Pain in Multiple System Atrophy: A Community-Based Survey.

BACKGROUND: Pain is a frequent yet poorly characterized symptom of multiple system atrophy (MSA). Understanding the factors influencing pain and its burden is crucial for improving the symptomatic treatment and quality of life of MSA individuals. OBJECTIVE: This study aimed at assessing the prevalence, characteristics, and current treatment strategies for pain in MSA. METHODS: A community-based, online survey was conducted from February to May 2023. Invitations were extended to MSA individuals and informal MSA caregivers through patient advocacies and social media. RESULTS: We included 190 persons with MSA and 114 caregivers. Eighty-seven percent of MSA individuals reported pain, which was more prevalent among women (odds ratio [OR]: 6.38 [95% confidence interval, CI: 1.27-32.08], P = 0.025) and low-income groups (OR: 5.02 [95% CI: 1.32-19.08], P = 0.018). Neck and shoulders (58%), back (45%), and legs (45%) were mostly affected. In the neck and shoulders, pain was associated with MSA core features, like orthostatic intolerance (OR: 4.80 [95% CI: 1.92-12.02], P = 0.001) and antecollis (OR: 3.24 [95% CI: 1.54-6.82], P = 0.002). Seventy-six percent of individuals experiencing pain received treatment, mostly nonsteroidal anti-inflammatory drugs (47%), acetaminophen (39%), and opioids (28%). Only 53% of respondents reported at least partial satisfaction with their current pain management. Pain mostly impacted work, household activities, and hobbies of MSA individuals, and caregivers' social activities. CONCLUSIONS: Pain is more prevalent than previously reported in MSA and particularly affects women and low-income groups. Despite its frequency, pain management remains suboptimal, highlighting an urgent therapeutic need, likely entailing an optimized management of MSA core motor and non-motor features. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Cognitive, Mental Health, Functional, and Quality of Life Outcomes 1 Year After Spontaneous Subarachnoid Hemorrhage: A Prospective Observational Study.

BACKGROUND: Patients with spontaneous subarachnoid hemorrhage (SAH) frequently encounter cognitive dysfunction and mental health issues with negative effects on health-related quality of life (HR-QoL). Here, we aimed to describe the prevalence of cognitive deficits, mental health problems, and HR-QoL impairments 1 year after SAH. METHODS: In this prospective observational study, 177 patients with SAH admitted to our neurointensive care unit over a time span of ten years followed the invitation for an in-person 1-year follow-up, including a standardized neuropsychological test battery. Mental health issues (anxiety and depression) and HR-QoL were evaluated using questionnaires (Hospital Anxiety and Depression Scale; 36-item Short Form questionnaire). Functional outcome was assessed with the modified Rankin Scale (mRS) score. RESULTS: Patients were 54 years of age (interquartile range 47-62 years) and presented with a median Hunt and Hess score of 2 (interquartile range 1-3) at admission. Most patients (93%) achieved good functional 1-year outcomes (mRS score 0-2). Seventy-one percent of patients had deficits in at least one cognitive domain, with memory deficits being the most prevalent (51%), followed by deficits in executive functions (36%), visuoconstruction (34%), and attention (21%). Even patients with perimesencephalic SAH (18%) or with full functional recovery (mRS score = 0, 46%) had a comparable prevalence of cognitive deficits (61% and 60%, respectively). Symptoms of depression and anxiety were reported by 16% and 33% of patients, respectively. HR-QoL was impaired in 37% (55 of 147). Patients with cognitive deficits (p = 0.001) or mental health issues (p < 0.001) more frequently reported impaired HR-QoL. CONCLUSIONS: Most patients with SAH have cognitive deficits and mental health issues 1 year after SAH. These deficits impair patients' quality of life.

Recognition and perception of emotions in juvenile myoclonic epilepsy.

OBJECTIVE: Perception and recognition of emotions are fundamental prerequisites of human life. Patients with juvenile myoclonic epilepsy (JME) may have emotional and behavioral impairments that might influence socially desirable interactions. We aimed to investigate perception and recognition of emotions in patients with JME by means of neuropsychological tests and functional magnetic resonance imaging (fMRI). METHODS: Sixty-five patients with JME (median age = 27 years, interquartile range [IQR] = 23-34) were prospectively recruited at the Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria. Patients were compared to 68 healthy controls (median age = 24 years, IQR = 21-31), matched for sex, age, and education. All study participants underwent the Networks of Emotion Processing test battery (NEmo), an fMRI paradigm of "dynamic fearful faces," a structured interview for psychiatric and personality disorders, and comprehensive neuropsychological testing. RESULTS: JME patients versus healthy controls demonstrated significant deficits in emotion recognition in facial and verbal tasks of all emotions, especially fear. fMRI revealed decreased amygdala activation in JME patients as compared to healthy controls. Patients were at a higher risk of experiencing psychiatric disorders as compared to healthy controls. Cognitive evaluation revealed impaired attentional and executive functioning, namely psychomotor speed, tonic alertness, divided attention, mental flexibility, and inhibition of automated reactions. Duration of epilepsy correlated negatively with parallel prosodic and facial emotion recognition in NEmo. Deficits in emotion recognition were not associated with psychiatric comorbidities, impaired attention and executive functions, types of seizures, and treatment. SIGNIFICANCE: This prospective study demonstrated that as compared to healthy subjects, patients with JME had significant deficits in recognition and perception of emotions as shown by neuropsychological tests and fMRI. The results of this study may have importance for psychological/psychotherapeutic interventions in the management of patients with JME.

Neurological outcomes 1 year after COVID-19 diagnosis: A prospective longitudinal cohort study.

BACKGROUND AND PURPOSE: Neurological sequelae from coronavirus disease 2019 (COVID-19) may persist after recovery from acute infection. Here, the aim was to describe the natural history of neurological manifestations over 1 year after COVID-19. METHODS: A prospective, multicentre, longitudinal cohort study in COVID-19 survivors was performed. At a 3-month and 1-year follow-up, patients were assessed for neurological impairments by a neurological examination and a standardized test battery including the assessment of hyposmia (16-item Sniffin' Sticks test), cognitive deficits (Montreal Cognitive Assessment < 26) and mental health (Hospital Anxiety and Depression Scale and Post-traumatic Stress Disorder Checklist 5). RESULTS: Eighty-one patients were evaluated 1 year after COVID-19, out of which 76 (94%) patients completed a 3-month and 1-year follow-up. Patients were 54 (47-64) years old and 59% were male. New and persistent neurological disorders were found in 15% (3 months) and 12% (10/81; 1 year). Symptoms at 1-year follow-up were reported by 48/81 (59%) patients, including fatigue (38%), concentration difficulties (25%), forgetfulness (25%), sleep disturbances (22%), myalgia (17%), limb weakness (17%), headache (16%), impaired sensation (16%) and hyposmia (15%). Neurological examination revealed findings in 52/81 (64%) patients without improvement over time (3 months, 61%, p = 0.230) including objective hyposmia (Sniffin' Sticks test <13; 51%). Cognitive deficits were apparent in 18%, whereas signs of depression, anxiety and post-traumatic stress disorders were found in 6%, 29% and 10% respectively 1 year after infection. These mental and cognitive disorders had not improved after the 3-month follow-up (all p > 0.05). CONCLUSION: Our data indicate that a significant patient number still suffer from neurological sequelae including neuropsychiatric symptoms 1 year after COVID-19 calling for interdisciplinary management of these patients.

Factors associated with impaired quality of life three months after being diagnosed with COVID-19.

PURPOSE: To assess patient characteristics associated with health-related quality of life (HR-QoL) and its mental and physical subcategories 3 months after diagnosis with COVID-19. METHODS: In this prospective multicentre cohort study, HR-QoL was assessed in 90 patients using the SF-36 questionnaire (36-item Short Form Health Survey), which consists of 8 health domains that can be divided into a mental and physical health component. Mental health symptoms including anxiety, depression, and post-traumatic stress disorders were evaluated using the Hospital Anxiety and Depression Scale (HADS) and Post-traumatic Stress Disorder Checklist-5 (PCL-5) 3 months after COVID-19. Using descriptive statistics and multivariable regression analysis, we identified factors associated with impaired HR-QoL 3 months after COVID-19 diagnosis. RESULTS: Patients were 55 years of age (IQR, 49-63; 39% women) and were classified as severe (23%), moderate (57%), or mild (20%) according to acute disease severity. HR-QoL was impaired in 28/90 patients (31%). Younger age [per year, adjOR (95%CI) 0.94 (0.88-1.00), p = 0.049], longer hospitalization [per day, adjOR (95%CI) 1.07 (1.01-1.13), p = 0.015], impaired sleep [adjOR (95%CI) 5.54 (1.2-25.61), p = 0.028], and anxiety [adjOR (95%CI) 15.67 (3.03-80.99), p = 0.001) were independently associated with impaired HR-QoL. Twenty-nine percent (n = 26) scored below the normal range on the mental health component of the SF-36 and independent associations emerged for anxiety, depression, and self-reported numbness. Impairments in the physical health component of the SF-36 were reported by 12 (13%) patients and linked to hypogeusia and fatigue. CONCLUSION: Every third patient reported a reduction in HR-QoL 3 months after COVID-19 diagnosis and impairments were more prominent in mental than physical well-being.

Decision making and framing effects in multiple sclerosis.

BACKGROUND: Previous studies reported reduced decision-making abilities for patients with multiple sclerosis (MS) relative to healthy controls (HC). This study aimed to evaluate whether these problems arise when sampling information or when pondering about the evidence collected. METHODS: In a cross-sectional, controlled study, 43 relapsing-remitting MS patients (RRMS; Expanded Disability Status Scale 1.5, range 0-4) and 53 HC performed an information sampling task ('beads task'), a health-related framing task, and neuropsychological background tests. RESULTS: In the beads task, patients collected as much information as HC prior to a decision. However, there were twice as many patients as HC making irrational decisions, that is, decisions against the evidence collected (RRMS: 26/43, 60%; HC: 16/53, 30%; p = 0.003). Compared to HC, patients also showed a stronger framing effect, that is, they were more strongly biased by the way health-related information was presented (p < 0.05, Cohen's d = 0.5). Overall, the framing effect predicted whether a participant would make irrational decisions (OR 2.12, 95% CI 1.29-3.49, p < 0.001). CONCLUSIONS: Predecisional information sampling is intact in RRMS. However, compared to HC, patients are more likely to make irrational decisions and to be biased by the way health-related information is framed. This warrants caution in communication, especially in the medical context, with patients.

Neurological outcome and quality of life 3 months after COVID-19: A prospective observational cohort study.

BACKGROUND AND PURPOSE: To assess neurological manifestations and health-related quality of life (QoL) 3 months after COVID-19. METHODS: In this prospective, multicenter, observational cohort study we systematically evaluated neurological signs and diseases by detailed neurological examination and a predefined test battery assessing smelling disorders (16-item Sniffin Sticks test), cognitive deficits (Montreal Cognitive Assessment), QoL (36-item Short Form), and mental health (Hospital Anxiety and Depression Scale, Posttraumatic Stress Disorder Checklist-5) 3 months after disease onset. RESULTS: Of 135 consecutive COVID-19 patients, 31 (23%) required intensive care unit (ICU) care (severe), 72 (53%) were admitted to the regular ward (moderate), and 32 (24%) underwent outpatient care (mild) during acute disease. At the 3-month follow-up, 20 patients (15%) presented with one or more neurological syndromes that were not evident before COVID-19. These included polyneuro/myopathy (n = 17, 13%) with one patient presenting with Guillain-Barré syndrome, mild encephalopathy (n = 2, 2%), parkinsonism (n = 1, 1%), orthostatic hypotension (n = 1, 1%), and ischemic stroke (n = 1, 1%). Objective testing revealed hyposmia/anosmia in 57/127 (45%) patients at the 3-month follow-up. Self-reported hyposmia/anosmia was lower (17%) at 3 months, however, improved when compared to the acute disease phase (44%; p < 0.001). At follow-up, cognitive deficits were apparent in 23%, and QoL was impaired in 31%. Assessment of mental health revealed symptoms of depression, anxiety, and posttraumatic stress disorders in 11%, 25%, and 11%, respectively. CONCLUSIONS: Despite recovery from the acute infection, neurological symptoms were prevalent at the 3-month follow-up. Above all, smelling disorders were persistent in a large proportion of patients.

German translation, cultural adaptation and validation of the unidimensional self-efficacy scale for multiple sclerosis.

BACKGROUND: Self-efficacy concerns individuals' beliefs in their capability to exercise control in specific situations and complete tasks successfully. In people with multiple sclerosis (PwMS), self-efficacy has been associated with physical activity levels and quality of life. As a validated German language self-efficacy scale for PwMS is missing the aims of this study were to translate the Unidimensional Self-Efficacy Scale for Multiple Sclerosis (USE-MS) into German, establish face and content validity and cultural adaptation of the German version for PwMS in Austria. A further aim was to validate the German USE-MS (USE-MS-G) in PwMS. METHODS: Permission to translate and validate the USE-MS was received from the scale developers. Following guidelines for translation and validation of questionnaires and applying Bandura's concept of self-efficacy, the USE-MS was forward-backward translated with content and face validity established. Cultural adaptation for Austria was performed using cognitive patient interviews. Reliability was assessed using Cronbach's alpha, Person separation index and Lin's concordance correlation coefficient. Rasch analysis was employed to assess construct validity. Comparison was made to scales for resilience, general self-efficacy, anxiety and depression, multiple sclerosis fatigue and health-related quality of life. Data were also pooled with an historic English dataset to compare the English and German language versions. RESULTS: The translation and cultural adaptation were successfully performed in the adaptation process of the USE-MS-G. Pretesting was conducted in 30 PwMS, the validation of the final USE-MS-G involved 309 PwMS with minimal to severe disability. The USE-MS-G was found to be valid against the Rasch model when fitting scale data using a bifactor solution of two super-items. It was shown to be unidimensional, free from differential item functioning and well targeted to the study population. Excellent convergent and known-groups validity, internal consistency, person separation reliability and test-retest reliability were shown for the USE-MS-G. Pooling of the English and German datasets confirmed invariance of item difficulties between languages. CONCLUSION: The USE-MS-G is a robust, valid and reliable scale to assess self-efficacy in PwMS and can generate interval level data on an equivalent metric to the UK version. TRIAL REGISTRATION: ISRCTN Registry; ISRCTN14843579 ; prospectively registered on 02. 01. 2019.

The role of cortisol in trust behavior: Results from an experimental study on healthy controls and patients with juvenile myoclonic epilepsy.

Trust is one of the foundations of human society and pervades all aspects of human live. Research on humans focused primarily on identifying the biological basis of trust behavior in healthy subjects, and this evidence hints to certain brain areas, hormones, and genetic factors to be fundamentally involved. The contribution of cortisol in trust has not yet elicited much attention in research, especially when specifically examined at basal cortisol levels. Trust has been previously studied in some neurological diseases but not in patients with epilepsy, and the influence of hormones on trust in these diseases remains yet unknown. Against this background, we designed an experimental study with a group of patients with juvenile myoclonic epilepsy and a group of healthy controls to compare trust behavior and plasma cortisol levels between the two groups. This economic game is frequently used in research to operationalize trust behavior. All participants further underwent neuropsychological assessment. Our results showed that there was no significant difference in trust behavior during the trust game, but a trend toward lower trust in patients. Furthermore, there was a significant difference in cortisol levels between groups with lower levels in patients. Interestingly, cortisol levels correlated with trust only in the patient group, but not in the control group. Future studies should specifically differentiate the effect of induced cortisol increases (e.g., acute stress) versus the effect of basal cortisol levels reflecting homeostasis or chronic stress on trust behavior and leverage the potential of comparison between patients and healthy controls.

Effects of Cognitive Functioning and Education on Later-Life Health Numeracy.

INTRODUCTION: Previous studies have shown an association between a high health numeracy and good cognitive functioning. OBJECTIVE: To investigate the moderation effect of education on this relationship and which brain structures support health numeracy. METHODS: We examined 70 healthy older persons (66% females; mean ± SD: age, 75.73 ± 4.52 years; education, 12.21 ± 2.94 years). The participants underwent a T1-weighted 3-T MRI and a neuropsychological assessment including a health numeracy task. Statistical parametric mapping was applied to identify focal changes in cortical thickness throughout the entire brain and to correlate image parameters with behavioral measures. RESULTS: Executive functions and mental calculation emerged as predictors of health numeracy (B = 0.22, p < 0.05, and B = 0.38, p < 0.01). An interaction was found between education and executive functions (B = -0.16, p = 0.01) and between education and mental calculation (B = -0.11, p < 0.05). Executive functions and mental calculation had an impact on health numeracy in participants with a low to intermediate edu-cation (≤12 years) but not in those with a higher education (>12 years). Health numeracy scores were associated with cortical thickness in the right dorsomedial prefrontal cortex and the right superior temporal gyrus (p = 0.01). CONCLUSIONS: Older people with a higher education perform better in health numeracy tasks than those with a lower education. They have access to previously acquired knowledge about ratio concepts and do not need to rely on executive functions and computational skills. This is highly relevant when decisions about health care have to be made.

Is an intact hippocampus necessary for answering 3 × 3? - Evidence from Alzheimer's disease.

Recent evidence has suggested that the hippocampus supports learning and retrieval of arithmetic facts during childhood and adolescence. Whether the hippocampus is also involved in retrieving overlearned arithmetic facts (such as 3 × 5 = 15) during adult age is open for investigation. In this study, we assessed whether patients with hippocampal atrophy due to Alzheimer's disease (AD) are still able to retrieve overlearned arithmetic facts from memory. Sixteen patients (n = 13 with AD, n = 3 with Mild Cognitive Impairment - MCI) were evaluated using standard radiological, neurological, and neuropsychological test procedures. We adopted a multiple single-case analysis in order to acknowledge possible dissociations between hippocampal degeneration and intact arithmetic fact retrieval. All patients performed a neuropsychological screening battery assessing episodic memory as well as arithmetic processing, and underwent a 3-Tesla MRI procedure. A morphometric analysis comprising estimation of both cortical thickness and hippocampal volume, which also included a subfield analysis, was conducted. All patients had marked hippocampal atrophy (bilateral n = 15, unilateral n = 1) in comparison to healthy matched controls and showed deficits in episodic memory (delayed recall). However, 13 out of 16 patients performed in the average range of standardised norms during retrieval of overlearned arithmetic facts (i.e. multiplication tables). Our results suggest that intact retrieval of consolidated arithmetic facts from memory does not depend on the integrity of the hippocampus. This is in line with the view that the hippocampus plays a dynamic and time-limited role in arithmetic processing. While the hippocampus seems to be necessary for learning and consolidating new arithmetic facts in memory, it might not be critically involved in retrieving arithmetic facts when these are well consolidated in memory.

Wakeful resting and memory retention: a study with healthy older and younger adults.

Studies indicate that a brief period of wakeful rest after learning supports memory retention, whereas distraction weakens it. It is open for investigation whether advanced age has a significant effect on the impact of post-learning wakeful rest on memory retention for verbal information when compared to a cognitively demanding distraction task. In this study, we examined (1) whether post-learning rest promotes verbal memory retention in younger and older adults and (2) whether the magnitude of the rest benefit changes with increasing age. Younger adults and older adults learned and immediately recalled two consecutive word lists. After one word list, participants rested wakefully for 8 min; after the other list, they solved matrices. Memory performance was again tested in a surprise free recall test at the end of the experimental session. We found that, overall, younger adults outperformed older adults. Also, memory retention was higher following a wakeful rest phase compared to distraction. A detailed analysis revealed that this wakeful rest benefit was significant for the older adults group, whereas the younger adults group retained a similar amount of information in both post-encoding conditions. We assume that older adults can profit more from a wakeful rest phase after learning and are more prone to distraction than younger adults. With increasing age, a short break immediately after information uptake may help better retain the previously learned information, while distraction after learning tends to weaken memory retention.

Reasoning and mathematical skills contribute to normatively superior decision making under risk: evidence from the game of dice task.

In this study, we assessed to what extent reasoning improves performance in decision making under risk in a laboratory gambling task (Game of Dice Task-Double, GDT-D). We also investigated to what degree individuals with above average mathematical competence decide better than those with average mathematical competence. Eighty-five participants performed the GDT-D and several numerical tasks. Forty-two individuals were asked to calculate the probabilities and the outcomes associated with the different options of the GDT-D before performing it. The other 43 individuals performed the GDT-D at the beginning of the test session. Both reasoning and mathematical competence had a positive effect on decision making. Different measures of mathematical competence correlated with advantageous performance in decision making. Results suggest that decision making under explicit risk conditions improves when individuals are encouraged to reflect about the contingencies of a decision situation. Interventions based on numerical reasoning may also be useful for patients with difficulties in decision making.

Oxygen desaturation during night sleep affects decision-making in patients with obstructive sleep apnea.

This study assessed decision-making and its associations with executive functions and sleep-related factors in patients with obstructive sleep apnea. Thirty patients with untreated obstructive sleep apnea and 20 healthy age- and education-matched controls performed the Iowa Gambling Task, a decision-making task under initial ambiguity, as well as an extensive neuropsychological test battery. Patients, but not controls, also underwent a detailed polysomnographic assessment. Results of group analyses showed that patients performed at the same level of controls on the Iowa Gambling Task. However, the proportion of risky performers was significantly higher in the patient group than in the control group. Decision-making did not correlate with executive functions and subjective ratings of sleepiness, whereas there was a significant positive correlation between advantageous performance on the Iowa Gambling Task and percentage of N2 sleep, minimal oxygen saturation, average oxygen saturation and time spent below 90% oxygen saturation level. Also, the minimal oxygen saturation accounted for 27% of variance in decision-making. In conclusion, this study shows that a subgroup of patients with obstructive sleep apnea may be at risk of disadvantageous decision-making under ambiguity. Among the sleep-related factors, oxygen saturation is a significant predictor of advantageous decision-making.

Objective and subjective cognitive outcomes one year after COVID-19.

OBJECTIVE: This study aimed to evaluate subjective cognitive, physical, and mental health symptoms as well as objective cognitive deficits in COVID-19 patients 1 year after infection. METHODS: This was a cross-sectional study. Seventy-four patients, who contracted a SARS-CoV-2 infection in 2020, underwent an in-person neuropsychological assessment in 2021. This included standardized tests of memory, attention, and executive functions. In addition, participants also responded to scales on subjective attention deficits, mental health symptoms, and fatigue. Patients' scores were compared to published norms. RESULTS: Patients (N = 74) had a median age of 56 years (42% female). According to the initial disease severity, they were classified as mild (outpatients, 32%), moderate (hospitalized, non-ICU-admitted, 45%), or severe (ICU-admitted, 23%). Hospitalized patients were more often affected than outpatients. In general, deficits were most common in attention (23%), followed by memory (15%) and executive functions (3%). Patients reported increased levels of fatigue (51%), anxiety (30%), distractibility in everyday situations (20%), and depression (15%). An additional analysis suggested an association between lower scores in an attention task and hyperferritinemia. As indicated by a hierarchical regression analysis, subjective distractibility was significantly predicted by current anxiety and fatigue symptoms but not by objective attention performance (final model, adj-R2 = 0.588, P < 0.001). INTERPRETATION: One year after infection, COVID-19 patients can have frequent attention deficits and can complain about symptoms such as fatigue, anxiety, and distractibility. Anxiety and fatigue, more than objective cognitive deficits, have an impact on the patients' experienced impairments in everyday life.

Challenges in Understanding Numerical Learning: Editorial for Brain Sciences Special Issue "Neurocognitive Signatures of Math (Learning) across the Lifespan and Their Interrelation with Other Aspects of Cognition and Emotion".

Living in our information- and technology-driven society at the beginning of the 21st century requires the ability to understand and handle numbers not only for a successful career but also for coping with everyday life tasks [...].

Pain in Multiple System Atrophy a Systematic Review and Meta-Analysis.

Background: Individuals with multiple system atrophy (MSA) often complain about pain, nonetheless this remains a poorly investigated non-motor feature of MSA. Objectives: Here, we aimed at assessing the prevalence, characteristics, and risk factors for pain in individuals with MSA. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines, we systematically screened the PubMED, Cochrane, and Web of Science databases for papers published in English until September 30, 2022, combining the following keywords: "pain," "multiple system atrophy," "MSA," "olivopontocerebellar atrophy," "OPCA," "striatonigral degeneration," "SND," "Shy Drager," and "atypical parkinsonism." Results: The search identified 700 records. Sixteen studies provided information on pain prevalence in cohorts of MSA individuals and were included in a qualitative assessment based on the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Thirteen studies (11 cross-sectional, two longitudinal) scored ≥14 points on QUADAS assessment and were included in a quantitative analysis, pooling data from 1236 MSA individuals. The resulting pooled prevalence of pain in MSA was 67% (95% confidence intervals [CI] = 57%-75%), and significantly higher in individuals with MSA of parkinsonian rather than cerebellar type (76% [95% CI = 63%-87%] vs. 45% [95% CI = 33%-57%], P = 0.001). Pain assessment tools and collected information were highly heterogeneous across studies. Two studies reported pain treatment strategies and found that only every second person with MSA complaining about pain had received targeted treatment. Conclusions: We found that pain is a frequent, but still under-recognized and undertreated feature of MSA. Further research is needed to improve pain detection and treatment in MSA.

Brain microdialysate tau dynamics predict functional and neurocognitive recovery after poor-grade subarachnoid haemorrhage.

Subarachnoid haemorrhage is a devastating disease that results in neurocognitive deficits and a poor functional outcome in a considerable proportion of patients. In this study, we investigated the prognostic value of microtubule-associated tau protein measured in the cerebral microdialysate for long-term functional and neuropsychological outcomes in poor-grade subarachnoid haemorrhage patients. We recruited 55 consecutive non-traumatic subarachnoid haemorrhage patients who underwent multimodal neuromonitoring, including cerebral microdialysis. Mitochondrial dysfunction was defined as lactate-to-pyruvate ratio >30 together with pyruvate >70 mmol/L and metabolic distress as lactate-to-pyruvate ratio >40. The multidimensional 12-month outcome was assessed by means of the modified Rankin scale (poor outcome: modified Rankin scale ≥4) and a standardized neuropsychological test battery. We used multivariable generalized estimating equation models to assess associations between total microdialysate-tau levels of the first 10 days after admission and hospital complications and outcomes. Patients were 56 ± 12 years old and presented with a median Hunt & Hess score of 5 (interquartile range: 3-5). Overall mean total microdialysate-tau concentrations were highest within the first 24 h (5585 ± 6291 pg/mL), decreased to a minimum of 2347 ± 4175 pg/mL on Day 4 (P < 0.001) and remained stable thereafter (P = 0.613). Higher total microdialysate-tau levels were associated with the occurrence of delayed cerebral ischaemia (P = 0.001), episodes of metabolic distress (P = 0.002) and mitochondrial dysfunction (P = 0.034). Patients with higher tau levels had higher odds for a poor 12-month functional outcome (adjusted odds ratio: 2.61; 95% confidence interval: 1.32-5.17; P = 0.006) and impaired results in the trail making test-B (adjusted odds ratio: 3.35; 95% confidence interval: 1.16-9.68; P = 0.026) indicative of cognitive flexibility. Total microdialysate-tau levels significantly decreased over the first 10 days (P < 0.05) in patients without delayed cerebral ischaemia or good functional outcomes and remained high in those with delayed cerebral ischaemia and poor 12-month outcomes, respectively. Dynamic changes of total tau in the cerebral microdialysate may be a useful biomarker for axonal damage associated with functional and neurocognitive recovery in poor-grade subarachnoid haemorrhage patients. In contrast, ongoing axonal damage beyond Day 3 after bleeding indicates a higher risk for delayed cerebral ischaemia as well as a poor functional outcome.

Validation of the Innsbruck REM sleep behavior disorder inventory.

A diagnosis of definite REM sleep behavior disorder requires both a positive history for REM sleep behavior disorder and polysomnographic demonstration of REM sleep without atonia. To improve and facilitate screening for REM sleep behavior disorder, there is a need for simple clinical tools with sufficient sensitivity and specificity for the identification of subjects with probable REM sleep behavior disorder. We developed a short REM sleep behavior disorder screening questionnaire with 7 REM sleep behavior disorder- and 2 non-REM sleep behavior disorder-specific control items and performed a validation study in 70 REM sleep behavior disorder subjects and 140 sleep disorder controls. Response patterns to all 7 REM sleep behavior disorder-specific items differed between REM sleep behavior disorder and non-REM sleep behavior disorder patients (all P < 0.05), whereas the 2 non-REM sleep behavior disorder-specific control items did not differentiate between REM sleep behavior disorder and non-REM sleep behavior disorder (all P > .05). In 5 of the 7 REM sleep behavior disorder-specific items, AUC was greater than 0.700. These 5 items were included in the Innsbruck REM sleep behavior disorder inventory. In this questionnaire, a cutoff of 0.25 (number of positive symptoms divided by number of answered questions) had a sensitivity of 0.914 and a specificity of 0.857 for both idiopathic and Parkinson's-related REM sleep behavior disorder (AUC, 0.886). The Innsbruck REM sleep behavior disorder inventory is a promising, easy-to-use, short screening tool for REM sleep behavior disorder with excellent sensitivity and specificity for both idiopathic and Parkinson's-related REM sleep behavior disorder.

Selective IGT decision-making impairment in a patient with juvenile Parkinson's disease and pathological gambling: a role for dopaminergic therapy?

The orbitofrontal cortex and the dopaminergic system are structures involved in managing impulsivity and sensibility to reinforcements, and both are typically impaired in Parkinson's disease (PD). Also, l-DOPA treatment can contribute to the development of the 'Dopamine Dysregulation Syndrome', a syndrome that can influence the patients' personality and lead to risk-taking behaviors. In this study, we describe the case of a 42-year-old woman (LT) affected by juvenile PD, treated with both l-DOPA and dopamine agonists, who showed a sudden onset of pathological gambling (PG), as the only neuropsychiatric symptom. We assessed LT with a full neuropsychological battery and the Iowa Gambling Task (IGT), in order to describe her specific failure in decision making. LT's performance on the IGT is compared with that of 15 non-demented PD patients under therapy with dopamine agonists and no behavioral dysregulations and with that of 16 age- and education-matched healthy subjects. Results showed fully preserved memory, executive functions, and reasoning abilities for LT, but a remarkable and stable impairment in the IGT. Performance of LT on the IGT is significantly lower than that of both control groups. This case shows, for the first time, that high cognitive functioning and preserved executive functions are no guarantee for advantageous decision making, and that the onset of PG is consistent with selective orbitofrontal disruption and side-effects of dopamine agonist therapy. It is also showed that the IGT is a useful neuropsychological device to detect specific risk-taking behaviors, which compromise functioning in real life.