Neuropsychology and MRI correlates of neurodegeneration in SPG11 hereditary spastic paraplegia.

BACKGROUND: SPG11-linked hereditary spastic paraplegia is characterized by multisystem neurodegeneration leading to a complex clinical and yet incurable phenotype of progressive spasticity and weakness. Severe cognitive symptoms are present in the majority of SPG11 patients, but a systematic and multidimensional analysis of the neuropsychological phenotype in a larger cohort is lacking. While thinning of the corpus callosum is a well-known structural hallmark observed in SPG11 patients, the neuroanatomical pattern of cortical degeneration is less understood. We here aimed to integrate neuropsychological and brain morphometric measures in SPG11. METHODS: We examined the neuropsychological profile in 16 SPG11 patients using a defined neuropsychological testing battery. Long-term follow up testing was performed in 7 patients. Cortical and subcortical degeneration was analyzed using an approved, artificial intelligence based magnetic resonance imaging brain morphometry, comparing patients to established reference values and to matched controls. RESULTS: In SPG11 patients, verbal fluency and memory as well as frontal-executive functions were severely impaired. Later disease stages were associated with a global pattern of impairments. Interestingly, reaction times correlated significantly with disease progression. Brain morphometry showed a significant reduction of cortical and subcortical parenchymal volume following a rostro-caudal gradient in SPG11. Whereas performance in memory tasks correlated with white matter damage, verbal fluency measures showed strong associations with frontal and parietal cortical volumes. CONCLUSIONS: The present data will help define neuropsychological and imaging read out parameters in early as well as in advanced clinical stages for future interventional trials in SPG11.

A Multisensory Deficit in the Perception of Pleasantness in Parkinson's Disease.

BACKGROUND: There is growing interest in non-motor symptoms in Parkinson's disease (PD), due to the impact on quality of life. Anhedonia, the inability to experience joy and lust, has a prevalence of up to 46% in PD. The perception of pleasantness of an odor is reduced in anhedonia without PD. We previously showed a reduced hedonic olfactory perception in PD, i.e., patients evaluated odors as less pleasant or unpleasant compared to controls. This deficit correlated with anhedonia. OBJECTIVE: We aimed to confirm these findings. Moreover, we hypothesized that the perception of pleasantness in PD is affected on a multisensory level and correlates with anhedonia. Therefore, we assessed olfactory, visual and acoustic evaluation of pleasantness in PD and healthy individuals. METHODS: Participants had to rate the pleasantness of 22 odors, pictures, and sounds on a nine-point Likert scale. Depression, anhedonia, and apathy were assessed by means of questionnaires. Results of the pleasantness-rating were compared between groups and correlated to scores of the questionnaires. RESULTS: In particular pleasant and unpleasant stimuli across all three modalities are perceived less intense in PD, suggesting that a reduced range of perception of pleasantness is a multisensory phenomenon. However, only a reduction of visual hedonic perception correlated with anhedonia in PD. A correlation of reduced perception of pleasantness with apathy or depression was not present. CONCLUSION: We provide evidence for a multisensory deficit in the perception of pleasantness. Further studies should delineate the underlying neural circuity and the diagnostic value to detect neuropsychiatric symptoms in PD.

Longer-term effects of intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy: Who benefits?

Intravenous immunoglobulins (IVIg) represent an established cornerstone for the immunotherapy of chronic inflammatory demyelinating polyneuropathy (CIDP). Efficacy of IVIg for CIDP was proven in a large phase III trial. Yet, data on longer-term efficacy and effects in distinct subgroups are scarce. Our trial investigates the long-term efficacy of IVIg treatment in CIDP patients. In this observational real-world study, we retrospectively analyzed 49 CIDP patients receiving continuous IVIg treatment with a mean initial dosage of 87 g (1 g/kg body weight) every 4 weeks over a mean time of 45 months between 2010 and 2018. INCAT-Scores before the start of treatment and at the end of the observation period were compared. Over the observation period, IVIg treatment led to a median improvement of one INCAT score point. Subgroup analyses revealed a more pronounced improvement of INCAT scores in female CIDP patients, individuals with relapsing disease courses, patients with more pronounced motor impairment (higher initial INCAT scores) and in the cohort without need for concomitant other immunotherapies. These data argue for sustained beneficial effects of longer-term immunotherapy with IVIg in CIDP, particularly in females and relapsing disease forms with higher disease activity.

Real world application of ocrelizumab in multiple sclerosis: Single-center experience of 128 patients.

BACKGROUND: Pivotal trials showed good clinical efficiency of the monoclonal antibody ocrelizumab while being well tolerated and manageable in multiple sclerosis (MS). However, data on adverse events in everyday practice are scarce. Hence, our study aims at investigating short-term tolerability of ocrelizumab in a "real-world" setting. METHODS: In this retrospective cohort study, data of 128 (86 relapsing-remitting, 42 progressive) MS patients at initiation of ocrelizumab were analyzed at the MS center of the University of Erlangen, Germany. Additionally, follow-up data of 68 patients at 6-months retreatment were analyzed. Structured phone interviews were applied after ocrelizumab initiation to report undocumented side effects. RESULTS: Patients predominantly switched from monoclonal antibodies (46%), orals (20%), injectables (10%), steroids or immunosuppressants (each 8%), with a mean interval of 9.0 months after the last application of the previous immunotherapy. Applying a combined premedication with steroids, antihistamines and antipyretics for >90% of patients, ocrelizumab treatment was well tolerated and mainly comprised mild (n = 59/128 at initiation, n = 5/68 at 6 months retreatment) and rarely moderate (n = 7/128 at initiation, n = 2/68 at 6 months) side effects. Predominantly mild infusion related reactions (IRR) were reported with a declining percentage over the follow-up applications. Infections occurred rarely. No severe side effects were observed. Secondary, treatment appeared efficient when looking at clinical surrogates of stable disease. DISCUSSION: Our study delineates good short-term tolerability of ocrelizumab in a miscellaneous "real-world" MS cohort. Additional studies are warranted to confirm these beneficial findings and to reveal safety concerns in the longer-term follow-up.

Posttraumatic stress disorder in patients after transient ischemic attack: A one-year follow-up.

OBJECTIVE: We aimed to determine the prevalence of posttraumatic stress disorder (PTSD) 12 months after transient ischemic attack (TIA). METHOD: TIA patients of our previous investigation (examined 3 months after the event) were again examined 12 months after the diagnosis. PTSD and associated variables were assessed via self-rating instruments. RESULTS: Eighty-four patients were included in the analyses. Twelve months after TIA the prevalence of probable PTSD was reduced (8.3%) compared to that found 3 months after TIA (29.6%). Coping assessed 3 months after TIA predicted long-term PTSD severity. CONCLUSION: Although the prevalence of probable PTSD decreased 12 months after experiencing a TIA compared to 3 months after TIA, prevalence of probable PTSD is still increased relative to that in the general population.

No evidence of disease activity status over 3 years in a real-world cohort of relapsing remitting MS patients in Germany.

BACKGROUND: Over the last decade, therapy of relapsing remitting multiple sclerosis (RRMS) has evolved with the approval of several new treatment concepts. Thus, treatment goals have become more ambitious aiming at "no evidence of disease activity" (NEDA). As NEDA-3, this concept comprises freedom of clinical disease progression and relapses as well as inflammatory MRI activity. So far, data on NEDA status mainly stem from post-hoc analyses of drug approval studies. Yet, less is known about the significance of NEDA in "real-world" clinical settings. Hence, our study aims at investigation of NEDA in a heterogeneous cohort of relapsing MS patients. METHODS: This is a retrospective single-center study at the Department of Neurology of the University Hospital Erlangen, Germany, including data of 306 patients with relapsing forms of MS (RMS) or clinical isolated syndrome (CIS) from 2009 to 2016. Inclusion required sufficient clinical information and in house cranial MRI follow-up data sets at baseline and at follow-up after one year with a potential extension to two and three year follow-up, if possible. NEDA-3 status, its correlation to clinical features, associated medication and NEDA failure (EDA) were analyzed. RESULTS: In a cohort of RMS patients at the early stages of the disease (median EDSS 1.5, mean disease duration 30 months) at baseline, 45% retained NEDA-3 status after one year. This percentage decreased in year two (29%) and three (21%) of follow-up. MRI criteria were responsible for loss of NEDA status in 64% of cases and CIS patients were more likely to sustain NEDA status. Therapy with monoclonal antibodies appeared superior in sustaining NEDA status as compared to injectables or oral treatment options. DISCUSSION: In our real-world analysis, we confirm the potential of NEDA for the evaluation and surveillance of MS disease activity, progression and therapy efficacy. Despite highly efficient immunomodulatory treatment, NEDA-3 was only preserved in a minority of patients. Monoclonal antibodies may yield best NEDA rates. Further studies are warranted to evaluate the value of the NEDA concept in real-world settings beyond standardized clinical studies.

Visual feedback explains why propointing is better than antipointing in spatial neglect.

Rossit et al. (2011) showed that neglect patients perform normally in a propointing task but not in an antipointing task which requires pointing towards the mirrored position of a target. It is assumed that antipointing relies on information from the perceptual pathway of our visual brain. Therefore, this finding supports the notion that neglect is a disorder that primarily affects perceptual spatial representations within the brain leaving spatial maps used for visuomotor guidance intact. Alternatively, performance of patients might be compromised in both tasks, but only obviously so in tasks in which online corrections are made more difficult. It can be argued that online-corrections via visual feedback are less effective in antipointing because a direct comparison between hand and target is not possible in this condition. Secondly, it is also known that neglect patients have a pronounced egocentric bias which is assumed to be associated with a deviation of the perceived body midline. Since the midline is used to compute the end-position in the antipointing task this could also explain why patients are worse in antipointing. We investigated the influence of visual feedback on pro- and antipointing and the effect of providing a visual reference line for the antipointing task in right-brain damaged patients with neglect (n = 20), right-brain damaged patients without neglect (n = 23) and in a group of healthy participants (n = 22). The withdrawal of visual feedback had a stronger effect on propointing compared to antipointing. This effect was stronger in neglect patients than in patients without neglect or healthy controls. The introduction of a reference line reduced errors in antipointing performance, particularly in neglect patients with a strong egocentric bias. The results support our alternative account and challenge the hypothesis that the spatial disorder in neglect affects primarily perceptual maps within the visual system.

Violations of Weber's law tell us more about methodological challenges in sensorimotor research than about the neural correlates of visual behaviour.

The violation of Weber's law in grasping has been presented as evidence for the claim that grasping is guided by visual information which is distinct from the information used in perceptual tasks. Previously, we contested this claim and argued that biomechanical constraints of the hand might explain why Weber's law cannot be reliably uncovered in grasping movements. In a recent article Manzone and colleagues (2017) show that pantomime grasping follows Weber's law even with objects whose width is close to the hand's biomechanical limit. In this commentary we explain why the biomechanical account does not necessarily predict the violation of Weber's law in a pantomime grasping task and why it seems problematic to use adherence or violation of Weber's law as a criterion to assign tasks to different anatomical pathways.

Cognitive functions over the course of 1 year in multiple sclerosis patients treated with disease modifying therapies.

OBJECTIVES: Disease-modifying therapies (DMTs) are applied to delay or prevent disease progression in multiple sclerosis (MS). While this has mostly been proven for physical symptoms, available studies regarding long-term effects of DMTs on cognitive functions are rare and sometimes inconsistent due to methodological shortcomings. Particularly in the case of fingolimod, comprehensive data on cognitive functions are not yet available. Therefore, we set out to reliably assess cognitive functions in patients with relapsing-remitting MS (RRMS) treated with DMTs over 1 year. METHODS: Cognitive functions were assessed with eight tests at three timepoints: baseline, 6-month follow up and 12-month follow up. First, we investigated whether the stability of cognitive functions (i.e. not falling below the 5% cut-off in more than one test) over 1 year in RRMS patients (n = 41) corresponds to the stability in healthy individuals (n = 40) of a previous study. Second, we compared the percentage of declined and improved patients in the different tests. Third, we compared patients treated with fingolimod (n = 22) with patients treated with natalizumab (n = 11) with regard to cognitive stability. Fourth, based on the patient data, the Reliable Change Index was applied to compute cut-offs for reliable cognitive change. RESULTS: Approximately 75% of RRMS patients treated with DMTs remained stable over the course of 1 year. The Paced Auditory Serial Addition Test (PASAT) and the Spatial Recall Test (SPART), produced improvements in 12.5% and 30.6%, respectively, probably due to practice effects. Patients treated with fingolimod did not differ from patients treated with natalizumab with regard to cognitive stability. CONCLUSIONS: Cognitive functions remain relatively stable under DMT treatment over 1 year, irrespective of the type of medication. Furthermore, the tests PASAT and SPART should be interpreted cautiously in studies examining performance changes over time. The provided RCI norms may help clinicians to determine whether a difference in two measurements observed in a RRMS patient is reliable.

Biomechanical factors may explain why grasping violates Weber's law.

For grasping, Ganel, Chajut, and Algom (2008) demonstrated that the variability of the maximum grip aperture (MGA) does not increase with the size of the target object. This seems to violate Weber's law, a fundamental law of psychophysics. They concluded that the visual representations guiding grasping are distinct from representations used for perceptual judgments. Weber's law is however only relevant for one component of the measurable variability of MGA, namely the variability in the sensory system. We argue that when looking at the relationship between object size and grasping, the gain (often called slope) governing the relationship between target size and MGA can be used as an approximation to estimate the contribution of sensory noise to MGA variability. To test the idea that differences in gain modulate the relationship between target size and MGA variability, we examined grasping under a variety of conditions. We found that gain varied quite significantly across different tasks, but irrespective of gain Weber's law could not be found in any of the grasping tasks. Instead we repeatedly found an inverse relationship between variability and object size, i.e. variability decreased for bigger objects. This trend may reflect the reduced biomechanical freedom found for movements at the end an effector's effective range of motion. MGA variability may thus be dominated by non-sensory factors and therefore may constitute a poor choice to estimate the variability of the visual signals used by the brain to guide our grasping actions.

Subliminal galvanic-vestibular stimulation recalibrates the distorted visual and tactile subjective vertical in right-sided stroke.

Stroke of the right cerebral hemisphere often causes deficits in the judgement of the subjective visual vertical (SVV) and subjective tactile vertical (STV) which are related to central vestibular functioning. Clinically, deficits in the SVV/STV are linked to balance problems and poor functional outcome. Galvanic Vestibular Stimulation (GVS) is a non-invasive, save stimulation technique that induces polarity-specific changes in the cortical vestibular systems. Subliminal GVS induces imperceptible vestibular stimulation without unpleasant side effects. Here, we applied bipolar subliminal GVS over the mastoids (mean intensity: 0.7 mA, 20 min duration per session) to investigate its online-influence on constant errors, difference thresholds and range values in the SVV and STV. 24 patients with subacute, single, unilateral right hemisphere stroke were studied and assigned to two patient groups (impaired vs. normal in the SVV and STV) on the basis of cut-off scores from healthy controls. Both groups performed these tasks under three experimental conditions on three different days: a) sham GVS where electric current was applied only for 30s and then turned off, b) left-cathodal GVS and c) right-cathodal GVS, for a period of 20 min per session. Left-cathodal GVS, but not right-cathodal GVS significantly reduced all parameters in the SVV. Concerning STV GVS also reduced constant error and range numerically, though not significantly. These effects occurred selectively in the impaired patient group. In conclusion, we found that GVS rapidly influences poststroke verticality deficits in the visual and tactile modality, thus highlighting the importance of the vestibular system in the multimodal elaboration of the subjective vertical.

Baseline magnetic resonance imaging of the optic nerve provides limited predictive information on short-term recovery after acute optic neuritis.

BACKGROUND: In acute optic neuritis, magnetic resonance imaging (MRI) may help to confirm the diagnosis as well as to exclude alternative diagnoses. Yet, little is known on the value of optic nerve imaging for predicting clinical symptoms or therapeutic outcome. PURPOSE: To evaluate the benefit of optic nerve MRI for predicting response to appropriate therapy and recovery of visual acuity. METHODS: Clinical data as well as visual evoked potentials (VEP) and MRI results of 104 patients, who were treated at the Department of Neurology with clinically definite optic neuritis between December 2010 and September 2012 were retrospectively reviewed including a follow up within 14 days. RESULTS: Both length of the Gd enhancing lesion (r = -0.38; p = 0.001) and the T2 lesion (r = -0.25; p = 0.03) of the optic nerve in acute optic neuritis showed a medium correlation with visual acuity after treatment. Although visual acuity pre-treatment was little but nonsignificantly lower if Gd enhancement of the optic nerve was detected via orbital MRI, improvement of visual acuity after adequate therapy was significantly better (0.40 vs. 0.24; p = 0.04). Intraorbitally located Gd enhancing lesions were associated with worse visual improvement compared to canalicular, intracranial and chiasmal lesions (0.35 vs. 0.54; p = 0.02). CONCLUSION: Orbital MRI is a broadly available, valuable tool for predicting the improvement of visual function. While the accurate individual prediction of long-term outcomes after appropriate therapy still remains difficult, lesion length of Gd enhancement and T2 lesion contribute to its prediction and a better short-term visual outcome may be associated with detection and localization of Gd enhancement along the optic nerve.

Patient preferences for disease-modifying drugs in multiple sclerosis therapy: a choice-based conjoint analysis.

OBJECTIVES: With an increasing number of disease-modifying treatments (DMTs) for multiple sclerosis (MS), patient preferences will gain importance in the decision-making process. We assessed patients' implicit preferences for oral versus parenteral DMTs and identified factors influencing patients' treatment preference. METHODS: Patients with relapsing-remitting MS (n = 156) completed a questionnaire assessing treatment preferences, whereby they had to decide between pairs of hypothetical treatment scenarios. Based on this questionnaire a choice-based conjoint analysis was conducted. RESULTS: Treatment frequency and route of administration showed a stronger influence on patient preference compared with frequency of mild side effects. The latter attribute was more important for treatment-naïve patients compared with DMT-experienced patients. The higher the Extended Disability Status Scale score, the more likely pills, and the less likely fewer side effects were preferred. Pills were preferred over injections by 93% of patients, when treatment frequency and frequency of side effects were held constant. However, preference switched to injections when pills had to be taken three times daily and injections only once per week. Injections were also preferred when pills were associated with frequent side effects. CONCLUSIONS: Our results suggest that route of administration and treatment frequency play an important role in the patients' preference for a given DMT.

Increased prevalence of posttraumatic stress disorder in patients after transient ischemic attack.

BACKGROUND AND PURPOSE: A transient ischemic attack (TIA) involves temporary neurological symptoms but leaves a patient symptom-free. Patients are faced with an increased risk for future stroke, and the manifestation of the TIA itself might be experienced as traumatizing. We aimed to investigate the prevalence of posttraumatic stress disorder (PTSD) after TIA and its relation to patients' psychosocial outcome. METHODS: Patients with TIA were prospectively studied, and 3 months after the diagnosis, PTSD, anxiety, depression, quality of life, coping strategies, and medical knowledge were assessed via self-rating instruments. RESULTS: Of 211 patients with TIA, data of 108 patients were complete and only those are reported. Thirty-two (29.6%) patients were classified as having PTSD. This rate is 10× as high as in the general German population. Patients with TIA with PTSD were more likely to show signs of anxiety and depression. PTSD was associated with the use of maladaptive coping strategies, subjectively rated high stroke risk, as well as with younger age. Finally, PTSD and anxiety were associated with decreased mental quality of life. CONCLUSIONS: The experience of TIA increases the risk for PTSD and associated anxiety, depression, and reduced mental quality of life. Because a maladaptive coping style and a subjectively overestimated stroke risk seem to play a crucial role in this adverse progression, the training of adaptive coping strategies and cautious briefing about the realistic stroke risk associated with TIA might be a promising approach. Despite the great loss of patients to follow-up, the results indicate that PTSD after TIA requires increased attention.

Visual search as a tool for a quick and reliable assessment of cognitive functions in patients with multiple sclerosis.

BACKGROUND: Despite the high frequency of cognitive impairment in multiple sclerosis, its assessment has not gained entrance into clinical routine yet, due to lack of time-saving and suitable tests for patients with multiple sclerosis. OBJECTIVE: The aim of the study was to compare the paradigm of visual search with neuropsychological standard tests, in order to identify the test that discriminates best between patients with multiple sclerosis and healthy individuals concerning cognitive functions, without being susceptible to practice effects. METHODS: Patients with relapsing remitting multiple sclerosis (n = 38) and age-and gender-matched healthy individuals (n = 40) were tested with common neuropsychological tests and a computer-based visual search task, whereby a target stimulus has to be detected amongst distracting stimuli on a touch screen. Twenty-eight of the healthy individuals were re-tested in order to determine potential practice effects. RESULTS: Mean reaction time reflecting visual attention and movement time indicating motor execution in the visual search task discriminated best between healthy individuals and patients with multiple sclerosis, without practice effects. CONCLUSIONS: Visual search is a promising instrument for the assessment of cognitive functions and potentially cognitive changes in patients with multiple sclerosis thanks to its good discriminatory power and insusceptibility to practice effects.

Now You Feel both: Galvanic Vestibular Stimulation Induces Lasting Improvements in the Rehabilitation of Chronic Tactile Extinction.

Tactile extinction is frequent, debilitating, and often persistent after brain damage. Currently, there is no treatment available for this disorder. In two previous case studies we showed an influence of galvanic vestibular stimulation (GVS) on tactile extinction. Here, we evaluated in further patients the immediate and lasting effects of GVS on tactile extinction. GVS is known to induce polarity-specific changes in cerebral excitability in the vestibular cortices and adjacent cortical areas. Tactile extinction was examined with the Quality Extinction Test (QET) where subjects have to discriminate six different tactile fabrics in bilateral, double simultaneous stimulations on their dorsum of hands with identical or different tactile fabrics. Twelve patients with stable left-sided tactile extinction after unilateral right-hemisphere lesions were divided into two groups. The GVS group (N = 6) performed the QET under six different experimental conditions (two Baselines, Sham-GVS, left-cathodal/right-anodal GVS, right-cathodal/left-anodal GVS, and a Follow-up test). The second group of patients with left-sided extinction (N = 6) performed the QET six times repetitively, but without receiving GVS (control group). Both right-cathodal/left-anodal as well as left-cathodal/right-anodal GVS (mean: 0.7 mA) improved tactile identification of identical and different stimuli in the experimental group. These results show a generic effect of GVS on tactile extinction, but not in a polarity-specific way. These observed effects persisted at follow-up. Sham-GVS had no significant effect on extinction. In the control group, no significant improvements were seen in the QET after the six measurements of the QET, thus ruling out test repetition effects. In conclusion, GVS improved bodily awareness permanently for the contralesional body side in patients with tactile extinction and thus offers a novel treatment option for these patients.

Galvanic vestibular stimulation improves arm position sense in spatial neglect: a sham-stimulation-controlled study.

BACKGROUND: Disturbed arm position sense (APS) is a frequent and debilitating condition in patients with hemiparesis after stroke. Patients with neglect, in particular, show a significantly impaired contralesional APS. Currently, there is no treatment available for this disorder. Galvanic vestibular stimulation (GVS) may ameliorate neglect and extinction by activating the thalamocortical network. OBJECTIVE: The present study aimed to investigate the immediate effects and aftereffects (AEs; 20 minutes) of subsensory, bipolar GVS (M = 0.6 mA current intensity) on APS in stroke patients with versus without spatial neglect and matched healthy controls. METHODS: A novel optoelectronic arm position device was developed, enabling the precise measurement of the horizontal APS of both arms. In all, 10 healthy controls, 7 patients with left-sided hemiparesis and left-spatial neglect, and 15 patients with left hemiparesis but without neglect were tested. Horizontal APS was measured separately for both forearms under 4 experimental conditions (baseline without GVS, left-cathodal/right-anodal GVS, right-cathodal/left-anodal GVS, sham GVS). The immediate effects during GVS and the AEs 20 minutes after termination of GVS were examined. RESULTS: Patients with neglect showed an impaired contralateral APS in contrast to patients without neglect and healthy controls. Left-cathodal/right-anodal GVS improved left APS significantly, which further improved into the normal range 20 minutes poststimulation. GVS had no effect in patients without neglect but right-cathodal/left-anodal GVS worsened left APS in healthy participants significantly. CONCLUSIONS: GVS can significantly improve the impaired APS in neglect. Multisession GVS can be tested to induce enduring therapeutic effects.

Effects of feedback-based visual line-orientation discrimination training for visuospatial disorders after stroke.

BACKGROUND: Patients with right or more rarely left parietotemporal lesions after stroke may have profound visuospatial disorders that impair activities of daily living (ADL) and long-term outcome. Clinical studies indicate improvements with systematic training of perception. Studies of perceptual learning in healthy persons suggest rapid improvements in perceptual learning of spatial line orientation with partial transfer to nontrained line orientations. OBJECTIVE: The authors investigated a novel feedback-based perceptual training procedure for the rehabilitation of patients after stroke. METHODS: In an uncontrolled trial, 13 participants showing profound deficits in line orientation and related visuospatial tasks within 12 to 28 weeks of onset performed repetitive feedback-based, computerized training of visual line orientation over 4 weeks of treatment. Visual line-orientation discrimination and visuospatial and visuoconstructive tasks were assessed before and after training. RESULTS: The authors found (a) rapid improvements in trained but also in nontrained spatial orientation tests in all 13 participants, partially up to a normal level; (b) stability of the obtained improvements at 2-month follow-up; (c) interocular transfer of training effects to the nontrained eye in 2 participants suggesting a central, postchiasmatic locus for this perceptual improvement; and (d) graded transfer of improvements to related spatial tasks, such as horizontal writing, analog clock reading, and visuoconstructive capacities but no transfer to unrelated measures of visual performance. CONCLUSIONS: These results suggest the potential for treatment-induced improvements in visuospatial deficits by feedback-based, perceptual orientation training as a component of rehabilitation after stroke.

Minor adverse effects of galvanic vestibular stimulation in persons with stroke and healthy individuals.

OBJECTIVE: Galvanic vestibular stimulation (GVS) induces polarity-specific activations in the vestibular nerves and upstream in the vestibular and parietotemporal cortices as well as sub-cortical regions. This makes it an attractive technique for cognitive neuromodulation. However, systematic studies regarding adverse effects of GVS are unavailable. Thus, this study assessed adverse effects during and after sub-sensory GVS (mean: 0.6 mA) and GVS with 1.5 mA. METHODS: Two hundred and fifty-five GVS sessions delivered to 55 persons with stroke and 30 healthy individuals were analysed using a 34-item-questionnaire including potential symptoms and rating scales for adverse effects. RESULTS: The most frequent symptoms during and after GVS were slight itching (mean: 10.2%) and tingling (mean: 10.7%) underneath the electrodes. Healthy individuals and persons with stroke did not differ in their incidence and rated intensity of adverse effects, nor did persons with or without unilateral spatial neglect. Adverse effects were found more frequently with GVS with 1.5 mA as with sub-sensory GVS. Participants were unable to differentiate real from sham conditions during sub-sensory GVS. Importantly, neither seizures nor vertigo or nausea were observed. CONCLUSION: Sub-sensory GVS and GVS with 1.5 mA induce very few and mild adverse effects in healthy and persons with stroke and are safe when safety guidelines are followed.