Karoline Wenzel

The Onset of Nonmotor Symptoms in Parkinson's disease (The ONSET PD Study)

Nonmotor symptoms (NMS) in Parkinsons disease (PD) can precede onset of motor symptoms. Relationship between premotor symptoms onset and motor features is limited. Our aim is to describe the presence and perceived onset of NMS in PD as well as their possible association with motor phenotype. Presence and onset of NMS were assessed by a custom‐made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls from 11 Spanish and Austrian centers. Seventeen of thirty‐one NMS were more common in patients than controls (P < 0.05). They were usually mild and frequently reported to occur at different time‐spans before motor symptoms. Anhedonia, apathy, memory complaints, and inattention occurred more frequently during the 2‐year premotor period. Those reported more frequently in the 2‐ to 10‐year premotor period were smell loss, mood disturbances, taste loss, excessive sweating, fatigue, and pain. Constipation, dream‐enacting behavior, excessive daytime sleepiness, and postprandial fullness were frequently perceived more than 10 years before motor symptoms. No correlation between NMS burden and motor severity, age, or gender was observed. NMS associated in four clusters: rapid eye movement sleep behavior disorder symptoms‐constipation, cognition‐related, mood‐related, and sensory clusters. No cluster was associated with a specific motor phenotype or severity. NMS are common in early unmedicated PD and frequently reported to occur in the premotor period. They are generally mild, but a patient subgroup showed high NMS burden mainly resulting from cognition‐related symptoms. Certain NMS when present at the time of assessment or in the premotor stage, either alone or in combination, allowed discriminating PD from controls.

EuroInf: A multicenter comparative observational study of apomorphine and levodopa infusion in Parkinson's disease

Subcutaneous apomorphine infusion (Apo) and intrajejunal levodopa infusion (IJLI) are two treatment options for patients with advanced Parkinsons disease (PD) and refractory motor complications, with varying cost of treatment. There are no multicenter studies comparing the effects of the two strategies. This open‐label, prospective, observational, 6‐month, multicenter study compared 43 patients on Apo (48.8% males, age 62.3 ± 10.6 years; disease duration: 14 ± 4.4 years; median H & Y stage 3; interquartile range [IQR]: 3‐4) and 44 on IJLI (56.8% males, age 62.7 ± 9.1 years; disease duration: 16.1 ± 6.7 years; median H & Y stage 4; IQR, 3‐4). Cohens effect sizes (≥0.8 considered as large) were “large” with both therapies with respect to total motor, nonmotor, and quality‐of‐life scores. The Non‐Motor Symptoms Scale (NMSS) with Apo showed moderate improvement, whereas sleep/fatigue, gastrointestinal, urinary, and sexual dimensions of the NMSS showed significantly higher improvement with IJLI. Seventy‐five percent on IJLI improved in their quality‐of‐life and nonmotor symptoms (NMS), whereas in the Apo group, a similar proportion improved in quality of life, but 40% in NMS. Adverse effects included peritonitis with IJLI and skin nodules on Apo. Based on this open‐label, nonrandomized, comparative study, we report that, in advanced Parkinsons patients, both IJLI and Apo infusion therapy appear to provide a robust improvement in motor symptoms, motor complications, quality‐of‐life, and some NMS. Controlled, randomized studies are required.

Quantitative Susceptibility Mapping in Parkinson's Disease

Background Quantitative susceptibility mapping (QSM) and R2* relaxation rate mapping have demonstrated increased iron deposition in the substantia nigra of patients with idiopathic Parkinson’s disease (PD). However, the findings in other subcortical deep gray matter nuclei are converse and the sensitivity of QSM and R2* for morphological changes and their relation to clinical measures of disease severity has so far been investigated only sparsely. Methods The local ethics committee approved this study and all subjects gave written informed consent. 66 patients with idiopathic Parkinson’s disease and 58 control subjects underwent quantitative MRI at 3T. Susceptibility and R2* maps were reconstructed from a spoiled multi-echo 3D gradient echo sequence. Mean susceptibilities and R2* rates were measured in subcortical deep gray matter nuclei and compared between patients with PD and controls as well as related to clinical variables. Results Compared to control subjects, patients with PD had increased R2* values in the substantia nigra. QSM also showed higher susceptibilities in patients with PD in substantia nigra, in the nucleus ruber, thalamus, and globus pallidus. Magnetic susceptibility of several of these structures was correlated with the levodopa-equivalent daily dose (LEDD) and clinical markers of motor and non-motor disease severity (total MDS-UPDRS, MDS-UPDRS-I and II). Disease severity as assessed by the Hoehn & Yahr scale was correlated with magnetic susceptibility in the substantia nigra. Conclusion The established finding of higher R2* rates in the substantia nigra was extended by QSM showing superior sensitivity for PD-related tissue changes in nigrostriatal dopaminergic pathways. QSM additionally reflected the levodopa-dosage and disease severity. These results suggest a more widespread pathologic involvement and QSM as a novel means for its investigation, more sensitive than current MRI techniques.

The role of subcutaneous infusion of apomorphine in Parkinson's disease

Continuous subcutaneous apomorphine infusion therapy (CSAI) has proved to be effective in advanced Parkinson’s Disease patients with motor fluctuations not controlled by oral or transdermal medication. In this clinical setting it competes directly with intrajejunal levodopa and deep brain stimulation (DBS), however randomised controlled comparative studies are lacking. The advantages of CSAI is that it is the least invasive of these three therapeutic options, is reversible, practical to use and has shown significant efficacy for the management of both peak-effect dyskinesias and off-period nonmotor-symptoms. Contraindications to the use of CSAI are severe dementia or neuropsychiatric symptoms and severe biphasic dyskinesias, however unlike DBS, advanced age is not a contraindication. This review summarises the evidence regarding efficacy, safety and tolerability of CSAI, provides guidance on the selection of suitable patients and gives practical instructions on how to initiate CSAI and manage possible adverse events.

Facial Emotion Recognition in Parkinson's Disease: An fMRI Investigation

Background Findings of behavioral studies on facial emotion recognition in Parkinson’s disease (PD) are very heterogeneous. Therefore, the present investigation additionally used functional magnetic resonance imaging (fMRI) in order to compare brain activation during emotion perception between PD patients and healthy controls. Methods and Findings We included 17 nonmedicated, nondemented PD patients suffering from mild to moderate symptoms and 22 healthy controls. The participants were shown pictures of facial expressions depicting disgust, fear, sadness, and anger and they answered scales for the assessment of affective traits. The patients did not report lowered intensities for the displayed target emotions, and showed a comparable rating accuracy as the control participants. The questionnaire scores did not differ between patients and controls. The fMRI data showed similar activation in both groups except for a generally stronger recruitment of somatosensory regions in the patients. Conclusions Since somatosensory cortices are involved in the simulation of an observed emotion, which constitutes an important mechanism for emotion recognition, future studies should focus on activation changes within this region during the course of disease.

Intact emotion recognition and experience but dysfunctional emotion regulation in idiopathic Parkinson's disease

BACKGROUND A specific non-motor impairment in Parkinsons disease (PD) concerns difficulties to accurately identify facial emotions. Findings are numerous but very inconsistent, ranging from general discrimination deficits to problems for specific emotions up to no impairment at all. By contrast, only a few studies exist about emotion experience, altered affective traits and states in PD. OBJECTIVE To investigate the decoding capacity for affective facial expressions, affective experience of emotion-eliciting images and affective personality traits in PD. METHODS The study sample included 25 patients with mild to moderate symptom intensity and 25 healthy controls (HC) of both sexes. The participants were shown pictures of facial expressions depicting disgust, fear, and anger as well as disgusting and fear-relevant scenes. Additionally, they answered self-report scales for the assessment of affective traits. RESULTS PD patients had more problems in controlling anger and disgust feelings than HC. Higher disgust sensitivity in PD was associated with lower functioning in everyday life and lower capacity to recognize angry faces. Furthermore, patients reported less disgust towards poor hygiene and spoiled food and they stated elevated anxiety. However, the clinical group displayed intact facial emotion decoding and emotion experience. Everyday life functionality was lowered in PD and decreased with stronger motor impairment. Furthermore, disease duration was negatively associated to correct classification of angry faces. CONCLUSIONS Our data indicate that problems with emotion regulation may appear already in earlier disease stages of PD. By contrast, PD patients showed appropriate emotion recognition and experience. However, data also point to a deterioration of emotion recognition capacity with the course of the disease. Compensatory mechanisms in PD patients with less advanced disease are discussed.

Case of a palatal tic resembling palatal tremor in a patient with tourette syndrome

We describe a case of a palatal tic resembling palatal tremor (PT) in a young female patient with a previously unrecognized mild Tourette syndrome. At the time of her visit, the patient complained about ear clicks that were audible to others. We discuss the differential diagnoses of hyperkinetic palatal movements emphasizing the ongoing discussion about essential PT representing a more heterogeneous disorder than previously thought.

Role of Disgust Proneness in Parkinson’s Disease: A Voxel-Based Morphometry Study

The knowledge about personality traits in Parkinsons disease (PD) is still limited. In particular, disgust proneness has not been investigated as well as its neuronal correlates. Although several morphometric studies demonstrated that PD is associated with gray matter volume (GMV) reduction in olfactory and gustatory regions involved in disgust processing, a possible correlation with disgust proneness has not been investigated. We conducted a voxel-based morphometry analysis to compare GMV between 16 cognitively normal male PD patients with mild to moderate symptoms and 24 matched control subjects. All participants had answered questionnaires for the assessment of disgust proneness, trait anger and trait anxiety. We correlated questionnaire scores with GMV in both groups. The clinical group reported selectively reduced disgust proneness toward olfactory stimuli associated with spoilage. Moreover, they showed GMV reduction in the central olfactory system [orbitofrontal cortex (OFC) and piriform cortex]. Disgust items referring to olfactory processing were positively correlated with OFC volume in PD patients. Our data suggest an association between PD-associated neurodegeneration and olfactory related facets of the personality trait disgust proneness.