Patients with dementia with Lewy bodies and Parkinson disease dementia share the same dopaminergic and cholinergic deficit profile in the brain and seem to represent 2 sides of the same coin in a continuum of Lewy body diseases. Cholinergic deficits seem to be crucial for the development of dementia in addition to motor symptoms. The spatial congruence of cholinergic deficits and energy hypometabolism argues for cortical deafferentation due to the degeneration of projection fibers from the basal forebrain.

Patients with Parkinson disease (PD) can experience hallucinations (spontaneous aberrant perceptions) and illusions (misinterpretations of real perceptual stimuli). Of such phenomena, visual hallucinations (VHs) and illusions are the most frequently encountered, although auditory, olfactory and tactile hallucinations can also occur. In cross-sectional studies, VHs occur in approximately one-third of patients, but up to three-quarters of patients might develop VHs during a 20-year period. Hallucinations can have substantial psychosocial effects and, historically, were the main reason for placing patients in nursing homes. Concomitant or overlapping mechanisms are probably active during VHs, and these include the following: central dopaminergic overactivity and an imbalance with cholinergic neurotransmission; dysfunction of the visual pathways, including specific PD-associated retinopathy and functional alterations of the extrastriate visual pathways; alterations of brainstem sleep-wake and dream regulation; and impaired attentional focus. Possible treatments include patient-initiated coping strategies, a reduction of antiparkinson medications, atypical neuroleptics and, potentially, cholinesterase inhibitors. Evidence-based studies, however, only support the use of one atypical neuroleptic, clozapine, and only in patients without dementia. Better phenomenological discrimination, combined with neuroimaging tools, should refine therapeutic options and improve prognosis. The aim of this Review is to present epidemiological, phenomenological, pathophysiological and therapeutic aspects of hallucinations in PD.

Parkinson's disease (PD) is a major neurodegenerative chronic disease, most likely caused by a complex interplay of genetic and environmental factors. Information on various aspects of PD pathogenesis is rapidly increasing and needs to be efficiently organized, so that the resulting data is available for exploration and analysis. Here we introduce a computationally tractable, comprehensive molecular interaction map of PD. This map integrates pathways implicated in PD pathogenesis such as synaptic and mitochondrial dysfunction, impaired protein degradation, alpha-synuclein pathobiology and neuroinflammation. We also present bioinformatics tools for the analysis, enrichment and annotation of the map, allowing the research community to open new avenues in PD research. The PD map is accessible at http://minerva.uni.lu/pd_map.Electronic supplementary materialThe online version of this article (doi:10.1007/s12035-013-8489-4) contains supplementary material, which is available to authorized users.

Visual hallucinations (VH) in Parkinson's disease (PD) are a chronic complication in 30 to 60% of treated patients and have a multifaceted phenomenology. Flickering, faultive impressions, and illusionary misperceptions precede the core syndrome of stereotyped, colorful images. The patient variably recognizes these images as hallucinations, being rarely irritated or frightened and more often amused as a bystander. Although studies on VH in PD focus on several research domains, no comprehensive, unified theory has been developed to study their pathophysiology. We have adapted Hobson's work on the states of consciousness and propose a model integrating seemingly disparate data on VH. We suggest that VH should be considered as a dysregulation of the gating and filtering of external perception and internal image production. Contributive elements and anatomical links for the model include poor primary vision, reduced activation of primary visual cortex, aberrant activation of associative visual and frontal cortex, lack of suppression or spontaneous emergence of internally generated imagery through the ponto-geniculo-occipital system, intrusion of rapid eye movement dreaming imagery into wakefulness, errative changes of the brainstem filtering capacities through fluctuating vigilance, and medication-related overactivation of mesolimbic systems. Different etiologies likely produce different phenomenologies and the prognosis may not be uniform. This new conceptual framework permits an anatomical view of VH and suggests new, testable hypotheses regarding their pathophysiology and therapy.

Since the discovery of dopamine as a neurotransmitter in the 1950s, Parkinson's disease (PD) research has generated a rich and complex body of knowledge, revealing PD to be an age-related multifactorial disease, influenced by both genetic and environmental factors. The tremendous complexity of the disease is increased by a nonlinear progression of the pathogenesis between molecular, cellular and organic systems. In this minireview, we explore the complexity of PD and propose a systems-based approach, organizing the available information around cellular disease hallmarks. We encourage our peers to adopt this cell-based view with the aim of improving communication in interdisciplinary research endeavors targeting the molecular events, modulatory cell-to-cell signaling pathways and emerging clinical phenotypes related to PD.

PD patients with SRI frequently have behavioral features of RBD. If RBD underlies most SRI, treatment with appropriate pharmacologic agents, such as clonazepam, may prevent future occurrences of SRI.

In PD, the impact of nocturnal respiration on sleep continuity and architecture has not been systematically investigated by polysomnography (PSG). We performed a case-control study with retrospective analysis of PSG data of 49 PD patients. After classifying the PD patients according to their apnea/hypopnea index (AHI), they were matched with 49 controls in terms of age, gender, and AHI. There were 21 PD patients (43%) who had sleep apnea syndrome (SAS), classified as mild (AHI, 5-15) in 10 patients, moderate (AHI, >15-30) in 4 patients, and severe (AHI, > 30) in 7 patients. PD patients had more deep sleep (P = 0.02) and more nocturnal awakenings (P < 0.001) than the controls. Their body mass index (BMI) was lower (P = 0.04), and they maintained a more favorable respiratory profile, with higher mean and minimal oxygen saturation values (P = 0.006 and 0.01, respectively). These differences were preserved when only considering PD patients with AHI > 15. PD patients had less obstructive sleep apneas (P = 0.035), independently from the factor AHI. Only the respiratory changes of 4 PD patients with BMI > 27 and AHI > 15 (8%) approximated those seen in the controls. At an early or middle stage of the disease, non-obese PD patients frequently have AHI values suggesting SAS, however, without the oxygen desaturation profile of SAS. Longitudinal studies of patients with such "abortive" SAS are warranted to establish if this finding reflects benign nocturnal respiratory muscle dyskinesia or constitutes a precursor sign of dysautonomia in PD.

The usefulness of deep brain stimulation (DBS) of thalamic nuclei in Gilles de la Tourette syndrome (GTS) has recently been advocated. We report on a 14-month follow-up study of a patient with intractable GTS in whom bilateral DBS of the internal globus pallidus was carried out. Tic frequency per minute decreased by 73% in the postoperative phase and in particular the vocal tics became less intense. Pronation/ supination bradykinesia of the left extremities was a well-tolerated, permanent side effect. Pallidal DBS could become a valuable rescue therapy for otherwise intractable GTS.