Ankle joint pressure changes in a pes cavovarus model: supramalleolar valgus osteotomy versus lateralizing calcaneal osteotomy

BACKGROUND: A fixed cavovarus foot deformity can be associated with anteromedial ankle arthrosis due to elevated medial joint contact stresses. Supramalleolar valgus osteotomies (SMOT) and lateralizing calcaneal osteotomies (LCOT) are commonly used to treat symptoms by redistributing joint contact forces. In a cavovarus model, the effects of SMOT and LCOT on the lateralization of the center of force (COF) and reduction of the peak pressure in the ankle joint were compared. METHODS: A previously published cavovarus model with fixed hindfoot varus was simulated in 10 cadaver specimens. Closing wedge supramalleolar valgus osteotomies 3 cm above the ankle joint level (6 and 11 degrees) and lateral sliding calcaneal osteotomies (5 and 10 mm displacement) were analyzed at 300 N axial static load (half body weight). The COF migration and peak pressure decrease in the ankle were recorded using high-resolution TekScan pressure sensors. RESULTS: A significant lateral COF shift was observed for each osteotomy: 2.1 mm for the 6 degrees (P = .014) and 2.3 mm for the 11 degrees SMOT (P = .010). The 5 mm LCOT led to a lateral shift of 2.0 mm (P = .042) and the 10 mm LCOT to a shift of 3.0 mm (P = .006). Comparing the different osteotomies among themselves no significant differences were recorded. No significant anteroposterior COF shift was seen. A significant peak pressure reduction was recorded for each osteotomy: The SMOT led to a reduction of 29% (P = .033) for the 6 degrees and 47% (P = .003) for the 11 degrees osteotomy, and the LCOT to a reduction of 41% (P = .003) for the 5 mm and 49% (P = .002) for the 10 mm osteotomy. Similar to the COF lateralization no significant differences between the osteotomies were seen. CONCLUSION: LCOT and SMOT significantly reduced anteromedial ankle joint contact stresses in this cavovarus model. The unloading effects of both osteotomies were equivalent. More correction did not lead to significantly more lateralization of the COF or more reduction of peak pressure but a trend was seen. CLINICAL RELEVANCE: In patients with fixed cavovarus feet, both SMOT and LCOT provided equally good redistribution of elevated ankle joint contact forces. Increasing the amount of displacement did not seem to equally improve the joint pressures. The site of osteotomy could therefore be chosen on the basis of surgeon's preference, simplicity, or local factors in case of more complex reconstructions.

Outcome and patients' satisfaction after functional treatment of acute lateral ankle injuries at emergency departments versus family doctor offices

BACKGROUND: In some Western countries, more and more patients seek initial treatment even for minor injuries at emergency units of hospitals. The initial evaluation and treatment as well as aftercare of these patients require large amounts of personnel and logistical resources, which are limited and costly, especially if compared to treatment by a general practitioner. In this study, we investigated whether outsourcing from our level 1 trauma center to a general practitioner has an influence on patient satisfaction and compliance. METHODS: This prospective, randomized study, included n = 100 patients who suffered from a lateral ankle ligament injury grade I-II (16, 17). After radiological exclusion of osseous lesions, the patients received early functional treatment and were shown physical therapy exercises to be done at home, without immobilization or the use of stabilizing ortheses. The patients were randomly assigned into two groups of 50 patients each: Group A (ER): Follow-up and final examination in the hospital's emergency unit. Group B (GP): Follow-up by general practitioner, final examination at hospital's emergency unit. The patients were surveyed regarding their satisfaction with the treatment and outcome of the treatment. RESULTS: Female and male patients were equally represented in both groups. The age of the patients ranged from 16 - 64 years, with a mean age of 34 years (ER) and 35 years (GP). 98% (n = 98) of all patients were satisfied with their treatment, and 93% (n = 93) were satisfied with the outcome. For these parameters no significant difference between the two groups could be noted (p = 0.7406 and 0.7631 respectively). 39% of all patients acquired stabilizing ortheses like ankle braces (Aircast, Malleoloc etc.) on their own initiative. There was a not significant tendency for more self-acquired ortheses in the group treated by general practicioners (p = 0,2669). CONCLUSION: Patients who first present at the ER with a lateral ankle ligament injury grade I-II can be referred to a general practitioner for follow-up treatment without affecting patient satisfaction regarding treatment and treatment outcome.

Control of ventricular ciliary beating by the melanin concentrating hormone-expressing neurons of the lateral hypothalamus: a functional imaging survey

The cyclic peptide Melanin Concentrating Hormone (MCH) is known to control a large number of brain functions in mammals such as food intake and metabolism, stress response, anxiety, sleep/wake cycle, memory, and reward. Based on neuro-anatomical and electrophysiological studies these functions were attributed to neuronal circuits expressing MCHR1, the single MCH receptor in rodents. In complement to our recently published work (1) we provided here new data regarding the action of MCH on ependymocytes in the mouse brain. First, we establish that MCHR1 mRNA is expressed in the ependymal cells of the third ventricle epithelium. Second, we demonstrated a tonic control of MCH-expressing neurons on ependymal cilia beat frequency using in vitro optogenics. Finally, we performed in vivo measurements of CSF flow using fluorescent micro-beads in wild-type and MCHR1-knockout mice. Collectively, our results demonstrated that MCH-expressing neurons modulate ciliary beating of ependymal cells at the third ventricle and could contribute to maintain cerebro-spinal fluid homeostasis.

Differential activation of the lateral premotor cortex during action observation

Background Action observation leads to neural activation of the human premotor cortex. This study examined how the level of motor expertise (expert vs. novice) in ballroom dancing and the visual viewpoint (internal vs. external viewpoint) influence this activation within different parts of this area of the brain. Results Sixteen dance experts and 16 novices observed ballroom dance videos from internal or external viewpoints while lying in a functional magnetic resonance imaging scanner. A conjunction analysis of all observation conditions showed that action observation activated distinct networks of premotor, parietal, and cerebellar structures. Experts revealed increased activation in the ventral premotor cortex compared to novices. An internal viewpoint led to higher activation of the dorsal premotor cortex. Conclusions The present results suggest that the ventral and dorsal premotor cortex adopt differential roles during action observation depending on the level of motor expertise and the viewpoint.

Spinal Cord Diffusion-Tensor Imaging and Motor-evoked Potentials in Multiple Sclerosis Patients: Microstructural and Functional Asymmetry

Purpose: To assess possible association between intrinsic structural damage and clinical disability by correlating spinal cord diffusion-tensor (DT) imaging data with electrophysiological parameters in patients with a diagnosis of multiple sclerosis (MS). Materials and Methods: This study was approved by the local ethical committee according to the declaration of Helsinki and written informed consent was obtained. DT images and T1- and T2-weighted images of the spinal cord were acquired in 28 healthy volunteers and 41 MS patients. Fractional anisotropy (FA) and apparent diffusion coefficients were evaluated in normal-appearing white matter (NAWM) at the cervical level and were correlated with motor-evoked potentials (n = 34). Asymmetry index was calculated for FA values with corresponding left and right regions of interest as percentage of the absolute difference between these values relative to the sum of the respective FA values. Statistical analysis included Spearman rank correlations, Mann-Whitney test, and reliability analysis. Results: Healthy volunteers had low asymmetry index (1.5%-2.2%). In MS patients, structural abnormalities were reflected by asymmetric decrease of FA (asymmetry index: 3.6%; P = .15). Frequently asymmetrically affected among MS patients was left and right central motor conduction time (CMCT) to abductor digiti minimi muscle (ADMM) (asymmetry index, 15%-16%) and tibialis anterior muscle (TAM) (asymmetry index, 9.5%-14.1%). Statistically significant correlations of functional (ie, electrophysiological) and structural (ie, DT imaging) asymmetries were found (P = .005 for CMCT to ADMM; P = .007 for CMCT to TAM) for the cervical lateral funiculi, which comprise the crossed pyramidal tract. Interobserver reliability for DT imaging measurements was excellent (78%-87%). Conclusion: DT imaging revealed asymmetric anatomic changes in spinal cord NAWM, which corresponded to asymmetric electrophysiological deficits for both arms and legs, and reflected a specific structure-function relationship in the human spinal cord. © RSNA, 2013.

Lateral external fixation: a new surgical technique for displaced unreducible supracondylar humeral fractures in children

BACKGROUND: Percutaneous Kirschner wire fixation represents the classic treatment for displaced supracondylar humeral fractures in childhood. This type of treatment first requires satisfactory reduction of the fracture. Failure to achieve a satisfactory reduction or inadequate stabilization can result in instability of the fracture fragments, which can result in either an unsatisfactory cosmetic or functional outcome. In our experience, these problems can be overcome with the use of a small lateral external fixator. METHODS: Between 1999 and 2005, thirty-one of 170 Gartland type-III supracondylar humeral fractures were treated with a lateral external fixator. The outcome of treatment was analyzed with regard to limb alignment, elbow movement, cosmetic appearance, and patient satisfaction. RESULTS: In twenty-eight of the thirty-one patients, a satisfactory reduction was achieved with closed methods. All children except one had a normal or good range of movement. The cosmetic result was excellent in all cases. All of the children and their parents stated that they would choose this treatment again. CONCLUSIONS: The use of a small lateral external fixator seems to be a safe alternative for the treatment of displaced supracondylar fractures of the humerus when a closed reduction appears to be unattainable by means of manipulation alone or when sufficient stability is not achieved with standard methods of Kirschner wire fixation.

Posterolateral approach to the displaced posterior malleolus: functional outcome and local morbidity

BACKGROUND: Stable anatomical reconstruction of the joint surface in ankle fractures is essential to successful recovery. However, the functional outcome of fractures involving the posterior tibial plafond is often poor. We describe the morbidity and functional outcome for plate fixation of the displaced posterior malleolus using a posterolateral approach. MATERIALS AND METHODS: The posterolateral approach was used for osteosynthesis of the posterior malleolus in 45 consecutive patients (median age 54 years) with AO/Muller-classification type 44-A3 (n = 1), 44-B3 (n = 35), 44-C1 (n = 7), and 44-C2 (n = 2) ankle fractures. Thirty-three of the patients suffered complete fracture dislocation. Functional outcome at followup was measured using the modified Weber protocol and the standardized AAOS foot and ankle questionnaire. Radiological evaluation employed standardized anterior-posterior and lateral views. RESULTS: The fragment comprised a median of 24% (range, 10% to 48%) of the articular surface. Postoperative soft tissue problems were encountered in five patients (11%), one of whom required revision surgery. Two patients (4%) developed Stage I complex regional pain syndrome. Clinical and radiological followup at 25 months disclosed no secondary displacement of the fixed fragment. The median foot and ankle score was 93 (range, 58 to 100), shoe comfort score was 77 (range, 0 to 100). A median score of 7 (range, 5 to 16) was documented using the modified Weber protocol. CONCLUSION: The posterolateral approach allowed good exposure and stable fixation of a displaced posterior malleolar fragment with few local complications. The anatomical repositioning and stable fixation led to good functional and subjective outcome.

Mini-arthrotomy for lateral discoid menisci in children

BACKGROUND: Long-term results after partial, extended, or complete resection of lateral discoid meniscus in children revealed knee arthritis. The purpose of this study was to evaluate whether the operative approach, arthrotomy or arthroscopy, has an impact on the outcome and the development of arthritis. METHODS: A retrospective comparison of 2 well matching groups totaling 40 children with symptomatic lateral discoid meniscus (48 knees, mean age 8.9 years, 13 male and 27 female patients). Meniscus resection was performed via mini-arthrotomy in group 1 (n=17 patients, 20 knees) and arthroscopically in group 2 (n=23 patients, 28 knees). RESULTS: In the follow-up (mean 57 months in group 1, 62 months in group 2), functional results indicated a trend to better results in the International Knee Documentation Committee score (P=0.12) and in the Lysholm score for group 1 (P=0.13) but not in the Ikeuchi score (P=0.48). The comparison of the radiographic arthritis grading in the follow-up showed no significant arthritis in either group (P=0.22). The overall complication rate was similar in both groups (2/20, 10% in group 1; 3/28, 12% in group 2). CONCLUSIONS: Most likely because of the appropriate visualization of the children's joint and the easier instrumentation, the mini-arthrotomy led to slightly superior results compared with those after arthroscopic resection regarding functional outcome and 5 years after surgery. We can recommend the mini-arthrotomy for the resection of lateral discoid meniscus particularly in young children with narrow joint spaces and for surgeons that are not familiar with arthroscopies of small joints. LEVEL OF EVIDENCE: III (therapeutic study, case series with control group).

Unique mixed phenotype and unexpected functional effect revealed by novel compound heterozygosity mutations involving SCN5A.

BACKGROUND Functional characterization of mutations involving the SCN5A-encoded cardiac sodium channel has established the pathogenic mechanisms for type 3 long QT syndrome and type 1 Brugada syndrome and has provided key insights into the physiological importance of essential structure-function domains. OBJECTIVE This study sought to present the clinical and biophysical phenotypes discerned from compound heterozygosity mutations in SCN5A on different alleles in a toddler diagnosed with QT prolongation and fever-induced ventricular arrhythmias. METHODS A 22-month-old boy presented emergently with fever and refractory ventricular tachycardia. Despite restoration of sinus rhythm, the infant sustained profound neurological injury and died. Using polymerase chain reaction, denaturing high-performance liquid chromatography, and direct DNA sequencing, comprehensive open-reading frame/splice mutational analysis of the 12 known long QT syndrome susceptibility genes was performed. RESULTS The infant had 2 SCN5A mutations: a maternally inherited N-terminal frame shift/deletion (R34fs/60) and a paternally inherited missense mutation, R1195H. The mutations were engineered by site-directed mutagenesis and heterologously expressed transiently in HEK293 cells. As expected, the frame-shifted and prematurely truncated peptide, SCN5A-R34fs/60, showed no current. SCN5A-R1195H had normal peak and late current but abnormal voltage-dependent gating parameters. Surprisingly, co-expression of SCN5A-R34fs/60 with SCN5A-R1195H elicited a significant increase in late sodium current, whereas co-expression of SCN5A-WT with SCN5A-R34fs/60 did not. CONCLUSIONS A severe clinical phenotype characterized by fever-induced monomorphic ventricular tachycardia and QT interval prolongation emerged in a toddler with compound heterozygosity involving SCN5A: R34fs/60, and R1195H. Unexpectedly, the 94-amino-acid fusion peptide derived from the R34fs/60 mutation accentuated the late sodium current of R1195H-containing Na(V)1.5 channels in vitro.

Evaluation of a new six degrees of freedom couch for radiation therapy

Purpose: The aim of this work is to evaluate the geometric accuracy of a prerelease version of a new six degrees of freedom (6DoF) couch. Additionally, a quality assurance method for 6DoF couches is proposed. Methods: The main principle of the performance tests was to request a known shift for the 6DoF couch and to compare this requested shift with the actually applied shift by independently measuring the applied shift using different methods (graph paper, laser, inclinometer, and imaging system). The performance of each of the six axes was tested separately as well as in combination with the other axes. Functional cases as well as realistic clinical cases were analyzed. The tests were performed without a couch load and with a couch load of up to 200 kg and shifts in the range between −4 and +4 cm for the translational axes and between −3° and +3° for the rotational axes were applied. The quality assurance method of the new 6DoF couch was performed using a simple cube phantom and the imaging system. Results: The deviations (mean ± one standard deviation) accumulated over all performance tests between the requested shifts and the measurements of the applied shifts were −0.01 ± 0.02, 0.01 ± 0.02, and 0.01 ± 0.02 cm for the longitudinal, lateral, and vertical axes, respectively. The corresponding values for the three rotational axes couch rotation, pitch, and roll were 0.03° ± 0.06°, −0.04° ± 0.12°, and −0.01° ± 0.08°, respectively. There was no difference found between the tests with and without a couch load of up to 200 kg. Conclusions: The new 6DoF couch is able to apply requested shifts with high accuracy. It has the potential to be used for treatment techniques with the highest demands in patient setup accuracy such as those needed in stereotactic treatments. Shifts can be applied efficiently and automatically. Daily quality assurance of the 6DoF couch can be performed in an easy and efficient way. Long-term stability has to be evaluated in further tests.

Rivastigmine effects on EEG spectra and three-dimensional LORETA functional imaging in Alzheimer's disease

OBJECTIVE The objective of the study is to investigate the electrocortical and the global cognitive effects of 3 months rivastigmine medication in a group of mild to moderate Alzheimer's disease patients. MATERIALS AND METHODS Multichannel EEG and cognitive performances measured with the Mini Mental State Examination in a group of 16 patients with mild to moderate Alzheimer's Disease were collected before and 3 months after the onset of rivastigmine medication. RESULTS Spectral analysis of the EEG data showed a significant power decrease in the delta and theta frequency bands during rivastigmine medication, i.e., a shift of the power spectrum towards 'normalization'. Three-dimensional low resolution electromagnetic tomography (LORETA) functional imaging localized rivastigmine effects in a network that includes left fronto-parietal regions, posterior cingulate cortex, bilateral parahippocampal regions, and the hippocampus. Moreover, a correlation analysis between differences in the cognitive performances during the two recordings and LORETA-computed intracortical activity showed, in the alpha1 frequency band, better cognitive performance with increased cortical activity in the left insula. CONCLUSION The results point to a 'normalization' of the EEG power spectrum due to medication, and the intracortical localization of these effects showed an increase of cortical activity in frontal, parietal, and temporal regions that are well-known to be affected in Alzheimer's disease. The topographic convergence of the present results with the memory network proposed by Vincent et al. (J. Neurophysiol. 96:3517-3531, 2006) leads to the speculation that in our group of patients, rivastigmine specifically activates brain regions that are involved in memory functions, notably a key symptom in this degenerative disease.

CD62L (L-selectin) shedding for assessment of functional blockade of TNF alpha in anti-TNF treated IBD patients: clinical feasibility and perspectives (DOP060)

Background Tumor necrosis factor (TNF) inhibition is central to the therapy of inflammatory bowel diseases (IBD). However, loss of response (LOR) is frequent and additional tests to help decision making with costly anti-TNF Therapy are needed. Methods Consecutive IBD Patients receiving anti-TNF therapy (Infliximab (IFX) or Adalimumab (after IFX LOR) from Bern University Hospital were identified and followed prospectively. Patient whole blood was stimulated with a dose-titration of two triggers of TLR receptors human: TNF and LPS. Median fluorescence intensity of CD62L on the surface of granulocytes was quantified by surface staining with specific antibodies (CD33, CD62L) and flow cytometry and logistic curves to these data permits the calculation of EC50 or the half maximal effective concentration TNF concentration to induce shedding [1]. A shift in the concentration were CD62L shedding occurred was seen before and after the anti-TNF agent administraion which permits to predict the response to the drug. This predicted response was correlated to the clinical evolution of the patients in order to analyze the ability of this test to identify LOR to IFX. Results We collected prospective clinical data and blood samples, before and after anti-TNF agent administration, on 33 IBD patients, 25 Crohn's disease and 8 ulcerative colitis patients (45% females) between June 2012 and November 2013. The assay showed a functional blockade of IFX (PFR) for 22 patients (17 CD and 5 UC) whereas 11 (8 CD and 3 UC) had no functional response (NR) to IFX. Clinical characteristics (e.g. diagnosis, disease location, smoking status, BMI and number of infusions) were no significantly different between predicted PFR and NR. Among the 22 Patients with PRF, only 1 patient was a clinical non responder (LOR to IFX), based on clinical prospective evaluation by IBD gastroenterologists (PJ, AM), and among the 11 predicted NR, 3 had no clinical LOR. Sensitivity of this test was 95% and specificity 73% and AUC adjusted for age and gender was 0.81 (Figure 1). During follow up (median 10 mo, 3–15) 8 “hard” outcomes occured (3 medic. flares, 4 resections and 1 new fistula) 2 in the PFR and 6 in the NR group (25% vs. 75%; p < 0.01). Correlation with clinical response is presented in Figure 2. Figure 1. Figure 2. Correlation clinical response - log EC50 changes: 1 No, 2 partial, 3 complete clinical response. Conclusion CD62L (L-Selectin) shedding is the first validated test of functional blockade of TNF alpha in anti-TNF treated IBD patients and will be a useful tool to guide medical decision on the use of anti-TNF agents. Comparative studies with ATI and trough level of IFX are ongoing. 1. Nicola Patuto, Emma Slack, Frank Seibold and Andrew J. Macpherson, (2011), Quantitating Anti-TNF Functionality to Inform Dosing and Choice of Therapy, Gastroenterology, 140 (5, Suppl. I), S689.

Neurotized lateral gastrocnemius muscle transfer for persistent traumatic peroneal nerve palsy: Surgical technique

INTRODUCTION Persistent traumatic peroneal nerve palsy, following nerve surgery failure, is usually treated by tendon transfer or more recently by tibial nerve transfer. However, when there is destruction of the tibial anterior muscle, an isolated nerve transfer is not possible. In this article, we present the key steps and surgical tips for the Ninkovic procedure including transposition of the neurotized lateral gastrocnemius muscle with the aim of restoring active voluntary dorsiflexion. SURGICAL TECHNIQUE The transposition of the lateral head of the gastrocnemius muscle to the tendons of the anterior tibial muscle group, with simultaneous transposition of the intact proximal end of the deep peroneal nerve to the tibial nerve of the gastrocnemius muscle by microsurgical neurorrhaphy is performed in one stage. It includes 10 key steps which are described in this article. Since 1994, three clinical series have highlighted the advantages of this technique. Functional and subjective results are discussed. We review the indications and limitations of the technique. CONCLUSION Early clinical results after neurotized lateral gastrocnemius muscle transfer appear excellent; however, they still need to be compared with conventional tendon transfer procedures. Clinical studies are likely to be conducted in this area largely due to the frequency of persistant peroneal nerve palsy and the limitations of functional options in cases of longstanding peripheral nerve palsy, anterior tibial muscle atrophy or destruction.

Functional importance of conserved nucleotides at the histone RNA 3' processing site.

Histone pre-mRNA 3' processing is controlled by a hairpin element preceding the processing site that interacts with a hairpin-binding protein (HBP) and a downstream spacer element that serves as anchoring site for the U7 snRNP. In addition, the nucleotides following the hairpin and surrounding the processing site (ACCCA'CA) are conserved among vertebrate histone genes. Single to triple nucleotide mutations of this sequence were tested for their ability to be processed in nuclear extract from animal cells. Changing the first four nucleotides had no qualitative and little if any quantitative effects on histone RNA 3' processing in mouse K21 cell extract, where processing of this gene is virtually independent of the HBP. A gel mobility shift assay revealing HBP interactions and a processing assay in HeLa cell extract (where the contribution of HBP to efficient processing is more important) showed that only one of these mutations, predicted to extend the hairpin by one base pair, affected the interaction with HBP. Mutations in the next three nucleotides affected both the cleavage efficiency and the choice of processing sites. Analysis of these novel sites indicated a preference for the nucleotide 5' of the cleavage site in the order A > C > U > G. Moreover, a guanosine in the 3' position inhibited cleavage. The preference for an A is shared with the cleavage/polyadenylation reaction, but the preference order for the other nucleotides is different [Chen F, MacDonald CC, Wilusz J, 1995, Nucleic Acids Res 23:2614-2620].

Bilateral deep brain stimulation: the placement of the second electrode is not necessarily less accurate than that of the first one.

BACKGROUND Deep brain stimulation (DBS) is recognized as an effective treatment for movement disorders. We recently changed our technique, limiting the number of brain penetrations to three per side. OBJECTIVES The first aim was to evaluate the electrode precision on both sides of surgery since we implemented this surgical technique. The second aim was to analyse whether or not the electrode placement was improved with microrecording and macrostimulation. METHODS We retrospectively reviewed operation protocols and MRIs of 30 patients who underwent bilateral DBS. For microrecording and macrostimulation, we used three parallel channels of the 'Ben Gun' centred on the MRI-planned target. Pre- and post-operative MRIs were merged. The distance between the planned target and the centre of the implanted electrode artefact was measured. RESULTS There was no significant difference in targeting precision on both sides of surgery. There was more intra-operative adjustment of the second electrode positioning based on microrecording and macrostimulation, which allowed to significantly approach the MRI-planned target on the medial-lateral axis. CONCLUSION There was more electrode adjustment needed on the second side, possibly in relation with brain shift. We thus suggest performing a single central track with electrophysiological and clinical assessment, with multidirectional exploration on demand for suboptimal clinical responses.