettes test was most accurate in discriminating manifest HD from premanifest HD (AUC = 0.90, SE = 0.048, p < .001). CONCLUSION: Visual perceptual deficits are present in early manifest HD, especially an impaired recognition of animals and objects from sketched silhouettes, and not in premanifest HD. This suggests that decline in visual processing only occurs in clinical disease stages. The visual cognitive battery, especially the Silhouettes tasks used in this study is sensitive in discriminating manifest HD from premanifest HD and controls.

Value of multidisciplinary reassessment in attribution of neuropsychiatric events to systemic lupus erythematosus: prospective data from the Leiden NPSLE cohort.

Objective: To determine the contribution of reassessment in the attribution process of neuropsychiatric (NP) events to SLE or other aetiologies in a large, prospective and multidisciplinary assessed NPSLE cohort and to compare these results with other available attribution models for NP events occurring in SLE. Methods: Three hundred and four consecutive SLE patients presenting NP events were evaluated. All subjects underwent standardized multidisciplinary medical, neuropsychological, laboratory and radiological examination on the inclusion and reassessment dates. Diagnosis was always established by multidisciplinary consensus. The final diagnosis after reassessment also took into account disease course and response to treatment. These data were compared with currently available attribution models for NP events in SLE. Results: A total of 463 NP events were established. After reassessment, attribution to SLE was discordant in 64 (13.8%) NP events when compared with the first visit. We show that 14.5% of NP events previously attributed to SLE reclassified as non-NPSLE. In 86.4% of these patients immunosuppressive therapy was started after the first visit. When reassessment and available attribution models were compared, NPSLE cases overlapped considerably. Although specificity was high for all comparisons (0.81-0.95), an important variation in sensitivity (0.39-0.83) and agreement estimates (κ = 0.29-0.68) was observed. The Italian algorithm showed the highest sensitivity and specificity (>0.80) and moderate agreement (0.59-0.64). Conclusion: In clinical practice NP events presenting in SLE are too often attributed to an immune-mediated origin. Multidisciplinary reassessment avoids misclassification in NPSLE. Multidisciplinary reassessment is the reference standard in NP events presenting in SLE and cannot be replaced by available attribution models.

Early Magnetic Resonance Imaging and Cognitive Markers of Hereditary Cerebral Amyloid Angiopathy.

BACKGROUND AND PURPOSE: Early markers for cerebral amyloid angiopathy are largely unknown. We aimed to identify which magnetic resonance imaging (MRI) (performed at 7 and 3T) and cognitive markers are an early sign in (pre) symptomatic subjects with hereditary cerebral hemorrhage with amyloidosis-Dutch type. METHODS: Twenty-seven DNA-proven Dutch-type mutation carriers (15 symptomatic and 12 presymptomatic) (mean age of 45.9 years) and 33 controls (mean age of 45.6 years) were included. 7T and 3T MRI was performed, cerebral amyloid angiopathy and small-vessel disease type MRI markers were estimated, and cognitive performance was assessed. Univariate general linear modeling analysis was used to assess the association between MRI markers and cognitive performance on the one hand and on the other, mutation status, adjusted for age, sex, and education. RESULTS: In symptomatic patients, all established cerebral amyloid angiopathy MRI markers (microbleeds, intracerebral hemorrhages, subarachnoid hemorrhages, superficial siderosis, microinfarcts, volume of white matter hyperintensities, and dilated perivascular spaces in centrum semiovale) were increased compared with controls (P<0.05). In presymptomatic subjects, the prevalence of microinfarcts and median volume of white matter hyperintensities were increased in comparison to controls (P<0.05). Symptomatic patients performed worse on all cognitive domains, whereas presymptomatic subjects did not show differences in comparison with controls (P<0.05). CONCLUSIONS: White matter hyperintensities and microinfarcts are more prevalent among presymptomatic subjects and precede cognitive and neuropsychiatric symptoms and intracerebral hemorrhages.

Changes in White Matter Microstructure Suggest an Inflammatory Origin of Neuropsychiatric Systemic Lupus Erythematosus.

OBJECTIVE: To assess white matter (WM) and gray matter (GM) magnetization transfer ratio histogram peak heights (MTR-HPHs) in different subsets of patients with neuropsychiatric systemic lupus erythematosus (NPSLE) who have unremarkable findings on 3T magnetic resonance imaging of the brain and to evaluate whether these values could be used to highlight different clinically suspected underlying pathogenic processes or identify the clinical NPSLE status or whether they could be associated with a specific NPSLE syndrome. METHODS: Sixty-four SLE patients with neuropsychiatric symptoms were included. The initial NPSLE diagnosis and suspected underlying pathogenic process were established by multidisciplinary evaluation. The final diagnosis was made after also considering the disease course 6-18 months later. Thirty-three patients with central nervous system (CNS) NPSLE and 31 SLE patients with neuropsychiatric symptoms unrelated to SLE (non-SLE-related NP) were included. Twenty SLE patients without neuropsychiatric symptoms and 36 healthy control subjects were included for comparison. Differences in the WM and GM mean MTR-HPHs and between the different NPSLE subgroups (CNS NPSLE diagnosis, NPSLE phenotype [inflammatory or ischemic], and clinical changes after treatment) and the relationship to NPSLE syndromes were evaluated. RESULTS: Patients with inflammatory NPSLE had significantly lower WM MTR-HPHs than did the healthy controls, the SLE patients, and the non-SLE-related NP patients. Cognitive disorder, mood disorder, and psychosis were related to lower WM MTR-HPH values and cerebrovascular symptoms to higher values. Furthermore, the mean MTR-HPHs in the WM increased when the clinical status of the NPSLE patients improved. CONCLUSION: Measurement of MTR-HPH of the WM has the potential to identify inflammatory NPSLE with CNS involvement. This finding underscores the usefulness of this technique for the detection of cerebral changes in NPSLE patients and for the assessment of clinical changes after treatment.