Introduction
Somatosensory evoked potentials (SSEP) play a pivotal role in the diagnosis and disease monitoring of multiple sclerosis (MS). Delayed latencies are a surrogate for demyelination along ...the sensory afference. This study aimed to evaluate if SSEP latencies are representative of demyelination of the brain overall, by correlating with cerebral microstructural integrity as measured by Magnetic resonance (MR) diffusion tensor imaging (DTI). Analysis was performed in a hypothesis-free whole brain approach using tract-based spatial statistics (TBSS).
Material and methods
A total of 46 patients with MS or clinically isolated syndrome were included in the study. Bilateral SSEPs of the median nerve measuring mean N20 latencies (mN20) and Central Conduction Time (CCT), were acquired. MRI scans were performed at 3T. DTI acquisition was done with a single-shot echoplanar imaging technique with 80 diffusion directions. The FSL software package was used to process the DTI datasets and to calculate maps of fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD). These maps were then further analyzed using the TBSS module. The mean N20 and CCT and the right- and left-sided N20 and CCT were separately correlated to FA, AD, and RD, controlled for age, gender, and EDSS as variables of non-interest.
Results
Widespread negative correlations of SSEP latencies with FA (
p
= 0.0005) and positive correlations with RD (
p
= 0.0003) were measured in distinct white matter tracts, especially the optic tracts, corpus callosum, and posterior corona radiata. No correlation with AD was found in any white matter tract.
Conclusion
Highly significant correlations of FA and RD to SSEPs suggest that their latency is representative of widespread microstructural change, and especially demyelination in patients suffering from MS, reaching beyond the classic somatosensory regions. This points to the usefulness of SSEPs as a non-invasive tool in the evaluation of microstructural damage to the brain.
Rats exposed to chronic predator scent stress mimic the phenotype of complex post-traumatic stress disorder (PTSD) in humans, including altered adrenal morphology and function. High- and low-anxiety ...phenotypes have been described in rats exposed to predator scent stress (PSS). This study aimed to determine whether these high- and low-anxiety phenotypes correlate with changes in adrenal histomorphology and corticosteroid production.
Rats were exposed to PSS for ten days. Thirty days later, the rats' anxiety index (AI) was assessed with an elevated plus-maze test. Based on differences in AI, the rats were segregated into low- (AI ≤ 0.8, n = 9) and high- (AI > 0.8, n = 10) anxiety phenotypes. Plasma corticosterone (CORT) concentrations were measured by ELISA. Adrenal CORT, desoxyCORT, and 11-dehydroCORT were measured by high-performance liquid chromatography. After staining with hematoxylin and eosin, adrenal histomorphometric changes were evaluated by measuring the thickness of the functional zones of the adrenal cortex.
Decreased plasma CORT concentrations, as well as decreased adrenal CORT, desoxyCORT and 11-dehydroCORT concentrations, were observed in high- but not in low-anxiety phenotypes. These decreases were associated with increases in AI. PSS led to a significant decrease in the thickness of the
and an increase in the thickness of the
. The increase in the thickness of the
was more pronounced in low-anxiety than in high-anxiety rats. A decrease in the adrenal capsule thickness was observed only in low-anxiety rats. The nucleus diameter of cells in the
of high-anxiety rats was significantly smaller than that of control or low-anxiety rats.
Phenotype-associated changes in adrenal function and histomorphology were observed in a rat model of complex post-traumatic stress disorder.
IntroductionMajor depressive disorder (MDD) and obesity are both common disorders associated with significant burden of disease worldwide. Importantly, MDD and obesity often co-occur, with each ...disorder increasing the risk for developing the other by about 50%–60%. Statins are among the most prescribed medications with well-established safety and efficacy. Statins are recommended in primary prevention of cardiovascular disease, which has been linked to both MDD and obesity. Moreover, statins are promising candidates to treat MDD because a meta-analysis of pilot randomised controlled trials has found antidepressive effects of statins as adjunct therapy to antidepressants. However, no study so far has tested the antidepressive potential of statins in patients with MDD and comorbid obesity. Importantly, this is a difficult-to-treat population that often exhibits a chronic course of MDD and is more likely to be treatment resistant. Thus, in this confirmatory randomised controlled trial, we will determine whether add-on simvastatin to standard antidepressant medication with escitalopram is more efficacious than add-on placebo over 12 weeks in 160 patients with MDD and comorbid obesity.Methods and analysisThis is a protocol for a randomised, placebo-controlled, double-blind multicentre trial with parallel-group design (phase II). One hundred and sixty patients with MDD and comorbid obesity will be randomised 1:1 to simvastatin or placebo as add-on to standard antidepressant medication with escitalopram. The primary outcome is change in the Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to week 12. Secondary outcomes include MADRS response (defined as 50% MADRS score reduction from baseline), MADRS remission (defined as MADRS score <10), mean change in patients’ self-reported Beck Depression Inventory (BDI-II) and mean change in high-density lipoprotein, low-density lipoprotein and total cholesterol from baseline to week 12.Ethics and disseminationThis protocol has been approved by the ethics committee of the federal state of Berlin (Ethik-Kommission des Landes Berlin, reference: 19/0226—EK 11) and by the relevant federal authority (Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), reference: 4043387). Study findings will be published in peer-reviewed journals and will be presented at (inter)national conferences.Trial registration numbersNCT04301271, DRKS00021119, EudraCT 2018-002947-27.
The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little ...is known so far about the clinical impact of AQP4-Ab seropositivity.
To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus.
Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%).
Seropositive patients were found to be predominantly female (p < 0.0003), to more often have signs of co-existing autoimmunity (p < 0.00001), and to experience more severe clinical attacks. A visual acuity of ≤ 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p < 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse, and MRC grades ≤ 2 more frequent, in particular if patients met the 2006 revised criteria (p < 0.005, p < 0.006 and p < 0.01, respectively), the total spinal cord lesion load was higher (p < 0.006), and lesions ≥ 6 vertebral segments as well as entire spinal cord involvement more frequent (p < 0.003 and p < 0.043). By contrast, bilateral ON at onset was more common in seronegatives (p < 0.007), as was simultaneous ON and myelitis (p < 0.001); accordingly, the time to diagnosis of NMO was shorter in the seronegative group (p < 0.029). The course of disease was more often monophasic in seronegatives (p < 0.008). Seropositives and seronegatives did not differ significantly with regard to age at onset, time to relapse, annualized relapse rates, outcome from relapse (complete, partial, no recovery), annualized EDSS increase, mortality rate, supratentorial brain lesions, brainstem lesions, history of carcinoma, frequency of preceding infections, oligoclonal bands, or CSF pleocytosis. Both the time to relapse and the time to diagnosis was longer if the disease started with ON (p < 0.002 and p < 0.013). Motor symptoms or tetraparesis at first myelitis and > 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome.
This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients.
Autoimmune encephalitis (AE) can rarely manifest as a predominantly psychiatric syndrome without overt neurological symptoms. This study's aim was to characterize psychiatric patients with AE; ...therefore, anonymized data on patients with suspected AE with predominantly or isolated psychiatric syndromes were retrospectively collected. Patients with readily detectable neurological symptoms suggestive of AE (e.g., epileptic seizures) were excluded. Patients were classified as "probable psychiatric AE (pAE)," if well-characterized neuronal IgG autoantibodies were detected or "possible pAE" (e.g., with detection of nonclassical neuronal autoantibodies or compatible cerebrospinal fluid (CSF) changes). Of the 91 patients included, 21 (23%) fulfilled our criteria for probable (autoantibody-defined) pAE and 70 (77%) those for possible pAE. Among patients with probable pAE, 90% had anti-NMDA receptor (NMDA-R) autoantibodies. Overall, most patients suffered from paranoid-hallucinatory syndromes (53%). Patients with probable pAE suffered more often from disorientation (p < 0.001) and impaired memory (p = 0.001) than patients with possible pAE. Immunotherapies were performed in 69% of all cases, mostly with high-dose corticosteroids. Altogether, 93% of the patients with probable pAE and 80% of patients with possible pAE reportedly benefited from immunotherapies (p = 0.251). In summary, this explorative, cross-sectional evaluation confirms that autoantibody-associated AE syndromes can predominantly manifest as psychiatric syndromes, especially in anti-NMDA-R encephalitis. However, in three out of four patients, diagnosis of possible pAE was based on nonspecific findings (e.g., slight CSF pleocytosis), and well-characterized neuronal autoantibodies were absent. As such, the spectrum of psychiatric syndromes potentially responding to immunotherapies seems not to be limited to currently known autoantibody-associated AE. Further trials are needed.
Simultaneous PET/Mri in Stroke: A Case Series Werner, Peter; Saur, Dorothee; Zeisig, Vilia ...
Journal of cerebral blood flow and metabolism,
09/2015, Letnik:
35, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Prospective studies on magnetic resonance imaging (MRI)-guided systemic thrombolysis 44.5 hours after stroke onset did not reach their primary end points. It was discussed and observed in post hoc ...data re-assessment that this was partly because of limited MRI accuracy to measure critical hypoperfusion. We report the first cases of simultaneous 15OH2O-positron emission tomography (PET)/MRI in stroke patients and an ovine model. Discrepancies between simultaneously obtained PET and MRI readouts were observed that might explain the above current limitations of stroke MRI. By offering highly complementary information, 15OH2O-PET/MRI might help to identify critically hypoperfused tissue resulting in an improved patient stratification in thrombolysis trials.
Objectives: The Sig-1R is a chaperone protein localized at the endoplasmatic reticulum (ER) that can translocate under ER stress, a mechanism which is critically involved in the pathophysiology of ...MDD. In order to investigate the pathophysiology of Sig-1R regulation in MDD, for the first time we quantitatively assessed Sig-1R binding in the brain of unmedicated, acute MDD and compared it with healthy controls (HC) using the novel radioligand (-)-18FFluspidine and PET. Methods: Unmedicated patients with moderate to severe, acute MDD (n=12; 33±13ys; 6 males; HAMD: 19.0±4.3; MDD+ with family history n=6 and MDD- without family history of depression n=6), were investigated using (-)-18FFluspidine PET (~300 MBq, ECAT Exact HR+) and compared with age-/sex-matched healthy controls (HC; n=9; 37±16ys n.s.; 4 males n.s.). Distribution volume parameters (VT) were determined using full pharmacokinetic modelling (2TCM, metabolite correction). Regional VOI analyses were carried out. Results: Compared with HC, in MDD, VT was significantly higher within the ncl. Caudatus, ncl. Accumbens, fronto-temporo-parieto-occipital and cingulate cortices, insula, amygdala, thalamus and midbrain/raphe (+15 to +24%, P<0.05). Compared with MDD-, in MDD+, VT was higher in the fronto-temporo and cingulate cortices, insula, hippocampus, putamen, thalamus (P<0.05). There was an inverted-U relationship between the severity of MDD (HAMD) and VT in the fronto-temporo-parietal and posterior cingulate cortices and thalamus (P<0.05). Conclusions: Using (-)-18FFluspidine PET, we demonstrate for the first time higher Sig-1R binding in meso-striato-cortico-limbic and paralimbic brain regions of unmedicated patients with acute MDD. Higher Sig-1R binding in MDD+, compared with MDD-, may express different subtypes of depression. Increased Sig-1Rs in acute MDD and the inverted-U relationship between severity and Sig-1R may reflect neuroadaptive upregulation of Sig-1R counteracting ER stress that is exhausted in the severest stages of MDD leading to apoptosis.
Purpose: This study aimed to evaluate correlations of Somatosensory Evoked Potentials (SSEP) with DTI parameters in white matter tracts in patients with Multiple Sclerosis (MS). Methods: 46 Patients ...with MS or clinical isolated syndromes were recruited. Bilateral SSEPs of the Nervus medianus were measured. The mean N20 latencies and Central Conducting Time (CCT) were calculated. MRI scans were made at 3T, DTI acquisition was done with single-shot EPI--technique with 80 diffusion directions. FSL (FMRIB, Oxford, Great Britain) and TBSS were used to process the images and calculate maps of Fractional Anisotropy (FA), Axial Diffusivity (AD) and Radial Diffusivity (RD). The mean N20 and BCT were separately correlated to FA, AD and RD, controlled for age and gender as variables of non-interest. Regions with high correlations (p < 0,05) were highlighted. Results: Significant negative correlations with FA and significant positive correlations with RD were measured for mean N20 and CCT in white matter tracts, in the optic tracts, the genu and splenium of the corpus callosum, the deep frontal white matter of both hemispheres. No correlation with AD was found. Conclusion: The widespread correlations of parameters derived from SSEP with microstructural alterations indicates SSEP as a surrogate marker for microstructural damage in multiple sclerosis, that goes beyond the primary sensory functional areas.
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