Visual Hallucinations In Parkinson's Disease Research Articles

The metabolic correlate of visual hallucinations in Parkinson's disease

Backgound: Visual hallucinations (VH) occur in about 25% of patients with Parkinson's disease (PD). However, the pathophysiological mechanisms of VH in PD are not well understood.

Factors associated with drug–induced visual hallucinations in Parkinson's disease

Visual hallucinations are common in medication-treated Parkinson's disease (PD) patients. Although their etiology is unknown several factors seem to be involved in their pathogenesis. The aim of this study was to identify possible risk factors and determine clinical characteristics associated with the development of visual hallucinations in PD. 166 consecutive patients fulfilling clinical criteria for PD were studied. During a semi-structured interview, demographic characteristics and clinical variables were recorded. Motor, cognitive and psychiatric status was also assessed. Patients with and without visual hallucinations were compared using non-parametric tests, and logistic regression was applied to significant data. During the month before evaluation 20.4% of our patients experienced visual hallucinations (11.4% benign, 9% malignant). Logistic regression analysis identified three factors independently associated with visual hallucinations: long duration of Parkinson's disease, dementia, and disease severity as measured by the UPDRS total score. Our findings indicate that apart from well established risk factors such as cognitive impairment and disease duration, disease severity is also important for the development of visual hallucinations in PD. Furthermore, the presence of bradykinesia and instability, the absence of tremor and the severity of rigidity and bradykinesia (limb and axial) may act as cofactors.

Altered cortical visual processing in PD with hallucinations

To compare fMRI activation during two visual stimulation paradigms in Parkinson disease (PD) subjects with chronic visual hallucinations vs PD patients who had never hallucinated. Twelve pairs of PD subjects, matched for age, PD duration, and dopaminergic drug exposure duration, participated in this study. The authors examined group differences in activation during stroboscopic (flashing) vs no visual stimulation and kinematic (apparent motion) vs stationary visual stimulation. During stroboscopic stimulation, non-hallucinating PD subjects showed significantly greater activation in the parietal lobe and cingulate gyrus compared to hallucinating PD subjects. In contrast, the hallucinating subjects showed significantly greater activation in the inferior frontal gyrus and the caudate nucleus. During kinematic stimulation, non-hallucinating PD subjects showed significantly greater activation in area V5/MT, parietal lobe, and cingulate gyrus compared to hallucinating PD subjects. Hallucinating PD subjects showed significantly greater activation in the superior frontal gyrus. PD patients with chronic visual hallucinations respond to visual stimuli with greater frontal and subcortical activation and less visual cortical activation than non-hallucinating PD subjects. Shifting visual circuitry from posterior to anterior regions associated primarily with attention processes suggests altered network organization may play a role in the pathophysiology of visual hallucinations in PD.

Hallucinations and sleep disturbances in Parkinson’s disease

Visual hallucinations (VHs) occur frequently in Parkinson's disease (PD). VHs occur more frequently in elderly patients with longer duration of illness, cognitive impairment, and sleep disturbances. The relationship between the use of antiparkinsonian drugs and VHs is complicated, but most drugs used to treat parkinsonian motor symptoms induce VHs and psychosis in some PD patients. The "continuum hypothesis" proposing that medication-induced psychiatric symptoms in PD begin with drug-induced sleep disturbances, followed by vivid dreams, with progression to hallucinatory and delusional experiences has been challenged. In some patients, VHs may represent intrusion of REM sleep-related imagery into wakefulness. Improving REM sleep abnormalities in PD (e.g., stimulants, anticholinesterase inhibitors) is one strategy now being tested to improve VHs in PD.

Visual hallucinations as REM sleep behavior disorders in patients with Parkinson's disease.

To clarify whether visual hallucinations in patients with Parkinson's disease (PD) are related to rapid eye movement (REM) sleep, nocturnal polysomnographic variables were compared between a group with hallucinations (hallucinators, n = 14) and a group without hallucinations (nonhallucinators, n = 8). A multiple sleep latency test (MSLT) was performed on 3 hallucinators, and the content of dreams during daytime REM sleep was investigated. The efficacy of clonazepam, a standard treatment choice for REM sleep behavior disorders, was investigated in 8 hallucinators. Nocturnal polysomnograms of the hallucinators showed a higher amount of stage 1-REM sleep with tonic electromyogram (stage 1-REM) than the nonhallucinators, and the reported occurrences of nocturnal hallucinations corresponded with the periods of stage REM or stage 1-REM in most hallucinators. The frequency of sleep onset REM periods (SOREMP) on the MSLT were pathologically high in the hallucinators, and the content of the dreams during the MSLT period was quite similar to their hallucinations. During clonazepam treatment, the frequency of hallucinatory symptoms decreased in 5 of 8 hallucinators. These results indicate that visual hallucinations in PD are likely to be related to a REM sleep disorder manifested as the appearance of both stage 1-REM during the night and SOREMP in the daytime.

54th annual meeting of the American Academy of Neurology, Denver, Colorado, April 13-20, 2002.

54th annual meeting of the American Academy of Neurology, Denver, Colorado, April 13-20, 2002.

Genetic variation analysis in parkinson disease patients with and without hallucinations: case-control study.

Visual hallucinations in Parkinson disease (PD) occur in approximately one third of patients treated long-term with dopaminergic medications. In Alzheimer disease, hallucinations and psychosis have been linked to increased representations of B2/B2 homozyogotes for the dopamine receptor gene DRD1 and 1/1 or 2/2 homozygotes for DRD3. In addition, a previous study of PD patients with and without hallucinations did not show differences in D2 and D3 polymorphisms, although careful case-control matching was not performed. Another study linked the apolipoprotein E4 (APOE4) allele to hallucinations in PD. To determine whether the frequency of dopamine receptor genetic variants and APOE alleles in patients with PD with and without chronic visual hallucinations resembles the pattern previously documented in patients with Alzheimer disease. We conducted a case-control study of 44 patients with PD and chronic hallucinations and 44 patients with PD who had never hallucinated. Cases and controls were matched for current age and medications. DNA was isolated from blood samples and assayed for DRD1, DRD2, DRD3, DRD4, and APOE polymorphisms. Receptor polymorphisms were genotyped by polymerase chain reaction. Genotypes in hallucinators and nonhallucinators were compared using Mantel-Haenszel tests stratified by pair, and allele frequencies were compared using Wilcoxon signed rank tests within pairs. Neither D1 receptor genotypes (P =.37) nor allele frequencies (P =.38) differed, and there was no predominance of B2/B2 homozygotes in the hallucinators. For D3, there was a higher frequency of allele 2 (P =.047), but there was no significant difference between frequencies of homozygotes vs heterozygotes (P =.39) as reported in Alzheimer disease. D4 receptor distribution of long and short alleles did not differ between the 2 patient groups, and there were too few C alleles (3 of 86) to compare D2 allele genotypes or frequencies. For APOE, 12 cases and 12 controls carried E4 alleles (P>.99). With careful case-control matching, visual hallucinations in PD are not associated with the pattern seen for patients with Alzheimer disease and visual hallucinations. Furthermore, there was no association between hallucinations and APOE. Similar methods using larger sample sizes might be adapted to test whether specific dopaminergic receptor genetic variants are associated with visual hallucinations in PD. Based on our data, the DRD3 allele 2 may merit further study.

Human spatiotemporal contrast sensitivity: dopaminergic induced variations

Visual hallucinations (VH) occur in the clinical course of Parkinson's disease (PD) and are predictive for PD dementia. The genesis of VH is related to impaired bottom-up and/or top-down visual processing which can be linked to cholinergic dysfunction and mono-amine imbalance. The risk of developing VH with oral dopamine agonists seems to increase with advancing disease, while in contrast some clinical studies suggest that apomorphine does not worsen VH, or might even improve VH.The aim of this study is to review the current evidence of apomorphine and its effects on VH in PD patients.Apomorphine is well-tolerated in PD patients with VH, also in long-term follow-up studies. Apomorphine is also suggested to have the potential to alleviate VH. Some data suggest that the positive effect of apomorphine on VH is related to its piperidine moiety, part of many anti-psychotics. Irrespective this piperidine moiety, apomorphine has a high D1–like receptor affinity, and acts as a serotonin 5-HT2A receptor antagonist, which might explain the potential anti-hallucinogenic properties as well.The anecdotal evidence suggesting that apomorphine has a relatively low proclivity to induce VH in PD may be due to its capacity to reduce serotonergic activity in particular. Therefore apomorphine is still an option to consider in fluctuating PD patients with VH, if they are treated properly with respect to their cholinergic deficits and existing VH.