[Consensus recommendations on regional interdisciplinary standardization of MRI diagnostics for multiple sclerosis in the metropolitan area of Essen]. / Konsensusempfehlungen zur regionalen fächerübergreifenden Standardisierung der MRT-Diagnostik bei Multipler Sklerose im Großraum Essen.

Magnetic resonance imaging (MRI) is of exceptional importance in the diagnostics and monitoring of multiple sclerosis (MS); however, a close interdisciplinary cooperation between neurologists in private practice, (neuro)radiological practices, hospitals or specialized MS centers is only rarely established. In particular, there is a lack of standardized MRI protocols for image acquisition as well as established quality parameters, which guarantee the comparability of MRI records; however, this is a fundamental prerequisite for an effective application of MRI in the treatment of MS patients, e.g., for making the diagnosis or treatment monitoring. To address these challenges a group of neurologists and (neuro)radiologists developed a consensus proposal for standardization of image acquisition, interpretation and transmission of results and for improvement in interdisciplinary cooperation. This pilot project in the metropolitan area of Essen used a modified Delphi process and was based on the most up to date scientific knowledge. The recommendation takes the medical, economic, temporal and practical aspects of MRI in MS into consideration. The model of interdisciplinary cooperation between radiologists and neurologists with the aim of a regional standardization of MRI could serve as an example for other regions of Germany in order to optimize MRI for MS.

The prognostic value of radiologic parameters for long-term outcome assessment after an isolated unilateral calcaneus fracture.

OBJECTIVE: The current retrospective case-control study examines the prognostic value of radiologic parameters for long-term clinical outcome assessment after a calcaneus fracture. METHODS: In the authors' trauma department 262 adult patients with an isolated calcaneus fracture were treated from 1995 to 2005. Using conventional x-ray and computed tomography imaging. the calcaneal fractures were classified according to Sanders system. In addition, Boehler's and Gissane's angles were measured before and after therapy and the Larsen stage of subtalar arthrosis was determined. After a mean follow-up interval of 9.5 years, 44 patients were available for clinical and radiological assessment. RESULTS: At the time of trauma the average age of the study group was 52 (range, 29-79) years. Thirty-seven patients were treated operatively and seven conservatively. Patients with a negative Boehler's angle, upon admission, exhibited significantly worse results using four of the five clinical scoring systems than patients with a preserved or slight reduced Boehler's angle. Operative treatment in patients whose Boehler's angle was elevated to normal range or beyond exhibited %worse better results than patients with an over-correction of Boehler's angle. In 11 cases, two primary and nine secondary subtalar arthrodeses were performed. The degree of subtalar arthrosis as per Larsen was increased 2.54 ± 1.14 in the course of hospital admission, arthrodesis and/or follow up examination. The results show no significant difference between operative and conservative treatment. CONCLUSIONS: Boehler's angle at time of admission appears to be a valuable prognosticator for functional long-term results after calcaneus fracture. An operative over-correction of a reduced Boehler's angle should be avoided.

Auditory-visual localization in hemianopia.

OBJECTIVE: Beyond visual field defects, patients with hemianopia have been suggested to perceive horizontal visual space in a distorted manner. However, the pattern of these distortions remained debatable. The aim of this study was to estimate the geometry of the visual representation of space in hemianopia using an auditory marker. METHOD: Patients with pure left or right hemianopia (without neglect) were tested in tasks requiring them to bring a visual stimulus into spatial alignment with a target sound (Experiment 1) or vice versa (Experiment 2). RESULTS: In Experiment 1, patients adjusted the location of a light such that it was displaced toward the anopic side with reference to the physical sound position. In Experiment 2, patients adjusted the location of a sound such that it was displaced opposite to the anopic side with reference to the actual position of the visual target. Both experiments consistently indicated that hemianopic patients perceived a sound and a light to be in spatial alignment when the physical position of the light deviated by several degrees from the sound toward the side of the anopic hemifield, that is, to the contralesional side. CONCLUSIONS: Given that auditory localization in patients with hemianopia has been previously shown to be only slightly biased toward the anopic side, the observed distortion of visual space with reference to auditory space can be explained by assuming that visual positions were, in absolute terms, perceived as shifted toward the intact side. As a result, HA patients may perceive visual space as compressed on their ipsilesional (intact), in comparison with their contralesional (anopic) side.

Levodopa increases speed of alternating movements in Parkinson's disease patients.

Disturbances of alternating movement execution are a characteristic clinical sign of patients with Parkinson's disease (PD). Objectives were to compare instrumentally measured diadochokinetic motion series carrying out before and 1 h after standardised levodopa intake and to correlate the device results with the respective rating scores of the PD patients. Maximum velocity and interval improved following levodopa application. The amplitude of motions did not differ between both assessment moments. Closer correlations between rating- and diadochokinesimeter outcomes appeared before levodopa intake.

Differential reward processing in subtypes of adult attention deficit hyperactivity disorder.

OBJECTIVES: Abnormalities in reward processing have been found in adolescents and adults with ADHD using the 'Monetary Incentive Delay' (MID) task. However, ADHD groups in previous studies were heterogeneous regarding ADHD subtype, gender and, in part, drug treatment status. This study sought to compare neural activations in the ventral striatum (VS) and prefrontal regions during reward processing in homogenous ADHD subtype groups and healthy adults, using the MID task. METHODS: In total, 24 drug-naïve, right-handed male adults with ADHD (12 subjects with combined type (ADHD-ct) and 12 subjects with predominantly inattentive (ADHD-it) type ADHD), and twelve healthy right-handed male control subjects were included. RESULTS: Compared to ADHD-ct and healthy subjects, ADHD-it subjects showed a bilateral ventral striatal deficit during reward anticipation. In contrast, ADHD-ct subjects showed orbitofrontal hyporesponsiveness to reward feedback when compared with ADHD-it and healthy subjects. CONCLUSIONS: This is the first fMRI study that delineates dysfunctional and subtype-divergent neural and behavioural reward processing in adults with ADHD.

Long-term sensory stimulation therapy improves hand function and restores cortical responsiveness in patients with chronic cerebral lesions. Three single case studies.

Rehabilitation of sensorimotor impairment resulting from cerebral lesion (CL) utilizes task specific training and massed practice to drive reorganization and sensorimotor improvement due to induction of neuroplasticity mechanisms. Loss of sensory abilities often complicates recovery, and thus the individual's ability to use the affected body part for functional tasks. Therefore, the development of additional and alternative approaches that supplement, enhance, or even replace conventional training procedures would be advantageous. Repetitive sensory stimulation protocols (rSS) have been shown to evoke sensorimotor improvements of the affected limb in patients with chronic stroke. However, the possible impact of long-term rSS on sensorimotor performance of patients with CL, where the incident dated back many years remains unclear. The particular advantage of rSS is its passive nature, which does not require active participation of the subjects. Therefore, rSS can be applied in parallel to other occupations, making the intervention easier to implement and more acceptable to the individual. Here we report the effects of applying rSS for 8, 36, and 76 weeks to the paretic hand of three long-term patients with different types of CL. Different behavioral tests were used to assess sensory and/or sensorimotor performance of the upper extremities prior, after, and during the intervention. In one patient, the impact of long-term rSS on restoration of cortical activation was investigated by recording somatosensory evoked potentials (SEP). After long-term rSS all three patients showed considerable improvements of their sensory and motor abilities. In addition, almost normal evoked potentials could be recorded after rSS in one patient. Our data show that long-term rSS applied to patients with chronic CL can improve tactile and sensorimotor functions, which, however, developed in some cases only after many weeks of stimulation, and continued to further improve on a time scale of months.

Pathophysiology of protein aggregation and extended phenotyping in filaminopathy.

Mutations in FLNC cause two distinct types of myopathy. Disease associated with mutations in filamin C rod domain leading to expression of a toxic protein presents with progressive proximal muscle weakness and shows focal destructive lesions of polymorphous aggregates containing desmin, myotilin and other proteins in the affected myofibres; these features correspond to the profile of myofibrillar myopathy. The second variant associated with mutations in the actin-binding domain of filamin C is characterized by weakness of distal muscles and morphologically by non-specific myopathic features. A frameshift mutation in the filamin C rod domain causing haploinsufficiency was also found responsible for distal myopathy with some myofibrillar changes but no protein aggregation typical of myofibrillar myopathies. Controversial data accumulating in the literature require re-evaluation and comparative analysis of phenotypes associated with the position of the FLNC mutation and investigation of the underlying disease mechanisms. This is relevant and necessary for the refinement of diagnostic criteria and developing therapeutic approaches. We identified a p.W2710X mutation in families originating from ethnically diverse populations and re-evaluated a family with a p.V930_T933del mutation. Analysis of the expanded database allows us to refine clinical and myopathological characteristics of myofibrillar myopathy caused by mutations in the rod domain of filamin C. Biophysical and biochemical studies indicate that certain pathogenic mutations in FLNC cause protein misfolding, which triggers aggregation of the mutant filamin C protein and subsequently involves several other proteins. Immunofluorescence analyses using markers for the ubiquitin-proteasome system and autophagy reveal that the affected muscle fibres react to protein aggregate formation with a highly increased expression of chaperones and proteins involved in proteasomal protein degradation and autophagy. However, there is a noticeably diminished efficiency of both the ubiquitin-proteasome system and autophagy that impairs the muscle capacity to prevent the formation or mediate the degradation of aggregates. Transfection studies of cultured muscle cells imitate events observed in the patient's affected muscle and therefore provide a helpful model for testing future therapeutic strategies.

Passive auditory stimulation improves vision in hemianopia.

UNLABELLED: Techniques employed in rehabilitation of visual field disorders such as hemianopia are usually based on either visual or audio-visual stimulation and patients have to perform a training task. Here we present results from a completely different, novel approach that was based on passive unimodal auditory stimulation. Ten patients with either left or right-sided pure hemianopia (without neglect) received one hour of unilateral passive auditory stimulation on either their anopic or their intact side by application of repetitive trains of sound pulses emitted simultaneously via two loudspeakers. Immediately before and after passive auditory stimulation as well as after a period of recovery, patients completed a simple visual task requiring detection of light flashes presented along the horizontal plane in total darkness. The results showed that one-time passive auditory stimulation on the side of the blind, but not of the intact, hemifield of patients with hemianopia induced an improvement in visual detections by almost 100% within 30 min after passive auditory stimulation. This enhancement in performance was reversible and was reduced to baseline 1.5 h later. A non-significant trend of a shift of the visual field border toward the blind hemifield was obtained after passive auditory stimulation. These results are compatible with the view that passive auditory stimulation elicited some activation of the residual visual pathways, which are known to be multisensory and may also be sensitive to unimodal auditory stimuli as were used here. TRIAL REGISTRATION: DRKS00003577.

Altered ventral striatal activation during reward and punishment processing in premanifest Huntington's disease: a functional magnetic resonance study.

Recent research using various neuroimaging methods revealed the crucial role of the striatum concerning the neuropathology of Huntington's disease. Degenerative changes located in the basal ganglia are already observable in premanifest stages of Huntington's disease (pre-HD), i.e., before the onset of manifest motor symptoms. Although the impact of the striatum on reward and punishment processing is well-established in healthy subjects, these processes have not been investigated in manifest and premanifest HD subjects using functional magnetic resonance imaging (fMRI) so far. We used the Monetary Incentive Delay Task to investigate valence discrimination in terms of rewarding and punishing cues in 30 pre-HD and 15 healthy subjects. According to the probability of disease onset within the next 5 years, pre-HD subjects were categorized as either near to motor symptom onset (pre-HD(near); 9.9 [±2.91] years to onset) or far from manifest disease onset (pre-HD(far); 23.49 [±5.99] years to onset). Compared to pre-HD(far) and healthy subjects, pre-HD(near) subjects showed a disturbed neuronal differentiation between reward and control anticipation located in the left ventral striatum. In contrast to pre-HD(far) and healthy subjects, no significant ventral striatal discrimination between punishing and control cues was detected in pre-HD(near) subjects. In the present study, we demonstrated for the first time significant differences in valence discrimination in pre-HD(near) subjects compared to pre-HD(far) subjects and healthy controls. Altered reward and punishment processing could therefore reflect a motivational deficit that may contribute to the pathogenesis of Huntington's disease.

An fMRI study of "theory of mind" in at-risk states of psychosis: comparison with manifest schizophrenia and healthy controls.

OBJECTIVE: Poor social functioning is a hallmark of schizophrenia and may precede the onset of illness. One of the most robust predictors of social impairment is a deficit in the ability to appreciate the mental states of others ("theory of mind"; ToM). We therefore examined ToM in subjects at risk of developing psychosis using an fMRI paradigm and compared brain activations with those of patients with manifest schizophrenia and healthy controls. METHOD: Ten subjects with at-risk ("prodromal") states of psychosis, 22 schizophrenia patients and 26 healthy controls were recruited. During fMRI scanning, participants were shown a series of cartoons. The task was to infer the mental states of the cartoon characters in terms of beliefs, states of knowledge and intentions. RESULTS: Subjects at risk of psychosis activated the ToM neural network comprising the prefrontal cortex, the posterior cingulate cortex, and the temporoparietal cortex more strongly than patients with manifest schizophrenia, and, in part, also more strongly than healthy controls. Manifest schizophrenia patients and controls activated the ToM neural network differently with little overlap of activated regions, where overall, controls showed stronger activations than schizophrenia patients. CONCLUSIONS: Individuals with at-risk states of schizophrenia activate the ToM neural network differently, and in part, more strongly compared to patients with schizophrenia and controls. This could suggest a compensatory overactivation of brain regions critical for empathic responses during mental state attribution in at-risk subjects for schizophrenia.

Paediatric radiology and scientific contributions to radiation dose at the meeting of the German Radiological Society--an analysis of an 11-year period.

AIM: Evaluation of the emphasis on themes pertaining to paediatric radiology and radiation dose at the Meeting of the German Radiological Society from 1998 to 2008 in comparison to international data. MATERIALS AND METHODS: Retrospective analysis of 9440 abstracts with documentation of type of contribution, imaging modality, and examined body region. Abstracts primarily dealing with paediatric radiology and those stating radiation dose were documented. Results were compared with a Pubmed query. RESULTS: 448 contributions in paediatric radiology were presented corresponding to 5% of all abstracts with an increase from 5 (1998) to 7% (2008). The proportion of prospective studies of all congress contributions was 10%, whereas in paediatric radiology, the share of prospective studies was 6%. From 1998 to 2008, the share of MRI fell from 48 to 38%, while CT contributions rose from 30 to 34%. Within paediatric radiology, the proportion of CT rose from 23 to 29%, while MRI and ultrasound fell from 63 to 48% and 35 to 19%, respectively. The share of abstracts dealing with radiation dose rose from 7 to 10% while that primarily pertaining to dose reduction grew from 2 to 4%. Of all abstracts concerning CT, 15% touched on radiation dose, whereas 6% primarily dealt with dose reduction. Among all abstracts dealing with paediatric radiology, 20 and 6% mentioned radiation dose and dose reduction, respectively. In the subgroup of paediatric radiology CT abstracts, radiation dose and dose reduction were mentioned in 34 and 16%, respectively. An online query produced 137,791 publications on CT, of whose abstracts 3% mentioned radiation dose and 0.5% mentioned dose reduction. 11% of all CT publications dealt with paediatric populations and 2% of these publications examined questions of radiation dose. CONCLUSIONS: In the last 11 years the Meeting of the German Radiological Society has presented a growing number of contributions pertaining to paediatric radiology. CT has shown the most pronounced growth of all contributions. Paediatric radiology has significantly more often dealt with questions of radiation exposure than those from general radiology. However, contributions with definite reference to radiation dose, both pertaining to all publications and specifically to those dealing with CT, remain a minority, albeit with a higher proportion when compared to international data.

Paediatrician awareness of radiation dose and inherent risks in chest imaging studies--a questionnaire study.

OBJECTIVE: To assess paediatricians' knowledge regarding radiation exposure of chest imaging. MATERIALS AND METHODS: German paediatricians were surveyed using a questionnaire. Participants were asked to estimate effective dose (ED) of radiographs (CR) and computed tomography (CT). Further questions included dose-saving of paediatric CT-protocols, ALARA principle, and awareness of the link between radiation and cancer development. Length and type of occupation and amount of ordered procedures were evaluated. RESULTS: 137 paediatricians participated with 59% and 39% correctly estimating ED of an adult (0.01-0.1mSv) and newborn CR (0.01-0.1mSv), respectively. ED of an adult chest CT (1-10mSv) was underestimated by 28%, whereas ED of cardiac CT (10-100mSv) was underestimated by 54%. 35% of participants correctly estimated ED of a chest CT in an infant (10-100mSv) which was underestimated by 56%. Neither length nor type of occupation showed significant impact on dose estimations. 14% of paediatricians stated that MRI causes radiation, whereas 4% correctly estimated the potential of paediatric CT-protocols. 15% were familiar with the ALARA principle and 26% were aware of a publication concerning radiation and malignancy. CONCLUSION: Paediatricians demonstrated an increased level of awareness compared to previous surveys. However, estimation of ED of CT remained difficult. Increased information transfer and education seem pressing in the light of increasing radiological examinations.

Distortion of auditory space in hemianopia.

Sound localization was investigated in patients with homonymous hemianopia, a visual field defect characterized by a loss of vision in one hemifield that is caused by unilateral brain lesions involving the visual cortex or its afferents. The primary aim was to clarify whether or not the known distortion of visual space in hemianopia results in processes of long-term cross-modal spatial adaptation, thus eventually inducing related alterations in auditory space perception. For this purpose, patients were tested by using tasks of either head pointing or manual pointing to acoustic targets in the azimuthal plane, under anechoic conditions in total darkness. The results obtained with both tasks consistently indicated slight, but significant, systematic errors compared with normal controls. In particular, the errors found can be interpreted by both rotation and compression of auditory space toward the anopic side. These findings can be explained by a visual miscalibration of the auditory space, as has been analogously demonstrated in studies on normal-sighted subjects after exposure to consistent auditory-visual disparity, for example by wearing prism lenses. The precision in sound localization of hemianopic patients was generally reduced across both hemispaces. Taken together, one may conclude that processes of cross-modal spatial adaptation, but not those of compensatory plasticity, occurred in patients with hemianopia.

Dissociation of auditory and visual straight ahead in hemianopia.

The perception of body orientation in space can be significantly affected by unilateral brain damage. One syndrome associated with such a disorder is homonymous hemianopia, resulting from lesions in postchiasmatic afferent visual pathways. Several studies in patients with hemianopia have shown that their subjective straight ahead is shifted to the anopic (contralesional) side. However, subjective straight ahead was mostly measured with reference to visual stimuli. As visual space perception is known to be distorted in hemianopia, it thus remained unclear whether the previous findings reflected this unisensory deficit or a genuine abnormality of subjective body orientation in multisensory space. In the present study, the auditory and visual straight ahead directions were assessed in twelve patients with persistent pure hemianopia (without neglect) by using related adjustment methods. As in previous studies, the visual straight ahead was found to be significantly shifted toward the anopic side. By contrast, the patients' auditory straight ahead was approximately veridical, as in healthy controls. These results indicate that in hemianopia the subjective straight ahead, in its genuine sense as the perceived orientation of the body median sagittal plane in frontal multisensory space, is unaffected. This suggests that visual brain areas, as are damaged in hemianopia, are not directly involved in relating body position to the external space. With respect to therapies for rehabilitation of hemianopia, these findings may support recent approaches, in which visual stimuli are combined with auditory stimuli in order to improve visual search behaviour.

Immobilization impairs tactile perception and shrinks somatosensory cortical maps.

Use is a major factor driving plasticity of cortical processing and cortical maps. As demonstrated of blind Braille readers and musicians, long-lasting and exceptional usage of the fingers results in the development of outstanding sensorimotor skills and in expansions of the cortical finger representations. However, how periods of disuse affect cortical representations and perception in humans remains elusive. Here, we report that a few weeks of hand and arm immobilization by cast wearing significantly reduced hand use and impaired tactile acuity, associated with reduced activation of the respective finger representations in the somatosensory cortex (SI), measured by functional magnetic resonance imaging. Hemodynamic responses in the SI correlated positively with hand-use frequency and negatively with discrimination thresholds, indicating that reduced activation was most prominent in subjects with severe perceptual impairment. We found, strikingly, compensatory effects on the contralateral, healthy hand consisting of improved perceptual performance compared to healthy controls. Two to three weeks after cast removal, perceptual and cortical changes recovered, whereas tactile acuity on the healthy side remained superior to that on the formerly immobilized side. These findings suggest that brief periods of reduced use of a limb have overt consequences and thus constitute a significant driving force of brain organization equivalent to enhanced use.

Perception of stationary and moving sound following unilateral cortectomy.

The perception of motion is an essential prerequisite to responding adequately to the dynamic aspects of sensory information in the environment. The neural substrates of auditory motion processing are, at present, still a matter of debate. It has been hypothesized that motion information is, as in the visual system, processed separately from other aspects of auditory information, such as stationary location. Here we report data on auditory perception of stationary and motion stimuli from a subject with right-sided resection of the anterior temporal-lobe region including medial aspects of Heschl's gyrus, and from three subjects with unilateral (right-sided or left-sided) hemispherectomy. All these subjects had undergone cortectomy decades earlier. The subjects with hemispherectomy were completely unable to perceive auditory motion, but showed slight to moderate deficits in judging stationary location. The subject with temporal lobectomy exhibited quite similar stationary auditory deficits as found in the subjects with hemispherectomy, but was completely normal in judging auditory motion. Thus, there was a clear dissociation of the effects of unilateral temporal lobectomy and hemispherectomy on auditory motion perception. Collectively, these findings suggest that the unilateral anterior temporal-lobe region plays a significant role in the analysis of stationary, but not moving, sound. One may assume that the cortical "motion network" is distinct from the "stationary network", and is located either in the most posterior aspects of temporal lobe, or in non-temporal, most likely parietal, areas.

Cooperation and deception recruit different subsets of the theory-of-mind network.

The term "theory of mind" (ToM) describes an evolved psychological mechanism that is necessary to represent intentions and expectations in social interaction. It is thus involved in determining the proclivity of others to cooperate or defect. While in cooperative settings between two parties the intentions and expectations of the protagonists match, they diverge in deceptive scenarios, in which one protagonist is intentionally manipulated to hold a false belief about the intention of the other. In a functional magnetic resonance imaging paradigm using cartoons showing social interactions (including the outcome of the interaction) between two or three story characters, respectively, we sought to determine those brain areas of the ToM network involved in reasoning about cooperative versus deceptive interactions. Healthy volunteers were asked to reflect upon the protagonists' intentions and expectations in cartoons depicting cooperation, deception or a combination of both, where two characters cooperated to deceive a third. Reasoning about the mental states of the story characters yielded substantial differences in activation patterns: both deception and cooperation activated bilateral temporoparietal junction, parietal and cingulate regions, while deception alone additionally recruited orbitofrontal and medial prefrontal regions. These results indicate an important role for prefrontal cortex in processing a mismatch between a character's intention and another's expectations as required in complex social interactions.

An fMRI study of theory of mind in schizophrenic patients with "passivity" symptoms.

Several studies have shown that patients with schizophrenia underactivate brain regions involved in theory of mind relative to controls during functional brain imaging. However, in most studies the samples were fairly heterogeneous in terms of clinical symptomatology. We examined a group of nine patients with first episode or recurrent episodes, who clinically presented with predominant "passivity" symptoms such as third-person auditory hallucinations or delusion of control, using a cartoon-based theory of mind task and compared activation patterns with a group of 13 healthy controls. All patients responded well to antipsychotic treatment and were only mildly symptomatic at the time of testing. The patient group showed significantly less activation of the right anterior cingulate cortex (ACC) and right insula compared with controls, but greater activation in dorsal areas of the medial prefrontal cortex, right temporal areas and left temporo-parietal junction. Patients with schizophrenia with predominant "passivity" symptoms and good response to antipsychotic treatment show a markedly diverging pattern of brain activation during theory of mind task performance compared with healthy controls. These findings suggest abnormal activation of those brain areas involved in the evaluation of self-reference during mental state attribution.

Clinical and morphological phenotype of the filamin myopathy: a study of 31 German patients.

Mutations in the filamin C gene (FLNC) cause a myofibrillar myopathy (MFM), morphologically characterized by focal myofibrillar destruction and abnormal accumulation of several proteins within skeletal muscle fibres. We studied 31 patients from four German families to evaluate the phenotype of filaminopathy. All patients harboured the same p.W2710X mutation in FLNC. Haplotype analysis suggested a founder mutation in these German filaminopathy families. The mean age at onset of clinical symptoms was 44 +/- 6 years (range, 24-57 years). Slowly progressive muscle weakness was mostly pronounced proximally, initially affecting the lower extremities and involving the upper extremities in the course of disease progression, similar to the distribution of weakness seen in limb-girdle muscular dystrophies (LGMD). Patients frequently developed respiratory muscle weakness. About one-third of the patients showed cardiac abnormalities comprising conduction blocks, tachycardia, diastolic dysfunction and left ventricular hypertrophy indicating a cardiac involvement in filaminopathy. Serum creatine kinase levels varied from normal up to 10-fold of the upper limit. Magnetic resonance imaging studies showed a rather homogenous pattern of muscle involvement in the lower extremities differing from that in other types of MFM. Myopathological features included perturbation of myofibrillar alignment, accumulation of granulofilamentous material similar to that seen in primary desminopathies and abnormal intracellular protein deposits typical of MFM. Decreased activities of oxidative enzymes and fibre hypertrophy seem to be early features, whereas dystrophic changes were present in advanced stages of filaminopathy. Rimmed vacuoles were detected in only a few cases. The intracellular aggregates were composed of a variety of proteins including filamin C, desmin, myotilin, Xin, dystrophin and sarcoglycans. Therapy is so far limited to symptomatic treatment. The German filaminopathy cohort, the largest group of patients studied so far, shares phenotypic features with LGMD and presents with characteristic histopathological findings of MFM.

Sex differences in cortical and subcortical recruitment during simple and complex motor control: an fMRI study.

In this study, we compared brain activation patterns in men and women during performance of a fine motor task, in order to investigate the influence of motor task complexity upon asymmetries of hemispheric recruitment. Thirty-three right-handed participants (17 males, 16 females) performed a self-paced finger-tapping task comprising three conditions of increasing complexity with both the dominant and the non-dominant hand. Imaging results demonstrated significant sex differences in brain activation patterns. While women showed significantly larger activation of ipsi- and contralateral task-related cortical areas than men, men exhibited significantly stronger subcortical activation in striatal regions. The observed activation differences may reflect sex differences in control of voluntary motor skills related to differential emphasis upon cortical and subcortical correlates of motor sequence processing, as well as differences in hemispheric recruitment, by means of which men and women can nevertheless achieve comparable motor performance.