Prospective study validating a multidimensional treatment decision score predicting the 24-month outcome in untreated patients with clinically isolated syndrome and early relapsing-remitting multiple sclerosis, the ProVal-MS study.

INTRODUCTION: In Multiple Sclerosis (MS), patients´ characteristics and (bio)markers that reliably predict the individual disease prognosis at disease onset are lacking. Cohort studies allow a close follow-up of MS histories and a thorough phenotyping of patients. Therefore, a multicenter cohort study was initiated to implement a wide spectrum of data and (bio)markers in newly diagnosed patients. METHODS: ProVal-MS (Prospective study to validate a multidimensional decision score that predicts treatment outcome at 24 months in untreated patients with clinically isolated syndrome or early Relapsing-Remitting-MS) is a prospective cohort study in patients with clinically isolated syndrome (CIS) or Relapsing-Remitting (RR)-MS (McDonald 2017 criteria), diagnosed within the last two years, conducted at five academic centers in Southern Germany. The collection of clinical, laboratory, imaging, and paraclinical data as well as biosamples is harmonized across centers. The primary goal is to validate (discrimination and calibration) the previously published DIFUTURE MS-Treatment Decision score (MS-TDS). The score supports clinical decision-making regarding the options of early (within 6 months after study baseline) platform medication (Interferon beta, glatiramer acetate, dimethyl/diroximel fumarate, teriflunomide), or no immediate treatment (> 6 months after baseline) of patients with early RR-MS and CIS by predicting the probability of new or enlarging lesions in cerebral magnetic resonance images (MRIs) between 6 and 24 months. Further objectives are refining the MS-TDS score and providing data to identify new markers reflecting disease course and severity. The project also provides a technical evaluation of the ProVal-MS cohort within the IT-infrastructure of the DIFUTURE consortium (Data Integration for Future Medicine) and assesses the efficacy of the data sharing techniques developed. PERSPECTIVE: Clinical cohorts provide the infrastructure to discover and to validate relevant disease-specific findings. A successful validation of the MS-TDS will add a new clinical decision tool to the armamentarium of practicing MS neurologists from which newly diagnosed MS patients may take advantage. Trial registration ProVal-MS has been registered in the German Clinical Trials Register, `Deutsches Register Klinischer Studien` (DRKS)-ID: DRKS00014034, date of registration: 21 December 2018; https://drks.de/search/en/trial/DRKS00014034.

Inflammation biomarkers in acute ischemic stroke according to different etiologies.

BACKGROUND: High throughput technologies provide new opportunities to further investigate the pathophysiology of ischemic strokes. The present cross-sectional study aimed to evaluate potential associations between the etiologic subtypes of ischemic stroke and blood-based proteins. METHODS: We investigated the associations between ischemic stroke subtypes and a panel of circulating inflammation biomarkers in 364 patients included in the Stroke Cohort Augsburg (SCHANA). Stroke etiologies were categorized according to the TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. Serum concentrations of 52 biomarkers were measured using the Bio-Plex Pro™ Human Cytokine Screening Panel, ICAM-1 set and VCAM-1 set, plus the Pro™ Human TH17 cytokine sCD40L set and IL31 set (all Bio-Rad, USA). Multivariable linear regression models were used to examine associations. Point estimates were calculated as the mean difference in σ -standardized cytokine levels on the log2 -scale. RESULTS: Stromal-cell-derived-factor 1 alpha (SDF-1a) showed significantly higher serum levels in cardioembolic compared with large vessel atherosclerotic stroke (ß = 0.48; 95% CI 0.22; 0.75; Padj = 0.036). Significantly lower levels of interleukin-6 (IL-6) (ß = -0.53; 95% CI -0.84; -0.23; Padj = 0.036) and macrophage migration inhibitory factor (MIF) (ß = -0.52; 95% CI -0.84; -0.21; Padj = 0.043) were found in the small vessel versus large vessel stroke subtype. CONCLUSIONS: Immune dysregulations observed in different stroke subtypes might help uncover pathophysiological mechanisms of the disease. Further studies are needed to validate identified biomarkers in diverse study populations before they can potentially be used in clinical practice to further improve stroke management and patient outcomes.

[Diagnostics and treatment of hourglass-like nerve constrictions and torsions in neuralgic amyotrophy]. / Diagnostik und Therapie sanduhrförmiger Nervenstrikturen und -torsionen bei neuralgischer Amyotrophie.

Neuralgic amyotrophy is a disease of the peripheral nervous system characterized by severe neuropathic pain followed by peripheral paralysis. A distinction is made between a hereditary and an idiopathic form, which is assumed to have an autoimmunological origin. Conservative medicinal treatment mainly consists of nonsteroidal anti-inflammatory drugs (NSAID), opioids and glucocorticoids; however, despite treatment, symptoms in the form of pain or paralysis persist in over 50% of cases. Inflammation can lead to strictures and torsions of peripheral nerves, which can be visualized by imaging using nerve sonography or magnetic resonance (MR) neurography and confirmed intraoperatively during surgical exploration. Based on the currently available data, patients with strictures and torsions of peripheral nerves can benefit from neurosurgical treatment.

Treatment of hyperhidrosis with Botox (onabotulinumtoxinA): Development, insights, and impact.

Hyperhidrosis (chronic excessive sweating) may substantially affect an individual's emotional and social well-being. Therapies available before onabotulinumtoxinA were generally topical, with limited effectiveness, application-site skin reactions, and frequent, time-consuming treatments. Intradermal injection of onabotulinumtoxinA to treat sweat glands arose as a novel therapeutic approach. To develop this treatment, appropriate dosing needed to be established, and training on administration was required. Further, no previous scale existed to measure the effects of hyperhidrosis on patients' lives, leading Allergan to develop and validate the 4-point Hyperhidrosis Disease Severity Scale (HDSS), which measures the disease's impact on daily activities. The onabotulinumtoxinA clinical development program for hyperhidrosis included 2 double-blind, placebo-controlled pivotal trials, immunogenicity studies, long-term studies of safety and efficacy, and quality of life assessments. In Europe and North America, the primary efficacy measures were, respectively, axillary sweat production measured gravimetrically and HDSS improvement. Compared with placebo, onabotulinumtoxinA treatment significantly reduced axillary sweat production and axillary hyperhidrosis severity, as measured by a 2-point or greater reduction on the HDSS. The effects of onabotulinumtoxinA occurred rapidly, within 1 week after injection, and lasted ≥6 months. Treatment with onabotulinumtoxinA was associated with significant quality of life improvements based on Short Form-12 physical and mental component scores. The Hyperhidrosis Impact Questionnaire also indicated greater treatment satisfaction, reduced negative impact on aspects of daily life, and improved emotional well-being with onabotulinumtoxinA versus placebo. The clinical development program and subsequent clinical experience showed that onabotulinumtoxinA treatment for hyperhidrosis was well tolerated with no new safety signals, and led to greater disease awareness.

Giant cell arteritis with vertebral artery involvement-baseline characteristics and follow-up of a monocentric patient cohort.

Vertebral artery (VA) involvement in giant cell arteritis (GCA) has rarely been reported. We aimed to evaluate the prevalence, patients' characteristics, and immunotherapies used in patients with GCA and VA involvement at diagnosis and 1 year follow-up, retrospectively including patients being diagnosed between January 2011 and March 2021 in our department. Clinical features, laboratory data, VA imaging, immunotherapy, and 1 year follow-up data were analyzed. Baseline characteristics were compared to GCA patients without VA involvement. Among all 77 cases with GCA, 29 patients (37.7%) had VA involvement, as diagnosed by imaging and/or clinical signs and symptoms. Gender distribution and erythrocyte sedimentation rate (ESR) were significantly different in the groups with and without VA involvement, with more women being affected (38/48 patients, 79.2%) and a significantly higher median ESR in patients without VA involvement (62 vs. 46 mm/h; p = 0.012). MRI and/or CT showed vertebrobasilar stroke at GCA diagnosis in 11 cases. 67/77 patients (87.0%) received high-dose intravenous glucocorticosteroids (GCs) at diagnosis, followed by oral tapering. Six patients were treated with methotrexate (MTX), one with rituximab, and five with tocilizumab (TCZ). 2/5 TCZ patients achieved clinical remission after 1 year, vertebrobasilar stroke within the first year occurred in 2/5 patients. Diagnosis of VA involvement might be underrecognized in GCA patients. VA imaging should be performed in elderly patients with vertebrobasilar stroke presenting with GCA symptoms, not to miss GCA as the etiology of stroke. Efficacy of immunotherapies in GCA with VA affection and long-term outcomes need to be investigated further.

Novel inflammatory biomarkers associated with stroke severity: results from a cross-sectional stroke cohort study.

BACKGROUND: Stroke is a leading cause of mortality and disability worldwide and its occurrence is expected to increase in the future. Blood biomarkers have proven their usefulness in identification and monitoring of the disease. Stroke severity is a major factor for estimation of prognosis and risk of recurrent events, but knowledge on respective blood biomarkers is still scarce. Stroke pathophysiology comprises a multitude of ischemia-induced inflammatory and immune mediated responses. Therefore, the assessment of an immune-related panel in correlation with stroke severity seems promising. METHODS: In the present cross-sectional evaluation, a set of 92 blood biomarkers of a standardized immune panel were gathered (median 4.6 days after admission) and related to stroke severity measures, assessed at hospital admission of acute stroke patients. Multivariable logistic regression models were used to determine associations between biomarkers and modified Rankin Scale (mRS), linear regression models were used for associations with National Institute of Health Stroke Scale. RESULTS: 415 patients (mean age 69 years; 41% female) were included for biomarker analysis. C-type lectin domain family 4 member G (CLEC4G; OR = 2.89, 95% CI [1.49; 5.59], padj = 0.026, Cytoskeleton-associated protein 4 (CKAP4; OR = 2.38, 95% CI [1.43; 3.98], padj = 0.019), and Interleukin-6 (IL-6) (IL6; OR = 1.97, 95% CI [1.49; 2.62], padj < 0.001) were positively associated with stroke severity measured by mRS, while Lymphocyte antigen 75 (LY75; OR = 0.37, 95% CI [0.19; 0.73], padj = 0.049) and Integrin alpha-11 (ITGA11 OR = 0.24, 95% CI [0.14, 0.40] padj < 0.001) were inversely associated. When investigating the relationships with the NIHSS, IL-6 (ß = 0.23, 95% CI [0.12, 0.33] padj = 0.001) and ITGA11 (ß = - 0.60, 95% CI [- 0.83, - 0.37] padj < 0.001) were significantly associated. CONCLUSIONS: Higher relative concentrations of plasma CLEC4G, CKAP4, and IL-6 were associated with higher stroke severity, whereas LY75 and ITGA11 showed an inverse association. Future research might show a possible use as therapeutic targets and application in individual risk assessments.

Neutralizing Antibody Formation with OnabotulinumtoxinA (BOTOX®) Treatment from Global Registration Studies across Multiple Indications: A Meta-Analysis.

Though the formation of neutralizing antibodies (NAbs) during treatment with botulinum neurotoxin is rare, their presence may nonetheless affect the biological activity of botulinum toxin and negatively impact clinical response. The goal of this updated meta-analysis was to evaluate and characterize the rate of NAb formation using an expanded dataset composed of 33 prospective placebo-controlled and open-label clinical trials with nearly 30,000 longitudinal subject records prior to and following onabotulinumtoxinA treatment in 10 therapeutic and aesthetic indications. Total onabotulinumtoxinA doses per treatment ranged from 10 U to 600 U administered in ≤15 treatment cycles. The NAb formation at baseline and post-treatment was tested and examined for impact on clinical safety and efficacy. Overall, 27 of the 5876 evaluable subjects (0.5%) developed NAbs after onabotulinumtoxinA treatment. At study exit, 16 of the 5876 subjects (0.3%) remained NAb positive. Due to the low incidence of NAb formation, no clear relationship was discernable between positive NAb results and gender, indication, dose level, dosing interval, treatment cycles, or the site of injection. Only five subjects who developed NAbs post-treatment were considered secondary nonresponders. Subjects who developed NAbs revealed no other evidence of immunological reactions or clinical disorders. This comprehensive meta-analysis confirms the low NAb formation rate following onabotulinumtoxinA treatment across multiple indications, and its limited clinical impact on treatment safety and efficacy.

Association of blood lipids with onset and prognosis of amyotrophic lateral sclerosis: results from the ALS Swabia registry.

BACKGROUND: To date, the role of blood lipid levels and their association with the onset and prognosis of ALS is controversial. We explored these associations in a large, population-based case-control study. METHODS: Between October 2010 and June 2014, 336 ALS patients (mean age 65.7 ± 10.7; 57.7% male) and 487 sex- and age-matched controls from the same geographic region were recruited within the ALS registry in Southwest Germany. Triglycerides and cholesterol (high-density lipoprotein (HDL), low-density lipoprotein (LDL), total) were measured. The ALS cohort was followed up for vital status. Conditional logistic regression models were applied to calculate odds ratio (OR) for risk of ALS associated with serum lipid concentrations. In ALS patients only, survival models were used to appraise the prognostic value. RESULTS: High concentration of total cholesterol (OR 1.60, 95% confidence interval (CI) 1.03-2.49, top vs. bottom quartile), but not HDL, LDL, LDL-HDL ratio, or triglycerides, was positively associated with the risk of ALS. During the median follow-up time of 88.9 months, 291 deaths occurred among 336 ALS patients. In the adjusted survival analysis, higher HDL (HR 1.72, 95% CI 1.19-2.50) and LDL cholesterol levels (HR 1.58, 95% CI 1.11-2.26) were associated with higher mortality in ALS patients. In contrast, higher triglyceride levels were associated with lower mortality (HR 0.68, 95% CI 0.48-0.96). CONCLUSION: The results highlight the importance to distinguish cholesterol from triglycerides when considering the prognostic role of lipid metabolism in ALS. It further strengthens the rationale for a triglyceride-rich diet, while the negative impact of cholesterol must be further explored.

Old name, new face: A systematic analysis of flexor digitorum superficialis muscle with "chiasma antebrachii".

The gross anatomy of the forearm flexors, particularly that of the flexor digitorum superficialis (FDS) muscle, has been described and graphically illustrated in several anatomical books and atlases starting in the middle of the century before last. However, in anatomical dissection studies as well as in clinical-anatomical courses training muscle-specific targeted injections due to movement disorders such as dystonia or spasticity, it has become apparent that there is a need for a closer investigation of the complex construction of the FDS muscle. To this end, we studied the structure of the muscle bellies and tendons of FDS on 46 human body donates that have been used either in our dissection or clinical-anatomical training courses. With this, we demonstrate here the topographical configuration of the individual muscle belly for each of digits 2 through 5 and the exact paths of their tendons until their passing through the carpal tunnel. Furthermore, we demonstrate the presence of a chiasm of the FDS tendons for the digits 2 and 3, approximately 3-4 cm proximal of the carpal tunnel. Thus, we introduce herewith the terminology "chiasma antebrachii". These findings were confirmed in situ by imaging of fixed human body donates via MRI and corroborated by MRI and ultrasound imaging in two volunteers. Taken together, the present findings enable an updated understanding of the complex organization of the heads, bellies, and tendons of FDS that is relevant not only for anatomical teaching but also clinical interventions.

Hyperhidrosis: A Central Nervous Dysfunction of Sweat Secretion.

Hyperhidrosis (HH) is a central nervous dysfunction characterized by abnormally increased sweating due to a central dysregulation of sweat secretion. HH significantly affects the quality of life of patients in their private, social and professional environments. Physiologically, sweating is a mechanism that regulates body temperature, but it may also be triggered by emotional or gustatory stimuli. There are two main types of sweat glands: eccrine and apocrine glands. The central nervous system controls sweat secretion through the release of neurotransmitters into the autonomous nervous system (ANS) that activate the sweat glands. The hypothalamus has two separate neuronal pathways, one for thermoregulation and one for emotions. HH may thus be due to either a neuronal dysfunction of ANS regulation leading to a hyperactivity of the sympathetic nervous system, or to abnormal central processing of emotions. Crucially, there is no dysfunction of the sweat glands themselves. Various pathogenic mechanisms have been proposed to be involved in pathological sweat secretion in HH, ranging from structural changes within the ANS to increased expression of aquaporin 5 and upregulation of activin A receptor type 1 in eccrine sweat glands. Although a genetic predisposition has been demonstrated, it remains unclear exactly which genes are involved. To identify new, potential therapeutic targets and to improve treatment options, a good understanding of the signaling pathways involved, the underlying mechanisms, and the genetic components is essential. In this review we discuss the various aspects of sweat physiology and function that are necessary to explain pathological sweating. Our aim is to raise awareness of the complexity of HH to promote a better understanding of the disorder.

Association of post-stroke-depression and health-related quality of life three months after the stroke event. Results from the Stroke Cohort Augsburg (SCHANA) study.

Approximately one-third of patients with stroke show depressive symptoms. The so-called post-stroke depression (PSD) has a negative influence on mortality as well as physical and mental conditions. The aim of this study was to analyse the association between PSD and health-related quality of life (HRQOL) in patients with stroke. The analysis was based on data of 326 patients from the Stroke Cohort Augsburg (SCHANA Study) collected after the stroke event by interview and three months later using a postal survey. Depressive symptoms were measured with the Patient-Health Questionnaire (PHQ-9), subjective health status with the EuroQol 5D visual analogue scale (EQ-5D VAS), and HRQOL with the Stroke Impact Scale (SIS). Patients with depressive symptoms were compared to those without depressive symptoms in terms of sociodemographic characteristics and scores of the SIS and the EQ-5D VAS. Multiple linear regression models were calculated to investigate the association between PSD and subjective health status and HRQOL. Three months after the stroke, 17.8% of patients had depressive symptoms. Patients with PSD showed significantly worse SIS and EQ-5D VAS scores. In addition, an independent negative linear association between PSD and subjective health status and between PSD and all domains of SIS could be found. The study confirmed that PSD is common in patients with mild stroke and negatively related to all stroke-specific HRQOL domains. The results underline the importance of early screening for PSD in stroke patients since it may hinder a successful rehabilitation.

Influence of educational status and migration background on the long-term health-related quality of life after stroke.

BACKGROUND AND PURPOSE: Acute stroke treatment and secondary prevention have tremendously improved functional outcomes after stroke. However, this does not always imply a likewise improvement in health-related quality of life (HRQoL). Knowledge on factors influencing HRQoL after stroke is still scarce, especially regarding social aspects like the level of education and the presence of migration background. METHODS: In the present stroke cohort study, participants were interviewed during their hospital stay and completed a postal questionnaire at 3 and 12 months post stroke. Functional outcomes were assessed by the modified Rankin Scale and HRQoL by evaluating the detailed Stroke Impact Scale (SIS). Logistic regression models were used to determine associations between education, migration background and quality of life end-points. RESULTS: A total of 945 (mean age 69 years; 56% male) stroke patients were enrolled. After adjusting for confounders, a lower educational level was associated with worse functional outcomes in the SIS domain 'strength' (odds ratio 2.67, 95% confidence interval 1.6-4.4, p < 0.001). Migration background was associated with worse outcomes in the SIS domain 'emotion' (p = 0.007, odds ratio 1.71, 95% confidence interval 1.2-2.5). Additionally, for female patients worse HRQoL outcomes were found in multiple other SIS domains. CONCLUSIONS: Migration background and a lower educational level were significantly associated with lower long-term HRQoL after stroke. These aspects should be considered in targeted rehabilitation programmes and follow-up support of stroke patients.

Associations between pre-stroke physical activity and physical quality of life three months after stroke in patients with mild disability.

BACKGROUND: Much is known about the association between physical activity and the occurrence of stroke. However, the evidence about the correlation between pre-stroke physical activity and post-stroke quality of life remains inconsistent. Thus, there is a high public health relevance to the topic. AIM: The aim of this study was to investigate the association between pre-stroke physical activity and physical quality of life after three months. METHODS: Data arises from 858 patients with stroke included a prospective single-centre observational cohort study in Augsburg, Germany, between September 2018 and November 2019. The participants were recruited at the Department of Neurology and Clinical Neurophysiology, University Hospital of Augsburg after their stroke event. The level of physical activity was determined following the short form of the International Physical Activity Questionnaire at baseline. Physical quality of life was assessed three months after hospital discharge using the German version of the Stroke Impact Scale (SIS). A multiple linear regression model and a quantile regression were carried out. RESULTS: A total of 497 patients were included in the analysis (mean age 69.6, 58.8% male), 26.2% had a high, 18.9% a moderate and 54.9% a low level of pre-stroke physical activity. Patients with high pre-stroke physical activity had a significantly better physical quality of life three months after stroke in the SIS physical domain (beta = 4.1) and in the SIS subdomains hand function (beta = 5.6), mobility (beta = 4.1) and activities of daily living (beta = 3.7). In the physical domain and the subdomain mobility, the effect was especially strong for persons with low physical quality of life after three months. CONCLUSION: Pre-stroke physical activity seems to have an important and positive association with physical quality of life after three months in patients with mild disability. Further studies are needed to confirm these results.

Factors Associated With Early and Late Post-stroke Fatigue in Patients With Mild Impairment. Results From the Stroke Cohort Study Augsburg.

Background: Post-stroke fatigue is a common symptom after stroke. However, studies on the factors associated with early and late fatigue are scarce. The objective of this study was to identify variables associated with early and late fatigue. Methods: In the German Stroke Cohort Augsburg (SCHANA) study, participants were interviewed during their hospital stay and completed a postal questionnaire 3 and 12 months post-stroke. Fatigue was assessed using the Fatigue Assessement Scale (FAS). In addition, depression was measured by the Patient Health Questionnaire (PHQ-9), general health status by the EQ-5D visual analog scale, and physical activity by the International Physical Activity Questionnaire (IPAQ). Multivariable regression models were used to determine the associations between FAS scores at 3 and 12 months post-stroke and demographic, psychosocial and health-related covariables. Results: Among 505 participants, the frequency of fatigue was 31.1% 3 months and 29.1% 12 months post-stroke. Prior stroke (ß = 2.37, p = 0.0076), prior diagnosis of depression (ß = 5.04, p = 0.0001), higher NIHSS (ß = 0.25, p = 0.0360) and higher PHQ-9 scores (ß = 0.55, p < 0.0001) were significantly associated with higher fatigue levels 3 months post-stroke. Additionally, younger age (ß = -0.07, p = 0.0219), a worse rating of general health at baseline (ß = -0.04, p = 0.0287) and low pre-stroke physical activity (ß = -0.0004, p = 0.0089) were significantly associated with higher fatigue levels 12 months after stroke. Conclusions: Fatigue is a common and persisting symptom even in patients with mild impairment. Prior depressive disorder and early depressive symptoms were the most relevant predictors of both early and late fatigue.

Prolonged-release fampridine for the treatment of myoclonus after cervical myelitis: a case report.

Prolonged-release fampridine (PR-FAM), a potassium channel blocker, is approved for improving walking ability in patients with multiple sclerosis (MS). Beyond this, positive effects on other MS symptoms like fatigue, cognition, and tremor have been described. To our knowledge, a positive effect of PR-FAM on spinal myoclonus has not been described so far. Here, we report a 32-year-old female with myoclonus after cervical myelitis affecting both hands which markedly improved after administration of PR-FAM. Treatments used before such as carbamazepine or levetiracetam had to be withdrawn because of intolerable side effects or lack of efficacy. The positive effect of PR-FAM could be confirmed by transient suspension. PR-FAM may be considered as a treatment option in refractory spinal myoclonus after myelitis in selected cases.

Incidence, clinical spectrum, and immunotherapy of non-ischemic cerebral enhancing lesions after endovascular therapy.

BACKGROUND: Symptomatic and asymptomatic delayed non-ischemic cerebral enhancing (NICE) lesions in magnetic resonance imaging (MRI) have been reported as a rare complication after endovascular therapy (EVT) in recent years with incidence rates between 0.05% and 0.9% in most studies. Information on long-term clinical course and immunotherapies is scarce or has not been reported in detail in the literature. Objective: Aims of our study were to assess the incidence of NICE lesions in patients after cerebral EVT over a period of more than 12 years, describe clinical and EVT characteristics, and immunotherapies applied. METHODS: A retrospective chart review of all patients treated by endovascular therapy for symptomatic or asymptomatic aneurysms at the University Hospital of Augsburg from May 1, 2008 to December 31, 2020 was performed. Patients were identified retrospectively and followed-up prospectively where appropriate. In addition, one case treated at another institution was included. RESULTS: Five out of 746 patients, 0.67%, developed NICE lesions after EVT, all with non-ruptured aneurysms and all symptomatic upon detection of NICE lesions by MRI. In total, the disease course of 6 female patients is reported. Symptoms occurred after a mean time of 15 days (±13.42, SD) after EVT with headache (6/6 patients), focal neurological signs (6/6 patients), epileptic seizures (2/6 patients) and cognitive deficits (3/6 patients). All 6 patients received glucocorticosteroids (GCS), 1/6 azathioprine (AZA), 4/6 mycophenolate mofetil (MMF), 1/6 methotrexate (MTX), 1/6 rituximab (RTX), 2/6 cyclophosphamide (CYC) and 3/6 tocilizumab (TCZ). A treatment response could be observed for GCS, TCZ and MMF (in two of four cases), RTX and AZA did not result in disease stabilization. CONCLUSIONS: Delayed NICE lesions are a rare complication after EVT, requiring immunotherapies in all patients reported here. Physicians should be aware of this disorder in case of new symptoms or contrast enhancing lesions after EVT.

Nerve Echogenicity: Changes in High-Resolution Nerve Ultrasound in Carpal Tunnel Syndrome after Surgery.

The aim of our prospective study was to detect changes in nerve echogenicity of the median nerve before and after successful surgery in patients with carpal tunnel syndrome (CTS) using high-resolution ultrasound. Fifteen patients with a definite diagnosis of CTS who underwent surgery were scanned by one examiner with high-resolution ultrasound, and images were analyzed by two blinded raters using ImageJ to assess the echogenicity of the median nerve (fraction of black) with a semiautomated thresholding technique before and 3 mo after surgery compared with 15 controls. In CTS patients, nerve echogenicity before surgery was significantly lower compared with that of controls (fraction of black: mean 63.9 vs. 44.6, p < 0.0001). Three months after surgery nerve echogenicity significantly increased (fraction of black was lower, mean 55.5; p < 0.0001) as a possible sign of reduction of intraneural edema, but did not reach the values of healthy controls. Semi-automated evaluation of the echogenicity of the median nerve may be used as a marker of successful carpal tunnel release. Further studies are warranted to detect how nerve echogenicity changes after unsuccessful carpal tunnel release.

Association between fatigue and cytokine profiles in patients with ischemic stroke.

Background: Chronic fatigue is a common symptom after a stroke. Studies suggested that chronic fatigue is caused by inflammatory or immunological processes but data are limited and contradictory. Thus, the present study aimed to identify specific biomarkers associated with fatigue in post-stroke patients and replicated the findings in a population-based study. Methods: We investigated associations between 39 circulating biomarkers of inflammation and fatigue in 327 patients after an ischemic stroke included in the Stroke Cohort Augsburg (SCHANA) study and the "Metabolism, Nutrition and Immune System in Augsburg" (MEIA) study (n = 140). The Fatigue Assessment Scale (FAS) was used to assess the severity of fatigue. The serum concentrations of the biomarkers were measured using the Bio-Plex Pro™ Human Cytokine Screening Panel (Bio-Rad, USA). Multiple linear regression models adjusted for possible confounders were used to examine associations. Results: In patients with stroke, SCGFb was inversely associated [-1.67, 95% confidence interval (CI) (-3.05; -0.29) p = 0.018], and in healthy subjects, G-CSF was positively associated [1.56, 95% CI (0.26; 2.87), p = 0.020] with an increasing FAS-score, while SCF was positively related in both samples [1.84, 95% CI (0.27; 3.42), p = 0.022 and 1.40, 95% CI (0.29; 2.52), p = 0.015]. However, after correction for multiple testing, all of these associations lost statistical significance. Conclusion: The present findings suggested an association between the growth factor SCF and fatigue. Future research on cytokines as possible markers of fatigue should focus on a longitudinal design including a sufficiently large number of study participants to enable testing associations between certain cytokines and sub-groups of chronic fatigue.