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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and purpose: The effects of the coronavirus disease 2019 (COVID‐19) pandemic on telemedical care have not been described on a national level. Thus, we investigated the medical stroke treatment situation before, during, and after the first lockdown in Germany. Methods: In this nationwide, multicenter study, data from 14 telemedical networks including 31 network centers and 155 spoke hospitals covering large parts of Germany were analyzed regarding patients' characteristics, stroke type/severity, and acute stroke treatment. A survey focusing on potential shortcomings of in‐hospital and (telemedical) stroke care during the pandemic was conducted. Results: Between January 2018 and June 2020, 67,033 telemedical consultations and 38,895 telemedical stroke consultations were conducted. A significant decline of telemedical (p < 0.001) and telemedical stroke consultations (p < 0.001) during the lockdown in March/April 2020 and a reciprocal increase after relaxation of COVID‐19 measures in May/June 2020 were observed. Compared to 2018–2019, neither stroke patients' age (p = 0.38), gender (p = 0.44), nor severity of ischemic stroke (p = 0.32) differed in March/April 2020. Whereas the proportion of ischemic stroke patients for whom endovascular treatment (14.3% vs. 14.6%; p = 0.85) was recommended remained stable, there was a nonsignificant trend toward a lower proportion of recommendation of intravenous thrombolysis during the lockdown (19.0% vs. 22.1%; p = 0.052). Despite the majority of participating network centers treating patients with COVID‐19, there were no relevant shortcomings reported regarding in‐hospital stroke treatment or telemedical stroke care. Conclusions: Telemedical stroke care in Germany was able to provide full service despite the COVID‐19 pandemic, but telemedical consultations declined abruptly during the lockdown period and normalized after relaxation of COVID‐19 measures in Germany. [ABSTRACT FROM AUTHOR]

Background: Clinicians have questioned whether any disorder involving seizures and neural antibodies should be called "(auto)immune epilepsy." The concept of "acute symptomatic seizures" may be more applicable in cases with antibodies against neural cell surface antigens. We aimed at determining the probability of achieving seizure-freedom, the use of anti-seizure medication (ASM), and immunotherapy in patients with either constellation. As a potential pathophysiological correlate, we analyzed antibody titer courses. Methods: Retrospective cohort study of 39 patients with seizures and neural antibodies, follow-up ≥ 3 years. Results: Patients had surface antibodies against the N-methyl-d-aspartate receptor (NMDAR, n = 6), leucine-rich glioma inactivated protein 1 (LGI1, n = 11), contactin-associated protein-2 (CASPR2, n = 8), or antibodies against the intracellular antigens glutamic acid decarboxylase 65 kDa (GAD65, n = 13) or Ma2 (n = 1). Patients with surface antibodies reached first seizure-freedom (88% vs. 7%, P < 0.001) and terminal seizure-freedom (80% vs. 7%, P < 0.001) more frequently. The time to first and terminal seizure-freedom and the time to freedom from ASM were shorter in the surface antibody group (Kaplan–Meier curves: P < 0.0001 for first seizure-freedom; P < 0.0001 for terminal seizure-freedom; P = 0.0042 for terminal ASM-freedom). Maximum ASM defined daily doses were higher in the groups with intracellular antibodies. Seizure-freedom was achieved after additional immunotherapy, not always accompanied by increased ASM doses. Titers of surface antibodies but not intracellular antibodies decreased over time. Conclusion: Seizures with surface antibodies should mostly be considered acute symptomatic and transient and not indicative of epilepsy. This has consequences for ASM prescription and social restrictions. Antibody titers correlate with clinical courses. [ABSTRACT FROM AUTHOR]

Background: We analyzed risk factors for venous thromboembolism (VTE) within 6 months after surgery for closed ankle fractures.Methods: This was a case-control study based on data from chart review in a cohort of patients having open reduction and internal fixation (ORIF) for closed ankle fractures in two large general hospitals 2009-2011. Cases with symptomatic VTE (pulmonary embolism or deep venous thrombosis) were identified in the cohort, and additional cases of VTE were identified by computerized search of discharge diagnoses in the same hospitals in 2004-2008 and 2012-2016. In total, we identified 60 cases with VTE and compared with 240 randomly selected controls among 998 patients without VTE in the cohort. Risk factors were assessed using logistic regression analysis.Results: Among cases, 27 (45%) had pulmonary embolism, 33 (55%) deep venous thrombosis. Those with VTE were older, had higher BMI, had more often a family history of VTE, and more often had antibiotic prophylaxis during surgery than controls. In multivariable logistic regression analysis age/10 (OR 25.75, 95%CI 3.52-188.44, p=0.001), (age/10)2 (OR 0.77, 95%CI 0.65-0.93, p=0.005), BMI (1.15 per kg/m2, 95%CI 1.07-1.24, p<0.001) and Charlson comorbidity index ≥2 vs.0 (OR 0.27, 95%CI 0.08-0.92, p=0.036) and 1 vs. 0 (OR 0.27, 95%CI 0.09-0.86, p=0.026) were associated with VTE within 6 months of surgery.Conclusions: The odds of symptomatic VTE within 6 months of ORIF increased with increasing age and BMI, but were lower with increasing comorbidity. [ABSTRACT FROM AUTHOR]

Aim: With the resolution from April 28, 2014, the Bavarian state government in Germany decided to found a new medical school at Augsburg University, thereby requiring the development of a competency-based medical curriculum. Methods: Two interdisciplinary groups developed a spiral curriculum (following Harden) employing the model of Thumser-Dauth & Ochsner. The curriculum focuses on specifically defined competencies: medical expertise, independent scientific reasoning, argumentation and scholarship, as well as communication skills. Results: The spiral curriculum was developed as a hybrid curriculum. Its modular structure incorporates the mandatory subjects required by the German regulations for medical licensure (Approbationsordnung) into organ- and system-centered blocks which are integrated both horizontally and vertically. Basic preclinical sciences are covered in the blocks "Movement" "Balance" and "Contact." The clinical sciences are organized according to six pillars (conservative medicine, surgical medicine, men's-women's-children's medicine, the senses, the nervous system and the mind, and general medicine) which students revisit three times each over the course of the program. A longitudinal clinical course incorporates interdisciplinary education. A particular focus is on scientific education encompassinga longitudinal course in the sciences (including interdisciplinary classes with other university departments), block practicums, and two scientific projects. Conclusion: It is not only the degree of integration und intensity of the Augsburg University undergraduate medical degree program, but also its targeted advancement of academic, social and communication skills that have not yet been realized to such an extent elsewhere in Germany. On July 8, 2016, the German Council of Science and Humanities unanimously gave this concept a positive evaluation. Future research will examine and evaluate the Augsburg medical curriculum and the impact of the new medical school on the hospital and university in Augsburg. [ABSTRACT FROM AUTHOR]

Abstract: Botulinum neurotoxin (BoNT) can be injected to achieve therapeutic benefit across a large range of clinical conditions. To assess the efficacy and safety of BoNT injections for the treatment of certain urologic conditions, including detrusor sphincter dyssynergia (DSD), lower urinary tract symptoms due to benign prostatic hyperplasia (BPH), and detrusor overactivity (both neurogenic [NDO] and idiopathic [IDO]), an expert panel reviewed evidence from the published literature. Data sources included English-language studies identified via MEDLINE, EMBASE, CINAHL, Current Contents, and the Cochrane Central Register of Controlled Trials. Evidence tables generated in the 2008 Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (AAN) review of the use of BoNT for autonomic disorders were also reviewed and updated. The panel evaluated evidence at several levels, supporting BoNT as a class, for the serotypes BoNT-A and BoNT-B, as well as for the four individual commercially available formulations: abobotulinumtoxinA (A/Abo), onabotulinumtoxinA (A/Ona), incobotulinumtoxinA (A/Inco), and rimabotulinumtoxinB (B/Rima). The panel ultimately made recommendations on the use of BoNT for the management of these urologic conditions based upon the strength of clinical evidence and following the AAN classification scale. For the treatment of DSD, the evidence supported a Level B recommendation for the use of A/Ona; A/Abo, A/Inco, and B/Rima received a Level U recommendation. For the treatment of NDO, there was sufficient clinical evidence to support a Level A recommendation for BoNT-A as well as for both A/Ona and A/Abo; no published data were identified for either A/Inco or B/Rima (Level U). For the treatment of IDO, the evidence supported a Level A recommendation for A/Ona; A/Inco, A/Abo, and B/Rima received a Level U recommendation. For the management of BPH, the evidence supported a Level B recommendation for BoNT and A/Ona; no published studies were identified for A/Abo, A/Inco, or B/Rima, warranting a Level U recommendation for these three formulations. Further studies are needed to evaluate the efficacy and safety of BoNT for the management of urologic conditions. [Copyright &y& Elsevier]

Continuous delivery of antiparkinsonian medication during a perioperative period is desirable to avoid ‘off’-symptom complications in surgical patients with concomitant Parkinson’s disease (PD). Fourteen PD patients undergoing surgery under general anesthesia were switched from oral dopaminergic medication to transdermally delivered 24-h rotigotine (median dose 12 mg/24 h) for the perioperative period. Rotigotine treatment was considered feasible by patients, their anesthesiologists and neurologists with good control of PD symptoms and easy switching and re-switching of PD medication. [ABSTRACT FROM AUTHOR]

Abstract: Three experiments were performed in an attempt to achieve a better understanding of the effect of dopamine on handwriting. In the first experiment, kinematic aspects of handwriting movements were compared between healthy participants and patients with Parkinson’s disease (PD) on their usual dopaminergic treatment and following withdrawal of dopaminergic medication. In the second experiment, the writing performance of healthy participants with a hyperechogenicity of the substantia nigra as detected by transcranial sonography (TCS) was compared with the performance of healthy participants with low echogenicity of the substantia nigra. The third experiment examined the effect of central dopamine reduction on kinematic aspects of handwriting movements in healthy adults using acute phenylalanine and tyrosine depletion (APTD). A digitising tablet was used for the assessment of handwriting movements. Participants were asked to perform a simple writing task. Movement time, distance, velocity, acceleration and measures of fluency of handwriting movements were measured. The kinematic analysis of handwriting movements revealed that alterations of central dopaminergic neurotransmission adversely affect movement execution during handwriting. In comparison to the automatic processing of handwriting movements displayed by control participants, participants with an altered dopaminergic neurotransmission shifted from an automatic to a controlled processing of movement execution. Central dopamine appears to be of particular importance with regard to the automatic execution of well-learned movements. [Copyright &y& Elsevier]

Background: Mirror movements (MM) are commonly caused by a defect of interhemispheric pathways also affected in multiple sclerosis (MS), particularly the corpus callosum. We investigated the prevalence of MM in MS in relation to functional and morphological callosal fiber integrity by transcranial magnetic stimulation (TMS), magnetic resonance imaging (MRI), as well as fatigue., Methods: In 21 patients with relapsing-remitting MS and 19 healthy controls, MM were assessed and graded (Woods and Teuber scale: MM 1-4) using a bedside test. Fatigue was evaluated using the Fatigue Scale for Motor and Cognitive Functions (FSMC) questionnaire. TMS measured ipsilateral silent period latency and duration. MRI assessed callosal atrophy by measuring the normalized corpus callosum area (nCCA), corpus callosum index (CCI), and lesion volume., Results: MS patients had significantly more often and pronounced MM compared to healthy controls (p = 0.0002) and nCCA was significantly lower (p = 0.045) in MRI studies. Patients with higher MM scores (MM > 1 vs. MM 0/1) showed significantly more fatigue (higher FSMC sum score, p = 0.04, motor score, p = 0.01). In TMS and MRI studies, no significant differences were found between patients with MM 0/1 and those with MM > 1 (ipsilateral silent period measurements, CCA, CCI and lesion volume)., Conclusions: MM are common in MS and can easily be detected through bedside testing. As MM are associated with fatigue, they might indicate fatigue in MS. It is possible that other cerebral structures, in addition to the corpus callosum, may contribute to the origin of MM in MS., (© 2024. The Author(s).)

Background and Aims: In recent decades, nighttime temperatures have increased faster than daytime temperatures. The increasing prevalence of nocturnal heat exposure may pose a significant risk to cardiovascular health. This study investigated the association between nighttime heat exposure and stroke risk in the region of Augsburg, Germany, and examined its temporal variations over 15 years., Methods: Hourly meteorological parameters, including mean temperature, relative humidity, and barometric pressure, were acquired from a local meteorological station. A data set was obtained consisting of 11 037 clinical stroke cases diagnosed during warmer months (May to October) between the years 2006 and 2020. The average age of cases was 71.3 years. Among these cases, 642 were identified as haemorrhagic strokes, 7430 were classified as ischaemic strokes, and 2947 were transient ischaemic attacks. A time-stratified case-crossover analysis with a distributed lag non-linear model was used to estimate the stroke risk associated with extreme nighttime heat, as measured by the hot night excess (HNE) index after controlling for the potential confounding effects of daily maximum temperature and other climatic variables. Subgroup analyses by age group, sex, stroke subtype, and stroke severity were performed to identify variations in susceptibility to nighttime heat., Results: Results suggested a significant increase in stroke risk on days with extreme nighttime heat (97.5% percentile of HNE) (odds ratio 1.07, 95% confidence interval 1.01-1.15) during the full study period. When comparing the results for 2013-20 with the results for 2006-12, there was a significant increase (P < .05) in HNE-related risk for all strokes and specifically for ischaemic strokes during the more recent period. Furthermore, older individuals, females, and patients with mild stroke symptoms exhibited a significantly increased vulnerability to nighttime heat., Conclusions: This study found nocturnal heat exposure to be related to elevated stroke risk after controlling for maximum daytime temperature, with increasing susceptibility between 2006 and 2020. These results underscore the importance of considering nocturnal heat as a critical trigger of stroke events in a warming climate., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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., (© 2024. The Author(s).)

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], p adj  = 0.026, Cytoskeleton-associated protein 4 (CKAP4; OR = 2.38, 95% CI [1.43; 3.98], p adj  = 0.019), and Interleukin-6 (IL-6) (IL6; OR = 1.97, 95% CI [1.49; 2.62], p adj  < 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], p adj  = 0.049) and Integrin alpha-11 (ITGA11 OR = 0.24, 95% CI [0.14, 0.40] p adj  < 0.001) were inversely associated. When investigating the relationships with the NIHSS, IL-6 (β = 0.23, 95% CI [0.12, 0.33] p adj  = 0.001) and ITGA11 (β =  - 0.60, 95% CI [- 0.83, - 0.37] p adj  < 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., (© 2023. The Author(s).)

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., Competing Interests: This manuscript was funded by AbbVie. AbbVie was involved in the manuscript concept and participated in writing, reviewing, and approval of the final version. No honoraria or payments were made for authorship. N Lowe has received past consultant fees, honoraria, and research grants from Allergan (prior to its acquisition by AbbVie). He owns stock in AbbVie. M Naumann has no funding and conflicts of interest to disclose. N Eadie was an employee of Allergan Aesthetics, an AbbVie Company, at the time of this research. Writing and editorial assistance was provided to the authors by Michelle McDermott, PharmD of Peloton Advantage, LLC, an OPEN Health company, and was funded by AbbVie., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Prünte, Naumann, Christ, Naumann and Bayas.)

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.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kirchberger, Meisinger, Freuer, Leone, Ertl, Zickler, Naumann and Linseisen.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kirchberger, Wallner, Linseisen, Zickler, Ertl, Naumann and Meisinger.)

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., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Antonios Bayas: received personal compensation from Merck Serono, Biogen, Novartis, TEVA, Roche, Sanofi/Genzyme and Celgene; he received grants for congress travel and participation from Biogen, TEVA, Novartis, Sanofi/Genzyme, Merck Serono and Celgene. None related to this manuscript. Ansgar Berlis: received within last three years proctor fees from Microvention and Stryker, lecture fees from Phenox, Penumbra, Stryker and CEC fee from Phenox. None related to this manuscript. Michael Ertl: received personal compensation from Bayer Healthcare, Daiichi-Sankyo and Boehringer Ingelheim; he received grants for congress travel and participation from Daiichi-Sankyo. None related to this manuscript. Christoph Maurer received an educational grant from Microvention and Stryker, none related to this manuscript. Monika Christ: no conflict of interests. Markus Naumann: no conflict of interests. Felix Joachimski: no conflict of interests. Mona Müller no conflict of interests. Julia Welzel: no conflict of interests. Lisa Ann Gerdes: no conflict of interests. Klaus Seelos: no conflict of interests., (© The Author(s), 2022.)

Introduction: As prospective data on long-term patient-reported outcome measures (PROMs) to assess Health related Quality of Life (HRQoL) after stroke are still scarce, this study examined the long-term course of PROMs and investigated influential factors such as recanalization therapies. Materials and Methods: A total of 945 (mean age 69 years; 56% male) stroke patients were enrolled with a personal interview and chart review performed at index event. One hundred forty (15%) patients received thrombolysis (IVT) and 53 (5%) patients received endovascular therapy (ET) or both treatments as bridging therapy (BT). After 3 and 12 months, a follow-up was conducted using a postal questionnaire including subjective quality of life EQ-5D-5L (European Quality of Life 5 Dimensions). At all time-points, Modified Rankin Scale (mRS) was additionally used to quantify functional stroke severity. Differences between therapy groups were identified using post-hoc -tests. Linear and logistic regression analyses were used to identify predictors of outcomes. Results: Recanalization therapies were associated with significant improvements of NIHSS (National Institutes of Health Stroke Scale [regression coefficient IVT 1.21 ( p = 0.01) and ET/BT 7.6; p = 0.001] and mRS (modified Rankin Scale) [regression coefficient IVT 0.83; p = 0.001 and ET/BT 2.0; p = 0.001] between admission and discharge compared to patients with stroke unit therapy only, with a trend toward improvement of EQ-5D after 12 months [regression coefficient 4.67 ( p = 0.17)] with IVT. HRQoL was considerably impaired by stroke and increased steadily in 3- and 12-months follow-up in patients with (mean EQ-5D from 56 to 68) and without recanalization therapy (mean EQ-5D from 62 to 68). In severe strokes a major and significant improvement was only detected during period of 3 to 12 months ( p = 0.03 in patients with and p = 0.005 in patients without recanalization therapy). Conclusions: Despite significant and continuous improvements after stroke the HRQoL after 12 months remained below the age-matched general population, but was still unexpectedly high in view of the accumulation of permanent disabilities in up to 30% of the patients. Especially in severe strokes, it is important to evaluate HRQoL beyond a 3-months follow-up as improvements became significant only between 3 months and 1 year., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kainz, Meisinger, Linseisen, Kirchberger, Zickler, Naumann and Ertl.)

Background and Purpose: Neuromuscular ultrasound in amyotrophic lateral sclerosis (ALS) is of increasing interest. As bulbar symptoms are commonly developed by most ALS patients during disease, the aim of our study was to find possible sonographic changes of vagus nerve size in bulbar affected ALS patients., Methods: We investigated 24 ALS patients and 19 controls without neuromuscular disorders. In ALS patients, bulbar affection was documented clinically (eg, dysarthria, dysphagia, and fasciculations) or subclinically using ultrasound and electromyography of bulbar muscles. Vagus nerve ultrasound was performed in all participants bilaterally at the level of the thyroid gland., Results: The cross-sectional area (CSA) of the vagus nerve in bulbar affected ALS patients (mean CSA right/left 1.9 ± .7 mm²/1.8 ± .6 mm²) was significantly reduced on both sides compared to controls (mean CSA right/left 2.2 ± .6 mm²/2.0 ± .3 mm²) - right: P = .0387, left: P = .0386. Receiver operating characteristic curve analysis of the vagus nerve CSA yielded a sensitivity of 66.7% and a specificity of 63.2% (cutoff value 1.85 mm²). Vagus nerve CSA did not correlate significantly with age in controls (right: P = .45, left: P = .66). In controls and ALS patients, there was no significant difference of vagus nerve CSA between the right and left sides (controls: P = .43; patients: P = .86)., Conclusion: Our study demonstrates vagus nerve atrophy in bulbar affected ALS patients. Further studies are warranted investigating the relevance of our finding for monitoring disease progression in ALS., (© 2020 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

Introduction: In Germany, stroke is the third leading cause of death, with more than 60,000 fatalities out of approximately 260,000 cases (first-ever and recurrent strokes) each year. So far, there are only a few long-term studies investigating determinants of the natural course of the disease, especially in the era of mechanical thrombectomy., Materials and Methods: The prospective single-center stroke cohort Augsburg (SCHANA) study will include about 1000 patients treated for stroke in the University Hospital of Augsburg. Patients aged 18 years or older with a confirmed diagnosis of ischemic or hemorrhagic stroke are included in the study. Information on demographic characteristics, onset of symptoms, etiologic factors, comorbidities, quality of life, invasive and non-invasive treatment, complications, and laboratory parameters are collected during a personal interview conducted during the patients' hospital stay and via a medical chart review. About 30 mL of blood is collected from each patient, and after processing and aliquoting, all blood specimens are frozen at -80° C. The study participants will be followed-up via postal questionnaires at three and 12 months after discharge from the hospital. Furthermore, mortality follow-ups will be conducted. Cox-regression analysis will be used to estimate relative risks., Conclusion: The SCHANA study will generate comprehensive data on the long-term course of the disease. In addition to the main outcomes, recurrent events and survival, patient-oriented outcomes such as health-related quality of life and depression are the focus of the study., Competing Interests: The authors declare that they have no competing interests.

Background: To compare the long-term functional outcomes of patients surgically treated for Weber B ankle fractures with or without syndesmotic fixation., Methods: In total, 959 adult patients with previous treatment with open reduction and internal fixation (ORIF) for closed ankle fractures were eligible for inclusion in a cross-sectional postal survey 3-6 years after surgery; 645 had Weber B fractures. The survey assessed functional outcomes with three validated ankle questionnaires., Results: In total 365 (57%) patients responded at a median of 4.2 years after the trauma. After adjusting for age, sex, education, smoking status, body mass index, diabetes, physical status before surgery, fracture classification, and duration of surgery, patients with a syndesmotic fixation had no different OMAS score (p = 0.98), LEFS score (p = 0.61), and SEFAS score (p = 0.98) than those without a syndesmotic fixation. Trimalleolar fracture was associated with worse functional outcomes than unimalleolar on two of the scales, the OMAS (p = 0.028) and LEFS (p = 0.046)., Conclusions: In multivariable analysis, patients with a syndesmotic fixation had no worse long-term functional outcomes than those without syndesmotic fixation., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Programming deep brain stimulation in dystonia is difficult because of the delayed benefits and absence of evidence-based guidelines. Therefore, we evaluated the efficacy of a programming algorithm applied in a double-blind, sham-controlled multicenter study of pallidal deep brain stimulation in dystonia., Methods: A standardized monopolar review to identify the contact with the best acute antidystonic effect was applied in 40 patients, who were then programmed 0.5 V below the adverse effect threshold and maintained on these settings for at least 3 months, if tolerated. If no acute effects were observed, contact selection was based on adverse effects or anatomical criteria. Three-year follow-up data was available for 31 patients, and five-year data for 32 patients. The efficacy of the algorithm was based on changes in motor scores, adverse events, and the need for reprogramming., Results: The mean (±standard deviation) dystonia motor score decreased by 73 ± 24% at 3 years and 63 ± 38% at 5 years for contacts that exhibited acute improvement of dystonia ( n  = 17) during the monopolar review. Contacts without acute benefit improved by 58 ± 30% at 3 years ( n  = 63) and 53 ± 31% at 5 years ( n  = 59). Interestingly, acute worsening or induction of dystonia/dyskinesia ( n  = 9) correlated significantly with improvement after 3 years, but not 5 years., Conclusions: Monopolar review helped to detect the best therapeutic contact in approximately 30% of patients exhibiting acute modulation of dystonic symptoms. Acute improvement, as well as worsening of dystonia, predicted a good long-term outcome, while induction of phosphenes did not correlate with outcome., Trial Registration: ClinicalTrials.gov NCT00142259., Competing Interests: Competing interestsAll authors report no potential conflict of interest regarding this manuscript. Over the last 12 months FS report grants and personal fees from Boston Scientific, a research grant from Medtronic and personal fees from Abbott for educational trainings, JV received grants from Medtronic and Boston Scientific as well as personal fees from Medtronic, Abbott, Boston Scientifc, UCB, Merz, Allergan, TEVA, Novartis, Abbvie, Grünenthal and Newronika. GD has received lecture fees from Boston Scientific and has been serving as a consultant for Boston Scientific. He received royalties from Thieme publishers. He is a government employee and receives through his institution funding for his research from the German Research Council, the German Ministery of Education and Research and Medtronic. JVe reports grants and consultancies from Abbott and Boston Scientific over the last 12 months. CWI reports honoraria from Allergan Inc., Merz Pharmaceutical and Ipsen Pharm and travel grants from Desitin over the last 12 months. AS has been serving as a consultant for Medtronic Inc., Boston Scientific, St. Jude Medical, Grünenthal and has received lecture fees from Abbvie, Boston Scientific, St. Jude Medical, Medtronic Inc., UCB, MEDA Pharma, Teva Pharma, and GlaxoSmithKline. AS is a government employee and receives through his institution funding for his research from the German Research Council, the German Ministery of Education and Health, and the Gossweiler Foundation. JM reports honoraria from Merz Pharmaceutical over the last 12 months. AKü reports consultancies for Boston Scientific and Abbott. AKu reports honoraria from Zamson and Merz DF, JVH, MN and WE report no financial disclosure over the last 12 months., (© The Author(s) 2019.)

Background: To compare the functional outcomes between patients with and without postoperative surgical-site infection (SSI) after surgical treatment in closed ankle fractures., Methods: Retrospective cohort study with prospective follow-up. Of 1011 treated patients, 959 were eligible for inclusion in a postal survey. Functional outcomes were assessed using three self-reported questionnaires., Results: In total 567 patients responded a median of 4.3 years (range 3.1-6.2 years) after surgery. In total 29/567 had an SSI. The mean Olerud and Molander Ankle Score was 19.8 points lower for patients with a deep SSI (p=0.02), the Lower Extremity Functional Scale score was 10.2 points lower (p<0.01) and the Self-Reported Foot & Ankle Questionnaire score was 5.0 points higher (p=0.10) than for those without an SSI, after adjusting for age, sex, smoking status, diabetes, physical status, fracture classification and duration of surgery., Conclusions: Patients with a deep SSI had worse long-term functional outcomes than those without an SSI., (Copyright © 2016 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.)

Background: The purposes of the present study were to identify the determinants of health status 3 to 6 years after open reduction and internal fixation (ORIF) for the treatment of closed ankle fracture and to compare the health status of patients who had undergone this procedure with that in the general population after adjusting for sociodemographic variables, body mass index (BMI), and smoking status., Methods: The present study was a historical cohort study combined with a postal survey. In total, 1,149 patients who underwent ORIF for the treatment of closed ankle fractures at 2 hospitals were eligible for chart review; 959 with low-energy fractures were eligible for a postal survey, and 471 (49%) responded to the Short Form Health Survey-36 (SF-36) health status questionnaire and provided data on BMI. Determinants of the physical functioning (PF), physical component summary (PCS), and mental component summary (MCS) scores of the SF-36 were analyzed by means of multivariable linear regression analysis. The health status of patients with an ankle fracture (n = 471) was compared with that in a sample of the general population (n = 5,396) by means of multivariable regression., Results: Age, American Society of Anesthesiologists (ASA) class III, and complications following surgery were associated with PF and PCS scores, and a BMI of ≥30 kg/m 2 and current smoking status was associated with PF and MCS scores. However, the PF, PCS, and MCS scores of patients with ankle fractures did not differ from those of the general population, with unstandardized regression coefficients of 0.25 (95% confidence interval [CI], -1.67 to 2.16; p = 0.80), 0.67 (95% CI, -0.35 to 1.70; p = 0.199), and -0.57 (95% CI, -1.63 to 0.49; p = 0.29), respectively., Conclusions: Age, ASA class III, and complications following surgery were associated with PF and PCS scores at 3 to 6 years after surgery for the treatment of closed ankle fractures. However, the health status of patients with ankle fractures did not differ from that in the general population after adjusting for differences in demographic variables, BMI, and smoking status., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

The present retrospective cohort study assessed the association of body mass index (BMI) with the pattern of ankle fractures using 2 classifications systems. Of the 1011 consecutive patients who underwent surgery for ankle fractures in 2 hospitals from January 2009 to December 2011, 837 had a classifiable fracture according to 1 of 2 classification systems and complete information available for covariates. The association of BMI, adjusted for age, sex, corticosteroid use, diabetes, and smoking status with having a more proximal fibula fracture (Weber class A to C) and an increasing number of malleoli involved (uni-, bi-, or trimalleolar) was assessed using multivariable ordered logistic regression analysis. The mean age of the patients was 50.9 ± 16.9 years, and 461 (55%) were female. On multivariable analysis, BMI and male sex were associated with having a more proximal fibula fracture using the Weber classification, with an odds ratio (OR) of 1.07 (95% confidence interval [CI] 1.04 to 1.11; p < .001) per 1 kg/m 2 increase and OR of 2.96 (95% CI 2.13 to 4.11; p < .001) compared with female sex, respectively. Age was not associated with this fracture classification. In an analysis of uni-, bi-, and trimalleolar fractures, age per 10 years showed higher odds (OR 1.24, 95% CI 1.14 to 1.36; p < .001) and male sex lower odds compared with female sex (OR 0.36, 95% CI 0.27 to 0.48; p < .001) of having trimalleolar fractures than uni- or bimalleolar fractures. An increasing BMI did not seem to be a risk factor, although an inverse U-shaped relationship was seen between quintiles of BMI and the OR of having trimalleolar versus uni- or bimalleolar fractures. Corticosteroid use, diabetes, and smoking status were not significantly associated with the pattern of the ankle fractures using either classification system. In conclusion, an increasing BMI and male sex were risk factors for proximal fibula fractures, and female sex and age were risk factors for bi- and trimalleolar fractures., (Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Primary focal hyperhidrosis is a common autonomic disorder that significantly impacts quality of life. It is characterized by excessive sweating confined to circumscribed areas, such as the axillae, palms, soles, and face. Less frequent types of focal hyperhidrosis secondary to underlying causes include gustatory sweating in Frey's syndrome and compensatory sweating in Ross' syndrome and after sympathectomy. Approval of onabotulinumtoxinA for severe primary axillary hyperhidrosis in 2004 has revolutionized the treatment of this indication. Meanwhile further type A botulinum neurotoxins like abobotulinumtoxinA and incobotulinumtoxinA, as well as the type B botulinum neurotoxin rimabotulinumtoxinB are successfully used off-label for axillary and various other types of focal hyperhidrosis. For unexplained reasons, the duration of effect differs considerably at different sites. Beside hyperhidrosis, botulinum neurotoxin is also highly valued for the treatment of sialorrhea affecting patients with Parkinson's disease, cerebral palsy, amyotrophic lateral sclerosis, motor neuron disease, and other neurologic conditions. With correct dosing and application, side effects are manageable and transient., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Botulinum neurotoxin (BoNT) can be injected to achieve therapeutic benefit across a large range of clinical conditions. To assess the efficacy and safety of BoNT injections for the treatment of certain hypersecretory disorders, including hyperhidrosis, sialorrhea, and chronic rhinorrhea, an expert panel reviewed evidence from the published literature. Data sources included English-language studies identified via MEDLINE, EMBASE, CINAHL, Current Contents, and the Cochrane Central Register of Controlled Trials. Evidence tables generated in the 2008 Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (AAN) review of the use of BoNT for autonomic disorders were also reviewed and updated. The panel evaluated evidence at several levels, supporting BoNT as a class, the serotypes BoNT-A and BoNT-B, as well as the four individual commercially available formulations: abobotulinumtoxinA (A/Abo), onabotulinumtoxinA (A/Ona), incobotulinumtoxinA (A/Inco), and rimabotulinumtoxinB (B/Rima). The panel ultimately made recommendations for each therapeutic indication, based upon the strength of clinical evidence and following the AAN classification scale. For the treatment of axillary hyperhidrosis in a total of 923 patients, the evidence supported a Level A recommendation for BoNT-A, with a Level B recommendation for A/Abo and A/Ona and a Level U recommendation (insufficient data) for A/Inco and B/Rima. Five trials in 82 patients supported the use of BoNT in palmar hyperhidrosis, with a Level B recommendation for BoNT-A and a Level C recommendation for BoNT-B; individual formulations received a Level U rating due to insufficient data. BoNT (and all individual formulations) received a Level U recommendation for the treatment of gustatory sweating. Support for use of BoNT in sialorrhea was derived from eight trials in a total of 222 adults and children. Evidence supported a Level B recommendation for A/Abo, A/Ona, and B/Rima and a Level U recommendation for A/Inco. Evidence supported a Level B recommendation for A/Ona for the treatment of allergic rhinitis, based on two Class II studies in 73 patients. A lack of published studies for A/Abo, A/Inco, or B/Rima supported a Level U recommendation for those formulations. Further clarity on the optimal mode of administration and additional studies using other BoNT formulations are needed to fill current evidence gaps., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Botulinum neurotoxins are formulated biologic pharmaceuticals used therapeutically to treat a wide variety of chronic conditions, with varying governmental approvals by country. Some of these disorders include cervical dystonia, post-stroke spasticity, blepharospasm, migraine, and hyperhidrosis. Botulinum neurotoxins also have varying governmental approvals for cosmetic applications. As botulinum neurotoxin therapy is often continued over many years, some patients may develop detectable antibodies that may or may not affect their biological activity. Although botulinum neurotoxins are considered "lower risk" biologics since antibodies that may develop are not likely to cross react with endogenous proteins, it is possible that patients may lose their therapeutic response. Various factors impact the immunogenicity of botulinum neurotoxins, including product-related factors such as the manufacturing process, the antigenic protein load, and the presence of accessory proteins, as well as treatment-related factors such as the overall toxin dose, booster injections, and prior vaccination or exposure. Detection of antibodies by laboratory tests does not necessarily predict the clinical success or failure of treatment. Overall, botulinum neurotoxin type A products exhibit low clinically detectable levels of antibodies when compared with other approved biologic products. This review provides an overview of all current botulinum neurotoxin products available commercially, with respect to the development of neutralizing antibodies and clinical response.

Background: Severe forms of primary dystonia are difficult to manage medically. We assessed the safety and efficacy of pallidal neurostimulation in patients with primary generalised or segmental dystonia prospectively followed up for 5 years in a controlled multicentre trial., Methods: In the parent trial, 40 patients were randomly assigned to either sham neurostimulation or neurostimulation of the internal globus pallidus for a period of 3 months and thereafter all patients completed 6 months of active neurostimulation. 38 patients agreed to be followed up annually after the activation of neurostimulation, including assessments of dystonia severity, pain, disability, and quality of life. The primary endpoint of the 5-year follow-up study extension was the change in dystonia severity at 3 years and 5 years as assessed by open-label ratings of the Burke-Fahn-Marsden dystonia rating scale (BFMDRS) motor score compared with the preoperative baseline and the 6-month visit. The primary endpoint was analysed on an intention-to-treat basis. The original trial is registered with ClinicalTrials.gov (NCT00142259)., Findings: An intention-to-treat analysis including all patients from the parent trial showed significant improvements in dystonia severity at 3 years and 5 years compared with baseline, which corresponded to -20·8 points (SD 17·1; -47·9%; n=40) at 6 months; -26·5 points (19·7; -61·1%; n=31) at 3 years; and -25·1 points (21·3; -57·8%; n=32). The improvement from 6 months to 3 years (-5·7 points [SD 8·4]; -34%) was significant and sustained at the 5-year follow-up (-4·3 [10·4]). 49 new adverse events occurred between 6 months and 5 years. Dysarthria and transient worsening of dystonia were the most common non-serious adverse events. 21 adverse events were rated serious and were almost exclusively device related. One patient attempted suicide shortly after the 6-month visit during a depressive episode. All serious adverse events resolved without permanent sequelae., Interpretation: 3 years and 5 years after surgery, pallidal neurostimulation continues to be an effective and relatively safe treatment option for patients with severe idiopathic dystonia. This long-term observation provides further evidence in favour of pallidal neurostimulation as a first-line treatment for patients with medically intractable, segmental, or generalised dystonia., Funding: Medtronic., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

This meta-analysis evaluated the frequency of neutralizing antibody (nAb) conversion with onabotulinumtoxinA (BOTOX®; Allergan) across five studied indications. The analysis was based on large, controlled or prospective, open-label trials (durations 4 months to ≥2 years). Serum samples were analyzed for nAbs using the Mouse Protection Assay. Subjects who were antibody negative at baseline and had at least one analyzable postbaseline antibody assay result were included. The 16 clinical studies included 3,006 subjects; of these, 2,240 met the inclusion criteria for this analysis. Subjects received 1-15 treatments (mean 3.8 treatments) with onabotulinumtoxinA. Total doses per treatment cycle ranged from 10 or 20 units in glabellar lines to 20-500 units in cervical dystonia. The numbers of subjects who converted from an antibody-negative status at baseline to antibody-positive status at any post-treatment time point were: cervical dystonia 4/312 (1.28%), glabellar lines 2/718 (0.28%), overactive bladder 0/22 (0%), post-stroke spasticity 1/317 (0.32%), and primary axillary hyperhidrosis 4/871 (0.46%). Across all indications, 11/2,240 subjects (0.49%) converted from antibody negative at baseline to positive at one or more post-treatment time points, but only three subjects became clinically unresponsive to onabotulinumtoxinA at some point following a positive assay. Based on these large trials, the frequency of antibody conversion after onabotulinumtoxinA treatment is very low, and infrequently leads to loss of efficacy. © 2010 Movement Disorder Society.

The aim of the study was to investigate the efficacy of the antibiotic minocycline as a drug treatment in patients with Multiple-System-Atrophy Parkinson-type (MSA-P). Sixty-three patients were randomized to minocycline 200 mg/d (n = 32) or a matching placebo (n = 31). The primary outcome variable was the change in the value of the motor score of the Unified Multiple-System-Atrophy Rating-Scale (UMSARSII) from baseline to 48 weeks. Secondary outcome variables included subscores and individual Parkinsonian symptoms as determined by the UMSARS and the Unified-Parkinson's-Disease Rating-Scale (UPDRS). Health-related quality of life (HrQoL) was assessed using the EQ-5D and SF-12. "Progression rate" was assumed to be reflected in the change in motor function over 48 weeks. At 24 weeks and 48 weeks of follow-up, there was a significant deterioration in motor scores in both groups, but neither the change in UMSARSII nor in UPDRSIII differed significantly between treatment groups, i.e. "progression rate" was considered to be similar in both treatment arms. HrQoL did not differ among the two treatment arms. In a small subgroup of patients (n = 8; minocycline = 3, placebo = 5)[(11)C](R)-PK11195-PET was performed. The three patients in the minocycline group had an attenuated mean increase in microglial activation as compared to the placebo group (P = 0.07) and in two of them individually showed decreased [11C](R)-PK11195 binding actually decreased. These preliminary PET-data suggest that minocycline may interfere with microglial activation. The relevance of this observation requires further investigation. This prospective, 48 week, randomized, double-blind, multinational study failed to show a clinical effect of minocycline on symptom severity as assessed by clinical motor function.

Background: Neurostimulation of the internal globus pallidus has been shown to be effective in reducing symptoms of primary dystonia. We compared this surgical treatment with sham stimulation in a randomized, controlled clinical trial., Methods: Forty patients with primary segmental or generalized dystonia received an implanted device for deep-brain stimulation and were randomly assigned to receive either neurostimulation or sham stimulation for 3 months. The primary end point was the change from baseline to 3 months in the severity of symptoms, according to the movement subscore on the Burke-Fahn-Marsden Dystonia Rating Scale (range, 0 to 120, with higher scores indicating greater impairment). Two investigators who were unaware of treatment status assessed the severity of dystonia by reviewing videotaped sessions. Subsequently, all patients received open-label neurostimulation; blinded assessment was repeated after 6 months of active treatment., Results: Three months after randomization, the change from baseline in the mean (+/-SD) movement score was significantly greater in the neurostimulation group (-15.8+/-14.1 points) than in the sham-stimulation group (-1.4+/-3.8 points, P<0.001). During the open-label extension period, this improvement was sustained among patients originally assigned to the neurostimulation group, and patients in the sham-stimulation group had a similar benefit when they switched to active treatment. The combined analysis of the entire cohort after 6 months of neurostimulation revealed substantial improvement in all movement symptoms (except speech and swallowing), the level of disability, and quality of life, as compared with baseline scores. A total of 22 adverse events occurred in 19 patients, including 4 infections at the stimulator site and 1 lead dislodgment. The most frequent adverse event was dysarthria., Conclusions: Bilateral pallidal neurostimulation for 3 months was more effective than sham stimulation in patients with primary generalized or segmental dystonia. (ClinicalTrials.gov number, NCT00142259 [ClinicalTrials.gov].)., (Copyright 2006 Massachusetts Medical Society.)

Recent studies have revealed autonomic dysfunction in amyotrophic lateral sclerosis (ALS). We studied salivary gland function by quantitative scintigraphy in ALS patients (n = 30) and healthy controls (n = 30). Uptake of (99m)Tc-pertechnetate in the parotid and submandibular glands was significantly decreased in ALS patients. No correlation was found between radiotracer uptake and regions of onset (bulbar-limb), duration of disease, or functional scores. Our data show early subclinical autonomic involvement supporting the view that ALS is a multisystem degenerative disease.