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Williams and Lees’ study,1 which is unique because ofthe impressive sample size and autopsy control, clearlyestablished a strong relation between visualhallucinations and the presence of Lewy-bodypathology in Parkinson’s disease. The results willprobably become a milestone in the operational clinicalcriteria for the diagnosis of Parkinson’s disease, and thepresence of visual hallucinations should be regarded as anew red flag from now on.

The results strongly challenge the common notionthat visual hallucinations in Parkinson’s disease are

mainly related to antiparkinsonian chronic treatmentand probably occur as a drug-induced adverse effect inthe frame of a multifactorial origin, as suggested in anevidence-based review.2 Indeed, Williams and Leesshowed only weak correlations between visualhallucinations and the use of selegiline and ergotdopamine agonists, and no association at all with theuse of levodopa, non-ergot dopamine agonists,amantadine, and anticholinergic drugs. These negativecorrelations will certainly seem puzzling for all thoseclinicians dealing in the everyday clinical practice with

Antiparkinsonian drugs and visual hallucinations

with epilepsy in China, a feasible and safe method ofreducing this number is offered. There are of coursemethodological questions to be answered in suggestingthe transition from a research project to health policy.Was careful supervision and training by neurologistscentral to the success of the scheme, and can it beimplemented nationally? Will there be adequatecapacity to continue the educational and training effortson a much larger scale? Can these results be translatedto other countries?

Certainly poverty, rural populations, and culturalbarriers are encountered worldwide.5 China does havethe advantage of a health system with relatively largenumbers of trained staff. In most African countries itwould be impossible to consider having all people withepilepsy diagnosed and treated by medical practitioners,when the ratio of the number of people in thepopulation per doctor frequently exceeds 10 000 toone.6 Primary-health-care nurses, and in some countriesclinical officers, are usually the most available healthprofessionals to undertake community-basedinterventions, and they have been shown to be effectivein this role.7

An interesting demographic difference between Chinaand other developing populations is the relativelysmaller number of children. Although the large overallsample size of Wang and colleagues’ study ensured thatthere were still 268 children younger than 14 yearstaking part, the small proportion (11%) of the studypopulation this represents raises the possibility of minoradverse effects being overlooked and diluted out. Theauthors specifically address this question but do leavethe possibility of unrecognised minor effects open.

Certainly, the anecdotal experience of manyneurologists practising in developing countries is thatsome patients who have received phenobarbitalwithout suspected adverse effects for years experiencealarming cognitive improvement on withdrawing fromthe drug.

There is much to be hopeful about. It is appropriatethat Chinese investigators, situated in the world’slargest developing nation, lead the way in showingsubstantial and sustainable improvements in seizurecontrol, and that there is already a plan to implementthe results of the project nationally. The GlobalCampaign against Epilepsy can point to solid outcomesfrom this cooperative work. Neurologists and healthplanners in other developing continents are encouragedto identify problem areas and to adapt to local needs.

Jens MielkeCollege of Health Sciences, University of Zimbabwe , Harare,Zimbabwemielke@ecoweb.co.zw

I have no conflicts of interest.

1 Adamolekun B, Mielke JK, Ball DE. An evaluation of the impact of healthworker and patient education on the care and compliance of patients withepilepsy in Zimbabwe. Epilepsia 1999; 40: 507–11.

2 Wang WZ, Wu JZ, Ma GY, et al. Efficacy assessment of phenobarbital inepilepsy: a large community-based intervention in rural China.Lancet Neurol 2006; 5: 46–52.

3 World Health Organization. The global campaign against epilepsy: out ofthe shadows. Geneva: WHO, 2000.

4 Wang WZ, Wu JZ, Wang DS, et al. The prevalence and treatment gap inepilepsy in China: an ILAE/IBE/WHO study. Neurology 2003; 60: 1544–45.

5 Scott RA, Lhatoo SD, Sander JW. The treatment of epilepsy in developingcountries: where do we go from here? Bull World Health Organ 2001;79: 344–51.

6 Dekker PA. Epilepsy a manual for medical and clinical officers in Africa,revised edn. WHO/MSD/MBD/02.02. Geneva: WHO, 2002.

7 Ndoye NF, Sow AD, Diop AG, et al. Prevalence of epilepsy, its treatmentgap and knowledge, attitude and practice of its population in suburbanSenegal: an ILAE/IBE/WHO study. Seizure 2005; 14: 106–11.

Reflection and Reaction

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patients with advanced Parkinson’s disease who areundergoing chronic pharmacological treatment and whohave visual hallucinations.

Some of these negative findings can possibly beexplained by the study design, which did not specificallyaddress the relation between antiparkinsonian drugsand visual hallucinations. Indeed, many patients weregiven more than one drug, but this is not taken intoaccount in the statistical analysis. The chronicadministration of more than one antiparkinsonian drugis probably one of the main risk factors for developmentof visual hallucinations.2,3 Moreover, a close inspection ofdata shows that the group of patients with Parkinson’sdisease who were taking non-ergot dopamine agonistsrepresents only 9% of the whole sample, suggesting apossible statistical bias that could underestimate thepotential of this class of drugs to induce visualhallucinations. Williams and Lees could not explain whythe use of anticholinergic drugs (the most likely toinduce delirium and visual hallucinations)3 did not resultin a significant association with visual hallucinations,despite this drug being used by more than 60% of thewhole sample of patients. Nevertheless, because of thepoor effects of anticholinergics on motor symptoms inadvanced disease, Williams and Lees strongly suggestthat treating physicians should not administer thesedrugs.1

So, findings of the current study simultaneouslyprovide important evidence for the diagnosis ofParkinson’s disease and a probably misleadingperspective on this apparent negative association ofdopaminergic treatment in the pathogenesis of visualhallucinations. These findings raise provocative, butessential, questions on how treating physicians shouldbehave when faced with a patient with Parkinson’sdisease and persistent visual hallucinations. Afterexclusion of an overt cause for this adverse effect (eg,infection, dehydration, electrolyte imbalance), areduction in dose or gradual discontinuation of a givendopaminergic drug (without inducing a meaningfuldeterioration in Parkinson’s disease characteristics)before starting antipsychotic treatment, as suggested byproposed treatment guidelines, might not benecessary.3 Further studies are urgently needed toaddress this crucial and common (about 40% of patientswith advanced disease have visual hallucinations today1

vs fewer than 5% in the predopaminergic drugs era4)clinical issue.

Simone Rossi, Sabina Bartalini, Monica UlivelliDipartimento di Neuroscienze, Sezione Neurologia, Università diSiena, ItalyRossisimo@unisi.it

We have no conflicts of interest.

1 Williams DR, Lees AJ. Visual hallucinations in the diagnosis of idiopathicParkinson’s disease: a retrospective autopsy study. Lancet Neurol 2005;4: 605–10.

2 Papapetropoulos S, Mash DC. Psychotic symptoms in Parkinson’s disease:from description to etiology. J Neurol 2005; 252: 753–64

3 Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for themanagement of Parkinson’s disease (2001): treatment guidelines.Neurology 2001; 56 (suppl 5): S1–S88.

4 Schwab RS, Fabing HD, Prichard JS. Psychiatric symptoms and syndromesin Parkinson’s disease. Am J Psychiatry 1950; 107: 901–07.

Authors’ responseVisual hallucinations occur in Parkinson’s disease,especially in patients who take antiparkinsonian drugs.Our report of a large cohort of pathologically diagnosedpatients with bradykinetic rigid syndromes confirmedthis notion and also showed that in non-Lewy bodydisorders, including progressive supranuclear palsy andmultisystem atrophy, visual hallucinations are rare. Weshowed that the types of medication used were similarin Lewy-body and in non-Lewy-body pathologies andthat medication per se could not account for thedifference in incidence of visual hallucinations betweenthese groups.

We also noted that in many patients with Lewy-bodypathology, visual hallucinations did not occur during thedisease course, despite medication similar to that usedby those who had hallucinations during their disease.Our study identified several clinical characteristics thatseemed to indicate widespread Lewy-body pathology(cognitive decline, autonomic dysfunction, andsymmetrical disease) and to affect the time to onset ofvisual hallucinations. Together, these findings argueagainst an independent relation between medicationuse and the emergence of visual hallucinations. Wesuggested, therefore, that drugs per se do not directlycause these side-effects, but that an interaction betweenwidespread Lewy-body pathology and antiparkinsoniantreatment is more important.1

Rossi and colleagues seem to have missed severalimportant points of our article. The strengths of ourstudy included the sample size, the detailed medicalnotes, and the assessment of the presence ofhallucinations in all patients throughout their entiredisease course. The lack of correlation betweenmedication use and visual hallucinations is underlined by