Plasma Inflammatory Biomarkers Are Associated With Poststroke Cognitive Impairment: The Nor-COAST Study.

BACKGROUND: Inflammation is proposed to be involved in the pathogenesis of poststroke cognitive impairment. The aim of this study was to investigate associations between concentrations of systemic inflammatory biomarkers after ischemic stroke and poststroke cognitive impairment. METHODS: The Nor-COAST study (Norwegian Cognitive Impairment After Stroke) is a prospective observational multicenter cohort study, including patients hospitalized with acute stroke between 2015 and 2017. Inflammatory biomarkers, including the TCC (terminal C5b-9 complement complex) and 20 cytokines, were analyzed in plasma, collected at baseline, 3-, and 18 months poststroke, using ELISA and a multiplex assay. Global cognitive outcome was assessed with the Montreal Cognitive Assessment (MoCA) scale. We investigated the associations between plasma inflammatory biomarkers at baseline and MoCA score at 3-, 18-, and 36-month follow-ups; the associations between inflammatory biomarkers at 3 months and MoCA score at 18- and 36-month follow-ups; and the association between these biomarkers at 18 months and MoCA score at 36-month follow-up. We used mixed linear regression adjusted for age and sex. RESULTS: We included 455 survivors of ischemic stroke. Higher concentrations of 7 baseline biomarkers were significantly associated with lower MoCA score at 36 months; TCC, IL (interleukin)-6, and MIP (macrophage inflammatory protein)-1α were associated with MoCA at 3, 18, and 36 months (P<0.01). No biomarker at 3 months was significantly associated with MoCA score at either 18 or 36 months, whereas higher concentrations of 3 biomarkers at 18 months were associated with lower MoCA score at 36 months (P<0.01). TCC at baseline and IL-6 and MIP-1α measured both at baseline and 18 months were particularly strongly associated with MoCA (P<0.01). CONCLUSIONS: Higher concentrations of plasma inflammatory biomarkers were associated with lower MoCA scores up to 36 months poststroke. This was most pronounced for inflammatory biomarkers measured in the acute phase following stroke. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02650531.

Multiple sclerosis imaging in clinical practice: a European-wide survey of 428 centers and conclusions by the ESNR Working Group.

OBJECTIVES: To evaluate compliance with the available recommendations, we assessed the current clinical practice of imaging in the evaluation of multiple sclerosis (MS). METHODS: An online questionnaire was emailed to all members and affiliates. Information was gathered on applied MR imaging protocols, gadolinium-based contrast agents (GBCA) use and image analysis. We compared the survey results with the Magnetic Resonance Imaging in MS (MAGNIMS) recommendations considered as the reference standard. RESULTS: A total of 428 entries were received from 44 countries. Of these, 82% of responders were neuroradiologists. 55% performed more than ten scans per week for MS imaging. The systematic use of 3 T is rare (18%). Over 90% follow specific protocol recommendations with 3D FLAIR, T2-weighted and DWI being the most frequently used sequences. Over 50% use SWI at initial diagnosis and 3D gradient-echo T1-weighted imaging is the most used MRI sequence for pre- and post-contrast imaging. Mismatches with recommendations were identified including the use of only one sagittal T2-weighted sequence for spinal cord imaging, the systematic use of GBCA at follow-up (over 30% of institutions), a delay time shorter than 5 min after GBCA administration (25%) and an inadequate follow-up duration in pediatric acute disseminated encephalomyelitis (80%). There is scarce use of automated software to compare images or to assess atrophy (13% and 7%). The proportions do not differ significantly between academic and non-academic institutions. CONCLUSIONS: While current practice in MS imaging is rather homogeneous across Europe, our survey suggests that recommendations are only partially followed. CLINICAL RELEVANCE STATEMENT: Hurdles were identified, mainly in the areas of GBCA use, spinal cord imaging, underuse of specific MRI sequences and monitoring strategies. This work will help radiologists to identify the mismatches between their own practices and the recommendations and act upon them. KEY POINTS: • While current practice in MS imaging is rather homogeneous across Europe, our survey suggests that available recommendations are only partially followed. • Several hurdles have been identified through the survey that mainly lies in the areas of GBCA use, spinal cord imaging, underuse of specific MRI sequences and monitoring strategies.

Predictors of outcome after endovascular treatment for tandem occlusions: a single center retrospective analysis.

BACKGROUND: The endovascular treatment procedure in tandem occlusions (TO) is complex compared to single occlusion (SO) and optimal management remains uncertain. The aim of this study was to identify clinical and procedural factors that may be associated to efficacy and safety in the management of TO and compare functional outcome in TO and SO stroke patients. METHODS: This is a retrospective single center study of medium (MeVO) and large vessel occlusion (LVO) of the anterior circulation. Clinical, imaging, and interventional data were analyzed to identify predictive factors for symptomatic intracranial hemorrhage (sICH) and functional outcome after endovascular treatment (EVT) in TO. Functional outcome in TO and SO patients was compared. RESULTS: Of 662 anterior circulation stroke patients with MeVO and LVO stroke, 90 (14%) had TO. Stenting was performed in 73 (81%) of TO patients. Stent thromboses occurred in 8 (11%) patients. Successful reperfusion with modified thrombolysis in cerebral infarction (mTICI) ≥ 2b was achieved in 82 (91%). SICH occurred in seven (8%). The strongest predictors for sICH were diabetes mellitus and number of stent retriever passes. Good functional clinical outcome (mRS ≤ 2) at 90-day follow up was similar in TO and SO patients (58% vs 59% respectively). General anesthesia (GA) was associated with good functional outcome whereas hemorrhage in the infarcted tissue, lower mTICI score and history of smoking were associated with poor outcome. CONCLUSIONS: The risk of sICH was increased in patients with diabetes mellitus and those with extra stent-retriever attempts. Functional clinical outcomes in patients with TO were comparable to patients with SO.

Functional connectivity in multiple sclerosis modelled as connectome stability: A 5-year follow-up study.

BACKGROUND: Brain functional connectivity (FC) in multiple sclerosis (MS) is abnormal compared to healthy controls (HCs). More longitudinal studies in MS are needed to evaluate whether FC stability is clinically relevant. OBJECTIVE: To compare functional magnetic resonance imaging (fMRI)-based FC between MS and HC, and to determine the relationship between longitudinal FC changes and structural brain damage, cognitive performance and physical disability. METHODS: T1-weighted MPRAGE and resting-state fMRI (1.5T) were acquired from 70 relapsing-remitting MS patients and 94 matched HC at baseline (mean months since diagnosis 14.0 ± 11) and from 60 MS patients after 5 years. Independent component analysis and network modelling were used to measure longitudinal FC stability and cross-sectional comparisons with HC. Linear mixed models, adjusted for age and sex, were used to calculate correlations. RESULTS: At baseline, patients with MS showed FC abnormalities both within networks and in single connections compared to HC. Longitudinal analyses revealed functional stability and no significant relationships with clinical disability, cognitive performance, lesion or brain volume. CONCLUSION: FC abnormalities occur already at the first decade of MS, yet we found no relevant clinical correlations for these network deviations. Future large-scale longitudinal fMRI studies across a range of MS subtypes and outcomes are required.

Serum neurofilament light chain concentration predicts disease worsening in multiple sclerosis.

BACKGROUND: Serum neurofilament light (sNfL) chain is a promising biomarker reflecting neuro-axonal injury in multiple sclerosis (MS). However, the ability of sNfL to predict outcomes in real-world MS cohorts requires further validation. OBJECTIVE: The aim of the study is to investigate the associations of sNfL concentration, magnetic resonance imaging (MRI) and retinal optical coherence tomography (OCT) markers with disease worsening in a longitudinal European multicentre MS cohort. METHODS: MS patients (n = 309) were prospectively enrolled at four centres and re-examined after 2 years (n = 226). NfL concentration was measured by single molecule array assay in serum. The patients' phenotypes were thoroughly characterized with clinical examination, retinal OCT and MRI brain scans. The primary outcome was disease worsening at median 2-year follow-up. RESULTS: Patients with high sNfL concentrations (⩾8 pg/mL) at baseline had increased risk of disease worsening at median 2-year follow-up (odds ratio (95% confidence interval) = 2.8 (1.5-5.3), p = 0.001). We found no significant associations of MRI or OCT measures at baseline with risk of disease worsening. CONCLUSION: Serum NfL concentration was the only factor associated with disease worsening, indicating that sNfL is a useful biomarker in MS that might be relevant in a clinical setting.

Enhancement of cranial nerves in Lyme neuroborreliosis: incidence and correlation with clinical symptoms and prognosis.

PURPOSE: Symptoms of cranial neuritis are a common presentation of Lyme neuroborreliosis (LNB). Imaging studies are scarce and report contradictory low prevalence of enhancement compared to clinical studies of cranial neuropathy. We hypothesized that MRI enhancement of cranial nerves in LNB is underreported, and aimed to assess the prevalence and clinical impact of cranial nerve enhancement in early LNB. METHODS: In this prospective, longitudinal cohort study, 69 patients with acute LNB were examined with MRI of the brain. Enhancement of cranial nerves III-XII was rated. MRI enhancement was correlated to clinical findings of neuropathy in the acute phase and after 6 months. RESULTS: Thirty-nine of 69 patients (57%) had pathological cranial nerve enhancement. Facial and oculomotor nerves were most frequently affected. There was a strong correlation between enhancement in the distal internal auditory canal and parotid segments of the facial nerve and degree of facial palsy (gamma = 0.95, p < .01, and gamma = 0.93, p < .01), despite that 19/37 nerves with mild-moderate enhancement in the distal internal auditory canal segment showed no clinically evident palsy. Oculomotor and abducens nerve enhancement did not correlate with eye movement palsy (gamma = 1.00 and 0.97, p = .31 for both). Sixteen of 17 patients with oculomotor and/or abducens nerve enhancement had no evident eye movement palsy. CONCLUSIONS: MRI cranial nerve enhancement is common in LNB patients, but it can be clinically occult. Facial and oculomotor nerves are most often affected. Enhancement of the facial nerve distal internal auditory canal and parotid segments correlate with degree of facial palsy.

Pre-stroke cognitive impairment is associated with vascular imaging pathology: a prospective observational study.

BACKGROUND: Chronic brain pathology and pre-stroke cognitive impairment (PCI) is predictive of post-stroke dementia. The aim of the current study was to measure pre-stroke neurodegenerative and vascular disease burden found on brain MRI and to assess the association between pre-stroke imaging pathology and PCI, whilst also looking for potential sex differences. METHODS: This prospective brain MRI cohort is part of the multicentre Norwegian cognitive impairment after stroke (Nor-COAST) study. Patients hospitalized with acute ischemic or hemorrhagic stroke were included from five participating stroke units. Visual rating scales were used to categorize baseline MRIs (N = 410) as vascular, neurodegenerative, mixed, or normal, based on the presence of pathological imaging findings. Pre-stroke cognition was assessed by interviews of patients or caregivers using the Global Deterioration Scale (GDS). Stroke severity was assessed with the National Institute of Health Stroke Scale (NIHSS). Univariate and multiple logistic regression analyses were performed to investigate the association between imaging markers, PCI, and sex. RESULTS: Patients' (N = 410) mean (SD) age was 73.6 (±11) years; 182 (44%) participants were female, the mean (SD) NIHSS at admittance was 4.1 (±5). In 68% of the participants, at least one pathological imaging marker was found. Medial temporal lobe atrophy (MTA) was present in 30% of patients, white matter hyperintensities (WMH) in 38% of patients and lacunes in 35% of patients. PCI was found in 30% of the patients. PCI was associated with cerebrovascular pathology (OR 2.5; CI = 1.4 to 4.5, p = 0.001) and mixed pathology (OR 3.4; CI = 1.9 to 6.1, p = 0.001) but was not associated with neurodegeneration (OR 1.0; CI = 0.5 to 2.2; p = 0.973). Pathological MRI markers, including MTA and lacunes, were more prevalent among men, as was a history of clinical stroke prior to the index stroke. The OR of PCI for women was not significantly increased (OR 1.2; CI = 0.8 to 1.9; p = 0.3). CONCLUSIONS: Pre-stroke chronic brain pathology is common in stroke patients, with a higher prevalence in men. Vascular pathology and mixed pathology are associated with PCI. There were no significant sex differences for the risk of PCI. TRIAL REGISTRATION: NCT02650531 , date of registration: 08.01.2016.

Associations between post-stroke motor and cognitive function: a cross-sectional study.

BACKGROUND: Motor and cognitive impairments are frequently observed following stroke, but are often managed as distinct entities, and there is little evidence regarding how they are related. The aim of this study was to describe the prevalence of concurrent motor and cognitive impairments 3 months after stroke and to examine how motor performance was associated with memory, executive function and global cognition. METHODS: The Norwegian Cognitive Impairment After Stroke (Nor-COAST) study is a prospective multicentre cohort study including patients hospitalized with acute stroke between May 2015 and March 2017. The National Institutes of Health Stroke Scale (NIHSS) was used to measure stroke severity at admission. Level of disability was assessed by the Modified Rankin Scale (mRS). Motor and cognitive functions were assessed 3 months post-stroke using the Montreal Cognitive Assessment (MoCA), Trail Making Test Part B (TMT-B), 10-Word List Recall (10WLR), Short Physical Performance Battery (SPPB), dual-task cost (DTC) and grip strength (Jamar®). Cut-offs were set according to current recommendations. Associations were examined using linear regression with cognitive tests as dependent variables and motor domains as covariates, adjusted for age, sex, education and stroke severity. RESULTS: Of 567 participants included, 242 (43%) were women, mean (SD) age was 72.2 (11.7) years, 416 (75%) had an NIHSS score ≤ 4 and 475 (84%) had an mRS score of ≤2. Prevalence of concurrent motor and cognitive impairment ranged from 9.5% for DTC and 10WLR to 22.9% for grip strength and TMT-B. SPPB was associated with MoCA (regression coefficient B = 0.465, 95%CI [0.352, 0.578]), TMT-B (B = -9.494, 95%CI [- 11.726, - 7.925]) and 10WLR (B = 0.132, 95%CI [0.054, 0.211]). Grip strength was associated with MoCA (B = 0.075, 95%CI [0.039, 0.112]), TMT-B (B = -1.972, 95%CI [- 2.672, - 1.272]) and 10WLR (B = 0.041, 95%CI [0.016, 0.066]). Higher DTC was associated with more time needed to complete TMT-B (B = 0.475, 95%CI [0.075, 0.875]) but not with MoCA or 10WLR. CONCLUSION: Three months after suffering mainly minor strokes, 30-40% of participants had motor or cognitive impairments, while 20% had concurrent impairments. Motor performance was associated with memory, executive function and global cognition. The identification of concurrent impairments could be relevant for preventing functional decline. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02650531 .

Carotid Atherosclerosis and Longitudinal Changes of MRI Visual Rating Measures in Stroke Survivors: A Seven-Year Follow-Up Study.

OBJECTIVES: We aimed to assess longitudinal changes in MRI measures of brain atrophy and white matter lesions in stroke and transient ischemic attack (TIA) survivors, and explore whether carotid stenosis predicts progression of these changes, assessed by visual rating scales. MATERIALS AND METHODS: All patients with a first-ever stroke or TIA admitted to Bærum Hospital, Norway, in 2007/2008, were invited in the acute phase and followed for seven years. Carotid ultrasound was performed during the hospital stay. Carotid stenosis was defined as ≥50% narrowing of lumen. MRI was performed one and seven years after the index event and analyzed according to the visual rating scales Fazekas scale (0-3), Medial Temporal Lobe Atrophy (MTLA) (0-4) score, and Global Cortical Atrophy (GCA) scale (0-3). Patients with MRI scans at both time points were included in this sub-study. RESULTS: Of 227 patients recruited, 76 had both MRI examinations. Mean age 73.9±10.6, 41% women, and 9% had ≥50% carotid stenosis. Mean Fazekas scale was 1.7±0.9 and 1.8±1.0, mean MTLA score 1.0 ±1.0 and 1.7±1.0, and mean GCA scale score 1.4±0.7 and 1.4±0.6 after one and seven years, respectively. 71% retained the same Fazekas scale score, while 21% showed progression. Deterioration in GCA scale was seen in 20% and increasing MTLA score in 57%. Carotid stenosis was not associated with progression on Fazekas score, MTLA score or GCA scale. CONCLUSIONS: Three out of five showed progression on the MTLA score. Carotid stenosis was not associated with longitudinal change of visual rating scales.

No evidence for amyloid pathology as a key mediator of neurodegeneration post-stroke - a seven-year follow-up study.

BACKGROUND: Cognitive impairment (CI) with mixed vascular and neurodegenerative pathologies after stroke is common. The role of amyloid pathology in post-stroke CI is unclear. We hypothesize that amyloid deposition, measured with Flutemetamol (18F-Flut) positron emission tomography (PET), is common in seven-year stroke survivors diagnosed with CI and, further, that quantitatively assessed 18F-Flut-PET uptake after 7 years correlates with amyloid-ß peptide (Aß42) levels in cerebrospinal fluid (CSF) at 1 year, and with measures of neurodegeneration and cognition at 7 years post-stroke. METHODS: 208 patients with first-ever stroke or transient Ischemic Attack (TIA) without pre-existing CI were included during 2007 and 2008. At one- and seven-years post-stroke, cognitive status was assessed, and categorized into dementia, mild cognitive impairment or normal. Etiologic sub-classification was based on magnetic resonance imaging (MRI) findings, CSF biomarkers and clinical cognitive profile. At 7 years, patients were offered 18F-Flut-PET, and amyloid-positivity was assessed visually and semi-quantitatively. The associations between 18F-Flut-PET standardized uptake value ratios (SUVr) and measures of neurodegeneration (medial temporal lobe atrophy (MTLA), global cortical atrophy (GCA)) and cognition (Mini-Mental State Exam (MMSE), Trail-making test A (TMT-A)) and CSF Aß42 levels were assessed using linear regression. RESULTS: In total, 111 patients completed 7-year follow-up, and 26 patients agreed to PET imaging, of whom 13 had CSF biomarkers from 1 year. Thirteen out of 26 patients were diagnosed with CI 7 years post-stroke, but only one had visually assessed amyloid positivity. CSF Aß42 levels at 1 year, MTA grade, GCA scale, MMSE score or TMT-A at 7 years did not correlate with 18F-Flut-PET SUVr in this cohort. CONCLUSIONS: Amyloid binding was not common in 7-year stroke survivors diagnosed with CI. Quantitatively assessed, cortical amyloid deposition did not correlate with other measures related to neurodegeneration or cognition. Therefore, amyloid pathology may not be a key mediator of neurodegeneration 7 years post-stroke. TRIAL REGISTRATION: Clinicaltrials.gov (NCT00506818). July 23, 2007. Inclusion from February 2007, randomization and intervention from May 2007 and trial registration in July 2007.

Restriction spectrum imaging of white matter and its relation to neurological disability in multiple sclerosis.

BACKGROUND: Restriction spectrum imaging (RSI) is a recently introduced magnetic resonance imaging diffusion technique. The utility of RSI in multiple sclerosis (MS) is unknown. OBJECTIVE: To investigate the association between RSI-derived parameters and neurological disability in MS. METHODS: Seventy-seven relapsing-remitting MS patients were scanned with RSI on a 3-T scanner. RSI-derived parameters: fast and slow apparent diffusion coefficient (sADC), fractional anisotropy, restricted fractional anisotropy, neurite density (ND), cellularity, extracellular water fraction, and free water fraction, were obtained in white matter lesions (WML) and normal appearing white matter (NAWM). Patients were divided into three groups according to their expanded disability status scale (EDSS): with minimal, low, and substantial disability (<2.5, 2.5-3, and >3, respectively). Group comparisons and correlation analyses were performed. RESULTS: All tested RSI-derived parameters differed between WML and NAWM ( p < 0.001 for all pairwise comparisons). The sADC in WML showed largest difference across disability subgroups (analysis of variance (ANOVA): F = 5.1, η2 = 0.12, p = 0.008). ND in NAWM showed strongest correlation with disability (ϱ = -0.39, p < 0.001). CONCLUSION: The strongest correlation with EDSS of ND obtained in NAWM indicates that processes outside lesions are important for disability in MS. Our study suggests that RSI-derived parameters may help understand the "clinico-radiological paradox" and improve disease monitoring in MS.

Predictors for Favorable Cognitive Outcome Post-Stroke: A-Seven-Year Follow-Up Study.

BACKGROUND AND PURPOSE: Knowledge of the burden and development of post-stroke cognitive impairments (CIs) in the long-term after the first event is limited. We aimed to assess the prevalence of mild CI (MCI) and dementia 7 years after first-ever stroke or transient ischemic attack (TIA), to subclassify the impairments, and to identify predictors for a favorable cognitive outcome. MATERIALS AND METHODS: During 2007 and 2008, 208 patients with first-ever stroke or TIA without preexisting CI were included. After 1 and 7 years, survivors were invited to a follow-up. Transitions of cognitive status from 1 to 7 years were recorded based on the 3 categories dementia, MCI, or none. Etiologic subclassification was based on clinical cognitive profile, magnetic resonance imaging (MRI) findings, and biomarkers at both time points. Favorable outcome was defined as normal cognitive function or MCI after 7 years with exclusion of those who had progression from normal to MCI. RESULTS: Eighty patients died during follow-up, 12 patients refused further participation. After 7 years, 109 completed follow-up of whom 40 (37%) were diagnosed with MCI and 24 (22%) with dementia. Of the 64 patients diagnosed with CI, 9 were subclassified with degenerative cognitive disease, 13 with vascular disease, and 42 had mixed cognitive disease. In all, 65 patients (60%) had a favorable outcome. In multivariable logistic regression analysis, lower age and lower medial temporal lobe atrophy (MTLA) grade on MRI at 12 months were independently associated with a favorable outcome, adjusted OR (95% CI), 0.94 (0.86-0.92), and 0.55 (0.35-0.85), respectively. CONCLUSIONS: Sixty percent of stroke survivors have a favorable cognitive outcome. Lower age and lower MTLA grade on MRI were associated with favorable outcome.

The Norwegian Cognitive impairment after stroke study (Nor-COAST): study protocol of a multicentre, prospective cohort study.

BACKGROUND: Early and late onset post-stroke cognitive impairment (PCI) contributes substantially to disability following stroke, and is a high priority within stroke research. The aetiology for PCI is complex and related to the stroke itself, brain resilience, comorbid brain diseases, prestroke vulnerability and complications during the hospital stay. The aim of the Norwegian Cognitive Impairment After Stroke study (Nor-COAST) is to quantify and measure levels of cognitive impairments in a general Norwegian stroke population and to identify biological and clinical markers associated with prognosis for cognitive disorders following incident stroke. The study will be organised within five work packages: 1) Incidence and trajectories 2) Pathological mechanisms 3) Development of a risk score 4) Impact of physical activity and 5) Adherence to secondary prevention. METHODS: Nor-COAST is an ongoing multicentre (five participating hospitals), prospective, cohort study with consecutive inclusion during the acute phase and with follow-up at three and 18 months, and at three years. Inclusion criteria are stroke defined according to the WHO criteria. During the recruitment period from 18.05.2015 to 31.03.2017, 816 participants have been included. Cognitive impairment will be classified according to the DSM-5 criteria using a consensus group. Cognitive function is assessed by a standardised neuropsychological test battery, the Montreal Cognitive Assessment, Trail making A and B, ten-word immediate and delayed recall test, the Controlled Oral Word Association, Global Deterioration Scale and proxy based information by and the Ascertain Dementia 8 item informant questionnaire. Biomarkers include magnetic resonance imaging, routine blood samples and bio-banking. Clinical assessments include characteristics of the stroke, comorbidity, delirium, frailty and tests for cognitive and physical function, sensor based activity monitoring and adherence to secondary prophylaxis. DISCUSSION: Nor-COAST is the first Norwegian multicentre study to quantify burden of PCI that will provide reliable estimates in a general stroke population. A multidisciplinary approach aiming to identify biomarkers and clinical markers of overall prognosis will add new knowledge about risk profiles, including pre-stroke vulnerability and modifiable factors such as physical activity and secondary prophylaxis of relevance for clinical practice and later intervention studies. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02650531 . Retrospectively registered January 8, 2016. First participant included May 18, 2015.

Within- and between-session reproducibility of GABA measurements with MR spectroscopy.

PURPOSE: The reproducibility of the MEGA-PRESS (MEshcher-GArwood Point RESolved Spectroscopy) MR spectroscopy sequence for the measurement of gamma- aminobutyric acid (GABA) is addressed, focusing on optimizing the number of repetitions at two voxel locations in the human brain and associated possibilities in analysis tools. MATERIALS AND METHODS: Two 20-min MEGA-PRESS acquisitions were run (echo time = 68 ms, repetition time = 1800 ms, repetitions = 328): one from a 21 mL volume in the anterior cingulate cortex (ACC) and one from a 22 mL volume in the left Broca's area in 21 healthy male volunteers (age 32 years ± 6[SD]). Subjects were scanned twice with identical protocols, 1 week apart. Data were acquired on a 3 Tesla GE Discovery 750 scanner using a 32-channel head coil. Spectroscopy data were partitioned into shorter epochs, numerically equivalent to scans of progressively increasing duration, and compared both within and between sessions. Three different analysis schemes were applied: (1) Vendor prototype preprocessor, with quantification by LCModel. (2) Pure Gannet pipeline. (3) Preprocessing with Gannet, and quantification with LCModel. The coefficient of variation (CV) were calculated as a measure of reproducibility. RESULTS: Increasing the number of repetitions showed improvements for within- and between-session reproducibility up to around 218 repetitions. (CV ranging from 4 to 14%). Gannet combined with LCModel approach proved the best method. (CV = 4-5%). Measurements from the ACC area had higher CVs than the Broca area. (CV = 6-14% versus 4-7%). CONCLUSION: Measurement in the Broca area yields better reproducibility than the ACC. With appropriate acquisition times and preprocessing tools, measurements from the ACC area are also reliable. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:421-430.

Power estimation for non-standardized multisite studies.

A concern for researchers planning multisite studies is that scanner and T1-weighted sequence-related biases on regional volumes could overshadow true effects, especially for studies with a heterogeneous set of scanners and sequences. Current approaches attempt to harmonize data by standardizing hardware, pulse sequences, and protocols, or by calibrating across sites using phantom-based corrections to ensure the same raw image intensities. We propose to avoid harmonization and phantom-based correction entirely. We hypothesized that the bias of estimated regional volumes is scaled between sites due to the contrast and gradient distortion differences between scanners and sequences. Given this assumption, we provide a new statistical framework and derive a power equation to define inclusion criteria for a set of sites based on the variability of their scaling factors. We estimated the scaling factors of 20 scanners with heterogeneous hardware and sequence parameters by scanning a single set of 12 subjects at sites across the United States and Europe. Regional volumes and their scaling factors were estimated for each site using Freesurfer's segmentation algorithm and ordinary least squares, respectively. The scaling factors were validated by comparing the theoretical and simulated power curves, performing a leave-one-out calibration of regional volumes, and evaluating the absolute agreement of all regional volumes between sites before and after calibration. Using our derived power equation, we were able to define the conditions under which harmonization is not necessary to achieve 80% power. This approach can inform choice of processing pipelines and outcome metrics for multisite studies based on scaling factor variability across sites, enabling collaboration between clinical and research institutions.

Cortical thickness and surface area relate to specific symptoms in early relapsing-remitting multiple sclerosis.

BACKGROUND: Cortical atrophy is common in early relapsing-remitting multiple sclerosis (RRMS). Whether this atrophy is caused by changes in cortical thickness or cortical surface area is not known, nor is their separate contributions to clinical symptoms. OBJECTIVES: To investigate the difference in cortical surface area, thickness and volume between early RRMS patients and healthy controls; and the relationship between these measures and neurological disability, cognitive decline, fatigue and depression. METHODS: RRMS patients (n = 61) underwent magnetic resonance imaging (MRI), neurological and neuropsychological examinations. We estimated cortical surface area, thickness and volume and compared them with matched healthy controls (n = 61). We estimated the correlations between clinical symptoms and cortical measures within the patient group. RESULTS: We found no differences in cortical surface area, but widespread differences in cortical thickness and volume between the groups. Neurological disability was related to regionally smaller cortical thickness and volume. Better verbal memory was related to regionally larger surface area; and better visuo-spatial memory, to regionally larger cortical volume. Higher depression scores and fatigue were associated with regionally smaller cortical surface area and volume. CONCLUSIONS: We found that cortical thickness, but not cortical surface area, is affected in early RRMS. We identified specific structural correlates to the main clinical symptoms in early RRMS.

Cortical changes associated with depression and antidepressant use in Alzheimer and Lewy body dementia: an MRI surface-based morphometric study.

CONTEXT: Depression is common in dementia, especially in the early stages, with important clinical implications, but the etiology is unknown and most likely heterogeneous. Antidepressant use in the elderly without dementia has previously been shown to be associated with high risks of adverse events and with structural brain alterations. OBJECTIVE: To investigate cortical changes associated with depression and antidepressant use in patients with mild Alzheimer's disease (AD) and Lewy body dementia (LBD). METHODS: 74 subjects with mild AD and LBD from geriatric and psychiatry outpatient clinics in Western Norway were included. The Montgomery-Asberg Depression Rating Scale (MADRS) was used to assess depression. Automatic preprocessing using Freesurfer included steps for white and grey matter surface reconstruction. The resulting cortical thickness was analyzed using linear modeling. RESULTS: Clusters of depression-associated thinning were found in prefrontal and temporal areas. Treatment-associated thinning was observed in the parahippocampal region and was significant even after correction for age, sex, AD/LBD diagnosis, and MADRS scores. CONCLUSION: Depression in mild AD and LBD is associated with cortical thinning in prefrontal and temporal areas. The findings suggest that depressive symptoms in mild dementia could develop due to neurodegeneration in the same neural circuits that are critical for depression across different brain disorders. Antidepressant use in patients with mild AD and LBD is associated with parahippocampal thinning. Taken together with low efficacy of antidepressants in cognitively impaired patients and high risks of adverse events, our results suggest a need to re-evaluate the treatment approaches for depression and the role of antidepressants in patients with dementia.

Memory dysfunction in primary Sjögren's syndrome is associated with anti-NR2 antibodies.

OBJECTIVE: Our understanding of the etiology and pathogenesis of neuropsychiatric involvement in primary Sjögren's syndrome (SS) is incomplete. In systemic lupus erythematosus, it has been reported that antibodies directed against N-methyl-D-aspartate receptor subtype NR2 (anti-NR2) interfere with memory and learning function, as well as mood. This has not been investigated in primary SS; however, the present study was undertaken to advance our understanding of neuropsychiatric involvement in this disease. METHODS: Sixty-six patients with primary SS and 66 age- and sex-matched healthy control subjects underwent clinical examination and neuropsychological evaluation. Anti-NR2 antibodies were measured in serum and cerebrospinal fluid. Hippocampus volume was estimated using software extensions to SPM5. RESULTS: Patients with primary SS had smaller hippocampi than healthy subjects (mean ± SD 8.15 ± 0.98 cm(3) versus 8.49 ± 0.88 cm(3); P = 0.01). In patients with primary SS, anti-NR2 antibodies in cerebrospinal fluid were associated with a worse performance in 8 of 10 memory and learning tests, and anti-NR2 antibodies in serum were associated with a worse performance in 6 of those same tests. In addition, a higher proportion of patients with depression than patients without depression had serum anti-NR2 antibody levels above the cutoff value. CONCLUSION: Results of this study indicate that anti-NR2 antibodies may represent one of the pathogenetic mechanisms for cognitive disturbances and mood disorders in patients with primary SS.

External validation of clinical risk prediction score for elderly treated with endovascular thrombectomy.

BACKGROUND AND AIM: The thrombectomy in the elderly prediction score (TERPS) for functional outcome after anterior circulation endovascular therapy (EVT) in patients ≥ 80 years was recently developed. The aim of this study was to assess predictors of functional outcome in the elderly and validate the prediction model. METHODS: Consecutive patients treated with EVT from the Oslo Acute Reperfusion Stroke Study were evaluated for inclusion. Clinical and radiological parameters were used to calculate the TERPS, and functional outcome were assessed at 3-month follow-up. RESULTS: Out of 1028 patients who underwent EVT for acute ischemic stroke from January 2017 to July 2022, 218 (21.2%) patients ≥ 80 years with anterior ischemic stroke were included. Fair outcome, defined as modified Rankin scale ≤ 3 (mRS), was achieved in 117 (53.7%). In bivariate analyses, male sex (p 0.035), age (p 0.025), baseline National Institute of Health Stroke Scale (NIHSS, p < 0.001), pre-stroke mRS (p 0.002) and Alberta Stroke Program Early Computed Tomography score (ASPECTS, p 0.001) were associated with fair outcome. Significant predictors for fair outcome in regression analyses were lower pre-stroke mRS, adjusted odd ratio, (aOR) 0.67 (95% CI 0.50-0.91, p 0.01), NIHSS, aOR 0.92 (95% CI 0.87-0.97, p 0.002), and higher ASPECTS, aOR 1.22 (95% CI 1.03-1.44, p 0.023). The area under the curve (AUC) using TERPS was 0.74 (95% CI 0.67-0.80). CONCLUSIONS: The risk prediction score TERPS showed moderate performance in this external validation. Other variables may still be included to improve the model and validation using other cohorts is recommended. TRIAL REGISTRATION: NCT06220981.

Arachidonic and docosahexaenoic acid supplementation and brain maturation in preterm infants; a double blind RCT.

BACKGROUND: Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are important structural components of neural cellular membranes and possess anti-inflammatory properties. Very preterm infants are deprived of the enhanced placental supply of these fatty acids, but the benefit of postnatal supplementation on brain development is uncertain. The aim of this study was to test the hypothesis that early enteral supplementation with ARA and DHA in preterm infants improves white matter (WM) microstructure assessed by diffusion-weighted MRI at term equivalent age. METHODS: In this double-blind, randomized controlled trial, infants born before 29 weeks gestational age were allocated to either 100 mg/kg ARA and 50 mg/kg DHA (ARA:DHA group) or medium chain triglycerides (control). Supplements were started on the second day of life and provided until 36 weeks postmenstrual age. The primary outcome was brain maturation assessed by diffusion tensor imaging (DTI) using Tract-Based Spatial Statistics (TBSS) analysis. RESULTS: We included 120 infants (60 per group) in the trial; mean (range) gestational age was 26+3 (22+6 - 28+6) weeks and postmenstrual age at scan was 41+3 (39+1 - 47+0) weeks. Ninety-two infants underwent MRI imaging, and of these, 90 had successful T1/T2 weighted MR images and 74 had DTI data of acceptable quality. TBSS did not show significant differences in mean or axial diffusivity between the groups, but demonstrated significantly higher fractional anisotropy in several large WM tracts in the ARA:DHA group, including corpus callosum, the anterior and posterior limb of the internal capsula, inferior occipitofrontal fasciculus, uncinate fasciculus, and the inferior longitudinal fasciculus. Radial diffusivity was also significantly lower in several of the same WM tracts in the ARA:DHA group. CONCLUSION: This study suggests that supplementation with ARA and DHA at doses matching estimated fetal accretion rates improves WM maturation compared to control treatment, but further studies are needed to ascertain any functional benefit. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov; ID:NCT03555019.