[Loss of contact between doctor and patient: early signaling can prevent escalation]. / Verbroken arts-patiëntcontact.

A good therapeutic relationship leads to better outcomes. In the event of an imminent break in contact, discussing the alliance rupture can be helpful. Optimal use of the countertransference also contributes. Metacommunication can be useful. In this article, some cases illustrating these concepts, are being discussed.

Changes in Self-Reported and Device-Measured Physical Activity Before Abdominal Resection Surgery: A Meta-Analysis.

OBJECTIVE: To determine the effect of interventions on physical activity levels of patients awaiting abdominal resection surgery using self-reported as well as device-measured outcome measures. DATA SOURCE: PubMed and EMBASE databases were searched on the 18th of April 2023 up to April 2023 for studies on interventions to promote physical activity during the preoperative phase. REVIEW METHODS: Studies were included if pre- and post-intervention physical activity was measured between diagnosis and abdominal surgery. Risk of bias was assessed by the Physiotherapy Evidence Database (PEDro) assessment tool for trials. Meta-analyses were performed to assess the effect of the pre-surgery activity promoting interventions on self-reported and device-measured physical activity. RESULTS: Seventeen studies were included in the analysis with 452 subjects in the intervention groups. The random-effect meta-analysis showed a moderate improvement in intervention groups measures in pre-surgery physical activity levels compared to the baseline (SMD = 0.67, [CI = 0.30;1.03], I2 = 79%). The self-reported subgroup meta-analysis showed the largest increase in performed physical activity, (SMD = 0.78, [CI = 0.4;1.15], I2 = 79%) whilst non-significant increase was shown in the device-measured subgroup (SMD = 0.16, [CI = -0.64;0.97], I2 = 58%). CONCLUSION: Increasing physical activity in the preoperative phase is feasible. Self-reported physical activity outcome measures show larger effects compared to device-measured outcome measures. More high-quality research should be performed utilizing objective measures.

Objectively measured preoperative physical activity is associated with time to functional recovery after hepato-pancreato-biliary cancer surgery: a pilot study.

BACKGROUND: Surgical resection is currently the cornerstone of hepato-pancreato-biliary (HPB) cancer treatment. A low preoperative aerobic fitness level has been identified as a modifiable risk factor associated with complications after major abdominal surgery. A person's aerobic fitness is influenced by performing moderate to vigorous physical activity (MVPA). This study aims to determine the activity monitor measured levels of MVPA performed among patients on the waiting list for HPB cancer surgery and their association with postoperative outcomes. METHODS: A prospective, observational multi-center cohort pilot study was conducted. Patients enlisted for resection surgery on suspicion of HPB (pre)malignancy were enrolled. Performed MVPA was measured by an Actigraph wGT3X-BT. Additionally, aerobic fitness was measured via the Incremental Shuttle Walk Test, and (post)operative variables were collected from the electronic patient files. The association between MVPA and the pre- and postoperative variables was determined by univariate and multivariable (logistic) robust regression. RESULTS: A total of 38 participants, median age 66.0 (IQR 58.25-74.75) years, were enrolled. The median daily MVPA was 10.7 (IQR 6.9-18.0) min; only 8 participants met the Dutch MVPA guidelines. Participant's age and aerobic fitness were associated with MVPA by multivariable statistical analysis. Time to functional recovery was 8 (IQR 5-12) days and was associated with MVPA and type of surgery (major/minor) in multivariable analysis. CONCLUSION: Seventy-six percent of patients enlisted for resection of HPB (pre)malignancy performed insufficient MVPA. A higher level of MVPA was associated with a shorter time to functional recovery.

Protein, Calcium, Vitamin D Intake and 25(OH)D Status in Normal Weight, Overweight, and Obese Older Adults: A Systematic Review and Meta-Analysis.

The aging process is often accompanied by increase in body weight. Older adults with overweight or obesity might have an overconsumption in energy that is accompanied by inadequate intake of protein, vitamin D, and calcium. It is unclear if intake of protein and vitamin D and calcium is sufficient in older adults with overweight/obesity, and whether it differs from older adults with normal weight, since a recent overview of the literature review is lacking. Therefore, we systematically analyzed the current evidence on differences in nutrient intake/status of protein, vitamin D and calcium between older adults with different body mass index (BMI) categories. Randomized controlled trials and prospective cohort studies were identified from PubMed and EMBASE. Studies reporting nutrient intake/status in older adults aged ≥50 years with overweight/obesity and studies comparing between overweight/obesity and normal weight were included. Nutrient intake/status baseline values were reviewed and when possible calculated for one BMI category (single-group meta-analysis), or compared between BMI categories (meta-analysis). Nutrient intake/status was compared with international recommendations. Mean protein (N = 8) and calcium intake (N = 5) was 0.98 gram/kilogram body weight/day (g/kg/d) [95% Confidence Interval (CI) 0.89-1.08] and 965 mg [95% CI: 704-1225] in overweight/obese. Vitamin D intake was insufficient in all BMI categories (N = 5). The pooled mean for vitamin D intake was 6 ug [95% CI 4-9]. For 25(OH)D, the pooled mean was 54 nmol/L [95% CI 45-62], 52 nmol/L [95% CI 46-58], and 48 nmol/l [95% CI 33-62] in normal (N = 7), combined overweight and obese (N = 12), and obese older adults (N = 4), respectively. In conclusion, older adults with overweight and obesity have a borderline sufficient protein and sufficient calcium intake, but insufficient vitamin D intake. The 25(OH)D concentration is deficient for the obese older adults.

Quantum mechanics-free subsystem with mechanical oscillators.

Quantum mechanics sets a limit for the precision of continuous measurement of the position of an oscillator. We show how it is possible to measure an oscillator without quantum back-action of the measurement by constructing one effective oscillator from two physical oscillators. We realize such a quantum mechanics-free subsystem using two micromechanical oscillators, and show the measurements of two collective quadratures while evading the quantum back-action by 8 decibels on both of them, obtaining a total noise within a factor of 2 of the full quantum limit. This facilitates the detection of weak forces and the generation and measurement of nonclassical motional states of the oscillators. Moreover, we directly verify the quantum entanglement of the two oscillators by measuring the Duan quantity 1.4 decibels below the separability bound.

Nonreciprocal Transport Based on Cavity Floquet Modes in Optomechanics.

Directional transport is obtained in various multimode systems by driving multiple, nonreciprocally interfering interactions between individual bosonic modes. However, systems sustaining the required number of modes become physically complex. In our microwave-optomechanical experiment, we show how to configure nonreciprocal transport between frequency components of a single superconducting cavity coupled to two drumhead oscillators. The frequency components are promoted to Floquet modes and generate the missing dimension to realize an isolator and a directional amplifier. A second cavity left free by this arrangement is used to cool the mechanical oscillators and bring the transduction noise close to the quantum limit. We furthermore uncover a new type of instability specific to nonreciprocal coupling. Our approach is generic and can greatly simplify quantum signal processing and the design of topological lattices from low-dimensional systems.

Afferent Visual Pathway Affection in Patients with PMP22 Deletion-Related Hereditary Neuropathy with Liability to Pressure Palsies.

BACKGROUND: The PMP22 gene encodes a protein integral to peripheral myelin. Its deletion leads to hereditary neuropathy with liability to pressure palsies (HNPP). PMP22 is not expressed in the adult central nervous system, but previous studies suggest a role in CNS myelin development. The objective of this study was to identify potential structural and functional alterations in the afferent visual system in HNPP patients. METHODS: Twenty HNPP patients and 18 matched healthy controls (HC) were recruited in a cross-sectional study. Participants underwent neurological examination including visual acuity, visual evoked potential (VEP) examination, optical coherence tomography (OCT), and magnetic resonance imaging with calculation of brain atrophy, regarding grey and white matter, and voxel based morphometry (VBM), in addition answered the National Eye Institute's 39-item Visual Functioning Questionnaire (NEI-VFQ). Thirteen patients and 6 HC were additionally examined with magnetic resonance spectroscopy (MRS). RESULTS: All patients had normal visual acuity, but reported reduced peripheral vision in comparison to HC in the NEI-VFQ (p = 0.036). VEP latency was prolonged in patients (P100 = 103.7±5.7 ms) in comparison to healthy subjects (P100 = 99.7±4.2 ms, p = 0.007). In OCT, peripapillary retinal nerve fiber layer thickness RNFL was decreased in the nasal sector (90.0±15.5 vs. 101.8±16.5, p = 0.013), and lower nasal sector RNFL correlated with prolonged VEP latency (Rho = -0.405, p = 0.012). MRS revealed reduced tNAA (731.4±45.4 vs. 814.9±62.1, p = 0.017) and tCr (373.8±22.2 vs. 418.7±31.1, p = 0.002) in the visual cortex in patients vs. HC. Whole brain volume, grey and white matter volume, VBM and metabolites in a MRS sensory cortex control voxel did not differ significantly between patients and HC. CONCLUSION: PMP22 deletion leads to functional, metabolic and macro-structural alterations in the afferent visual system of HNPP patients. Our data suggest a functional relevance of these changes for peripheral vision, which warrants further investigation and confirmation.

European Psychiatric Association Guidance on psychotherapy in chronic depression across Europe.

PURPOSE: Patients with chronic depression (CD) by definition respond less well to standard forms of psychotherapy and are more likely to be high utilizers of psychiatric resources. Therefore, the aim of this guidance paper is to provide a comprehensive overview of current psychotherapy for CD. The evidence of efficacy is critically reviewed and recommendations for clinical applications and research are given. METHODS: We performed a systematic literature search to identify studies on psychotherapy in CD, evaluated the retrieved documents and developed evidence tables and recommendations through a consensus process among experts and stakeholders. RESULTS: We developed 5 recommendations which may help providers to select psychotherapeutic treatment options for this patient group. The EPA considers both psychotherapy and pharmacotherapy to be effective in CD and recommends both approaches. The best effect is achieved by combined treatment with psychotherapy and pharmacotherapy, which should therefore be the treatment of choice. The EPA recommends psychotherapy with an interpersonal focus (e.g. the Cognitive Behavioural Analysis System of Psychotherapy [CBASP]) for the treatment of CD and a personalized approach based on the patient's preferences. DISCUSSION: The DSM-5 nomenclature of persistent depressive disorder (PDD), which includes CD subtypes, has been an important step towards a more differentiated treatment and understanding of these complex affective disorders. Apart from dysthymia, ICD-10 still does not provide a separate entity for a chronic course of depression. The differences between patients with acute episodic depression and those with CD need to be considered in the planning of treatment. Specific psychotherapeutic treatment options are recommended for patients with CD. CONCLUSION: Patients with chronic forms of depression should be offered tailored psychotherapeutic treatments that address their specific needs and deficits. Combination treatment with psychotherapy and pharmacotherapy is the first-line treatment recommended for CD. More research is needed to develop more effective treatments for CD, especially in the longer term, and to identify which patients benefit from which treatment algorithm.

Optic radiation damage in multiple sclerosis is associated with visual dysfunction and retinal thinning--an ultrahigh-field MR pilot study.

OBJECTIVE: To investigate posterior visual pathway damage in multiple sclerosis using ultrahigh-field magnetic resonance imaging (MRI) at 7 Tesla (7 T), and to determine its correlation with visual disability and retinal fibre layer (RNFL) damage detectable by optic coherence tomography (OCT). METHODS: We studied 7 T MRI, OCT, functional acuity contrast testing (FACT), and visually evoked potentials (VEP, n = 16) in 30 patients (including 26 relapsing-remitting MS and four clinically isolated syndrome patients) and 12 healthy controls to quantify RNFL thickness, optic radiation lesion volume, and optic radiation thickness. RESULTS: Optic radiation lesion volume was associated with thinning of the optic radiation (p < 0.001), delayed VEP (p = 0.031), and visual disability indicated by FACT (p = 0.020). Furthermore, we observed an inverse correlation between optic radiation lesion volume and RNFL thickness (p < 0.001), including patients without previous optic neuritis (p < 0.001). CONCLUSIONS: Anterior visual pathway damage, but also (subclinical) optic radiation integrity loss detectable by 7 T MRI are common findings in MS that are mutually affected. Given the association between optic radiation damage, visual impairment, and increased VEP latency in this exploratory study of a limited sample size, clinicians should be aware of acute lesions within the optic radiation in patients with (bilateral) visual disturbances. KEY POINTS: • Focal destruction of the optic radiation is detectable by 7 T MRI. • Focal optic radiation damage is common in MS. • Optic radiation damage is associated with RNFL thinning, detectable by OCT. • Optic radiation damage is associated with delayed VEP and visual dysfunction. • RNFL thickness in non-optic neuritis eyes correlates with optic radiation demyelination.

Modulation of dendritic cell immunobiology via inhibition of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase.

The maturation status of dendritic cells determines whether interacting T cells are activated or if they become tolerant. Previously we could induce T cell tolerance by applying a 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor (HMGCRI) atorvastatin, which also modulates MHC class II expression and has therapeutic potential in autoimmune disease. Here, we aimed at elucidating the impact of this therapeutic strategy on T cell differentiation as a consequence of alterations in dendritic cell function. We investigated the effect of HMGCRI during differentiation of peripheral human monocytes and murine bone marrow precursors to immature DC in vitro and assessed their phenotype. To examine the stimulatory and tolerogenic capacity of these modulated immature dendritic cells, we measured proliferation and suppressive function of CD4+ T cells after stimulation with the modulated immature dendritic cells. We found that an HMGCRI, atorvastatin, prevents dendrite formation during the generation of immature dendritic cells. The modulated immature dendritic cells had a diminished capacity to take up and present antigen as well as to induce an immune response. Of note, the consequence was an increased capacity to differentiate naïve T cells towards a suppressor phenotype that is less sensitive to proinflammatory stimuli and can effectively inhibit the proliferation of T effector cells in vitro. Thus, manipulation of antigen-presenting cells by HMGCRI contributes to an attenuated immune response as shown by promotion of T cells with suppressive capacities.

Effects of deep repetitive transcranial magnetic stimulation on brain-derived neurotrophic factor serum concentration in healthy volunteers.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive, safe and efficacious technique for treating various neuropsychiatric disorders, but its underlying mechanisms are poorly understood. A newly developed H-coil allows the stimulation of deeper brain regions. This study is the first to investigate the effects of deep high-frequency rTMS on brain-derived neurotrophic factor (BDNF) serum concentrations in healthy volunteers. We aimed to evaluate the short-term effect of deep rTMS on BDNF serum concentrations. METHODS: This was a double-blind, randomized deep high-frequency rTMS study using an H-coil on a cohort of 13 healthy volunteers (NCT01106365). The following stimulation protocols were applied: 18-Hz stimulation of the left dorsolateral prefrontal cortex (PFC), 5-Hz stimulation of the primary motor cortex (MC) and sham stimulation in random order. Blood samples were obtained before, 30 min after and 60 min after each treatment. RESULTS: The BDNF serum concentration decreased significantly after MC and PFC stimulation, but not after sham stimulation. Furthermore, BDNF serum level changes were associated with changes in individual alertness. CONCLUSION: Although BDNF serum concentrations do not necessarily correlate with BDNF levels in the cerebrospinal fluid or the brain, these results indicate an acute biological effect of deep rTMS on BDNF release, and demonstrate that this change correlates with alertness.

Quantum metrology with a scanning probe atom interferometer.

We use a small Bose-Einstein condensate on an atom chip as an interferometric scanning probe to map out a microwave field near the chip surface with a few micrometers resolution. With the use of entanglement between the atoms, our interferometer overcomes the standard quantum limit of interferometry by 4 dB and maintains enhanced performance for interrogation times up to 10 ms. This corresponds to a microwave magnetic field sensitivity of 77 pT/√Hz in a probe volume of 20 µm(3). Quantum metrology with entangled atoms is useful in measurements with high spatial resolution, since the atom number in the probe volume is limited by collisional loss. High-resolution measurements of microwave near fields, as demonstrated here, are important for the development of integrated microwave circuits for quantum information processing and applications in communication technology.

Periventricular venous density in multiple sclerosis is inversely associated with T2 lesion count: a 7 Tesla MRI study.

BACKGROUND: Damage to venules in multiple sclerosis was first described decades ago. Today, ultrahigh magnetic field strength T2*-weighted magnetic resonance imaging (MRI) techniques depict very small cerebral veins in vivo with great anatomical detail. OBJECTIVE: We aimed to investigate alterations of periventricular small blood vessel appearance in relation to T2 lesion count and distribution in multiple sclerosis and clinically isolated syndrome in comparison with healthy control subjects at 7 Tesla MRI. METHODS: We investigated 38 patients (including 16 with early multiple sclerosis and seven with clinically isolated syndrome) and 22 matched healthy controls at 7 Tesla. The protocol included T2*-weighted Fast Low Angle Shot, and T2-weighted Turbo Inversion Recovery Magnitude sequences. We quantified periventricular venous density by a novel region-of-interest-based algorithm, expressing the ratio of 'veins per region-of-interest' as well as of 'periventricular vascular area'. RESULTS: Our study revealed significantly decreased venous density in multiple sclerosis patients compared with healthy controls. Venous alterations were already detectable in clinically isolated syndrome and early multiple sclerosis, although to a smaller extent. Venous density correlated inversely with periventricular and whole-brain T2 lesion count. Furthermore, we found no indication for cerebral venous congestion in multiple sclerosis. CONCLUSION: High spatially resolving anatomical T2*-weighted MRI revealed vascular alterations in early stages of multiple sclerosis, presumably as a part of widespread haemodynamic and metabolic alterations.

[Psychotherapy of chronic depression: contributions of CBASP by McCullough]. / Psychothérapie de la dépression chronique : l'apport du modèle CBASP selon McCullough.

INTRODUCTION: Chronic depression is a frequent disorder and is usually treated using traditional approaches. These approaches rarely take into account the psychopathological specificities of the chronic evolution of the disorder. OBJECTIVE: The present article aims at presenting the specific psychopathological nature of chronic depression and puts forward a treatment model that is particularly adapted to these specificities. TREATMENT MODEL: The treatment model, Cognitive Behavioral Analysis System of Psychotherapy (CBASP; according to McCullough) is based on two theoretical models: the developmental theory by J. Piaget and the interpersonal model by D. Kiesler. According to McCullough, the cognitive affective functioning of chronically depressed patients is comparable with the one of a child who has not reached the Piagetian stage of logical operations. Their thinking is global, pre-logical and presents with monologues, instead of internal dialogues. These patients are incapable of effective controlling and regulating of emotions and of constructive accommodation of established schemas, when confronted with novel experiences. Finally, these patients are unaware of their interpersonal effects on the environment they unwillingly have. The latter are conceptualized using Kiesler's conceptualization of psychopathology. According to this model, the patient sends implicit relational "messages" provoking interpersonal "pulls" in the interaction partner (e.g., the therapist). These pulls are assessed and may be graphically represented using a Circumplex Model, also called the Kiesler-circle, and is the basis of the case conceptualization in the psychotherapy with chronically depressed patients. CBASP has developed based on the clinical implications of these models and combines them in an original fashion. PRESENTATION OF MAIN THERAPEUTIC INTERVENTIONS: Two lines of intervention result from the models: (1) situational analysis, which analyzes the links between behavior in a particular situation and the person's goal or desire related to the particular situation, and (2) interpersonal techniques based on the notions of transference and counter-transference. On one hand, situational analysis follows several steps linking the patient's behavior with his/her desired outcome, which is compared to the real outcome in the situation. The patient's interpretations are amended in a second step, using the desired outcome as an anchor. On the other hand, interpersonal techniques imply the therapist's stance of disciplined personal involvement, meaning a controlled way of therapist self-disclosure facing the patient, with the aim of experiencing by the patient, that his/her behavior does not remain without specific, immediate and authentic consequences in the environment. This experience by the patient should allow him/her to (re-)establish the perceived functionality of the patient's behavior in interpersonal encounters. DISCUSSION AND CONCLUSIONS: We underline the relevance of the approach by citing several empirical studies which have established the efficacy of the model, in specific clinical conditions that are the combined treatment with anti-depressant medication, a sufficient number of sessions and in the case of early trauma as etiological factor of the chronic depression. We discuss the application of CBASP to other clinical diagnoses, such as borderline and avoidant personality disorder as well as disorders related to substance abuse and thus argue in favor of CBASP as a central model in the treatment of various mental illnesses.

Distinct lesion morphology at 7-T MRI differentiates neuromyelitis optica from multiple sclerosis.

OBJECTIVE: To investigate distinct white matter and cortical gray matter pathology in neuromyelitis optica spectrum disorders (NMOSDs) and multiple sclerosis (MS) at 7-T MRI in a cross-sectional study. METHODS: We included 10 patients with NMOSDs and 18 patients with MS in our 7-T MRI study. The imaging protocol comprised T2*-weighted fast low angle shot and turbo inversion recovery magnitude sequences. White matter and cortical gray matter lesions were assessed with special regard to their (perivascular) localization as well as the expression of a hypointense rim. RESULTS: In total, we detected 140 white matter lesions in 7 of 10 patients with NMOSDs. In contrast to MS plaques, which were nearly exclusively centered by a small vein (92%) and showed a characteristic hypointense rim (23%), white matter changes in patients with NMOSDs were nonspecific in appearance and were only infrequently neighbored by a blood vessel (49 lesions [35%], p = 0.003). Hypointense rims were very rarely detectable (3 lesions [2%], p < 0.001). Cortical pathology was absent in NMOSDs. In our MS cohort, we detected 36 leukocortical, 8 intracortical, and 8 subpial cortical lesions in 7 of 18 patients. CONCLUSION: The MRI features of white matter and the absence of cortical gray matter findings substantially differentiate NMOSDs from MS and can be used as a potential marker to distinguish these 2 entities. The fact that cortical pathology is common in MS but is not present in patients with NMOSDs may reflect the difference in the underlying pathogenesis.

Expert recommendations to personalization of medical approaches in treatment of multiple sclerosis: an overview of family planning and pregnancy.

Multiple sclerosis is the most common chronic autoimmune disease of the central nervous system which preferentially affects females at childbearing age. For this reason, patients and treating physicians were frequently confronted with questions concerning family planning, pregnancy and birth. Preventive and personalized treatment approaches are considered, because topics as heredity, risk of congenital malformations, influence of pregnancy on MS and aspects of drug therapy during the period of conception, pregnancy, puerperium and lactation have to be discussed. Here, we provide an overview about the current state of knowledge regarding these issues.

Can we overcome the 'clinico-radiological paradox' in multiple sclerosis?

The association between common neuroradiological markers of multiple sclerosis (MS) and clinical disability is weak, a phenomenon known as the clinico-radiological paradox. Here, we investigated to which degree it is possible to predict individual disease profiles from conventional magnetic resonance imaging (MRI) using multivariate analysis algorithms. Specifically, we conducted cross-validated canonical correlation analyses to investigate the predictive information contained in conventional MRI data of 40 MS patients for the following clinical parameters: disease duration, motor disability (9-Hole Peg Test, Timed 25-Foot Walk Test), cognitive dysfunction (Paced Auditory Serial Addition Test), and the expanded disability status scale (EDSS). It turned out that the information in the spatial patterning of MRI data predicted the clinical scores with correlations of up to 0.80 (p < 10(-9)). Maximal predictive information for disease duration was identified in the precuneus and somatosensory cortex. Areas in the precuneus and precentral gyrus were maximally informative for motor disability. Cognitive dysfunction could best be predicted using data from the angular gyrus and superior parietal lobe. For EDSS, the inferior frontal gyrus was maximally informative. In conclusion, conventional MRI is highly predictive of clinical disability in MS when pattern-based algorithms are used for prediction. Thus, the so-called clinico-radiological paradox is not apparent when using suitable analysis techniques.

Multiple sclerosis lesions and irreversible brain tissue damage: a comparative ultrahigh-field strength magnetic resonance imaging study.

BACKGROUND: In current clinical practice, T2-weighted magnetic resonance imaging (MRI) is commonly applied to quantify the accumulated multiple sclerosis (MS)lesion load, whereas T1-weighted sequences are used to differentiate edema, blood-brain barrier breakdown by contrast enhancement, and irreversible brain tissue damage(commonly called "black holes" owing to the loss of signal intensity in T1-weighted sequences). Black holes are histopathologically associated with axonal loss and severe tissue destruction. In addition, double inversion recovery techniques were developed to improve the sensitivity to cortical lesions. OBJECTIVE: To demonstrate the potential of ultrahigh-field 3-dimensional T1-weighted imaging using magnetization-prepared rapid acquisition and multiple gradient echoes(MPRAGE) to detect and characterize white and gray matter pathology in MS. DESIGN: Comparative study. SETTING: The patients with MS were recruited from the outpatient clinics of the Neuro Cure Clinical Research Center and underwent 7-T brain MRI at the Berlin Ultrahigh Field Facility, both of which are in Berlin, Germany. PATIENTS: Twenty patients with relapsing-remitting MS and 14 healthy controls underwent 7-T brain MRI, using a 24-channel receive head coil, and a subgroup of 18 patients with relapsing-remitting MS also underwent 1.5-T brain MRI. The imaging protocol included 2-dimensional T2-weighted fast low-angle shot (FLASH) and turbo inversion recovery magnitude (TIRM) sequences. For 3-dimensional T1-weighted imaging, the MPRAGE sequence was used. Each sequence was initially examined independently in separate analyses by an investigator blinded to all other data. In a second study, all detected lesions were retrospectively analyzed in a side-by-side comparison of all sequences. RESULTS: By use of 7-T T2-weighted FLASH imaging, 604 cerebral lesions were detected in the patients with relapsing-remitting MS (mean, 30.2 lesions per patient[range, 2-107 lesions per patient]), but none were detected in healthy controls. Cortical pathology was visible in 10 patients (6 cortical lesions and 37 leukocortical lesions). Within the 7-T acquisitions, each lesion detected at T2-weighted sequences and/or double inversion recovery sequences was also clearly delineated on corresponding MPRAGE sequences in side-by-side analysis.However, at 1.5 T, the MPRAGE images depicted only 452 of 561 lesions visualized in T2-weighted sequences and/or double inversion recovery sequences. In contrast,when analyzing each sequence separately, we found that the 7-T MPRAGE depicted more lesions than the 7-TFLASH (728 lesions vs 584 lesions), and almost twice as many as the 1.5-T MPRAGE (399 lesions). The 7-TMPRAGE also improved the detection of cortical and leukocortical lesions (15 lesions vs 58 lesions). CONCLUSIONS: At ultrahigh-field strength, T1-weighted MPRAGE is highly sensitive in detecting MS plaques within the white and the gray brain parenchyma. Our results indicate structural damage beyond demyelination in every lesion depicted, which is in accordance with postmortem histopathological studies. The 7-T MPRAGE clearly delineated every cortical lesion that was visualized by any other MRI sequence at 1.5 or 7 T.

Impairment of contrast visual acuity as a functional correlate of retinal nerve fibre layer thinning and total macular volume reduction in multiple sclerosis.

OBJECTIVES: To analyse the association between retinal nerve fibre layer thickness (RNFLT) and total macular volume (TMV) as measured by optical coherence tomography, and contrast sensitivity (CS) measured by Functional Acuity Contrast Testing (FACT) in relapsing-remitting multiple sclerosis; and to investigate whether FACT testing by a contrast box device is feasible in multiple sclerosis (MS). METHODS: fact was performed using the Optec 6500 P vision testing system with best correction under photopic and mesopic conditions without glare. The Area Under the Log Contrast Sensitivity Function (AUC) was calculated. RNFLT and TMV were assessed by Stratus optical coherence tomography. All participants underwent visual acuity testing (Snellen), spherical refractive error testing and cylindrical refractive error testing. RESULTS: 85 relapsing-remitting multiple sclerosis patients (170 eyes) and 35 healthy controls (HC, 70 eyes) were measured. AUC Day and Night were lower in MS than in HC (p<0.001) when correcting for age, as were mean RNFLT and TMV (p<0.001 and p=0.018, respectively). Both RNFLT and TMV predicted contrast sensitivity in MS (AUC Day: standardised coefficient ß=0.277, p<0.001, and ß=0.262, p<0.001, respectively; AUC Night: ß=0.202, p=0.009 and ß=0.222, p=0.004, respectively, linear regressions). In HC, there was no correlation between RNFLT or TMV and contrast sensitivity. CONCLUSION: (1) Contrast sensitivity is reduced in MS versus HC; (2) RNFL and TMV as morphological measures of retinal axonal loss are predictors of contrast sensitivity as a functional visual parameter in MS but not in HC; and (3) FACT with the contrast box is a novel, feasible and rapid method to assess contrast sensitivity in MS.

Magnetic resonance elastography reveals altered brain viscoelasticity in experimental autoimmune encephalomyelitis.

Cerebral magnetic resonance elastography (MRE) measures the viscoelastic properties of brain tissues in vivo. It was recently shown that brain viscoelasticity is reduced in patients with multiple sclerosis (MS), highlighting the potential of cerebral MRE to detect tissue pathology during neuroinflammation. To further investigate the relationship between inflammation and brain viscoelasticity, we applied MRE to a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). EAE was induced and monitored by MRE in a 7-tesla animal MRI scanner over 4 weeks. At the peak of the disease (day 14 after immunization), we detected a significant decrease in both the storage modulus (G') and the loss modulus (G″), indicating that both the elasticity and the viscosity of the brain are reduced during acute inflammation. Interestingly, these parameters normalized at a later time point (day 28) corresponding to the clinical recovery phase. Consistent with this, we observed a clear correlation between viscoelastic tissue alteration and the magnitude of perivascular T cell infiltration at both day 14 and day 28. Hence, acute neuroinflammation is associated with reduced mechanical cohesion of brain tissues. Moreover, the reduction of brain viscoelasticity appears to be a reversible process, which is restored when inflammation resolves. For the first time, our study has demonstrated the applicability of cerebral MRE in EAE, and showed that this novel imaging technology is highly sensitive to early tissue alterations resulting from the inflammatory processes. Thus, MRE may serve to monitor early stages of perivascular immune infiltration during neuroinflammation.