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Patients with Parkinson's Disease or a tremor syndrome may present with additional functional movement disorders. The differential diagnosis is particularly difficult. In some cases, functional symptoms occur either before the manifestation of the organic disease or can emerge as an additional symptom after Parkinson's disease or tremor became apparent. In patients with Parkinson's disease the prevalence for additional functional symptoms is 7 %. In the case that patients with Parkinson's diseases have one side that is more severely affected, additional functional motor symptoms such as functional rest tremor also occur on that same, predominantly affected side. Functional gait disorders occur frequently. Clinically, patients appear notably slow in automatized, daily tasks. Their speech is more whispering than hypophonic, bradykinesia during finger tapping manifest without a decrement. The Dopamintransporterszintigraphy (123) I FP-CIT SPECT; DaTSCANTM) may be helpful to differentiate between functional Parkinsonism and Parkinson's disease. Functional tremor in patients with an organic tremor syndrome is diagnosed with the same distraction techniques as in solely functional tremor. This includes cognitive, motor, and suggestive distraction maneuvers. In some cases, additional neurophysiological investigations such as accelerometry are useful for the differential diagnosis. It is most important to identify patients with additional functional symptoms in non-functional movement disorders, because the therapeutic approach differs and a multi professional team is required to initiate effective treatment strategies., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

The background of the freezing-of-gait (FOG) phenomenon in Parkinson's syndrome is presented in this review. The following issues are addressed: characterization of the symptom freezing and its subtypes that challenge standardized diagnostic procedures; available assessment methods generating freezing-related parameters that not only support clinical studies but can also be applied in everyday care, and current therapy options. FOG exists in different subtypes, and clinical and diagnostic definitions are limited by subjective characterization and semi-standardized tests. FOG-specific drug options are not existing, apart from the optimization of dopaminergic medication, which may also be due to the poor discriminatory power of standardized diagnostics. This is also true for deep brain stimulation. Both of these therapeutic options may be due not only to the complex neural network alterations as a motor-control correlate of FOG, but also because of challenging diagnostic assessments methodologies. Innovative, wearable, sensor-based diagnostic strategies are currently being developed, and supportive therapies using tools and technologies focusing on 'cueing' are becoming increasingly well accepted. Even though high level evidence is missing, they provide a helpful treatment option for individualized therapy. It can be assumed that these options will become particularly popular due to technological progress and likely alter the everyday treatment challenges faced by doctors and therapists., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

At least 300,000 people with idiopathic Parkinson's disease are living in Germany. Due to the demographic change the number of affected patients is expected to increase continuously. This article presents the evidence-based diagnostics and therapy of idiopathic Parkinson's disease. It provides an overview especially on new findings and developments in recent years., Competing Interests: Die Autoren geben an, dass keine Interessenkonflikte vorliegen., (© Georg Thieme Verlag KG Stuttgart · New York.)

Over the last two decades important achievements in research of Parkinson's disease led to the identification of specific pathways as well as histopathological fingerprints underlying the pathophysiology of the disease. This knowledge represents the basis for targeted disease-modifying treatment strategies. These treatment options target specific molecular defects in the causal chain or focus on the pathological α‑synuclein species and their propagation. This article highlights the most relevant treatment approaches that are currently being addressed in preliminary clinical trials.

Aim: Safinamide (Xadago ® ) is a newly approved selective MAO-B inhibitor for the treatment of Parkinson's Disease (PD). The X-TRA study investigated the efficacy and tolerability of the substance under clinical practice conditions., Methods: Prospective, observational study in unselected patients in line with safinamide product specifications., Results: Of the 299 patients included (65.9 % males, age 72.7 ± 9.0 years, duration of disease 7.8 ± 5.9 years), at the beginning of the documentation 229 patients (81.2 %) received L-dopa, 108 (39.3 %) combination drugs containing L-dopa, 172 (59.3 %) a dopamine agonist and 23 (8.3 %) a COMT inhibitor. Of these, 203 patients were followed-up over a period of 6 months. The MDS-UPDRS Part III score for motor symptoms decreased from a baseline value of 48.2 ± 22.1 points by 6.8 ± 14.5 points at the end of the study. The Non-Motor Symptoms Scale score indicating the presence or absence of motor symptoms decreased from a baseline value of 57.6 ± 42.1 by 9.3 ± 2.1 points, the Abnormal Involuntary Movement Score from 4.6 ± 5.8 points by 0.9 ± 2.7 points.The Parkinson's Disease Score (PDQ-8) for assessing quality of life decreased from a baseline value of 39.4 ± 18.2 points by 4.3 ± 13.7 points, reflecting an improvement. In total, 300 adverse events were classified as related to safinamide in 132 patients (44.1 %). Fifty-three events were serious (in 15 patients; 5 %). Seventy-four patients (24.7 %) discontinued safinamide therapy because of adverse drug reactions., Conclusions: Safinamide therapy improved the motor and non-motor symptoms as well as the quality of life in PD. Most patients tolerated the therapy well. The only side effects that occurred are those described in the patient information leaflet., Competing Interests: W.H. Jost ist Berater und Referent für Zambon und war PI der veröffentlichten Studie.D. Bosse ist Mitarbeiter der Fa. Zambon.Die anderen Autoren waren Studienteilnehmer und geben keine Interessenskonflikte an., (© Georg Thieme Verlag KG Stuttgart · New York.)

Epidemiological studies suggest an association of certain foods with the risk of Parkinson's disease. Also, a number of studies revaeled positive effects on disease progression by caffeine, higher uric acid and total cholesterol levels - especially in men. However, it is not yet clear whether a specific dietary concept or the effects of the intestinal microbiota on the human metabolism could play a role in the course of the disease. Given the lack of prospective nutrition studies, only general recommendations can be given: a "balanced" seasonal regional diet with emphasis on vegetables, fruits, nuts, fish, low amount of red meat, and non-processed foods with a low level of simple carbohydrates may be helpful. Especially for the elderly, a low-protein diet should be avoided. Rather, in order to prevent the development of sarcopenia and malnutrition, particular attention must be paid to adequate protein intake. The supply of vitamins B12 and D3 must be ensured - at the same time, the non-critical use of dietary supplements, especially micronutrients with presumed anti-oxidative properties, should be discouraged., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Development of motor fluctuations and dyskinesia characterizes the transition from the early to the advanced Parkinson stage. Current oral therapeutic strategies aim at increasing the number of levodopa administrations and extending its benefit by the association of enzyme blockers (MAO- and COMT-inhibitors) and dopamine agonists. However, as disease progresses, mobility becomes progressively dependent on levodopa absorption and plasma bioavailability, resulting in disabling motor complications. If patients continue to experience off time with functional impact on activities of daily living after best oral medication adjustments, implementation of infusion therapies with apomorphine or levodopa, and surgical techniques should be considered. Compared with pulsatile oral therapy implementation of apomorphine and levodopa infusion determines more continuous striatal dopamine receptors stimulation resulting in significant reduction of off-time and dyskinesia, particularly peak-dose. However, long-term experience with these treatments shows that motor complications are not abolished by continuous receptor stimulation suggesting that synaptic plasticity and connectivity changes are not easily reversed once they are established. Early intervention ideally would target patients as soon as motor complications begin rather than at late stage. Preliminary evidence from early deep brain stimulation or early pump treatment suggests that this is feasible but before it is implemented in clinical practice it would require a detailed cost-benefit analysis., Competing Interests: Prof. Antonini Angelo war in Advisory boards von AbbVie, UCB, Bial und hat Honore von Lundbeck, Neuroderm, GE, UCB und Zambon erhalten. Prof. Jost ist Referent und / oder Berater für Abbvie, Bial, Desitin, UCB und Zambon., (© Georg Thieme Verlag KG Stuttgart · New York.)

Parkinson's disease (PD) is the second most prevalent chronic neurodegenerative disorder worldwide, following Alzheimer's disease. Along with the characteristic motor symptoms of the disorder, especially bradykinesia, cognitive deficits can often be found prior to the onset of the disorder. These mainly concern executive functioning. To detect cognitive deficits at an early stage, initial screening procedures are recommended. The new cognitive rapid test Paarassoziationslernen-5 ("PAL-5") has been developed to detect the most prevalent cognitive symptoms - namely executive impairments - of PD patients. It consists of a direct recall of five incompatible and newly jointed word pairs (capitals vs. countries), an intermediate formal lexical word fluency task ("FAS-Test") and a delayed recall. Thereby, the three major executive functioning processes are tested: cognitive flexibility, inhibition and memory. In the department of neurology of the University Clinic of Cologne, the PAL-5 was completed by 154 PD patients, 115 participants with cognitive deficits without a PD diagnosis and 115 controls (N = 384) between 2014 and 2016. For purposes of retest reliability determination, another 42 controls were examined from February to July 2017, with a four-month time interval between the initial and second test. Highly significant group differences have been found. PD patients and cognitive impaired participants scored significantly lower than the control group. A comparison of PD patients and cognitively impaired participants did not reveal significant group differences. Additionally, a moderate to high correlation between PAL-5 and MMST as well as PAL-5 and PANDA was found (respectively p < .001). An ROC analysis of the PAL-5 total score of PD patients with a score lower than 11 showed an AUC of .91. Therefore, a cut-off of ≤ 10 seems to be practicable to detect cognitive deficits - especially executive functioning deficits and memory impairments - in PD patients. It has been shown that cognitive flexibility, inhibition and memory is a short useful combination for a screening procedure of PD patients., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Tremor is clinically defined as a rhythmic, oscillating movement of parts of the body, which functionally leads to impairment of the coordination and execution of targeted movements. It can be a symptom of a primary disease, such as resting tremor in Parkinson's disease or occur as an independent disease, such as essential or orthostatic tremor. For the development of tremor, cerebral components as well as mechanisms at the spinal and muscular level play an important role. This review presents the results of new imaging and electrophysiological studies that have led to important advances in our understanding of the pathophysiology of tremor. We discuss pathophysiological models for the development of resting tremor in Parkinson's disease, essential and orthostatic tremor. We describe recent developments starting from the classical generator model, with an onset of pathological oscillations in distinct cerebral regions, to a network perspective in which tremor arises and spreads through existing anatomical or newly emerged pathological brain networks. In particular translational approaches are presented and discussed. These could serve in the future as a basis for the development of new therapeutic strategies.

Pharmacotherapy in Parkinson’s disease is complex and requires expertise in all health-care professions. Besides idiopathic Parkinson’s disease (IPD) secondary parkinsonism, monogenetic Parkinson’s disease and atypical syndromes need to be differentiated. The prevalence in the European population is estimated to be approximately 1 %. Lifestyle and age are closely linked to IPD. Neurodegeneration with formation of Lewy-bodies and increased oxidative stress in the pars compacta of the substantia nigra are closely linked to IPD. Lewy-bodies show misfolded α-Synuclein. The balance of glutamate, GABA and dopamine is essential for motor complications. Bradykinesia/akinesia, rigidity, rest tremor and postural instability are typical symptoms along with dissymmetry, shuffling gait and camptocormia, micrographia, aphasia, hypophonia, dysphagia, and hypomimia. Early symptoms are akathisia/restlessness, insomnia, somnolence, hyposmia and neck pain. With further progression of IPD, neurons of the ventral tegmental area are affected and lead to non-motor symptoms, which hence are directly related to the underlying disease. Gastric dysmotility, depression, urinary incontinence, excessive sweating, hallucinations, spasticity, muscle pain and Parkinson’s disease dementia are part of IPD.

Transcranial alternating current stimulation (tACS) is a new technique for the modulation of oscillatory brain activity as measured in the electroencephalogram (EEG). In contrast to well-established stimulation techniques, such as transcranial direct current stimulation and transcranial magnetic stimulation, tACS applies a sinusoidal alternating current at a specific frequency. This enables the modulation of the amplitude and frequency of endogenous brain oscillations as well as related cognitive processes. Therefore, the use of tACS has the possibility to evaluate well-known correlations between brain oscillations and cognitive processes in terms of causality. Such causal relationships have been documented in numerous neurocognitive studies on sensory, motor and perceptual processes; however, the clinical application of tACS is still in its infancy. In principle, any pathology that can reliably be connected with brain oscillations of a defined frequency is treatable. A current main focus of clinical research is on symptoms of Parkinson's disease and to a lesser degree, tinnitus. For an effective application of tACS it is important to choose the electrode positions as well as the frequency, intensity and duration of the stimulation in a theory-based and symptom-related manner. A successful therapeutic intervention requires the persistence of the tACS effect after stimulation has ceased. A mechanism that offers not only an explanation to the origin of persistent tACS effects but is also of high therapeutic benefit is neural plasticity. Therefore, one current focus of research aims at a better understanding of tACS after effects.

Psychotic symptoms are common in Parkinson's disease (PD) and are associated with increased disability, worsened quality of life, and poor long-term prognosis. In this article, clinical features, hypotheses on pathogenesis, and current treatment strategies for Parkinson's disease psychosis (PDP) are reviewed. According to epidemiological studies, the prevalence of PDP is between 20 to 40 %. Complex visual hallucinations are the most common psychotic symptoms and are present in 17-72 % of the patients. Other sensory disturbances encompass tactile hallucinations and minor hallucinatory phenomena, such as sense of presence and visual illusions. Hallucinations are often accompanied by delusions, whose most frequent themes are persecution and jealousy. The pathophysiology of PDP remains unclear. Different factors have been implicated, including Levo-dopa and dopaminergic medications, neurotransmitter imbalances, neuroanatomic alterations, abnormal visuospatial processes, and genetic predisposition. The first-line strategy in the treatment of persistent and problematic PDP is represented by reduction in anti-PD medications. Second-generation antipsychotics are the treatment of choice, with clozapine being demonstrated as the most effective and tolerable drug for PD patients.

Numerous neurological patients suffer from speech and language disorders but the underlying pathomechanisms are not well understood. Imaging studies on speech production disorders lag behind aphasiological research on speech perception, probably due to worries concerning movement artifacts. Meanwhile, modern neuroimaging techniques allow investigation of these processes. This article summarizes the insights from neuroimaging on physiological speech production and also on the pathomechanisms underlying Parkinson's disease and developmental stuttering.

Myeloperoxidase (MPO) is a hemoprotein which is involved in the unspecific immune response. In this process hypochloric acid is released. Hypochloric acid can react with lipids and proteins and thus lead to cell damage. We were able to show that MPO, as well as a biomarker for MPO - 3-Chlorotyrosine - are upregulated in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-model of Parkinson's disease as well as in the disease itself. Ablation of MPO resulted in a neuroprotective effect in the MPTP-model. Herein we describe the different function of MPO, and how these can lead to the cellular demise as seen in Parkinson's disease., (© Georg Thieme Verlag KG Stuttgart · New York.)

Parkinson's disease (PD) is caused by degeneration of the dopaminergic neurons in the substantia nigra (SN) and a resulting dysfunction of the nigrostriatal pathways including the basal ganglia. Beside motor symptoms, different types of pain (e.g., dystonic musculoskeletal pain or central pain) occur in a considerable number of patients. In addition, abnormalities in pain processing have been observed in PD patients, which may present as increased pain sensitivity. The pathophysiological mechanisms involved in disturbed pain processing of PD, however, are still poorly understood. The present article gives an overview of the relevant experimental studies, investigating the abnormalities of pain processing in PD by means of electrophysiological [electroencephalography (EEG), sympathetic skin response (SSR)] and psychophysical methods [quantitative sensory testing (QST), RIII reflex threshold]. Based on a review of the literature, it is postulated that dysfunction in endogenous pain inhibition caused by dopaminergic deficiency in the basal ganglia, especially in the striatum, but also in mesolimbic areas is a main pathophysiological mechanism involved in nociceptive abnormalities in PD.

Introduction: Clinical assessment of hand bradykinesia in Parkinson's disease (PD) focuses mainly on the frequency, amplitude and rhythm of movements, thereby subjectively evaluating the correct performance of hand movements. The aim of the study was to quantify hand bradykinesia with kinematic data in different Parkinsonian syndromes., Patients and Methods: This retrospective study compared patients with idiopathic PD (IPD, n = 18), atypical Parkinson's syndrome (APS, n = 17), secondary Parkinson's syndrome (SPS, n = 18) and healthy controls (C, n = 18). All patients were receiving the best medical treatment. Hand movements were recorded using an ultrasound-system (Zebris®, Isny, Germany). Subjects were asked to perform pronation/supination of the forearm (diadochokinesis), flexion/extension of the hand (hand tapping) and tapping of the index finger. Mean amplitude, mean frequency and mean variability of movements were determined., Results: APS patients had significant complex hand movement disability with reduced amplitude and frequency in combination with increased motion variability in all movement tasks. The key disturbance in the IPD group concerned the rhythm in hand tapping and index finger tapping in combination with moderately reduced velocity and range of motion in all conditions. The cyclical hand movement characteristics in SPS patients showed movement slowness with normal amplitude and variability in all motor conditions., Conclusion: Our results suggest that computerized quantitative analysis of cyclical hand movements can characterize and identify different representations of hand bradykinesia in different Parkinsonian disorders and hence may help clinicians to accurately assess therapeutic targets and outcome of interventions.

Patients with congenital and acquired neurogenic bladder dysfunction due to central and peripheral nervous lesions are significantly limited in their daily lives. The neurogenic dysfunction of the bladder and lower urinary tract are often misinterpreted and later fed to a diagnosis. Without therapy severe complications, including renal damage, could be the consequence in the follow up. Therefore, dedicated diagnostics have to be done to recognize the different disorders and to determine the specific therapy. For these patients a lifelong bladder monitoring and neuro-urological management is necessary. This article describes techniques of neuro-urological testings and the interpretation in case of neurogenic disorders.

The lower urinary tract (LUT) is regulated by a complex neural network that is subject to supraspinal control. Neurological disorders, especially of the central nervous system (CNS), can rapidly lead to disruption of this control. Multiple sclerosis, Parkinson's disease, multiple system atrophy, and stroke are neurological disorders which quite frequently cause dysfunction of the LUT. With respect to the pathophysiology of bladder dysfunction in CNS diseases there are various hypotheses regarding the individual disorders: disturbances of neural communication between the frontal cortex and pontine micturition center, between the pontine micturition center and the lumbosacral parts of the spinal cord, and between the basal ganglia, thalamus, and anterior cingulate gyrus appear to play a pivotal role in the development of bladder dysfunction. The symptoms and urodynamic presentation of LUT dysfunction can vary considerably depending on the disease and disease progression and can change in the course of the disease. The incidence and prevalence of LUT dysfunctions rise with increasing progression of the underlying neurological disease.Various conservative, minimally invasive, and open surgical procedures are available to prevent harmful sequelae and to improve the quality of life of these patients. As yet, however, few data exist on most of the treatment options in cases of the above-mentioned CNS diseases. Intermittent self-catheterization and antimuscarinic medications are among the most important conservative treatment options. Injection of botulinum neurotoxin type A into the detrusor muscle and increasingly sacral or pudendal neuromodulation are among the most important minimally invasive treatment options. Surgical methods include reconstructive continent or incontinent urinary diversion.When planning therapy the patient's current needs and neurological limitations as well as possible disease progression must be taken into consideration. It is often advisable to consult with and enlist the cooperation of the attending neurologist when planning treatment.

Approximately 10,000-15,000 Parkinson's disease (PD) patients per year undergo surgery in Germany. The demographic developments along with further surgical progress and procedural refinements will lead to increasing numbers of PD patients in the operating theatre (OR). There are several perioperative risk factors for PD patients, they more often require prolonged intensive care treatment and warrant particular anesthesiological attention with regard to the choice of drugs and equipment. Careful evaluation of concomitant diseases, maintenance of oral Parkinson therapeutic drugs up to the time of surgery and continuous perioperative dopaminergic therapy are key factors for reducing postoperative morbidity in PD patients undergoing surgery.

Through cortico-subcortico-cortical loop systems, the dopaminergic modulation influences not only motor, but also other executive functions. Neuropsychological findings in Parkinson's disease are reviewed and physiologically interpreted. The theory of a "supervisory attentional system" according to Norman and Shallice (1986) seems to be an adequate model of the interaction of cortex and basal ganglia in executive function and control., (© Georg Thieme Verlag KG Stuttgart · New York.)

For more than 15 years deep brain stimulation of the subthalamic nucleus and globus pallidus internus have become therapeutic options in advanced Parkinson's disease. The number of patients with long-term treatment is increasing steadily. This review focuses on issues of the long-term care of these Parkinson's patients, including differences of the available deep brain stimulation systems, recommendations for follow-up examinations, implications for medical diagnostics and therapies and an algorithm for symptom deterioration. Today, there is no profound evidence that deep brain stimulation prevents disease progression. However, symptomatic relief from motor symptoms is maintained during long-term follow-up and interruption of the therapy remains an exception., (© Georg Thieme Verlag KG Stuttgart · New York.)

Brain imaging enables the investigation of brain morphology and function in patients with Parkinson's disease (PD). Innovative magnetic resonance imaging (MRI) techniques have recently been established as a new research tool in PD. They are based on the investigation of neuronal tissue properties (MR relaxometry, SWI, DWI, DTI, VBM) and of cerebral perfusion and neuronal activity (ASL, fcMRI). Besides a better understanding of the pathophysiology of PD, these innovative MR techniques might be suitable for measuring progression of PD and the effect of therapeutic interventions on brain functioning. In the clinical setting, they could help to advance the differential diagnosis of parkinsonian disorders.

Nuclear medicine imaging using positron emission tomography (PET) or single photon emission computed tomography (SPECT) has enabled to study not only the metabolism and blood flow in specific brain areas but also the quantification of the function of distinct molecules. With respect to Parkinson's disease PET and later SPECT allowed the number of dopaminergic neurons to be assessed in vivo. These quantifications are relevant to establishing a clinical diagnosis, assessing the progression of the disease or the survival of transplanted dopaminergic neurons. In addition both techniques have markedly contributed to our understanding of the pathophysiology of this disorder. More recently, molecular imaging has been directed towards understanding the pathophysiology of non-motor symptoms in this disorder.

Functional brain imaging allows the effects of deep brain stimulation (DBS) on the living human brain to be investigated. In patients with advanced Parkinson's disease (PD), positron emission tomography (PET) studies were undertaken at rest as well as under motor, cognitive or behavioral activation. DBS leads to a reduction of abnormal PD-related network activity in the motor system, which partly correlates with the improvement of motor symptoms. The local increase of energy consumption within the direct target area suggests a predominant excitatory influence of the stimulation current on neuronal tissue. Remote effects of DBS of the subthalamic nucleus (STN) on frontal association cortices indicate an interference of stimulation energy with associative and limbic basal ganglia loops. Taken together, functional brain imaging provides very valuable data for advancement of the DBS technique in PD therapy.

Although extrapyramidal diseases are commonly thought to solely affect the (extrapyramidal) motor system, non-motor symptoms such as behavioural abnormalities, dysautonomia, sleep disturbances and sensory dysfunctions are also frequently observed. Autonomic dysfunction as an important clinical component of extrapyramidal disease (idiopathic Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, dementia with Lewy bodies) is often not formally assessed and thus frequently misdiagnosed. Symptoms of autonomic dysfunction in general impact more on quality of life than motor symptoms. Appropriate symptom-oriented diagnosis and symptomatic treatment as part of an interdisciplinary approach can provide a great benefit for the patient. Unfortunately, double-blind, randomised, controlled studies are scarce with the consequence that most recommendations are not based on the highest level of evidence. This review presents a limited overview on the treatment of cardiovascular, gastrointestinal, urogenital and sudomotor autonomic dysfunctions in various extrapyramidal syndromes., (Copyright (c) Georg Thieme Verlag KG Stuttgart--New York.)

Deep brain stimulation (DBS) is an effective neurosurgical therapy for treatment of motor symptoms in Parkinson's disease (PD). DBS of the subthalamic nucleus (STN-DBS) leads to a significant reduction of hypokinetic and hyperkinetic symptoms and improvement in quality of life. STN-DBS is, however, associated with severe adverse effects including psychiatric symptoms, such as depression, apathy and increased suicidal tendencies. Pallidal DBS might be just as efficacious with fewer adverse effects. Future studies will prospectively compare the clinical effects of STN and pallidal DBS. Alternative targets for treatment of PD have to be considered including the pedunculopontine nucleus, thalamic CM/Pf complex and zona incerta.

Deep brain stimulation (DBS) is a safe and successful therapeutic option for patients with dystonia and tremor syndrome who do not respond sufficiently to conservative therapies. The most common target of DBS in patients with dystonia is the internal region of the globus pallidus (GPI). DBS of the GPI leads to long-lasting and remarkable improvement of dystonic movements in about 80% of patients. Recently it could be shown that not only patients with idiopathic dystonia but also patients with secondary dystonia can benefit from DBS although to a somewhat lesser extent. In patients with tremor syndromes, such as essential tremor, tremor-dominant Parkinson's disease or tremor in multiple sclerosis (MS) the intermediate ventral nucleus of the thalamus (VIM) as well as the subthalamic region proved to be promising targets for DBS electrodes. Especially in patients with essential tremor VIM-DBS leads to an often acute reduction of the tremor syndrome. In long-term observations, however, patients with essential tremor showed some tolerability to VIM-DBS leading to a slow increase of stimulation parameters to maintain a stable effect. VIM-DBS in patients with Parkinson's disease is rare and is reserved for elderly patients with pronounced tremor syndrome and little disease progression. Controlled studies and data on DBS in MS tremor are lacking and data are sparse and heterogeneous. Therefore, VIM-DBS in MS tremor patients has to be evaluated individually with caution. In summary patients with tremor syndromes as well as dystonia who cannot be adequately controlled with conservative therapy are good candidates for deep brain stimulation, a therapeutic option with moderate complications and risks and very good outcome for most patients.

Long-term care after deep brain stimulation for Parkinson's disease requires regular technical check-ups as well as clinical follow-up. Residual or emerging difficulties with gait, balance or speech should be addressed by specific rehabilitation programs. In cases of psychosocial maladjustment, psychotherapy or family counseling may prove helpful. After consolidation of stimulation parameters, pharmacotherapy can be tailored according to the individual needs, following the same guidelines as for Parkinson's disease patients without deep brain stimulation. In cases of clinical deterioration, malfunctioning of the stimulation system, comorbidity or disease progression has to be considered and treated accordingly. Structured long-term care programs may contribute to patient satisfaction and ensure quality of life.

Sporadic Parkinson's disease is a multisystem disorder that involves predisposed nerve cell types in circumscribed regions of the entire human nervous system (peripheral, enteric, and central nervous systems). A recent staging procedure for the pathological process proposes that, in the brain, the formation of intraneuronal Lewy bodies and Lewy neurites begins at two sites and continues in a topographically predictable sequence in 6 stages, during which components of the olfactory, autonomic, limbic, and somatomotor systems become progressively involved. In stages 1 - 2, the Lewy body pathology is confined to the medulla oblongata/pontine tegmentum and anterior olfactory structures. In stages 3 - 4, the substantia nigra, other nuclei of the basal mid- and forebrain, and the mesocortex become the focus of initially subtle and, then, severe changes. During this phase, the illness probably becomes clinically manifest. In the final stages 5 - 6, the lesions appear in the neocortex.

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.

Nigrostriatal and cerebellar systems are important postural subsystems in neurologic rehabilitation. In this study, we investigated the ability to differentiate both systems via posturography and spectral analysis. This cross-sectional study included 156 study subjects with 52 individuals in each group (healthy controls, Parkinson's disease and cerebellar disease patients). The mean age of all groups was 61.3+/-13.4 years. We used the interactive balance system (IBS) to differentiate vertical pressure fluctuations on four independent force plates, each supporting one heel or the toes of each leg in eight test positions. We also performed a frequency analysis of the force/time signal. The univariate, multifactor covariance analysis was used for statistical evaluation. Variance analysis of the Parkinson's group (mean/95% CI: 23.0/20.5-25.5) and control group (mean/95% CI: 16.7/14.2-19.2) revealed the greatest differences in frequency range F1. Subjects with cerebellar disease showed significant differences compared with controls in all frequency ranges. Furthermore, cerebellar disease subjects showed a consistently lower postural stability compared with the Parkinson's (p<0.001) and control groups (p<0.001). Results from the present study suggest that the cerebellar and nigrostriatal system can be effectively differentiated and assessed with frequency-analyzed posturographic parameters. Furthermore, the IBS allows a highly practical differential assessment in neurologic rehabilitation.

Freezing of gait (FOG) is a common disturbance in Parkinson's disease (PD) and other higher-level gait disorders. It appears most often during the later stages of PD but is seen also during the initial phases before oral substitution of levodopa has started. The disorder has its own pathophysiology and differs from bradykinesia. It can occur both on and off medication. It interferes with activities of daily life, reduces mobility, and is an important risk factor for falling. While patients with FOG during medication do not reliably respond to pharmacotherapy or deep brain stimulation, external cues have been demonstrated that influence FOG effectively. They are applied as auditory, visual, tactile, or mental cues. This article discusses available pharmacological and physiotherapeutic approaches to the treatment of FOG.

The pathophysiology of depression has been assigned to the noradrenalin and serotonin system. Results of different studies also support a role of the dopaminergic system in depression: In particular, psychomotor retarded depressive patients exhibited lower levels of homovanillic acid (metabolite of dopamine). While the moodimproving effect of methylphenidat, D-amphetamine and cocaine is also supportive for an involvement of the dopaminergic system, reserpine leads to diminished dopamine levels and may induce a depressive syndrome as well as dopamine receptor-blockers. Dopamine-mediated motor disturbances and accompanying changes in mood in Parkinson's disease likewise support pathophysiological similarities of depression and Parkinson's disease. Psychomotor inhibition, reduced facial expression and decreased speech production in depression are in line with a hypodopaminergic state of the respective motor areas. There is evidence from open studies for the ergotalkaloids bromocriptine and pergolide to have anti-depressive effects. Controlled studies for the selective dopamine D2/D3-agonists pramipexole and ropinirole are existing. Bupropion, a selective dopamine and noradrenaline reuptake inhibitor (DNRI), has proven antidepressant efficacy in controlled studies and has been licensed for the treatment of depression.

The traditional model of corticostriatal-thalamocortical projections, with indirect and direct pathways, provides a simplified and useful explanation for the motor deficits (hypokinesia, bradykinesia) that develop in the course of sporadic Parkinson's disease. In the classic model, major emphasis is placed on the dopamine deficiency in the dorsal striatum that occurs as a result of neuronal loss in the substantia nigra of the midbrain. Nevertheless, because the pathological process that underlies Parkinson's disease also involves many key nondopaminergic connectivities, a revised model is needed that incorporates these projections. The focus on damage to nondopaminergic and extranigral sites is becoming increasingly important for clinical practice.

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.

Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are important tools in the differential diagnosis and therapeutic monitoring of cognitive disorders. SPECT and PET are highly sensitive methods for the early diagnosis of underlying neurodegeneration and the functional changes in the basal ganglia. Early and reliable diagnosis will become even more relevant with the development of options in the causal treatment of dementias, which would exert their most beneficial effects well before the onset of clinical symptoms. This review provides a brief survey on currently available methods of nuclear imaging in cortical (Alzheimer's disease) and subcortical forms of neurodegenerative dementia (Parkinson's disease; dementia with Lewy bodies).

The accuracy of the diagnosis of Parkinson's disease early in the course of the disease remains a clinical challenge. Imaging of dopamine transporters with DatSCAN and SPEC tomography contributes to identifying patients without nigral degeneration and thus helps preventing unnecessary and potentially harmful treatments. The cost of these imaging procedures needs to be set against the cost of unnecessary medication.

Geriatric patients are often treated with a variety of drugs. Due to the complex pharmacotherapy there is a high potential of drug-related problems such as drug-drug interactions, adverse effects and medication errors. This article describes how the drug therapy of a geriatric patient with Parkinson's disease was optimized using SOAP notes.

Parkinson's disease (PD), a slowly, progressive degenerative disorder of the central nervous system, which affects about ten million people world-wide, is currently treated symptomatically. Current treatment aim i. e. to balance the decreased dopamine turnover in striatal neurons. Chronic exposure to dopaminergic agents, however, supports onset of motor complications and dyskinesia in the long term. Dyskinesia appear mainly as chorea, athetosis, dystonia, stereotypia, ballism or a combination. Sometimes excessive abnormal facial, body and limb movements depend on the overall dosage of dopaminergic substitution. This is why the main therapy is based on reducing the total dosage of dopaminergic substances. Either alternative or additional well-tried substances like apomorphine, amantadine or clozapine are used. New possibilities in treatment emerge from substances like sarizotan, istradefylline, fipampezol or talampanel. Even so disability and reduced quality of life in PD patients and their caregivers may exist. This survey describes the major clinical features, aetiology and demographics of treatment-associated dyskinesia in PD.

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.

The three different states of being (wakefulness, NREM and REM sleep) are associated with profound neurophysiological and neurochemical changes in the brain. These changes explain the existence of movement disorders appearing only or preferentially during sleep, and the effects of sleep on movement disorders. Sleep-related movement disorders are of clinical relevance for multiple reasons: 1) high frequency (e.g. restless legs syndrome (RLS)); 2) diagnostic relevance (e.g. REM sleep behavior disorder (RBD) as first manifestation of Parkinson disorder); 3) diagnostic uncertainty (e.g. parasomnias vs nocturnal epilepsy); 4) association with injuries (e.g. RBD, sleepwalking), sleep disruption/daytime sleepiness (e.g. RLS), and psycho-social burden (e.g. enuresis); 5) requirement of specific treatments (e.g. nocturnal epilepsy, stridor, RBD). This article gives an overview on clinical manifestations, pathophysiology, work-up and treatment of sleep-related movement disorders (e.g. RLS, bruxism), parasomnias (e.g. sleepwalking, RBD), sleep-related epilepsies, and on sleep-associated manifestations of movement disorders (e.g. Parkinson disease, multiple system atrophy).

Although most parkinsonian patients greatly benefit from medical and/or surgical treatment, their clinical management should not be limited to these two interventions. Axial symptoms, freezing, postural instability, speech and swallowing problems may be drug-resistant, and disability may persist in spite of improvement of motor symptoms. A coordinate interdisciplinary approach facilitates the clinical management of the disease. Physiotherapy, occupational therapy and speech therapy may contribute to reduce impairment and improve quality of life; a psychological and social support of patients and caregivers helps them carrying the burden of the disease; counseling through a specialized nurse may give practical solutions to problems like bladder incontinence, symptomatic hypotension or hypersalivation. As sensory cueing may help patients bypassing the disease-specific motor control deficits, it should be included in training programs. Rehabilitatory interventions are part of the standards of care of Parkinson's disease and their efficacy is supported by several neurophysiological and clinical investigations. However, the poor methodological quality of most clinical studies as compared with the standard of pharmacological investigations fails to provide clear-cut evidence in favour of rehabilitation.

Tremor is one of the most frequent neurological signs. The correct clinical classification is mainly clinical. The most frequent primarily neurological tremor is essential tremor (prevalence 2 to 5%). It presents in most cases as a more or less symmetrical postural and kinetic tremor. In about 60% of cases an autosomal-dominant inheritance is found. Tremor may manifest not only in the hands but also in the head and voice. In about 60 to 70% of the patients alcohol may improve the tremor. Parkinsonian tremor is normally a tremor at rest and it starts asymmetrically. The legs and the face are frequently involved. Cerebellar tremor is intentional. Orthostatic tremor, which has a high frequency, mainly manifests in the legs and gives rise to postural instability. Dystonic tremor is an action tremor of the affected region of the body. Drug therapy, which is purely symptomatic, mostly depends on clinical manifestation. Postural and action tremors respond to non selective betablockers (propranolol), primidone, some antiepileptics (gabapentin, toparimate) and benzodiazepines. Classical rest tremors are improved by dopaminergic substances (levodopa, dopamine agonists) or anticholinergics. Dystonic tremor may successfully be treated by injections of botulinum toxin. Orthostatic tremor responds to gabapentin or benzodiazepines in some of the patients. In severely handicapped patients with refractory tremors the implantation of thalamic stimulation electrodes may be considered. This treatment may be very successful, however, its inherent risks have to be taken into account.

Surgery for Parkinson's Disease (PD) is being increasingly used. The main reason for this renewal in surgical treatment for PD is the "deep brain stimulation" (DBS) that replaced the previously used stereotactic lesions in most centers. DBS allows a focal specific electrical stimulation of basal ganglia target instead of an irreversible lesion. Mainly bilateral DBS of the nucleus subthalamicus is now an established surgical treatment for PD. But DBS of the Globus pallidus internus and of the thalamus should still be considered in selected patients. DBS is an efficient treatment for motor complication of PD that can no longer be controlled by drug treatment. Dyskinesia, bradykinesia, tremor and rigor can be improved by DBS and the medication can be reduced. It is still unclear, however, how the improvement in motor symptoms affects quality of life in the long term. Furthermore, patients with severe cognitive and psychiatric symptoms as well as patients with severe axial symptoms should not be operated since these symptoms may worsen after surgery.

Ein neuer gentherapeutischer Ansatz adressiert nicht den Erhalt dopaminerger Neurone, sondern setzt auf die Unterstützung des inhibitorischen GABAergen Systems.

Neurodegenerative disorders are a group of heterogeneous, progressive disorders of varying etiology that affect one or more systems. They occur predominantly at older age, during which the structure and amount of sleep undergo changes. Neurodegenerative processes cause structural changes of the sleep/wake generators in the brainstem which result in disorders such as daytime sleepiness, insomnia, sleep-related movement and breathing disturbances, and disorders of the circadian rhythms. Some sleep disorders manifest years before the onset of neurodegenerative disorders and may serve as predictors. Polysomnography shows sleep fragmentation, tonic or phasic movements of the extremities, alteration of respiratory muscles, reduced slow wave sleep, REM sleep absence or without muscle atonia, increased arousal or wake activity, epileptiform EEG activity, and changes in sleep-related breathing. Very frequently, REM sleep behaviour disorder is associated with neurodegenerative disorders. In this overview we present symptoms, pathophysiology, and polysomnographic findings of sleep disorders in prevalent neurodegenerative disorders.