Diagnostics and treatment of impulse control disorders, psychosis and delirium: systemic review-based recommendations - guideline "Parkinson's disease" of the German Society of Neurology.

BACKGROUND AND OBJECTIVE: Impulse control disorders (ICD), psychosis and delirium are part of the spectrum of behavioural changes associated with Parkinson's disease (PD). The diagnostic and therapeutic management of these rather complex neuropsychiatric conditions has been updated in the clinical guideline by the German Society of Neurology (DGN). METHODS: Recommendations are based on a systematic literature reviews, other relevant guidelines and expert opinion. RESULTS: Patients receiving dopamine agonists (DA) therapy should be informed about the symptoms and risks of an ICD and should be routinely screened for ICD symptoms. In the presence of an ICD, DA should be reduced or discontinued and psychotherapeutic treatment may be considered. Non-oral therapies (levodopa/carbidopa intestinal gel infusion or deep brain stimulation) may also be an option for appropriate candidates. Psychosis in PD often has a gradual onset. Cognitive and affective disorders, psychiatric and medical comorbidities as well as polypharmacy are risk factors for a psychosis. Non-pharmacological treatments should be implemented as soon as possible and anti-parkinsonian medications should be adjusted/reduced if feasible. For psychosis associated with PD, quetiapine or clozapine should be used on an as-needed basis and for as short a time as is necessary, with safety monitoring. Delirium in PD may be underdiagnosed due to an overlap with chronic neuropsychiatric features of PD. Although transient by definition, delirium in PD can lead to permanent cognitive decline, motor impairment and increased mortality. Management of delirium includes pharmacological and non-pharmacological interventions. CONCLUSION: The updated guideline encompasses the evidence-based diagnostic, non-pharmacological and pharmacological management of ICD, psychosis and delirium in PD.

Dopamine regulates decision thresholds in human reinforcement learning in males.

Dopamine fundamentally contributes to reinforcement learning, but recent accounts also suggest a contribution to specific action selection mechanisms and the regulation of response vigour. Here, we examine dopaminergic mechanisms underlying human reinforcement learning and action selection via a combined pharmacological neuroimaging approach in male human volunteers (n = 31, within-subjects; Placebo, 150 mg of the dopamine precursor L-dopa, 2 mg of the D2 receptor antagonist Haloperidol). We found little credible evidence for previously reported beneficial effects of L-dopa vs. Haloperidol on learning from gains and altered neural prediction error signals, which may be partly due to differences experimental design and/or drug dosages. Reinforcement learning drift diffusion models account for learning-related changes in accuracy and response times, and reveal consistent decision threshold reductions under both drugs, in line with the idea that lower dosages of D2 receptor antagonists increase striatal DA release via an autoreceptor-mediated feedback mechanism. These results are in line with the idea that dopamine regulates decision thresholds during reinforcement learning, and may help to bridge action selection and response vigor accounts of dopamine.

Brain abscess with Ureaplasma parvum in a patient with granulomatosis with polyangiitis.

PURPOSE: Ureaplasma species are associated with urogenital infections, infertility and adverse pregnancy outcomes as well as neonatal infections. Involvement of the central nervous system in adults is extremely rare. We report an unusual case of a brain abscess secondary to otitis media with Ureaplasma parvum in a patient with granulomatosis with polyangiitis (GPA). METHODS: Imaging and laboratory findings, treatment decisions, and outcome of this case are explicated. RESULTS: A young adult with GPA presented with progredient earache after ambulant diagnosis of otitis media. Despite different courses of broad-spectrum antibiotic therapy, she developed meningoencephalitis due to mastoiditis following temporal abscess formation. Mastoidectomy and neurosurgical abscess removal were performed. Standard cultures of cerebrospinal fluid, blood and intracranial abscess material, as well as polymerase chain reaction (PCR) for common bacterial and viral meningitis pathogens remained negative. Only eubacterial PCR of intracranial abscess material returned positive for Ureaplasma parvum. The patient finally improved under antibiotic therapy with moxifloxacin and doxycycline. CONCLUSION: Ureaplasma species are rare causative pathogens in immunocompromised patients. They should be considered in patients with humoral immunodeficiencies with culture-negative infections failing standard therapy. Eubacterial PCR should be performed in early states of infection in these patients for immediate diagnosis and initiation of appropriate treatment to prevent adverse outcomes.

Hypothalamic Inflammation in Human Obesity Is Mediated by Environmental and Genetic Factors.

Obesity is associated with hypothalamic inflammation (HI) in animal models. In the current study, we examined the mediobasal hypothalamus (MBH) of 57 obese human subjects and 54 age- and sex- matched nonobese control subjects by MRI and analyzed the T2 hyperintensity as a measure of HI. Obese subjects exhibited T2 hyperintensity in the left but not the right MBH, which was strongly associated with systemic low-grade inflammation. MRS revealed the number of neurons in the left hypothalamic region to be similar in obese versus control subjects, suggesting functional but not structural impairment due to the inflammatory process. To gain mechanistic insights, we performed nutritional analysis and 16S rDNA microbiome sequencing, which showed that high-fat diet induces reduction of Parasutterella sp. in the gut, which is significantly correlated with MBH T2 hyperintensity. In addition to these environmental factors, we found subjects carrying common polymorphisms in the JNK or the MC4R gene to be more susceptible to HI. Finally, in a subgroup analysis, bariatric surgery had no effect on MBH T2 hyperintensity despite inducing significant weight loss and improvement of peripheral insulin sensitivity. In conclusion, obesity in humans is associated with HI and disturbances in the gut-brain axis, which are influenced by both environmental and genetic factors.

Relation of lead trajectory and electrode position to neuropsychological outcomes of subthalamic neurostimulation in Parkinson's disease: results from a randomized trial.

Deep brain stimulation of the subthalamic nucleus improves motor functions in patients suffering from advanced Parkinson's disease but in some patients, it is also associated with a mild decline in cognitive functioning about one standard deviation from the preoperative state. We assessed the impact of the cortical lead entry point, the subcortical electrode path and the position of the active electrode contacts on neuropsychological changes after subthalamic nucleus-deep brain stimulation compared to a control group of patients receiving best medical treatment. Sixty-eight patients with advanced Parkinson's disease were randomly assigned to have subthalamic nucleus-deep brain stimulation or best medical treatment for Parkinson's disease. All patients had a blinded standardized neuropsychological exam (Mattis Dementia Rating scale, backward digit span, verbal fluency and Stroop task performance) at baseline and after 6 months of treatment. Patients with subthalamic nucleus-deep brain stimulation were defined as impaired according to a mild decline of one or more standard deviations compared to patients in the best medical treatment group. The cortical entry point of the electrodes, the electrode trajectories and the position of the active electrode contact were transferred into a normalized brain volume by an automated, non-linear registration algorithm to allow accurate statistical group analysis using pre- and postoperative magnetic resonance imaging data. Data of 31 patients of the subthalamic nucleus-deep brain stimulation group and 31 patients of the best medical treatment group were analysed. The subthalamic nucleus-deep brain stimulation group showed impaired semantic fluency compared with the best medical treatment group 6 months after surgery (P = 0.02). Electrode trajectories intersecting with caudate nuclei increased the risk of a decline in global cognition and working memory performance. Statistically, for every 0.1 ml overlap with a caudate nucleus, the odds for a decline >1 standard deviation increased by a factor of 37.4 (odds ratio, confidence interval 2.1-371.8) for the Mattis Dementia Rating Scale and by a factor of 8.8 (odds ratio, confidence interval 1.0-70.9) for the backward digit span task. Patients with subthalamic nucleus-deep brain stimulation who declined in semantic verbal fluency, Stroop task and the backward digit span task performance showed a position of the active electrode outside the volume built by the active electrodes of stable performers. Passage of the chronic stimulation lead through the head of the caudate increases the risk of global cognitive decline and working memory performance after subthalamic nucleus-deep brain stimulation in Parkinson's disease. Therefore the electrode path should be planned outside the caudate nuclei, whenever possible. This study also stresses the importance of precise positioning of the active stimulating contact within the subthalamic volume to avoid adverse effects on semantic verbal fluency and response inhibition.