[The new Parkinson's disease pain classification system (PD-PCS)]. / Die neue Parkinson-Schmerzklassifikation (PSK).

BACKGROUND: Chronic pain is a common non-motor symptom in patients with Parkinson's disease (PD). AIM: To facilitate the diagnosis of pain in PD, we developed a new classification system the Parkinson's disease pain classification system (PD-PCS) and translated the corresponding validated questionnaire into German. METHODS: A causal relationship of the respective pain syndrome with PD can be determined by four questions before assigning it hierarchically into one of three pain categories (neuropathic, nociceptive and nociplastic). RESULTS: In the initial validation study 77% of the patients (122/159) had PD-associated pain comprising 87 (55%) with nociceptive, 36 (22%) with nociplastic and 24 (16%) with neuropathic pain. The study revealed a high validity of the questionnaire and a moderate intrarater and interrater reliability. The questionnaire has been adapted into German and employed in 30 patients. DISCUSSION: The PD-PCS questionnaire is a valid and reliable tool to determine the relationship of a pain syndrome with PD before classifying it according to the underlying category, facilitating further diagnostics and treatment.

Optical coherence tomography-based assessment of retinal vascular pathology in cerebral small vessel disease.

BACKGROUND: Cerebral small vessel disease (CSVD) is a disorder of brain vasculature that causes various structural changes in the brain parenchyma, and is associated with various clinical symptoms such as cognitive impairment and gait disorders. Structural changes of brain arterioles cannot be visualized with routine imaging techniques in vivo. However, optical coherence tomography (OCT) is thought to be a "window to the brain". Thus, retinal vessel parameters may correlate with CSVD characteristic brain lesions and cerebrospinal fluid biomarkers (CSF) of the neuropathological processes in CSVD like endothelial damage, microglial activation and neuroaxonal damage. METHODS: We applied OCT-based assessment of retinal vessels, magnetic resonance imaging (MRI), and CSF biomarker analysis in a monocentric prospective cohort of 24 patients with sporadic CSVD related stroke and cognitive impairment. MRI lesions were defined according to the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE). Biomarkers were assessed using commercially available ELISA kits. Owing to the unavailability of an age-matched control-group lacking MRI-characteristics of CSVD, we compared the retinal vessel parameters in CSVD patients (73.8 ± 8.5 years) with a younger group of healthy controls (51.0 ± 16.0 years) by using an age- and sex-adjusted multiple linear regression analysis model. RESULTS: Among the parameters measured with OCT, the Wall to Lumen Ratio (WLR) but not Mean Wall Thickness (MWT) of the superior branch of the retinal artery correlated significantly with the volume of white matter hyperintensities on MRI (rs = - 0.5) and with CSF-levels of Chitinase 3 like 1 protein (rs = - 0.6), zona occludens 1 protein (rs = - 0.5) and GFAP (rs = - 0.4). MWT and WLR were higher in CSVD than in controls (28.9 µm vs. 23.9 µm, p = 0.001 and 0.32 vs. 0.25, p = 0.001). CONCLUSIONS: In this exploratory study, WLR correlated with the volume of white matter hyperintensities, and markers of vascular integrity, microglial activation, and neuroaxonal damage in CSVD. Further prospective studies should clarify whether retinal vessel parameters and CSF biomarkers may serve to monitor the natural course and treatment effects in clinical studies on CSVD.

Disease modifying treatment trials in Parkinson's disease: how to balance expectations and interests of patients, physicians and industry partners?

BACKGROUND: The advent of therapeutic strategies designed to modify the disease course in Parkinson's disease has raised great expectations in the currently conducted clinical trials. However, we see ethical challenges in the cooperation of industry and clinical partners, specifically evident in the way recruitment is performed.We here discuss the different positions and challenges of all involved to set the stage for a study and recruitment culture taking into account the expectations of all: (i) patients and their caregivers, ready to take the considerable burden of clinical trials in hope for the development of disease-modifying treatments; (ii) physicians and study nurses, obligated to the patients' well-being and benefit who accompany and supervise patients closely as basis for the performance of elaborate clinical trials (iii) industrial partners, investing years of efforts and finances to develop new treatments. CONCLUSIONS: We conclude that the current competitive race for enrollment in clinical studies in PD is challenging the primary goal to ensure patients' benefit and formulate requests to the industrial partners to encounter these concerns.

Miller-Fisher syndrome after COVID-19: neurochemical markers as an early sign of nervous system involvement.

Miller-Fisher syndrome (MFS) is classified as a variant of Guillain-Barré syndrome (GBS), accounting for 5%-25% of all GBS cases. Since the coronavirus disease-2019 (COVID-19) outbreak, increasing evidence has been reported of the neurological manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, affecting both the central and peripheral nervous system. Here we report the clinical course, detailed cerebrospinal fluid (CSF) profile including CSF/blood antibody status, and neurochemical characteristics of a patient with a typical clinical presentation of MFS after a positive SARS-CoV-2 infection test.

Recent silent infarcts do not increase the risk of haemorrhage after intravenous thrombolysis.

BACKGROUND AND PURPOSE: Haemorrhagic transformation (HT) is one of the main risks of intravenous thrombolysis (IVT) for acute ischaemic stroke. Contraindications serve to exclude patients at high risk of HT after IVT. One of these contraindications is a stroke within the preceding 3 months. It is unclear if this contraindication should include recent clinically silent infarcts (RSIs). The aim of this study was to investigate whether RSIs are associated with a higher risk of HT and a worse clinical outcome after IVT for acute ischaemic stroke. METHODS: In a retrospective monocentric cohort study, all patients who received IVT for acute ischaemic stroke based on magnetic resonance imaging were assessed over 5 years. RSIs were defined as lesions with diffusion restriction and positive signal on fluid attenuated inversion recovery sequences. Patients with RSIs (RSI+) were compared to patients without RSIs (RSI-) regarding HT after IVT and clinical outcome. RESULTS: In all, 981 patients who had received IVT for acute ischaemic stroke demonstrated by magnetic resonance imaging were identified. RSIs were detected in 115 patients (11.5%). HT after IVT was observed in 32 (28.3%) RSI+ and 56 (25.8%) RSI- patients (P = 0.624). Symptomatic intracerebral haemorrhage was noted in two (1.8%) RSI+ and five (2.3%) RSI- patients (P = 1.000). No differences in clinical outcome were observed. CONCLUSIONS: The detection of RSIs in patients treated with IVT for acute ischaemic stroke was not associated with a higher risk of HT or a worse clinical outcome. The results of this study argue against considering RSIs as a contraindication for IVT.

MR-imaging pattern is not a predictor of occult atrial fibrillation in patients with cryptogenic stroke.

BACKGROUND: To date, insertable cardiac monitors (ICMs) are the most effective method for the detection of occult atrial fibrillation (AF) in cryptogenic stroke. The overall detection rate after 12 months, however, is low and ranges between 12.4 and 33.3%, even if clinical predictors are considered. Ischemic stroke patients due to cardiogenic embolism present with particular lesion patterns. In patients with cryptogenic stroke, MR-imaging pattern may be a valuable predictor for AF. METHODS: This is an MRI-based, retrospective, observational, comparative, single-center study of 104 patients who underwent ICM implantation after cryptogenic stroke. The findings were compared to a reference group with related stroke etiology, i.e., 166 patients with embolic stroke due to AF detected for the first time by long-term ECG. Lesion patterns were evaluated with regard to affected territories, distribution (cortical, lacunar, scattered), lesion volume, and lesion size (diameter of the lesion size > 20 mm). RESULTS: The MR-imaging analysis of acute ischemic lesions yielded no association between AF and lesion size or volume, arterial vessel distribution, or the number of affected territories. There was no significant difference between the cohorts regarding ischemic patterns (cortical lesions, scattered lesions, and lacunar infarcts). An important clinical inference of our findings is that 10% (2 of 20) of cases in the ICM group in whom AF was detected had a lacunar infarct pattern. Similar results were shown in cases of ischemic stroke patients with AF detected for the first time by long-term ECG, with 10.9% (16 of 147) of them showing lacunar infarcts. The analysis of chronic MRI lesions revealed no differences between the groups in the rate of chronic lesions, arterial vessel distribution, or the number of affected territories. Left atrial size (LA size) and the presence of atrial runs in long-term ECG were independently associated with AF. CONCLUSIONS: In this MRI-based analysis of patients with cryptogenic stroke who had received ICM implantation, the detection rate of AF in patients with ICM was not related to the imaging pattern. In addition, the lacunar infarct pattern should not be an exclusion criterion for ICM insertion in patients with cryptogenic stroke. ICM insertion in patients with cryptogenic stroke should not be evaluated solely on the basis of reference to infarct patterns.

Author Correction: Serum GFAP as a biomarker for disease severity in multiple sclerosis.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Serum GFAP as a biomarker for disease severity in multiple sclerosis.

While neurofilament light chain (NfL) measurement in serum is a well-established marker of neuroaxonal damage in multiple sclerosis (MS), data on astroglial markers in serum are missing. In our study, glial fibrillary acid protein (GFAP) and NfL were measured in cerebrospinal fluid (CSF) and serum of MS patients and patients with other non-inflammatory neurological diseases (OND) using the Simoa technology. Clinical data like age, gender, expanded disability status scale (EDSS) and MRI findings were correlated to neurochemical markers. We included 80 MS patients: 42 relapsing-remitting MS (RRMS), 38 progressive MS (PMS), as well as 20 OND. Serum GFAP levels were higher in PMS compared to RRMS and OND (p < 0.001, p = 0.02 respectively). Serum GFAP levels correlated with disease severity in the whole MS group and PMS (Spearman-rho = 0.5, p < 0.001 in both groups). Serum GFAP correlated with serum NfL in PMS patients (Spearman-rho = 0.4, p = 0.01). Levels of serum GFAP were higher with increasing MRI-lesion count (p = 0.01). in summary, we report elevated levels of GFAP in the serum of MS patients. Since serum levels of GFAP correlate with the clinical severity scores and MRI lesion count, especially in PMS patients, it might be a suitable disease progression marker.

Targeting head movements in humans: Compensation for disturbance from simultaneous body rotations.

Vestibular information plays an important role in spatially oriented motor control and perception. With regard to reorienting head movements, little is known of (1) how vestibular mechanisms compensate for disturbances from concurrent passive trunk rotations (e.g. in a veering vehicle), and (2) whether and how this disturbance compensation is related to the perception of body orientation in space. We here address these two questions in a single experiment. Six healthy subjects (Ss) seated on a turning chair in darkness performed two tasks. (1) Head pointing: Ss made swift head movements in darkness towards the angular position in space of a previously shown visual target. These movements were disturbed by concurrent rotations of the chair, and hence the trunk, which were driven by scaled down versions of the Ss' own head-on-trunk rotations. Although unaware of the disturbance, Ss adjusted their head movements so as to attenuate its effect on head-in-space (HS) position by about 45%. (2) Visual straight ahead (VSA): Using a light pointer, Ss indicated their VSA before each head-pointing trial and tried to reproduce it after the trial. In all Ss, VSA accounted for the disturbing trunk rotation, although to individually varying degrees. No correlation could be detected between VSA reproduction and motor performance, neither within nor across subjects. A vestibular loss subject who performed the same two tasks made no compensatory movements during head pointing and did not account for the disturbance of his HS position during VSA reproduction. Three concepts of vestibular information processing for head movement control were explored with regard to their compatibility with the head-pointing results: (1) Conventional negative feedback, (2) Interaction with an efference copy, and (3) Interaction with neck proprioceptive information. Theoretical analyses and model simulations indicated that all three concepts can explain the observed disturbance compensation. However, they differ in terms of control stability in the presence of feedback time delays, with (3) being best and (1) worst. The different concepts might correspond to fast simple and slower complex compensation mechanisms, respectively, and possibly complement each other during natural behaviours. VSA reproduction may be based on analogous processing principles, but appears to involve different neural circuitries.

In vivo assessment of retinal vessel pathology in amyotrophic lateral sclerosis.

BACKGROUND: Changes in skin and muscle small blood vessels (SBVs) and microvascular structures of the brain have been reported in patients with amyotrophic lateral sclerosis (ALS). A direct assessment of brain SBVs in vivo is currently not feasible. Retinal vessels are considered a "mirror" of brain SBVs. In this study, we used optic coherence tomography (OCT)-based measurements to detect changes in retinal blood vessels of ALS patients compared to those of healthy controls. METHODS: We analysed Spectralis-OCT images of 34 ALS patients and 20 HCs. The inner wall thickness (IWT), outer wall thickness (OWT), and lumen diameter (LD) of retinal vessels were assessed using intensity-based measurements. In addition, the different retinal layers were analysed using automated segmentation software. The correlations between the various retinal layers and clinical parameters [e.g., disease duration and revised ALS functional rating scale (ALS-FRS-R)] were examined. RESULTS: The OWT of retinal vessels was higher in ALS patients than in HCs (p = 0.04). There were no differences in the IWT, LD. ALS patients showed a thinning of the outer nuclear layer (ONL) compared to HCs (median 1.63 vs. 1.77, p = 0.002). The whole retinal thickness negatively correlated with the ALS-FRS scale (r = 0.3, p = 0.03). CONCLUSION: Our study reports retinal vessel pathology in ALS patients. These changes may be related to those observed in SBVs in skin and muscle biopsies. Furthermore, we report a thinning of the ONL in ALS, revealing a possible affection of rods and cones function in ALS.

[Management of dysphagia in acute stroke : A prospective study for validation of current recommendations]. / Dysphagiemanagement beim akuten Schlaganfall : Eine prospektive Studie zur Überprüfung der geltenden Empfehlungen.

BACKGROUND: The German expert recommendations on the management of dysphagia in patients after acute stroke suggest an algorithm for clinical and technical investigations to identify patients at risk for aspiration and thus reduce the rate of aspiration pneumonia. The effectiveness of this algorithm has, however, not yet been prospectively validated . METHODS: In this study 144 consecutive stroke patients were assessed by a full bedside swallowing assessment including the screening procedures of standardized swallowing assessment (SSA) and 2 out of 6. Flexible endoscopic evaluation of swallowing (FEES) was performed in all patients. RESULTS: Aspiration was diagnosed in 25 patients (17.4%) by FEES. The SSA predicted aspiration with a sensitivity of 76% and a specificity of 55.5% and the 2 out of 6 screening with a sensitivity of 68.0% and a specificity of 61.0%. Of the patients 7 with negative screening for 2 out of 6 and 6 patients with negative SSA showed silent aspiration with the penetration aspiration scale (PAS 8) during FEES (28% of all patients with aspiration). Significant predictors for aspiration were dysarthria, dysphonia, abnormal volitional cough and cough after swallowing water; however, in multivariable analysis only dysarthria and cough after swallowing water were identified as independent predictors for aspiration. The rate of aspiration pneumonia was 2.8%. CONCLUSION: Clinical screening alone is not sufficient to identify patients at risk for aspiration pneumonia. The FEES should be used at a low threshold in cases of severe stroke and minor clinical abnormalities, especially concerning isolated dysarthria and cough after swallowing water; therefore, current recommendations should be correspondingly modified.

Verbal memory declines more in female patients with Parkinson's disease: the importance of gender-corrected normative data.

BACKGROUND: Data on gender-specific profiles of cognitive functions in patients with Parkinson's disease (PD) are rare and inconsistent, and possible disease-confounding factors have been insufficiently considered. METHOD: The LANDSCAPE study on cognition in PD enrolled 656 PD patients (267 without cognitive impairment, 66% male; 292 with mild cognitive impairment, 69% male; 97 with PD dementia, 69% male). Raw values and age-, education-, and gender-corrected Z scores of a neuropsychological test battery (CERAD-Plus) were compared between genders. Motor symptoms, disease duration, l-dopa equivalent daily dose, depression - and additionally age and education for the raw value analysis - were taken as covariates. RESULTS: Raw-score analysis replicated results of previous studies in that female PD patients were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.03), while men outperformed women in visuoconstruction (p = 0.002) and figural memory (p = 0.005). In contrast, gender-corrected Z scores showed that men were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.02; recognition, p = 0.04), while no difference was found for visuospatial tests. This picture could be observed both in the overall analysis of PD patients as well as in a differentiated group analysis. CONCLUSIONS: Normative data corrected for gender and other sociodemographic variables are relevant, since they may elucidate a markedly different cognitive profile compared to raw scores. Our study also suggests that verbal memory decline is stronger in women than in men with PD. Future studies are needed to replicate these findings, examine the progression of gender-specific cognitive decline in PD and define different underlying mechanisms of this dysfunction.

Podokinetic circular vection: characteristics and interaction with optokinetic circular vection.

Stabilising horizontal body orientation in space without sight on a rotating platform by holding to a stationary structure and circular 'treadmill' stepping in the opposite direction can elicit an illusion of self-turning in space (Bles and Kapteyn in Agressologie 18:325-328, 1977). Because this illusion is analogous to the well-known illusion of optokinetic circular vection (oCV), we call it 'podokinetic circular vection' (pCV) here. Previous studies using eccentric stepping on a path tangential to the rotation found that pCV was always contraversive relative to platform rotation. In contrast, when our subjects stepped at the centre of rotation about their vertical axis, we observed an inverted, ipsiversive pCV as a reproducible trait in many of our subjects. This ipCV occurred at the same latency as the pCV of subjects reporting the actually expected contraversive direction, but had lower gain. In contrast to pCV, the nystagmus accompanying circular treadmill stepping had the same direction in all individuals (slow phase in the direction of platform motion). The direction of an individual's pCV predicted the characteristics of the CV resulting from combined opto- and podokinetic stimulation (circular treadmill stepping while viewing a pattern rotating together with the platform): in individuals with contraversive pCV, latency shortened and both gain and felt naturalness increased in comparison with pure oCV, whereas the opposite (longer latency, reduced gain and naturalness) occurred in individuals with ipCV. Taken together, the reproducibility of ipCV, the constant direction of nystagmus and the fact that pCV direction predicts the outcome of combined stimulation suggest that ipCV is an individual trait of many subjects during compensatory stepping at the centre of rotation. A hypothetical model is presented of how ipCV possibly could arise.

Optokinetic circular vection: a test of visual-vestibular conflict models of vection nascensy.

The propensity to experience circular vection (the illusory perception of self-turning evoked by a rotating scene, CV) as reflected by its onset latency exhibits considerable interindividual variation. Models of CV nascensy have linked this delay to the time it takes the visual-vestibular conflict to disappear. One line of these "conflict models" (Zacharias and Young in Exp Brain Res 41:159-171, 1981) predicts that, across individuals, CV latency (CVL) correlates positively with the vestibular time constant (TC) and negatively with the vestibular motion detection threshold (vTHR). A second type of models (Mergner et al. in Arch Ital Biol 138:139-166, 2000) predicts only an increase in CVL with TC. We here examine which of these predictions can be experimentally substantiated. Also, we ask whether the relative weight W O of the optokinetic contribution to the perception of real self-turning could also be a factor influencing CVL. We conducted 5 experiments in 29 subjects measuring: (1) CVL, (2) the TCs of velocity perception and of accompanying nystagmus during rotation in darkness and (3) likewise for displacement perception, (4) vTHR, and (5) W O as revealed by discordant visual-vestibular stimulation. CVL correlated with the nystagmus TC recorded during velocity estimation but with none of the other vestibular TCs nor with vTHR. Confirming earlier findings, CVL shortened with rising scene velocity. Finally, CVL correlated inversely with W O: the larger an individual's optokinetic weight, the shorter was his CVL. Taken together, our data favour the second type of models which invoke an antagonism between CV inhibition by the optokinetic-vestibular conflict and disinhibition by optokinetic stimulation. Idiosyncratic factors appear to strongly modulate the balance between inhibition and disinhibition, thus increasing CVL variability and obscuring the expected relation between CVL and TC.

Supratentorial white matter blurring associated with voltage-gated potassium channel-complex limbic encephalitis.

INTRODUCTION: Limbic encephalitis (LE) associated with voltage-gated potassium channel-complex antibodies (VGKC-LE) is frequently non-paraneoplastic and associated with marked improvement following corticosteroid therapy. Mesial temporal lobe abnormalities are present in around 80 % of patients. If associated or preceded by faciobrachial dystonic seizures, basal ganglia signal changes may occur. In some patients, blurring of the supratentorial white matter on T2-weighted images (SWMB) may be seen. The purpose of this study was to evaluate the incidence of SWMB and whether it is specific for VGKC-LE. METHODS: Two experienced neuroradiologists independently evaluated signal abnormalities on FLAIR MRI in 79 patients with LE while unaware on the antibody type. RESULTS: SWMB was independently assessed as present in 10 of 36 (28 %) compared to 2 (5 %) of 43 non-VGKC patients (p = 0.009). It was not related to the presence of LGI1 or CASPR2 proteins of VGKC antibodies. MRI showed increased temporomesial FLAIR signal in 22 (61 %) VGKC compared to 14 (33 %) non-VGKC patients (p = 0.013), and extratemporomesial structures were affected in one VGKC (3 %) compared to 11 (26 %) non-VGKC patients (p = 0.005). CONCLUSION: SWMB is a newly described MRI sign rather specific for VGKC-LE.

The neuroanatomy of subthreshold depressive symptoms in Huntington's disease: a combined diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) study.

BACKGROUND: Depressive symptoms are prominent psychopathological features of Huntington's disease (HD), making a negative impact on social functioning and well-being. METHOD: We compared the frequencies of a history of depression, previous suicide attempts and current subthreshold depression between 61 early-stage HD participants and 40 matched controls. The HD group was then split based on the overall HD group's median Hospital Anxiety and Depression Scale-depression score into a group of 30 non-depressed participants (mean 0.8, s.d. = 0.7) and a group of 31 participants with subthreshold depressive symptoms (mean 7.3, s.d. = 3.5) to explore the neuroanatomy underlying subthreshold depressive symptoms in HD using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI). RESULTS: Frequencies of history of depression, previous suicide attempts or current subthreshold depressive symptoms were higher in HD than in controls. The severity of current depressive symptoms was also higher in HD, but not associated with the severity of HD motor signs or disease burden. Compared with the non-depressed HD group DTI revealed lower fractional anisotropy (FA) values in the frontal cortex, anterior cingulate cortex, insula and cerebellum of the HD group with subthreshold depressive symptoms. In contrast, VBM measures were similar in both HD groups. A history of depression, the severity of HD motor signs or disease burden did not correlate with FA values of these regions. CONCLUSIONS: Current subthreshold depressive symptoms in early HD are associated with microstructural changes - without concomitant brain volume loss - in brain regions known to be involved in major depressive disorder, but not those typically associated with HD pathology.

[The eye as a window to the pathophysiology in Parkinson's syndromes]. / Das Auge als Zugang zur Pathophysiologie von Parkinson-Syndromen.

Although dysfunction of the visual system and dysfunctional eye movements during sporadic Parkinson's disease have been reported for more than 40 years, they have never been the focus of early and/or differential diagnosis. To date Parkinson's disease-related α-synuclein aggregates, i.e., Lewy pathology, are not known to develop either in the retina or in other components of the visual system. In a clinical context it is currently possible to test the involvement of the respective functional systems by means of optical coherence tomography and video oculography. Moreover, non-motor-related abnormalities are detectable both during psychophysical testing of visuospatial function as well as in the form of measurable deficits of color perception. These deficits of the visual and oculomotor systems could prove to be suitable candidates for diagnosing sporadic Parkinson's disease in its early phase in a non-invasive manner. This article is intended to provide an overview of the fundamental pathophysiological principles and clinical aspects of visual system involvement in sporadic Parkinson's disease together with currently available differential diagnostic options.

Evaluation of body fat composition after linagliptin treatment in a rat model of diet-induced obesity: a magnetic resonance spectroscopy study in comparison with sibutramine.

The effects of linagliptin on fat content in diet-induced obese rats were compared with those of the appetite suppressant sibutramine. Female Wistar rats fed a high-fat diet (HFD) for 3 months received vehicle, linagliptin (10 mg/kg) or sibutramine (5 mg/kg) treatment orally, once daily for 6 additional weeks, while continuing the HFD. Magnetic resonance spectroscopy analysis of fat content was performed at baseline and at the end of the 6-week treatment period. Linagliptin treatment profoundly reduced hepatic fat compared with vehicle, with an effect comparable to that of sibutramine. The vehicle-corrected mean change (95% CI) from baseline in hepatic fat and intramyocellular lipid was -59.0% (-104.3%, -13.6%; p = 0.015) and -62.1% (-131.6%, 7.4%; p = 0.073), respectively, for linagliptin compared with -54.3% (-101.5%, -7.1%; p = 0.027) and -72.4% (-142.4%, -2.4%; p = 0.044), respectively, for sibutramine.