Management and outcome of vagus nerve stimulator implantation: experience of an otolaryngeal/neuropediatric cooperation.

OBJECTIVE: Vagus nerve stimulator (VNS) implantation is an established therapy for pharmacoresistant epilepsy that is not amenable to curative epilepsy surgery. Historically, VNS implantation has been performed by neurosurgeons, but otolaryngologist involvement is increasingly common. In this retrospective study, we aimed to evaluate the efficacy and safety of VNS implantation in children and adolescents from the otolaryngologists' perspective. METHODS: This study included children and adolescents who had undergone VNS implantation at the study center between 2014 and 2018. Patient files were analyzed with regards to the durations of device implantation and hospitalization, postoperative complications, and clinical outcome, including seizure frequency, clinical global impression of improvement (CGI-I) score, and quality of life (QoL). RESULTS: A total of 73 children underwent VNS surgery. The median age at implantation was 9.3 ± 4.6 years, and median epilepsy duration before VNS surgery was 6 ± 4 years. Lennox-Gastaut syndrome was the most common syndrome diagnosis (62.3%), and structural abnormalities (49.3%) the most frequent etiology. Operation times ranged from 30 to 200 min, and median postoperative hospitalization length was 2 ± 0.9 days. No complications occurred, except for four revisions and two explantations due to local infections (2.7%). Among our patients, 76.7% were responders (≥ 50% reduction in seizure frequency), 72.1% showed improved CGI-I scores, and 18.6-60.5% exhibited considerable improvements in the QoL categories energy, emotional health, and cognitive functions. CONCLUSION: Our results indicate that VNS implantation is a highly effective and safe treatment option for children and adolescents with AED-refractory epilepsies who are not candidates for curative epilepsy surgery.

What are the factors to affect outcome and healing of meniscus bucket handle tears?

INTRODUCTION: The purpose of this study is to identify patient, meniscus rupture and surgical characteristics that influence the outcome and clinical healing following operative repair of bucket handle tears. METHODS: Between 02/2006 and 10/2012, a total of 38 patients (14 women, 24 men) with bucket handle tears underwent surgical meniscus repair. There were 27 isolated repairs and 11 with concomitant anterior cruciate ligament (ACL) replacement. Patients were analyzed on an average of 44.4 months (range 15-96 months) after surgery by the use of standardized subjective scoring instruments [Lysholm, International Knee Documentation Committee (IKDC), Knee Injury and Osteoarthritis Outcome Score (KOOS) and Tegner Activity Scale (TAS)]. To identify factors affecting the outcome and suture survival, patient-specific, trauma-specific as well as meniscus- and surgery-specific factors were collected. Patients were divided in two groups with healed menisci (group 1) and re-rupture subjects (group 2). Meniscus re-rupture was defined as a clinical failure. RESULTS: There were 25 patients with healed menisci and 13 (34.2%) that sustained re-rupture and underwent either partial meniscectomy (n = 8) or re-suture (n = 5). Group 1 achieved slightly higher outcome compared to group 2 [Lysholm: 87.8 vs. 84.3 (p = 0.35), IKDC: 86.9 vs. 85.7 (p = 0.67), KOOS: 91.3 vs. 90.5 (p = 0.74)]. TAS was better for group 2 [5.9 vs. 6.8 (p = 0.36)]. Strong impact to result in a significantly increased outcome was identified for higher age, subjective knee joint stability, high preoperative Lysholm Score, short trauma-to-repair time, previous ACL reconstruction and a smaller number of sutures to fulfill meniscus repair. Lower patient age, male gender and higher activity level had the strongest impact to provoke re-rupture. CONCLUSION: Clinical outcome after meniscus bucket handle suture is satisfying. Re-rupture rate among this collective was 34.2%. Clear risk factors were identified for diminished clinical healing and outcome.

Operative versus conservative treatment of apophyseal avulsion fractures of the pelvis in the adolescents: a systematical review with meta-analysis of clinical outcome and return to sports.

BACKGROUND: Avulsion fractures of the pelvic apophyses typically occur in adolescent athletes due to a sudden strong muscle contraction while growth plates are still open. The main goals of this systematic review with meta-analysis were to summarize the evidence on clinical outcome and determine the rate of return to sports after conservative versus operative treatment of avulsion fractures of the pelvis. METHODS: A systematic search of the Ovid database was performed in December 2016 to identify all published articles reporting outcome and return to preinjury sport-level after conservative or operative treatment of avulsion fractures of the pelvis in adolescent patients. Included studies were abstracted regarding study characteristics, patient demographics and outcome measures. The methodological quality of the studies was assessed with the Coleman Methodology Score (CMS). RESULTS: Fourteen studies with a total of 596 patients met the inclusion criteria. The mean patient age was 14.3 ± 0.6 years and 75.5% of patients were male. Affected were the anterior inferior iliac spine (33.2%), ischial tuberosity (29.7%), anterior superior iliac spine (27.9%), iliac crest (6.7%) lesser trochanter (1.8%) and superior corner of the pubic symphysis (1.2%). Mean follow-up was 12.4 ± 11.7 months and most of the patients underwent a conservative treatment (89.6%). The overall success rate was higher in the patients receiving surgery (88%) compared to the patients receiving conservative treatment (79%) (p = 0,09). The rate of return to sports was 80% in conservative and 92% in operative treated patients (p = 0,03). Overall, the methodological quality of the included studies was low, with a mean CMS of 41.2. CONCLUSION: On the basis of the present meta-analysis, the overall success and return to sports rate was higher in the patients receiving surgery. Especially in patients with fragment displacement greater 15 mm and high functional demands, surgical treatment should be considered.

Patellar tendinopathy in young elite soccer- clinical and sonographical analysis of a German elite soccer academy.

BACKGROUND: The prevalence of patellar tendinopathy is elevated in elite soccer compared to less explosive sports. While the burden of training hours and load is comparably high in youth elite players (age < 23 years), little is known about the prevalence of patellar tendinopathy at this age. There is only little data available on the influence of age, the amount of training, the position on the field, as well as muscular strength, range of motion, or sonographical findings in this age group. The purpose of the present study was to examine the above-mentioned parameters in all age groups of a German youth elite soccer academy. METHODS: One hundred nineteen male youth soccer players (age 15,97 ± 2,24 years, height 174, 60 ± 10,16 cm, BMI 21, 24 ± 2,65) of the U-13 to U-23 teams were part of the study. Data acquisition included sport specific parameters such as footwear, amount of training hours, leg dominance, history of tendon pathologies, and clinical examination for palpatory pain, indurations, muscular circumference, and range of motion. Subjective complaints were measured with the Victorian Institute of Sport Assessment Patellar (VISA-P) Score. Furthermore, sonographical examinations (Aplio SSA-770A/80; Toshiba, Tokyo, Japan) with 12-MHz multifrequency linear transducers (8-14 MHz) of both patellar tendons were performed with special emphasis on hyper- and hypo echogenic areas, diameter and neovascularization. RESULTS: The prevalence of patellar tendinopathies was 13.4%. Seventy-five percent of the players complained of pain of their dominant leg with onset of pain at training in 87.5%. The injured players showed a medium amount of 10.34 ± 3.85 training hours and a medium duration of symptoms of 11.94 ± 18.75 weeks. Two thirds of players with patellar tendinopathy were at the age of 15-17 (Odds ratio 1.89) while no differences between players of the national or regional league were observed. In case of patellar tendinopathy, VISA-P was significantly lower in comparison to healthy players (mean ± SD 76.80 ± 28.56 points vs. 95.85 ± 10.37). The clinical examination revealed local pain at the distal patella, pain at stretching, and thickening of the patellar tendon (p = 0.02). The mean tendon diameter measured 2 cm distally to the patella was 4.10 ± 0.68 mm with a significantly increased diameter of 0.15 mm in case of an underlying tendinopathy (p = 0.00). The incidence of hypo-echogenic areas and neovascularizations was significantly elevated in players with patellar tendon syndrome (PTS) (p = 0.05). CONCLUSION: The prevalence of patellar tendinopathy in youth elite soccer is relatively high in comparison to available data of adult players. Especially players at the age of 15 to 17 are at considerable risk. Tendon thickening, hypo-echogenic areas, and neovascularization are more common in tendons affected by PTS.

[Osteotomies around the knee for ligament insufficiency]. / Kniegelenknahe Osteotomien bei Bandinsuffizienzen.

BACKGROUND: The osseous geometry of the lower limb has a significant impact on knee instability after ligament injuries, and osseous malalignment has been shown to be a significant risk factor for the failure of ligament reconstruction procedures. Therefore, osteotomies around the knee have gained importance as a combined or isolated treatment option in the ligament deficient and malaligned knee. In addition to unloading of an arthritic knee compartment, osteotomies are also performed to protect a reconstructed ligament and to stabilize the joint without ligament surgery. PROCEDURE: In addition to the correction of varus or valgus malalignment, correction of sagittal imbalance by modifying the tibial slope is an emerging concept. Even small modifications of the tibial slope (≤5°) have been shown to change the anterior-posterior translation in a clinically significant manner. Especially in the case of chronic posterior or posterolateral instability, a valgus-producing and slope-increasing high tibial osteotomy is usually the first treatment option, and ligament surgery is only performed optionally. Isolated modification of the tibial slope is performed infrequently, however, a slope-decreasing osteotomy should be considered in patients with multiple failed ACL reconstructions and a tibial slope of >12°.

Expression of microRNAs miR21, miR146a, and miR155 in tuberous sclerosis complex cortical tubers and their regulation in human astrocytes and SEGA-derived cell cultures.

Tuberous sclerosis complex (TSC) is a genetic disease presenting with multiple neurological symptoms including epilepsy, mental retardation, and autism. Abnormal activation of various inflammatory pathways has been observed in astrocytes in brain lesions associated with TSC. Increasing evidence supports the involvement of microRNAs in the regulation of astrocyte-mediated inflammatory response. To study the role of inflammation-related microRNAs in TSC, we employed real-time PCR and in situ hybridization to characterize the expression of miR21, miR146a, and miR155 in TSC lesions (cortical tubers and subependymal giant cell astrocytomas, SEGAs). We observed an increased expression of miR21, miR146a, and miR155 in TSC tubers compared with control and perituberal brain tissue. Expression was localized in dysmorphic neurons, giant cells, and reactive astrocytes and positively correlated with IL-1ß expression. In addition, cultured human astrocytes and SEGA-derived cell cultures were used to study the regulation of the expression of these miRNAs in response to the proinflammatory cytokine IL-1ß and to evaluate the effects of overexpression or knockdown of miR21, miR146a, and miR155 on inflammatory signaling. IL-1ß stimulation of cultured glial cells strongly induced intracellular miR21, miR146a, and miR155 expression, as well as miR146a extracellular release. IL-1ß signaling was differentially modulated by overexpression of miR155 or miR146a, which resulted in pro- or anti-inflammatory effects, respectively. This study provides supportive evidence that inflammation-related microRNAs play a role in TSC. In particular, miR146a and miR155 appear to be key players in the regulation of astrocyte-mediated inflammatory response, with miR146a as most interesting anti-inflammatory therapeutic candidate.

Dysregulation of the (immuno)proteasome pathway in malformations of cortical development.

BACKGROUND: The proteasome is a multisubunit enzyme complex involved in protein degradation, which is essential for many cellular processes. During inflammation, the constitutive subunits are replaced by their inducible counterparts, resulting in the formation of the immunoproteasome. METHODS: We investigated the expression pattern of constitutive (ß1, ß5) and immunoproteasome (ß1i, ß5i) subunits using immunohistochemistry in malformations of cortical development (MCD; focal cortical dysplasia (FCD) IIa and b, cortical tubers from patients with tuberous sclerosis complex (TSC), and mild MCD (mMCD)). Glial cells in culture were used to elucidate the mechanisms regulating immunoproteasome subunit expression. RESULTS: Increased expression was observed in both FCD II and TSC; ß1, ß1i, ß5, and ß5i were detected (within cytosol and nucleus) in dysmorphic neurons, balloon/giant cells, and reactive astrocytes. Glial and neuronal nuclear expression positively correlated with seizure frequency. Positive correlation was also observed between the glial expression of constitutive and immunoproteasome subunits and IL-1ß. Accordingly, the proteasome subunit expression was modulated by IL-1ß in human astrocytes in vitro. Expression of both constitutive and immunoproteasome subunits in FCD II-derived astroglial cultures was negatively regulated by treatment with the immunomodulatory drug rapamycin (inhibitor of the mammalian target of rapamycin (mTOR) pathway, which is activated in both TSC and FCD II). CONCLUSIONS: These observations support the dysregulation of the proteasome system in both FCD and TSC and provide new insights on the mechanism of regulation the (immuno)proteasome in astrocytes and the molecular links between inflammation, mTOR activation, and epilepsy.

Outcome and predictors for successful resuscitation in the emergency room of adult patients in traumatic cardiorespiratory arrest.

BACKGROUND: Data of the TraumaRegister DGU® were analyzed to derive survival rates, neurological outcome and prognostic factors of patients who had suffered traumatic cardiac arrest in the early treatment phase. METHODS: The database of the TraumaRegister DGU® from 2002 to 2013 was analyzed. The main focus of this survey was on different time points of performed resuscitation. Descriptive and multivariate analyses (logistic regression) were performed with the neurological outcome (Glasgow Outcome Scale) and survival rate as the target variable. Patients were classified according to CPR in the prehospital phase and/or in the emergency room (ER). Patients without CA served as a control group. The database does not include patients who required prehospital CPR but did not achieve ROSC. RESULTS: A total of 3052 patients from a total of 38,499 cases had cardiac arrest during the early post-trauma phase and required CPR in the prehospital phase and/or in the ER. After only prehospital resuscitation (n = 944) survival rate was 31.7 %, and 14.7 % had a good/moderate outcome. If CPR was required in the ER only (n = 1197), survival rate was 25.6 %, with a good/moderate outcome in 19.2 % of cases. A total of 4.8 % in the group with preclinical and ER resuscitation survived, and just 2.7 % had a good or moderate outcome. Multivariate logistic regression analysis revealed the following prognostic factors for survival after traumatic cardiac arrest: prehospital CPR, shock, coagulopathy, thorax drainage, preclinical catecholamines, unconsciousness, and injury severity (Injury Severity Score). CONCLUSIONS: With the knowledge that prehospital resuscitated patients who not reached the hospital could not be included, CPR after severe trauma seems to yield a better outcome than most studies have reported, and appears to be more justified than the current guidelines would imply. Preclinical resuscitation is associated with a higher survival rate and better neurological outcome compared with resuscitation in the ER. If resuscitation in the ER is necessary after a preclinical performed resuscitation the survival rate is marginal, even though 56 % of these patients had a good and moderate outcome. The data we present may support algorithms for resuscitation in the future.

Differential functional benefits of ultra highfield MR systems within the language network.

Several investigations have shown limitations of fMRI reliability with the current standard field strengths. Improvement is expected from ultra highfield systems but studies on possible benefits for cognitive networks are lacking. Here we provide an initial investigation on a prominent and clinically highly-relevant cognitive function: language processing in individual brains. 26 patients evaluated for presurgical language localization were investigated with a standardized overt language fMRI paradigm on both 3T and 7T MR scanners. During data acquisition and analysis we made particular efforts to minimize effects not related to static magnetic field strength differences. Six measures relevant for functional activation showed a large dissociation between essential language network nodes: although in Wernicke's area 5/6 measures indicated a benefit of ultra highfield, in Broca's area no comparison was significant. The most important reason for this discrepancy was identified as being an increase in susceptibility-related artifacts in inferior frontal brain areas at ultra high field. We conclude that functional UHF benefits are evident, however these depend crucially on the brain region investigated and the ability to control local artifacts.

Long-term follow-up of pediatric patients treated with mitoxantrone for multiple sclerosis.

The chemotherapeutic agent mitoxantrone is approved for the treatment of aggressive multiple sclerosis (MS) in adults. Its use, however, is limited by the risk of severe adverse events including cardiotoxicity, myelosuppression, liver toxicity and secondary leukemia. The aim of this retrospective study is to present data on the safety, tolerability and efficacy of mitoxantrone in a small cohort of children with MS. 4 pediatric MS patients with a high relapse rate or severe, disabling relapses were treated with mitoxantrone and followed for 3.8-18 years. The cumulative dose of mitoxantrone was 36, 68, 84 and 120 mg/m (2), respectively. The frequency and severity of relapses as well as disability scores, decreased in the year after treatment onset. Short-term adverse events were transient in all cases. Cardiac monitoring by transthoracic echocardiography (TTE) showed asymptomatic left ventricular dysfunction during treatment in 1 patient, which was again normal at the next assessment. Long-term adverse events, including late-onset mitoxantrone-induced cardiotoxicity or secondary leukemia did not occur during the follow-up period. In our cohort of pediatric MS patients, mitoxantrone showed short-term reduction of disease activity and no long-term adverse events on follow-up. However, the risk of mitoxantrone-induced cardiotoxicity or toxic leukemia remains a life-long threat.

Arthroscopic transtibial pullout repair for posterior meniscus root tears.

OBJECTIVE: Anatomic repair of the torn meniscal root using transosseous sutures through the proximal tibia. INDICATIONS: Nontraumatic meniscal root tears without severe degenerative changes (Kellgren-Lawrence grade ≤ 2), good quality meniscal tissue, traumatic root tears with or without concomitant anterior cruciate ligament tears or multiligament injuries. CONTRAINDICATIONS: Uncorrected varus or valgus malalignment (>3°), osteoarthritis Kellgren-Lawrence grades III and IV, and diffuse articular cartilage changes International Cartilage Regeneration and Joint Preservation Society (ICRS) grades III and IV of the effected compartment, noncompliance. SURGICAL TECHNIQUE: Root tear confirmed by probing; location for the planned root refixation on the tibial plateau is identified. A tibial socket or full transtibial tunnel created with an aiming drill guide. Using a self-retrieving suture passing device or a curved suture passer, the torn meniscus root sutured with no. 0 non-absorbable braided suture. Meniscal sutures passed through the tibial tunnel and the meniscus root reduced into the socket or tunnel by tensioning the free ends of the sutures, followed by fixation on the tibial cortex. FOLLOW-UP: Toe touch weight-bearing for 6 weeks, restricted range of motion (0-60° of flexion) for 6 weeks, no axial loading at flexion angles >90° until 6 months postoperatively. RESULTS: For medial root tears, pullout repair significantly improves functional outcome scores and seems to prevent the progression of osteoarthritis in the short-term. Complete healing observed in only 60% of patients. Negative prognostic factors: varus malalignment > 5°, cartilage degeneration Outerbridge grade III and IV, and older age. Outcomes after lateral root repair are encouraging with apparent prevention of progression of osteoarthritis.

Assessing Corticospinal Tract Asymmetry in Unilateral Polymicrogyria.

BACKGROUND AND PURPOSE: Asymmetry of the corticospinal tract in congenital lesions is a good prognostic marker for preserved motor function after hemispherectomy. This study aimed to assess this marker and provide a clinically feasible approach in selected cases of unilateral polymicrogyria. MATERIALS AND METHODS: Corticospinal tract asymmetry of 9 patients with unilateral polymicrogyria substantially affecting the central region was retrospectively assessed on axial T1WI and DTI. Volumes of the brain stem and thalamus and DTI parameters of the internal capsule were measured. Two neuroradiologists independently rated the right-left asymmetry at 4 levels along the corticospinal tract. DTI tractography was used to determine the motor cortex within polymicrogyria, with task-based functional MR imaging available in 3/9 cases. RESULTS: Visual assessment of the brain stem asymmetry showed excellent correlation with quantitative measures on both T1WI and color-coded DTI maps (P = .007 and P = .023). Interrater reliability regarding structural and DTI-based corticospinal tract asymmetry was best at the midbrain (Cohen κ = 0.77, P = .018). Three patients underwent functional hemispherectomy with postsurgical stable motor function, all showing marked corticospinal tract asymmetry preoperatively. Following the DTI-based corticospinal tract trajectories allowed identifying the presumed primary motor region within the dysplastic cortex in 9/9 patients, confirmed by functional MR imaging in 3/3 cases. CONCLUSIONS: Visual assessment of corticospinal tract asymmetry in unilateral polymicrogyria involving the motor cortex is most reliable with T1WI and color-coded DTI maps at the level of the midbrain. Pronounced asymmetry predicts preserved motor function after hemispherectomy. DTI-based tractography can be used as a guidance tool to the motor cortex within polymicrogyria.

[Distal femoral osteotomy using a lateral opening wedge technique]. / Distale Femurosteotomie in lateraler Open-wedge-Technik.

OBJECTIVE: To shift the weight-bearing axis of the lower limb medially by opening a lateral-based metaphyseal osteotomy at the distal femur. INDICATIONS: Femoral-based valgus malalignment and symptomatic lateral unicompartimental osteoarthritis, lateral hyperpression syndrome, cartilage therapy of the lateral compartment, lateral meniscal replacement/transplantation, medial instability with valgus thrust, reconstruction of the medial collateral ligament, patellar instability and/or maltracking. CONTRAINDICATIONS: Advanced cartilage damage (>grade 2) or subtotal meniscal loss of the medial compartment, age >65 years (relative), nicotine abuse, body mass index >30, flexion contracture >25°, corrections with a wedge base >10 mm in case of congenital deformities, inflammatory or septic arthritis, severe osteoporosis. SURGICAL TECHNIQUE: Lateral approach to the distal femur; biplanar osteotomy (frontal + axial osteotomy), gradual opening of the osteotomy, osteotomy fixation with a locking plate. POSTOPERATIVE MANAGEMENT: Free range of motion. Partial weight bearing with 20 kg for 2 weeks, followed by progressive weight bearing thereafter. RESULTS: Mean improvement of knee scores from 20-30 points and mean 10-year survival rate of 80% in patients with lateral unicompartimental osteoarthritis. Mean complication rate of 9%.

Spacial perception and spatial memory in children with benign childhood epilepsy with centro-temporal spikes (BCECTS).

Despite the benign prognosis regarding the response of seizures to treatment, some evidence now exists that patients with benign childhood epilepsy with centro-temporal spikes (BCECTS) may have neuropsychological deficits sometimes leading to academic underachievement. There is, however, no general agreement on the exact profile of functions disturbed. This study was designed to identify significant deficits in spatial perception and memory in children with BCECTS (ages 6-10 years) compared with healthy controls matched for age, sex and socioeconomic status. The neuropsychological test battery administered consisted of the HAWIK-III, the "Tübinger Luria Christensen Neuropsychological Test Set for Children", the "Kaufman Assessment Battery for Children" and the "Differential Neuropsychological Test". Twenty-two patients and 22 control subjects completed all tests. Children with BCECTS exhibited significant deficits in higher functions of spatial perception, including spatial orientation, as well as in basal and complex spatial memory. Deficits were independent of the lateralization of the epileptogenic foci and independent of anti-convulsive drug treatment.

Promoter-Specific Hypomethylation Correlates with IL-1ß Overexpression in Tuberous Sclerosis Complex (TSC).

In tuberous sclerosis complex (TSC), overexpression of numerous genes associated with inflammation has been observed. Among different proinflammatory cytokines, interleukin-1ß (IL-1ß) has been shown to be significantly involved in epileptogenesis and maintenance of seizures. Recent evidence indicates that IL-1ß gene expression can be regulated by DNA methylation of its promoter. In the present study, we hypothesized that hypomethylation in the promoter region of the IL-1ß gene may underlie its overexpression observed in TSC brain tissue. Bisulfite sequencing was used to study the methylation status of the promoter region of the IL-1ß gene in TSC and control samples. We identified hypomethylation in the promoter region of the IL-1ß gene in TSC samples. IL-1ß is overexpressed in tubers, and gene expression is correlated with promoter hypomethylation at CpG and non-CpG sites. Our results provide the first evidence of epigenetic modulation of the IL-1ß signaling in TSC. Thus, strategies that target epigenetic alterations could offer new therapeutic avenues to control the persistent activation of interleukin-1ß-mediated inflammatory signaling in TSC brain.

Prediction of transition from ultra-high risk to first-episode psychosis using a probabilistic model combining history, clinical assessment and fatty-acid biomarkers.

Current criteria identifying patients with ultra-high risk of psychosis (UHR) have low specificity, and less than one-third of UHR cases experience transition to psychosis within 3 years of initial assessment. We explored whether a Bayesian probabilistic multimodal model, combining baseline historical and clinical risk factors with biomarkers (oxidative stress, cell membrane fatty acids, resting quantitative electroencephalography (qEEG)), could improve this specificity. We analyzed data of a UHR cohort (n=40) with a 1-year transition rate of 28%. Positive and negative likelihood ratios were calculated for predictor variables with statistically significant receiver operating characteristic curves (ROCs), which excluded oxidative stress markers and qEEG parameters as significant predictors of transition. We clustered significant variables into historical (history of drug use), clinical (Positive and Negative Symptoms Scale positive, negative and general scores and Global Assessment of Function) and biomarker (total omega-3, nervonic acid) groups, and calculated the post-test probability of transition for each group and for group combinations using the odds ratio form of Bayes' rule. Combination of the three variable groups vastly improved the specificity of prediction (area under ROC=0.919, sensitivity=72.73%, specificity=96.43%). In this sample, our model identified over 70% of UHR patients who transitioned within 1 year, compared with 28% identified by standard UHR criteria. The model classified 77% of cases as very high or low risk (P>0.9, <0.1) based on history and clinical assessment, suggesting that a staged approach could be most efficient, reserving fatty-acid markers for 23% of cases remaining at intermediate probability following bedside interview.

[Development of an epiretinal prosthesis for stimulation of the human retina]. / Entwicklung einer epiretinalen Prothese zur Stimulation der humanen Netzhaut.

Degenerations of the outer retina in retinal diseases such as retinitis pigmentosa lead to blindness due to photoreceptor loss. A therapeutic option for visual rehabilitation is presently not available. Over the last few years, a retinal prosthesis has been developed and its use has been tested in animal experiments as well as in humans. With the epiretinal implant images of the environment are taken by a camera, these data are transmitted to an intraocular encoder, and the retina is electrically stimulated by a retinal stimulator placed epiretinally. The stimulation electrodes are placed as flexible microcontact electrodes by pars plana vitrectomy in an epimacular position. The threshold is determined by stimulations of increasing amplitudes. Initial results of acute epiretinal stimulation using an epiretinal implant in legally blind patients demonstrate that acute epiretinal stimulation of the human retina is feasible and safe.

Assignment of Empirical Mode Decomposition Components and Its Application to Biomedical Signals.

OBJECTIVES: Empirical mode decomposition (EMD) is a frequently used signal processing approach which adaptively decomposes a signal into a set of narrow-band components known as intrinsic mode functions (IMFs). For multi-trial, multivariate (multiple simultaneous recordings), and multi-subject analyses the number and signal properties of the IMFs can deviate from each other between trials, channels and subjects. A further processing of IMFs, e.g. a simple ensemble averaging, should determine which IMFs of one signal correspond to IMFs from another signal. When the signal properties have similar characteristics, the IMFs are assigned to each other. This problem is known as correspondence problem. METHODS: From the mathematical point of view, in some cases the correspondence problem can be transformed into an assignment problem which can be solved e.g. by the Kuhn-Munkres algorithm (KMA) by which a minimal cost matching can be found. We use the KMA for solving classic assignment problems, i.e. the pairwise correspondence between two sets of IMFs of equal cardinalities, and for pairwise correspondences between two sets of IMFs with different cardinalities representing an unbalanced assignment problem which is a special case of the k-cardinality assignment problem. RESULTS: A KMA-based approach to solve the correspondence problem was tested by using simulated, heart rate variability (HRV), and EEG data. The KMA-based results of HRV decomposition are compared with those obtained from a hierarchical cluster analysis (state-of-the-art). The major difference between the two approaches is that there is a more consistent assignment pattern using KMA. Integrating KMA into complex analysis concepts enables a comprehensive exploitation of the key advantages of the EMD. This can be demonstrated by non-linear analysis of HRV-related IMFs and by an EMD-based cross-frequency coupling analysis of the EEG data. CONCLUSIONS: The successful application to HRV and EEG analysis demonstrates that our solutions can be used for automated EMD-based processing concepts for biomedical signals.

The original Gerstmann-Sträussler-Scheinker family of Austria: divergent clinicopathological phenotypes but constant PrP genotype.

We present new data on the original Austrian kindred with Gerstmann-Sträussler-Scheinker disease (GSS) which encompasses currently 221 members in 9 generations. The mode of inheritance is autosomal dominant. Predominant clinical features are slowly progressive ataxia and late impairment of higher cerebral functions. In contrast, a recent case with proven P102L mutation of the PRNP gene had rapidly developing dementia and severe cortical damage indistinguishable from the clinicopathological phenotype of Creutzfeldt-Jakob disease (CJD). PRNP codon 129 was homozygous for methionine in both the historic and recent cases. Neuropathology confirms spongiosis of variable degree and numerous protease resistant/prion protein (PrP) amyloid plaques scattered throughout most of the brain as constant features in this family. Some amyloid deposits are surrounded by dystrophic neurites with accumulation of phosphorylated neurofilaments and abnormal organelles, reminiscent of Alzheimer-type plaques. Severe telencephalic damage and a synaptic-type fine granular immunoreactivity in laminar distribution in the cortex with anti-PrP after hydrated autoclaving of sections were seen only in the recent patient. In conclusion, factors in addition to the PRNP genotype at codons 102 and 129 must play a role in determining clinicopathological characteristics of this inherited brain amyloidosis.

Possible association between childhood absence epilepsy and the gene encoding GABRB3.

BACKGROUND: Childhood Absence Epilepsy (CAE) is considered to have a predominantly, perhaps exclusively, genetic background. To date, genes responsible for susceptibility to CAE have not been identified. The object of the present study was to test association between CAE and the genes encoding the gamma-aminobutyric acid (GABA) type-A receptor subunits alpha 5 (GABRA5) and beta 3 (GABRB3) located on the long arm of chromosome 15 (15q11-q13). METHODS: A family-based candidate gene approach was applied: 50 Austrian nuclear families ascertained for the presence of an affected child were investigated. GABRA5 and GABRB3 subunit genes were genotyped using DNA gained from peripheral blood samples by Polymerase Chain Reactions (PCR). Genetic association was tested using a Monte Carlo Version of the multi-allele Transmission-Disequilibrium Test (TDT). RESULTS: The TDT displayed significant overall association with GABRB3 (p = .0118). CONCLUSIONS: The present data suggest that the tested polymorphism may be either directly involved in the etiology of CAE or in linkage disequilibrium with disease-predisposing sites.