4
taking the average score of the two trials instead of the best score. This practice is consistent with CAPSIT guidelines, a deviation from earlier CAPIT instructions. Regardless, the clinical relevance of these differences is limited, as these indi- viduals were extremely slow on both occasions. Taken together, the excellent test–retest reliability of all tests examined and the almost binary clinical condition of patients with advanced PD seem to justify the elimination of multiple baseline evaluations from the Core Assessment Programs. This would offer a welcome simplification of current pub- lished guidelines, 7,8 for several reasons. First, there is the issue of how to deal statistically with multiple baseline data sets. Should one use means, medians, or worst/best scores for the baseline score? Second, comparisons are made with postoper- ative scores that are obtained during only a single evaluation. Why the repetition of baseline but not follow-up visits? Third, multiple evaluations (especially off exams) place a significant and often traumatic burden on the patient. Fourth, core evalu- ations require a considerable time commitment from investi- gators. It has been argued that multiple baseline visits would improve patients’ awareness of their symptoms and expecta- tions, and establish better rapport between patients and surgical team. 15 Although important, these issues are addressed prefer- ably during regular patient–physician interactions in clinic, before formal core assessments. Finally, a one-visit baseline evaluation does not eliminate the option of a second evaluation if, for any reason, the individual does not seem to be in his usual off or on condition. In conclusion, test–retest reliability of UPDRS-III as well as dyskinesia scales and timed motor test in patients with advanced Parkinson’s disease is high and justifies single baseline evaluations before surgical and pharma- cologic trials in this patient group. Obvious prerequisites are that the assessments are carried out under standard conditions (defined off and on conditions, same time of day), and by the same experienced rater. Acknowledgments: This research was supported in part by the National Institutes of Health (RO1-NS4092) and the Charles H. and Bertha L. Boothroyd Foundation. REFERENCES 1. Fahn S, Elton RL, the UPDRS Development Committee. Unified Par- kinson’s Disease Rating Scale. In: Fahn S, Marsden CD, Calne D, Goldstein M, editors. Recent developments in Parkinson’s disease. Flo- rham Park, NJ: Macmillan Health Care Information; 1987. p 153–164. 2. Richards M, Marder K, Cote L, Mayeux R. Interrater reliability of the Unified Parkinson’s Disease Rating Scale motor examination. Mov Disord 1994;9:89 –91. 3. van Hilten JJ, van der Zwan AD, Zwinderman AH, Roos RA. Rating impairment and disability in Parkinson’s disease: evalua- tion of the Unified Parkinson’s Disease Rating Scale. Mov Disord 1994;9:84 – 88. 4. Martinez-Martin P, Gil-Nagel A, Gracia LM, Gomez JB, Martinez- Sarries J, Bermejo F. Unified Parkinson’s Disease Rating Scale characteristics and structure. The Cooperative Multicentric Group. Mov Disord 1994;9:76 – 83. 5. Stebbins GT, Goetz CG. Factor structure of the Unified Parkin- son’s Disease Rating Scale: motor examination section. Mov Dis- ord 1998;13:633– 636. 6. Siderowf A, McDermott M, Kieburtz K, Blindauer K, Plumb S, Shoulson I, the Parkinson Study Group. Test–retest reliability of the Unified Parkinson’s Disease Rating Scale in patients with early Parkinson’s disease: results from a multicenter clinical trial. Mov Disord 2002;17:758 –763. 7. Langston JW, Widner H, Goetz CG, Brooks D, Fahn S, Freeman T, Watts R. Core assessment program for intracerebral transplan- tations (CAPIT). Mov Disord 1992;7:2–13. 8. Defer GL, Widner H, Marie RM, Remy P, Levivier M. Core assessment program for surgical interventional therapies in Parkin- son’s disease (CAPSIT-PD). Mov Disord 1999;14:572–584. 9. Guy W, editor. ECDEU assessment manual for psychopharmacol- ogy. Washington: Government Printing Office; 1976. p 534 –537. 10. Goetz CG, Stebbins GT, Shale HM, Lang AE, Chernik DA, Chmura TA, Ahlskog JE, Dorflinger EE. Utility of an objective dyskinesia rating scale for Parkinson’s disease: inter- and intrarater reliability assessment. Mov Disord 1994;9:390 –394. 11. Goetz CG, Stebbins GT, Chmura TA, Fahn S, Klawans HL, Marsden CD. Teaching tape for the motor section of the Unified Parkinson’s Disease Rating Scale. Mov Disord 1995;10:263–266. 12. Fleiss JL. The measurement of interrater agreement. In: Fleiss JL, editor. Statistical methods for rates and proportions. New York: Wiley and Sons; 1981. p 212–236. 13. Nutt JG, Woodward WR. Levodopa pharmacokinetics and phar- macodynamics in fluctuating parkinsonian patients. Neurology 1986;36:739 –774. 14. Verhagen Metman L, van den Munckhof P, Klaassen AA, Blanchet P, Mouradian MM, Chase TN. Effects of supra-threshold levodopa doses on dyskinesias in advanced Parkinson’s disease. Neurology 1997;49:711–713. 15. Lang AE, Widner H. Deep brain stimulation for Parkinson’s dis- ease: patient selection and evaluation. Mov Disord 2002; 17(Suppl.):94 –101. Restless Legs in Tourette Syndrome P. Lespe ´rance, MD, 1 N. Djerroud, BSc, 2 A. Diaz Anzaldua, BSc, 3 G.A. Rouleau, MD, PhD, 3 S. Chouinard, MD, 1 F. Richer, PhD, 1,2 * and the Montre ´al Tourette Study Group 1 Centre Hospitalier de l’Universite ´ de Montre ´al, Montre ´al, Que ´bec, Canada; 2 Universite ´ du Que ´bec a ` Montre ´al, Montre ´al, Que ´bec, Canada; 3 McGill University Health Center, Montre ´al, Que ´bec, Canada Abstract: Restless legs syndrome (RLS) and Tourette’s syn- drome (TS) share some common features, including the phenomenology of sensations relieved by movements, but *Correspondence to: Dr. Francois Richer, Neuroscience Center, UQM, Montre ´al, Que ´bec, Canada H2W 1T8. E-mail: [email protected] Received 20 August 2003; Revised 12 December 2003; Accepted 19 January 2004 Published online 24 March 2004 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.20100 1084 P. LESPE ´ RANCE ET AL. Movement Disorders, Vol. 19, No. 9, 2004

Restless legs in Tourette syndrome

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taking the average score of the two trials instead of the bestscore. This practice is consistent with CAPSIT guidelines, adeviation from earlier CAPIT instructions. Regardless, theclinical relevance of these differences is limited, as these indi-viduals were extremely slow on both occasions.

Taken together, the excellent test–retest reliability of all testsexamined and the almost binary clinical condition of patientswith advanced PD seem to justify the elimination of multiplebaseline evaluations from the Core Assessment Programs.This would offer a welcome simplification of current pub-lished guidelines,7,8 for several reasons. First, there is the issueof how to deal statistically with multiple baseline data sets.Should one use means, medians, or worst/best scores for thebaseline score? Second, comparisons are made with postoper-ative scores that are obtained during only a single evaluation.Why the repetition of baseline but not follow-up visits? Third,multiple evaluations (especially off exams) place a significantand often traumatic burden on the patient. Fourth, core evalu-ations require a considerable time commitment from investi-gators. It has been argued that multiple baseline visits wouldimprove patients’ awareness of their symptoms and expecta-tions, and establish better rapport between patients and surgicalteam.15 Although important, these issues are addressed prefer-ably during regular patient–physician interactions in clinic,before formal core assessments. Finally, a one-visit baselineevaluation does not eliminate the option of a second evaluationif, for any reason, the individual does not seem to be in hisusual off or on condition.

In conclusion, test–retest reliability of UPDRS-III aswell as dyskinesia scales and timed motor test in patientswith advanced Parkinson’s disease is high and justifiessingle baseline evaluations before surgical and pharma-cologic trials in this patient group. Obvious prerequisitesare that the assessments are carried out under standardconditions (defined off and on conditions, same time ofday), and by the same experienced rater.

Acknowledgments: This research was supported in part bythe National Institutes of Health (RO1-NS4092) and theCharles H. and Bertha L. Boothroyd Foundation.

REFERENCES

1. Fahn S, Elton RL, the UPDRS Development Committee. Unified Par-kinson’s Disease Rating Scale. In: Fahn S, Marsden CD, Calne D,Goldstein M, editors. Recent developments in Parkinson’s disease. Flo-rham Park, NJ: Macmillan Health Care Information; 1987. p 153–164.

2. Richards M, Marder K, Cote L, Mayeux R. Interrater reliability ofthe Unified Parkinson’s Disease Rating Scale motor examination.Mov Disord 1994;9:89–91.

3. van Hilten JJ, van der Zwan AD, Zwinderman AH, Roos RA.Rating impairment and disability in Parkinson’s disease: evalua-tion of the Unified Parkinson’s Disease Rating Scale. Mov Disord1994;9:84–88.

4. Martinez-Martin P, Gil-Nagel A, Gracia LM, Gomez JB, Martinez-Sarries J, Bermejo F. Unified Parkinson’s Disease Rating Scale

characteristics and structure. The Cooperative Multicentric Group.Mov Disord 1994;9:76–83.

5. Stebbins GT, Goetz CG. Factor structure of the Unified Parkin-son’s Disease Rating Scale: motor examination section. Mov Dis-ord 1998;13:633–636.

6. Siderowf A, McDermott M, Kieburtz K, Blindauer K, Plumb S,Shoulson I, the Parkinson Study Group. Test–retest reliability ofthe Unified Parkinson’s Disease Rating Scale in patients with earlyParkinson’s disease: results from a multicenter clinical trial. MovDisord 2002;17:758–763.

7. Langston JW, Widner H, Goetz CG, Brooks D, Fahn S, FreemanT, Watts R. Core assessment program for intracerebral transplan-tations (CAPIT). Mov Disord 1992;7:2–13.

8. Defer GL, Widner H, Marie RM, Remy P, Levivier M. Coreassessment program for surgical interventional therapies in Parkin-son’s disease (CAPSIT-PD). Mov Disord 1999;14:572–584.

9. Guy W, editor. ECDEU assessment manual for psychopharmacol-ogy. Washington: Government Printing Office; 1976. p 534–537.

10. Goetz CG, Stebbins GT, Shale HM, Lang AE, Chernik DA,Chmura TA, Ahlskog JE, Dorflinger EE. Utility of an objectivedyskinesia rating scale for Parkinson’s disease: inter- and intraraterreliability assessment. Mov Disord 1994;9:390–394.

11. Goetz CG, Stebbins GT, Chmura TA, Fahn S, Klawans HL,Marsden CD. Teaching tape for the motor section of the UnifiedParkinson’s Disease Rating Scale. Mov Disord 1995;10:263–266.

12. Fleiss JL. The measurement of interrater agreement. In: Fleiss JL,editor. Statistical methods for rates and proportions. New York:Wiley and Sons; 1981. p 212–236.

13. Nutt JG, Woodward WR. Levodopa pharmacokinetics and phar-macodynamics in fluctuating parkinsonian patients. Neurology1986;36:739–774.

14. Verhagen Metman L, van den Munckhof P, Klaassen AA,Blanchet P, Mouradian MM, Chase TN. Effects of supra-thresholdlevodopa doses on dyskinesias in advanced Parkinson’s disease.Neurology 1997;49:711–713.

15. Lang AE, Widner H. Deep brain stimulation for Parkinson’s dis-ease: patient selection and evaluation. Mov Disord 2002;17(Suppl.):94–101.

Restless Legs in Tourette Syndrome

P. Lesperance, MD,1 N. Djerroud, BSc,2

A. Diaz Anzaldua, BSc,3 G.A. Rouleau, MD, PhD,3

S. Chouinard, MD,1 F. Richer, PhD,1,2*and the Montreal Tourette Study Group

1Centre Hospitalier de l’Universite de Montreal, Montreal,Quebec, Canada; 2Universite du Quebec a Montreal,

Montreal, Quebec, Canada; 3McGill University HealthCenter, Montreal, Quebec, Canada

Abstract: Restless legs syndrome (RLS) and Tourette’s syn-drome (TS) share some common features, including thephenomenology of sensations relieved by movements, but

*Correspondence to: Dr. Francois Richer, Neuroscience Center, UQM,Montreal, Quebec, Canada H2W 1T8. E-mail: [email protected]

Received 20 August 2003; Revised 12 December 2003; Accepted 19January 2004

Published online 24 March 2004 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/mds.20100

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Movement Disorders, Vol. 19, No. 9, 2004

few studies have examined the links between RLS and TS.We examined RLS and other TS comorbidities in 144 pro-bands with TS or chronic tics and their parents. RLS waspresent in 10% of probands and 23% of parents with nogender differences. RLS in probands was linked signifi-cantly to maternal RLS but not paternal RLS, suggestingthat a maternal RLS factor may contribute to the variableexpression of TS. © 2004 Movement Disorder Society

Key words: Gilles de la Tourette syndrome; basal ganglia;maternal transmission

In Gilles de la Tourette syndrome (TS), tics are oftenaccompanied by comorbidities including obsessive–compulsive symptoms (OCS) and attention deficit hyper-activity disorder (ADHD).1 Restless legs syndrome(RLS), can also be observed in TS.2–4 RLS is character-ized by unpleasant sensations in the extremities that arerelieved by movement.5 This phenomenology bearssome similarity to the tics and compulsions of TS, whichare also often preceded by urges or sensations. Also likeTS, RLS has been linked with dysfunction in frontostria-tal systems.1,6 Despite these similarities, the links be-tween RLS and TS have received little attention. RLS ismore prevalent in older adults but it can also affectchildren. The prevalence of RLS in the general popula-tion is estimated at about 3% in individuals younger than30 years and about 10% in individuals between 30 and79 years of age.7 Genetic factors have been implicated inRLS, with either dominant or multifactorial inheri-tance.1,7 A concordance of 83% for RLS symptoms wasfound in monozygotic twins.8 Moreover, patients withfamilial RLS show an earlier onset of symptoms than donon-familial patients.9 The present study examined theprevalence and transmission of RLS in Tourette syn-drome families in a clinical setting.

SUBJECTS AND METHODS

As part of a study of the genetics of TS, 114 French-Canadian families with at least one child (144 probands;6–31 years; 75% boys) diagnosed with TS or chronic tics(CT) were recruited from the McGill University HealthCenter and Ste-Justine Hospital. Exclusion criteria were:(1) inability to provide consent; (2) history of otherneurological disorders; and (3) induction of tics by drugsor other causes. Of TS probands, 63% were medicatedwith either stimulants (39%), clonidine (24%), selectiveserotonin reuptake inhibitors (SSRIs) or tricyclics (12%),neuroleptics (34%), benzodiazepines (2%), medicationcontrolling extrapyramidal symptoms (7%), or othermedications (3%).

Before the evaluation, the families filled out a ques-tionnaire to obtain demographic data, medical history,development, education, and history of tics, as well as

OCS, ADHD, and RLS. After informed consent, expe-rienced professionals (neurologists, psychiatrists, andneuropsychologists) completed diagnostic evaluationsduring direct family interviews. TS and CT were diag-nosed using the Diagnostic and Statistical Manual ofMental Disorders-IV (DSM-IV) criteria and classified asdefinite if they met all criteria, probable if tics were notobserved by a specialist, and possible if the tics beganafter 21 years of age, lasted less than 1 year, or if theperson was not conscious of the tics. Tic severity wasevaluated through the Yale Global Tic Severity Scale.10

RLS was evaluated using the criteria of the InternationalRestless Legs Study Group. RLS symptoms were definedas unpleasant feelings in the legs (criterion 1) at rest(criterion 2) that were relieved by movement (criterion 3)and more frequent in the evening or night (criterion 4).The frequency of RLS symptoms in the last month wasnoted. OCS were evaluated by the Yale–Brown Obses-sive–Compulsive Scale (YBOCS)11 and were classifiedas present or absent (� or �9 points). ADHD symptomswere evaluated with an interview using the DSM-IVcriteria and were classified as definite, probable, or pos-sible when 6, 5, or 4 criteria, respectively, were met ineither the inattention or hyperactivity classes . Dichoto-mous variables were computed for TS (definite or prob-able vs. other), for ADHD (definite or probable vs.other), for OCS (Y-BOCS �9 vs. �9), and for RLS(definite [4 criteria] vs. 0 or 1 criteria). Associationsbetween symptoms and other measures were examinedusing �2 tests for categorical variables and t tests forcontinuous variables (age).

RESULTS

Symptom frequencies are shown in Figure 1. Ticswere exhibited by 43% of fathers (46/106), and 33% ofmothers (37/112). A majority of probands showed OCS(61%, 83/136) or ADHD (72%, 89/124) along with tics.RLS was present in 10% (15/142) of probands, 21%(24/111) of mothers, and 25% (27/107) of fathers, (33%and 26% in mothers with tics or CT and fathers with ticsor CT, respectively). No gender difference was found forRLS in probands (P � 0.581) or parents (P � 0.505).The presence of RLS in probands was significantly cor-related with maternal RLS (P � 0.011, odds ratio [OR]� 4.5, 95% confidence interval [CI] � 1.3–15.3) but notwith paternal RLS (P � 0.452), despite an equal preva-lence of RLS in both parents.

RLS in probands was not correlated with medication(P � 0.910). Specific correlations revealed a small rela-tion between the presence of RLS and consumption ofclonidine (P � 0.031), but not with the consumption of

RESTLESS LEGS IN TOURETTE’S SYNDROME 1085

Movement Disorders, Vol. 19, No. 9, 2004

stimulants (P � 0.591), SSRIs or tricyclics (P � 0.577),or neuroleptics (P � 0.717).

Probands with RLS were significantly older than pro-bands without RLS (P � 0.001). In both probands andfathers, RLS was not associated with ADHD (all P �0.3), or OCS (all P � 0.3). In mothers, the presence ofRLS was associated with OCS (P � 0.004), tics (P �0.012), and ADHD (P � 0.022).

Compared with female probands, male probands weremore likely to show ADHD (77 vs. 58%; P � 0.034,OR � 2.46, 95% CI � 1.06–5.7) but as likely to showOCS (P � 0.143). Fathers were more likely to showADHD than were mothers (38 vs. 21%, P � 0.01, OR �2.29, 95% CI � 1.2–4.3). Mothers were more likely toshow OCS than were fathers (58 vs. 38%; P � 0.004,OR � 2.25, 95% CI � 1.3–3.9).

DISCUSSION

Our results show a high prevalence of RLS in childrenand adolescents with TS or CT. The use of direct inter-views with experienced professionals helped differenti-ate RLS from other symptoms. The diagnosis of RLS isdifficult in children, however, because it depends on thepatient’s own interpretation of symptoms and thus prev-alence may be underestimated. RLS symptoms were notsecondary to medication, as their frequency was similarin medicated and unmedicated subjects.

Because of the restlessness common to both RLS andADHD, RLS can be mistaken for ADHD. The presenceof RLS, however, was not correlated with the presence ofADHD, which suggests that there was little diagnosticconfusion between these comorbidities. The lack of re-lationship between ADHD and RLS may not hold in

other samples12; also, RLS seems to be frequent inADHD patients without TS.13,14 There may be complexinteractions between RLS and ADHD at the symptomlevel (exacerbation of one by the other) and at the patho-physiological level.

RLS may also be confused with compulsions or com-plex tics because all these symptoms involve relativelystereotyped movements often preceded by urges or sen-sations. The presence of RLS was not correlated with thepresence of OCS, and unlike tics, RLS affected bothgenders equally. As with all clinic-based studies, thesample was likely affected by a referral bias with moresevere symptoms and more medication in families re-cruited in a tertiary center than in community samples.However, symptoms in the sample were similar to thosein other studies on TS families who seek treatment.1

RLS thus seems to be a significant comorbidity in TS.RLS seems to have a pathophysiology distinct from ticsand OCS. RLS and OCS tend to worsen with age,whereas tics decrease with age after childhood. More-over, SSRIs, which reduce OCS, can aggravate RLS.15

Our results also indicate that despite the similar preva-lence of RLS in both parents, inheritance of RLS in TSis linked to maternal RLS. Previous studies have reportedthat the gender of the affected parent influences the TSphenotype. OCS has been found to be more frequent inTS probands with a maternal transmission of TS.16,17

Maternal factors in transmission suggest that influencessuch as genomic imprinting, a modifier X-chromosomallocus or a mitochondrial locus may be involved. TheRLS transmission pattern in TS provides additional ev-idence that parental gender effects may contribute to the

FIG. 1. Frequency of tics, RLS, OCS, and ADHD in probands (black), and their mothers (dark grey) and fathers (white).

1086 P. LESPERANCE ET AL.

Movement Disorders, Vol. 19, No. 9, 2004

complex inheritance and variable expression of TS. Fur-ther studies on the links between restless legs syndromeand Tourette syndrome may help shed some light on thepathophysiology of these disorders.

Acknowledgments: This work was supported in part by theTourette Syndrome Association. We thank the families for theircollaboration. We also thank S. Lemay for analyses, S. Toupinfor patient recruitment, and M.J. Lesperance for the develop-ment of the database.

REFERENCES

1. Singer HS. Current issues in Tourette syndrome. Mov Disord2000;15:1051–1063.

2. Voderholzer U, Muller N, Haag C, Riemann D, Straube A. Peri-odic limb movements during sleep are a frequent finding in patientswith Gilles de la Tourette’s syndrome. J Neurol 1997;244:521–526.

3. Lipinski JF, Sallee FR, Jackson C, Sethuraman G. Dopamineagonist treatment of Tourette disorder in children: results of anopen-label trial of pergolide. Mov Disord 1997;12:402–407.

4. Muller N, Voderholzer U, Kurtz G, Straube A. Tourette’s syn-drome associated with restless legs syndrome and akathisia in afamily. Acta Neurol Scand 1994;89:429–432.

5. Walters AS. Toward a better definition of the restless legs syn-drome. The International Restless Legs Syndrome Study Group.Mov Disord 1995;10:634–642.

6. Turjanski N, Lees AJ, Brooks DJ. Striatal dopaminergic functionin restless legs syndrome: 18F-dopa and 11C-raclopride PET stud-ies. Neurology 1999;52:932–937.

7. Phillips B, Young T, Finn L, Asher K, Hening WA, Purvis C.Epidemiology of restless legs symptoms in adults. Arch InternMed 2000;160:2137–2141.

8. Ondo WG, Vuong KD, Wang Q. Restless legs syndrome in monozy-gotic twins: clinical correlates. Neurology 2000;55:1404–1406.

9. Bassetti CL, Mauerhofer D, Gugger M, Mathis J, Hess CW.Restless legs syndrome: a clinical study of 55 patients. Eur Neurol2001;45:67–74.

10. Leckman JF, Riddle MA, Hardin MT, et al. The Yale Global TicSeverity Scale: initial testing of a clinician-rated scale of tic se-verity. J Am Acad Child Adolesc Psychiatry 1989;28:566–573.

11. Goodman WK, Price LH, Rasmussen SA, et al. The Yale-BrownObsessive Compulsive Scale. I. Development, use, and reliability.Arch Gen Psychiatry 1989;46:1006–1011.

12. Wagner ML, Piscataway NJ, Walters AS, et al. The prevalence ofattention deficit hyperactivity disorder and oppositional defiantdisorder symptoms in adults is greater in RLS patients than incontrols. Neurology 2001;56(Suppl.):4–5.

13. Picchietti DL, England SJ, Walters AS, Willis K, Verrico T.Periodic limb movement disorder and restless legs syndrome inchildren with attention-deficit hyperactivity disorder. J Child Neu-rol 1998;13:588–594.

14. Picchietti DL, Underwood DJ, Farris WA, et al. Further studies onperiodic limb movement disorder and restless legs syndrome inchildren with attention-deficit hyperactivity disorder. Mov Disord1999;14:1000–1007.

15. Lipinski JF Jr, Mallya G, Zimmerman P, Pope HG Jr. Fluoxetine-induced akathisia: clinical and theoretical implications. J ClinPsychiatry 1989;50:339–342.

16. Lichter DG, Jackson LA, Schachter M. Clinical evidence ofgenomic imprinting in Tourette’s syndrome. Neurology 1995;45:924–928.

17. Eapen V, O’Neill J, Gurling HM, Robertson MM. Sex of parenttransmission effect in Tourette’s syndrome: evidence for earlierage at onset in maternally transmitted cases suggests a genomicimprinting effect. Neurology 1997;48:934–937.

Cigarette Smoking inParkinson’s Disease: Influence on

Disease Progression

Guido Alves, MD,1 Martin Kurz, MD,1

Stein A. Lie, PhD,2 and Jan P. Larsen, PhD1*1Department of Neurology, Central Hospital of Rogaland,

Stavanger, Norway; 2Section for Medical Statistics,Department of Public Health and Primary Health Care,

University of Bergen, Norway

Abstract: Previous studies have shown an inverse associa-tion between smoking and the prevalence of Parkinson’sdisease (PD), suggesting that smoking may induce a biolog-ical protection against nigral neuronal damage. In 1993, weexamined the frequency of cigarette smokers among 239patients with PD and two control groups. In addition, theprogression of parkinsonism and other clinical featureswere followed prospectively in smoking and nonsmokingPD patients over an 8-year period. Mortality in the two PDgroups was also examined. We found a 50% higher preva-lence of smokers in the control groups than in patients withPD. In contrast, during the follow-up period, there were nosignificant differences in progression of parkinsonism, cog-nitive impairment, and mood in smoking and nonsmokingpatients with PD. Mortality was also similar in the twogroups. The lack of influence on disease progression mayindicate that cigarette smoking does not have a majorneuroprotective effect in patients with already diagnosedPD. © 2004 Movement Disorder Society

Key words: Parkinson’s disease; cigarette smoking; diseaseprogression; mortality

Cigarette smoking is suggested to have a protectiveeffect against Parkinson’s disease (PD).1 In case–controlstudies, a consistent and robust inverse association be-tween smoking and PD has been shown, and prospectivecohort investigations have supported this observation.2–5

Furthermore, a dose–response relationship has beenfound between smoking and PD.6 These findings suggesta pharmacological action of some compound in cigarettesmoke that may induce a biological protection against orslowing down of nigral neuronal damage. Based on theseassumptions, one could hypothesize that cigarette smok-ing should also induce a slower rate of disease develop-

*Correspondence to: Dr. Jan P. Larsen, Department of Neurology,Central Hospital of Rogaland, Postboks 8100, N-4068 Stavanger, Nor-way. E-mail: [email protected]

Received 14 September 2003; Revised 9 December 2003; Accepted2 February 2004

Published online 8 April 2004 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/mds.20117

CIGARETTE SMOKING IN PARKINSON’S DISEASE 1087

Movement Disorders, Vol. 19, No. 9, 2004