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Background Causes of voriconazole-related visual adverse events (VVAE) remained controversial. Objectives We aimed to explore the relationship between voriconazole serum concentrations and VVAE as well as the potential influence of transient receptor potential melastatin 1 (TRPM1) on VVAE. Patients/methods This prospective observational cohort study was done in two stages. Patients who received voriconazole for invasive fungal diseases were consecutively enrolled. Correlations between voriconazole trough levels and VVAE were explored in 76 patients. Genotyping was further conducted for 17 tag SNPs of TRPM1 in a larger population of 137 patients. Genotype distributions were compared between patients with and without VVAE. Result Of the 76 patients, a total of 229 steady-state voriconazole trough levels were evaluated, 69.9% of which were within the target range (1-5.5 mg/L). No correlations were found between voriconazole trough levels and VVAE. Of the total 137 patients, VVAE occurred in 37 (27.0%) patients, including visual hallucination (13.9%, 19/137) and visual disturbances (19.0%, 26/137). Significant difference in TRPM1 genotype distribution was only observed in patients with visual hallucination but not with visual disturbances. We found that rs890160 G/T genotype was under-presented (OR, 0.11; 95% CI, 0.01-0.84; P = .011) and rs1378847 C/C genotype was more frequently detected (OR, 8.89; 95% CI, 1.14-69.02; P = .013) in patients with visual hallucination when compared with those without. Conclusion Transient receptor potential melastatin 1 was genetically associated with voriconazole-related visual hallucination. The correlation was failed to found between voriconazole trough levels and VVAE.

Introduction Patients with schizophrenia frequently present with visual disturbances including hallucination, and this symptom is particularly prevalent in individuals with comorbid depressive disorders. Currently, little is known about the neurobiological mechanisms of such psychiatric symptoms, and few explanations for the co‐occurrence of schizophrenia, depression, and visual disturbances are available. Methods In this study, we generated a mouse schizophrenia model in which depressive symptoms were also induced. We adopted in vivo two‐photon calcium imaging and ex vivo electrophysiological recording of the primary visual cortex to reveal the synaptic transmission and neural activity in the mouse schizophrenia model. Results In vivo two‐photon calcium imaging and ex vivo electrophysiological recording of the primary visual cortex revealed impaired synaptic transmission and abnormal neural activity in the schizophrenia model, but not in the depression model. These functional deficits were most prominent in the combined schizophrenia and depression model. Conclusion Overall, our data support a mechanism by which the visual cortex plays a role in visual disturbances in schizophrenia., In our mouse model of schizophrenia, the hyperactivation of cortical neurons occurred without exposure to sensory stimuli, as supported by in vivo and ex vivo recordings. This elevated spontaneous activity was attributable mainly to a greater frequency, but not amplitude, of calcium activity spikes, indicating the potentiation of presynaptic transmission. Notably, comorbidity with depression further aggravated the cortical synapse pathology. These pathophysiological alterations in the visual cortex provide a possible explanation for the occurrence of visual hallucination in patients with schizophrenia.

Oral isotretinoin is an effective treatment for severe acne. However, psychiatric side effects are noted, including a few cases of psychosis and mania triggered by isotretinoin. In this report, we present a case of visual hallucinations due to isotretinoin. In our case, with the discontinuation of isotretinoin, the hallucinations regressed and no other cause was found.

Introduction We investigated whether disruption of the inferior longitudinal fasciculus and inferior fronto‐occipital fasciculus are associated with visual hallucinations in Parkinson's disease (PD). Methods Sixty consecutive right‐handed patients with PD with and without visual hallucinations were enrolled in this cross‐sectional study. Diffusion tensor imaging was acquired by 3.0 T magnetic resonance imaging. We measured fractional anisotropy and mean diffusivity of the bilateral inferior longitudinal fasciculus and inferior fronto‐occipital fasciculus using diffusion tensor tractography analysis software. Results Seventeen patients with PD had visual hallucinations; these patients tended to have lower fractional anisotropy and higher mean diffusivity values in all fasciculi than did patients without visual hallucinations. A univariate logistic analysis showed that the presence of visual hallucinations was significantly associated with lower fractional anisotropy and higher mean diffusivity of the left inferior longitudinal fasciculus, and lower Mini‐Mental State Examination (MMSE) scores. A multivariable logistic analysis adjusted by MMSE scores and disease duration showed a significant association between the presence of visual hallucinations and fractional anisotropy and mean diffusivity values of the left inferior longitudinal fasciculus. Conclusions Our results suggest that disruption of left inferior longitudinal fasciculus integrity is associated with visual hallucinations in patients with PD, independent of cognitive impairment and disease duration., We investigated whether disruption of the inferior longitudinal fasciculus is associated with visual hallucinations in Parkinson's disease (PD) used by diffusion tensor imaging. A multivariable logistic analysis adjusted by MMSE scores showed a significant association between the presence of visual hallucinations and fractional anisotropy and mean diffusivity values of the left inferior longitudinal fasciculus. Our results suggest that disruption of left inferior longitudinal fasciculus integrity is associated with visual hallucinations in patients with PD, independent of cognitive impairment.

Introduction Schizophrenia patients often experience auditory hallucinations (AHs) and visual hallucinations (VHs). However, the degree and type of brain and retinal alterations associated with combined AHs and VHs in schizophrenia patients remain unknown. There is an urgent need for a study that investigates the trajectory of brain and retinal alterations in patients with first‐episode untreated schizophrenia accompanied by combined AHs and VHs (FUSCHAV). Methods FUSCHAV patients (n = 120), divided into four groups according to AH and VH symptom severity (severe AHs combined with severe VHs [FUSCHSASV, 20 patients]; middle‐to‐moderate AHs combined with severe VHs [FUSCHMASV, 23 patients]; severe AHs combined with middle‐to‐moderate VHs [FUSCHSAMV, 28 patients]; and middle‐to‐moderate AHs combined with middle‐to‐moderate VHs [FUSCHMAMV, 26 patients]), were compared to healthy controls (n = 30). Gray matter volume (GMV) was adopted for brain structural alteration assessment. Total retinal thickness was adopted as a measure of retinal thickness impairment. Results In the pilot study, the rate of GMV reduction showed an inverted U‐shaped pattern across the different FUSCHAV patient groups according to AH and VH severity. The degree of retinal impairment remained stable across the groups. More notably, in the secondary follow‐up study, we observed that, after 6 months of treatment with antipsychotic agents, all the GMV reduction‐related differences across the different patient groups disappeared, and both GMV and retinal thickness demonstrated a tendency to deteriorate. Conclusions These findings indicate the need for heightened alertness on brain and retinal impairments in patients with FUSCHAV. Further deteriorations induced by antipsychotic agent treatment should be monitored in clinical practice., (1) GMV reduction and gFCD increases in the frontal–parietal lobule of FUSCHAV patients demonstrate an inverted U‐shape pattern according to differences in AH and VH severity, indicating functional compensation correlated with volume reduction. (2) There appears to be reciprocal deterioration in auditory and visual disturbances among FUSCHAV patients as observed through both brain and retinal abberations. (3) Although brain alterations in FUSCHAV patients differ with degree of AH and VH severity, retinal impairment remains constant among FUSCHAV groups.

Background Clinicians vary in their ability to elicit and interpret hallucinatory symptoms in patients with Parkinson's disease (PD). There is limited evidence for informant-report measures of PD hallucinations as adjuncts to clinician-rated scales. Objectives To determine the utility of an informant version of the validated Psychosis and Hallucinations Questionnaire (PsycH-Q) for assessing the presence and severity of hallucinations in PD; and, to evaluate accuracy of clinician judgements by comparison with informant report and self-report. Methods One hundred sixty-three PD patient-informant dyads completed self- and informant-report versions of PsycH-Q and three common questionnaire measures: Neuropsychiatric Inventory Questionnaire; Parkinson's Psychosis Questionnaire; and Scales for Outcomes in Parkinson's disease-Psychiatric Complications. We compared self-ratings and informant ratings across analogous subscales for the presence of hallucinations with clinician interview ratings on MDS-UPDRS as a diagnostic standard. Results There was a low level of agreement between dyads (average κ = 0.39; κ range = 0.32-0.47; P

Author(s): Holiday, Kelsey A; Pirogovsky-Turk, Eva; Malcarne, Vanessa L; Filoteo, J Vincent; Litvan, Irene; Lessig, Stephanie L; Song, David; Schiehser, Dawn M | Abstract: BackgroundVisual Hallucinations (VH) are a common symptom experienced by individuals with Parkinson's disease (PD); however, a validated measure of VH has yet to be established for this population. The North-East Visual Hallucinations Interview (NEVHI), a promising VH measure, has not been well validated in PD. The aim of this study was to evaluate the convergent and discriminant validity of the NEVHI as well as the proportional identification and characteristics of VH in PD.MethodsOne hundred seventeen individuals with PD completed the NEVHI as well as evaluations of psychological, cognitive, motor, and visual functioning as measures of convergent and divergent validity. The hallucination items from the Neuropsychiatric Inventory (NPI) and the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Scale (MDS-UPDRS) were used to assess convergent validity.ResultsThe NEVHI identified 20.5% of PD patients with VH, which consisted of all individuals detected by the MDS-UPDRS and NPI and nine additional individuals not detected by the other measures. The NEVHI was strongly correlated with the MDS-UPDRS hallucinations item, and weakly correlated with the NPI VH item. Weak to non-significant correlations were found between the NEVHI and measures of psychological, cognitive, motor, visual, and demographic characteristics.DiscussionThe NEVHI identified a greater number of individuals with VH than either the MDS-UPDRS or NPI. Results demonstrated good convergent validity between the NEVHI and a clinician-administered-to-patient-report measure of VH and excellent divergent validity, supporting the NEVHI as a valid and preferable measure for assessing the presence of VH in PD.

Background: There is growing evidence that the serotonergic system, in particular serotonin 2A receptors, is involved in neuropsychiatric symptoms in Parkinson's disease (PD), including cognitive processing and visual hallucinations. However, the relationship between serotonin 2A receptor availability, visual hallucinations, and cognitive profile is unknown. The objective of this study was to investigate the level of serotonin 2A receptor availability in brain regions affected by visual hallucinations and to test the association with cognitive/behavioral changes in patients who have PD with visual hallucinations. Methods: Nondemented patients who had PD with (n = 11) and without (n = 8) visual hallucinations and age‐matched controls (n = 10) were recruited. All participants completed neuropsychological testing, which consisted of visuoperceptual, executive, memory, language, and frontal‐behavioral function. Positron emission tomography scans using [18F]setoperone, a serotonin 2A antagonist radioligand, were acquired in patients with PD, and a parametric binding potential map of [18F]setoperone was calculated with the simplified reference tissue model using the cerebellum as a reference. Results: Patients who had PD with visual hallucinations exhibited significantly lower scores on measures of executive and visuoperceptual functions compared with age‐matched controls. These changes were paralleled by decreased [18F]setoperone binding in the right insula, bilateral dorsolateral prefrontal cortex, right orbitofrontal cortex, right middle temporal gyrus, and right fusiform gyrus. The psychometric correlation analysis revealed significant relationships among tests associated with visuoperceptual function, memory and learning, and serotonin 2A binding in different prefrontal and ventral visual stream regions. There was also reduced serotonin 2A receptor binding in patients who had PD with depression. Conclusions: These findings support a complex interaction between serotonin 2A receptor function and cognitive processing in patients who have PD with visual hallucinations. Fil: Cho, Sang Soo. University of Toronto; Canadá Fil: Strafella, Antonio P.. University of Toronto; Canadá Fil: Duff Canning, Sarah. University of Toronto; Canadá Fil: Zurowski, Mateusz. University of Toronto; Canadá Fil: Vijverman, Anne Catherine. Onze‐Lieve‐Vrouw Hospital; Bélgica Fil: Bruno, Veronica Andrea. University of Toronto; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Aquino, Camila C.. University of Toronto; Canadá Fil: Criaud, Marion. University of Toronto; Canadá Fil: Rusjan, Pablo M.. University of Toronto; Canadá Fil: Houle, Sylvain. University of Toronto; Canadá Fil: Fox, Susan H.. University of Toronto; Canadá

Introduction Defective visual information processing contributes to visual hallucination in PD, for which "top-down" and "bottom-up" impairment are suggested mechanisms. This study was aimed to investigate macro- and microstructural neural changes in afferent visual pathways in relation to visual hallucination in nondemented PD patients. Methods This study included 24 nondemented, nondepressed PD patients (10 hallucinating and 14 nonhallucinating) and 15 age-matched healthy controls. We analyzed volumetric and diffusion tensor MRI data by applying region of interest analyses on the visual pathways, including the optic chiasm, bilateral optic nerves, lateral geniculate bodies, optic radiations, and primary visual cortex. Results Patients' demographic characteristics, daily medication doses, as well as duration and motor severity of PD were similar in the two PD groups. Compared to PD patients without hallucination, those with hallucination had fractional anisotropy decrease in the left optic nerve and showed atrophy of lateral geniculate bodies, especially in the left side. In addition, the PD with hallucination group had diffusivity increase in the left optic radiation compared to that in the PD without hallucination and healthy control groups. There were no differences in the primary visual cortex volume among the study groups. Conclusions We found microstructural alterations in visual pathways in nondemented PD patients with hallucination, mainly in first-order neurons and atrophy in the lateral geniculate body where the retinal ganglion cells synapse to second-order neurons. Afferent visual pathway degeneration may occur in a trans-synaptic way in PD. Further studies warrant to be conducted.

Background Visual hallucinations (VH) are a common symptom of Parkinson's disease (PD), Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB) and other disorders. Several self-rated interviews (Queen Square Visual Hallucination Inventory, William et al. 2008; North East Visual Hallucinations Interview NEVHI, Mosimann et al. 2008; Tottori University Hallucinations Rating Scale TUHARS, Wada-Isoe et al. 2008; Rush Hallucination Inventory, Goetz et al. 2011) and informant-rated questionnaires (Neuropsychiatric Inventory NPI, Cummings et al.1994; Informant NEVHI) have been developed to assess the characteristics of VH. However, there is no validated measure of VH severity which would be usable in treatment trials. The aim of this study was to develop a new severity score for the NEVHI and to evaluate its reliability and convergent and discriminant validity. Methods Severity scores were designed for individual aspects of VH phenomenology (Complex, Illusions, Simple, Passage/Shadow, Presence). Sixty-four individuals recruited from three participant populations: PDD with VH (n = 32), PDD without VH (n = 11), and healthy age matched controls (n = 21) completed the NEVHI along with evaluations of cognitive (mini mental state exam MMSE, Folstein et al. 1975; Cambridge cognitive test battery CAMCOG, Roth et al.1986) and visual (pareidolia task, Uchiyama et al. 2012)functioning as part of the VEEGSTIM study based in Newcastle University, UK. The hallucination items from the informant-rated NPI were used to assess the convergent and discriminant validity of the NEVHI Severity scores. Results The NEVHI identified VH in 96.9% (n=31) PDD with VH group using the patient (self-rated) NEVHI, of which 40.6% were simple VH, 84.4% Complex VH, 48.4% Illusions, 64.5% Presence, 46.9% Shadow. The NEVHI Complex Severity score strongly correlated with the NPI hallucination severity (rho=0.642, p

Background Complex visual hallucinations are a common symptom in Parkinson’s disease dementia (PDD). Cortical alpha rhythm is a measure of attention and visual perception in healthy controls, and is reported to dysfunction in PDD. Additionally, previous research has related the likelihood to experience visual hallucinations with levels of neuronal excitability in alpha band rhythms from the visual cortex. Methods A group of controls participants (n=17) and recently diagnosed PDD patients (n=26) where recruited for the study. Concurrent transcranial magnetic stimulation and electroencephalogram (TMS-EEG) was delivered to all participants and brain signals recorded. Using stereotactic navigation, the cortical region for optimal phosphene experience was determined within the visual cortex in an incremental power stimulation design, where TMS power was increased up to 75% of stimulator output. Only 11 PDD (mean age = 75.47 ± 5.4) and 9 control participants (mean age 73.82 ± 5.4) experienced phosphenes on 50% of trials (240 trials). Mixed effect analysis was implemented to investigate the effects of scalp region (anterior, posterior), pre-stimulus EEG power (within theta, low-alpha and high alpha bands), and participant group on phosphene experience. Results In the anterior region, there was a significant effect of phosphene or no-phosphene condition on the low-alpha relative power (F(1,18)=4.72, p=0.043, η2=0.208). Both groups showed decreased low-alpha power before phosphene experience and low-alpha power was lower in PDD participants when compared to controls. When separating the PDD hallucinators from the non-hallucinators, a significant effect of phosphene condition was found in high-alpha band (F(1,17)=7.79, p=0.013, η2=0.314). The posterior high-alpha band power was lower in the PDD hallucinator subgroup at both phosphene/no-phosphene conditions, but higher in the non-hallucinator subgroup when phosphenes were not experienced. Conclusions Decreased neural excitability at low-alpha band within the visual cortex is a driver of phosphene experience in both control and PDD patients. However, our data suggests that patients that normally experience complex visual hallucinations are in constant state of decreased alpha power that may elicit this symptom.

The aim of this work was to report on 7 patients presenting a distinctive form of multimodal (tactile and visual) hallucinations for which the term “string hallucinations” is proposed. Having observed a patient interacting with imaginary strips of skin in his hands at our movement disorders unit, we prospectively studied PD patients and caregivers over a 6‐month period using a semistructured interview addressed to this particular phenomenon. Demographic characteristics as well as cognitive and motor function were assessed. A total of 7 of 164 PD patients (4.3%) observed during the study period had string hallucinations. One patient was cognitively intact and the other 6 had some degree of cognitive impairment. Common to the phenomenology of the hallucinations was the unpleasant feeling and vision of threads emerging from the subjects’ hands. Patients interacted with these “threads,” trying to remove them from their hands. Our study identifies a previously undescribed type of hallucinations in PD, characterized by a complex pattern of multimodal tactile and visual hallucinations.

Background Studying default mode network activity or connectivity in different parkinsonisms, with or without visual hallucinations, could highlight its roles in clinical phenotypes’ expression. Multiple system atrophy is the archetype of parkinsonism without visual hallucinations, variably appearing instead in Parkinson's disease (PD). We aimed to evaluate default mode network functions in multiple system atrophy in comparison with PD. Methods Functional magnetic resonance imaging evaluated default mode network activity and connectivity in 15 multiple system atrophy patients, 15 healthy controls, 15 early PD patients matched for disease duration, 30 severe PD patients (15 with and 15 without visual hallucinations), matched with multiple system atrophy for disease severity. Cortical thickness and neuropsychological evaluations were also performed. Results Multiple system atrophy had reduced default mode network activity compared with controls and PD with hallucinations, and no differences with PD (early or severe) without hallucinations. In PD with visual hallucinations, activity and connectivity was preserved compared with controls and higher than in other groups. In early PD, connectivity was lower than in controls but higher than in multiple system atrophy and severe PD without hallucinations. Cortical thickness was reduced in severe PD, with and without hallucinations, and correlated only with disease duration. Higher anxiety scores were found in patients without hallucinations. Conclusions Default mode network activity and connectivity was higher in PD with visual hallucinations and reduced in multiple system atrophy and PD without visual hallucinations. Cortical thickness comparisons suggest that functional, rather than structural, changes underlie the activity and connectivity differences. © 2015 International Parkinson and Movement Disorder Society

Background Migraine, a common brain disorder, disrupts vision more than any other motor or sensory function. The possible visual aura symptoms vary from occasional small flashes of light to complex visual hallucinations, the stereotyped teichopsia being the most typical pattern. It is unclear as to why aura occurs serendipitously, sometimes preceding, but also occurring after the headache, and why aura can present with multiple phenotypes. Methods To better understand the nature of visual disturbances in migraine, 4 aspects must be considered: What are the visual perceptions in migraine; why vision is affected in migraine; the role of cortical spreading depression (CSD); how does vision could affect migraine. Evidence supporting each of these topics is reviewed. Results CSD travels at a similar pace as the march of symptoms in the visual field. Functional neuroimaging studies show spreading changes compatible with CSD regardless of aura. Computerized models reproducing the CSD march on the visual cortex predict a sensory experience compatible with naturally occurring visual auras. Rather than spreading in all directions, these models suggest that CSD moves preferentially in one direction. Migraine-preventive drugs increase the CSD threshold and reduce CSD velocity. Blind migraineurs may present atypical visual aura, with more colors, shorter duration, different shapes, and atypical symptoms, such as auditory experiences. Conclusions CSD is the underlying phenomenon in migraine with and without aura. In migraine without aura, CSD probably does not run over silent areas of the cortex, but rather does not reach symptomatology threshold. Normal vision is important in migraine, as lack of sight may change the visual experience during migraine aura, probably due to cortical reorganization and changes in local susceptibility to CSD.

Objective It has been proposed that the thalamocortical system is an important site of action of hallucinogenic drugs and an essential component of the neural correlates of consciousness. Hallucinogenic drugs such as LSD can be used to induce profoundly altered states of consciousness, and it is thus of interest to test the effects of these drugs on this system. Method 100 μg LSD was administrated orally to 20 healthy participants prior to fMRI assessment. Whole brain thalamic functional connectivity was measured using ROI-to-ROI and ROI-to-voxel approaches. Correlation analyses were used to explore relationships between thalamic connectivity to regions involved in auditory and visual hallucinations and subjective ratings on auditory and visual drug effects. Results LSD caused significant alterations in all dimensions of the 5D-ASC scale and significantly increased thalamic functional connectivity to various cortical regions. Furthermore, LSD-induced functional connectivity measures between the thalamus and the right fusiform gyrus and insula correlated significantly with subjective auditory and visual drug effects. Conclusion Hallucinogenic drug effects might be provoked by facilitations of cortical excitability via thalamocortical interactions. Our findings have implications for the understanding of the mechanism of action of hallucinogenic drugs and provide further insight into the role of the 5-HT2A-receptor in altered states of consciousness.

Background The use of cholinesterase inhibitors is recommended for the treatment of dementia with Lewy bodies (DLB) in the guidelines of the DLB Consortium. However, no consensus regarding therapeutic approaches for DLB-related visual hallucinations has been reached. To the best of our knowledge, an appropriate dose of donepezil for the treatment of DLB at each stage has not been discussed. Methods Eight patients suffering from DLB with visual hallucinations were treated with donepezil. We summarize the effects of donepezil on these visual hallucinations chronologically in all cases and discuss its efficacy and characteristics. Results Donepezil contributed to the complete disappearance of visual hallucinations in all cases, and its effects were maintained for more than 6 months. However, relapses of visual hallucinations also occurred in all cases. Against these relapses, an increased dose of donepezil was very effective in resolving them again in almost all cases in this study. Conclusions Donepezil was highly effective against visual hallucinations in DLB patients, but there were some issues regarding pharmacotherapy for DLB.

One of the most challenging tasks in neuroscience is to be able to meaningfully connect information across the different levels of investigation, from molecular or structural biology to the resulting behavior and cognition. Visual hallucinations are a frequent occurrence in Parkinson's disease and significantly contribute to the burden of the disease. Because of the widespread pathological processes implicated in visual hallucinations in Parkinson's disease, a final common mechanism that explains their manifestation will require an integrative approach, in which consideration is taken across all complementary levels of analysis. This review considers the leading hypothetical frameworks for visual hallucinations in Parkinson's disease, summarizing the key aspects of each in an attempt to highlight the aspects of the condition that such a unifying hypothesis must explain. These competing hypotheses include implications of dream imagery intrusion, deficits in reality monitoring, and impairments in visual perception and attention.

Electrical brain stimulation can provide important information about the functional organization of the human visual cortex. Here, we report the visual phenomena evoked by a large number (562) of intracerebral electrical stimulations performed at low-intensity with depth electrodes implanted in the occipito-parieto-temporal cortex of 22 epileptic patients. Focal electrical stimulation evoked primarily visual hallucinations with various complexities: simple (spot or blob), intermediary (geometric forms), or complex meaningful shapes (faces); visual illusions and impairments of visual recognition were more rarely observed. With the exception of the most posterior cortical sites, the probability of evoking a visual phenomenon was significantly higher in the right than the left hemisphere. Intermediary and complex hallucinations, illusions, and visual recognition impairments were almost exclusively evoked by stimulation in the right hemisphere. The probability of evoking a visual phenomenon decreased substantially from the occipital pole to the most anterior sites of the temporal lobe, and this decrease was more pronounced in the left hemisphere. The greater sensitivity of the right occipito-parieto-temporal regions to intracerebral electrical stimulation to evoke visual phenomena supports a predominant role of right hemispheric visual areas from perception to recognition of visual forms, regardless of visuospatial and attentional factors.

Aim While much research has been conducted towards understanding the basis of visual hallucinations in Parkinson's disease, little has focused on characterizing the content and patients' emotional experience. These factors are likely very influential on a patient's decision to seek treatment, a critical aspect of any symptom from the clinical perspective. Methods A retrospective chart analysis was performed on Parkinson's disease patients seen in a community-based Parkinson's Disease and Movement Disorder Clinic between 2005 and 2010. Results The study consisted of 334 patients with Parkinson's disease, among whom 10.5% had visual hallucinations. Hoehn and Yahr disease stage (P = 0.001), concurrent presence of dementia (P = 0.001),and sex (P = 0.031) were significant onset predictors. The most significant determinant of treatment-seeking was emotional reaction, namely whether hallucinations were bothersome (P = 0.008). However, the specific type of content during hallucinations was sometimes more influential and contradicted emotional response. Conclusion Although treatment-seeking can be predicted by how individuals feel about hallucinations, a patient's decision may not be logically consistent. We suggest that clinicians offer treatment based on patients' recollections and opinions.

Defective visual information processing from both central and peripheral pathways is one of the suggested mechanisms of visual hallucination in Parkinson's disease (PD). To investigate the role of retinal thinning for visual hallucination in PD, we conducted a case-control study using spectral domain optical coherence tomography. We examined a representative sample of 61 patients with PD and 30 healthy controls who had no history of ophthalmic diseases. General ophthalmologic examinations and optical coherence tomography scans were performed in each participant. Total macular thickness and the thickness of each retinal layer on horizontal scans through the fovea were compared between the groups. In a comparison between patients with PD and healthy controls, there was significant parafoveal inner nuclear layer thinning, whereas other retinal layers, including the retinal nerve fiber layer, as well as total macular thicknesses were not different. In terms of visual hallucinations among the PD subgroups, only retinal nerve fiber layer thickness differed significantly, whereas total macular thickness and the thickness of other retinal layers did not differ. The retinal nerve fiber layer was thinnest in the group that had hallucinations without dementia, followed by the group that had hallucinations with dementia, and the group that had no hallucinations and no dementia. General ophthalmologic examinations did not reveal any significant correlation with hallucinations. There were no significant correlations between retinal thicknesses and duration or severity of PD and medication dosages. The results indicate that retinal nerve fiber layer thinning may be related to visual hallucination in nondemented patients with PD. Replication studies as well as further studies to elucidate the mechanism of thinning are warranted.

OBJECTIVE This study aimed to test the prediction from the Perception and Attention Deficit model of complex visual hallucinations (CVH) that impairments in visual attention and perception are key risk factors for complex hallucinations in eye disease and dementia. METHODS Two studies ran concurrently to investigate the relationship between CVH and impairments in perception (picture naming using the Graded Naming Test) and attention (Stroop task plus a novel Imagery task). The studies were in two populations-older patients with dementia (n = 28) and older people with eye disease (n = 50) with a shared control group (n = 37). The same methodology was used in both studies, and the North East Visual Hallucinations Inventory was used to identify CVH. RESULTS A reliable relationship was found for older patients with dementia between impaired perceptual and attentional performance and CVH. A reliable relationship was not found in the population of people with eye disease. CONCLUSIONS The results add to previous research that object perception and attentional deficits are associated with CVH in dementia, but that risk factors for CVH in eye disease are inconsistent, suggesting that dynamic rather than static impairments in attentional processes may be key in this population.

Visual Hallucinations are considered to affect about 20%-40% of patients with Parkinson's disease. They are generally seen as a side effect of this long-term illness and can severely affect the daily quality of life of patients. The aim of this study was to determine the coping patterns or strategies used by patients and establish whether the phenomenology and behaviours used by patients enabled control of the phenomenon. Demographic and clinical variables were recorded, including motor measures, cognitive status, and depressive symptoms. Patient with hallucinations were at a more advance stage of the disease and displayed more depressive symptoms than their non-hallucinating counterparts. Most patients used more than one constructive coping strategy, the most common were simple behavioural strategies based around motor action or cognitive approaches resulting in visual modification. In addition, humour was a common technique used by the patients to deal with the phenomenon. Emotional responses varied between patients, but it was found that the actual content of the hallucination was not directly associated with whether it caused trouble to the patient, but perceived stress was strongly correlated with the subjective disturbing nature of visual hallucinations (VHs). This study gives insight into the role of cognitive-behavioural approaches when dealing with VHs and opens up avenues for future studies in helping patient to deal with hallucinations.

Four patients experienced visual hallucinations that appear to have been precipitated by lisinopril. Other cases of visual hallucinations have been reported with other angiotensin-converting enzyme (ACE) inhibitors. Older patients, particularly those with a history of either dementia or mild cognitive impairment, may be at higher risk. Hallucinations resolved within 1 to 30 days after cessation of ACE inhibitors. Development of visual hallucinations after initiation of ACE inhibitors should prompt discontinuation of therapy. Visual hallucinations have been reported in one case involving an ARB. Visual hallucinations have not been associated with direct renin inhibitors. Consideration should be given to use of alternative, unrelated antihypertensive drug classes.

Visual hallucinations are common in advanced Parkinson's disease (PD). The pathophysiology of visual hallucinations may involve enhanced serotonergic neurotransmission. The atypical antipsychotics clozapine and quetiapine, which have affinity for 5-HT(2A) and 5-HT(1A) receptors, are effective against visual hallucinations in PD. 5-HT(2A) receptors are increased in ventral visual pathways in PD patients with visual hallucinations, and we hypothesized that 5-HT(1A) receptors were also involved in visual hallucinations in PD. Autoradiographic binding using [(3) H]-WAY-100,635 and NAN-190 was performed in brain sections from 6 PD patients with visual hallucinations, 6 PD patients without visual hallucinations, and 5 age-matched controls. All PD subjects had been treated with L-dopa. Brain areas studied were the orbitofrontal, inferolateral temporal, and motor cortices, as well as the striatum, globus pallidus, substantia nigra, and thalamus. 5-HT(1A) -binding levels were dramatically increased in the ventral visual pathways of all PD patients compared with controls (0 vs 11 and 0 vs 100 nmol/mg, respectively; both P .05). Gross abnormalities in 5-HT(1A) levels in ventral visual areas occurred in all PD patients exposed to L-dopa. However, as there was no difference in 5-HT(1A) -binding levels between hallucinators and nonhallucinators, alterations in 5-HT(1A) receptor levels may not contribute specifically to visual hallucinations in PD. However, the discrete anatomical distribution of rises to the ventral visual areas suggests some role in predisposing to visual hallucinations.

Visual misperception and hallucinations represent a major problem in advanced PD. The pathophysiological mechanisms underlying these symptoms remain poorly understood, with limited tests for their assessment. A recent hypothesis has suggested that visual misperception and hallucinations may arise from disrupted processing in the attentional networks. To assess and quantify visual misperceptions, we developed the novel bistable percept paradigm (BPP), which consists of a battery of “single” and “hidden” monochromatic images that subjects are required to study until they are satisfied that they have recognized everything that the image may represent. In this experiment, 45 patients and 18 age-matched controls performed the BPP. Using an error score value derived from the control group, 23 patients were identified as having significant deficits on the task. Compared to patients who were unimpaired on the task, this group of patients had significantly higher levels of self-reported hallucinations on the SCales for Outcomes in PArkinson's Disease–Psychiatric Complications and also symptoms of rapid eye movement sleep behavior disorder (RBD). Furthermore, impairment on the BPP was associated with significantly reduced performance on an attentional set-shifting task. Patients with impaired performance on the BPP had higher rates of hallucinations, increased symptoms of RBD, and poorer performance on set shifting, suggesting disrupted processing within the attentional control networks. We propose that the BPP may offer a novel approach for exploring the neural correlates underlying visual hallucinations and misperceptions in PD. © 2012 Movement Disorder Society

Charles Bonnet syndrome is a neurological disease characterised by clear, recurrent visual hallucinations usually following visual loss. It is often misdiagnosed as psychosis, delirium or early dementia, but patients generally retain insight. Mark Greener discusses what we currently know about this fascinating condition and what remains a mystery. Copyright © 2014 John Wiley & Sons

Introduction Visual hallucinations that arise following vision loss stem from aberrant functional activity in visual cortices and an imbalance of activity across associated cortical and subcortical networks subsequent to visual pathway damage. We sought to determine if structural changes in white matter connectivity play a role in cases of chronic visual hallucinations associated with visual cortical damage. Methods We performed diffusion tensor imaging (DTI) and probabilistic fiber tractography to assess white matter connectivity in a patient suffering from continuous and disruptive phosphene (simple) visual hallucinations for more than 2 years following right occipital stroke. We compared these data to that of healthy age-matched controls. Results Probabilistic tractography to reconstruct white matter tracts suggests regeneration of terminal fibers of the ipsilesional optic radiations in the patient. However, arrangement of the converse reconstruction of these tracts, which were seeded from the ipsilesional visual cortex to the intrahemispheric lateral geniculate body, remained disrupted. We further observed compromised structural characteristics, and changes in diffusion (measured using diffusion tensor indices) of white matter tracts in the patient connecting the visual cortex with frontal and temporal regions, and also in interhemispheric connectivity between visual cortices. Conclusions Cortical remapping and the disruption of communication between visual cortices and remote regions are consistent with our previous functional magnetic resonance imaging (fMRI) data showing imbalanced functional activity of the same regions in this patient (Rafique et al, 2016, Neurology, 87, 1493-1500). Long-term adaptive and disruptive changes in white matter connectivity may account for the rare nature of cases presenting with chronic and continuous visual hallucinations.

Visual hallucinations (VHs) are common in dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD), while auditory hallucinations are rare. To neurophysiologically investigate the pathophysiology of VHs in these disorders, we studied event-related potentials (ERPs) of DLB, PDD, and Alzheimer's disease (AD) patients. We compared visual and auditory ERP latencies among PDD patients with and without VHs (PDD-H: 11, PDD-N: 6), DLB patients (24), and AD patients (21). To elicit visual and auditory ERPs, a facial discrimination paradigm and a conventional auditory odd-ball paradigm, respectively, were used. The mean visual P3 latencies in the PDD-H and DLB groups were significantly longer than that in the AD group, while the mean auditory P3 latencies in all four patient groups were comparable. The mean visual P2 latencies in the PDD-N, PDD-H, and DLB groups were significantly longer than that in the control group. Our findings suggest that visual cognitive functions are selectively impaired in hallucinatory patients with DLB and PDD. VHs may be associated in part with predominant visual cognitive impairments attributable to PDD and DLB pathologies. Our findings also suggest that the impairments occur at the early stage of facial information processing.

Five children, admitted with acute psychotic reactions after use of Scopolamine eye drops 0.2%, are presented. The predominant symptoms were visual hallucinations, strange behaviour, and restlessness. In one case peripheral symptoms were observed. Recovery was complete in 24 h. Prescription of Scopolamine eye drops should be followed by information of possible adverse effects. Cyclopentolate might be used instead.