Brain fog in neuropathic postural tachycardia syndrome may be associated with autonomic hyperarousal and improves after water drinking.

Brain fog is a common and highly disturbing symptom for patients with neuropathic postural tachycardia syndrome (POTS). Cognitive deficits have been measured exclusively in the upright body position and mainly comprised impairments of higher cognitive functions. The cause of brain fog is still unclear today. This study aimed to investigate whether increased autonomic activation might be an underlying mechanism for the occurrence of brain fog in neuropathic POTS. We therefore investigated cognitive function in patients with neuropathic POTS and a healthy control group depending on body position and in relation to catecholamine release as a sensitive indicator of acute stress. The second aim was to test the effect of water intake on cardiovascular regulation, orthostatic symptoms, cognitive function and catecholamine release. Thirteen patients with neuropathic POTS and 15 healthy control subjects were included. All participants completed a total of four rounds of cognitive testing: two before and two after the intake of 500 ml still water, each first in the supine position and then during head-up tilt. At the end of each cognitive test, a blood sample was collected for determination of plasma catecholamines. After each head-up tilt phase participants were asked to rate their current symptoms on a visual analogue scale. Working memory performance in the upright body position was impaired in patients, which was associated with self-reported symptom severity. Patients had elevated plasma norepinephrine independent of body position and water intake that increased excessively in the upright body position. The excessive increase of plasma norepinephrine was related to heart rate and symptom severity. Water intake in patients decreased norepinephrine concentrations and heart rate, and improved symptoms as well as cognitive performance. Brain fog and symptom severity in neuropathic POTS are paralleled by an excessive norepinephrine secretion. Bolus water drinking down-regulates norepinephrine secretion and improves general symptom severity including brain fog

Single-pulse transcranial magnetic stimulation of parietal and prefrontal areas in a memory delay arm pointing task

Fifteen healthy volunteers performed a memory-pointing task using their right arm while single-pulse transcranial magnetic stimulation (TMS) above motor threshold was applied over the posterior parietal or prefrontal cortex of the left or right hemisphere in four blocks of trials. The stimulation was randomly delivered at one of three time intervals during the 3-s delay period (early: 300 ms, intermediate: 1,500 ms, late: 2,700 ms). A separate block with no stimulation was used as control. Only early left parietal stimulation resulted in an increase in the variance of movement amplitude but not direction for all targets in two-dimensional space (both hemifields). The results point to the significance of the contralateral posterior parietal cortex early on during the memorization of the target for an upcoming movement. Taking into consideration the limitations of TMS and those imposed by the particular task, the lack of specific effects of prefrontal stimulation provides evidence that these areas might not be involved in the performance of simple memorized arm movements

Screening for Language Disorders in Stroke: German Validation of the Language Screening Test (LAST)

Background: Screening of aphasia in acute stroke is crucial for directing patients to early language therapy. The Language Screening Test (LAST), originally developed in French, is a validated language screening test that allows detection of a language deficit within a few minutes. The aim of the present study was to develop and validate two parallel German versions of the LAST. Methods: The LAST includes subtests for naming, repetition, automatic speech, and comprehension. For the translation into German, task constructs and psycholinguistic criteria for item selection were identical to the French LAST. A cohort of 101 stroke patients were tested, all of whom were native German speakers. Validation of the LAST was based on (1) analysis of equivalence of the German versions, which was established by administering both versions successively in a subset of patients, (2) internal validity by means of internal consistency analysis, and (3) external validity by comparison with the short version of the Token Test in another subset of patients. Results: The two German versions were equivalent as demonstrated by a high intraclass correlation coefficient of 0.91. Furthermore, an acceptable internal structure of the LAST was found (Cronbach's α = 0.74). A highly significant correlation (r = 0.74, p Conclusion: The German version of the LAST, available in two parallel versions, is a new and valid language screening test in stroke

Auditory spatial cueing reduces neglect after right-hemispheric stroke: a proof of concept study

Spatial neglect after right-hemispheric stroke, characterized by the failure to attend or respond to the contralesional space, is a strong negative outcome predictor. Neglect is a supramodal syn-drome affecting not only the visual but also the auditory modality. Preliminary studies used this audio-visual cross-modal effect to show short-lasting effects on attention towards the neglected space. The aim of the present study was to introduce a new technique of auditory stimulation combining the unspecific effect of music (i.e. patients choose their preferred music) with the effects of auditory spatial cueing (i.e. the music is presented dynamically as moving from right to left). The effect of this new auditory stimulation technique was investigated in two proof-of-concept experiments using repeated-measures, cross-over designs including overall 21 patients with visual neglect after a first right-hemispheric stroke. In experiment I (n=9), neglect patients showed a significantly larger improvement in Letter Cancellation after listening to preferred music with than without auditory spatial cueing. After granting the feasibility of this new auditory stimulation technique, we investigated the long-term aftereffects in experiment II (n=12). Herefore, we used video-oculography during Free Visual Exploration, a sensitive and reliable tool to assess spatial attention over time. Listening to music with auditory spatial cueing – as compared to music without auditory spatial cueing – significantly improved neglect severity in terms of visual exploration behaviour for up to 3h. A voxel-based-lesion-symptom mapping analysis over all patients revealed that the response variability in listening to music with auditory spatial cueing is determined by the integrity of the right inferior parietal lobule, the second branch of the superior longitudinal fascicle, and parieto-parietal callosal fibres. Our study shows that listening to music with auditory spatial cueing significantly reduces neglect severity and has the potential to be used as an add-on in the neurorehabilitation of neglect

Supplementary Material for: Gesture Performance in First- and Multiple-Episode Patients with Schizophrenia Spectrum Disorders

<b><i>Background/Aim:</i></b> Gesturing plays an important role in social behavior and social learning. Deficits are frequent in schizophrenia and may contribute to impaired social functioning. Information about deficits during the course of the disease and presence of severity and patterns of impairment in first-episode patients is missing. Hence, we aimed to investigate gesturing in first- compared to multiple-episode schizophrenia patients and healthy controls. <b><i>Methods:</i></b> In 14 first-episode patients, 14 multiple-episode patients and 16 healthy controls matched for age, gender and education, gesturing was assessed by the comprehensive Test of Upper Limb Apraxia. Performance in two domains of gesturing - imitation and pantomime - was recorded on video. Raters of gesture performance were blinded. <b><i>Results:</i></b> Patients with multiple episodes had severe gestural deficits. For almost all gesture categories, performance was worse in multiple- than in first-episode patients. First-episode patients demonstrated subtle deficits with a comparable pattern. <b><i>Conclusions:</i></b> Subjects with multiple psychotic episodes have severe deficits in gesturing, while only mild impairments were found in first-episode patients independent of age, gender, education and negative symptoms. The results indicate that gesturing is impaired at the onset of disease and likely to further deteriorate during its course

Supplementary Material for: Screening for Language Disorders in Stroke: German Validation of the Language Screening Test (LAST)

<b><i>Background:</i></b> Screening of aphasia in acute stroke is crucial for directing patients to early language therapy. The Language Screening Test (LAST), originally developed in French, is a validated language screening test that allows detection of a language deficit within a few minutes. The aim of the present study was to develop and validate two parallel German versions of the LAST. <b><i>Methods:</i></b> The LAST includes subtests for naming, repetition, automatic speech, and comprehension. For the translation into German, task constructs and psycholinguistic criteria for item selection were identical to the French LAST. A cohort of 101 stroke patients were tested, all of whom were native German speakers. Validation of the LAST was based on (1) analysis of equivalence of the German versions, which was established by administering both versions successively in a subset of patients, (2) internal validity by means of internal consistency analysis, and (3) external validity by comparison with the short version of the Token Test in another subset of patients. <b><i>Results:</i></b> The two German versions were equivalent as demonstrated by a high intraclass correlation coefficient of 0.91. Furthermore, an acceptable internal structure of the LAST was found (Cronbach's α = 0.74). A highly significant correlation (r = 0.74, p < 0.0001) between the LAST and the short version of the Token Test indicated good external validity of the scale. <b><i>Conclusion:</i></b> The German version of the LAST, available in two parallel versions, is a new and valid language screening test in stroke

Supplementary Material for: Spatial Neglect Predicts Upper Limb Use in the Activities of Daily Living

<i>Background and Purpose:</i> Motor tests performed at stroke onset have been shown to predict the recovery of upper limb motor impairment. Less is known about upper limb recovery at the level of functional activity or of participation and how spatial neglect may influence the integration of the upper limb in the activities of daily living (ADL). Our objective was to investigate whether the initial severity of spatial neglect may predict upper limb use in ADL. <i>Methods:</i> Eighty-two patients with a right-hemispheric stroke (RHS) were prospectively included in the study. They were assessed twice in the acute/subacute and in the subacute/chronic phases (mean time interval of 45 days) after stroke. The Catherine Bergego Scale (CBS) was used to quantify the influence of spatial neglect on the ADL. Contralesional upper limb use in the ADL was evaluated with the Lucerne international classification of function, disability and health-based Multidisciplinary Observation Scale. Hand strength was measured using the Jamar, dexterity with the Nine Hole Peg test, and tactile perception using the stereognosis subtest of the Nottingham Sensory Assessment. Cognitive functions were assessed with the Montreal Cognitive Assessment. <i>Results:</i> Regression analyses revealed that spatial neglect is an independent and a significant predictor of upper limb outcome. A CBS score of ≤5 at the time of admission to neurorehabilitation care was highly predictive for good upper limb use in the ADL 45 days later. <i>Conclusions:</i> This study demonstrates that spatial neglect severity, as observed in the ADL, is a significant and an independent predictor of upper limb outcome. Neglect therapy is thus needed to further improve contralesional upper limb use in the ADL in RHS patients

Enhancement of STroke REhabilitation with Levodopa (ESTREL): Rationale and design of a randomized placebo-controlled, double blind superiority trial.

Novel therapeutic approaches are needed in stroke recovery. Whether pharmacological therapies are beneficial for enhancing stroke recovery is unclear. Dopamine is a neurotransmitter involved in motor learning, reward, and brain plasticity. Its prodrug levodopa is a promising agent for stroke recovery. To investigate the hypothesis that levodopa, in addition to standardized rehabilitation therapy based on active task training, results in an enhancement of functional recovery in acute ischemic or hemorrhagic stroke patients compared to placebo. ESTREL (Enhancement of Stroke REhabilitation with Levodopa) is a randomized (ratio 1:1), multicenter, placebo-controlled, double-blind, parallel-group superiority trial. 610 participants (according to sample size calculation) with a clinically meaningful hemiparesis will be enrolled ⩽7 days after stroke onset. Key eligibility criteria include (i) in-hospital-rehabilitation required, (ii) capability to participate in rehabilitation, (iii) previous independence in daily living. Levodopa 100 mg/carbidopa 25 mg three times daily, administered for 5 weeks in addition to standardized rehabilitation. The study intervention will be initiated within 7 days after stroke onset. Matching placebo plus standardized rehabilitation. The primary outcome is the between-group difference of the Fugl-Meyer-Motor Assessment (FMMA) total score measured 3 months after randomization. Secondary outcomes include patient-reported health and wellbeing (PROMIS 10 and 29), patient-reported assessment of improvement, Rivermead Mobility Index, modified Rankin Scale, National Institutes of Health Stroke Scale (NIHSS), and as measures of harm: mortality, recurrent stroke, and serious adverse events. The ESTREL trial will provide evidence of whether the use of Levodopa in addition to standardized rehabilitation in stroke patients leads to better functional recovery compared to rehabilitation alone