Chronic skin disease and levels of physical activity in 17 777 Spanish adults: a cross-sectional study.

BACKGROUND: To date there is limited literature on the prevalence of chronic skin conditions and its association with levels of physical activity (PA) in Spain. AIM: To determine the prevalence of chronic skin disease and to compare levels of PA between people with and without chronic skin disease in a large representative sample of Spanish adults aged 15-69 years. METHODS: Data from the Spanish National Health Survey 2017 were analysed. Chronic skin disease was assessed using a yes/no question. PA was measured using the short form of the International Physical Activity Questionnaire. Total PA metabolic equivalent of task min/week were calculated, and PA was included in the analyses as a continuous and a five-category variable. RESULTS: This cross-sectional study included 17 777 adult participants (52.0% women; mean ± SD age 45.8 ± 14.1 years), of whom 940 (5.3%) had chronic skin disease. After adjusting for several potential confounders, there was a negative association between chronic skin disease and PA (OR = 0.87, 95% CI 0.76-1.00, P = 0.05), which was significant for men (OR = 0.76, 95% CI 0.62-0.93, P = 0.01) but not for women (OR = 0.97, 95% CI 0.81-1.16, P = 0.72). CONCLUSIONS: In this large representative sample of Spanish adults, the prevalence of chronic skin disease was low. Levels of PA were lower in men with than in men without chronic skin conditions, but this association was not seen in women.

[Pathophysiology of tremor]. / Pathophysiologie des Tremors.

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.

Clinical value of R-spondins in triple-negative and metaplastic breast cancers.

BACKGROUND: RSPO ligands, activators of the Wnt/ß-catenin pathway, are overexpressed in different cancers. The objective of this study was to investigate the role of RSPOs in breast cancer (BC). METHODS: Expression of RSPO and markers of various cancer pathways were measured in breast tumours and cell lines by qRT-PCR. The effect of RSPO on the Wnt/ß-catenin pathway activity was determined by luciferase assay, western blotting, and qRT-PCR. The effect of RSPO2 inhibition on proliferation was determined by using RSPO2 siRNAs. The effect of IWR-1, an inhibitor of the Wnt/ß-catenin pathway, was examined on the growth of an RSPO2-positive patient-derived xenograft (PDX) model of metaplastic triple-negative BC. RESULTS: We detected RSPO2 and RSPO4 overexpression levels in BC, particularly in triple-negative BC (TNBC), metaplastic BC, and triple-negative cell lines. Various mechanisms could account for this overexpression: presence of fusion transcripts involving RSPO, and amplification or hypomethylation of RSPO genes. Patients with RSPO2-overexpressing tumours have a poorer metastasis-free survival (P=3.6 × 10-4). RSPO2 and RSPO4 stimulate Wnt/ß-catenin pathway activity. Inhibition of RSPO expression in a TN cell line inhibits cell growth, and IWR-1 significantly inhibits the growth of an RSPO2-overexpressing PDX. CONCLUSIONS: RSPO overexpression could therefore be a new prognostic biomarker and therapeutic target for TNBC.

Successive motor nerve blocks to identify the muscles causing a spasticity pattern: example of the arm flexion pattern.

Botulinum Toxin A has been the main treatment for spasticity since the beginning of the 1990s. Surprisingly, there is still no consensus regarding injection parameters or, importantly, how to determine which muscles to target to improve specific functions. The aim of this study was to develop a systematic approach to determine this, using the example of the arm flexion pattern. We first determined anatomical landmarks for selective motor block of the brachialis nerve, using 20 forearms from 10 fresh cadavers in Ecole Européenne de Chirurgie and a university-based dissection centre, Paris, France. We then carried out selective blocks of the motor nerves to the brachialis, brachioradialis and biceps brachii in patients with stroke with an arm flexion pattern, in a University Rehabilitation Hospital, Garches, France. We measured: the resting angle of the elbow angle in standing (manual goniometer), active and passive range of extension, and spasticity using the Held and Tardieu and the Modified Ashworth scales. Range of passive elbow extension was also measured with the shoulder in 90° of flexion. The resting angle of the elbow in standing decreased by 35.0° (from 87.6 ± 23.7 to 52.6 ± 24.2°) with inhibition of brachialis, by a further 3.9° (from 52.6 ± 24.2 to 48.7 ± 23.7°) with inhibition of brachioradialis and a further 14.5° (from 48.7 ± 23.7to 34.2 ± 20.7°) with inhibition of biceps brachii. These results were consistent with the clinical evaluation of passive elbow range of motion with the shoulder at 90°. Sequential blocking of the nerves to the three main elbow flexors revealed that the muscle that limited elbow extension the most, was brachialis. This muscle should be the main target to improve the arm flexion pattern. These results show that it is important not simply to inject the most superficial or powerful muscles to treat a spastic deformity. A comprehensive assessment is required. The strategy proposed in this paper should increase the effectiveness of botulinum toxin injections by ensuring that the relevant muscles are targeted.

Neurostimulation for Parkinson's disease with early motor complications.

BACKGROUND: Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease. METHODS: In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinson's Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinson's Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia. RESULTS: For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group. CONCLUSIONS: Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.).

ATM has a major role in the double-strand break repair pathway dysregulation in sporadic breast carcinomas and is an independent prognostic marker at both mRNA and protein levels.

BACKGROUND: Ataxia telangiectasia mutated (ATM) is a kinase that has a central role in the maintenance of genomic integrity by activating cell cycle checkpoints and promoting repair of DNA double-strand breaks (DSB). In breast cancer, a low level of ATM was correlated with poor outcome; however, the molecular mechanism of this downregulation is still unclear. METHODS: We used qRT-PCR assay to quantify mRNA levels of ATM gene in 454 breast tumours from patients with known clinical/pathological status and outcome; reverse phase protein arrays (RPPA) were used to assess the levels of ATM and 14 proteins in 233 breast tumours. RESULTS: ATM mRNA was associated with poor metastasis-free survival (MFS) (P=0.00012) on univariate analysis. ATM mRNA and protein levels were positively correlated (P=0.00040). A low level of ATM protein was correlated with poorer MFS (P=0.000025). ATM expression at mRNA or protein levels are independent prognostic factors on multivariate analysis (P=0.00046 and P=0.00037, respectively). The ATM protein level was positively correlated with the levels of six proteins of the DSB repair pathway: H2AX (P<0.0000001), XRCC5 (P<0.0000001), NBN (P<0.0000001), Mre11 (P=0.0000029), Rad50 (P=0.0064), and TP53BP1 (P=0.026), but not with proteins involved in other pathways that are altered in cancer. Low expression of ATM protein was significantly associated with high miR-203 expression (P=0.011). CONCLUSION: We confirmed that ATM expression is an independent prognostic marker at both RNA and protein levels. We showed that alteration of ATM is involved in dysregulation of the DSB repair pathway. Finally, miR-203 may be responsible for downregulation of ATM in breast cancers.

Patients with manifest hepatic encephalopathy can reveal impaired thermal perception.

OBJECTIVES: Previous evoked potential studies indicated central impairments of somatosensory function in patients suffering from hepatic encephalopathy (HE). The aim of this study was to quantify the somatosensory perception in patients with minimal and overt HE. MATERIALS AND METHODS: Forty-two patients with liver cirrhosis and HE up to grade 2 and 12 age-matched healthy controls underwent a comprehensive graduation of HE including the West Haven criteria, the critical flicker frequency (CFF), and neuropsychometric testing. Quantitative sensory testing, standardized by the German Research Network on Neuropathic Pain, was performed on both hands. RESULTS: Pain and mechanical detection thresholds were unchanged in HE. Tests of thermal processing revealed that patients with HE of grade 2 perceive cold at lower temperatures (cold detection threshold) and need a higher temperature difference to distinguish between warm and cold (thermal sensory limen). These impairments correlated with the CFF. A correction for attention deficits by performing partial correlations using neuropsychometric test results canceled these correlations. CONCLUSIONS: The present findings demonstrate an impairment of temperature perception in HE. The extent of this impairment correlates with HE severity as quantified by the CFF. The attenuation of the correlations after correction for attention deficits suggests a strong role of attention deficits for the impaired thermal perception. Thus, it provides initial evidence for a central impairment of thermal processing in HE due to alterations in high-level processes rather than due to peripheral neuropathic processes, which are a frequent complication in patients with liver cirrhosis.

Beliefs relating to recurrence of heterotopic ossification following excision in patients with spinal cord injury: a review.

STUDY DESIGN: Review of the literature. OBJECTIVES: It is widely believed that the timing of surgery and the size of the initial Neurological Heterotopic Ossification (NHO) affect the recurrence risk of NHO after SCI. A large number of studies were published in the 80s and the 90s, mostly of poor quality despite the fact that they were carried out by experienced surgical teams. The aim of this study was to suggest recommendations relating to the timing of excision of heterotopic ossification after SCI following the analysis of a recent review of the literature. SETTING: France. METHODS: A systematic literature search was performed in the PubMed Embase from January 2002 until June 2014 using the MESH headings 'spinal cord injury', 'paraplegia', 'heterotopic ossification' and 'surgery'. Results were compared with results from epidemiological studies based on the BANKHO database (patients who underwent surgery for troublesome HO after central neurological system (CNS) lesions in our center (357 patients, 539 surgeries)). RESULTS: Few studies were found in the literature, results were sometimes contradictory and practices heterogeneous. Results from the BANKHO database showed that troublesome recurrence of NHO was not associated with 'early' surgery (before 6 months), and no association was found between recurrence and the size of the NHO around the joint (Brooker status). CONCLUSION: We suggest that surgical excision of the NHO should be carried out when it begins to be troublesome, as soon as comorbid factors are under control and the HO is sufficiently constituted for excision.

Cortical activation associated with asterixis in manifest hepatic encephalopathy.

OBJECTIVES: Severe hepatic encephalopathy gives rise to asterixis, a striking motor symptom also called flapping tremor, which is characterized by a sudden ceasing of muscle tone in all muscles of a limb. In this study, we aimed at scrutinizing the cortical activation associated with asterixis and unraveling the underlying pathophysiological mechanisms. MATERIAL AND METHODS: We recorded simultaneously neural activity with magnetoencephalography (MEG) and muscle activity with surface EMG in nine patients with manifest hepatic encephalopathy showing asterixis. Asterixis events were detected semiautomatically and served as triggers for averaging MEG signals. Evoked responses averaged time-locked to asterixis events were subjected to equivalent current dipole (ECD) modeling. Additionally, we localized the strongest cortico-muscular coherence in the frequency of the co-occurring tremulousness. RESULTS: Evoked fields averaged time-locked to asterixis events were best explained by a single dipolar source in the contralateral primary motor cortex (M1, Talairach coordinates of mean localization: -40, -20, and 64; Brodmann area 4). This dipole showed a twofold field reversal, that is biphasic wave, with frontal dipole orientation at 49 ms before flap onset and 99 ms after flap onset. Conversely, two maxima with occipital dipole orientation were observed 2 ms and 160 ms after flap onset. Cortico-muscular coherence for the tremulousness was likewise localized in the contralateral M1 confirming earlier findings in the present patient cohort. CONCLUSIONS: Our results reveal an involvement of M1 in the generation of asterixis. As also tremulousness, also called mini-asterixis, was shown to originate in M1, asterixis and mini-asterixis may share common pathophysiological mechanisms.

Differential modulation of STN-cortical and cortico-muscular coherence by movement and levodopa in Parkinson's disease.

Previous research suggests that oscillatory coupling between cortex, basal ganglia and muscles plays an important role in motor behavior. Furthermore, there is evidence that oscillatory coupling is altered in patients with movement disorders such as Parkinson's disease (PD). In this study, we performed simultaneous magnetoencephalography (MEG), local field potential (LFP) and electromyogram (EMG) recordings in PD patients selected for therapeutic subthalamic nucleus (STN) stimulation. Patients were recorded (i) after withdrawal of anti-parkinsonian medication (OFF) and (ii) after levodopa administration (ON). We analyzed STN-cortical and cortico-muscular coherence during static forearm contraction and repetitive hand movement in order to evaluate modulations of coherence by movement and medication. Based on previous results from studies investigating resting state coherence in PD patients, we selected primary motor cortex (M1) and superior temporal gyrus (STG) as regions of interest. We found beta coherence between M1 and STN to be suppressed by administration of levodopa. M1-muscular coherence was strongly reduced in the alpha and beta band during repetitive movement compared to static contraction, but was unaffected by administration of levodopa. Strong STG-STN but not STG-muscular coherence could be observed in the alpha band. Coherence with STG was modulated neither by movement nor by medication. Finally, we found both M1-STN and M1-muscular beta coherence to be negatively correlated with UPDRS akinesia and rigidity sub-scores in the OFF state. The present study provides new insights into the functional roles of STN-cortical and cortico-muscular coherence and their relationship to PD symptoms. The results indicate that STN-cortical and cortico-muscular coupling are correlated, but can be modulated independently. Moreover, they show differences in their frequency-specific topography. We conclude that they represent partly independent sub-loops within the motor system. Given their negative correlation with akinesia, neither can be considered "antikinetic".

[Characteristics and prevention among patients with stroke: a study of 36,844 patients hospitalized in France]. / Caractéristiques et traitements des assurés du régime général hospitalisés pour accident vasculaire cérébral au cours du premier semestre 2008.

INTRODUCTION: This study evaluates comorbidities, primary and secondary drug prevention and two years survival among patients hospitalized for stroke during the first half of 2008. METHODS: First hospitalization with stroke diagnosis was identified by using the national hospital discharge database and linked to the reimbursement database of the beneficiaries covered by the general health insurance scheme (74% of the 64 million population). A medication was considered to be used when there were more than two reimbursements over the 6 months following or preceding hospitalization. RESULTS: Among the 36,844 patients with stroke, 31.6% had a main diagnosis of transient ischemic attack (TIA), 53.6% a cerebral infarct (CI) and 14.8% a cerebral hemorrhage (CH). For the 8429 patients aged less than 60 years, high frequency of low-income and full health insurance coverage (11% of the covered population) was found for CI (17.6%) and CH (24.6%). Specific refund for invalidating stroke before hospitalization was found for 16% of patients with CI and 10.5% of those with CH. During the two previous years, around 7% of all patients were hospitalized for stroke, 30% for arterial hypertension, 13% for cardiac electric disorders, 10% for coronary disease and 12% for diabetes. Death rates one month after hospitalization were 11.3% for CI and 33.8% for CH, and two years after 22.5% for CI, 43% for CH and 7.7% for TIA. At least one antihypertensive drug treatment was found for 55.2% of patients with a TIA before hospitalization and 62.9% after and respectively 59.4% and 65.8% for CI and 51.1% and 57.7% for CH. Before hospitalization, beta-blocker was the most frequent antihypertensive class (21 to 25.6% according to stroke type). After hospitalization, frequency increased for angiotensin-converting enzyme inhibitors among CI patients (31% vs. 18.7%) and calcium-channel blockers among CH patients (27.1% vs. 13.7%). Antiplatelet drugs were used by 58% of the patients with CI after hospitalization (27.8% before). An anticoagulant drug was present for 74.8% of patients with CI, 69.5% for TIA and 19.2% for CH. Among patients with ischemic stroke, half of them had a lipid-lowering drug after hospitalization. A combination of antihypertensive, anticoagulant and lipid lowering drugs was found for 32.9% of patients with a TIA, 39.9% for CI and 7.6% for CH after hospitalization. CONCLUSION: These patients presented frequently a history of stroke and comorbidities and their level of secondary prevention must be improved.

Motor-cortical oscillations in early stages of Parkinson's disease.

Pathophysiological changes in basal ganglia-thalamo-cortical circuits are well established in idiopathic Parkinson's disease (PD). However, it remains open whether such alterations already occur at early stages representing a characteristic neurophysiological marker of PD. Therefore, the present study aims at elucidating changes of synchronised oscillatory activity in early PD patients. In this study, we performed whole-head magnetoencephalography (MEG) in a resting condition and during steady state contraction of the more severely affected forearm in 10 drug­naive, de novo patients, in 10 early-stage patients with chronic medication and in 10 age-matched control subjects. While cortico-muscular coherence (CMC) did not differ between groups, patients showed increased sensori-motor cortical power at beta frequency (13­30 Hz) during rest as well as during isometric contraction compared to controls. In healthy control subjects the power of the contralateral hemisphere was significantly suppressed during isometric contraction. By contrast, both hemispheres were activated equally strongly in de novo patients. In medicated patients, the pattern was found to be reversed. Contralateral beta power was significantly correlated with motor impairment during isometric contraction but not during rest. The present results suggest that the reduced ability of the primary motor cortex to disengage from increased beta band oscillations during the execution of movements is an early marker of PD.

[Deep brain stimulation - expectations and doubts. A nationwide questionnaire study of patients with Parkinson's disease and their family members]. / Tiefe Hirnstimulation - Erwartungen und Bedenken. Bundesweite Fragebogenstudie mit Parkinson-Patienten und deren Angehörigen.

BACKGROUND: The aim of this questionnaire-based study was to determine the decision-making motives from Parkinson's patients and their family members for deep brain stimulation (DBS), which are crucial for the attitude towards this therapy and which should be considered during the clinical interview. MATERIAL AND METHODS: The questionnaire was sent out nationwide to members of the German Parkinson Association. Patient and family specific data as well as information sources, doubts and expectations with respect to DBS were assessed. RESULTS: A total of 582 patients and 476 family members answered the questionnaire, revealing that 96% of the patients and 91% of the family members already possessed information regarding DBS. While a large proportion of interviewees had specific expectations concerning DBS, more than two thirds expressed concerns regarding DBS; the most frequent with respect to intraoperative complications and stimulation-induced worsening of symptoms. The quantity of realistic patients and family expectations significantly correlated with a positive evaluation of DBS and doubts as well as unrealistic expectations of family members correlated with a negative attitude towards the operation. CONCLUSIONS: The findings suggest that patients and their relatives organized in support groups indeed possess detailed information regarding DBS. However, for the acceptance of the treatment a timely elucidation about DBS as well as responding to the individual concerns by the consulting physician is essential.

Clinical assessment of upper limb hypertonia in central neurological diseases.

The clinical assessment of a hypertonic upper limb in central neurological diseases should be analytical, systematic (shoulder, elbow, extrinsic and intrinsic hand) and focused on the patient or caregiver's wishes and on the expected objectives (esthetic, hygienic, functional). Nerve blocks can help to separate mixed contractures, show the existence of antagonist muscles or find a starter muscle in dystonia patterns. The etiology (especially the evolving nature of the disease), general health condition (especially in older adults), associated deficits (cerebellar, sensory and cognitive; hemineglect) are considered together to arrive at a contract with patients and/or caregivers.

Distinct oscillatory STN-cortical loops revealed by simultaneous MEG and local field potential recordings in patients with Parkinson's disease.

Neuronal oscillations are assumed to play a pivotal role in the pathophysiology of Parkinson's disease (PD). Neurons in the subthalamic nucleus (STN) generate oscillations which are coupled to rhythmic population activity both in other basal ganglia nuclei and cortical areas. In order to localize these cortical areas, we recorded local field potentials (LFPs) and magnetoencephalography (MEG) simultaneously in PD patients undergoing surgery for deep brain stimulation (DBS). Patients were withdrawn from antiparkinsonian medication and recorded at rest. We scanned the entire brain for oscillations coherent with LFPs recorded from the STN with a frequency domain beamformer. Coherent activity in the low (12-20 Hz) and high (20-35 Hz) beta range was found in the ipsilateral sensorimotor and the premotor cortex. Coherence in the alpha range (7-12 Hz) was observed at various locations in the ipsilateral temporal lobe. In a subset of subjects, the superior temporal gyrus consistently showed coherent alpha oscillations. Our findings provide new insights into patterns of frequency-specific functional connectivity between basal ganglia and cortex and suggest that simultaneous inter-regional interactions may be segregated in the frequency domain. Furthermore, they demonstrate that simultaneous MEG-LFP recordings are a powerful tool to study interactions between brain areas in PD patients undergoing surgery for DBS.

Dystonia in neurodegeneration with brain iron accumulation: outcome of bilateral pallidal stimulation.

Neurodegeneration with brain iron accumulation encompasses a heterogeneous group of rare neurodegenerative disorders that are characterized by iron accumulation in the brain. Severe generalized dystonia is frequently a prominent symptom and can be very disabling, causing gait impairment, difficulty with speech and swallowing, pain and respiratory distress. Several case reports and one case series have been published concerning therapeutic outcome of pallidal deep brain stimulation in dystonia caused by neurodegeneration with brain iron degeneration, reporting mostly favourable outcomes. However, with case studies, there may be a reporting bias towards favourable outcome. Thus, we undertook this multi-centre retrospective study to gather worldwide experiences with bilateral pallidal deep brain stimulation in patients with neurodegeneration with brain iron accumulation. A total of 16 centres contributed 23 patients with confirmed neurodegeneration with brain iron accumulation and bilateral pallidal deep brain stimulation. Patient details including gender, age at onset, age at operation, genetic status, magnetic resonance imaging status, history and clinical findings were requested. Data on severity of dystonia (Burke Fahn Marsden Dystonia Rating Scale-Motor Scale, Barry Albright Dystonia Scale), disability (Burke Fahn Marsden Dystonia Rating Scale-Disability Scale), quality of life (subjective global rating from 1 to 10 obtained retrospectively from patient and caregiver) as well as data on supportive therapy, concurrent pharmacotherapy, stimulation settings, adverse events and side effects were collected. Data were collected once preoperatively and at 2-6 and 9-15 months postoperatively. The primary outcome measure was change in severity of dystonia. The mean improvement in severity of dystonia was 28.5% at 2-6 months and 25.7% at 9-15 months. At 9-15 months postoperatively, 66.7% of patients showed an improvement of 20% or more in severity of dystonia, and 31.3% showed an improvement of 20% or more in disability. Global quality of life ratings showed a median improvement of 83.3% at 9-15 months. Severity of dystonia preoperatively and disease duration predicted improvement in severity of dystonia at 2-6 months; this failed to reach significance at 9-15 months. The study confirms that dystonia in neurodegeneration with brain iron accumulation improves with bilateral pallidal deep brain stimulation, although this improvement is not as great as the benefit reported in patients with primary generalized dystonias or some other secondary dystonias. The patients with more severe dystonia seem to benefit more. A well-controlled, multi-centre prospective study is necessary to enable evidence-based therapeutic decisions and better predict therapeutic outcomes.

Efficacy and safety of NT 201 for upper limb spasticity of various etiologies--a randomized parallel-group study.

OBJECTIVE: To assess efficacy and safety of two dilutions of botulinum neurotoxin type A NT 201 (Xeomin®) in patients with upper limb spasticity of diverse etiology. METHODS: Changes in functional disability and muscle tone from baseline to week 4 after NT 201 treatment. RESULTS: One hundred ninety-two patients with stroke, brain injury, multiple sclerosis, or cerebral palsy were randomized to either 50 or 20 U/ml NT 201 dilutions. The maximum total NT 201 dose was 495 units. Four weeks post-injection, a ≥ 1-point reduction was observed on the Disability Assessment Scale in 57.1%, and on the Ashworth scale in ≥ 62.2% of patients. The 20 U/ml NT 201 dilution was non-inferior to the 50 U/ml NT 201 dilution. Global improvement was rated high by patients (80.2%) and investigators (89.0%). CONCLUSIONS: NT 201 improved functional disability and muscle tone and was well tolerated in patients with upper limb spasticity of diverse etiology in both dilutions.

Motor impairment in liver cirrhosis without and with minimal hepatic encephalopathy.

AIM: Manifest hepatic encephalopathy (HE) goes along with motor symptoms such as ataxia, mini-asterixis, and asterixis. The relevance of motor impairments in cirrhotics without and with minimal HE (mHE) is still a matter of debate. PATIENTS AND METHODS: We tested three different groups of patients with liver cirrhosis: no signs of HE (HE 0), mHE, and manifest HE grade 1 according to the West Haven criteria (HE 1). All patients (n = 24) and 11 healthy control subjects were neuropsychometrically tested including critical flicker frequency (CFF), a reliable measure for HE. Motor abilities were assessed using Fahn Tremor Scale and International Ataxia Rating Scale. Fastest alternating index finger movements were analyzed for frequency and amplitude. RESULTS: Statistical analyses showed an effect of HE grade on tremor and ataxia (P < 0.01). Additionally, both ratings yielded strong negative correlation with CFF (P < 0.01, R = -0.5). Analysis of finger movements revealed an effect of HE grade on movement frequency (P < 0.03). Moreover, decreasing movement frequency and increasing movement amplitude parallel decreasing CFF (P < 0.01, R = 0.6). CONCLUSION: Our results indicate that ataxia, tremor, and slowing of finger movements are early markers for cerebral dysfunction in HE patients even prior to neuropsychometric alterations becoming detectable.

[Early deep brain stimulation for Parkinson's disease]. / Brauchen wir die frühzeitige tiefe Hirnstimulation beim Morbus Parkinson?

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a powerful treatment for advanced Parkinson's disease with levodopa-induced motor complications. Randomized controlled studies have shown that motor fluctuations and quality of life are significantly more improved by STN-DBS than by best medical treatment. The main delay before neurosurgery is currently 14 years after diagnosis. Clinical pilot data suggest that neurosurgery performed already with beginning motor fluctuations and an average disease duration of 7 years may lead to earlier improvement of motor deficits and quality of life, thus preventing disease-related psycho-social decline, and extending the period of beneficial effects of STN-DBS. Results of an ongoing multicenter trial (EARLYSTIM) comparing the effects of STN-DBS and best medical treatment on motor symptoms, quality of life, and psycho-social adaptation will be available in 2 years time and will clarify whether or not early STN-DBS is superior to best medical treatment.