The exact pathogenesis of visual hallucinations in Parkinson's disease is not known but an integrated model has been proposed that includes impaired visual input and central visual processing, impaired brainstem regulation of sleep-wake cycle with fluctuating vigilance, intrusion of rapid eye movement dream imagery into wakefulness and emergence of internally generated imagery, cognitive dysfunction and influence of dopaminergic drugs. In a clinical study, we assessed motor and non-motor function, including sleep, mood, autonomic and global, frontal and visuoperceptive cognitive function in patients with and without visual hallucinations. A subgroup of patients underwent detailed ophthalmological assessment. In a separate pathological study, histological specimens were obtained from cases of pathologically proven Parkinson's disease and a retrospective case notes review was made for reporting of persistent formed visual hallucinations. An assessment of Lewy body and Lewy neurite pathology was carried out in five cortical regions as recommended by diagnostic criteria for dementia with Lewy Bodies and in brainstem nuclei. Ninety-four patients (mean age 67.5 ± 9.5 years) participated in the clinical study of whom 32% experienced visual hallucinations. When corrected for multiple comparisons, patients with visual hallucinations had significantly greater disease duration, treatment duration, motor severity and complications, sleep disturbances, in particular excessive daytime somnolence and rapid eye movement sleep behavioural disorder, disorders of mood, autonomic dysfunction and global, frontal and visuoperceptive cognitive dysfunction. Of the 94 patients, 50 (53%) underwent ophthalmological assessment. There were no differences in ocular pathology between the visual hallucination and non-visual hallucination groups. In a logistic regression model the four independent determinants of visual hallucinations were rapid eye movement sleep behavioural disorder (P = 0.026), autonomic function (P = 0.004), frontal cognitive function (P = 0.020) and a test of visuoperceptive function (object decision; P = 0.031). In a separate study, post-mortem analysis was performed in 91 subjects (mean age at death 75.5 ± 8.0 years) and persistent visual hallucinations were documented in 63%. Patients in the visual hallucinations group had similar disease duration but had significantly higher Lewy body densities in the middle frontal (P = 0.002) and middle temporal gyri (P = 0.033) and transentorhinal (P = 0.005) and anterior cingulate (P = 0.020) cortices but not parietal cortex (P = 0.22). Using a comprehensive assessment of the clinical, demographic and ophthalmological correlates of visual hallucinations in Parkinson's disease, the combined data support the hypothesized model of impaired visual processing, sleep-wake dysregulation and brainstem dysfunction, and cognitive, particularly frontal, impairment all independently contributing to the pathogenesis of visual hallucinations in Parkinson's disease. These clinical data are support...

Pupil tests provide a convenient and simple method for evaluation of autonomic function. Most patients with autonomic disorders show evidence of sympathetic or parasympathetic deficits in the pupil, and these can be detected using a combination of clinical signs, pupillometric tests (measuring the responses to light, or an accommodative effort, or a sudden noise) and pharmacological tests (using topically applied drugs both to confirm a deficit and to localize the lesion). Caution is needed in the interpretation of these tests, particularly if the deficits are mixed (i.e. sympathetic and parasympathetic) or bilateral. The pattern of autonomic disturbance in the pupils often correlates poorly with autonomic function elsewhere, but may have diagnostic value in discriminating between different underlying conditions.

ObjectiveTo assess the role of visual measures and retinal volume to predict the risk of Parkinson disease (PD) dementia. MethodsIn this cohort study, we collected visual, cognitive, and motor data in people with PD. Participants underwent ophthalmic examination, retinal imaging using optical coherence tomography, and visual assessment including acuity and contrast sensitivity and highlevel visuoperception measures of skew tolerance and biological motion. We assessed the risk of PD dementia using a recently described algorithm that combines age at onset, sex, depression, motor scores, and baseline cognition. ResultsOne hundred forty-six people were included in the study (112 with PD and 34 age-matched controls). The mean disease duration was 4.1 (±2·5) years. None of these participants had dementia. Higher risk of dementia was associated with poorer performance in visual measures (acuity: ρ = 0.29, p = 0.0024; contrast sensitivity: ρ = −0.37, p < 0.0001; skew tolerance: ρ = −0.25, p = 0.0073; and biological motion: ρ = −0.26, p = 0.0054). In addition, higher risk of PD dementia was associated with thinner retinal structure in layers containing dopaminergic cells, measured as ganglion cell layer (GCL) and inner plexiform layer (IPL) thinning (ρ = −0.29, p = 0.0021; ρ = −0.33, p = 0.00044). These relationships were not seen for the retinal nerve fiber layer that does not contain dopaminergic cells and were not seen in unaffected controls. ConclusionVisual measures and retinal structure in dopaminergic layers were related to risk of PD dementia. Our findings suggest that visual measures and retinal GCL and IPL volumes may be useful to predict the risk of dementia in PD. Practical ImplicationsNeurology® Clinical Practice is committed to providing clinical insights helpful to neurologists in everyday practice. Each Full Case includes a "Practical Implications" statement, a pearl of wisdom for the practicing clinician.