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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. [ABSTRACT FROM AUTHOR]

Objectives: To analyse grey matter changes in early stages of Huntington's disease using magnetic resonance imaging (MRI) and the technique of voxel based morphometry (VBM).Methods: Forty four patients with a molecularly confirmed clinical diagnosis of Huntington's disease based on the presence of motor signs were included in the study. Patients were clinically rated using the Unified Huntington's Disease Rating Scale; all were in early clinical stages of the disease (that is, Shoulson stages I and II). High resolution volume rendering MRI scans (MP-RAGE) were acquired. MRI data were volumetrically analysed in comparison to an age matched normal database by VBM, using statistical parametric mapping (SPM99).Results: In Huntington's disease, robust regional decreases in grey matter density (p<0.001, corrected for multiple comparisons)-that is, atrophy-were found bilaterally in striatal areas as well as in the hypothalamus and the opercular cortex, and unilaterally in the right paracentral lobule. The topography of striatal changes corresponded to the dorso-ventral gradient of neuronal loss described in neuropathological studies. Stratification according to clinical severity showed a more widespread involvement extending into the ventral aspects of the striatum in the group of more severely affected patients.Conclusions: The topography of cerebral volume changes associated with Huntington's disease can be mapped using VBM. It can be shown that cerebral grey matter changes co-vary with clinical severity and CAG repeat length. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Tauopathies with parkinsonism represent a spectrum of disease entities unified by the pathologic accumulation of hyperphosphorylated tau protein fragments within the central nervous system. These pathologic characteristics suggest shared pathogenetic pathways and possible molecular targets for disease-modifying therapeutic interventions. Natural history studies, for instance, in progressive supranuclear palsy, frontotemporal dementia with parkinsonism linked to chromosome 17, corticobasal degeneration, and Niemann-Pick disease type C as well as in amyotrophic lateral sclerosis/Parkinson–dementia complex permit clinical characterization of the disease phenotypes and are crucial to the development and validation of biological markers for differential diagnostics and disease monitoring, for example, by use of neuroimaging or proteomic approaches. The wide pathologic and clinical spectrum of the tauopathies with parkinsonism is reviewed in this article, and perspectives on future advances in the understanding of the pathogenesis are given, together with potential therapeutic strategies. [ABSTRACT FROM AUTHOR]

Introduction. Neuropathological studies in amyotrophic lateral sclerosis (ALS) show that ALS may disseminate in a sequential regional pattern during four disease stages. The in vivo transfer of this propagation scheme can be performed by diffusion tensor imaging (DTI) based analysis of specific tracts [1]. This study investigates if these alterations can already be detected in asymptomatic ALS mutation carriers. Methods. The analysis of fractional anisotropy (FA) was performed by whole brain-based spatial statistics (WBSS) as well as by a tract-of-interest (TOI)-analysis for 45 positively tested asymptomatic ALS mutation carriers vs age- and gender-matched controls to detect specific white matter alterations. Furthermore, a longitudinal analysis was performed with a time-interval of 300 days of data of 20 positively tested asymptomatic ALS mutation carriers. Results. Neither WBSS nor TOI-based analysis were able to detect significant characteristic alteration patterns for asymptomatic ALS mutation carriers. Discussion. This study shows that microstructural alterations in ALS specific tracts in asymptomatic mutation carriers are not detectable by DTI-based analyses. That way, these tract alterations seem to be detectable with the beginning of the symptomatic stage. [1] Kassubek J, et al. J Neurol Neurosurg Psychiatry 2018; 89:374–381. [ABSTRACT FROM AUTHOR]

Abstract: Curvilinear reformatting of three-dimensional (3D) MRI data of the cerebral cortex is a well-established tool which improves the display of the gyral structure, permits a precise localization of lesions, and helps to identify subtle abnormalities difficult to detect in planar slices due to the brain''s complex convolutional pattern. However, the method is time consuming because it requires interactive manual delineation of the brain surface contour. Therefore, a novel technique for automatic curvilinear reformatting is presented. A T1-weighted MRI volume data set is normalized using SPM2. Due to the normalization to a common stereotactic space, predefined masks can be applied to cover skull and outer brain regions in different depths from the brain surface. Thereby, the outer brain regions are subsequently removed in 2-mm layers parallel to the brain surface like ‘peeling an onion’. The serial convex planes enclosing the residual inner part of the brain are presented 3-dimensionally. If necessary (e.g., for intraoperative navigation), the normalized data can be transferred to native space by inverse normalization. Compared to cross-sectional images, curvilinear reformatting offers a markedly superior visualization of topographic relations between lesions and cortical structures, helps to detect subtle cortical malformations and to assess the spatial extent of lesions, thus allowing a better planning of neurosurgical procedures. Compared to alternative methods, it is largely based on freely available software and does not require observer-dependent manual input. In conclusion, we present a simple, easy-to-use and fully automated method for curvilinear reformatting of 3D MRI. [Copyright &y& Elsevier]

The frequency and pattern of cognitive deficits in Parkinson’s disease (PD) is under discussion. We assessed 157 consecutive subjects with PD (66.4 ± 8.9 years (mean ± standard deviation); average duration of disease 3.5 ± 1.3 years; average Hoehn and Yahr stage 2.4 ± 0.9) diagnosed in centers specialized for the diagnosis and treatment of PD with brief tests for memory (Memory Impairment Screen), attention (Letter Sorting Test) and semantic fluency (category animals). Impaired memory was observed in about one half of the subjects regardless of severity of disease as assessed by staging according to Hoehn and Yahr. With greater severity, free recall was impaired and subjects required the cues to recall the items. Performance in the Letter Sorting Test and the semantic fluency task declined with increasing Hoehn and Yahr stage, also. We conclude that cognitive deficits are frequent in PD. Further analyses reveal that even in selected screening tests (e.g. semantic fluency) a significant impairment with increasing disease severity (Hoehn and Yahr stage) as opposed to disease duration alone can be demonstrated. [ABSTRACT FROM AUTHOR]

Hereditary spastic paraparesis (HSP) is a heterogeneous group of neurodegenerative disorders with progressive lower limb spasticity, categorized into pure (p-HSP) and complicated forms (c-HSP). The purpose of this study was to evaluate if brain volumes in HSP were altered compared with a control population. Brain volumes were determined in patients suffering from HSP, including both p-HSP ( n = 21) and c-HSP type ( n = 12), and 30 age-matched healthy controls, using brain parenchymal fractions (BPF) calculated from 3D MRI data in an observer-independent procedure. In addition, the tissue segments of grey and white matter were analysed separately. In HSP patients, BPF were significantly reduced compared with controls both for the whole patient group ( P < 0.001) and for both subgroups, indicating considerable brain atrophy. In contrast to controls who showed a decline of brain volumes with age, this physiological phenomenon was less pronounced in HSP. Therefore, global brain parenchyma reduction, involving both grey and white matter, seems to be a feature in both subtypes of HSP. Atrophy was more pronounced in c-HSP, consistent with the more severe phenotype including extramotor involvement. Thus, global brain atrophy, detected by MRI-based brain volume quantification, is a biological marker in HSP subtypes. [ABSTRACT FROM AUTHOR]

Els Th, Kassubek J, Kubalek R, Klisch J. Diffusion-weighted MRI during early global cerebral hypoxia: a predictor for clinical outcome? Acta Neurol Scand 2004 DOI: 10.1111/j.1600-0404.2004.00342.x© Blackwell Munksgaard 2004.As prognostic assessment of prolonged cerebral hypoxia is often difficult on clinical grounds, a tool for an early prognosis of clinical outcome is desirable.In a prospective study, we investigated the prognostic value of diffusion-weighted MRI (DWI) in 12 patients within 36 h after global cerebral hypoxia. Results of DWI including apparent diffusion coefficient maps (ADC) were analyzed and related to the clinical outcome after 6 months, in comparison with conventional magnetic resonance imaging (cMRI).Three patients with a short resuscitation time showed normal findings in cMRI and DWI and a good recovery. In seven patients, DWI revealed multiple large hyperintense areas although cMRI was normal. In two patients, large diffuse lesions were observed in DWI which were also found in cMRI. All of these nine patients developed a vegetative state in the follow-up examination.Pathological DWI during the early phase after cerebral hypoxia might be superior to cMRI as a predictor of a worse clinical outcome. [ABSTRACT FROM AUTHOR]

Malformations of cortical development (MCD) are a recognized cause of epilepsy. Their special significance lies in the fact that, once detected and delineated, they are amenable to surgical removal. However, diagnosis from high-resolution MRI is still difficult, time-consuming, and highly dependent on individual expertise. We have recently proposed a simple procedure to detect cortical dysplasias, using automated procedures available within SPM99 (Wellcome Department, University College London, UK). Here, we aimed to systematically determine the best combination of processing parameters, using an optimized voxel-based morphometry approach. We included 20 patients with a known MCD and compared them to a normal database of 53 healthy, age- and gender-matched controls. The approaches taken during spatial normalization and a number of other parameters were systematically altered in order to find the best combination of parameters. Overall, 99 different approaches were evaluated in different ways. As far as possible, automatic processing and evaluation steps were used. With the number of candidate regions for MCD limited to five per patient, the best approaches resulted in the correct identification of up to 16 of 20 malformations. However, a number of approaches failed to perform well. The reasons for these failures and the implications this has for other studies are discussed. We conclude that voxel-based morphometry is able to detect cortical malformations with a high degree of accuracy. However, specific problems seem to arise when using an optimized protocol for voxel-based morphometry, indicating that this protocol may not be optimal for all voxel-based studies on brain morphology. Our approach, involving systematic alterations of parameters and evaluation, may be useful for other studies. [Copyright &y& Elsevier]

Objectives – Tuberculous meningoencephalitis (TBM), an infrequent disease in Western European countries, shows a wide heterogeneity of clinical symptoms. Material and methods – We present 4 patients (age range 42–72 years) with the definite diagnosis of isolated TBM. All patients were HIV-seronegative, only 1 patient was known to be immunoincompetent on admission due to acute myelocytic leukemia; other reasons for immune suppression were detected in 2 other patients (leukemia and idiopathic CD4[sup +] T-lymphocytopenia, respectively). Results – The diagnosis of TBM was confirmed in 3 cases by culture from CSF, in 1 case Mycobacterium tuberculosis was proven only in tracheal aspirate. In 1 patient M. bovis was found, which is an extremely rare cause of TBM in Germany. We report the contributions of different diagnostic tools (CSF analysis, neuroimaging) in reaching the presumptive diagnosis and in monitoring the further course. All patients developed neurological complications despite prompt tuberculostatic treatment. Three of the patients presented a chronic severe loss of consciousness of unclear origin. Conclusion – The possible causative relationships of these complications and their impact on the prognosis are discussed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction Criteria for assessing upper motor neuron pathology in lower motor neuron disease (LMND) still remain a major issue in clinical diagnosis. This study was designed to investigate patients with the clinical diagnosis of adult pure LMND by use of whole-brain based diffusion tensor imaging (DTI) in order to delineate alterations of corticoefferent pathways in vivo. Methods Comparison of fractional anisotropy (FA) maps was performed by whole brain-based spatial statistics for 37 LMND patients vs. 53 matched controls to detect white matter structural alterations. LMND patients were clinically differentiated in fast and slow progressors. Tract specific alterations were investigated by fiber tracking techniques according to the staging hypothesis for amyotrophic lateral sclerosis (ALS). Results The analysis of white matter structural connectivity demonstrated widespread and characteristic patterns of alterations in patients with LMND, predominantly along the corticospinal tract (CST), with multiple clusters of regional FA reductions in the motor system at p < 0.05 (corrected for multiple comparisons). Fast progressing LMND showed substantial CST involvement, while slow progressors showed less CST alterations. In the tract-specific analysis according to the ALS-staging pattern ( Kassubek et al., 2014 ), fast progressing LMND showed significant alterations of ALS-related tract systems ( Müller et al., xxxx ) beyond the CST compared to slow progressors and controls. Conclusion In clinically pure LMND patients, the involvement of corticoefferent tracts was demonstrated, in particular along the CST, supporting the hypothesis that LMND is a phenotypical variant of ALS. This finding suggests to treat these patients like ALS, including the opportunity to participate in clinical trials. [ABSTRACT FROM AUTHOR]

Introduction Neuropathological studies in amyotrophic lateral sclerosis (ALS) have shown that ALS may disseminate in a regional sequence in four disease-related patterns ( Braak et al., 2013 ). Recently, our group reported the diffusion tensor imaging (DTI)-based analysis of sequential spreading of disease in ALS ( Kassubek et al., 2014; Müller et al., 2016 ). The aim of this study was to show that longitudinal data support the pathological findings and to establish DTI as an in vivo tool to image pathological ALS stages by testing for longitudinal consistency of the categorization results. Methods The application of in vivo DTI analysis to fiber structures that are prone to be involved at each neuropathological pattern of ALS was performed in a large-scale monocentre sample of ALS patients. A total of 584DTI datasets from ALS patients ( N = 425) and controls ( N = 159) were analyzed by tract of interest (TOI)-based fiber tracking; 52 ALS patients and 22 controls obtained at least one follow-ups can with different time-intervals of 10 months ( ± 9 months) in average. Results At the individual level, a categorization into ALS staging patterns was possible. At the group level, longitudinal ALS data showed significant differences for the stage-related tract systems ( p < 0.05, corrected for multiple comparisons).Out of the 52 longitudinally scanned ALS patients, 13 ALS patients showed an increase in ALS-stage, while the other ALS patients remained stable. Conclusion In summary, in vivo imaging of the disease patterns in ALS has become feasible cross-sectionally and longitudinally and has potential to be used as a non-invasive readout in ALS trials. [ABSTRACT FROM AUTHOR]

Objective In-vivo assessment of ALS-associated white matter alteration patterns by diffusion tensor imaging (DTI)-based metrics have been included in the NiSALS neuroimaging concept (Turner et al., LancetNeurol 2011). The objective of this multicenter study was to assess structural connectivity in ALS at a large sample-size. Methods Four-hundred-and-seven DTI data sets from patients with ALS ( N = 239) and controls ( N = 168) were collected from 8 international centers with different scanner systems and different DTI-protocols. Comparability of data with the aim of pooling was tested and differences were regressed out. Results Beyond patterns of alterations in the corticospinal tracts, whole brain-based statistical analysis, after pooling of data sets from all centers, additionally captured significant white matter tract changes in the frontal lobe, brainstem and hippocampal regions, in keeping with the DTI-based correlates of post mortem neuropathological ALS-stages 1–4 (Kassubek et al., Brain 2014). Conclusion This study using an unprecedented number of subjects has detected more wide spread changes than typical single-site studies.The observed pattern of fiber tract pathology has the potential to serve as a biomarker of disease and progression and as a read-out for future clinical trials. Key message By this multi-centre approach, it was possible to non-invasively confirm the pathoanatomy of ALS in vivo . [ABSTRACT FROM AUTHOR]

Introduction In Huntington’s disease (HD), cerebral white matter changes have been reported in a number of studies using diffusion tensor imaging (DTI) or T1-weighted magnetic resonance imaging (MRI). A key question is how brain structure changes (both grey and white matter) influence brain function. Intrinsic functional connectivity (ifc) MRI investigates intrinsic connectivity networks (ICN), i.e. large-scale distributed functionally coupled brain regions observed in the absence of a specific task. The objective of our study was to integrate structural connectivity data as assessed by DTI with ifcMRI changes in order to obtain a comprehensive picture of structural and functional changes with an emphasis on motor and basal ganglia thalamic networks. Methods Thirty-five early HD subjects (TFC stage 1 and 2) and 32 age- and sex-matched healthy controls underwent3T-MRI (T1w, DTI and ifcMRI sequences). DTI and ifcMRI data analyses were performed using the Tensor Imaging and Fiber Tracking (TIFT) software ( Müller et al., 2007 ) for complementary DTI fiber tracking (FT) and ifcMRI data analysis. For the motor ICN ifcMRI analyses, the dominant M1 was used as the seed, for the basal ganglia-thalamic ICN the thalamus was used. In addition, the cortico-spinal tract (CST) and the thalamocortical pathway were used for comparisons at the group level. Results Structural connectivity measured by DTI at the group level showed an increase of FA values in the basal ganglia as well as FA reductions in the external and internal capsule, in parts of the thalamus, and in subcortical white matter. Intrinsic functional connectivity (brain function) showed hyper-connectivity in the motor ICN, i.e. the insula was less connected in HD than in controls. The basal ganglia-thalamic ICN connectivity differed between HD and controls in the insula and the basal ganglia in both hemispheres. Conclusion At the group level, we confirmed microstructural changes identified in previous DTI studies in HD (e.g. ( Rosas et al., 2006 )). There is evidence that the insula becomes disconnected from the motor cortex. The caudatum seems to lose its functional integration with widely distributed cortical areas (basal ganglio-thalamic ICN). Abnormal connectivity of the insula and caudatum may be relevant in the emergence of clinical signs of HD. Acknowledgements This work was partially supported by the European Union under the Seventh Framework programme - PADDINGTON Project, Grant Agreement No.261358, and the European Huntington’s Disease Network (EHDN), project 070 - PADDINGTON. [ABSTRACT FROM AUTHOR]

English [ABSTRACT FROM AUTHOR]

2006; 16 (7): 916 - 28. 16 Radakovic R, Abrahams S. Developing a new apathy measurement scale: Dimensional Apathy Scale, Psychiatry Res. 2014; 219 (3): 658 - 63. 17 Huynh W, Ahmed R, Mahoney CJ, et al. Measurement of Social Cognition in Amyotrophic Lateral Sclerosis: A Population Based Study. 7 Girardi A, MacPherson SE, Abrahams S, Deficits in emotional and social cognition in amyotrophic lateral sclerosis, Neuropsychology. [Extracted from the article]

The author focuses on the possible treatment for restless legs syndrome (RLS), a disease which starts to appear way back to the 17th century but still considers to be an eigma of the 21st century. He cites that the International RLS Study Group (IRLSSG) has already proposed four essential diagnostic criteria in order to reduce the number of RLS patients. However, to fully help these patients, he mentions the utilization of one single question which is answerable by just either yes or no.

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. [ABSTRACT FROM AUTHOR]

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, ). 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. [ABSTRACT FROM AUTHOR]

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, ) 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, ) 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 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 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: 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. [ABSTRACT FROM AUTHOR]

Background and purpose: Hereditary spastic paraplegia (HSP) causes progressive gait disturbance because of degeneration of the corticospinal tract. To assess its impact on Health-Related Quality of Life (HRQoL), we analyzed the correlation of HRQoL with disease severity and clinical symptoms in HSP. Methods: HRQoL was assessed by the Short-Form 36 (SF-36) Mental and Physical Component summary scores (MCS and PCS) in 143 German patients with HSP. Disease severity was assessed by the Spastic Paraplegia Rating Scale (SPRS) and landmarks of walking ability. Patients with 'pure' or 'complicated' HSP were compared. Results: Higher SPRS scores indicating higher disease severity correlated significantly with lower PCS ( r = −0.63; P < 0.0005) and MCS ( r = −0.38; P < 0.0005) scores. MCS and PCS were reduced in patients with 'complicated' forms compared to 'pure' HSP and with decreasing walking ability. Conclusion: HRQoL is substantially impaired in patients with HSP and decreases with disease severity and the presence of 'complicating' symptoms. Patients are most affected by the physical restraints of their disease, but mental health is impaired as well. HRQoL is a valid parameter in HSP that should be considered in upcoming therapeutical trials. [ABSTRACT FROM AUTHOR]

In addition to many other symptoms, Huntington’s Disease (HD) also causes an impairment of oculomotor functions. In particular, saccadic eye movements become progressively slower and more difficult to initiate; ultimately, patients are forced to recur to large head thrusts as means to initiate gaze shifts. We wondered whether, as a precursor of this condition, head movements would facilitate gaze shifts already in early stages of the disease. We studied horizontal head movements and eye–head coordination in 29 early stage HD patients (Ps) and 24 age matched controls (Cs). Subjects tracked random horizontal steps of visual or auditory targets while their heads were either stabilised (saccade amplitudes ≤40°) or free to move (amplitudes ≤160°). Subjects were to react either immediately (reactive mode), or wait until a go signal was sounded (delayed mode), or by antisaccades. Ps’ head velocity was found to depend on the age of disease onset in a similar way as their saccadic eye velocity does, being clearly reduced in early affected Ps, but increasing to normal levels in lately affected Ps. Yet, saccade and head velocity were only loosely correlated although both exhibited a negative correlation with the severity of Ps’ genetic condition (number of Ps’ CAG repeats). Eye–head coordination turned out to be identical in Ps and Cs except for quantitative differences caused by the lower saccade and head velocities of Ps. Specifically, the timing between head and eyes and the head contribution to gaze shifts were similar in both groups. Moreover, preventing head movements did not affect the saccade latency or accuracy of Ps. Although Ps made more small involuntary head movements in this condition than Cs, these movements were not instrumental in generating saccades since they occurred only late after saccade onset. Thus, the head manoeuvres of severely affected patients must be considered a late adaptive behaviour. Finally, the ability of both Ps and Cs to suppress immediate reactions in the delayed and antisaccade conditions diminished as target distance decreased, with failure rates in Ps being much larger than in Cs. Unlike eye and head velocity, these failure rates were not correlated with age and, by the same token, neither with the variations in head and eye velocity nor with the number of CAG repeats. Hence, the pattern of brain areas prominently affected by HD is likely to vary significantly among individuals. [ABSTRACT FROM AUTHOR]

Background: SPG10 is an autosomal dominant form of hereditary spastic paraplegia (HSP), which is caused by mutations in the neural kinesin heavy chain KIF5A gene, the neuronal motor of fast anterograde axonal transport. Only four mutations have been identified to date. Objective: To determine the frequency of SPG10 in European families with HSP and to specify the SPG10 phenotype. Patients and methods: 80 index patients from families with autosomal dominant HSP were investigated for SPG10 mutations by direct sequencing of the KIF5A motor domain. Additionally, the whole gene was sequenced in 20 of these families. Results: Three novel KIF5A mutations were detected in German families, including one missense mutation (c.759G>T, p.K253N), one in frame deletion (c.768_770delCAA, p.N256del) and one splice site mutation (c.217G>A). Onset of gait disturbance varied from infancy to 30 years of age. All patients presented clinically with pure HSP, but a subclinical sensory-motor neuropathy was detected by neurophysiology studies. Conclusions: SPG10 accounts for approximately 3% of European autosomal dominant HSP families. All mutations affect the motor domain of kinesin and thus most likely impair axonal transport. Clinically, SPG10 is characterised by spastic paraplegia with mostly subclinical peripheral neuropathy. [ABSTRACT FROM AUTHOR]

The article presents a case study of 61-year-old Caucasian female with a history of Parkinson's disease. It examines the implications for the pathophysiology delusional infestation that is induced with Piribedil add-on. It also notes on the mechanism of actions of two drugs including ropinirole and pramipexole.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction The potential of magnetic resonance imaging (MRI) as a technical biomarker for cerebral alterations is under investigation in neurodegenerative diseases. In this study, a framework for the longitudinal analysis of diffusion tensor imaging (DTI)-based mapping with a series of follow-up scans was applied to longitudinal microstructure assessment of predefined white matter tracts in the course of amyotrophic lateral sclerosis (ALS), as an example for a rapidly progressive neurodegenerative disease. Methods Fifty-four longitudinal DTI datasets from 6 patients with ALS and 3 controls were recorded each 3 months (with up to 15 follow-up scans), yielding a total of 54 longitudinal DTI data sets. After individual alignment and stereotaxic normalization, an averaged DTI data set was created for fibertracking. Fractional anisotropy (FA) values of the tract structures were used to calculate progression rates based on DTI metrics. Results Patients with ALS showed an FA decline along the corticospinal tract (CST) which has been identified as the first affected tract structure in ALS and as the tract correlating with Braak‘s neuropathological stage 1 ( Kassubek et al., 2014 ). FA of controls remained stable in longitudinal DTI scans, whereas, FA decrease progression in the CST ranged from 0.5% to 6% per year in ALS-patients, i.e. four patients showed low progression rates between 0.5% and 2% per year and two patients showed fast progression rates between 3% and 6% per year. The ALS-FRS-R decline correlated significantly with FA decline over time. Conclusion On the basis of the longitudinal DTI data assessment with multiple follow-up measures, FA values were shown to be an in vivo marker for ALS-associated disease progression. That way, imaging-based progression rates at the individual patient level can be determined from DTI scans. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: The neuropathological process underlying amyotrophic lateral sclerosis (ALS) can be classified as a four-stage propagation scheme. An in vivo transfer of these stages using diffusion tensor imaging (DTI) in specific tract systems has been established [1]. Since cognitive functions are closely linked to microstructural changes, an analogous classification into four cognitive stages, with high congruence to DTI stages, was demonstrated [2]. Alterations in oculomotor functions in ALS can be characterized by two stages in oculomotor parameters [3]. The objective of the current study is to show congruence of methods by combining neuroimaging, cognitive testing, and video-oculography (VOG) and to potentially improve in vivo staging classification. Methods: A total of 4 microstructural, 2 cognitive, and 9 oculomotor parameters were obtained from each of 193 patients with ALS. To this end, patients underwent VOG und cognitive testing using Edinburgh Cognitive and Behavioural ALS Screen (ECAS). The regional fractional anisotropy (FA) of the tract systems involved in ALS [1] were studied using a tract-of-interest (TOI)-based approach. After z-standardization of all parameters, principal component analysis was performed. Hierarchical and k -means clustering of principal components was used to obtain an optimal cluster solution. Results: After reducing the considered parameters to four uncorrelated principal components, the patients were iteratively merged using pairwise distances. A division of patients into four clusters was used for further analysis. These clusters were different with regard to FA values during the progression of ALS-associated tract systems. Cluster 1 showed the highest FA values and thereby the best performances in executive VOG (e.g. performing correct anti-saccades) and cognitive tests, whereas ALS patients in cluster 4 showed lower FA values, lower ECAS scores and worse executive VOG performance. Patients in clusters 2 and 3 showed lower FA values compared to cluster 1 and higher FA values compared to cluster 4, while cognitive and executive VOG performance were altered only in cluster 2 compared to cluster 1. Conclusion: Cluster analysis of multimodal parameters, incorporating DTI, neuropsychologic testing, and VOG, showed high congruence of methodological approaches in ALS. References [1] Kassubek J et al. J Neurol Neurosurg Psychiatry 2018; 89:374-381. [2] Lulé D et al. Cortex 2018; 101:163-171. [3] Gorges M et al. PLoSOne 2015; 10:e0142546. [Display omitted] [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction. For progressive supranuclear palsy (PSP), oculomotor function is one of the core features on which the diagnosis is based upon according to the diagnostic criteria by the Movement Disorder Society (MDS) supported PSP-Study-Group from 2017 ("O criterion"). The aim of this study was to analyze the value of specific oculomotor parameters. Material/Method. An analysis of the videooculographic examinations of smooth pursuit eye movements and visually guided reactive saccades in 100 PSP patients and 49 matched control subjects was performed. Group differences as well as correlations were tested at a two-sided level α=0.05. Cut-off values for the development of new subgroups were defined by the fifth or 95th percentile of specific parameters of the control group. ROC-analyses were used to determine sensitivity and specificity. Results. Each of the investigated oculomotor parameters (for smooth pursuit eye movements gain, for saccades latency, gain, peak eye velocity, asymmetry of velocities up- and downwards, rate of saccadic intrusions (SI)) was significantly altered in PSP compared with the control population (p<0.0001 each). The threshold for vertical saccade velocity was approximately 240°/s for both components so that about 70% of the patients could be captured. A cut-off value of 9.60°/s was determined for SI, and approximately 56% of the patients achieved higher values. By combining both parameters, almost 80% of the patients could be classified. With regard to the specifically calculated asymmetry of the vertical saccade velocities, 34% of the patients were abnormal at a threshold of 0.42 (overview in Fig. 1). The majority of patients (63.5%) performed faster downward than upward saccades. The vertical saccade velocity and SI had a high specificity of more than 95%, while sensitivity was maximally 60% for the velocity components and 54.2% for the SI. At similar specificity, the asymmetry reached a sensitivity of 27.1%. Discussion. The results for vertical saccade velocity and SI, respectively, emphasized their relevance as part of the MDS-PSP diagnostic criteria, whereas the significance of the asymmetry of the vertical velocities was limited. With respect to directional tendency, the findings are still heterogeneous. In future evaluations, unbiased quantifications of clinical parameters offer a good possibility to further develop the quality of the diagnostic procedures used for PSP. ▪ Fig. 1. [ABSTRACT FROM AUTHOR]

BackgroundDepressive symptoms are prominent psychopathological features of Huntington's disease (HD), making a negative impact on social functioning and well-being.MethodWe 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).ResultsFrequencies 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.ConclusionsCurrent 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Objective: Knowledge of patients' treatment needs is an important requirement for comprehensive long-term patient care. The objective of this investigation was to assess the requirements of patients with Parkinson's disease (PD) regarding pharmacotherapy. Methods: A total of 17,500 members of the German Parkinson Association were given the opportunity to anonymously answer a questionnaire about their health-related quality of life, PD pharmacotherapy and their improvement suggestions for new PD medication. Results: Answers from 6351 patients were available for analysis. The majority (87.2%) of patients were older than 60 years; 88.9% had been diagnosed with PD for longer than 3 years and 84.4% selected one of the three most severe categories (categories 1-3 on a 6-point scale) when rating the impact of PD on their quality of life. Symptoms that were regarded as very important for improvement with pharmacotherapy included motor fluctuations (66.3%), early morning akinesia (55.4%) and sleep disturbances (43.5%). Properties of a new PD medication that were rated as very important included continuous drug delivery over 24 hours (66.6%) and 24-hour symptom control (55.8%). The majority of patients used physicians (84.2%) and/or self-help groups (69.4%) to obtain information about PD. Topics of particular interest included comorbid diseases (78.3%), mobility and exercise (77.3%) and research (53%). Conclusion: PD has a major impact on patients' quality of life. From the patient's perspective, PD pharmacotherapy needs to address a range of symptoms including not only motor symptoms, but also non-motor symptoms such as sleep disturbances. In selecting the most appropriate treatment regimen, patient preference is an important consideration. [ABSTRACT FROM AUTHOR]