Low-dose acetylsalicylic acid reduces local inflammation and tissue perfusion in dense breast tissue in postmenopausal women.

PURPOSE: One major risk factor for breast cancer is high mammographic density. It has been estimated that dense breast tissue contributes to ~ 30% of all breast cancer. Prevention targeting dense breast tissue has the potential to improve breast cancer mortality and morbidity. Anti-estrogens, which may be associated with severe side-effects, can be used for prevention of breast cancer in women with high risk of the disease per se. However, no preventive therapy targeting dense breasts is currently available. Inflammation is a hallmark of cancer. Although the biological mechanisms involved in the increased risk of cancer in dense breasts is not yet fully understood, high mammographic density has been associated with increased inflammation. We investigated whether low-dose acetylsalicylic acid (ASA) affects local breast tissue inflammation and/or structural and dynamic changes in dense breasts. METHODS: Postmenopausal women with mammographic dense breasts on their regular mammography screen were identified. A total of 53 women were randomized to receive ASA 160 mg/day or no treatment for 6 months. Magnetic resonance imaging (MRI) was performed before and after 6 months for a sophisticated and continuous measure breast density by calculating lean tissue fraction (LTF). Additionally, dynamic quantifications including tissue perfusion were performed. Microdialysis for sampling of proteins in vivo from breasts and abdominal subcutaneous fat, as a measure of systemic effects, before and after 6 months were performed. A panel of 92 inflammatory proteins were quantified in the microdialysates using proximity extension assay. RESULTS: After correction for false discovery rate, 20 of the 92 inflammatory proteins were significantly decreased in breast tissue after ASA treatment, whereas no systemic effects were detected. In the no-treatment group, protein levels were unaffected. Breast density, measured by LTF on MRI, were unaffected in both groups. ASA significantly decreased the perfusion rate. The perfusion rate correlated positively with local breast tissue concentration of VEGF. CONCLUSIONS: ASA may shape the local breast tissue microenvironment into an anti-tumorigenic state. Trials investigating the effects of low-dose ASA and risk of primary breast cancer among postmenopausal women with maintained high mammographic density are warranted. Trial registration EudraCT: 2017-000317-22.

Validation of Rapid Magnetic Resonance Myelin Imaging in Multiple Sclerosis.

OBJECTIVE: Magnetic resonance imaging (MRI) is essential for multiple sclerosis diagnostics but is conventionally not specific to demyelination. Myelin imaging is often hampered by long scanning times, complex postprocessing, or lack of clinical approval. This study aimed to assess the specificity, robustness, and clinical value of Rapid Estimation of Myelin for Diagnostic Imaging, a new myelin imaging technique based on time-efficient simultaneous T1 /T2 relaxometry and proton density mapping in multiple sclerosis. METHODS: Rapid myelin imaging was applied using 3T MRI ex vivo in 3 multiple sclerosis brain samples and in vivo in a prospective cohort of 71 multiple sclerosis patients and 21 age/sex-matched healthy controls, with scan-rescan repeatability in a subcohort. Disability in patients was assessed by the Expanded Disability Status Scale and the Symbol Digit Modalities Test at baseline and 2-year follow-up. RESULTS: Rapid myelin imaging correlated with myelin-related stains (proteolipid protein immunostaining and Luxol fast blue) and demonstrated good precision. Multiple sclerosis patients had, relative to controls, lower normalized whole-brain and normal-appearing white matter myelin fractions, which correlated with baseline cognitive and physical disability. Longitudinally, these myelin fractions correlated with follow-up physical disability, even with correction for baseline disability. INTERPRETATION: Rapid Estimation of Myelin for Diagnostic Imaging provides robust myelin quantification that detects diffuse demyelination in normal-appearing tissue in multiple sclerosis, which is associated with both cognitive and clinical disability. Because the technique is fast, with automatic postprocessing and US Food and Drug Administration/CE clinical approval, it can be a clinically feasible biomarker that may be suitable to monitor myelin dynamics and evaluate treatments aiming at remyelination. ANN NEUROL 2020;87:710-724.

High prevalence of pituitary hormone deficiency in both unilateral and bilateral optic nerve hypoplasia.

AIM: This study examined the prevalence of neurological impairment and pituitary hormone deficiency (PHD) in patients with unilateral and bilateral optic nerve hypoplasia (ONH). METHODS: A population-based cross-sectional cohort study of 65 patients (51% female) with ONH was conducted in Stockholm. Of these were 35 bilateral and 30 unilateral. The patients were below 20 years of age, living in Stockholm in December 2009 and found through database searching. The median age at the analysis of the results in January 2018 was 16.1 years (range 8.1-27.5 years). Neurological assessments and blood sampling were conducted, neuroradiology was reviewed and growth curves were analysed. Diagnoses of PHDs were based on clinical and biochemical evidence of hormone deficiency. RESULTS: Neurological impairments were identified in 47% of the patients and impairments in gross and fine motor function were more prevalent in bilateral ONH (p < 0.001). In addition, 9% had cerebral palsy and 14% had epilepsy. The prevalence of PHD was 29 and 19% had multiple PHD. CONCLUSION: Children with ONH had a high risk of neurological impairment, especially in bilateral disease. Both unilateral and bilateral ONH signified an increased prevalence of PHD and all these children should be endocrinologically followed up until completed puberty.

Corpus callosum atrophy is strongly associated with cognitive impairment in multiple sclerosis: Results of a 17-year longitudinal study.

BACKGROUND: Cognitive impairment is common in multiple sclerosis (MS) and may be subtle. The corpus callosum is essential for connectivity-demanding cognitive tasks and is significantly affected in MS, therefore it may serve as a marker for cognitive function. OBJECTIVE: The objective of this paper is to longitudinally study the normalized corpus callosum area (nCCA) as a marker of cognitive function and disability in MS. METHODS: Thirty-seven MS patients were followed from 1996 with follow-ups in 2004 and 2013. A healthy matched control group was recruited. The Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT) were assessed. The nCCA was measured on T2-weighted images. Volumetry was performed with FreeSurfer. RESULTS: Disease duration spanned five decades (1.6-46 years). Annual corpus callosal atrophy rate decreased with disease duration. nCCA was strongly correlated with SDMT (r = 0.793, p < 0.001) and moderately correlated with EDSS (r = -0.545, p < 0.001) after adjusting for disease duration, age and sex. The correlations of brain parenchymal fraction, white matter fraction, gray matter fraction and normalized lesion volume were less strong. CONCLUSIONS: The nCCA correlates well with physical and cognitive disability in time perspectives close to two decades, outperforming volumetric measurements. The nCCA is fast and could be feasible for clinical implementation where it may help identify patients in need of neuropsychological evaluation.

Changes in CSF cholinergic biomarkers in response to cell therapy with NGF in patients with Alzheimer's disease.

INTRODUCTION: The extensive loss of central cholinergic functions in Alzheimer's disease (AD) brain is linked to impaired nerve growth factor (NGF) signaling. The cardinal cholinergic biomarker is the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT), which has recently been found in cerebrospinal fluid (CSF). The purpose of this study was to see if EC-NGF therapy will alter CSF levels of cholinergic biomarkers, ChAT, and acetylcholinesterase. METHOD: Encapsulated cell implants releasing NGF (EC-NGF) were surgically implanted bilaterally in the basal forebrain of six AD patients for 12 months and cholinergic markers in CSF were analyzed. RESULTS: Activities of both enzymes were altered after 12 months. In particular, the activity of soluble ChAT showed high correlation with cognition, CSF tau and amyloid-ß, in vivo cerebral glucose utilization and nicotinic binding sites, and morphometric and volumetric magnetic resonance imaging measures. DISCUSSION: A clear pattern of association is demonstrated showing a proof-of-principle effect on CSF cholinergic markers, suggestive of a beneficial EC-NGF implant therapy.

Radiologically isolated syndrome--incidental magnetic resonance imaging findings suggestive of multiple sclerosis, a systematic review.

With increasing availability of magnetic resonance imaging (MRI), there is also an increase in incidental abnormal findings. MRI findings suggestive of multiple sclerosis in persons without typical multiple sclerosis symptoms and with normal neurological findings are defined as radiologically isolated syndrome (RIS). Half of the persons with RIS have their initial MRI because of headache, and some have a subclinical cognitive impairment similar to that seen in multiple sclerosis. Radiological measurements also show a similarity between RIS and multiple sclerosis. Approximately two-thirds of persons with RIS show radiological progression and one-third develop neurological symptoms during mean follow-up times of up to five years. Cervical cord lesions are important predictors of clinical conversion. Management has to be individualised, but initiation of disease modifying therapy is controversial and not recommended outside of clinical trials since its effects have not been studied in RIS. Future studies should try to establish the prevalence and long-term prognosis of RIS, its impact on quality of life, and define the role of disease modifying therapy in RIS.

MRI Markers of Small Vessel Disease and the APOE Allele in Cognitive Impairment.

Objective: The apolipoprotein E (APOE) ε4 allele is the main genetic risk factor for dementia and Alzheimer's disease (AD), but the underlying mechanism for the increased risk is not well understood. Cerebral small vessel disease (SVD) is prevalent among patients with cognitive impairment and is thought to play an important role in the pathophysiology of dementia. We aimed to investigate the association between the APOE ε genotype and magnetic resonance imaging (MRI) markers of SVD in a memory clinic population. Material and Methods: This is a cross-sectional study with a total of 520 patients undergoing dementia investigation, including an MRI brain scan and APOE genotyping in all patients enrolled, and cerebrospinal fluid (CSF) analysis for routine AD biomarkers in 399 patients. MR images were assessed for markers of SVD: cerebral microbleeds (CMBs), cortical superficial siderosis, intracerebral hemorrhage, white matter hyperintensities, lacunar infarcts, and enlarged perivascular spaces. Results: Apolipoprotein E carriers with AD had a higher number of CMBs when looking at all brain regions and lobar brain regions (p < 0.001). A lower number of CMBs were seen in APOE ε2 (p < 0.05), ε3 and ε3/3 carriers (p < 0.001) when looking at all brain regions. A higher number of CMBs in deep and infratentorial regions were seen in APOE ε2 and ε3 (p < 0.05). In APOE ε4/4 carriers, CMBs, cortical superficial siderosis, white matter hyperintensities, and enlarged perivascular spaces were associated with lower levels of CSF amyloid ß (Aß) 42 in the whole cohort, and in individuals with AD and mild cognitive impairment (p < 0.05). Conclusion: Apolipoprotein E ε4 is associated with MRI markers of SVD related to amyloid pathology, specifically CMBs and Aß42 plaque formation in the brain, as reflected by decreased CSF Aß42 levels, whereas APOE ε3 and ε2 are associated with the markers of hypertensive arteriopathy, as reflected by the association with CMBs in deep and infratentorial brain regions.

Cerebrospinal Fluid Metals and the Association with Cerebral Small Vessel Disease.

BACKGROUND: Brain metal homeostasis is essential for brain health, and deregulation can result in oxidative stress on the brain parenchyma. OBJECTIVE: Our objective in this study was to focus on two hemorrhagic MRI manifestations of small vessel disease [cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS)] and associations with cerebrospinal fluid (CSF) iron levels. In addition, we aimed to analyze CSF biomarkers for dementia and associations with CSF metal levels. METHODS: This is a cross-sectional study of 196 patients who underwent memory clinic investigation, including brain MRI. CSF was collected and analyzed for metals, amyloid-ß (Aß) 42, total tau (T-tau), and phosphorylated tau (P-tau), and CSF/serum albumin ratios. Statistical analyses were performed using generalized linear models. RESULTS: No significant difference was found between CSF metal levels across diagnostic groups. Higher iron and copper levels were associated with higher CSF levels of Aß42, T-tau, P-tau, and CSF/serum albumin ratios (p < 0.05). Zinc was associated with higher CSF/serum albumin ratios. There was no significant association between CMBs or cSS and CSF iron levels. An increase in CSF iron with the number of CMBs was seen in APOEɛ4 carriers. CONCLUSION: CSF iron levels are elevated with cerebral microbleeds in APOEɛ4 carriers, with no other association seen with hemorrhagic markers of small vessel disease. The association of elevated CSF iron and copper with tau could represent findings of increased neurodegeneration in these patients.

Decline in executive functions and speed in suspected low-grade gliomas: A 3-year follow-up of a clinical cohort.

Changes over time in information processing speed and executive functions (EFs) were studied in patients with suspected low-grade gliomas (LGG) 3 years after diagnosis. Using a person-oriented approach, the study aimed at focusing solely on two cognitive domains known to be significant in the understanding of the impact of white matter diseases. The Barkley's hybrid model of EFs was used as a theoretical framework for the evaluation of EFs. The majority of the patients showed a decline in at least one of these two cognitive domains indicating that the progress of diffuse brain injury cannot be neglected in understanding neuropsychological changes over time in patients with LGG. In our sample, higher age and radiological signs of radiotherapy-induced brain atrophy were seen in patients with a decline in both domains.

The contribution of small vessel disease to subtypes of Alzheimer's disease: a study on cerebrospinal fluid and imaging biomarkers.

We investigated whether subtypes of Alzheimer's disease (AD), that is, typical, limbic-predominant, hippocampal-sparing, and minimal atrophy AD, had a specific signature of small vessel disease and neurodegeneration. Four hundred twenty-three clinically diagnosed AD patients were included (161 typical, 121 limbic-predominant, 70 hippocampal-sparing, 71 minimal atrophy). One hundred fifty-six fulfilled a biomarkers-based AD diagnosis. White matter hyperintensities and cerebral microbleeds (CMB) had the highest prevalence in limbic-predominant AD, and the lowest prevalence in minimal atrophy AD. CMB existed evenly in lobar and deep brain areas in limbic-predominant, typical, and hippocampal-sparing AD. In minimal atrophy AD, CMB were mainly located in brain lobar areas. Perivascular spaces in the centrum semiovale were more prevalent in typical AD. Small vessel disease contributed to the prediction of Mini-Mental State Examination. Minimal atrophy AD showed highly pathological levels of cerebrospinal fluid Aß1-42, total tau, and phosphorylated tau, in the absence of overt brain atrophy. Cerebral amyloid angiopathy seems to have a stronger contribution to hippocampal-sparing and minimal atrophy AD, whereas hypertensive arteriopathy may have a stronger contribution to typical and limbic-predominant AD.

Lesion accumulation is predictive of long-term cognitive decline in multiple sclerosis.

OBJECTIVE: To investigate the long-term progression of cognitive dysfunction and its neuroanatomical correlates and predictors in multiple sclerosis (MS). METHODS: A cohort of 37 MS patients reflecting five decades of disease duration and all subtypes was followed over 17.5 years. Matched controls were recruited at the last follow-up. Global cognitive functioning was assessed using a principal component cognitive index based on comprehensive neuropsychological testing. During the last 8.5 years of the study, brain MRI was performed to analyze normalized volumetrics of three global tissue compartments (white and gray matter, lesions) and strategic regions (corpus callosum, thalamus, hippocampus). RESULTS: Cognitive decline progressed continuously throughout the study paralleled by atrophy and lesion accumulation. The cognitive index partly correlated with Expanded Disability Status Scale (ρ = -0.47, p < 0.001) and was mainly associated with the lesion fraction (ß = -0.48, p < 0.001) and callosal fraction (ß = 0.39, p = 0.002) in multiple linear regression analysis. The lesion fraction was an independent predictor of the cognitive performance 8.5 years later (ß = -0.35, p = 0.008). Symbol Digit Modalities Test was most frequently abnormal (40%), while Rey-Osterrieth Complex Figure Test was more sensitive to detect cognitive decline. CONCLUSIONS: Cognitive impairment progresses continuously in MS, associated with atrophy and lesion accumulation, suggesting that interventions targeting these processes could be beneficial at all disease stages. Widespread cognitive functions are more profoundly affected, associated with lesions and corpus callosal atrophy, supporting the idea of an underlying disconnection mechanism for cognitive decline in MS.

Progression of non-age-related callosal brain atrophy in multiple sclerosis: a 9-year longitudinal MRI study representing four decades of disease development.

BACKGROUND: In multiple sclerosis (MS), multiple periventricular lesions are commonly the first findings on MRI. However, most of these MS lesions are clinically silent. The brain atrophy rate has shown better correlation to physical disability, but it is not clear how atrophy develops over decades. Corpus callosum forms the roof of the third and lateral ventricles. The corpus callosum area (CCA) in a midsagittal image is age independent in a normal adult population up to the seventh decade; therefore it can be used as a marker for non-age-related, pathological brain atrophy. OBJECTIVES: To investigate whether and how CCA decreases in size over time in patients with MS. METHODS: In a clinical observational study, 37 patients with MS with a wide range of disease duration at baseline (1-33 years) were followed. Three different MS courses were represented. The mean of individual MRI follow-up was 9 years. Multiple sclerosis severity score (MSSS) was also applied to evaluate disability at baseline and after 9 years of follow-up. RESULTS: A significant decrease in CCA over 9 years (p<0.001) and a persisting association between CCA and the disability status were found. The atrophy rate was similar ever four decades of MS for all MS courses. The mean annual CCA decrease was 9.25 mm2 (1.8%). Surprisingly, atrophy rate did not correlate with sex, disease duration, age at MS onset or MS course. CONCLUSIONS: Serial evaluations of CCA might be a robust method in monitoring a non-age-related decrease in CCA, reflecting progression of irreversible destructive changes in MS.

Topography and Determinants of Magnetic Resonance Imaging (MRI)-Visible Perivascular Spaces in a Large Memory Clinic Cohort.

BACKGROUND: Magnetic resonance imaging-visible perivascular spaces (PVS) are related to interstitial fluid clearance pathways (including amyloid-ß) in the brain and are suggested to be a marker of cerebral small vessel disease. We investigated the role, topography, and possible implications of PVS in cognitive impairment. METHODS AND RESULTS: A total of 1504 patients undergoing memory clinic investigation and an associated brain magnetic resonance imaging scan were included in this cross-sectional study. Magnetic resonance images were assessed for markers of small vessel disease. Additionally, 1039 patients had cerebrospinal fluid analysis of amyloid-ß 42, total tau (T-tau), and phosphorylated tau (P-tau); 520 patients had apoE genotyping done. Results were analyzed with generalized linear models. A total of 289 (19%; 95% confidence interval, 17-21) had a high-grade PVS in the centrum semiovale (CSO) and 65 (4%; 95% confidence interval: 3%-5%) in the basal ganglia (BG). Centrum semiovale- and BG-PVS were both associated with high age (P<0.001), hypertension (P<0.001), probable cerebral amyloid angiopathy (P<0.05), moderate-to-severe white matter hyperintensities (P<0.001), cortical superficial siderosis (P<0.001), cerebral microbleeds (P<0.001), and PVS. centrum semiovale-PVS was separately associated with strictly lobar cerebral microbleeds (P=0.057). BG-PVS was associated with strictly deep cerebral microbleeds (P<0.001), lacunes (P<0.001), and vascular dementia (P=0.04). BG-PVS showed a tendency to be associated with high cerebrospinal fluid tau (B=0.002, P=0.04) in the whole cohort and in Alzheimer's disease (B=0.005; P=0.02). No other associations with cerebrospinal fluid or the apoE e4 allele was observed. CONCLUSIONS: Centrum semiovale-PVS and BG-PVS have different underlying etiology, being associated with cerebral amyloid angiopathy and hypertensive vasculopathy, respectively, although a significant overlap between these pathologies is likely to exist.

Cerebrospinal fluid profiles with increasing number of cerebral microbleeds in a continuum of cognitive impairment.

Cerebral microbleeds (CMBs) are hypothesised to have an important yet unknown role in the dementia disease pathology. In this study we analysed increasing number of CMBs and their independent associations with routine cerebrospinal fluid (CSF) biomarkers in a continuum of cognitive impairment. A total of 1039 patients undergoing dementia investigation were analysed and underwent lumbar puncture, and an MRI scan. CSF samples were analysed for amyloid ß (Aß) 42, total tau (T-tau), tau phosphorylated at threonine 18 (P-tau) and CSF/serum albumin ratios. Increasing number of CMBs were independently associated with low Aß42 levels, in the whole cohort, Alzheimer's disease and mild cognitive impairment (p < 0.05). CSF/serum albumin ratios were high with multiple CMBs (p < 0.001), reflecting accompanying blood-brain barrier dysfunction. T-tau and P-tau levels were lower in Alzheimer's patients with multiple CMBs when compared to zero CMBs, but did not change in the rest of the cohort. White matter hyperintensities were associated with low Aß42 in the whole cohort and Alzheimer's disease (p < 0.05). Aß42 is the routine CSF-biomarker mainly associated with CMBs in cognitive impairment, and there is an accumulative effect with increasing number of CMBs.

Cortical superficial siderosis: Prevalence and biomarker profile in a memory clinic population.

OBJECTIVE: To gain further insight into cortical superficial siderosis (cSS), a new hemorrhagic neuroimaging marker of cerebral amyloid angiopathy (CAA), and to investigate the clinical, neuroimaging, genetic, and CSF biomarker profile of cSS in a large, consecutive memory clinic series. METHODS: We included 1,504 memory clinic patients undergoing dementia investigation including a brain MRI in our center. Routine CSF biomarker analysis was performed in 1,039 patients and APOE genotyping in 520 patients. MRIs were systematically evaluated for presumed marker of small vessel disease: cSS, cerebral microbleeds, enlarged perivascular spaces, white matter hyperintensities, and lacunes. RESULTS: cSS was detected in 40 patients (2.7%; 95% confidence interval [CI] 1.9-3.6); cSS was focal in 33 cases (2.2%; 95% CI 1.5-3.1) and disseminated in 7 (0.5%; 95% CI 0.2-1). Vascular dementia had the highest cSS prevalence (13%; 95% CI 5.4-24.9), followed by Alzheimer disease (5%; 95% CI 3.1-7.5). The most commonly affected area was the occipital lobe (70%; 95% CI 53.5-83.4). cSS was associated with lobar cerebral microbleeds (odds ratio [OR] 7.9; 95% CI 3.4-18.1; p < 0.001), high-degree centrum semiovale perivascular spaces (OR 1.7; 95% CI 1.2-2.6; p = 0.008), and white matter hyperintensities (OR 1.5; 95% CI 1.0-2.2; p = 0.062). APOE ε4/4 genotype was more common in cSS cases compared to those without. CSF ß-amyloid 42 was lower in patients with cSS (coefficient -0.09; 95% CI -0.15 to -0.03; p = 0.004). CONCLUSIONS: Our large series of memory clinic patients provides evidence that cSS is related to cerebrovascular disease and may be a manifestation of severe CAA, even in patients without intracerebral hemorrhage.

MRI-Defined Corpus Callosal Atrophy in Multiple Sclerosis: A Comparison of Volumetric Measurements, Corpus Callosum Area and Index.

OBJECTIVE: To compare corpus callosum area (CCA) and corpus callosum index (CCI) in terms of feasibility and their performance as biomarkers for cognitive and physical disability in multiple sclerosis (MS). A secondary aim was to compare these two methods with volumetric measurements. METHODS: This study was based on a cohort of 37 MS patients and a group of age- and gender-matched healthy controls. Physical disability was assessed with the expanded disability status scale (EDSS) and cognitive disability with the symbol digit modalities test (SDMT). CCA and CCI were assessed on midsagittal brain MRI by 3 raters with varying radiological experience. Volumes of the brain, gray and white matter, corpus callosum, and MS lesions were acquired with Freesurfer and Lesion Segmentation Toolbox for Statistical Parametric Mapping. RESULTS: CCA and CCI were obtained within seconds with excellent intra- and inter-rater agreement, and outperformed volumetric measurements. CCA had the strongest correlations with both SDMT (r = .82, P < .001) and EDSS (r = -.56, P < .001), and the highest accuracy in differentiating patients from controls (95%) and relapse-remitting MS from progressive forms of MS (77%). CCI performed less well (r = .73, P < .001; r = -.45, P < .001; 94%; 71%). CCA also outperformed the volumetric measurements in these regards. CONCLUSIONS: CCA is a time-effective and robust biomarker that has stronger correlations with both EDSS and information processing speed than CCI and volumetric measurements that are commonly used as outcome measures in MS research and clinical trials.

Immediate Achilles tendon response after strength training evaluated by MRI.

PURPOSE: To evaluate the tendon response after acute strength training in chronic Achilles tendinosis using magnetic resonance imaging (MRI). METHODS: Twenty-two patients (44 Achilles tendons, 15 males, 8 patients with bilateral symptoms) with a median age of 45 yr (range 28-57 yr) were included in the study. In all patients, both Achilles tendons were examined with MRI before and immediately after a standardized training program. The most painful side underwent 6 sets and 15 repetitions of heavy-loaded eccentric training. The contralateral tendons underwent only concentric loading during the training program. The tendon volume and the intratendinous signal were evaluated and calculated by MRI using a seed-growing technique. RESULTS: The immediate response of eccentric loading on the symptomatic tendons resulted in a 12% increase of the tendon volume, evident on T2-WI, from 7.8 +/- 2.0 to 8.8 +/- 2.7 cm3 (P < 0.001), and a 31% increase of the intratendinous signal evident on PD-WI, from 221 +/- 74 to 278 +/- 78 signal units (SU) (P < 0.001). The corresponding sequences on the contralateral concentrically loaded tendons showed an increase of 17% of tendon volume, from 6.1 +/- 1.5 to 7.0 +/- 1.6 cm3 (P < 0.001), and an increase of 27% of the intratendinous signal, from 170 +/- 55 to 211 +/-57 SU (P < 0.001). There was no significant difference of the mean of the increased tendon volume and the intratendinous signal between the eccentrically heavily loaded symptomatic tendons and the concentrically loaded contralateral tendons. CONCLUSIONS: Both eccentric and concentric loading of the Achilles tendon resulted in increased total tendon volume and intratendinous signal. This increase may be explained by a higher water content and/or hyperemia in the Achilles tendon during and/or immediately after strength training of the gastrocnemius-soleus complex.

Differential Effects of Single-Dose Escitalopram on Cognitive and Affective Interference during Stroop Task.

BACKGROUND AND OBJECTIVE: Our aim was to study the regulatory role of serotonin [(5-hydroxytryptamine (5-HT)] on two key nodes in the cognitive control networks - the anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC). We hypothesized that increasing the levels of 5-HT would preferentially modulate the activity in ACC during cognitive control during interference by negative affects compared to cognitive control during interference by a superimposed cognitive task. METHODS: We performed a functional magnetic resonance imaging investigation on 11 healthy individuals, comparing the effects of the selective 5-HT reuptake inhibitor escitalopram on brain oxygenation level dependent signals in the ACC and the DLPFC using affective and cognitive counting Stroop paradigms (aStroop and cStroop). RESULTS: Escitalopram significantly decreased the activity in rostral ACC during aStroop compared to cStroop (p < 0.05). In the absence of escitalopram, both aStroop and cStroop significantly activated ACC and DLPFC (Z ≥ 2.3, p < 0.05). CONCLUSION: We conclude that escitalopram in a region and task specific manner modified the cognitive control networks and preferentially decreased activity induced by affective interference in the ACC.

Functional and structural alterations in the cingulate motor area relate to decreased fronto-striatal coupling in major depressive disorder with psychomotor disturbances.

Psychomotor disturbances are a classic feature of major depressive disorders. These can manifest as lack of facial expressions and decreased speech production, reduced body posture and mobility, and slowed voluntary movement. The neural correlates of psychomotor disturbances in depression are poorly understood but it has been suggested that outputs from the cingulate motor area (CMA) to striatal motor regions, including the putamen, could be involved. We used functional and structural magnetic resonance imaging to conduct a region-of-interest analysis to test the hypotheses that neural activation patterns related to motor production and gray matter volumes in the CMA would be different between depressed subjects displaying psychomotor disturbances (n = 13) and matched healthy controls (n = 13). In addition, we conducted a psychophysiological interaction analysis to assess the functional coupling related to self-paced finger-tapping between the caudal CMA and the posterior putamen in patients compared to controls. We found a cluster of increased neural activation, adjacent to a cluster of decreased gray matter volume in the caudal CMA in patients compared to controls. The functional coupling between the left caudal CMA and the left putamen during finger-tapping task performance was additionally decreased in patients compared to controls. In addition, the strength of the functional coupling between the left caudal CMA and the left putamen was negatively correlated with the severity of psychomotor disturbances in the patient group. In conclusion, we found converging evidence for involvement of the caudal CMA and putamen in the generation of psychomotor disturbances in depression.

Radiologically isolated syndrome: an uncommon finding at a university clinic in a high-prevalence region for multiple sclerosis.

OBJECTIVE: The improved availability of MRI in medicine has led to an increase in incidental findings. Unexpected brain MRI findings suggestive of multiple sclerosis (MS) without typical symptoms of MS were recently defined as radiologically isolated syndrome (RIS). The prevalence of RIS is uncertain. The aim of this study was to determine the prevalence of RIS at a university hospital in a region with a high prevalence for MS and describe the long-term prognosis of the identified patients. DESIGN: Retrospective cohort study conducted in 2012. SETTING: All brain MRI examinations performed at Karolinska University Hospital in Huddinge, Stockholm, Sweden during 2001 were retrospectively screened by a single rater for findings fulfilling the Okuda criteria. The sample year was chosen in order to establish the long-term prognosis of the patients identified. The examinations of interest were re-evaluated according to the Barkhof criteria by a neuroradiologist with long experience in MS. PARTICIPANTS: In total 2105 individuals were included in the study. Ages ranged from 0 to 90 years with a median age of 48 years. Only one patient with RIS was identified, equivalent to a prevalence of 0.05% in the studied population, or 0.15% among patients aged 15-40 years. The patient with RIS developed symptoms consistent with MS within 3 months accompanied with radiological progression and was diagnosed with MS. CONCLUSIONS: RIS, according to present criteria, is an uncommon finding in a tertiary hospital setting in a high-prevalence region for MS where awareness and clinical suspicion of MS is common. In order to study the prognosis of RIS, multicentre studies, or case-control studies are recommended.