The efficacy of lymphatic drainage and traditional massage in the prophylaxis of migraine: a randomized, controlled parallel group study.

This study aimed at examining the efficacy of lymphatic drainage (LD) and traditional massage (TM) in the prophylactic treatment of migraine using controlled prospective randomized clinical trial of 64 patients (57 women, 45 ± 10 years) with migraine with and without aura. Patients were randomized into three groups: LD (n = 21); TM (n = 21); waiting group (WG, n = 22). After a 4-week-baseline, a treatment period of 8 weeks was applied followed by a 4-week observation period. The patients filled in a headache diary continuously; every 4 weeks they filled in the German version of the CES-D and the German version of the Headache Disability Inventory. The main outcome measure was migraine frequency per month. At the end of the observation period, the number of migraine attacks and days decreased in the LD group by 1.8 and 3.1, respectively, in the TM group by 1.3 and 2.4, and in the WG by 0.4 and 0.2, respectively. The differences between LD and WG were significant (p = 0.006 and p = 0.015, respectively) as well as the differences between TM und WG (p = 0.042 and p = 0.016, respectively). There was a significant decrease in the amount of analgesic intake in the LD group compared to the two other groups (p = 0.004). TM and LD resulted in a reduction of migraine attack frequency. The analgesic intake only decreased significantly during LD intervention. Useful effects were identified for LD and TM as compared to WG for the prophylaxis of migraine. LD was more efficacious in some parameters than TM.

Sleep apnea in patients with cluster headache: a case-control study.

OBJECTIVE: Polysomnographic investigations have shown an unspecific association between cluster headache and obstructive sleep apnea syndrome. The aim of this study was to investigate this association in a cluster episode compared with a symptom free interval, and to further characterize this association. METHODS: We investigated 42 patients with episodic (n = 26) or chronic (n = 16) cluster headache by means of polygraphic screening for sleep apnea and compared the data to 28 healthy control subjects matched according to age, sex, and BMI. The patients with episodic cluster headache were screened twice, once in a cluster episode and once in a symptom free interval. RESULTS: Patients with active cluster headache showed a significantly higher respiratory distress index (8.6 ± 16.0) compared with healthy control subjects (3.4 ± 2.1; p = 0.002). More patients fulfilled the criteria for an obstructive sleep apnea syndrome (29%) than control subjects (7%; p = 0.018). Patients only, but not the control subjects, had central apneas. These differences were only significant when measured during an active cluster episode but not during a symptom free interval. CONCLUSION: Cluster headache is associated with a sleep apnea syndrome only in the active cluster episode. The increased rate of central apneas might be a result of involvement of the hypothalamus in the pathophysiology of cluster headache. Out of five anecdotal cases treated with nasal continuous positive airway pressure, only one patient showed benefit with respect to cluster headache attack frequency.

A time sequence analysis of the relationship between cardiovascular risk factors, vascular diseases and restless legs syndrome in the general population.

Previous cross-sectional studies regarding the association of restless legs syndrome (RLS) with cardiovascular morbidity are controversial. Our aim was to evaluate prospectively the relationship of cardiovascular risk factors and vascular diseases with incident RLS in the general population. The results are from two prospective population-based cohort studies: the Dortmund Health Study (n = 1312, median follow-up of 2.1 years) and the Study of Health in Pomerania (n = 4308, median follow-up of 5.0 years). RLS status was assessed twice according to the minimal criteria. Diabetes, hypertension, myocardial infarction and stroke, as well as currently taken medications, were assessed as self-reports. Body mass index and serum total cholesterol were also measured. The independent risks associated with each outcome were estimated by multivariable logistic regression models adjusted for comorbidities and behavioural factors. Obesity was an independent risk factor of incident RLS in the Dortmund Health Study, and higher body mass index was an independent risk factor in both studies. Diabetes, hypertension and hypercholesterolaemia were independent predictors of incident RLS in the Study of Health in Pomerania. The vascular comorbidity index, defined by the number of concurrent cardiovascular risk factors and vascular diseases, showed a positive association with incident RLS in both studies. RLS at baseline was not a significant predictor of any subsequent cardiovascular risk factors and/or vascular diseases in any of the studies. Cardiovascular risk factors and diseases predict the subsequent development of RLS in the general population. The presence of RLS is not a significant risk factor of cardiovascular morbidity.

Socio-economic risk factors for incident restless legs syndrome in the general population.

Few and controversial data exist about the relationship between socio-economic status and restless legs syndrome, and prospective analyses are lacking. We aimed to explore the associations between socio-economic factors and incident restless legs syndrome in the general population. Two prospective population-based cohort studies were conducted: the Dortmund Health Study with a mean follow-up of 2.2 years; and the Study of Health in Pomerania with a mean follow-up of 5.2 years. The studies included 1312 subjects and 4308 subjects, respectively. Restless legs syndrome was assessed twice according to the standard minimal criteria. The modified Winkler Index of social class, education, job status, partnership and income were assessed by interviews at baseline. The risk of restless legs syndrome associated with each socio-economic factor was estimated by multivariable logistic regression adjusted for behavioural factors and co-morbidities. Female gender, being retired and unemployment were independent risk factors of incident restless legs syndrome in both studies. Low level of education and income were independently associated with incident restless legs syndrome only in the Dortmund Health Study, but not in the other study. Migrational background and shiftwork were further independent risk factors of restless legs syndrome that were only assessed in the Dortmund Health Study. People with less favourable socio-economic situation are at an increased risk of developing restless legs syndrome. Behavioural variables and co-morbidities did not explain this association, thus further studies are required to reveal the mechanism behind the proposed relationship.

Electrical and transcranial magnetic stimulation of the facial nerve: diagnostic relevance in acute isolated facial nerve palsy.

UNLABELLED: Unilateral facial weakness is common. Transcranial magnetic stimulation (TMS) allows identification of a conduction failure at the level of the canalicular portion of the facial nerve and may help to confirm the diagnosis. METHODS: We retrospectively analyzed 216 patients with the diagnosis of peripheral facial palsy. The electrophysiological investigations included the blink reflex, preauricular electrical stimulation and the response to TMS at the labyrinthine part of the canalicular proportion of the facial nerve within 3 days after symptom onset. RESULTS: A similar reduction or loss of the TMS amplitude (p < 0.005) of the affected side was seen in each patient group. Of the 216 patients (107 female, mean age 49.7 ± 18.0 years), 193 were diagnosed with Bell's palsy. Test results of the remaining patients led to the diagnosis of infectious [including herpes simplex, varicella zoster infection and borreliosis (n = 13)] and noninfectious [including diabetes and neoplasma (n = 10)] etiology. CONCLUSIONS: A conduction block in TMS supports the diagnosis of peripheral facial palsy without being specific for Bell's palsy. SIGNIFICANCE: These data shed light on the TMS-based diagnosis of peripheral facial palsy, an ability to localize the site of lesion within the Fallopian channel regardless of the underlying pathology.

Thermal hypoaesthesia differentiates secondary restless legs syndrome associated with small fibre neuropathy from primary restless legs syndrome.

This study aimed to assess thermal and mechanical perception and pain thresholds in primary idiopathic restless legs syndrome and secondary restless legs syndrome associated with small fibre neuropathy. Twenty-one patients (age: 53.4 + or - 8.4, n = 3, male) with primary restless legs syndrome and 13 patients (age: 63.0 + or - 8.2, n = 1, male) with secondary restless legs syndrome associated with small fibre neuropathy were compared with 20 healthy subjects (age: 58.0 + or - 7.0; n = 2, male). Differential diagnosis of secondary restless legs syndrome associated with small fibre neuropathy was based on clinical symptoms and confirmed with skin biopsies in all patients. A comprehensive quantitative sensory testing protocol encompassing thermal and mechanical detection and pain thresholds, as devised by the German Research Network on Neuropathic Pain, was performed on the clinically more affected foot between 2 pm and 1 am when restless legs syndrome symptoms were present in all patients. Patients with primary restless legs syndrome showed hyperalgesia to blunt pressure (P < 0.001), pinprick (P < 0.001) and vibratory hyperaesthesia (P < 0.001). Patients with secondary restless legs syndrome associated with small fibre neuropathy showed thermal hypoaesthesia to cold (Adelta-fibre mediated) and warm (C-fibre mediated) (all P < 0.001) and hyperalgesia to pinprick (P < 0.001). Static mechanical hyperalgesia in primary and secondary restless legs syndrome is consistent with the concept of central disinhibition of nociceptive pathways, which might be induced by conditioning afferent input from damaged small fibre neurons in secondary restless legs syndrome.

Psychological distress of patients suffering from restless legs syndrome: a cross-sectional study.

BACKGROUND: Restless legs syndrome (RLS) is a chronic disorder with substantial impact on quality of life similar to that seen in diabetes mellitus or osteoarthritis. Little is known about the psychological characteristics of RLS patients although psychological factors may contribute to unfavourable treatment outcome. METHODS: In an observational cross-sectional design, we evaluated the psychological features of 166 consecutive RLS patients from three outpatient clinics, by means of the Symptom Checklist 90-R (SCL-90-R) questionnaire. Additionally, the Beck Depression Inventory-II (BDI-II) and the International RLS Severity Scale (IRLS) were measured. Both treated and untreated patients were included, all patients sought treatment. RESULTS: Untreated patients (n = 69) had elevated but normal scores on the SCL-90-R Global Severity Index (GSI; p = 0.002) and on the sub-scales somatisation (p < 0.001), compulsivity (p = 0.003), depression (p = 0.02), and anxiety (p = 0.004) compared with a German representative sample. In the treated group, particularly in those patients who were dissatisfied with their actual treatment (n = 62), psychological distress was higher than in the untreated group with elevated scores for the GSI (p = 0.03) and the sub-scales compulsivity (p = 0.006), depression (p = 0.012), anxiety (p = 0.031), hostility (p = 0.013), phobic anxiety (p = 0.024), and paranoid ideation (p = 0.012). Augmentation, the most serious side effect of dopaminergic, i.e. first-line treatment of RLS, and loss of efficacy were accompanied with the highest psychological distress, as seen particularly in the normative values of the sub-scales compulsivity and anxiety. Generally, higher RLS severity was correlated with higher psychological impairment (p < 0.001). CONCLUSION: Severely affected RLS patients show psychological impairment in multiple psychological domains which has to be taken into account in the treatment regimen.

Perception of sleep and dreams in alcohol-dependent patients during detoxication and abstinence.

AIMS: This study aims to investigate sleep quality and the subjective dream experience in alcohol-dependent patients during withdrawal and abstinence compared with healthy controls. METHODS: Thirty-seven patients with alcohol dependency and 35 healthy control subjects were asked to fill in several questionnaires and to give information about their subjective sleep and dream experiences. Twelve patients participated in a follow-up interview 4 weeks later. RESULTS: Sleep quality is impaired in alcohol-dependent patients during detoxication, and the subjective dream experience is more negatively toned compared with healthy controls. Both sleep quality and dream experience improves slightly after 4 weeks of abstinence. Patients with alcohol dependency during withdrawal and abstinence dream significantly more often about alcohol. However, none of the abstinent alcohol-dependent patients dreamed about alcohol during withdrawal. CONCLUSIONS: This study shows that the subjective sleep and dream quality is strongly impaired in patients with alcohol dependency. Differences in the dream experience between alcohol-dependent patients and healthy controls are in accordance with the continuity hypotheses of dreaming. The hypothesis of dreaming about alcohol as a compensatory effect, however, could not be confirmed.

Enhancing medication therapy in Parkinson's disease by establishing an interprofessional network including pharmacists.

Background Optimizing therapy regimens through collaboration and combination of available resources is a promising approach to improve quality of life for patients with Parkinson's disease (PD). Aim The aim of this project was to enhance patient-oriented therapy and interprofessional collaboration by establishing a regional PD network. Setting The network is located in a rural area in Germany. It covers primary, secondary and tertiary care facilities across professional boundaries. Development Recruitment of PD specialists and patient support groups was done by the local newspaper to spread the word. The network was initially open to all healthcare professionals, who stated a focus or special interest in PD. A working group for medication was founded within the network by asking for interested participants. Problems in the medication process were discussed within the group. As a consequence, therapy recommendations (quickcards) and a specific medication plan were developed and a certified education curriculum for pharmacists was developed. Implementation The network grew to > 150 participants across all disciplines and sectors. Quickcards were adjusted, approved and implemented by the network during interquartile meetings. Certified education was implemented and became a requirement for participating pharmacists. Evaluation The quickcards on medication plan and drug-drug-interactions were approved to be useful and feasible by the network by unanimous assent. Overall satisfaction with certified education was high (mean of 1.4 on a scale between 1 = high and 6 = low). Conclusion A regional interprofessional PD network with pharmacists was established and new standards were established. Future research needs to measure the effects on patient outcomes.

Insomnia in neurological diseases.

Insomnia is defined as difficulties of initiating and maintaining sleep, early awakening and poor subjective sleep quality despite adequate opportunity and circumstances for sleep with impairment of daytime performance. These components of insomnia - namely persistent sleep difficulties despite of adequate sleep opportunity resulting in daytime dysfunction - appear secondary or co-morbid to neurological diseases. Comorbid insomnia originates from neurodegenerative, inflammatory, traumatic or ischemic changes in sleep regulating brainstem and hypothalamic nuclei with consecutive changes of neurotransmitters. Symptoms of neurological disorders (i.e motor deficits), co-morbidities (i.e. pain, depression, anxiety) and some disease-specific pharmaceuticals may cause insomnia and/or other sleep problems.This guideline focuses on insomnias in headaches, neurodegenerative movement disorders, multiple sclerosis, traumatic brain injury, epilepsies, stroke, neuromuscular disease and dementia.The most important new recommendations are: Cognitive behavioral therapy (CBTi) is recommended to treat acute and chronic insomnia in headache patients. Insomnia is one of the most frequent sleep complaints in neurodegenerative movement disorders. Patients may benefit from CBTi, antidepressants (trazodone, doxepin), melatonin and gaba-agonists. Insomnia is a frequent precursor of MS symptoms by up to 10 years. CBTi is recommended in patients with MS, traumatic brain injury and. Melatonin may improve insomnia symptoms in children with epilepsies. Patients with insomnia after stroke can be treated with benzodiazepine receptor agonists and sedating antidepressants. For patients with dementia suffering from insomnia trazodone, light therapy and physical exercise are recommended.

Contribution of the premotor cortex to consolidation of motor sequence learning in humans during sleep.

Motor learning and memory consolidation require the contribution of different cortices. For motor sequence learning, the primary motor cortex is involved primarily in its acquisition. Premotor areas might be important for consolidation. In accordance, modulation of cortical excitability via transcranial DC stimulation (tDCS) during learning affects performance when applied to the primary motor cortex, but not premotor cortex. We aimed to explore whether premotor tDCS influences task performance during motor memory consolidation. The impact of excitability-enhancing, -diminishing, or placebo premotor tDCS during rapid eye movement (REM) sleep on recall in the serial reaction time task (SRTT) was explored in healthy humans. The motor task was learned in the evening. Recall was performed immediately after tDCS or the following morning. In two separate control experiments, excitability-enhancing premotor tDCS was performed 4 h after task learning during daytime or immediately before conduction of a simple reaction time task. Excitability-enhancing tDCS performed during REM sleep increased recall of the learned movement sequences, when tested immediately after stimulation. REM density was enhanced by excitability-increasing tDCS and reduced by inhibitory tDCS, but did not correlate with task performance. In the control experiments, tDCS did not improve performance. We conclude that the premotor cortex is involved in motor memory consolidation during REM sleep.

Quickcard-Based Approach to Guiding Specific Nonpharmacological Treatments in a German Parkinson's Network.

Interdisciplinary care has been shown to be effective at optimizing the treatment of patients with Parkinson's disease. An optimized collaboration between the various healthcare providers involved in the treatment process facilitates successful care. One of the main shortcomings in the German healthcare system is the limited and unstandardized communication between practitioners. The Parkinson's network Münsterland+ (PNM+) is an interdisciplinary network of medical and non-medical experts involved in the treatment of Parkinson's patients: neurologists, physiotherapists, occupational therapists, speech therapists, psychologists, Parkinson's nurses, pharmacists, patients, and relatives. The PNM+ elaborates guideline-based therapy recommendations, provided as so-called "Quickcards". Thereby, the communication of the treating neurologist and therapists is based on a coordinated feedback system and suggestions to adequately select and, if necessary, adjust the therapy. In the German healthcare system, with its fragmented structures, the PNM+ and its activities have been shown to enhance integration of the healthcare providers and thereby optimize the care of Parkinson's disease patients. Future research should evaluate the effects and cost-effectiveness.

Assessing health-related quality of life in patients with restless legs syndrome.

BACKGROUND: Restless Legs Syndrome (RLS) has a substantial impact on normal daily activities. Because of the high prevalence it is necessary to evaluate the impact on the health-related quality of life (HRQoL). OBJECTIVE: To assess health-related quality of life in patients with RLS. METHODS: A total of 519 patients (327 female patients; mean age: 64.2 y) were recruited in five different German centers according to the diagnostic criteria of the International RLS Study Group. Patients were either interviewed or completed a mailed questionnaire. The questionnaire consisted of an evaluation of the sociodemographic, clinical and health-related status. HRQoL was evaluated with the EuroQoL (EQ-5D). In addition, the IRLS scale, the MOS Sleep Scale, the Epworth Sleepiness Scale, and the BDI were applied as clinical rating scales. RESULTS: HRQoL is substantially affected by RLS. The mean EQ-5D-VAS was 55.6 and considerably lower compared to the general population. It was found to be as low as in other chronic neurological disorders such as Parkinson's disease and stroke. From different factors investigated by uni- and multivariate analyses, severity of RLS and depressive symptoms had the most significant impact on HRQoL. Additionally, sleep deficits, the duration of the disease and net household income were identified as predictors for different EQ-5D outcome scores. CONCLUSIONS: RLS considerably affects HRQoL. Further comparative studies are necessary to evaluate the effect of disease symptoms on HRQoL and their change due to medication.

Modulatory effects of transcranial direct current stimulation on laser-evoked potentials.

OBJECTIVE: Invasive stimulation of the motor cortex has been used for years to alleviate chronic intractable pain in humans. In our study, we have investigated the effect of transcranial direct current stimulation (tDCS), a noninvasive stimulation method, for manipulating the excitability of cortical motor areas on laser evoked potentials (LEP) and acute pain perception. DESIGNS AND SETTINGS: The amplitude of the N1, N2, and P2 LEP components of 10 healthy volunteers were evaluated prior to and following anodal, cathodal, and sham stimulation of the primary motor cortex. In a separate experiment subjective, pain rating scores of 16 healthy subjects in two perceptual categories (warm sensation, mild pain) were also analyzed. RESULTS: Cathodal tDCS significantly reduced the amplitude of N2 and P2 components compared with anodal or sham stimulation. However, neither of the tDCS types modified significantly the laser energy values necessary to induce moderate pain. In a separate experiment, cathodal stimulation significantly diminished mild pain sensation only when laser-stimulating the hand contralateral to the side of tDCS, while anodal stimulation modified warm sensation. CONCLUSIONS: The possible underlying mechanisms of our findings in view of recent neuroimaging studies are discussed. To our knowledge this study is the first to demonstrate the mild antinociceptive effect of tDCS over the primary motor cortex in healthy volunteers.

Homocysteine in restless legs syndrome.

BACKGROUND AND PURPOSE: Total plasma homocysteine (tHcy) may be a risk factor for vascular diseases and is associated with renal failure or deficiency of vitamin B12 or folate. Recently, elevated tHcy concentrations were observed in patients with Parkinson's disease (PD), particularly those under levodopa treatment. Our objective was to determine whether changes in tHcy are also found in patients with restless legs syndrome (RLS) in relation to levodopa treatment and whether folate and vitamins B6 and B12 play a role in RLS. METHODS: In a total of 228 subjects, tHcy and B vitamin status (vitamins B6 and B12, folate) were studied: 97 patients with idiopathic RLS (40 under levodopa therapy), 39 with PD (25 under levodopa therapy), and 92 healthy controls adjusted for age and gender. RESULTS: No significant differences were observed in tHcy levels between RLS patients and controls or between the RLS groups without treatment or with levodopa or dopamine agonist treatment. Mean tHcy was significantly higher in PD patients (13.8 micromol/l) than in either RLS patients (11.7 micromol/l) or controls (11.0 micromol/l; p<0.001). There was an inverse association between tHcy and vitamin B12 in each group. CONCLUSIONS: RLS and, in particular, levodopa treatment in RLS are not associated with hyperhomocysteinemia. Elevated tHcy could, however, be confirmed in PD patients.

Treatment wish of individuals with known and unknown restless legs syndrome in the community.

STUDY OBJECTIVES: Restless legs syndrome (RLS) is a frequent sleep disorder with a prevalence of 5% to 15% in Caucasian populations. Dopaminergic treatment is known to reduce sensorimotor RLS symptoms and is approved for RLS, but not all patients ask for treatment. About 2% to 3% of patients presenting to a primary care physician require RLS-specific treatment. The overall treatment preference of RLS sufferers, however, is still unknown. The aim of this study was to assess the prevalence and treatment preference in patients with previously diagnosed and those with yet undiagnosed RLS in a population-based survey in Germany. DESIGN AND SETTING: Cross-sectional health survey with face-to-face interviews with 1312 participants in the Dortmund Health Study. RLS was assessed with standardized, validated questions addressing the four minimal diagnostic criteria for RLS defined by the International Restless Legs Syndrome Study Group. PARTICIPANTS: Participants were aged 25 to 75 years and were randomly selected from the city register. RESULTS: The overall prevalence of individuals with a known doctor diagnosis of RLS was 2.3%. In addition, 6.5% fulfilled the four minimal criteria but did not know about this diagnosis yielding an overall prevalence of 8.8%. Prevalence was higher in women (10.2%) and German descendents (9.2%) compared to men (7.1%) and migrants (6.7%). Almost 60% of all RLS cases reported symptoms at least once a week. 33.3% of cases with a known RLS diagnosis and 14.1 % with an unknown diagnosis had an RLS treatment wish. The latter is determined by knowledge of the diagnosis, daily symptoms, diabetes and sleep disturbance. CONCLUSION: About every fourth RLS case knows about the diagnosis and overall every fifth RLS case wishes medication to effectively reduce symptoms, corresponding to 1.6% of the whole study population.

Growth hormone response to low-dose apomorphine in restless legs syndrome.

INTRODUCTION: Low-dose apomorphine challenge has been shown to cause a rise in growth hormone (GH) in patients with Parkinson's disease (PD). This was interpreted as an increased postsynaptic sensitivity of hypothalamic dopamine receptors in the course of a generalized degeneration of dopaminergic neurons. The dopaminergic system in the restless legs syndrome (RLS) has been assumed to play a role in its pathophysiology. It is therefore the aim of this study to determine whether the GH response to subcutaneously applied low-dose apomorphine is generally altered in patients with RLS as compared to healthy controls. PATIENTS AND METHODS: We examined 40 patients with idiopathic RLS as well as 20 age- and sex-matched healthy control subjects by means of the low-dose apomorphine test. GH was analyzed at baseline, as well as 45 and 60 min after subcutaneous low-dose apomorphine injection in the morning. RESULTS: Forty RLS patients (58.3+/-11.9 years, 32 females) with a mean RLS severity scale score of 23.9+/-6.6 (range 10-37) were examined. GH was not significantly increased 45 and 60 min after injection (p=0.397) (2.44+/-2.35 ng/ml at baseline versus 2.71+/-2.29 ng/ml after 45 min and 2.18+/-1.83 ng/ml after 60 min). The results were independent of pre-treatment with levodopa. Age, sex, duration, and severity of the disease did not show a covariate effect with GH levels. There was no difference compared with healthy controls. CONCLUSIONS: RLS patients did not show an increase in GH after stimulation with low-dose apomorphine. Lack of sensitivity alteration of extrastriatal hypothalamic dopamine receptors suggests that RLS is not a general dopaminergic degenerative disease or might only show circadian alterations.

Validation of the Augmentation Severity Rating Scale (ASRS): a multicentric, prospective study with levodopa on restless legs syndrome.

BACKGROUND: Augmentation is the main complication during long-term dopaminergic treatment of restless legs syndrome (RLS) and reflects an overall increase in RLS severity. Its severity varies considerably from a minor problem to a devastating exacerbation of disease. Despite its clinical relevance, systematic evaluations have rarely been undertaken and there has been no development of methods to assess the severity of augmentation. To fill this gap, the European RLS Study Group (EURLSSG) has developed the Augmentation Severity Rating Scale (ASRS), using three items that assess the degree of change in three specific dimensions of augmentation. The changes in each dimension are summed to give an ASRS total score. METHODS: The ASRS was developed to cover the basic dimensions defining RLS augmentation. The items were developed by an interactive process involving professional and patient input. The ASRS that was evaluated included four major items and two alternative forms of one item. The validation was conducted using 63 (85%) mostly untreated RLS patients from six centers, who were treated for six months with levodopa (L-Dopa) (up to 500 mg/day, as clinically needed). Two consecutive assessments before and at baseline measured test-retest reliability. Consecutive ASRS ratings by two independent raters on a subsample of patients evaluated inter-rater reliability. Comparison with clinical severity ratings of two independent experts provided external validation of the ASRS. Comparison of patients with and without augmentation with regard to the items and the total score of the ASRS added discriminant validity. RESULTS: Sixty patients (63% females, mean age: 53 years, baseline International RLS Severity Rating (IRLS) score 24.7+/-5.2) were treated with a median daily dose of 300 mg L-Dopa (range: 50-500 mg). Thirty-six patients (60%) experienced augmentation. Item analyses indicated that one item could be removed as it did not contribute significantly to the test score and only one form of the duplicated item needed to be used. The final ASRS then included three items. Test-retest reliability for the total score was rho=0.72, and inter-rater reliability was rcc=0.94. Cronbach's alpha was 0.62. Validity as assessed by the correlation between the worst ASRS total score during the trial and the expert rating was rho=0.72. ASRS total score differed between patients without versus with augmentation (mean: 7.4 (standard deviation (SD)=4.0) vs. 2.0 (2.7) (P<0.0001). CONCLUSIONS: The ASRS is a reliable and valid scale to measure the severity of augmentation. Due to the need to systematically quantify augmentation for both long-term efficacy and tolerability, the ASRS may become a useful tool to monitor augmentation in future clinical trials.

Association of daytime sleepiness with nigrostriatal dopaminergic degeneration in early Parkinson's disease.

INTRODUCTION: Many patients with Parkinson's disease (PD) report daytime sleepiness. Its etiology, however, is still not fully understood. The aim of this study was to examine if the amount of nigrostriatal dopaminergic degeneration is associated with subjective daytime sleepiness in patients with PD. PATIENTS AND METHODS: We investigated 21 patients with PD clinically and by means of [(123)I] FP-CIT-SPECT (DaTSCAN(R)). Each patient filled in the Epworth sleepiness scale (ESS), the Parkinson's Disease Sleep Scale (PDSS), and the self-rating depression scale according to Zung (SDS) to assess sleepiness, sleep quality, and depressive symptoms. RESULTS: The mean specific dopamine transporter binding in the 21 PD patients (60.8 +/- 10.4 years, nine females, median Hoehn and Yahr stage 2.0) was decreased. Nine patients were in Hoehn and Yahr stage 1 (58.7 +/- 6.6 years, four females; ESS score 7.4 +/- 4.5; PDSS score 105.1 +/- 30.9), the other 12 patients were in Hoehn and Yahr stage 2 (62.4 +/- 12.6 years, five females; ESS score 6.7 +/- 4.7, PDSS score 97.1 +/- 25.6). Age, gender, ESS, and PDSS scores were not significantly different in both groups. However, ESS scores showed an inverse correlation with mean DAT binding in the striatum (r = -0.627, p = 0.03), the caudate nucleus (r = -0.708, p = 0.01), and the putamen (r = -0.599, p = 0.04) in patients with Hoehn and Yahr stage 2. There was no correlation of the ESS score with age, disease duration, UPDRS motor score, PDSS score, or depression score. CONCLUSION: Subjective daytime sleepiness seems to be associated with dopaminergic nigrostriatal degeneration in early PD.