Restless legs syndrome [Elektronische Ressource] : diagnosis, treatment and pathophysiology / vorgelegt von Stephany Fulda

Por13084

Sujets

• Psychologie

Informations

• Publié par: universitat_regensburg
• Publié le: 01 janvier 2010
• Nombre de lectures: 25
• Langue: English
• Poids de l'ouvrage: 3 Mo

Extrait

Restless Legs Syndrome: Diagnosis,
Treatment and Pathophysiology

Inaugural-Dissertation
zur Erlangung der Doktorwürde
der Philosophischen Fakultät II
(Psychologie, Pädagogik und Sportwissenschaft)

der Universität Regensburg






vorgelegt von
Stephany Fulda
aus Essen
2010






München, Juni 2010


























Erstgutachter: Prof. Dr. Jürgen Zulley
Zweitgutachter: Prof. Dr. Mark W. Greenlee

Content
Content

I. Introduction.........................................................................................................................2
References………………………………………………………………………………………………...8

II. Short-term memory and verbal fluency is decreased in
restless legs syndrome patients. ............................................................................12
Abstract…………………………………………………………………………………………………. .12
Introduction……………………………….12
Methods………………………………………………………………………………………………. ....13
Subjects………………………….....13
Procedure ………………………………………………………………………………………….13
Performance scores and statistical analysis…………………....15
Results……………………………….......17
Discussion………………………………………………………………………………………………..19
References……………………………….22

III. Where dopamine meets opioids: a meta-analysis of the
placebo effect in restless legs syndrome treatment studies. ...........24
Abstract…………………………………………………………………………………………………. .24
Introduction……………………………….25
Methods………………………………………………………………………………………………. ....26
Location and selection of studies………………………………………………………………. .26
Outcome measures………………………………………………..26
Data extraction and computation of effect sizes………………………………………………. 26
Meta-regression………………………………………………. .................................................27
Results……………………………………………………………………………………………….......31
Response rates………………………………………………………………..............................31
IRLS and other RLS scores……………………………………………………………………....31
Subjective sleep parameters: sleep quality and sleep duration…………………. ..34
Polysomnographic sleep parameters: sleep efficiency and total sleep time…… .34
PLMS……………………………………………………………….............................................34
Daytime functioning: sleepiness and quality of life …………………………………...............36
Discussion………………………………………………………………………………………………..37
References……………………………….39
Appendix………………………………………………………………………………………………....43
Studies contributing to the meta-analysis……………………………………………………. ...44
Supplementary material………………………………………………………………………………...46
Supplement 1: Resources used for search …………………………………………………….46
ent 2: Between study heterogeneity……………………………..47
Supplementary Figures 1 to 3 …………………………………………………….....................49
Excluded studies ………………………………………….........................................51
I Content

IV. Prevalence of the restless legs syndrome in transsexual
patients: the hormonal hypothesis revisited.................................................55
Prevalence of the restless legs syndrome in transsexual patients………………………………...55
References………………………………………………………………………….57

V. Genome-wide association study of restless legs syndrome
identifies common variants in three genomic regions...........................59
Abstract…………………………………………………………………………………………………. .59
Genome-wide association………………………...60
Replication of genome-wide findings.………………………………………………………………. ..61
Fine mapping, haplotype and risk analysis…………………………. .63
Methods.…………………………………………………………………. ...........................................66
Study population and phenotype assessment………………………………………………….66
Genome-wide assays, SNP genotyping and quality control…………… 67
SNP selection for stage 2………………………………………………....................................67
SNP selection for fine mapping………………………………………………...........................67
Analysis of genetic effects………………………………………………...................................68
Multiple testing………………………………………………. ...................................................68
Power analysis……………………………………………….
Testing the mode of inheritance……………………………………..........................68
Attributable risk fraction……………………………………………….......................................69
References……………………………………………………………………………………………….70
Supplementary material…………………………...72
Supplementary Table 1: Stage 1 SNP exclusion……………………………………………….72
entary Table 2: Stage 1 association results…………………… 73
Supplementary Table 3: Stage 2a and 2b SNP selection……………………………………. 74
entary Table 4: Stage 2a association re…………..75
Supplementary Table 5: Stage 2b assosults………………………………………...76
entary Table 6: Delineation of genetic model……………………………. .77
Supplementary Table 7: Familial versus sporadic cases……………………………………. .77
entary Table 8: Description of study subjects……………………..78
Supplementary Table 2: Oligonucleotide sequences ………………………………………. ..79

VI. Discussion........................................................................................................................82
Cognitive functioning in RLS…………………………………………………………………………...82
Placebo effect in RLS treatment studies…………………...83
Prevalence of RLS in transsexual patients…………………………………………………………...85
Genome-wide association study of RLS……………………………...86
References…………………………………………………………………………………….87
VII. Appendix. .........................................................................................................................89

II Introduction
INTRODUCTION

The restless legs syndrome (RLS) is a neurological disorder characterized by the urge to
move the extremities associated with paresthesias, which are partially or totally relieved by
movement, a worsening of symptoms at rest and in the evening or at night and, as a
1consequence, sleep disturbances. RLS is a common but often under-diagnosed
sensorimotor disorder of sleep/wake motor regulation with prevalence rates estimated from
population surveys between 1 and 10%, increasing with age and considerably more
2prevalent in females than males . There exist many forms regarding the clinical course of the
disease, the severity and circadian expression of symptoms as well as associated features.
The first documented description of restless legs associated with severe sleep disturbances
thdates back to the 17 century and was reported by the English physician Sir Thomas Willis.
3Originally published in Latin in 1672 it was later published in English in the London Practice
4of Physick :
“Wherefore to some, when being a Bed they betake themselves to sleep, presently in the
Arms and Legs Leapings and Contractions to the Tendons, and so great a Restlessness
and Tossing of their Members ensue, that the diseased are no more able to sleep, than if
they were in a Place of the greatest Torture” (p. 404).
th thIn the 19 and 20 century several other names were given to the disorder such as anxietas
5 6tibiarum by Wittmaack and leg jitters by Allison . Karl Axel Ekbom was the first to provide a
7detailed description of the clinical features of the disorder and first named it asthenia crurum
8paraesthetica. In 1945 he coined the term restless legs syndrome (RLS) to distinguish it
from other similar conditions and already reported that the syndrome may cluster in families
and that there might be a secondary form of RLS in anaemia or pregnancy. In recognition of
Ekbom’s major contribution to the understanding of this condition, RLS has also been
9referred to as Ekbom syndrome. Alternate names include focal akathisia of the legs ,
although this term is used very infrequently nowadays. Scientific interest was slow to
respond to RLS in earlier years but picked up considerably during the 1980s when Akpinar
10reported that RLS was treated successfully with levodopa which remained first line
treatment for nearly two decades. Scientific developments were further helped along by the
foundation of the International RLS Study Group (IRLSSG) that in 1995 defined uniform and
11 1internationally accepted criteria for the diagnosis of RLS which were updated in 2003 .
Today, most authors agree that RLS has its origin in the central nervous system, however,
complex interactions between central and peripheral structures may contribute to the
disorder. Based on the knowledge of the efficacy of dopaminergic and opioidergic drugs and
the provocation or exacerbation of RLS symptoms following treatment with dopamine
receptor blocking agents, there is evidence of the involvement of the dopaminergic and
opioid system in the pathogenesis of RLS. Recent PET and SPECT studies revealed some
controversial results of the nigrostriatal dopaminergic neurotransmission probably reflecting a
12dysfunction of the central dopaminergic system . The aetiology, however, remains unclear,
13,14despite what is known about the conditions that may induce the syndrome .

Diagnosis of RLS
In 1995, the International RLS Study Group developed standardized criteria for the diagnosis
11