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Idiopathic Parkinson's disease (PD) is a multisytem degenerative disorder. In addition to motor symptoms such as akinesia, rigidity and tremor, various non-motor symptoms occur, which are still insufficiently diagnosed. Moreover, the frequently used scales and scores do not adequately detect these non-motor symptoms. The Non-motor Symptoms Questionnaire (NMSQuest) is an established self-completed patient questionnaire with 30 qualitative questions covering all important non-motor symptoms of PD. The Non-motor Symptoms Scale (NMSScale) is a grade rating scale for estimating the frequency and severity of non-motor symptoms in PD. Since there are only original English versions of both questionnaires available, self-translated versions were frequently used or the questionnaires were not used at all in native German patients. We used international guidelines for cross-cultural adaptation of questionnaires to provide standard versions of both non-motor symptoms questionnaires in the German language.

A good number of different methods and antidepressive agents are now available for the management of depressive symptoms, the efficacy of which has been confirmed by clinical studies. Various approaches--be it medication, electroconvulsive therapy (ECT), psychoeducation and psychotherapy--have also been developed to treat depression in patients with Parkinson's disease. Unfortunately, only a few controlled studies exist for this very specific group of patients. Systematic knowledge of treatment options, however, is lacking. Efficient management of depressive symptoms is absolutely indispensable considering the proven impact of a depression on the patients' quality of life. So far, more than half of the patients afflicted with Parkinson's disease and depression do not receive proper antidepressive therapy. This survey gives an overview on the pharmacological, somatic and psychological procedures of treatment applied in this group of patients, along with useful suggestions., (Copyright (c) Georg Thieme Verlag KG Stuttgart--New York.)

Beck depression inventory (BDI-1A) is the gold standard screening tool for Parkinson's disease (PD) depression, but as a result of its complexity, it is of limited suitability as a quick and easy screening device. We, therefore, validate the 5-item WHO-Five Well-being Index (WHO-5) as a screening tool for PD depression. Two hundred thirteen of 215 recruited PD patients (99.1%) completed the WHO-5. Receiver operating characteristic plots were used to calculate sensitivity/specificity for all cut-off scores for the detection of depression and combined depression/dysthymia as assessed by an independent investigator using the Mini International Neuropsychiatric Interview (MINI). Internal consistency of the WHO-5 was good (Cronbach's alpha = 0.83). WHO-5 showed high validity with adequate detection of depression without differences in the validity indices compared to BDI-1A (P = 0.234). The optimal cut-off value for detection of depression was 12 of 13 points. WHO-5 is a useful, brief, and easy instrument for identifying PD subjects with depression in daily practice., (2010 Movement Disorder Society)

Ropinirole is a non-ergoline dopamine agonist with medium elimination half time, which has been licensed for the therapy of idiopathic Parkinson syndrome in mono- and add-on therapy for more than 10 years. Since 2008 a prolonged-release formulation has been available in Germany, which can be taken once daily. This formulation results in less plasma level fluctuations compared to the thrice-daily immediate-release formulation enabling smoother dopaminergic therapy with symptomatic efficacy day and night. Ropinirole PR has shown good efficacy and tolerability in controlled trials in monotherapy in early patients as well as in add-on studies in advanced patients. In a head-to-head comparison of both formulations as add-on therapy in advanced patients higher doses were achieved with ropinirole PR accompanied by a higher mean decrease of L-Dopa dose. Under these conditions significantly higher efficacy was observed. The titration regime of ropinirole PR is faster with significant efficacy versus placebo as early as in week 2. Especially in patients with pre-existing Parkinson-related poor sleep quality positive effects on sleep and nocturnal symptoms were shown.

There is still uncertainty when to start medical treatment in Parkinson disease (PD). Lack of availability of an unambiguous neuroprotective treatment and concern of potential short or long term adverse effects of medication often lead to an "wait and see" policy regarding initiation of medical treatment. This can result in insufficient symptom control and potentially reduced quality of life. There is increasing evidence of negative influence on disease progression by delayed onset of medical drug treatment in PD. It is under discussion whether symptomatic treatment in PD supports compensatory mechanisms of the cortico-basalganglionar system which might have been responsible for a physically intact motor function despite considerable and increasing nigro-striatal dopaminergic deficit during the preclinical phase of the disease. Therefore, symptomatic treatment might modify disease progression by supporting compensatory mechanisms within the basal ganglia. In this paper we discuss pro and contra of early medical treatment onset in PD under consideration of hitherto available scientific investigations.

Gastrointestinal (GI) motility is very frequently disturbed in Parkinson's disease (PD), manifesting chiefly as dysphagia, impaired gastric emptying and constipation. All these symptoms - constipation in particular - may precede the clinical diagnosis of PD for years. In the future, these symptoms might serve as useful early indicators in the premotor stage. Disturbed gastric emptying is an important factor in unpredictable fluctuations. The most likely causes are degenerations of the dorsal vagal nucleus and the intramural plexus of the whole intestine. These degenerations are likely to develop prior to the degeneration of dopaminergic neurons of the substantia nigra. Diagnosis includes history, clinical examination, barium meal, breath test, scintiscan of stomach, and colonic transit time. Therapeutic efforts are limited when it comes to disturbed motility of the upper GI-tract. Hypersalivation can be reduced by anticholinergics or botulinum toxin injections; motility of the upper gastrointestinal tract is only moderately impacted on by domperidone. In constipation, the conservative therapeutic option is administration of macrogol (polyethylene glycol), which leads to marked improvement.

The goal of Parkinson syndrome diagnostics is twofold: early diagnosis on the one hand, and accurate differentiation among idiopathic and atypical Parkinson syndromes on the other. (123)I-metaiodobenzylguanidine scintigraphy is the only method that can distinguish with a high degree of sensitivity and specificity between atypical Parkinson syndromes and Parkinson's disease or dementia with Lewy bodies. Additional advantages are the method's widespread availability and radioactive exposure dose comparable to that for single photon emission computed tomography imaging with much lower costs. Only a single radiotracer study is necessary. (123)I-metaiodobenzylguanidine scintigraphy is an indispensable tool for purposes of differentiating among the various Parkinson syndromes., (Copyright 2010 S. Karger AG, Basel.)

Non-motor symptoms, such as psychiatric symptoms and autonomic dysfunction, are common co-morbid conditions in Parkinson's disease (PD) and major contributors to poor quality of life and disability. Within the group of neuropsychiatric conditions, depressive symptoms are the most common condition. Despite their frequency and importance, depressive symptoms can be difficult to assess and diagnose and thus depression in PD is frequently unrealized. Diagnostic challenges include the overlap of depressive symptoms with motor and non-motor symptoms of PD, such as dementia and apathy. Furthermore, there are no definite standards to assess and diagnose depression in PD leading also to the lack of exact data on the epidemiology of this non-motor symptom in PD. Depending on the diagnostic test and the study design the prevalence of depression in PD is reported between 7 and 72% of PD patients with approximately 40% in most cross-sectional studies. In contrast, the pathogenesis and long-term course of depression in PD remain elusive. Current hypothesis, however, includes that depressive symptoms are part of the core condition of PD when regarded as an entity. The present review summarizes the current knowledge on epidemiology, pathogenesis and diagnosis of depression in PD and proposes on this data base a standard procedure for screening and diagnosis of depressive symptoms in PD.

Rasagiline (Azilect) is a potent, highly selective and irreversible inhibitor of monoamine oxidase type B of the second generation. Rasagiline is indicated for the treatment of Parkinson's disease (PD) as monotherapy (without levodopa) or as adjunct therapy (with levodopa) in patients with end of dose fluctuations. The efficacy and tolerability of rasagiline has been demonstrated in large-scale, controlled clinical studies in patients with early PD as well as with more advanced PD. This multicentred post-marketing observational study included an investigation of the efficacy and tolerability of rasagiline in a large patient population under conditions of the daily routine in neurologic practice with a special attention on the collection of data regarding a patients' subjective evaluation of quality of life. A total of 754 patients with Parkinson's disease were enrolled, 545 of the patients (63% male patients, mean age 68 years, mean duration of PD 6 years, Hoehn & Yahr stage II to III in 69% of the patients) started rasagiline 1 mg/day as adjunct therapy for up to 4 months. The PD symptoms were rated by the physicians using the Columbia University Rating Scale (CURS) and the clinical fluctuations subscale of the Unified Parkinson's Disease Rating Scale (UPDRS, part IV B). Different aspects of quality of life were rated by the patients using the self-rating Parkinson's Disease Questionaire (PDQ-39). In addition, patients documented the number of hours spend in the OFF-state in "24-hour" home diaries prior to each of the assessment visits. During the treatment period rasagiline was most frequently co-administered with levodopa/DCI (81.7%) and/or dopamine agonists (65.8%). The mean treatment duration was 117.4 (+/-36.4) days, during which PD medication remained unchanged in 86.6% of the cases. The improvement rates in each of the CURS items ranged between 31.1% to 48.4% and the total score was reduced by 22% under the therapy of rasagiline. In the motor part (tremor, rigidity, bradykinesia) the total score was reduced from 6.2 to 4.8, within the other items from 14.7 to 11.5. The proportion of patients without OFF-periods increased from 33.3% to 49.5%. Determined from "24-hours" home diaries, time spend in the OFF-state during wake time decreased from 120 minutes to 45 minutes. In all 8 aspects of quality of life rated by the patients an reduction of the disability could be documented. The PDQ-39 total score was reduced from 36.4 by 7.3 points (20.1%). In total, 29 of the 545 patients who received rasagiline as combination therapy had switched directly from previous combination therapy with selegiline. In this subgroup CURS total score improved from 17.0 to 12.9 points during treatment. The proportion of patients without OFF-periods increased from 36% to 48% and the daily time spent in the OFF-state was reduced from 45 minutes to 30 minutes. The PDQ-39 total score improved by 6.5 points (22.2%). All in all, adverse events were reported by 8.4% of the patients. In conclusion this post-marketing observational study has shown that in patients with pre-existing combination therapy the add-on medication of rasagiline resulted in improvements of motor and non-motor functions. Furthermore, motor complications were significantly reduced and led to an improved quality of life in the self-estimation of the patients. This also applies to those patients with selegiline pre-treatment.

Ropinirole is a non-ergolinic dopamine agonist, which has been used for over 10 years for the treatment of Parkinson's disease. A new formulation (PR = prolonged release) has been developed, which allows the drug to be released slowly (continuously) so that it only has to be given once daily. Switching from the previous ropinirole immediate release ( ropinirole IR) to the prolonged release (ropinirole PR) formulation at the nearest equivalent total daily dose, can take place overnight and the acceptance and tolerability are good. The advantages are once-daily dosing, faster titration with good tolerability and more stable plasma levels. The new formulation is regarded as valuable addition to the currently available medications.

Botulinum toxin has been used in urology for more than 20 years. Its application, however, has been restricted to merely a few indications because of the lackof approval. Most studies available have focused on disturbed detrusor-sphincter synergy and overactive bladder. Results of a placebo-controlled study on overactive bladder have now been published. Further studies relevant to the approval of botulinum toxin are being conducted. This substance has also been successful in several other urologic indications.

Over the past 20 years, botulinum toxin has proved the treatment of choice for a number of symptoms and disorders. Its successful therapeutic use in certain other diseases, however, has been limited by lack of approval. In many indications ? for example headaches ? its value has not yet been definitely established. Botulinum toxin is meanwhile offered by four manufacturers, and we may expect additional preparations in future.

In pain therapy we are repeatedly faced with the problem that the available treatment methods are inadequate. For years we have also been using botulinum toxin especially for myofascial pain and chronic headaches. Unfortunately, the assessment of its efficacy in both everyday clinical conditions and in studies is very variable. A final evaluation is not yet possible. Until the results of current studies are available, the use of botulinum toxin should be limited to clinical studies and to particular cases at specialized centres.

Background: Major hallmarks in the pathophysiology of Parkinson disease are cellular energy depletion and oxidative stress leading to cellular dysfunction and death. Coenzyme Q(10) (CoQ(10)) is an electron acceptor bridging mitochondrial complexes I and II/III and a potent antioxidant that consistently partially recovers the function of dopaminergic neurons., Objective: To determine whether nanoparticular CoQ(10) is safe and displays symptomatic effects in patients with midstage Parkinson disease without motor fluctuations., Design: Multicenter, randomized, double-blind, placebo-controlled, stratified, parallel-group, single-dose trial., Setting: Academic and nonacademic movement disorder clinics., Patients: One hundred thirty-one patients with Parkinson disease without motor fluctuations and a stable antiparkinsonian treatment. Intervention Random assignment to placebo or nanoparticular CoQ(10) (100 mg 3 times a day) for a treatment period of 3 months. Stratification criterion was levodopa treatment., Main Outcome Measure: The subjects underwent evaluation with the Unified Parkinson's Disease Rating Scale (UPDRS) at each visit on a monthly basis. The primary outcome variable was the change of the sum score of the UPDRS parts II and III between the baseline and 3-month visits., Results: One hundred thirty-one subjects were randomized according to the protocol. The mean changes of the sum UPDRS parts II/III score were -3.69 for the placebo group and -3.33 for the CoQ(10) group (P = .82). Statistical analysis according to the stratification did not result in significant changes of the primary outcome variable. No secondary outcome measure showed a significant change between the placebo group and the CoQ(10) group. The frequency and quality of adverse events were similar in both treatment groups., Conclusions: Nanoparticular CoQ(10) at a dosage of 300 mg/d is safe and well tolerated and leads to plasma levels similar to 1200 mg/d of standard formulations. Add-on CoQ(10) does not display symptomatic effects in midstage Parkinson disease.

In idiopathic Parkinson's disease (PD), different clinical subtypes are distinguished due to predominant motor symptoms: a tremor-dominant type (TDT), an akinetic rigid type (ART), and a mixed type (MT). We compared myocardial sympathetic innervation, measured by MIBG scintigraphy, in different subtypes of PD at early and advanced stages of PD. We applied MIBG scintigraphy in 102 patients with PD. About 57 patients were at Hoehn and Yahr (H&Y) stage 1, 22 at H&Y stage 2, and 23 at H&Y stages 3 and 4. For quantification of myocardial MIBG uptake, the heart-to-mediastinum (H/M) count-ratio was calculated. At all H&Y stages, myocardial MIBG uptake was significantly higher in TDT patients than in ART or MT patients (P < 0.05; ANOVA). Furthermore, at each H&Y stage, myocardial MIBG uptake correlated significantly with severity of hypokinesia (P < 0.05; Spearman's correlation) and rigidity (P < 0.05), but not with severity of resting or postural tremor. The significant correlation between myocardial sympathetic degeneration and severity of hypokinesia and rigidity suggests that myocardial sympathetic degeneration and hypokinetic-rigid symptoms develop in a closely coupled manner in early as well as advanced PD. No such correlation can be found between myocardial sympathetic degeneration and parkinsonian tremor., ((c) 2007 Movement Disorder Society.)

Ropinirole is a non-ergoline selective D2 dopamine agonist. Its efficacy and safety has been established in several controlled double-blind studies in patients with early and advanced Parkinson's disease. It is assumed that the improvement in the activities of daily living under ropinirole is not only due to the improved motor symptoms but also due to the improvement of non-motor symptoms like symptoms of mood and anxiety. The objective of this post marketing surveillance study was to show that under the conditions of the daily routine in the neurologic practice ropinirole may not only improve motor symptoms, the activity of daily living and complications of the treatment (dystonia, dyskinesia) but also alleviate symptoms of depression and anxiety. A total of 110 neurological practices enrolled 327 patients in early and advanced stages of the disease (139 females, 188-males; mean age: 67 years). They were treated with ropinirole as monotherapy and as adjunctive therapy with l-dopa over a period of 12 - 14 weeks. Selected symptoms of the Unified Parkinson's Disease Rating Scale (UPDRS) part II-IV and symptoms of depression and anxiety were rated by the clinicians. Mood and functional impairment in job, family and social life were rated by the patients using selected items of the Beck Depression Inventory and the Sheehan Disability Scale (SDS). The different subtypes, i. e. the akinetic-rigid, tremor-dominant and the mixed subtype, are described separately. The total UPDRS score at baseline was similar for all three subtypes and there was also a similar improvement in the three groups under ropinirole. Both according to self-rating and to clinician rating the symptoms of depression and anxiety at baseline were more severe in the akinetic-rigid and the mixed subtype compared to the tremor-dominant subtype. The symptoms considerably improved and were reduced by 48 % under therapy with ropinirole. Adverse events were reported by 7.7 % of the patients. The surveillance study has shown that ropinirole may improve not only motor symptoms, activities of daily living and complications of treatment but also symptoms of mood and anxiety.

In idiopathic Parkinson's disease (PD), a generalized Lewy body type-degeneration in the brain as well as extracranial organs was identified. It is unclear, whether cerebral and extracranial Lewy body type-degeneration in PD are coupled or not. To address this question, cerebral [(123)I]FP-CIT SPECT - to quantify cerebral nigrostriatal dopaminergic degeneration - and myocardial [(123)I]MIBG scintigraphy - to quantify extracranial myocardial sympathetic degeneration - were performed in 95 PD patients and 20 healthy controls. At each Hoehn and Yahr stage separately, myocardial MIBG uptake correlated significantly with striatal FP-CIT uptake. No such correlation was found in the controls. Cerebral and extracranial Lewy body type-degeneration in PD do not develop independently from each other but develop in a strongly coupled manner. Obviously cerebral and extracranial changes are driven by at least similar pathomechanisms. Our findings in controls contradict a physiological correlation between nigrostriatal dopaminergic and myocardial sympathetic function.

Idiopathic Parkinson's disease is a chronic progressive neurodegenerative disorder that remains refractory to curative treatment. Most patients are afflicted for many years, and the disease frequently results in severe physical handicap. Statements on the considerable cost of treatment are largely based on estimates and retrospective studies. To obtain more substantial data, we conducted a 3-year study of the economic aspects. Direct and indirect costs incurred by 117 patients (78 male, mean age 67.5 years) at the Deutsche Klinik für Diagnostik in Wiesbaden, Germany, were prospectively followed. The average cost per patient and month ran to 1007.55. Of that, direct costs amounted to 603.33 (55.9%), with drugs taking up the major share at 480.23. Indirect costs were 404.22 per patient and month, with 76% thereof related to nursing care and the incapacity to earn a living. Cost increased in proportion to Hoehn and Yahr stage, declining again with stages 4 and 5. The data we gathered confirm that Parkinsonism is responsible for sizeable expenses for not only the treating unit but the national economy as a whole.

Botulinum toxin has been used in pain therapy for several years. Its application in migraine and headaches is particularly interesting. Clinical results have not yet been definitely conclusive, and a uniform model of the mode of action has not been established either. Apart from a purely muscular effect, a direct antinociceptive effect of botulinum toxin has been found in patients, in the preclinical model, and in a clinical pain model. This is contradicted by negative observations in the clinical model of pain, which might be related to methodological deficits. Further basics need to be worked out before arriving at any final result. Clinical studies with patients and pain models should then follow. Studying botulinum toxin within the context of pain will also provide many new insights into pain therapy in general. In which pain model botulinum toxin may play a role in the future, has to be awaited.

Since its development for the use of blepharospasm and strabismus more than 2.5 decades ago, botulinum neurotoxin (BoNT) has become a versatile drug in various fields of medicine. It is the standard of care in different disorders such as cervical dystonia, hemifacial spasm, focal spasticity, hyperhidrosis, ophthalmological and otolaryngeal disorders. It has also found widespread use in cosmetic applications. Many other indications are currently under investigation, including gastroenterologic and urologic indications, analgesic management and migraine. This paper is an extensive review of the spectrum of BoNT clinical applications.

The clinical methods of olfactory testing and color discrimination as well as apparative methods such as transcranial ultrasound, dopamine transporter imaging and MIBG scintigraphy reveal a high sensitivity concerning the diagnosis of idiopathic Parkinson's disease (PD). The specificity of the presented methods, in particular of the dopamine transporter imaging--seems to be limited. All these methods and primarily their combination allow the detection of PD in early and--probably--preclinical stages. This requires sufficient therapeutic strategies to prevent and treat preclinical and early PD.

Ropinirole is a modern dopamine agonist with a half-life of medium extent that is highly selective for D(2)-receptors. Ropinirole is an indole derivative and thus does not belong to the group of ergoline dopamine receptor agonists. Its effect has been proved in a number of controlled studies in both monotherapy and combination treatments of Parkinson's disease. We can meanwhile refer to the long-term data of studies that have been run for more than 10 years. The substance has also been approved for the management of restless legs syndrome. A long-acting formula of the substance will be available soon.

NT 201 is a new development of Botulinum Toxin Type A free of complexing proteins. In this double-blind Phase III trial, we compared the efficacy and safety of NT 201 and BOTOX in patients suffering from blepharospasm. Of 304 enrolled patients, 300 patients received study medication (intent-to-treat population), and 256 patients completed the study as planned (per-protocol population). At baseline, patients received a single injection of NT 201 or BOTOX (

Local administration of botulinum toxin (BoTx) inhibits presynaptic acetylcholine release. All cholinergically innervated muscles and glands can be paralyzed accordingly. Studies on the application of BoTx in multiple sclerosis have shown good results for focal spasticity, in particular, of the extremities. The first promising data were published on bladder disorders, especially with regard to detrusor sphincter dyssynergia and detrusor hyperreflexia. Hyperhidrosis, hypersalivation and proctologic symptoms might be other areas of application. Approval, however, has been greatly restricted which limits the therapeutic range of use.

The therapeutic possibilities of botulinum toxin are manifold and certainly not yet fully exhausted. Apart from the classical indications--focal dystonia and focal spasticity--its use in the management of wrinkles has become well known. Moreover, the toxin is now being administered in many medical fields, including many other kinetic disorders like rare dystonias and tremor. The toxin is also used in a great number of autonomic disorders such as focal hyperhidrosis and even rhinitis. Substantial advances have been made in the field of urology after injections into the sphincter and detrusor muscle. Studies for approval are meanwhile under way concerning the treatment of detrusor hyperreflexia. Gastroenterology is another important field for application of botulinum toxin--be it to the esophagus (e.g. achalasia), stomach, gallbladder, or anorectum. Anal fissure is considered a particularly common indication. Controlled studies for many indications are frequently lacking because of the limited incidence of some of these disorders and symptoms.

The aim of our study was to observe the effects on gait parameters induced by STN stimulation and levodopa medication in patients with advanced Parkinson's disease in order to determine different or additive effects. Therefore we examined 12 patients with advanced Parkinson disease after bilateral implantation of DBS into the STN. We assessed the motor score of the UPDRS and quantitative gait analysis under 4 treatment conditions: with and without stimulation as well as with and without levodopa. The mean improvement of the UPDRS motor score was almost the same with levodopa and DBS. Combining both therapies we saw a further improvement of the motor score. Gait parameters of patients with PD treated either with levodopa or STN stimulation were greatly improved. A significant difference between levodopa and STN stimulation could only be shown for the parameters velocity and step length. These parameters improved more with levodopa than with stimulation. The combination of both therapeutic methods showed the best results on the UPDRS motor score and gait parameters.

Nearly all patients with multiple sclerosis (MS) will develop spasticity in the course of their disease. This symptom accounts for most of the handicap and impairment in the quality of life. Treatment with botulinum toxin will enable an efficient and safe alleviation of spasticity and the problems involved, given a realistic definition of the therapeutic target and a graded multimodal approach. Treatment may fail for a great number of reasons that require diligent analysis. Compared with other disorders resulting in spasticity as well, MS does not constitute a monophasic disorder but is influenced by many factors. Treatment of spasticity in MS must therefore be guided by its particular aspects.

Stress urinary incontinence (SUI) is the most common form of urinary incontinence and occurs more frequently in women than in men. Duloxetine is a balanced dual serotonin (5-HT) and norepinephrine (NE) reuptake inhibitor and shows no relevant binding affinity for histaminergic, dopaminergic, cholinergic, and adrenergic receptors. The efficacy of duloxetine in SUI is based on the inhibition of the presynaptic reuptake of 5-HT and NE in Onuf's nucleus of the sacral spinal cord, whereby it may increase the concentration of 5-HT and NE in the synaptic cleft. The effectiveness of duloxetine was studied in a cat model of acetic acid-induced bladder irritation. The results showed that in cats with previous irritated bladder function, there was a dosage-dependent improvement of bladder capacity and periurethral electromyography (EMG) activity. In women with SUI, it is assumed that the clinical efficacy of duloxetine is based on stronger urethral contraction and persistent sphincter tone during the storage phase. In clinical trials in women with SUI, duloxetine has demonstrated efficacy in reducing incontinence episodes and increasing quality of life. Nausea was the most common adverse event and the main cause for discontinuation. In summary, duloxetine appears to be a promising new option for the treatment of SUI.

For a long time, autonomic dysregulations in Parkinson's syndrome have been underrated as to their incidence and severity. Meanwhile, we know about their occurrence in the early stage of illness and that they do affect all patients in different ways and varyingly degrees. Patients should thus be interviewed and tested accordingly, and have treatment as needed. Cardiovascular, gastrointestinal and urogenital symptoms are most commonly found. However, any organic system can be involved.

Female urinary incontinence is a medical and social problem with a large prevalence. Stress urinary incontinence (SUI) is the most common form of urinary incontinence and is responsible for 49 % of all incontinence, if mixed forms are included even for 78 %. As of yet, apart from "off-label" treatment, there is no pharmacological treatment available for stress urinary incontinence. For instance, estrogens are used in menopausal patients but a substantial effect in the treatment of SUI has not been demonstrated. a-Adrenergics, such as phenylpropanolamine and midodrine, and b-adrenergics, such as clenbuterol, are also used in "off-label" therapy. A recently conducted meta-analysis of 15 randomised studies with female patients who received a- und b-adrenergics as part of their therapy, failed to detect efficacy compared to placebo. Tricyclic antidepressives, such as imipramine and doxepine, which are used for the treatment of urge incontinence, are also used "off-label" in the treatment of SUI. However, no placebo-controlled studies have been conducted so far. The serotonin-norepinephrine reuptake inhibitor duloxetine represents a new therapeutic approach in the treatment of SUI. It has shown positive effects on bladder and urethra in animal experiments, most likely through an effect on the Onuf's nucleus in the spinal cord. In randomised, placebo-controlled studies (phase II and III) in women with SUI, a significant and clinically relevant reduction in urinary incontinence episodes as well as an improvement in the quality of life compared to placebo was shown.

Dopamine agonists have become indispensable in the treatment of Parkinson's disease. In every-day practice, however, the decision to select the best compound for an individual patient is rendered difficult because of the large number of substances available on the market. This review article provides a closer look at the experimental and clinical studies with ropinirole published so far. Ropinirole is a non-ergoline dopamine agonist which has been proven to be effective in both, monotherapy and combination therapy of idiopathic Parkinson's disease. In addition to ameliorating bradykinesia, rigor, and tremor, ropinirole facilitates the daily life and improves depressive moods of patients with Parkinson's disease. The long-term complications of levodopa are avoided, and problems commonly associated with levodopa treatment are reduced. Ropinirole appears to have a neuroprotective effect. In addition to Parkinson's disease, ropinirole has also been used successfully in the treatment of restless legs syndrome.

Purpose: This randomized controlled trial was performed to compare the novel botulinum toxin type A free of complexing proteins (NT 201) with the marketed preparation BOTOX degrees regarding efficacy and tolerability., Methods: Fourteen healthy volunteers received a single intramuscular injection into the extensor digitorum brevis (EDB) muscle of either 4 units NT 201, or 4 units of BOTOX degrees randomised by foot. Compound muscle action potential (CMAP) measurements were recorded for up to 90 days after injection., Results: Both drugs produced a maximum decline between Day 7 and Day 14. At Day 90, administration of both drugs resulted in approximately a 40% CMAP decline as compared to baseline. Duration of paralytic effect was comparable in both groups, at all response thresholds tested. Both drugs were well tolerated., Conclusion: The effects of small amounts of NT 201 and BOTOX degrees injected into the EDB muscle are comparable in terms of efficacy, time to onset of action, duration of action, and tolerability.

Unlabelled: Increasing evidence has suggested that oxidative stress may be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). The antioxidant vitamin E (alpha-tocopherol) has been shown to slow down the onset and progression of the paralysis in transgenic mice expressing a mutation in the superoxide dismutase gene found in certain forms of familial ALS. The current study, a double blind, placebo-controlled, randomised, stratified, parallel-group clinical trial, was designed to determine whether vitamin E (5000 mg per day) may be efficacious in slowing down disease progression when added to riluzole., Methods: 160 patients in 6 German centres with either probable or definite ALS (according to the El Escorial Criteria) and a disease duration of less than 5 years, treated with riluzole, were included in this study and were randomly assigned to receive either alpha-tocopherol (5000 mg per day) or placebo for 18 months. The Primary outcome measure was survival, calculating time to death, tracheostomy or permanent assisted ventilation, according to the WFN-Criteria of clinical trials. Secondary outcome measures were the rate of deterioration of function assessed by the modified Norris limb and bulbar scales, manual muscle testing (BMRC), spasticity scale, ventilatory function and the Sickness Impact Profile (SIP ALS/19). Patients were assessed at entry and every 4 months thereafter during the study period until month 16 and at a final visit at month 18. Vitamin E samples were taken for compliance check and Quality Control of the trial. For Safety, a physical examination was performed at baseline and then every visit until the treatment discontinuation at month 18. Height and weight were recorded at baseline and weight alone at the follow-up visits. A neurological examination as well as vital signs (heart rate and blood pressure), an ECG and VEP's were recorded at each visit. Furthermore, spontaneously reported adverse experiences and serious adverse events were documented and standard laboratory tests including liver function tests performed. For Statistical Analysis, the population to be considered for the primary outcome measure was an "intent-to-treat" (ITT) population which included all randomised patients who had received at least one treatment dose (n = 160 patients). For the secondary outcome measures, a two way analysis of variance was performed on a patient population that included all randomised patients who had at least one assessment after inclusion., Results: Concerning the primary endpoint, no significant difference between placebo and treatment group could be detected either with the stratified Logrank or the Wilcoxon test. The functional assessments showed a marginal trend in favour of vitamin E, without reaching significance., Conclusion: Neither the primary nor the secondary outcome measures could determine whether a megadose of vitamin E is efficacious in slowing disease progression in ALS as an add-on therapy to riluzol. Larger or longer studies might be needed. However, administration of this megadose does not seem to have any significant side effects in this patient population.

Methods provided by nuclear medicine may be helpful in diagnosis of Parkinson's disease (PD). For that purpose, the sensitivity of iodine-123 metaiodobenzylguanidine ([123I]MIBG) scintigraphy and [123I]FP-CIT single photon emission computed tomography (SPECT) was studied in patients with PD onset (Hoehn and Yahr Stage 1). Cerebral [123I]FP-CIT and cardiac [123I]MIBG scintigraphy were carried out in 18 patients with idiopathic Parkinson's disease, according to Hoehn and Yahr Stage 1. For quantification purposes, we calculated the striatum/posterior lobe binding of FP-CIT and the heart-to-mediastinum (H/M) count ratio regarding MIBG scintigraphy. In 15 of 18 patients, we observed markedly reduced or asymmetric striatal FP-CIT tracer accumulation. FP-CIT binding of the affected striatum was significantly lower as compared with that of the unaffected side. Striatal FP-CIT binding correlated significantly with the motor part of the Unified Parkinson's disease rating scale (UPDRS) but not with age, disease duration, or gender. MIBG scintigraphy delivered significant pathological results in 13 of 18 patients. There was no significant correlation between the H/M ratio relating to MIBG scintigraphy and the motor part of UPDRS, age, disease duration, or gender; however, binding of striatal FP-CIT correlated significantly with cardiac MIBG accumulation. According to the clinical criteria, it might be difficult to prove the diagnosis of PD in patients with slight symptoms and in these cases, FP-CIT SPECT and MIBG scintigraphy may contribute to the early diagnosis of PD. In addition, the functional loss of nigrostriatal and cardiac sympathetic neurons seems to be coupled closely., (Copyright 2005 Movement Disorder Society.)

The economic impact of parkinsonism has been getting more significant due to the increasing prevalence of Parkinson's disease and the modern therapies available nowadays. The present study is supposed to update the existing databases and to provide a sound foundation for rational decision-making in the health care sector. It does not only focus on the direct costs of this disease incurred by 75 patients over a longer period, but also and for the first time, takes a look on the indirect cost as well. The study shows that the expenses for PD-related house rebuilding and early retirement make up for a substantial share among the indirect costs. In the overall analysis, the ratio between both, direct and indirect costs appear to be relatively balanced with slight domination of the direct costs.

Autonomic nervous system (ANS) dysfunction is a serious complication of lightning and electrical trauma (L/ET). The ANS regulates the normal vegetative functioning of many organ systems. When ANS is compromised after lightning and electric trauma, patients are vulnerable to serious medical problems. Three conditions of ANS dysfunction of particular concern for L/ET patients are complex regional pain syndrome (CRPS), cardiovascular abnormalities, and keraunoparalysis (KP). The patient with CRPS presents with pain, hyperpathia, sweating, and edema hours to days after trauma. Neurorehabilitation is exceedingly important. A primary goal is to keep the affected extremity mobile and functional. Some patients benefit from sympathetic blockade. Cardiovascular abnormalities associated with lightning and electrical trauma can be life threatening. Care for these patients require a multidisciplinary team including a cardiologist. Keraunoparalysis is a frightening and distressing complication of lightning strikes. The syndrome consists of limb paralysis, sensory symptoms, pallor, coolness and absent pulses. Release of excessive catecholamines is said to be responsible for these findings. Fortunately, the condition is transient.

Urinary continence and voiding are complex physiological processes and require the coordination of all three efferent areas of the nervous system (parasympathetic, sympathetic, somatic). The pudendal nerve contains efferent as well as afferent fibers, the former ones having their origin in Onuf's nucleus. A number of studies see a link in the central modulation of lower urinary tract activity through 5-HT and NE receptor agonists as well as antagonists. Previous information about the modulation of the lower urinary tract in humans has been obtained from animal experiments. Duloxetin, a combined serotonin/norepinephrine reuptake inhibitor may prove to be a new therapeutic agent for stress urinary incontinence. Duloxetin appears to act at the presynaptic neuron of Onuf's nucleus. A phase II and three phase III studies have shown significant and clinically relevant improvement in several parameters in comparison to placebo control. The most frequent adverse event observed was nausea.

The objective of this workshop was to review and discuss the debate on neurotoxicity of levodopa in the treatment of Parkinson's disease (PD) with consideration of preclinical and clinical findings. We concluded that in particular preclinical outcomes of in vitro models of neurodegeneration describe neurotoxic effects of levodopa, whereas trials in animal models provided controversial results. To date, clinical trials in PD patients showed no convincing proof of direct neurotoxic effects of levodopa on progression of neurodegeneration with various applied functional imaging techniques particularly with specific radiotracers for nigral dopaminergic neurotransmission. However, the controversy on neurotoxicity of levodopa only partially considered indirect mechanisms, i. e. levodopa-associated homocysteine elevation. But there is accumulating evidence that this long-term side effect of chronic levodopa administration dose dependently individually contributes to progression of neurodegeneration due to increased release of neurotoxins, induction of oxidative stress and mitochondrial dysfunction according to results of in vitro and animal trials and to at least peripheral neuronal degeneration and increased risk for onset of atherosclerosis-related disorders according to clinical trials in PD patients. From this point of view we demand that future research on the efficacy and putative neurotoxicity of antiparkinsonian compounds should also consider putative toxic long-term effects of drug administration and should look for putative peripheral biomarkers and individual, environmental or nutritative risk factors in order to establish a preventive therapy, i. e. folic acid administration in the case of levodopa-associated homocysteine elevation.

Ropinirole is a modern, non-ergoline dopamine agonist which has been shown to be effective as monotherapy as well as combination therapy against idiopathic Parkinson's disease. In addition to improving bradykinesia, rigor and tremor, it will ameliorate the abilities of daily living as well as depressive mood. The long-term complications of L-dopa are diminished and the existing complications are reduced. A neuroprotective effect is under discussion. In addition to Parkinson's disease, ropinirole is also used successfully in the treatment of restless legs syndrome.

Botulinum toxin has been used in urology since the end of the 1980s. However, this therapeutic option has not been firmly established yet. Valid studies have merely been conducted on detrusor sphincter dyssynergia (DSD) and on detrusor overactivity (hyperreflexia), but even those findings do not allow final conclusions. Success rates in DSD are between 58% and 88%, in detrusor overactivity approximately 80%. Further possible indications for botulinum toxin are motor and sensory urge, urethrospasm, spasticity of the pelvic floor, neobladder, and even chronic prostatic pain. To reach firmer conclusions, controlled studies with well-defined patient populations and using validated and reproducible outcome measures are needed. In addition, we also need information on repeated injections over a long period of time. These data are not available to date. At present, the application of botulinum toxin should be reserved for experienced users only., (Copyright 2004 Movement Disorder Society)

The increasing prevalence of Parkinson syndrome and its cost-intensive modern therapies make for a growing economic burden. Studies on cost to date have limited validity owing to the various methods employed (retrospective, focus on partial expenses, minimal case numbers, etc.). The present study collected data pertaining to direct costs. Seventy-seven patients were followed for 10 months. They had been outpatients when enrolled in the study. Hospitalization or comparable changes during the course of observation were registered accordingly. The most significant result revealed by the study is that expenses for medication by far take up the biggest share of the direct costs. In the early stage of the disease (H and Y I), the monthly costs of drug treatment amount to 397.67 Euros. With advancing ailment, costs rose to 561.56 Euros in H and Y 2, 588.30 Euros in H and Y 3, 604.86 Euros in H and Y 4, and 645.77 Euros in H and Y 5. (Average costs for disease remedies amount to 25.46 Euros.) Inpatient costs were 13.47 Euros (with DBS, 19.04 Euros). Adjuvants aggregated to 3.50 Euros per month, medical technical diagnostic workup to 18.74 Euros (47.60 Euros including DBS), and medical services to 15.73 Euros.

Botulinum toxin has meanwhile been approved for a number of indications. It is also gaining acceptance in other indications with a major focus on pain. The most common type of headache is tension-type headache (TTH) the pathogenesis of which has not yet been unfolded. As it looks there are vascular, myofascial and supraspinal factors intertwined. It is felt that headache is triggered by myofascial stimuli. The application of botulinum toxin is an intelligent alternative since the favorable effect of pharmacologic and other therapies is limited. Application of BTX should be considered when the pericranial muscles are involved. One of the effects produced lies in the reduction of muscular stress, muscular ischemia and muscle tone. We still don't know whether additional mechanisms such as retrograde uptake and direct antiinflammatory potential are involved. Current data permit the conclusion that headaches are decreased in their frequency and distinctiveness. Significant untoward effects are not to be expected. Neither the ideal dose nor the optimum selection of injection sites have been established as yet, an individual injection scheme is apparently most promising. Injection of the trigger points seems to make sense.

Botulinum toxin has been used for therapeutic purposes in medicine for more than 20 years. Its effective use now covers more than 50 conditions in a wide variety of areas. Its medicinal use was initially based on its blockade of neuromuscular and neurosecretory transfers. Its use for conditions in the field of specific pain therapy is currently authorized in Germany for spastic torticollis, blepharospasm, hemifacial spasm, spastic equine gait in cases of idiopathic cerebral paresis, and spasticity of the arm following stroke. New publications suggest that it can usefully be employed for numerous other painful conditions. The modes of action known today are not confined to the blockade of cholinergic innervation.Indeed, there is also evidence that therapeutic effects are mediated through a normalization of muscle spindle activity, retrograde intake into the CNS with modulation of the central neuropeptide function, inhibition of sterile neurogenic inflammation, and normalization of endplate dysfunction. In view of the methodological peculiarities of studies in the field of pain therapy, such as injection techniques, injection sites, blind study techniques, dosage etc., the scientific evidence for its use in a wide variety of pain syndromes is still patchy in many areas. For this reason the use of botulinum toxin for these syndromes is only justified after full use has been made of standard therapeutic methods and evaluation in specialized centers. The possibility of considering botulinum toxin in specific pain therapy contexts is a new option for patients and doctors.However, its use calls for detailed knowledge of functional neuroanatomy and extensive practical experience and expertise.

Most patients with Parkinson's disease experience autonomic dysfunction at some point in the course of their disease. In contrast to autonomic dysregulation in multisystem atrophy, they are less severe, and they frequently cause troublesome symptoms only in advanced stages of the disease. The quality of life is nevertheless substantially restricted. Cardiovascular, gastrointestinal and urogenital autonomic dysfunction is predominant. Appropriate diagnosis and treatment can greatly benefit the patient. An interdisciplinary approach is desirable in most cases.

In recent years, the antiparkinsonian drug regime has become increasingly complicated. A wide range of antiparkinson agents is meanwhile available. Combination therapies may unfortunately induce interactions up to the point of life-threatening events. The potential of drug-drug interactions must be taken into account before starting a patient on combination treatment. Moreover, the frequent multimorbidity of patients with Parkinson's disease necessitates the application of additional drugs. A general overview is difficult to maintain because of the countless number of possible interactions. Cautious proceeding is certainly indicated in particular cases. The most common interactions will be discussed below. We should bear in mind that many of the interactions related to drug combinations are unknown yet.

Current findings suggest that multipotent stem cells may be suitable for cell replacement therapies in the treatment of neurodegenerative disorders. Embryonic stem (ES) cells are pluripotent cells isolated from the inner cell mass of the preimplantation blastocyst, which give rise to all cells in the organism. Similarly, multipotent stem cells are also able to regenerate, but are believed to have a more restricted potential than ES cells, and are often defined by the organ from which they are derived. Neural stem cells have been categorized as multipotent stem cells derived from the nervous system with the capacity to regenerate and to give rise to cells belonging to all three cell lineages in the nervous system: neurons, oligodendrocytes, and astrocytes. It is hoped that research on stem cells may reveal methods for producing an infinite supply of dopamine neurons for transplant into Parkinson's disease (PD) patients. The problem is controlling cell growth and differentiation. We will briefly review the current state of stem cell research and will critically discuss the potential of stem cells for the treatment of PD.