Publications by authors named "Beatrice Heim"

26 Publications

  • Page 1 of 1

Tit for tat: costly punishment in manifest Huntington's disease.

Neurodegener Dis 2021 Oct 27. Epub 2021 Oct 27.

Objective: We aimed to investigate costly punishment in patients with HD.

Background: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease with motor, cognitive, and psychiatric symptoms. As neuropsychiatric abnormalities often precede motor symptoms, we wanted to assess whether costly punishment is part of the neuropsychological profile of patients with HD.

Methods: A total of 40 non demented subjects were prospectively enrolled in this study with a between-subject design comparing manifest HD patients (n=18) to healthy controls (HC; n=22). All participants performed eight rounds of a costly punishment task, in which money was shared unevenly in 5 rounds or in a fair manner in the remaining three rounds. Participants then had to decide whether they wanted to punish the trustee. Furthermore, all participants underwent neuropsychological background tasks.

Results: HD patients performed worse in the neuropsychological background tests compared to HC (all p-values<0.05). Moreover, HD patients punished more often in fair (Wald x2=5.03, p=0.025) but not in unfair rounds (Wald x2=1.63, p=0.202).

Conclusions: Our results demonstrate increased costly punishment during fair conditions in HD patients. Whether this behaviour is due to a lack of recognition of social norms, an impairment in top-down inhibition, or an effect of anti-dopaminergic medication remains unclear.
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http://dx.doi.org/10.1159/000520303DOI Listing
October 2021

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

Qual Life Res 2021 Sep 28. Epub 2021 Sep 28.

Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.

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.
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http://dx.doi.org/10.1007/s11136-021-02998-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476326PMC
September 2021

Extending the Spectrum of Nonmotor Symptoms with Olfaction in Premotor Huntington's Disease: A Pilot Study.

Neurodegener Dis 2020 9;20(5-6):207-211. Epub 2021 Jul 9.

Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.

Objective: The aim of this pilot study was to investigate change of olfactory functions in Huntington's disease (HD).

Background: HD is a neurodegenerative disease characterized by motor, cognitive, and behavioral abnormalities. There are several studies reporting olfactory dysfunction in manifest and some studies in premanifest HD carriers, and a recent neuropathological study demonstrated HD-specific protein aggregation in the anterior olfactory nucleus in HD patients. In this study, we wanted to assess olfactory functions as a possible early nonmotor symptom of HD mutation carriers without disease-specific motor symptoms and HD patients.

Methods: All participants had genetic confirmed HD and were prospectively recruited during their routine control in a specialized outpatient clinic of the Medical University of Innsbruck, Department of Neurology, Austria. Healthy controls (HCs) were caregivers from patients. They were only included if they were younger than 70 years, scored more than 24/30 points on the Mini Mental State Examination, and had no other disease compromising olfactory function. Furthermore, all participants were tested on the Sniffin' sticks 16-items identification test.

Results: We included 23 patients with manifest HD, 13 HD mutation carriers, and 19 HCs. Mutation carriers showed significant impaired odor identification compared to HCs (p < 0.001), as well as Huntington's patients compared with both mutation carriers (p = 0.003) and HCs (p < 0.001).

Conclusions: The results of this pilot study suggest that olfactory dysfunction may be an early nonmotor symptom of HD and could be a potential marker to assess disease progression.
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http://dx.doi.org/10.1159/000518136DOI Listing
July 2021

Differentiating PSP from MSA using MR planimetric measurements: a systematic review and meta-analysis.

J Neural Transm (Vienna) 2021 10 8;128(10):1497-1505. Epub 2021 Jun 8.

Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.

Differential diagnosis of parkinsonian syndromes is considered one of the most challenging in neurology. Quantitative MR planimetric measurements were reported to discriminate between progressive supranuclear palsy (PSP) and non-PSP-parkinsonism. Several studies have used midbrain to pons ratio (M/P) and the Magnetic Resonance Parkinsonism Index (MRPI) in distinguishing PSP patients from those with Parkinson's disease. The current meta-analysis aimed to compare the performance of these measures in discriminating PSP from multiple system atrophy (MSA). A systematic MEDLINE review identified 59 out of 2984 studies allowing a calculation of sensitivity and specificity using the MRPI or M/P. Meta-analyses of results were carried out using random effects modelling. To assess study quality and risk of bias, the QUADAS-2 tool was used. Eight studies were suitable for analysis. The meta-analysis showed a pooled sensitivity and specificity for the MRPI of PSP versus MSA of 79.2% (95% CI 72.7-84.4%) and 91.2% (95% CI 79.5-96.5%), and 84.1% (95% CI 77.2-89.2%) and 89.2% (95% CI 81.8-93.8%), respectively, for the M/P. The QUADAS-2 toolbox revealed a high risk of bias regarding the methodological quality of patient selection and index test, as all patients were seen in a specialized outpatient department without avoiding case control design and no predefined threshold was given regarding MRPI or M/P cut-offs. Planimetric brainstem measurements, in special the MRPI and M/P, yield high diagnostic accuracy for the discrimination of PSP from MSA. However, there is an urgent need for well-designed, prospective validation studies to ameliorate the concerns regarding the risk of bias.
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http://dx.doi.org/10.1007/s00702-021-02362-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528799PMC
October 2021

Safety and Tolerability of Active Immunotherapy Targeting α-Synuclein with PD03A in Patients with Early Parkinson's Disease: A Randomized, Placebo-Controlled, Phase 1 Study.

J Parkinsons Dis 2021 ;11(3):1079-1089

AFFiRiS AG, Vienna, Austria.

Background: Immunotherapies targeting α-synuclein aim to limit its extracellular spread in the brain and prevent progression of pathology in Parkinson's disease (PD). PD03A is a specific active immunotherapy (SAIT) involving immunization with a short peptide formulation.

Objective: This phase 1 study characterized the safety and tolerability of PD03A in patients with early PD. A key secondary objective was to evaluate immunological activity following immunization.

Methods: This was a phase 1 study of two different doses of PD03A versus placebo in PD patients. Patients were randomized (1:1:1) to receive four priming plus one booster vaccination of PD03A 15μg, PD03A 75μg or placebo and were followed for 52 weeks.

Results: Overall, 36 patients were randomized, of which 35 received five immunizations and completed the study. All patients experienced at least one adverse event. Transient local injection site reactions affected all but two patients; otherwise most AEs were considered unrelated to study treatment. A substantial IgG antibody response against PD03 was observed with a maximum titer achieved at Week-12. Differences in titers between both active groups versus placebo were statistically significant from the second immunization at Week-8 until Week-52.

Conclusion: The safety profile and positive antibody response of PD03A supports the further development of active immunotherapeutic approaches for the treatment of PD.
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http://dx.doi.org/10.3233/JPD-212594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461711PMC
January 2021

Alpha-synuclein seeds in olfactory mucosa of patients with isolated REM sleep behaviour disorder.

Brain 2021 05;144(4):1118-1126

Department of Neurosciences, Biomedicine and Movement Sciences University of Verona, Verona, Italy.

Isolated REM sleep behaviour disorder (RBD) is an early-stage α-synucleinopathy in most, if not all, affected subjects. Detection of pathological α-synuclein in peripheral tissues of patients with isolated RBD may identify those progressing to Parkinson's disease, dementia with Lewy bodies or multiple system atrophy, with the ultimate goal of testing preventive therapies. Real-time quaking-induced conversion (RT-QuIC) provided evidence of α-synuclein seeding activity in CSF and olfactory mucosa of patients with α-synucleinopathies. The aim of this study was to explore RT-QuIC detection of α-synuclein aggregates in olfactory mucosa of a large cohort of subjects with isolated RBD compared to patients with Parkinson's disease and control subjects. This cross-sectional case-control study was performed at the Medical University of Innsbruck, Austria, the Hospital Clinic de Barcelona, Spain, and the University of Verona, Italy. Olfactory mucosa samples obtained by nasal swab in 63 patients with isolated RBD, 41 matched Parkinson's disease patients and 59 matched control subjects were analysed by α-synuclein RT-QuIC in a blinded fashion at the University of Verona, Italy. Median age of patients with isolated RBD was 70 years, 85.7% were male. All participants were tested for smell, autonomic, cognitive and motor functions. Olfactory mucosa was α-synuclein RT-QuIC positive in 44.4% isolated RBD patients, 46.3% Parkinson's disease patients and 10.2% control subjects. While the sensitivity for isolated RBD plus Parkinson's disease versus controls was 45.2%, specificity was high (89.8%). Among isolated RBD patients with positive α-synuclein RT-QuIC, 78.6% had olfactory dysfunction compared to 21.4% with negative α-synuclein RT-QuIC (P < 0.001). The extent of olfactory dysfunction was more severe in isolated RBD patients positive than negative for olfactory mucosa a-synuclein RT-QuIC (P < 0.001). We provide evidence that the α-synuclein RT-QuIC assay enables the molecular detection of neuronal α-synuclein aggregates in olfactory mucosa of patients with isolated RBD and Parkinson's disease. Although the overall sensitivity was moderate in this study, nasal swabbing is attractive as a simple, non-invasive test and might be useful as part of a screening battery to identify subjects in the prodromal stages of α-synucleinopathies. Further studies are needed to enhance sensitivity, and better understand the temporal dynamics of α-synuclein seeding in the olfactory mucosa and spreading to other brain areas during the progression from isolated RBD to overt α-synucleinopathy, as well the impact of timing, disease subgroups and sampling technique on the overall sensitivity.
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http://dx.doi.org/10.1093/brain/awab005DOI Listing
May 2021

Birds of a Feather Flock Together: Disadvantageous Decision Making in Augmented Restless Legs Syndrome Patients with and without Impulse Control Disorders.

Brain Sci 2021 Mar 17;11(3). Epub 2021 Mar 17.

Department of Neurology, Medical University of Innsbruck, 6020 Innsbruck, Austria.

Background: Augmentation (AUG) in patients with restless legs syndrome (RLS) can be associated with impulse control disorder (ICD) symptoms, such as compulsive sexual behavior, gambling disorder or compulsive shopping. In this study, we wanted to assess whether RLS patients with AUG differ in decision making from those patients who have augmentation and in addition ICD symptoms (AUG + ICD) in a post hoc analysis of a patient cohort assessed in a previous study.

Methods: In total, 40 RLS patients with augmentation (19 AUG + ICD, 21 AUG without ICDs) were included. RLS diagnosis, severity, and diagnosis of augmentation were made by sleep disorder specialists. ICD symptoms were assessed using semi-structured interviews. All patients performed the beads task, which is an information sampling task where participants must decide from which of the two cups colored beads were drawn. Results were compared to 21 healthy controls (HC).

Results: There was no difference in information sampling or irrational decision making between AUG and AUG + ICD patients ( = 0.67 and = 1.00, respectively). Both patient groups drew less beads and made more irrational decisions than HC (all -values < 0.03, respectively).

Conclusions: Our results suggest that augmentation itself is associated with poorer decision making even in the absence of ICD symptoms. Further studies are necessary to explore whether rapid and hasty decision making are a harbinger of augmentation in RLS.
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http://dx.doi.org/10.3390/brainsci11030383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002414PMC
March 2021

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

Eur J Neurol 2021 Oct 3;28(10):3348-3359. Epub 2021 May 3.

Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.

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.
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http://dx.doi.org/10.1111/ene.14803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250725PMC
October 2021

Diagnostic accuracy of MR planimetry in clinically unclassifiable parkinsonism.

Parkinsonism Relat Disord 2021 01 24;82:87-91. Epub 2020 Nov 24.

Department of Neurology, Medical University of Innsbruck, Austria; Neuroimaging Core Facility, Medical University Innsbruck, Innsbruck, Austria. Electronic address:

Introduction: Quantitative MR planimetric measurements were reported to discriminate between progressive supranuclear palsy (PSP) and non-PSP parkinsonism, yet few data exist on the usefulness of these markers in early disease stages.

Methods: The pons-to-midbrain area ratio (P/M) and the Magnetic Resonance Parkinsonism Index (MRPI) as well as new indices, termed P/M2.0 and MRPI2.0, multiplying the former by a ratio of the third ventricle (3rdV) width/frontal horns (FH) width, were calculated on T1-weighted images in 84 patients with clinically unclassifiable neurodegenerative parkinsonism (CUP) at the time of imaging. Areas under the curve (AUCs) of these markers for predicting future PSP was determined. The final clinical diagnosis was made after at least 24 months of follow-up.

Results: Final diagnosis was Parkinson's disease in 55 patients, multiple system atrophy in 12 cases, and PSP in 17. At baseline imaging, patients with a final PSP diagnosis had significantly higher MRPI, P/M, MRPI2.0 and P/M2.0 values compared to the other groups. AUCs in discriminating between future PSP and non-PSP parkinsonism were 0.91 for both the P/M and the MRPI and 0.98 for the P/M2.0 and the MRPI2.0.

Conclusions: Brainstem-derived MR planimetric measures yield high diagnostic accuracy for separating PSP from non-PSP parkinsonism in early disease stages when clinical criteria are not yet fully met. Consistent with the underlying pathology in PSP, our study suggests that inclusion of 3V width makes P/M2.0 and MRPI2.0 more accurate in diagnosing early stage PSP patients than the P/M and MRPI.
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http://dx.doi.org/10.1016/j.parkreldis.2020.11.019DOI Listing
January 2021

The Frontal Assessment Battery in RLS patients with and without augmentation.

Sleep Med 2020 11 10;75:456-458. Epub 2020 Sep 10.

Department of Neurology, Medical University of Innsbruck, Christoph-Probst-Platz 1, 6020, Innsbruck, Austria. Electronic address:

Objective: We assessed frontal executive functions in patients with RLS/WED with and without augmentation and compared the results to healthy controls.

Methods: We recruited 38 patients with RLS/WED. A total of 23 patients were treated with dopaminergic therapy and showed no signs of augmentation and 15 patients had a history of augmentation (AUG). Results were compared to 21 healthy controls. All individuals were assessed by the Frontal Assessment Battery (FAB) and the MMSE. Furthermore, impulsivity was assessed during a semi-structured interview.

Results: Patients with AUG performed worse in the FAB than healthy controls and RLS/WED patients without AUG (p = 0.001, η = 0.201). When we assessed the subtests of the FAB separately, we found a significant difference in the subtest assessing inhibitory control (p = 0.008, η = 0.138).

Conclusions: Our findings suggest an impaired executive function in RLS/WED patients with augmentation compared to RLS/WED patients without augmentation and healthy controls. Long term neuroplastic changes within the prefrontal cortex may be the underlying cause for these results. However, further studies in a larger sample size and with a more extensive neuropsychological test battery are needed to confirm our preliminary results.
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http://dx.doi.org/10.1016/j.sleep.2020.09.010DOI Listing
November 2020

Time will tell: Decision making in premanifest and manifest Huntington's disease.

Brain Behav 2020 11 26;10(11):e01843. Epub 2020 Sep 26.

Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.

Objective: To investigate cognitive flexibility in premanifest and manifest Huntington's disease (HD).

Background: HD is an autosomal dominant neurodegenerative disease characterized by motor, cognitive, and behavioral abnormalities with typical motor symptoms. In this study, we wanted to assess decision making in premanifest (pre-HD) and manifest HD patients.

Methods: A total of 77 non-demented subjects including 29 pre-HD, 22 manifest HD patients, and 26 healthy controls (HC) were included. We stratified the pre-HD group based on their estimated years to disease onset into a far (FAR, n = 13) and a near (NEAR, n = 16) group. Furthermore, participants performed the Montreal cognitive assessment battery (MoCA), the trail making task part A and B (TMT A, TMT B), the Symbol digit modalities test (SDMT), and the beads task.

Results: In the beads task, HD patients gathered less information than all other groups (all p-values < .001). Furthermore, the NEAR group gathered less information than the FAR group (p < .001) and HC (p = .001). There was no difference between the HC and the FAR group (p = 1.0). In the TMT and the SDMT, HD patients were slower than all other groups (all p-values < .01) but there were no other significant differences.

Conclusions: Decision making with a higher degree of uncertainty may be an early neuropsychological sign to indicate the disease process prior to reaching criteria for motor diagnosis of HD.
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http://dx.doi.org/10.1002/brb3.1843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667290PMC
November 2020

Augmentation in restless legs syndrome: an eye tracking study on emotion processing.

Ann Clin Transl Neurol 2020 09 12;7(9):1620-1627. Epub 2020 Aug 12.

Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.

Objective: To assess emotional processing and alexithymia in patients with restless legs syndrome (RLS) with augmentation versus those who never had augmentation.

Methods: We recruited 26 patients who had a history of augmentation (AUG), either current or past, 27 RLS patients treated with dopamine agonists who never had augmentation (RLS controls), and 21 healthy controls (HC). All participants were screened for impulse control disorders (ICDs). Alexithymia was assessed by means of the Toronto Alexithymia Scale - 20 (TAS-20). Facial emotion recognition was tested through an eye-tracking task. Furthermore, all participants performed neuropsychological tests assessing global cognitive status, impulsivity, anxiety, and depression.

Results: ICD symptoms occurred more frequently in AUG patients than in RLS controls (P = 0.047). Patients with AUG scored higher on the TAS-20 (P = 0.007) and the attentional subdomain of an impulsivity scale (BIS-11; P = 0.015) compared to HC. Patients with AUG also performed worse on the facial emotion recognition task relative to RLS controls (P = 0.009) and HC (P = 0.003). We found a group difference for the time to first fixation and the fixation count in the mouth region (P = 0.019 and P = 0.021, respectively). There were no other differences in the eye tracking examination.

Interpretation: This study showed evidence of poorer emotional processing in patients who had augmentation compared to RLS patients without augmentation and healthy controls. The altered exploration pattern of faces and the higher alexithymia scores suggest abnormalities in emotion processing in patients with augmentation.
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http://dx.doi.org/10.1002/acn3.51144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480921PMC
September 2020

Non-Motor Symptoms in Parkinson's Disease are Reduced by Nabilone.

Ann Neurol 2020 10 31;88(4):712-722. Epub 2020 Aug 31.

Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.

Objective: The objective of this study was to assess the efficacy and safety of nabilone, a synthetic tetrahydrocannabinol analogue, as a treatment for non-motor symptoms (NMS) in Parkinson's disease (PD).

Methods: This was a phase II placebo-controlled, double-blind, parallel-group, enriched enrollment randomized withdrawal trial conducted at the Medical University Innsbruck. A random sample of 47 patients with PD with stable motor disease and disturbing NMS defined by a score of ≥4 points on the Movement Disorder Society - Unified PD Rating Scale-I (MDS-UPDRS-I) underwent open-label nabilone titration (0.25 mg once daily to 1 mg twice daily, phase I). Responders were randomized 1:1 to continue with nabilone or switch to placebo for 4 weeks (phase II). The primary efficacy criterion was the change of the MDS-UPDRS-I between randomization and week 4. Safety was analyzed in all patients who received at least one nabilone dose.

Results: Between October 2017 and July 2019, 19 patients received either nabilone (median dose = 0.75 mg) or placebo. At week 4, mean change of the MDS-UPDRS-I was 2.63 (95% confidence interval [CI] 1.53 to 3.74, p = 0.002, effect size = 1.15) in the placebo versus 1.00 (95% CI -0.16 to 2.16, p = 0.280, effect size = 0.42) in the nabilone-group (difference: 1.63, 95% CI 0.09 to 3.18, p = 0.030, effect size = 0.66). Seventy-seven percent of patients had adverse events (AEs) during open-label titration, most of them were transient. In the double-blind phase, similar proportions of patients in each group had AEs (42% in the placebo group and 32% in the nabilone group). There were no serious AEs.

Interpretation: Our results highlight the potential efficacy of nabilone for patients with PD with disturbing NMS, which appears to be driven by positive effects on anxious mood and night-time sleep problems.

Trial Registry: ClinicalTrials.gov (NCT03769896) and EudraCT (2017-000192-86). ANN NEUROL 2020;88:712-722.
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http://dx.doi.org/10.1002/ana.25864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540547PMC
October 2020

Cognition in multiple system atrophy: a single-center cohort study.

Ann Clin Transl Neurol 2020 02 7;7(2):219-228. Epub 2020 Feb 7.

Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.

Objective: Cognitive impairment in multiple system atrophy (MSA) is common, but remain poorly characterized. We evaluated cognitive and behavioral features in MSA patients and assessed between-group differences for MSA subtypes and the effect of orthostatic hypotension (OH) on cognition.

Methods: This retrospective study included 54 patients with clinical diagnosis of possible and probable MSA referred to the Department of Neurology at Medical University of Innsbruck between 2000 and 2018. Neurological work-up included comprehensive neuropsychological testing including Consortium to Establish a Registry for Alzheimer's Disease (CERAD-plus) test battery, Frontal Assessment Battery (FAB), digit span test (DST), clock drawing task (CLOX1), and Hospital Anxiety and Depression Scale (HADS-D).

Results: The mean MMSE score was 27.6 points. Overall, slight to moderate cognitive impairment was noted in up to 40% of patients, with predominant impairment of executive function and verbal memory. Patients with the cerebellar variant performed significantly worse than patients with the parkinsonian type (P < 0.05) in a screening of executive functions (FAB) and in phonemic verbal fluency. Depression and anxiety scores were elevated in 28% and 22% of MSA patients, respectively. Cognitive profile, depression, and anxiety levels were comparable between patients with and without OH.

Interpretation: Cognitive deficits are relatively frequent in MSA and primarily affect executive functions and verbal memory. Future comparative studies including Parkinson dementia, Lewy body disease, and MSA cases with and without OH are required to elucidate disease-specific cognitive profiles in these synucleinopathies and to examine the influence of cardiovascular autonomic dysfunction on cognitive function in MSA.
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http://dx.doi.org/10.1002/acn3.50987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034507PMC
February 2020

Structural Imaging in Atypical Parkinsonism.

Int Rev Neurobiol 2018 24;142:67-148. Epub 2018 Sep 24.

Department of Neurology, Medical University Innsbruck, Innsbruck, Austria; Neuroimaging Research Core Facility, Medical University Innsbruck, Innsbruck, Austria. Electronic address:

Qualitative and quantitative structural magnetic resonance imaging offer objective measures of the underlying neurodegeneration in atypical parkinsonism. Regional changes in tissue volume, signal changes and increased deposition of iron as assessed with different structural MRI techniques are surrogate markers of underlying neurodegeneration and may reflect cell loss, microglial proliferation and astroglial activation. Structural MRI has been explored as a tool to enhance diagnostic accuracy in differentiating atypical parkinsonian disorders (APDs). Moreover, the longitudinal assessment of serial structural MRI-derived parameters offers the opportunity for robust inferences regarding the progression of APDs. This review summarizes recent research findings as (1) a diagnostic tool for APDs as well as (2) as a tool to assess longitudinal changes of serial MRI-derived parameters in the different APDs.
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http://dx.doi.org/10.1016/bs.irn.2018.08.010DOI Listing
May 2019

Prevalence and Associated Factors of Sarcopenia and Frailty in Parkinson's Disease: A Cross-Sectional Study.

Gerontology 2019 10;65(3):216-228. Epub 2018 Sep 10.

Department of Neurology, Innsbruck Medical University, Innsbruck, Austria,

Background: Sarcopenia and frailty are found in up to one-third of the general elderly population. Both are associated with major adverse health outcomes such as nursing home placement, disability, decreased quality of life, and death. Data on the frequency of both syndromes in Parkinson's disease (PD), however, are very limited.

Objective: We aimed to screen for sarcopenia and frailty in PD patients and to assess potential associations of both geriatric syndromes with demographic and clinical parameters as well as quality of life.

Methods: In this observational, cross-sectional study, we included 104 PD patients from a tertiary center and 330 non-PD controls from a population-based cohort aged > 65 years. All groups were screened for sarcopenia using the SARC-F score and for frailty using the Clinical Frailty Scale of the Canadian Study of Health and Aging (CSHA CFS). Prevalence rates of sarcopenia and frailty were also assessed in 18 PD patients from a population-based cohort aged > 65 years. Moreover, PD patients from the tertiary center were evaluated for motor and non-motor symptoms, quality of life, and dependency.

Results: The prevalence of sarcopenia was 55.8% (95% CI: 46.2-64.9%) in PD patients from the tertiary center and 8.2% (5.7-11.7%; p < 0.001) in non-PD controls. Frailty was detected in 35.6% (27.0-45.2%) and 5.2% (3.2-8.1%; p < 0.001). Prevalence rates for sarcopenia and frailty were 33.3% (16.1-56.4%; p = 0.004) and 22.2% (8.5-45.8%; p = 0.017) in the community-based PD sample. Both sarcopenia and frailty were significantly associated with longer disease duration, higher motor impairment, higher Hoehn and Yahr stages, decreased quality of life, higher frequency of falls, a higher non-motor symptom burden, institutionalization, and higher care levels in PD patients from a tertiary center compared to not affected PD patients (all p < 0.05).

Conclusions: Both frailty and sarcopenia are more common in PD patients than in the general community and are associated with a more adverse course of the disease. Future studies should look into underlying risk factors for the occurrence of sarcopenia and frailty in PD patients and into adequate management to prevent and mitigate them.
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http://dx.doi.org/10.1159/000492572DOI Listing
January 2020

Movement disorder society criteria for clinically established early Parkinson's disease.

Mov Disord 2018 10 25;33(10):1643-1646. Epub 2018 Aug 25.

Department of Neurology, Montreal General Hospital, Montreal, Quebec, Canada.

Background: In 2015, the International Parkinson and Movement Disorder Society published clinical diagnostic criteria for Parkinson's disease (PD). Although recent validation studies suggest high accuracy, one unmet need is for highly specific criteria for clinical trials in early/de novo PD.

Objectives: The objective of this study was to generate and test a PD diagnostic criteria termed "clinically established early PD."

Methods: We modified the Movement Disorder Society criteria to increase specificity for early PD by removing all disease duration components and changing red flags to absolute exclusions. We then estimated the sensitivity/specificity of clinically established early PD criteria in patients with disease duration <5 years, selected from a 626-patient validation study.

Results: After documentation of parkinsonism, 18 individual exclusion criteria are assessed that preclude the diagnosis of "clinically established early PD." Among 212 PD and 152 non-PD patients, the estimated specificity was 95.4%, with 69.8% sensitivity.

Conclusions: We describe high-specificity criteria for de novo PD, which are freely available for use in clinical trials. © 2018 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.27431DOI Listing
October 2018

Validation of the MDS clinical diagnostic criteria for Parkinson's disease.

Mov Disord 2018 10 25;33(10):1601-1608. Epub 2018 Aug 25.

Klinik für Neurologie, UKSH, Campus Kiel, Christian-Albrechts-Universität, Kiel, Germany.

Background: In 2015, the International Parkinson and Movement Disorder Society published clinical diagnostic criteria for Parkinson's disease. These criteria aimed to codify/reproduce the expert clinical diagnostic process and to help standardize diagnosis in research and clinical settings. Their accuracy compared with expert clinical diagnosis has not been tested. The objectives of this study were to validate the International Parkinson and Movement Disorder Society diagnostic criteria against a gold standard of expert clinical diagnosis, and to compare concordance/accuracy of the International Parkinson and Movement Disorder Society criteria to 1988 United Kingdom Brain Bank criteria.

Methods: From 8 centers, we recruited 626 parkinsonism patients (434 PD, 192 non-PD). An expert neurologist diagnosed each patient as having PD or non-PD, regardless of International Parkinson and Movement Disorder Society criteria (gold standard, clinical diagnosis). Then a second neurologist evaluated the presence/absence of each individual item from the International Parkinson and Movement Disorder Society criteria. The overall accuracy/concordance rate, sensitivity, and specificity of the International Parkinson and Movement Disorder Society criteria compared with the expert gold standard were calculated.

Results: Of 434 patients diagnosed with PD, 94.5% met the International Parkinson and Movement Disorder Society criteria for probable PD (5.5% false-negative rate). Of 192 non-PD patients, 88.5% were identified as non-PD by the criteria (11.5% false-positive rate). The overall accuracy for probable PD was 92.6%. In addition, 59.3% of PD patients and only 1.6% of non-PD patients met the International Parkinson and Movement Disorder Society criteria for clinically established PD. In comparison, United Kingdom Brain Bank criteria had lower sensitivity (89.2%, P = 0.008), specificity (79.2%, P = 0.018), and overall accuracy (86.4%, P < 0.001). Diagnostic accuracy did not differ according to age or sex. Specificity improved as disease duration increased.

Conclusions: The International Parkinson and Movement Disorder Society criteria demonstrated high sensitivity and specificity compared with the gold standard, expert diagnosis, with sensitivity and specificity both higher than United Kingdom Brain Bank criteria. © 2018 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.27362DOI Listing
October 2018

The diagnostic accuracy of the hummingbird and morning glory sign in patients with neurodegenerative parkinsonism.

Parkinsonism Relat Disord 2018 09 3;54:90-94. Epub 2018 Apr 3.

Department of Neurology, Innsbruck Medical University, Austria; Neuroimaging Core Facility, Medical University Innsbruck, Innsbruck, Austria. Electronic address:

Introduction: The hummingbird sign and the morning glory flower sign, reflecting midbrain pathology on MRI, have previously been shown to separate patients with progressive supranuclear palsy (PSP) from those with Parkinson's disease (PD) and multiple system atrophy (MSA). The aim of the present study was to determine the diagnostic accuracy and reproducibility of visual assessment of midbrain atrophy patterns in a large cohort of patients with neurodegenerative parkinsonism.

Methods: Retrospective analysis of midbrain atrophy patterns on T1-weighted MRI in a large cohort of patients with neurodegenerative parkinsonism and healthy controls who underwent MR imaging during their diagnostic work-up.

Results: 481 patients with neurodegenerative parkinsonism and 79 healthy controls were included in the present study. The presence of the hummingbird sign had a specificity of 99.5% and a positive predictive value of 96.1% for a diagnosis of PSP while sensitivity was suboptimal with 51.6%. Similarly, the presence of the morning glory flower sign yielded a specificity of 97.7% for a diagnosis of PSP, but sensitivity was only 36.8%. Sensitivity of both signs was 35.3% in early, clinically unclassifiable parkinsonism. Visual assessment of these midbrain alterations showed excellent inter-rater agreement.

Conclusion: Midbrain atrophy patterns are useful in the differential diagnosis of neurodegenerative parkinsonism but both the hummingbird sign and more so the morning glory flower sign suffer from low sensitivity, especially in early disease stages.
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http://dx.doi.org/10.1016/j.parkreldis.2018.04.005DOI Listing
September 2018

Cannabinoids for Treatment of Dystonia in Huntington's Disease.

J Huntingtons Dis 2018 ;7(2):167-173

Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.

Background: Motor symptoms in Huntington's disease (HD) are heterogeneous with dystonia being described as a symptom with a very high prevalence not only in juvenile cases.

Objective: Treatment options for dystonia are limited. Cannabinoids have been described as a potential treatment for patients with dystonia of a different origin. Here, we present early onset HD patients with a marked improvement of motor symptoms mainly due to alleviation of dystonia due to treatment with cannabinoids. In addition we review the current literature concerning the use of cannabinoids in HD.

Method: The Unified Huntington's Disease Rating Scale (UHDRS) motor score, including a chorea and dystonia subscore, was conducted before and after the start of cannabinoids in seven patients without any other changes in medication.

Results: The UHDRS motor score and the dystonia subscore (±SD) improved from 70.9 (25.5) to 60.6 (26.9) with a mean change of 10.3 [95% CI 6.0-14.6] and from 12.3 (4.0) to 8.0 (3.6) with a mean change of 4.3 [95% CI 2.3-6.3], respectively (both p = 0.018).

Conclusion: Improvement of motor symptoms, mainly dystonia, led to several relevant improvements from a global clinical perspective such as improvement of care, gait and fine motor skills and weight gain. Moreover, we observed changes in behavior with less irritability and apathy, as well as less hypersalivation in some cases.
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http://dx.doi.org/10.3233/JHD-170283DOI Listing
October 2019

Reflection impulsivity perceptual decision-making in patients with restless legs syndrome.

Ann Clin Transl Neurol 2018 03 30;5(3):315-322. Epub 2018 Jan 30.

Department of Neurology Medical University of Innsbruck Innsbruck Austria.

Objectives: The objective of this study was to investigate perceptual decision-making and reflection impulsivity in drug naïve patients with restless legs syndrome (RLS) and patients with dopaminergic therapy.

Methods: A total of 35 RLS patients (20 who were drug naïve regarding dopaminergic medication and 15 patients treated with dopaminergic therapy without augmentation or impulse control disorders) were included in this study. We used the Beads task and the Pixel task which assess reflection impulsivity and perceptual decision-making, respectively. Results were compared to 20 healthy controls.

Results: Both RLS patient groups gathered less evidence than healthy controls in the Beads task before making a decision ( < 0.001), but patients with dopaminergic treatment gathered less information than drug naïve patients ( = 0.026). Moreover, both patient groups made more choices against the evidence than healthy controls (both < 0.01), but there was no difference between the two patient groups. In the Pixel task, we found an effect of task difficulty on reaction times with patients and controls responding faster with reduced task difficulty. There was neither an effect of group on reaction times nor an effect of group on error rates.

Conclusions: Reflection impulsivity is common in RLS patients, regardless whether they are drug naïve or treated with dopaminergic therapy. Thus, RLS patients tend to gather less information compared to healthy controls which could have a negative effect on decision-making in daily life and should be investigated further.
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http://dx.doi.org/10.1002/acn3.535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5846451PMC
March 2018

Haste makes waste: Decision making in patients with restless legs syndrome with and without augmentation.

PLoS One 2017 5;12(4):e0174793. Epub 2017 Apr 5.

Department of Neurology, Medical University of Innsbruck, Innsbruck, Tyrol, Austria.

Objectives: To investigate decision making in patients with primary restless legs syndrome (RLS) with and without augmentation treated with dopaminergic medication.

Methods: A total of 64 non-demented RLS patients treated with dopaminergic medication with and without augmentation were included in this study. We used an information sampling task to assess how much evidence participants gather before making a decision. Performance was compared to the results of 21 healthy controls.

Results: All patients with and without augmentation gathered less information than healthy controls before making a decision (p<0.001), but there was no difference between the two patient groups (p = 1.0). Furthermore, both patient groups made more irrational decisions (e.g. decisions against the evidence they had at the time) than healthy controls (p≤0.002). In addition, RLS patients with augmentation made significantly more irrational decisions than RLS patients without augmentation (p = 0.037) and controls (p<0.001).

Conclusions: Our results show that RLS patients treated with dopaminergic drugs, regardless of having augmentation or not, jumped to conclusions and decided significantly more often against the evidence they had at the time of their decision. However, those with augmentation performed worse than all other groups and made more often irrational decisions, a phenomenon which is also common in patients with substance abuse or behavioural addictions. Thus, jumping to conclusions and deciding with a higher degree of uncertainty as well as irrational decision making is more common in RLS patients treated with dopaminergic medication particularly in those with augmentation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0174793PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381880PMC
September 2017

Magnetic resonance imaging for the diagnosis of Parkinson's disease.

J Neural Transm (Vienna) 2017 08 4;124(8):915-964. Epub 2017 Apr 4.

Department of Neurology, Medical University of Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria.

The differential diagnosis of parkinsonian syndromes is considered one of the most challenging in neurology and error rates in the clinical diagnosis can be high even at specialized centres. Despite several limitations, magnetic resonance imaging (MRI) has undoubtedly enhanced the diagnostic accuracy in the differential diagnosis of neurodegenerative parkinsonism over the last three decades. This review aims to summarize research findings regarding the value of the different MRI techniques, including advanced sequences at high- and ultra-high-field MRI and modern image analysis algorithms, in the diagnostic work-up of Parkinson's disease. This includes not only the exclusion of alternative diagnoses for Parkinson's disease such as symptomatic parkinsonism and atypical parkinsonism, but also the diagnosis of early, new onset, and even prodromal Parkinson's disease.
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http://dx.doi.org/10.1007/s00702-017-1717-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514207PMC
August 2017

Augmentation and impulsive behaviors in restless legs syndrome: Coexistence or association?

Neurology 2016 07 3;87(1):36-40. Epub 2016 Jun 3.

From the Departments of Neurology (B. Heim, A.D., A.H., A.S., L.Z., M.-T.P., E.B., M.D., K.S., W.P., B. Högl) and Psychology (M.-T.P.), Medical University Innsbruck, Austria; and Department of Molecular Neuroscience and Reta Lila Weston Institute for Neurological Studies (A.D.), University of London, UK.

Objectives: To assess the frequency of impulse control disorders (ICDs) in patients with restless legs syndrome (RLS) with and without augmentation under dopaminergic therapy in a case-control study. Augmentation and ICDs are both serious complications of dopaminergic treatment of RLS but little is known about possible associations between these drug-induced disorders.

Methods: In total, 58 patients with idiopathic RLS diagnosed according to the International Restless Legs Syndrome Study Group criteria were recruited. Of these, 35 patients had augmentation. The frequency of ICD symptoms was assessed using semi-structural interviews.

Results: Demographic variables did not differ between patients with RLS with and without augmentation but those with augmentation took higher dopaminergic medication than patients without augmentation. Twenty-three patients with RLS (39.7%) had ICD symptoms, with 12 patients (20.7%) having definitive ICDs. Patients with augmentation had an increased risk of expressing ICD symptoms (p = 0.007, odds ratio 5.64, 95% confidence interval 1.59-20.02).

Conclusions: Patients with RLS with augmentation have an almost 6-fold increased risk of exhibiting ICD symptoms. This implies that augmentation and ICDs are related and may share a common pathophysiology. Moreover, our results have clinical implications, suggesting that patients with RLS with augmentation should be screened for ICD symptoms.
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http://dx.doi.org/10.1212/WNL.0000000000002803DOI Listing
July 2016

Clinical Heterogeneity in Cerebral Hemiatrophy Syndromes.

Mov Disord Clin Pract 2016 Jul-Aug;3(4):382-388. Epub 2016 Jan 18.

Department of Neurology Innsbruck Medical University Innsbruck Austria.

Background: Cerebral hemiatrophy syndromes can present with variable neurological symptoms. In childhood epilepsy, mental retardation and neuropsychiatric disorders are common while in adults movement disorders, such as highly asymmetric parkinsonism or hemidystonia as well as neuropsychiatric problems have been reported.

Methods: Here, we present three adult patients with features that expand the clinical spectrum and give an overview of the most common clinical signs associated with this rare condition.

Results: All three patients had prominent neuropsychiatric symptoms such as mood swings and increased irritability. Furthermore, one patient developed hemichorea which can be a rare presentation of cerebral hemiatrophy.

Conclusions: Cerebral hemiatrophy syndromes are a heterogeneous group of disorders that may also present with neuropsychiatric symptoms or hemichorea.
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http://dx.doi.org/10.1002/mdc3.12301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6353474PMC
January 2016
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