Chronic inflammatory demyelinating polyneuropathy (CIDP) is defined as a dysimmune disorder of the peripheral nervous system (PNS) resulting in sensorimotor deficits. However, an increasing body of data suggests that CIDP also goes along with features, such as autonomic, circadian, fatigue, mood, and subtle cognitive dysfunctions. Some of these non-sensorimotor symptoms (NSMS) challenge the concept of an exclusive PNS disease. Pragmatically, the high prevalence of NSMS calls for a more holistic disease assessment and surveillance to achieve optimal therapeutic results.

BACKGROUND AND OBJECTIVES:Focal dystonia (FD) is an extrapyramidal movement disorder, but various disease aspects challenge the view of a condition only involving neuronal motor systems. Here, we were interested in potential changes of retinal functions, accessible by chromatic pupillometry. METHODS:Quantitative chromatic pupillometry was performed in 26 persons with FD and 20 age-/sex-matched healthy controls. Upon dark adaptation, standardized red (632 nm) and blue (462 nm) light pulses (100 cd/m2) were delivered to the pupils. Constrictions were recorded one and 6 s after the stimuli. The 1s-constriction is rod/cone-mediated, whereas the post illumination pupil response (PIPR) reflects the melanopsin-related activity of intrinsic photosensitive retinal ganglion cells (ipRGC) to blue light only. RESULTS:Compared with controls, dystonia patients did not differ in baseline pupil diameter prior to red-light stimulation. Peak transient constriction, indexed by the minimal pupil size during the 1-s light pulse, was similar between groups for both red and blue light. The blue light-specific PIPR was significantly attenuated in patients. DISCUSSION:The findings point to altered retinal light sensitivity in FD with a hypofunctional ipRGC system. This suggests an impact of the disease beyond movement-related neuronal systems.

BACKGROUND:Parkinson's disease (PD) disturbs basal ganglia functioning and the precise coding of time-critical information. Beyond its known impact on movement capacities, it may therefore affect cognitive functions with high demands of temporal information coordination. We studied this via the processing of syntactic boundaries during auditory sentence parsing. OBJECTIVE:To analyze the processing of syntactic structure as a function of position and duration of prosodic breaks in persons with PD compared to controls. METHODS:27 persons with PD and 26 healthy controls judged the grammatical correctness of auditorily presented sentences. Prosodic breaks, occurred at syntactically grammatical or ungrammatical positions, with either short or prolonged duration. Accuracy and decision time were analyzed as a function of break position and length. As motor baseline, an auditory reaction time task was included to control for slowness of movement. RESULTS:Persons with PD compared to controls made more errors and slower judgments for both correct and incorrect sentences. For incorrect sentences, however, the prolongation of breaks enhanced the judgment accuracy in PD, eliminating statistical group differences. PD-related abnormalities of task performance were not correlated with the motor severity, duration, or other cognitive aspects of the disease. Prolonged reaction time could not be explained by PD-related motor slowing. CONCLUSION:Impaired temporal sequencing of auditory language input declines sentence parsing in PD. This calls for higher awareness of perceptual deficits of linguistic processing in clinical routine.

Background and Objectives: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a dysimmune disease leading to sensorimotor deficits due to peripheral nerve dysfunction, but recently additional non-sensorimotor symptoms (NSMS) were increasingly recognized. In this context, we compared the sleep behavior in persons with versus without CIDP and discussed the results with respect to further NSMS. Methods: Twenty-five CIDP patients and 27 controls took part in this prospective, cross-sectional study. Clinically, sensorimotor disability (RODS), affective state (DESC-I), and fatigue levels (FSMC scores) were assessed. Regarding sleep-wake behavior, they wore actigraphic devices over 14 consecutive days and completed sleep diaries, chronotype questionnaires, and the Pittsburgh Sleep Quality Index (PSQI). The actigraphic data were analyzed with respect to sleep efficiency, wake after sleep onset (WASO), sleep onset latency, total sleep duration, intradaily variability (IV), and interdaily stability (IS). Results: Patients with CIDP reported significantly worse subjective sleep quality (p < 0.001). They also showed higher levels of fatigue (p < 0.001) and depressiveness (p = 0.046). The actigraphic results showed significantly reduced WASO (p(bonf) = 0.012), especially early in the morning and immediately preceding waking up (p = 0.010). The sleep abnormalities were not linked to the raised clinical data (p > 0.05). Discussion: Beyond subjectively reduced sleep quality, actigraphic data show that persons with CIDP have lowered sleep efficacy and experience increased nocturnal arousals. This suggests that sleep disturbance is a genuine aspect of CIDP adding to the underrecognized problem of NSMS in this condition.

Though classified as a movement disorder, essential tremor (ET) goes along with minor cognitive change. This mainly refers to executive functions, thought to be of paramount importance for social cognition, particularly cognitive theory of mind (ToM). Therefore, different ToM and executive tasks were assessed in persons with versus without essential tremor. 21 non-demented patients with essential tremor and 29 healthy controls underwent cognitive screening, different tasks addressing executive functions, and the faux pas recognition test (FPRT) as well as the reading the mind in the eye test (RMET), focusing on cognitive and affective ToM, respectively. Patients performed significantly worse than controls in the verbal fluency and the digit span tests as well as in the FPRT. No significant group differences were identified with respect to RMET performance. The results are compatible with the idea that persons with ET develop subtle cognitive ToM deficits in the context of executive dysfunction. This extends descriptions of the non-motor impact of ET by deficits in social cognition and raises the question whether potential cognitive change of affected patients is sufficiently acknowledged in clinical routine.

BACKGROUND:Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is the most prevalent dysimmune disease of sensorimotor nerves. However, based on various non-sensorimotor symptoms (NSMS), the concept of a purely peripheral condition has recently been challenged. Against this background, we aimed to differentiate motor and cognitive components of fatigue as the most prominent NSMS in CIDP. METHODS:Cognitive and motor fatigue constructs were assessed in 47 CIDP patients and 31 healthy controls (HC) using the Fatigue Scale for Motor and Cognitive Functions (FSMC). The results were referred to score data for sensorimotor disability as well as for depressiveness, sleep quality, and alertness, describing functional levels potentially related to fatigue. Further, they were analyzed with respect to serum neurofilament light chain (sNfL), a biomarker of disease progression and potentially central involvement in CIDP. RESULTS:CIDP patients reported significantly higher scores of total (p < 0.001), motor (p < 0.001), and cognitive (p = 0.005) fatigue compared to HC. Within the CIDP group, motor fatigue was more pronounced than cognitive fatigue compared to HC (p < 0.001). Although alertness levels did not differ significantly between the groups, poorer alertness correlated with cognitive fatigue in the CIDP cohort (p = 0.02). Notably, only functional disability and depressiveness served as predictors for both fatigue components (p < 0.05). sNfL levels showed no significant association with fatigue. DISCUSSION:These findings show that the burden of CIDP is not sufficiently described by sensorimotor disability. A clinically relevant NSMS aspect of the disease is fatigue in motor as well as cognitive dimensions.

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is a dysimmune disease primarily targeting the Schwann cell myelin sheath in the peripheral nervous system (PNS), resulting in sensorimotor deficits. Surprisingly, subtle cognitive impairments as well as axonal damage, indicated by elevated serum neurofilament light chain (sNfL), prevail in CIDP. This study investigated whether elevated sNfL is associated with lower cognitive performance in CIDP. Thirty-five CIDP patients underwent digital cognitive testing across multiple domains, alongside assessments of sociodemographic, clinical, and sNfL measures. Patients were stratified into low- and high-sNfL groups based on the median value, and clinical variables were compared. Further, general linear models, controlled for clinical and sociodemographic factors, were employed to evaluate the predictive value of sNfL for global and domain-specific cognitive functioning. Higher sNfL values were associated with worse general cognitive performance (β = −0.31, p = 0.016) and reduced processing speed (β = −0.40, p = 0.008). Patients with increased sNfL levels had a longer disease duration (p = 0.016), also linked to poorer cognitive outcome (β = −0.26, p = 0.045). In this CIDP cohort, high sNfL levels were associated with reduced cognitive performance and longer disease duration. The findings suggest that sNfL is a clinical meaningful biomarker for the detection and monitoring of central involvement in the course of CIDP, a condition traditionally viewed as purely peripheral.

Cognitive dysfunction has been repeatedly described as an aspect of chronic inflammatory demyelinating polyneuropathy (CIDP), but to which capacities this exactly refers and how it is embedded in the clinical phenotype of the condition remains unknown. Therefore, the detailed cognitive profiles of persons with and without CIDP were compared with each other and the disease-related results analyzed in view of main symptom complexes. 44 persons with CIDP were studied with respect to their cognitive performances in an extensive computer-based test battery and described clinically in terms of sensorimotor disability (R-ODS), fatigue (FSMC), and mood (DESC-I). The cognitive test results were compared to those of 33 age-matched healthy controls. The overall cognitive performance of persons with CIDP was significantly worse than that of controls (composite score for CIDP: 33.34 ± 17.96; for Controls: 48.73 ± 18.31; U = 382, p < 0.001). Pronounced deficits prevailed in processing speed (q = 0.018), executive function (q = 0.018), memory (short-term: q = 0.020; long-term: q = 0.025) and visuoconstruction (q = 0.018). Using a hierarchical regression model, the inclusion of the factor sensorimotor disability improved the prediction of overall cognitive performance in persons with CIDP (p = 0.027). Cognitive impairment is an under-recognized aspect of CIDP, characterized by reduced processing speed, executive functioning, and memory performance. These cognitive deficits grow together with sensorimotor impairment. The findings show that CIDP goes along with functional changes beyond its classical lead symptoms.

Chronic inflammatory demyelinating polyneuropathy (CIDP) compromises functions of the peripheral nervous system (PNS). Recently, however, symptoms such as cognitive deficits, visual dysfunction and circadian disorders were reported, compatible with additional involvement of the central nervous system (CNS) in CIDP. Against this background, we were interested in the functional state of melanopsin-expressing retinal ganglion cells (mRGCs) as a potential biomarker for sleep-wake abnormalities and CNS involvement in CIDP. Based on a chromatic pupillometry protocol, we examined the integrity of the melanopsin system in a prospective case-control study in 20 persons with CIDP compared to 20 controls without CIDP. The results were referred to clinical measures of disease severity and sleep behaviour. Patients with CIDP had a significantly reduced melanopsin-mediated post-illumination pupil response (PIPR) compared to healthy controls (25% versus 36%; P < 0.01). This reduction correlated with disease severity (r = 0.478, P < 0.05). Further, patients with CIDP reported diminished sleep quality (P < 0.05); however, there was no significant correlation with the melanopsin-mediated PIPR. The results demonstrate an impairment of mRGC function related to CIDP. Since the PIPR reduction correlated with disease severity, it could be an easily available biomarker for CNS affection in CIDP, a condition defined as PNS disorder.

Aim of this review is to discuss the value of current ongoing research initiatives in Parkinson’s disease from the clinicians’ point of view. The repeat, recent failures on progress slowing reflect the drifting apart between initially promising experimental and then disappointing clinical outcomes in the translational trials with well selected Parkinson’s disease patients. A similar development concerns the emerging gap between novel developed drugs with improved pharmacokinetic behaviour and their limited use in the clinical practice following approval. Restricted regional different worldwide availability and direct, respectively indirect budget limitations for neurologists in private practice are essential hurdles. They prevent the widespread prescription of these compounds. As a result return of investment for the pharmaceutical industry becomes more and more uncertain. The interest for research on novel treatment approaches for the amelioration of motor and non motor symptoms declines. Clinicians crucially scrutinize the claim for an optimum patient care by payers and regulators.

Words would only be sounds, if they did not activate phonemic and semantic operations in separate cortical regions, and their serial occurrence would remain incomprehensible without integration into a suitable syntactic frame. Coming from this simple notion, two components of biolinguistic processing seem principally relevant, first, the flexible binding of distributed cortical areas to recruit the material for meaningful messages and, second, the structuring of this material according to habitual language features. Based on studies in patients with deep-brain stimulation (DBS) for the treatment of neurological movement disorders, we propose that thalamic nuclei contribute to the former operation, whereas the basal ganglia rather support the latter aspect of language processing. The current review summarizes DBS-dependent task performances and neurophysiological recordings from thalamic and basal ganglia DBS that target nuclei underlying this view.

Introduction. Cervical dystonia (CD) is viewed as a circumscribed movement disorder. However, beyond motor symptoms, it can imply subtle cognitive change, among others with respect to theory of mind (ToM) capacities. Here, affective and cognitive ToM performances and potential relations to other mental functions were investigated to refine the concept of social cognitive dysfunction in CD. Methods. 20 persons with CD were clinically assessed, together with 20 healthy controls engaged in overview cognitive testing, executive function (EF) tasks, and the Faux Pas Recognition Test (FPRT) as well as the Reading the Mind in the Eyes Tests (RMET) addressing cognitive and affective ToM functions, respectively. Results. Persons with CD showed lower cognitive, but not affective ToM performance than controls. Further, they had abnormally low word production in verbal fluency (VF) tasks, imposing high EF demands. Generally, ToM performance correlated with VF and, further, with the decreased quality of life score in persons with CD. Conclusion. Cognitive ToM deficits seem to occur in the context of executive dysfunction in CD. They belong to an underrecognized spectrum of nonmotor symptoms of likely clinical relevance.

BACKGROUND AND PURPOSE:Although chronic inflammatory demyelinating polyneuropathy (CIDP) is understood as a disease affecting the peripheral nervous system, mild cognitive dysfunction, particularly in the executive domain, has been described to form part of the condition. Here our interest lay in CIDP-related theory of mind (ToM) capacities as an aspect of social cognition relevant for many aspects of everyday life. METHODS:Twenty-nine patients with CIDP and 23 healthy controls participated in this study. They were subjected to overview cognitive testing, different executive function (EF) tasks, as well as to the Faux Pas Recognition Task (FPRT) for assessing cognitive ToM and the Reading the Mind in the Eyes Test (RMET) with respect to affective ToM. RESULTS:Persons with CIDP and controls did not differ with respect to their overall cognitive state. However, in the German verbal fluency standard, the digit span forward and the digit span backward tests used as EF tasks patients performed significantly worse than controls. Further, performance was abnormally low in the FPRT, whilst the groups did not differ with respect to RMET results. The FPRT and digit span backward results correlated with each other. CONCLUSIONS:Patients with CIDP showed deficits in cognitive ToM performance together with EF dysfunction, whilst affective ToM was preserved. Altogether, the results suggest that low cognitive ToM capacities in patients with CIDP arise as a particular aspect of disease-related executive dysfunction.

The perception of everyday events implies the segmentation into discrete sub-events (i.e. event segmentation). This process is relevant for the prediction of upcoming events and for the recall of recent activities. It is thought to involve dopaminergic networks which are strongly compromised in Parkinson’s disease (PD). Indeed, deficits of event segmentation have been previously shown in PD, but underlying neuronal mechanisms remain unknown. We therefore investigated 22 persons with PD and 22 age-matched healthy controls, who performed an event segmentation task with simultaneous electroencephalography (EEG). Both groups had to indicate by button press the beginning of sub-events within three movies showing persons performing everyday activities. The segmentation performance of persons with PD deviated significantly from that of controls. Neurophysiologically, persons with PD expressed reduced theta (4–7 Hz) activity around identified event boundaries compared to healthy controls. Together, these results point to disturbed event processing in PD. According to functions attributed to EEG activities in particular frequency ranges, the PD-related theta reduction could reflect impaired matching of perceptual input with stored event representations and decreased updating processes of event information in working memory and, thus, event boundary identification.

IntroductionPatients with Parkinson’s disease (PD) exhibit deficits in social cognition, particularly with respect to Theory of Mind (ToM) capacities. It is unclear whether they are associated with PD-related dopamine deficiency and modulated by levodopa replacement therapy.MethodsA total of 15 persons with PD and 13 healthy controls (HC) participated in the study. They performed different neuropsychological tasks, including the Faux Pas Recognition Test (FPRT), assessing different dimensions of cognitive ToM (e.g., detection, inappropriateness, intentions), and the Reading the Mind in the Eyes Test (RMET) as an index of affective ToM. Persons with PD were tested twice, once under their regular treatment and another time after at least 18 h of levodopa withdrawal (MED-ON and MED-OFF, respectively). On either occasion, serum drug levels and motor symptom severity [Unified Parkinson’s Disease Rating Scale (UPDRS)] were measured.ResultsMED-ON and MED-OFF conditions in patients with PD were confirmed by higher serum drug levels in the former than in the latter state and a corresponding amelioration of the motor deficit. In so doing, no performance difference in any ToM-related task was identified as a function of the levodopa therapy. Generally, patients performed worse than controls in both affective and cognitive ToM tests.ConclusionPatients with PD have deficits in cognitive and affective ToM. Dopamine replacement, effective for improving the motor condition, does not appear to counteract these dysfunctions.

Embodied cognition theories posit direct interactions between sensorimotor and mental processing. Various clinical observations have been interpreted in this controversial framework, amongst others, low verb generation in word production tasks performed by persons with Parkinson's disease (PD). If this were the consequence of reduced motor simulation of prevalent action semantics in this word class, reduced PD pathophysiology should result in increased verb production and a general shift of lexical contents towards particular movement-related meanings. 17 persons with PD and bilateral deep brain stimulation (DBS) of the subhtalamic nucleus (STN) and 17 healthy control persons engaged in a semantically unconstrained, phonemic verbal fluency task, the former in both DBS-off and DBS-on states. The analysis referred to the number of words produced, verb use, and the occurrence of different dimensions of movement-related semantics in the lexical output. Persons with PD produced fewer words than controls. In the DBS-off, but not in the DBS-on condition, the proportion of verbs within this reduced output was lower than in controls. Lowered verb production went in parallel with a semantic shift: in persons with PD in the DBS-off, but not the DBS-on condition, the relatedness of produced words to own body-movement was lower than in controls. In persons with PD, DBS induced-changes of the motor condition appear to go along with formal and semantic shifts in word production. The results are compatible with the idea of some impact of motor system states on lexical processing.

Persons with Parkinson's disease (PD) often show particular problems in seemingly simple routines despite relatively preserved cognitive function. We therefore investigated the processing of everyday events on behavioral and neurophysiological levels in a PD and control group. The participants had to indicate via button press whether three sequentially presented sub-events described a previously defined event (e.g., going grocery shopping). Sub-event sequences were either correct or included an event that did not belong to the event (content violation), or events were chronologically wrong (temporal violation). During task execution event-related potentials (ERPs) were recorded. Generally, the PD group showed less accurate performance independently from task conditions, and reaction times to temporal violations were particularly slow compared to the control group. Regarding ERP results, the control group showed a right lateralized N400 effect in response to content violations, which was absent in the PD group indicating altered content event processing. Concerning the reanalysis of content event violations, the expression of late positive components (LPCs) was similar between both groups. Upon temporal violations, both groups also showed a LPC with a tendentially earlier onset in the PD group, resembling positive components indicative of novelty processing. Together, these findings suggest poor event prediction in PD, which may originate from weak event representation or retrieval and possibly relate to prevalent behavioral dysfunctions in everyday life in PD.

Background Excessive daytime sleepiness (EDS) is a frequent and disabling symptom of Parkinson's disease (PD) without approved treatment. THN102 is a novel combination drug of modafinil and low-dose flecainide. Objective The aim of this study is to evaluate the safety and efficacy of THN102 in PD patients with EDS. Methods The method involved a randomized, double-blind, placebo-controlled, crossover trial testing two doses of THN102 (200 mg/d modafinil with 2 mg/d [200/2] or 18 mg/d flecainide [200/18]) versus placebo; 75 patients were exposed to treatment. The primary endpoint was safety. The primary efficacy outcome was the change in Epworth Sleepiness Scale (ESS) score. Results Both doses of THN102 were well tolerated. ESS significantly improved with THN102 200/2 (least square means vs. placebo [95% confidence interval, CI]: -1.4 [-2.49; -0.31], P = 0.012) but did not change significantly with the 200/18 dosage. Conclusions THN102 was well tolerated and showed a signal of efficacy at the 200/2 dose, supporting further development for the treatment of EDS in PD. (c) 2021 International Parkinson and Movement Disorder Society

Zusammenfassung Mehr als 20% der Patienten mit idiopathischem Parkinson-Syndrom (IPS) entwickeln Psychosen. Am haufigsten sind visuelle Halluzinationen. Bei der Entwicklung der Psychosen scheinen die Pathogenese der Parkinson-Erkrankung sowie ihre Dauer ebenso eine Rolle zu spielen wie modulierende Effekte der dopaminergen Therapie. Beim Therapiemanagement steht neben allgemeinen Ma ss nahmen zunachst die Anpassung der dopaminergen Therapie im Vordergrund. Dies kann zu einer Gratwanderung werden zwischen Besserung der Halluzinationen und Verschlechterung der Motorik. Bei unzureichendem Erfolg kann eine antipsychotische Therapie notwendig werden - dabei ist die Auswahl auf sehr wenige Antipsychotika beschrankt, um nicht ernsthafte motorische Verschlechterungen zu riskieren. In der vorliegenden Arbeit wurden basierend auf dem aktuellen Stand der Literatur sowie empirischen Experten-basierten Erfahrungen aus dem klinischen Alltag relevante Aspekte zu Halluzinationen bei IPS-Patienten in der Praxis zusammengefasst und Empfehlungen zum Therapiemanagement erarbeitet. Abstract Patients with idiopathic Parkinson's disease develop symptoms of the hallucination-psychosis spectrum in more than 20%. Most common are visual hallucinations. The pathogenesis of hallucinations mainly depends on disease duration, the distribution and extent of alpha-synuclein pathology, and modulating effects of the dopaminergic therapy. When managing PD hallucinations both anti-delirogenic actions and medication management are important. However, decrease in dopaminergic medication may lead to critical worsening of akinesia. If appropriate neuroleptic medication - essentially quetiapin or clozapin - can be considered. Instead, anti-dopaminergic neuroleptics should not be used owing to their pro-akinetic side-effects. Here, we provide therapy recommendations to manage PD hallucinations based on an up-to-date targeted review of the literature and expert-based empirical evidence.