Visual hallucinations in the diagnosis of idiopathic Parkinson’s disease: a retrospective autopsy study
Williams DR and Lees AJ;
Commented by , 22 Nov 2005
Background
Visual hallucinations frequently occur in patients with idiopathic Parkinson’s disease. In the past, this has been primarily related to antiparkinsonian, particularly dopaminergic treatment. Recent findings, however, suggest that visual hallucinations can at least partly be an integral part of the disease pathology.
Aims of the study
The aims of this study were to investigate the relationship between pathological diagnosis of a bradykinetic-rigid syndrome and visual hallucinations (VH), and the relation between VH and other factors, such as medication.
Methods
The study was conducted in 788 cases with parkinsonism archived at the Queen Square Brain Bank for Neurological Diseases. These patients had not been given standardised antemortem assessments, rather clinical records were assessed for reporting of VH during their lifetime.
The incidence of VH in pathologically diagnosed cases was calculated, and factors affecting the presence of VH were investigated.
Results
All together 44 cases were excluded from the analysis because of insufficient clinical data. In the remaining 744 cases VH were found in 37%. Out of these VH occurred in 50% (221/445) of patients with Parkinson’s disease (PD), in 73% (32/44) with dementia with Lewy Bodies (DLB), and in 7% (18/255) of patients with non-Lewy-body parkinsonism such as PSP and MSA.
The specificty of VH for Lewy-body parkinsonism (combining PD and DLB) was 92.9% (95% CI 89.1-95.8) and the positive predictive value was 93.4% (CI 89.7-95.8), whereas sensitivity was 50.7% and negative predictive value was 50.1%.
VH were associated with cognitive dysfunction (hazard ratio 5.62; CI 3.37-9.35), autonomic dysfunction (hazard ratio 3.13; CI 1.77-5.52), axial rigidity (2.22; CI 1.26-3.85) within the first 2 years of disease onset and also age of onset (1.05; CI 1.03-1.07).
In patients with PD, the onset of VH typically occurred in the second half of the disease course, and the time to onset of VH was only weakly correlated with use of selegiline (p=0.005) and ergot dopamine agonists (p=0.006), but not correlated with use of levodopa, amantadine, or anticholinergic drugs.
The authors concluded that the presence of VH is helpful in the differentiation of PD from other non-Lewy-body causes of parkinsonism and proposed that VH be added to the operational clinical criteria for the diagnosis of PD, as a supportive criterion.
Professor Emre’s comments
Visual hallucinations are a frequent and troublesome problem encountered in patients with PD. Their appearence early in the disease course, especially in young patients is rare, when this happens patients are at inreased risk to develep dementia within the next few years (ref. 1).
For many years VH were thought to be a complication of antiparkinsonian, especially dopaminergic medication. The question, however, remained unanswered why some patients receiving high doses of dopaminergic medication do not develop VH and why they occur rather late in the disease process, especially in the context of impaired intellectual functions.
Indeed a recent study revealed that there was no correlation between the dose of dopaminergic medication and the occurrence of visual hallucnations (ref. 2), although clinical experience suggests that visual hallucinations usually improve when dopaminergic medication is reduced, suggesting a facilitating role for these drugs.
Part of the explanation may be the extent of disease pathology and the related amount of dopaminergic denervation. It was suggested by Kulisevky (ref. 3) that there is an optimal level of dopaminergic stimulation needed in prefrontal cortex for normal cognitive functioning, the width of optimal stimulation for normal functioning may vary depending on the disease stage and the consequent amount of dopaminergic deficit, overstimulation at later stages, at which this window has been narrowed, may cause cognitive impairment and hallucinations.
Recently, it has been suggested that, rather than being due to medication, visual hallucinations may be due to cellular loss and Lewy-body (LB) pathology in the ventral-temporal regions of the brain (ref. 4). The results of the current study support the notion that VH are related to disease pathology.
It was remarkable that 50% of those pathologically diagnosed PD cases and 73% of those with DLB were found to have reported visual hallucinations during their lifetime. The correlation between the onset of VH and antiparkinsonian medication was rather weak, whereas early occurrence of cognitive dysfunction, autonomic dysfunction and axial rigidity imposed a high risk for development of VH.
Another remarkable finding was that the specificity and positive predictive value for VH were very high, whereas sensitivity and negative predictive value were low. In other words not all patients with PD develop VH, but if a patient with parkinsonism develop VH this feature reliably differentiates patients with Lewy-body related pathology from those without.
This study confirms and extends the previous findings that VH in PD and DLB are largely a consequence of disease pathology and highly associated with LB formation. One can conclude that it may be quite helpful to actively inquire for the presence of VH in the differentiation of LB-related disorders such as PD and DLB from other, non-LB related causes of parkinsonism, such as PSP and MSA.
References
1. Goetz CG, Vogel C, Tanner CM and Stebbins GT. Early dopaminergic drug-induced hallucinations in parkinsonian patients. Neurology 1998; 51 (3); 811-814
2. Merims D, Shabtai H, Korczyn AD, Peretz C, Weizman N and Giladi N. Antiparkinsonian medication is not a risk factor for the development of hallucinations in Parkinson's disease. Journal of Neuralal Transmission 2004; 111 (10-11); 1447-1453
3. Kulisevsky J. Role of dopamine in learning and memory: implications for the treatment of cognitive dysfunction in patients with Parkinson’s disease. Drugs and Aging 2000; 16 (5); 365-379
4. Harding AJ, Broe GA and Halliday GM. Visual hallucinations in Lewy body disease relate to Lewy bodies in the temporal lobe. Brain 2002; 125 (2); 391-403 (Free full text article)