[Delirium in idiopathic Parkinson's disease]. / Das Delir beim idiopathischen Parkinson-Syndrom.

BACKGROUND: The development of delirium in patients with idiopathic Parkinson's disease (IPD) is a feared complication, which is often associated with sustained worsening of motor symptoms and psychopathological sequelae. Little is known regarding the prevalence and incidence rates, course and prognosis. Clinical studies from which recommendations for evidence-based management of delirium in IPD can be derived are lacking. OBJECTIVE: To summarize the state of the art regarding epidemiological and clinical features of delirium in IPD. Discussion of prevention strategies and non-pharmacological and pharmacological treatment options. METHODS: A literature search was carried out in PubMed. RESULTS: The IPD is an independent risk factor for the development of delirium. Patients with IPD show poorer clinical outcome frequently with cognitive worsening and motor complications following development of delirium. CONCLUSION: So far no validated rating scales for recognition and course evaluation of delirium in IPD are available. Preventive strategies and non-pharmacological measures should be consistently implemented to improve management. There are insufficient data concerning pharmacotherapy with quetiapine and clozapine, whereas other neuroleptics are contraindicated for delirium in IPD due to antidopaminergic side effects.

[Nonpharmacological treatment procedures for Parkinson's disease]. / Nichtmedikamentöse Therapieverfahren beim Morbus Parkinson.

Nonpharmacological treatment strategies in Parkinson' disease include heterogeneous treatment modalities, such as physiotherapy, occupational therapy, speech therapy, cognitive training and deep brain stimulation as well as noninvasive brain stimulation strategies. Even in the early stages of Parkinson's disease nonpharmacological interventions, such as active exercise therapy and speech therapy can be indicated taking the individual symptoms of a patient into account. Mild cognitive deficits are frequently detected in the course of the disease and progression of these disorders to dementia in the advanced stages of the disease is not uncommon. The starting point for a cognitive training, training strategy and training frequency is unknown and currently under investigation. Deep brain stimulation is an established treatment modality, which should be considered when motor fluctuations cannot be adequately controlled by pharmacological treatment. This therapeutic option depends on patient-specific needs and has to be managed by a multiprofessional team. Non-invasive neurostimulation techniques, such as transcranial magnetic stimulation and transcranial direct current stimulation are experimental tools and cannot currently be recommended for general use.

[Practical Use of the Levodopa Pump]. / Praktische Anwendung der Levodopa-Pumpe.

Patients with advanced Parkinson's disease and motor complications undergoing optimized oral therapy can significantly benefit from continuous intrajejunal levodopa/carbidopa infusion applied by means of a medication pump. However, this requires a correctly positioned PEG-J tube and finely adjusted pump settings. Although this method is a routine procedure in specialist centers, no standard procedure has been defined up to now. For this reason, an expert recommendation regarding the practical application has been developed in order to standardize the procedure and facilitate patient access to this treatment option.

Subjective Visual Vertical in PD Patients with Lateral Trunk Flexion.

Lateral trunk flexion (LTF) is a common phenomenon in patients with Parkinson's disease (PD) and has recently been associated with peripheral vestibular dysfunction. Since deviation of the subjective visual vertical (SVV) is a well-recognized feature of disorders involving vestibular processing, we analyzed SVV angles in 30 PD patients with and without LTF to assess the possible role of vestibular dysfunction in the pathogenesis of LTF in PD. Quantification of SVV was obtained using a simple bedside test. PD patients with LTF had significantly greater SVV angles as compared to PD patients without LTF (median: 4.3° [range: 0.1-17.7], n = 21, versus 0.8° [0.1-1.9], n = 9; p < 0.001). 14 of 21 patients with LTF showed pathological SVV, while all 9 patients without LTF had normal SVV. Abnormal SVV was more frequent when LTF was reversible in the supine position compared to fixed LTF. In a subgroup of PD patients with LTF, pathological SVV suggests vestibular dysbalance, which might be involved in the pathophysiological mechanisms underlying LTF.

Early botulinum toxin treatment for spastic pes equinovarus--a randomized double-blind placebo-controlled study.

BACKGROUND AND PURPOSE: Spastic pes equinovarus is a frequent pathological posture of the lower extremity. Botulinum toxin (BoNT/A) has been successfully applied to treat lower limb spasticity. However, the best time to initiate treatment remains unclear. A beneficial effect of an early treatment has been suggested in previous studies. METHODS: A single-centre double-blind randomized placebo-controlled trial was performed to investigate the efficacy of BoNT/A to reduce muscle hypertonicity at the ankle. Fifty-two patients with unilateral or bilateral spastic pes equinovarus with a modified Ashworth score (mAS) of at least 1+ after stroke, traumatic brain injury or hypoxic encephalopathy were allocated to receive either BoNT/A or placebo treatment. A second, open injection was optional at week 12. Patients received unilateral or bilateral injections with 230 or 460 U onabotulinumtoxinA, respectively. The course of the mAS was explored during the open study phase. RESULTS: Patients who had received BoNT/A treatment had lower mAS compared with placebo at week 12 (P < 0.01). During the open label phase, patients from the placebo group showed further deterioration of muscle tone despite starting from a similar baseline and receiving BoNT treatment. Spastic feet that had received BoNT/A in the first cycle had comparatively lower mAS scores over all follow-up data and at week 24 (P < 0.01). CONCLUSIONS: The study demonstrates a reduction of muscular hypertonicity in spastic pes equines with BoNT/A treatment given during the first 3 months after the lesion. Exploratory analyses of the course of muscular hypertonicity during the open phase favour earlier to later treatment.

[Depression in Parkinson's disease--Part 2: Therapy and management]. / Depression beim idiopathischen Parkinson-Syndrom--Teil 2: Therapie und Management.

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.

[Long-term care after deep brain stimulation of patients with Parkinson's disease]. / Nachsorge nach tiefer Hirnstimulation bei Patienten mit M. Parkinson.

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.

[Non-motor Symptoms Questionnaire and Scale for Parkinson's disease. Cross-cultural adaptation into the German language]. / Non-motor Symptoms Questionnaire und Scale für das idiopathische Parkinson-Syndrom. Interkulturell adaptierte Versionen in deutscher Sprache.

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.

Botulinum toxin B increases mouth opening in patients with spastic trismus.

BACKGROUND: Severe generalized spastic movement disorders of various aetiologies often involve the jaw muscles and lead to a spastic trismus with masseter muscle hypertonia. We report a placebo-controlled randomized study on patients with spastic trismus. METHODS: Eleven patients with masseter hypertonia because of stroke, hypoxic encephalopathy or traumatic brain injury were allocated to either botulinum toxin serotype B (BoNT/B) injections into the masseter muscles or placebo treatment. The dental gap, the amount of saliva, salivation scales, and a clinical goal attainment were evaluated. RESULTS: Three weeks after injection the BoNT/B group showed a significantly increased mouth opening compared with placebo treatment (P < 0.05). In addition to the muscle paralysing effect, a goal attainment scale demonstrated a clinical benefit for the BoNT/B group (P < 0.01). CONCLUSIONS: Botulinum toxin serotype B injections into the masseter muscles effectively reduce hypertonia and provide for better mouth opening, thereby contributing to a positive and desired clinical goal.

[Depression in Parkinson's disease. Part 1: epidemiology, signs and symptoms, pathophysiology and diagnosis]. / Depression beim idiopathischen Parkinson-Syndrom. Teil 1: Epidemiologie, Pathophysiologie, Klinik und Diagnostik.

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.

Screening for cognitive impairment in Parkinson's disease--which marker relates to disease severity?

The frequency and pattern of cognitive deficits in Parkinson's disease (PD) is under discussion. We assessed 157 consecutive subjects with PD (66.4 +/- 8.9 years (mean +/- standard deviation); average duration of disease 3.5 +/- 1.3 years; average Hoehn and Yahr stage 2.4 +/- 0.9) diagnosed in centers specialized for the diagnosis and treatment of PD with brief tests for memory (Memory Impairment Screen), attention (Letter Sorting Test) and semantic fluency (category animals). Impaired memory was observed in about one half of the subjects regardless of severity of disease as assessed by staging according to Hoehn and Yahr. With greater severity, free recall was impaired and subjects required the cues to recall the items. Performance in the Letter Sorting Test and the semantic fluency task declined with increasing Hoehn and Yahr stage, also. We conclude that cognitive deficits are frequent in PD. Further analyses reveal that even in selected screening tests (e.g. semantic fluency) a significant impairment with increasing disease severity (Hoehn and Yahr stage) as opposed to disease duration alone can be demonstrated.

[Vascular parkinsonian syndrome]. / Das vaskuläre Parkinson-Syndrom.

The present review shows that vascular parkinsonian syndrome (VPS) fulfilling stringent diagnostic criteria for parkinsonism is a rare disease that cannot always be distinguished from neurodegenerative parkinsonism on clinical grounds. Thus VPS needs to be differentiated from other disturbances, which have distinct phenomenological and therapeutical features including isolated gait disturbances associated with subcortical arteriosclerotic encephalopathy and neurodegenerative parkinsonism complicated by comorbid vascular encephalopathy. Acute or subacute VPS is usually caused by contralateral infarctions involving the external globus pallidus, ventrolateral thalamus, and, less often, the substantia nigra. Chronic VPS with insidious onset is related to bilateral subcortical infarctions affecting thalamocortical projections. Differentiation from degenerative parkinsonism is difficult in cases of VPS that display a progressive course and response to levodopa.

The DONPAD-study--treatment of dementia in patients with Parkinson's disease with donepezil.

Inhibition of acetylcholinesterase improves symptoms of dementia in patients with Parkinson's disease (PD). Dementia in PD has a cumulative incidence of up to 80% and is mainly caused by a distinct cholinergic deficit. Objectives of this investigator initiated multicenter open label trial were to confirm the efficacy of donepezil in the treatment of dementia in PD patients and to investigate the tolerability and safety of donepezil. The Mini Mental State Examination (MMSE)-score significantly increased in patients, who finished the trial. A detailed analysis of the various items of the MMSE revealed, that only task performance of orientation and recall significantly improved. Scores of the short syndrome test and the Clinical Global Impression Scale improved, motor impairment did not increase. Only 14 out of 24 PD patients finished the trial due to predominant onset of vomiting, nausea, dizziness and confusion. This may result from the titration regime of donepezil, that allows only 5 and 10 mg dosages. Participants with premature study termination had a significant longer duration of PD, less motivation and sleep disturbances at night. Treatment with donepezil was only effective in PD patients with dementia, who experience nearly no side effects from the drug.

[Dysequilibrium in idiopathic Parkinson disease. The effect of cerebrovascular comorbidity]. / Gleichgewichtsstörungen bei idiopathischer Parkinson-Erkrankung. Der Einfluss zerebrovaskulärer Komorbidität.

Disturbance of balance in idiopathic Parkinson's disease (IPD) has a significant effect on disability. Yet the underlying mechanisms and the contribution of age-associated comorbidity to dysequilibrium are unclear. In this study, static posturography was performed in 30 healthy controls and 40 patients with IPD. Comparison of sway during quiet stance did not show significant differences between patients and controls. Multiple linear regression analysis was used to identify factors responsible for the considerable interindividual variance in patients. Results of the pull test, CT-verified cerebral microangiopathy, dementia, and age were assessed, but only cerebrovascular comorbidity contributed significantly to variance. Apart from increased sway, patients with coinciding cerebral microangiopathy (n = 20) more frequently had a history of falls or pathological responses in the pull test. The present results suggest that cerebrovascular comorbidity enhances dysequilibrium in IPD. Pathological sway in IPD can indicate comorbidity and may have implications for further diagnostics.

The double par locus of virulence factor pB171: DNA segregation is correlated with oscillation of ParA.

Prokaryotic plasmids and chromosomes encode partitioning (par) loci that segregate DNA to daughter cells before cell division. Recent database analyses showed that almost all known par loci encode an ATPase and a DNA-binding protein, and one or more cis-acting regions where the proteins act. All par-encoded ATPases belong to one of two protein superfamilies, Walker-type and actin-like ATPases. This property was recently used to divide par loci into Types I and II loci. We show here that the Escherichia coli virulence factor pB171 encodes a double par locus that consists of one Type I and one Type II locus. Separately, each locus stabilized a test-plasmid efficiently. Together, the two loci mediated even more efficient plasmid stabilization. The par loci have a unique genetic organization in that they share a common central region at which the two different DNA-binding proteins probably act. Interestingly, a fusion protein consisting of the Walker-type ParA ATPase and Gfp was functional and oscillated in nucleoid regions on a time scale of minutes. ParA-green fluorescent protein (Gfp) oscillation depended on both ParB and parC but was independent of minCDE. Point mutations in the Walker A box motif simultaneously abolished plasmid stabilization and ParA-Gfp oscillation. These observations raise the possibility that ParA oscillation is prerequisite for active plasmid segregation.

Rhythmic feet movements while falling asleep.

During the wake-sleep transition and sleep, diverse motor phenomena such as hypnagogic foot tremor may occur in the lower extremities. We investigated the relevance of this phenomenon in 375 consecutive subjects examined polysomnographically in a sleep disorders center. Rhythmic feet movements while falling asleep (RFM) were found in 28 subjects (7.5%). RFM occurred mostly as single, short series with a duration of between 10 and 15 seconds. They had a high night-to-night variability and were detected as rhythmic, oscillating movements of the whole foot or toes. Surface electromyographic (EMG) recordings displayed series of repetitive phasic bursts with a periodicity mostly between 1 and 2 per second. Single EMG burst duration varied between 300 and 700 msec. RFM at highest intensity occurred during presleep wakefulness, and usually persisted in sleep stages 1 and 2. RFM did not have a major sleep-disturbing effect in any of the affected subjects. Due to its high prevalence and the lack of a major sleep-disturbing effect, short series of RFM could be considered a quasiphysiological phenomenon. However, in more severe forms of RFM with evidence of a sleep-disturbing effect, RFM should be considered abnormal.

Dynamic balance function in phasic cervical dystonia following Botulinum toxin therapy.

Previous research by our group revealed normal dynamic balance function in pure tonic cervical dystonia (CD) with impaired equilibrium in phasic CD patients investigated at least 3 months following Botulinum toxin (BtxA) treatment. The current study was performed to determine whether impaired dynamic equilibrium in phasic CD is influenced by symptomatic treatment with BtxA. Dynamic balance was tested in 20 patients with phasic CD on a dynamic platform with a cylindrical curved base (stabilometer) 4 weeks following BtxA treatment. Balance was assessed by the linear displacement of the platform and the maximum amplitude of platform displacement with open and closed eyes and compared with pre-BtxA data. Despite a clinically significant BtxA-induced reduction of phasic head movements, none of the platform measures improved significantly. In addition, there was no correlation between the BtxA-induced clinical improvement and changes in any of the dynamic balance measures pre- vs. post-BtxA. In conclusion, the persistent dynamic balance impairment after effective BtxA therapy may indicate that disequilibrium in phasic CD does not simply reflect disturbed vestibular input from repetitive head oscillations, but argues in favour of different sensorimotor processing in tonic and phasic CD.

Clinical characteristics of the geste antagoniste in cervical dystonia.

The geste antagoniste (moving an arm to the face or head) is a well-known clinical feature in cervical dystonia (CD) to alleviate the abnormal posture. The clinical phenomenology of these manoeuvres has not so far been assessed systematically. Fifty patients with idiopathic CD aware of at least one geste antagoniste (60% women, mean age at onset 44.1 years, mean disease duration 7.5 years) were subjected to a standardized investigation including a semiquantitative clinical rating scale and polymyographic recordings of six cervical muscles. Twenty-seven patients (54%) demonstrated more than one geste antagoniste (range 2-5). A clinically significant (> or = 30%) reduction of head deviation was observed in 41 patients (82 %). Dystonic head posture improved by a mean of 60 % along all planes by the geste manoeuvre with a complete cessation of head oscillations in nine of 33 patients (27 %) with phasic CD. No significant laterality of the "geste-arm" or the facial target area was found. The duration of geste-effects depended significantly on disease duration and determined the patient's self-rating of the benefit of the manoeuvre. EMG-polygraphy revealed two types of geste-induced polymyographic changes: a decrease in recruitment density and amplitude in at least one dystonic muscle (66%), and an increased tonic muscle activation in the remaining patients. The remarkable efficacy of the geste antagoniste and the considerable variety in performance, duration, and EMG-pattern of these manoeuvres warrant further investigation of the therapeutic use of sensorimotor stimulation, in particular for those CD patients who experience limited or no effect from botulinum toxin therapy.

Sudden daytime sleep onset in Parkinson's disease: polysomnographic recordings.

Sleep attacks in Parkinson's disease are controversially discussed. This paper describes a patient with Parkinson's disease suffering from sudden, irresistible onset of sleep during daytime. Medication included levodopa, entacapone, budipine, and cabergoline. Introduction of entacapone was the last therapeutic action preceding onset of sleep events, suggesting increased bioavailabilty of levodopa to be provocative in this case. In contrast to previous cases, the sudden sleep events were witnessed by clinical staff members and documented by polysomnographic and video recordings. Polysomnography during these sleep events remarkably showed abrupt slowing of EEG-background activity and occurrence of slow eye movements and K-complexes within 10 seconds after stable wakefulness. Within 60 seconds, the polysomnographic pattern proceeded to stable sleep stage 2.