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Introduction: Herbal products are beneficial compounds with many applications in human life. In this study the chemical composition and cytotoxic activity of the essential oil of the aerial parts of Dorema aucheri were assessed. Methods: The essential oil was extracted by hydrodistillation after drying the aerial parts of D. aucheri, collected from the mountains around Yasuj city in the South-West of Iran. The oil composition was determined by GC/MS. To evaluate in vitro cytotoxic activity, the apoptotic effects of the essential oil were investigated against SW48 and SW1116 colorectal cancer cell lines by (3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium) bromide (MTT) assay and flow cytometry. Results: The essential oil yield was obtained 0.02% (W/W). Twenty-five compounds were identified in the oil, and the main constituents were caryophyllene (E) (31.29%), Phytol (14.92%), gurjunene (β-) (9.84%), 3,7,11,15-tetramethyl-2-hexadecen-1-ol (8.7%), and n-hexadecanoic acid (8.09%). The MTT assay showed that the IC50 values of the essential oil for SW48 and SW1116 cell lines were 1.4 and 1.2 mg/mL, respectively. The results of flow cytometry showed that the essential oil significantly increased the apoptosis in SW48 cell line compared with the vincristine (P < 0.05). It also increased the apoptosis in SW1116 cells compared with the vincristine, but this difference is not significant. Conclusion: The essential oil of D. aucheri consisted of high amounts of caryophyllene and showed significant cytotoxic effects against SW48 and SW1116 cancerous cell lines.

Precise control of movement and timing play a key role in musical performance. This motor skill requires coordination across multiple joints, muscles, and limbs, which is acquired through extensive musical training from childhood on. Thus, making music can be a strong driver for neuroplasticity. We here present the rare case of a professional french horn player with a congenital bilateral amelia of the upper limbs. We were able to show a unique cerebral and cerebellar somatotopic representation of his toe and feet, that do not follow the characteristic patterns of contralateral cortical and ipsilateral cerebellar layout. Although being a professional horn player who trained his embouchure muscles, including tongue, pharyngeal, and facial muscle usage excessively, there were no obvious signs for an expanded somatosensory representation in this part of the classic homunculus. Compared to the literature and in contrast to control subjects, the musicians’ foot movement-related activations occurred in cerebellar areas that are typically more related to hand than to foot activation.

Background: Acute Flaccid Paralysis(AFP) is a clinical syndrome characterized by acute progressive weakness in limbs and respiratory and swallowing muscles. Etiologies of AFP mostly include infections in anterior horn cells of the spinal cord, Guillain-Barre syndrome(GBS), transverse myelitis, viral myositis, myasthenia gravis and botulism. An accurate and early diagnosis of AFP is crucial. The aims of this study were to determine the main etiologies and characteristics of AFP in children and also design a diagnostic approach for AFP based on a hospital-based registry system.Method: This retrospective, cross-sectional study is a five-years survey, from 2011 to 2016 in Children’s Medical Center as the main children referral hospital in Iran. Totally 118 patients who had met AFP ICD-10- CM and inclusion criteria were included. All clinical and Paracinical data were collected based on a prepared questionnaire for the study.Result: The mean age of the patients was 6.09 ± 3.60 years old. The most frequent underlying etiologies were GBS, viral myositis and Vaccine-Associated Paralytic Poliomyelitis(VAPP) accounting for 67.8%, 15.3% and 5% of the patients, respectively. In terms of preceding clinical symptoms coryza, fever and gastrointestinal symptoms were more common. The most common neurologic presenting symptom was motor dysfunction. Cerebrospinal fluid analysis mainly indicated increase level of protein in favor of GBS. Elevated Creatine kinase level with the mean of 2184 IU/L has been reported in patients with viral myositis. Brain imaging principally revealed normal results and spinal MRI findings were compatible with the diagnoses of GBS and transvers myelitis. All stool sample results for polio virus detection were negative.Conclusion: In this study, we determined the etiologies of AFP in Iranian children referred to Children’s Medical Center. Guillain-Barre syndrome, viral myositis, transverse myelitis and VAPP were the most common etiologies. We also recommended a diagnostic approach for AFP in pediatric population regards to main etiologies in emergency room of a children referral hospital.

BackgroundAbout 6.2 million adults in Germany cannot read and write properly despite attending school for several years. They are considered to be functional illiterates (FI). Since the ability to read and write is crucial for being employed and socially accepted, we developed a special literacy training to overcome these deficits.MethodsIn this study, we investigate training-related changes in intrinsic functional connectivity (iFC) at rest in a group of 20 FI and 20 adult normal readers using resting state functional magnetic resonance imaging (rsfMRI). We used independent component analysis (ICA) to define different networks.ResultsBefore training, the between group analysis showed increased iFC in FI in a left-fronto-parietal network (LFPN; anterior insula, medial frontal cortex, lateral and frontal parietal regions) and in the Basal Ganglia network (BGN: thalamus, caudate, putamen, pallidum, amygdala, supplementary motor cortex and cingulate gyrus). Furthermore, the Visual Network-1 (VN1; temporal occipital fusiform gyrus, lateral occipital cortex, occipital pole, lingual gyrus, thalamus) showed decreased iFC in FI. After training the FI group showed reversal of the “hyperconnectivity” in middle frontal gyrus and in the frontal orbital cortex and between supramarginal gyrus and the BGN. Furthermore, functional connectivity increased in FI VN1 (lateral occipital cortex, insular cortex). These changes in connectivity correlated with gains in reading speed and spelling accuracy.ConclusionsThese findings show that poor reading and writing abilities are associated with abnormalities in iFC in several brain areas subserving cognitive processes important for reading. Intensive literacy training induces changes in the functional connectivity between and within neural networks important for literacy skills.

Abstract. Interpersonal and intrapersonal differences in brain responses to sexual stimuli have been linked with individuals’ testosterone levels. However, it remains unclear how hormones modulate brain functions underlying sexual arousal. In order to assess the effects of chronic hormonal treatment, we used functional magnetic resonance imaging in a group of female-to-male transsexuals before and during androgen therapy while they watched a set of pictures representing dressed or nude (erotic content) men or women (sex information). A broad network of cortical and subcortical regions were activated during the processing of erotic stimuli (nude vs. dressed), including the insula, amygdala, and hypothalamus. The insula activity in response to erotic male stimuli decreased over the initial 4 months of hormonal therapy. In the following 8 months, the insula response to erotic female stimuli increased. In other words, long-term androgen administration makes the brain more “male” by reducing the sexual arousal caused by male stimuli and amplifying that caused by female stimuli.

About 7.5million adults in Germany cannot read and write properly despite attending school for several years. They are considered to be functional illiterates. Since the ability to read and write is crucial for being employed and socially accepted, we developed a literacy training to overcome these deficits. In this study, we investigate the structural changes induced by the training. A group of 20 functional illiterates and 20 adult normal readers participated in the study. Group differences as well as intervention-related changes in gray (voxel-based morphometry, VBM) and white matter (Tract-Based Spatial Statistics, TBSS, applied to fractional anisotropy, FA, obtained with diffusion tensor imaging, DTI) were assessed in functional illiterates and normal reading controls. VBM analyses revealed decreased gray matter intensities in functional illiterates compared to normal readers before training in several reading-related brain regions such as the superior temporal gyrus, supramarginal gyrus, and angular gyrus. Using TBSS, functional illiterates showed reduced FA values in the genu of the corpus callosum. After training, both the gray matter intensities and FA values increased in functional illiterates and were no longer statistically different from controls' pre-test data. Moreover, the increase was positively correlated with reading and writing skills. The findings suggest that poor literacy skills are associated with several structural abnormalities in reading-related brain areas. In addition, we showed that while literacy skills of functional illiterates improved after training, the structural differences to controls disappeared.

Dopamine agonist (DA) medications commonly used to treat, or ‘normalise’, motor symptoms of Parkinson’s disease (PD) may lead to cognitive-neuropsychiatric side effects, such as increased impulsivity in decision-making. Subject-dependent variation in the neural response to dopamine modulation within cortico-basal ganglia circuitry is thought to play a key role in these latter, non-motor DA effects. This neuroimaging study combined resting-state functional magnetic resonance imaging (fMRI) with DA modification in patients with idiopathic PD, investigating whether brain ‘resting-state network’ (RSN) functional connectivity metrics identify disease-relevant effects of dopamine on systems-level neural processing. By comparing patients both ‘On’ and ‘Off’ their DA medications with age-matched, un-medicated healthy control subjects (HCs), we identified multiple non-normalising DA effects on frontal and basal ganglia RSN cortico-subcortical connectivity patterns in PD. Only a single isolated, potentially ‘normalising’, DA effect on RSN connectivity in sensori-motor systems was observed, within cerebro-cerebellar neurocircuitry. Impulsivity in reward-based decision-making was positively correlated with ventral striatal connectivity within basal ganglia circuitry in HCs, but not in PD patients. Overall, we provide brain systems-level evidence for anomalous DA effects in PD on large-scale networks supporting cognition and motivated behaviour. Moreover, findings suggest that dysfunctional striatal and basal ganglia signalling patterns in PD are compensated for by increased recruitment of other cortico-subcortical and cerebro-cerebellar systems.

Motor unit number estimation (MUNE) techniques such as motor unit number index (MUNIX) have been used to quantify lower motor neuron loss and disease progression in amyotrophic lateral sclerosis (ALS). We investigated the consistency of reproducibility of MUNIX in 30 ALS-patients during the course of the disorder.MUNIX was recorded in abductor pollicis brevis and tibialis anterior muscles bilaterally in ALS-patients by two measurements at the first and at one follow-up visit and once in healthy controls. Intra-rater reproducibility was evaluated by three statistical methods: interclass correlation coefficient (ICC), correlation coefficient analysis (CCA), and coefficient of variation (CV).We found significant correlation between the first and second measurement of MUNIX in all tested muscles and at the follow-up visit (r⩾0.891, p0.01) and good statistically significant reproducibility of MUNIX in all four measured muscles at the follow-up visit (ICC⩾0.946, p0.01). The CV of MUNIX at the follow-up visit ranged from 13.90% to 32.95%.This study shows good consistency of reproducibility of MUNIX in the course of ALS.This study suggests that MUNIX can be used to track the progression of the disorder both in clinical routine and in treatment trials.

In the last decade, several studies have investigated the neuroplastic changes induced by long-term musical training. Here we investigated structural brain differences in expert pianists compared to non-musician controls, as well as the effect of the age of onset (AoO) of piano playing. Differences with non-musicians and the effect of sensitive periods in musicians have been studied previously, but importantly, this is the first time in which the age of onset of music-training was assessed in a group of musicians playing the same instrument, while controlling for the amount of practice. We recruited a homogeneous group of expert pianists who differed in their AoO but not in their lifetime or present amount of training, and compared them to an age-matched group of non-musicians. A subset of the pianists also completed a scale-playing task in order to control for performance skill level differences. Voxel-based morphometry analysis was used to examine gray-matter differences at the whole-brain level. Pianists showed greater gray matter (GM) volume in bilateral putamen (extending also to hippocampus and amygdala), right thalamus, bilateral lingual gyri and left superior temporal gyrus, but a GM volume shrinkage in the right supramarginal, right superior temporal and right postcentral gyri, when compared to non-musician controls. These results reveal a complex pattern of plastic effects due to sustained musical training: a network involved in reinforcement learning showed increased GM volume, while areas related to sensorimotor control, auditory processing and score-reading presented a reduction in the volume of GM. Behaviorally, early-onset pianists showed higher temporal precision in their piano performance than late-onset pianists, especially in the left hand. Furthermore, early onset of piano playing was associated with smaller GM volume in the right putamen and better piano performance (mainly in the left hand). Our results, therefore, reveal for the first time in a single large dataset of healthy pianists the link between onset of musical practice, behavioral performance, and putaminal gray matter structure. In summary, skill-related plastic adaptations may include decreases and increases in GM volume, dependent on an optimization of the system caused by an early start of musical training. We believe our findings enrich the plasticity discourse and shed light on the neural basis of expert skill acquisition.

Excessive video gaming has a number of psychological and social consequences. In this study, we looked at possible changes in gray and white matter and asked whether these changes are correlated to psychological measures. Twentynine players of violent videogames (mean daily playing time 4.7 h) and age matched controls were subjected to a battery of questionnaires assessing aggression, empathy, hostility, internet addiction and psychological well-being. Diffusion tensor and 3D T1-weighted MR images were obtained to examine gray (via voxel-based morphometry) and white (via tract-based spatial statistics) matter changes. Widespread regions of decreased gray matter in the players were found but no region showed increased intensity of gray matter. Density of gray matter showed a negative correlation with the total length of playing in years in the right posterior cingulate gyrus, left pre- and postcentral gyrus, right thalamus, among others. Furthermore, fractional anisotropy, a marker for white matter structure, was decreased in the left and right cingulum in the players. Both, gray and white matter changes correlated with measures of aggression, hostility, self esteem, and the degree of internet addiction. This study thus shows profound changes of brain structure as a function of excessive playing of violent video games.

Die Frage inwieweit das Spielen von First-Person-Shootern (FPS) eine Wirkung auf reale aggressive Verhaltensweisen hat, ist noch nicht abschliesend geklart und weiter heftig umstritten. Inwiefern hierbei quantitative Aspekte einer exzessiven bzw. abhangigen FPS-Nutzung von Bedeutung sind, wurde bislang kaum untersucht. Die vorliegende Studie beschaftigt sich mit Abhangigkeitsaspekten einer Gruppe von Exzessivspielern und ihrem Zusammenhang mit Faktoren von Aggressivitat und Empathie. 25 junge Manner mit einem FPS-Konsum von mindestens 4 h/d fur die vorangegangen 2 Jahre wurden psychometrisch untersucht und mit einer im Hinblick auf Geschlecht, Alter und Schulbildung gleichsinnig verteilten Gruppe verglichen. Die durchschnittlich 23,5 Jahre alten Exzessivspieler spielen hauptsachlich Online-Spiele und weisen in der Internetsuchtskala (ISS) signifikant hohere Werte als die Vergleichsgruppe auf. Bei den Exzessivspielern korrelieren die ISS-Werte mit der Globalskala des Kurzfragebogens fur Aggressionsfaktoren (K-FAF). Im Hinblick auf verschiedene erhobene Faktoren von Aggressivitat und Empathiefahigkeit zeigt sich ein uneinheitliches Bild, wobei sich fur die Exzessivspieler signifikant niedrigere Werte in der FAF-Subskala fur Aggressionshemmung und der Eysenck Empathieskala ergeben, die mit einander signifikant positiv korrelieren. Die 8 Exzessivspieler (32%), welche die Kriterien fur Internetabhangigkeit erfullen, zeigen signifikant starkere Auspragungen hinsichtlich spontaner Aggressivitat, Feindseligkeit und antisozialer Merkmale. Die Ergebnisse deuten darauf hin, dass online genutzte FPS ein Suchtpotenzial aufweisen. Nicht nur qualitative sondern auch quantitative Faktoren einer suchtartigen Nutzung gewalthaltiger Computerspiele im Hinblick auf Aggressivitat fordernde Aspekte durften in Forschung und Pravention starker zu berucksichtigen sein.

The steepness of the delay discounting function shows considerable interindividual differences. Moreover, faster devaluation of future rewards has been consistently observed in pathological gamblers (PGs). Here, we asked whether variability in delay discounting is at least partially driven by differences in the anatomy of gray and white matter. For 40 healthy young subjects (study 1) as well as 15 PG and 15 age-matched healthy controls (HCs, study 2), the individual discounting parameter k was obtained. Based on 3D T1-weighted high-resolution magnetic resonance scans and diffusion tensor imaging, we performed voxel-based morphometry and tract-based spatial statistics, respectively, to examine the relation of gray matter volume (GMV) and white matter properties (as indicated by fractional anisotropy, FA) to k. Healthy groups from both studies showed a negative correlation between k and FA for the superior longitudinal fascicle and inferior longitudinal fascicle, whereas a positive correlation was found in the PG group for the inferior longitudinal fascicle and left inferior fronto-occipital fascicle. The latter also was significantly different between HC and PG in the group statistics (albeit on the right side), thus suggesting that this is a significant structure for the development of pathological gambling. GMV of the right frontal orbital cortex, left insular cortex and right lateral occipital cortex showed a positive correlation to k HC (studies 1 and 2) and PG, whereas a negative correlation was found for the left frontal pole in all three groups. Group comparison of GMV (study 2) revealed a decrease in PG for several cortical and subcortical areas.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by muscular atrophy, spasticity, and bulbar signs caused by loss of upper and lower motor neurons. Evidence suggests that ALS additionally affects other brain areas including premotor cortex and supplementary motor area. Here, we studied movement execution and inhibition in ALS patients using a stop-signal paradigm and functional magnetic resonance imaging. Seventeen ALS patients and 17 age-matched healthy controls performed a stop-signal task that required responding with a button press to a right- or left-pointing black arrow (go-stimuli). In stop-trials, a red arrow (stop-stimulus) was presented shortly after the black arrow indicating to withhold the prepared movement. Patients had by trend higher reaction times in go-trials but did not differ significantly in their inhibition performance. Patients showed stronger inhibition-related activity in inferior, superior, and middle frontal gyri as well as in putamen and pallidum. Error-related activity, conversely, was found to be stronger in healthy controls, particularly in the insula bilaterally. Patients also showed increased activity in the motor cortex during button presses. The results provide evidence for altered prefrontal and subcortical networks underlying motor execution, motor inhibition, and error monitoring in ALS.

Background: Current changing lifestyles of Iranians, especially in childhood, may affect the risk of developing cardiovascular diseases. Objectives: The purpose of this study was to determine the effects of endurance, resistance, and combined training on cardiovascular risk factors in male obese children. Methods: Sixty male obese children (age 8 - 12 years, BMI between 30 - 35 kg and Z-score above +2) were chosen randomly divided into four groups of exercise training: group I, endurance exercise training (EET); group II, resistance exercise training (RET); group III, combined exercise training (CET); group IV, controls (C). Exercise training programs were performed for eight weeks, 4 sessions per week, with the same intensity and duration in all types of exercise training groups. Blood samples were collected 24 and 48 hours before and after exercise training, respectively. Data were obtained in all groups and analyzed by repeated measurement and one way ANOVA using SPSS software (version 21). Results: Results indicated that fasting glucose, BMI, TC, TG, LDL, VLDL, TC/HDL, and LDL/HDL ratio decreased significantly and HDL increased in three types of exercise training compared to the control group (P 0.05). Conclusions: The three types of exercise training, especially endurance training method, decrease the risk factors for occurrence of cardiovascular diseases and health complications related to obesity in inactive male obese children.

The use of violent video games has been often linked to increase of aggressive behaviour. According to the General Aggression Model, one of the central mechanisms for this aggressiveness inducing impact is an emotional desensitization process resulting from long lasting repeated violent game playing. This desensitization should evidence itself in a lack of empathy. Recent research has focused primarily on acute, short term impact of violent media use but only little is known about long term effects. In this study 15 excessive users of violent games and control subjects matched for age and education viewed pictures depicting emotional and neutral situations with and without social interaction while fMRI activations were obtained. While the typical pattern of activations for empathy and theory of mind networks was seen, both groups showed no differences in brain responses. We interpret our results as evidence against the desensitization hypothesis and suggest that the impact of violent media on emotional processing may be rather acute and short-lived.

IntroductionNatural speech perception relies on both, auditory and visual information. Both sensory channels provide redundant and complementary information, such that speech perception is enhanced in healthy subjects, when both information channels are present.ObjectivesPatients with schizophrenia have been reported to have problems regarding this audiovisual integration process, but little is known about which neural processes are altered.AimsIn this study we investigated functional connectivity of Broca’s area in patients with schizophrenia.MethodsFunctional magnetic resonance imaging (fMRI) was performed in 15 schizophrenia patients and 15 healthy controls to study functional connectivity of Broca’s area during perception of videos of bisyllabic German nouns, in which audio and video either matched (congruent condition) or die not match (incongruent; e.g. video = hotel, audio = island).ResultsThere were differences in connectivity between experimental groups and between conditions. Broca’s area of the patient group showed connections to more brain areas than the control group. This difference was more prominent in the incongruent condition, for which only one connection between Broca's area and the supplementary motor area was found in control participants, whereas patients showed connections to 8 widely distributed brain areas.ConclusionsThe findings imply that audiovisual integration problems in schizophrenia result from maladaptive connectivity of Broca's area in particular when confronted with incongruent stimuli and are discussed in light of recent audio visual speech models.

The commission of an error triggers cognitive control processes dedicated to error correction and prevention. Post - error adjustments leading to response slowing following an error (“post-error slowing”; PES) might be driven by changes in excitability of the motor regions and the corticospinal tract (CST). The time-course of such excitability modulations of the CST leading to PES is largely unknown. To track these presumed excitability changes after an error, single pulse transcranial magnetic stimulation (TMS) was applied to the motor cortex ipsilateral to the responding hand, while participants were performing an Eriksen flanker task. A robotic arm with a movement compensation system was used to maintain the TMS coil in the correct position during the experiment. Magnetic pulses were delivered over the primary motor cortex ipsilateral to the active hand at different intervals (150, 300, 450 ms) after correct and erroneous responses, and the motor-evoked potentials (MEP) of the first dorsal interosseous muscle (FDI) contralateral to the stimulated hemisphere were recorded. MEP amplitude was increased 450 ms after the error. Two additional experiments showed that this increase was neither associated to the correction of the erroneous responses nor to the characteristics of the motor command. To the extent to which the excitability of the motor cortex ipsi- and contralateral to the response hand are inversely related, these results suggest a decrease in the excitability of the active motor cortex after an erroneous response. This modulation of the activity of the CST serves to prevent further premature and erroneous responses. At a more general level, the study shows the power of the TMS technique for the exploration of the temporal evolution of post-error adjustments within the motor system.

Background Despite substantial research into the topic and valiant surgical efforts, reconstruction of peripheral nerve injury remains a challenging surgery. This study was conducted to evaluate the effectiveness of axonal regeneration of a transected sciatic nerve through a vein conduit containing degenerated skeletal muscle compared with axonal regeneration in a transected sciatic nerve through degenerated skeletal muscle alone. Methods In two of the three experimental rat groups, 10 mm of the left sciatic nerve was transected and removed. The proximal and distal ends of the transected sciatic nerve were then approximated and surrounded with either (a) a degenerated skeletal muscle graft; or (b) a graft containing both degenerated skeletal muscle and vein. In the group receiving the combined vein and skeletal muscle graft, the vein walls were subsequently sutured to the proximal and distal nerve stump epineurium. Sciatic functional index (SFI) was used for assessment of functional recovery. Tracing study and histological procedures were used to assess axonal regeneration. Results At 60 days, the gait functional recovery as well as the mean number of myelinated axons in the middle and distal parts of the sciatic nerve significantly increased in the group with the vein graft compared to rats with only the muscular graft (P

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disorder which is incurable to date. As there are many ongoing studies with therapeutic candidates, it is of major interest to develop biomarkers not only to facilitate early diagnosis but also as a monitoring tool to predict disease progression and to enable correct randomization of patients in clinical trials. Magnetic resonance imaging (MRI) has made substantial progress over the last three decades and is a practical, noninvasive method to gain insights into the pathology of the disease. Disease-specific MRI changes therefore represent potential biomarkers for ALS. In this paper we give an overview of structural and functional MRI alterations in ALS with the focus on task-free resting-state investigations to detect cortical network failures.

OBJECTIVES: Writer's cramp (WC) is characterized by excessive cocontractions of agonist and antagonist hand and forearm muscles during writing. Changes in functional magnetic resonance imaging activation patterns in such conditions can be ambiguous as they might either reflect some aspect of the primary pathophysiological mechanism or, alternatively, may be the result of adaptive actions during task execution. To circumvent this problem, we examined WC patients during rest, i.e., without a task, using independent component analysis (ICA) applied to the blood oxygen level‐dependent time series. METHODS: Functionally connected brain networks during rest were defined by ICA to assess differences between WC patients (n = 16) and healthy controls (n = 16). Analysis was carried out using FMRIB's Software Library. RESULTS: Two functional networks showed between‐group differences, the sensorimotor network and the default‐mode network. In WC patients, the connectivity was reduced in the left postcentral area and increased in basal ganglia in contrast to healthy controls. These changes were not reversed after treatment with botulinum toxin. CONCLUSIONS: In line with other studies, the results show a dysfunction in cortico‐subcortical circuits in WC involving somatosensory cortex, areas interfacing the sensory and motor systems, and putamen contralateral to symptomatic hand. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.

Women show higher sensitivity than men to emotional and social cues and are therefore better in showing empathy with others and in deciphering other’s intentions and mental states. These sex differences have been linked to hormonal levels. However, it remains unclear how hormones modulate neural mechanisms underlying empathic processes. To assess effects of chronic hormonal treatment, functional magnetic resonance imaging was used in a group of female-to-male transsexuals before and during androgen therapy and a group of female and male controls while they watched pictures portraying emotionally negative or neutral situations (emotional content) involving one or two persons (social relation). Before therapy, the medial superior frontal gyrus and left inferior frontal gyrus showed greater activations for emotional than neutral stimuli. The posterior superior temporal sulcus showed greater activations for emotional vs. neutral stimuli and for social relations relative to pictures of single persons. Long-term androgen administration reduced the pSTS activity in response to emotional stimuli as well as its response to social relation. More importantly, the functional connectivity among frontal, temporal and striatal regions was weakened while the connectivity among limbic regions was strengthened as the androgen level increased during hormone therapy. This pattern of change was similar to the sex difference observed between female vs. male controls. Thus, making a brain more male by the application of androgens not only reduced the activity of a core neural hub but also markedly altered the organization of the brain network supporting emotional and social cognitive processes related to empathy and mentalizing.

Spasticity is a complex disorder that causes significant disability in affected patients. We here present long-term results of botulinum toxin type A (BoNT-A) treatment in spasticity of various etiologies in the upper and lower limbs.We evaluated long-term results of BoNT-A treatment with Dysport and Botox for up to 12 years in 137 patients with spasticity of various etiologies. The focus was laid on efficacy, dosage, safety and side effects over time in a retrospective analysis of the database of our movement disorder clinic.The mean clinical benefit, latency and duration of response were comparable for both products. Side effects were generally mild and comparable for the two products. We found a significant negative correlation between time from onset of spasticity to start of BoNT-A treatment and degree of improvement after treatment.Our data confirm the safety and efficacy of BoNT-A treatment of spasticity of different etiologies over a long period of time. Furthermore, the data imply that BoNT-A treatment should be started early after appearance of spasticity to obtain better treatment response.

Introduction. Phantom limb pain and sensations are common in amputees. The pathophysiology remains unclear and the treatment difficult and often unsuccessful. Opioids are frequently used when non-narcotics have failed, but are not effective in many cases. We report on three phantom and stump pain patients, refractive to previous treatments, who were successfully treated with botulinum toxin A (BoNT-A). Methods. Three patients who had previously undergone amputation of their leg due to accident (N = 2) or injury by a landmine (N = 1) were treated with BoNT-A (Dysport®). We injected a total dose of up to 500 units (U) BoNT-A under EMG-control. Global clinical improvement was based on a 0–3 scale (0 = no effect; 3 = marked improvement) and on a questionnaire rating pain intensity (based on the visual analog scale), intake of pain medication and phantom limb sensations. Results. All three patients evaluated the clinical global improvement with 3 (marked improvement). The pain intensity and pain medication was reduced significantly in all three cases. No side effects were reported. The duration of response lasted up to 11 weeks. Discussion. These three successfully treated phantom and stump pain patients show that therapy with BoNT-A may be worth studying as an effective and safe treatment option for this kind of pain.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. To determine predictors of survival, we studied different parameters in our ALS Database including 479 patients. The effects of individual prognostic factors of survival were studied using Kaplan-Meier life table. The prognostic value of each factor of interest was expressed in terms of a hazard ratio. Survival from symptom-onset ranged from 4 months up to 11.9 years. Gender had no effect on survival in our cohort. However, age, site of onset, forced vital capacity, symptom duration and ALSFRS-R score at the first visit were independent prognostic factors in our population (log-rank p

Mice with a knockout (KO) of muscle LIM protein (MLP) exhibit many morphologic and clinical features of human cardiomyopathy. In humans, MLP-expression is downregulated both in ischemic and dilative cardiomyopathy. In this study, we investigated the effects of MLP on the electrophysiologic phenotype in vivo and on outward potassium currents.MLP-deficient (MLPKO) and wild-type (MLPWT) mice were subjected to long-term electrocardiogram (ECG) recording and in vivo electrophysiologic study. The whole-cell, patch-clamp technique was applied to measure voltage dependent outward K+ currents in isolated cardiomyocytes. Long-term ECG revealed a significant prolongation of RR mean (108 +/- 9 versus 99 +/- 5 ms), P (16 +/- 3 versus 14 +/- 1 ms), QRS (17 +/- 3 versus 13 +/- 1 ms), QT (68 +/- 8 versus 46 +/- 7 ms), QTc (66 +/- 6 versus 46 +/- 7 ms), JT (51 +/- 7 versus 34 +/- 7 ms), and JTc (49 +/- 5 versus 33 +/- 7 ms) in MLPKO versus MLPWT mice (P.05). During EP study, QT (80 +/- 8 versus 58 +/- 7 ms), QTc (61 +/- 6 versus 45 +/- 5 ms), JT (62 +/- 9 versus 43 +/- 6 ms), and JTc (47 +/- 5 versus 34 +/- 5 ms) were also significantly prolonged in MLPKO mice (P.05). Nonsustained VT was inducible in 9/16 MLPKO versus 2/15 MLPWT mice (P.05). Analysis of outward K+ currents in revealed a significantly reduced density of the slowly inactivating outward K+ current IK, slow in MLPKO mice (11 +/- 5 pA/pF versus 18 +/- 7 pA/pF; P.05).Mice with KO of MLP exhibit significant prolongation of atrial and ventricular conduction and an increased ventricular vulnerability. A reduction in repolarizing outward K+ currents may be responsible for these alterations.

Objectives: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, characterized by a selective progressive degeneration of the motor system. Electromyography is essential for the diagnosis of ALS. The measurement of motor conduction of peripheral nerves is of major importance to recognize other possible causes of progressive muscle wasting. However, there are also pathologic changes in nerve conduction studies in ALS patients. Methods: In this study we analysed the values of distal motor latency (DML), compound muscle action potential (CMAP) and motor nerve conduction velocity (MNCV) in 95 patients with definite ALS. Results: We found slight slowing of MNCV and moderate to strong reduction of CMAP and a prolongation of DML. We found no significant correlation between MNCV and CMAP. Discussion: The main finding of the present work was the negative correlation between DML and CMAP. It is interpreted as a very distal axonal damage as the main reason for prolongation of DML in AL...

Transcranial magnetic stimulation (TMS) is a useful method to study pharmacological effects on motor cortex excitability. Zolpidem is a selective agonist of the benzodiazepine receptor subtype BZ1 and has a distinct pharmacological profile compared to diazepam. To study the different effects of these two drugs on the cortical inhibitory system, TMS was performed before and after administration of a single oral dose of zolpidem (10 mg) and diazepam (5 mg) in six healthy volunteers. TMS tests included the determination of resting and active motor threshold (MT) and measurements of the amplitudes of motor evoked potentials, intracortical facilitation (ICF), short-latency intracortical inhibition (SICI), and long-latency intracortical inhibition (LICI), and determination of the cortical silent period (CSP). Both drugs were without effect on the active or resting MT and decreased the ICF. Prolongation of the CSP and enhancement of LICI only in the presence of zolpidem point to a specific BZ1-related mechanism underlying the long-lasting component of cortical inhibition. This selective modulation of the CSP and the LICI points to a specific role of BZ1 receptors in the control of inhibitory neuronal loops within the primary motor cortex.

Glycine receptor channels are pentameric ligand-gated ion channels that respond to the application of inhibitory neurotransmitters by opening of a chloride-selective central pore. Topiramate (TPM) is a broad-spectrum antiepileptic drug used as add-on or monotherapy for focal seizures. In the present study the interaction of TPM with glycine receptor channels was studied on outside-out patches from HEK293 cells expressing α 1 β glycine receptor channels. The patch clamp techniques combined with ultra fast solution exchange enabled us to investigate the kinetics of receptor channels in presence of TPM. Our study showed no agonistic or potentiating effect for TPM on glycine receptor channels. However, in presence of 1 mM glycine + 1 mM TPM, the desensitization got faster and the peak current amplitude decreased. After the end of glycine + TPM pulses, off-currents occurred, suggestive for a specific channel block mechanism.

It can be difficult to detect upper motor neuron (UMN) involvement in early amyotrophic lateral sclerosis (ALS). The present study tested the usefulness of mirror movements (MMs), i.e., contralateral coactivation of hand muscles, as a UMN sign in ALS. Thirty-seven patients with possible, probable or definite ALS and 19 patients with suspected ALS without clinical signs of UMN involvement, 21 disease controls and 15 healthy volunteers were included. MMs were studied clinically, electromyographically and by transcranial magnetic stimulation (TMS), looking for ipsilateral motor evoked potentials (IMEPs). MMs were observed clinically in 15 ALS patients (27%) and electromyographically in 28 (50%). IMEPs in the abductor pollicis brevis muscle following TMS were recorded in 34 (61%) of all ALS patients and in nine (47%) out of 19 patients with suspected ALS, but not in healthy controls. Central motor conduction times were prolonged in 15 ALS patients (27%). It is concluded that MMs, especially if studied by EMG and TMS (IMEPs) can essentially improve detection of UMN involvement, especially in early stages of ALS.

We report on a case of polymicrogyria with benign childhood epilepsy and amyotrophic lateral sclerosis (ALS). While performing dexterity tasks with either hand, strong unsustained mirror movements of the unintended hand were observed. The patient was seen over a period of three years and, as often seen in ALS, there was a moderate progress of the motor neuron disease affecting the upper and lower motor neuron in an asymmetrical manner. In addition, more rapidly progressive bulbar symptoms could be observed by the clinical and neurophysiological examination. MRI revealed polymicrogyria of the right frontal lobe with irregular bumpy inner and outer surface and abnormally thick and smooth cortex, dysplastic insular cortex and asymmetrically widened Sylvial fissure. No signs of atrophy, especially of the motorcortex and corticospinal tract were observed. The corpus callosum was completely developed and of normal size. We hypothesize an enrolment of the dysplastic right frontal lobe pathophysiology of the observed mirror movements.

In Guillain-Barre syndrome (GBS), immunoglobulin G (IgG) antibodies block neuromuscular transmission pre- and postsynaptically and thus are of potential pathogenic relevance. We investigated whether IgG from GBS patients has a direct interaction with nicotinic acetylcholine receptor (nAChR) channels. Purified IgG fractions from six GBS patients that blocked neuromuscular transmission in a previous study were analyzed by the patch-clamp technique in combination with an ultrafast system for solution exchange. Sera from three patients with other inflammatory neurological disorders were used as controls. Mouse myotubes expressing native embryonic-type nAChR channels and human embryonic kidney (HEK) 293 cells transiently transfected with recombinant adult-type nAChR channels were used. Repeated 20-ms pulses of acetylcholine (ACh) were applied to outside-out patches in the presence of GBS-IgG. IgG of the patients had a significant reversible blocking action on embryonic- and adult-type nAChR channels with some variability in the magnitude of the block. Activation and desensitization kinetics were not affected when GBS-IgG was applied. None of the control sera blocked the AChR channels. The observed postsynaptic block effect fulfills the criteria of a channel-blocking IgG antibody similar to those seen in autoimmune myasthenia and may contribute to muscle weakness during the acute phase of GBS.

Background & Aims: Hepatic myelopathy is a rare complication of chronic liver disease, causing progressive spastic paraparesis. Today, no therapy of this disorder has been established. Commonly used therapeutic strategies for hepatic encephalopathy aiming at the reduction of plasma ammonia levels such as protein restriction, oral neomycin, lactulose, or ornithine aspartate fail to improve the symptoms of hepatic myelopathy. The aim of this study was to find out whether orthotopic liver transplantation (OLT) may improve hepatic myelopathy. Methods: Follow-up examinations of 3 patients with severe hepatic myelopathy before and after OLT. Results: In all 3 patients, the neurologic status improved significantly after liver transplantation. The grade of improvement was related to the time interval between onset of the first symptoms of hepatic myelopathy and liver transplantation. Conclusions: Early recognition of hepatic myelopathy is important because timely liver transplantation as an established therapy for end-stage liver disease offers the chance of complete recovery from hepatic paraparesis.

Riluzole is a neuroprotective drug that modulates glutamergic transmission but also blocks the inactivated state of voltage-gated neuronal sodium channels at very low concentrations (about 0.1 microM). After nausea, the most common adverse effect of riluzole is asthenia, which could be due to a block of muscle sodium channels or acetylcholine receptor channels. Using the patch-clamp technique, we applied riluzole on recombinant voltage-gated skeletal muscle sodium and adult nicotinic acetylcholine receptor channels expressed in a mammalian cell line (HEK 293). Riluzole blocked the inactivated state of voltage-gated skeletal muscle sodium channels, shifting the midpoint of the steady-state inactivation curve to more negative potentials, but only in comparatively high concentrations (> or = 0.1 mM). At these concentrations, riluzole also caused an open-channel block at acetylcholine receptor channels. We conclude that riluzole has only a mild blocking effect on the inactivated state of voltage-gated skeletal muscle sodium channels and nicotinic acetylcholine receptor channels. As the plasma concentration of riluzole in amyotrophic lateral sclerosis (ALS) patients approximates 2 microM, it seems unlikely that asthenia is caused by a block of skeletal muscle sodium channels or acetylcholine receptor channels by riluzole.

We retrospectively screened a large cohort of 554 ALS patients with regard to documented nerve compression syndromes and identified 23 patients, mostly with carpal tunnel syndrome. Patients could be subdivided into three groups. Group A comprised 13 patients in whom nerve compression was apparently confused with early ALS signs. Group B consisted of six patients diagnosed with carpal tunnel syndrome who had experienced improvement after surgery years before they eventually developed ALS. Group C consisted of four patients who, after diagnosis of ALS, additionally developed a nerve compression syndrome. Altogether, the frequency of true nerve compression syndromes in our ALS cohort (1.8%) was no higher than in the general population (0.3-10.8%). In group A, the initial confusion with a nerve compression syndrome led to a slight though not significant delay (15.2 vs. 12.9 months; p = 0.32) of the diagnosis of ALS. Survival was no different between group A and the cohort. It can also be concluded that the misdiagnoses could have been avoided by thorough electrophysiological examination using a standardized protocol.

Although neuroimaging studies using standard subtraction-based analysis from functional magnetic resonance imaging (fMRI) have suggested that frontal and temporal regions are involved in word learning from fluent speech, the possible contribution of different brain networks during this type of learning is still largely unknown. Indeed, univariate fMRI analyses cannot identify the full extent of distributed networks that are engaged by a complex task such as word learning. Here we used Independent Component Analysis (ICA) to characterize the different brain networks subserving word learning from an artificial language speech stream. Results were replicated in a second cohort of participants with a different linguistic background. Four spatially independent networks were associated with the task in both cohorts: (i) a dorsal Auditory-Premotor network; (ii) a dorsal Sensory-Motor network; (iii) a dorsal Fronto-Parietal network; and (iv) a ventral Fronto-Temporal network. The level of engagement of these networks varied through the learning period with only the dorsal Auditory-Premotor network being engaged across all blocks. In addition, the connectivity strength of this network in the second block of the learning phase correlated with the individual variability in word learning performance. These findings suggest that: (i) word learning relies on segregated connectivity patterns involving dorsal and ventral networks; and (ii) specifically, the dorsal auditory-premotor network connectivity strength is directly correlated with word learning performance.

BackgroundSeveral recently developed therapies targeting motor disabilities in stroke sufferers have shown to be more effective than standard neurorehabilitation approaches. In this context, several basic studies demonstrated that music training produces rapid neuroplastic changes in motor-related brain areas. Music-supported therapy has been recently developed as a new motor rehabilitation intervention.Methods and resultsIn order to explore the plasticity effects of music-supported therapy, this therapeutic intervention was applied to twenty chronic stroke patients. Before and after the music-supported therapy, transcranial magnetic stimulation was applied for the assessment of excitability changes in the motor cortex and a 3D movement analyzer was used for the assessment of motor performance parameters such as velocity, acceleration and smoothness in a set of diadochokinetic movement tasks. Our results suggest that the music-supported therapy produces changes in cortical plasticity leading the improvement of the subjects' motor performance.ConclusionOur findings represent the first evidence of the neurophysiological changes induced by this therapy in chronic stroke patients, and their link with the amelioration of motor performance. Further studies are needed to confirm our observations.

Botulinum toxin (BT) therapy is the treatment of choice for blepharospasm (BPS). Currently available BT type A drugs include Botox(®), Dysport(®) and Xeomin(®). Until now, there are few long-term studies on BT therapy for BPS. This is the first long-term study comparing all three major BT drugs. We collected treatment, efficacy and adverse effect data on BPS patients treated with either Botox(®), Dysport(®) or Xeomin(®) for at least eight consecutive treatments. Two hundred and eighty-eight patients (208 females, 80 males, age 62 ± 12 years) were included in this study. The treatment time was 11.2 ± 4.1 years covering 10,701 injection series. Doses were 47 ± 10 MU for Botox(®), 120 ± 35 MU for Dysport(®) and 62 ± 11 MU for Xeomin(®) (Botox(®) dose vs Xeomin(®) dose: p0.001, unpaired t test). 85 % of all patients had stable doses. The onset of the therapeutic effect was after 6.1 ± 3.3 days and its duration lasted 10.2 ± 3.5 weeks. The Global Clinical Improvement (GCI, 0 = no, 1 = slight, 2 = moderate, 3 = marked improvement in severity and function) as estimated by the patient was 2.5 ± 0.6. It was stable in 90% of the patients. Adverse effect frequency was 3.0% (ptosis 2.3%, dry eye 0.5%, diplopia 0.2%). None of these findings was significantly different between Botox(®), Dysport(®) and Xeomin(®). Our study, one of the largest studies on BT therapy of BPS and the study with the longest follow-up, confirms that BT therapy produces robust clinical improvement which is stable throughout the treatment time. Therapeutic effects start after 6.1 days and last for about 10 weeks before they start to vanish. With this, they are approximately 2 weeks shorter than the recommended inter-injection interval. Adverse effects were rare, mild and always transient. BT therapy is a safe and effective treatment for BSP. Shorter inter-injection intervals may improve therapeutic results.

We examined the effects of propofol on a paramyotonia congenita mutant skeletal muscle sodium channel in vitro, because life-threatening complications resulting from severe muscle rigidity during induction of anesthesia have been observed using other anesthetics in patients with hereditary sodium channel myopathies. Our hypothesis was that propofol might interact directly with mutant channels, causing enhanced muscle excitability in affected patients. Whole-cell voltage-clamp experiments were performed on HEK 293 cells expressing R1448H mutant sodium channels. Propofol blocked sodium inward current at clinical concentrations (5 μmol/L) when depolarizing pulses were started from holding potentials close to the physiological resting potential (−70 mV). Higher propofol concentrations (≥25 μmol/L) accelerated pathologically delayed inactivation kinetics and delayed pathologically enhanced recovery from inactivation. Our in vitro results show that inactivation-deficient sodium channels are specifically targeted and blocked by propofol. This might reduce enhanced muscle excitability experienced by affected patients in vivo. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 736–743, 2001

In recent years, the use of medicinal plants increased considerably; so that today, the use of traditional medicine, as well as medicinal plants is necessary for the aim of producing more effective drugs with fewer side effects and determining the effective doses. With the scientific name of Juglans regia, walnut plant is a medicinal plant with different properties that is considered less, despite having great therapeutic potential in the traditional medicine. The aim of this study was to review the dispersal of walnut plants, the chemical compounds, and therapeutic effects of walnuts on antioxidant activity, antidiabetic, hypolipidemic, antimicrobial, and antihypertensive activities, as well as liver protection. Data of this review study have been collected from the books and scientific articles published in databases such as Science Direct, Web of Science, Scopus, PubMed, and Scientific Information Database. While this plant having high antioxidant capabilities, walnuts are composed of many chemical compounds such as ascorbic acid, flavonoids, quercetin, and caffeic acid. Experimental studies have shown that walnuts reduced blood glucose and lipids and also decreased blood pressure. They have antioxidant, antidiabetic, antimicrobial, and liver-protective properties. The use of walnuts in traditional medicine and review of experimental studies demonstrated the presence of multiple, effective, and useful compounds which may provide the opportunity for the production of lipid-lowering, antidiabetes, and liver protective drugs. Due to the effects of walnuts on improving the complications of various diseases, the need for doing comprehensive clinical trials for the use of walnuts in the treatment of diseases is necessary.

Background We report the case of a chronic stroke patient (62 months after injury) showing total absence of motor activity evoked by transcranial magnetic stimulation (TMS) of spared regions of the left motor cortex, but near-to-complete recovery of motor abilities in the affected hand. Case presentation Multimodal investigations included detailed TMS based motor mapping, motor evoked potentials (MEP), and Cortical Silent period (CSP) as well as functional magnetic resonance imaging (fMRI) of motor activity, MRI based lesion analysis and Diffusion Tensor Imaging (DTI) Tractography of corticospinal tract (CST). Anatomical analysis revealed a left hemisphere subinsular lesion interrupting the descending left CST at the level of the internal capsule. The absence of MEPs after intense TMS pulses to the ipsilesional M1, and the reversible suppression of ongoing electromyographic (EMG) activity (indexed by CSP) demonstrate a weak modulation of subcortical systems by the ipsilesional left frontal cortex, but an inability to induce efficient descending volleys from those cortical locations to right hand and forearm muscles. Functional MRI recordings under grasping and finger tapping patterns involving the affected hand showed slight signs of subcortical recruitment, as compared to the unaffected hand and hemisphere, as well as the expected cortical activations. Conclusions The potential sources of motor voluntary activity for the affected hand in absence of MEPs are discussed. We conclude that multimodal analysis may contribute to a more accurate prognosis of stroke patients.

Background Errorless learning is advantageous over trial and error learning (errorful learning) as errors are avoided during learning resulting in increased memory performance. Errorful learning challenges the executive control system of memory processes as the erroneous items compete with the correct items during retrieval. The left dorsolateral prefrontal cortex (DLPFC) is a core region involved in this executive control system. Transcranial direct current stimulation (tDCS) can modify the excitability of underlying brain functioning. Results In a single blinded tDCS study one group of young healthy participants received anodal and another group cathodal tDCS of the left DLPFC each compared to sham stimulation. Participants had to learn words in an errorless and an errorful manner using a word stem completion paradigm. The results showed that errorless compared to errorful learning had a profound effect on the memory performance in terms of quality. Anodal stimulation of the left DLPFC did not modulate the memory performance following errorless or errorful learning. By contrast, cathodal stimulation hampered memory performance after errorful learning compared to sham, whereas there was no modulation after errorless learning. Conclusions Concluding, the study further supports the advantages of errorless learning over errorful learning. Moreover, cathodal stimulation of the left DLPFC hampered memory performance following the conflict-inducing errorful learning as compared to no modulation after errorless learning emphasizing the importance of the left DLPFC in executive control of memory.

Functional magnetic resonance imaging (fMRI) of hand movements in amyotrophic lateral sclerosis (ALS) has repeatedly demonstrated increased activation in cortical and subcortical areas, whereas a single study has suggested decreased rather than increased activations for tongue movements in patients with bulbar involvement. This points to differences in the pathophysiology and may correspond to the different time-course of disease for patients with and without bulbar involvement. We, therefore, compared the cortical activity during movements of the tongue and right hand using fMRI to delineate the neurofunctional correlates of bulbar versus limb symptoms in 20 ALS patients (11 with bulbar signs) and age-matched controls. During vertical tongue movements, the cortical activation pattern in ALS patients without bulbar signs did not differ from the control group. However, presence of bulbar signs caused a significant decrease of cortical activation. An increased cortical activity during the hand movement in all ALS patients was evident, regardless of site of onset and presence of bulbar signs. Thus, two different patterns of cortical activation changes suggesting fundamental differences in the neurodegenerative process and subsequent reorganisation processes exist for limb and bulbar movements.

Botulinum toxin is considered the treatment of choice for hemifacial spasm (HFS) and reinnervation synkinesias (RS). We present 133 patients with HFS (n = 97) and RS (n = 36) who have been treated with either Botox (n = 78) or Dysport (n = 55) exclusively for 6 years (range 2-12 years). The Botox dose was 21 +/- 8 MU, the Dysport dose 46 +/- 22 MU. The therapeutic effect started after 7.1 +/- 2.3 days and lasted for 12.5 +/- 3.9 weeks. It was stable throughout the observation period in 85% of all patients. Adverse effects occurred in 5.4% of injection series. No patient terminated treatment because of unsatisfactory results. Secondary therapy failure did not occur. With an effective conversion ratio of Botox:Dysport = 1:2.56 there were no differences between both drugs with respect to therapeutic efficacy and adverse effects thus confirming the hypothesis that there may not be intrinsic differences between both products.

Objective: Cervical dystonia (CD) is the most common form of adult-onset focal dystonia, and botulinum toxin A (BoNT-A) has become the first-line treatment for this condition. Methods: In this work, we present data of 207 CD patients treated with BoNT-A for 6.7 ± 3.5 years. One hundred and sixty-three patients were treated with Dysport (mean dose, 389 ± 144 U) and 44 with Botox (mean dose, 145 ± 44 U). Results: The mean clinical benefit, based on a 0–3 scale (0=no effect, 1=slight, 2=moderate and 3=marked improvement) was similar for Dysport (2.5 ± 0.3) and Botox (2.2 ± 0.4). Adverse events were mild and similar for both products. Fewer than 2% of the patients developed neutralizing antibodies. Discussion: These data confirm the efficacy and safety of BoNT-A treatment in CD over an extended period of up to 14 years.