Search

Thomas Ferbert, Christina Münch, Sebastian Findeisen, William Pauly, Matthias Miska, Tobias Grossner, Michael C Tanner, Gerhard Schmidmaier, Lars Helbig Clinic for Trauma and Reconstructive Surgery, Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital, Heidelberg, D-69118, GermanyCorrespondence: Lars Helbig, Clinic for Trauma and Reconstructive Surgery, Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital, Schlierbacher Landstrasse 200a, Heidelberg, D-69118, Germany, Tel +496221/5635371, Fax +496221/5626300, Email lars.helbig@med.uni-heidelberg.dePurpose: A central aspect of the treatment of non-unions is the filling of bone defects. The quantity of available autologous bone for this purpose is limited. Alternatively, or additionally, bone substitutes may be used. The aim of this retrospective, single-center study including 404 non-unions in 393 patients is to investigate the effect of tricalcium phosphate (TCP) on the healing of non-unions. Furthermore, the influence of gender, age, smoking status, comorbidities, type of surgical procedure, presence of infection, and length of treatment was investigated.Methods: We evaluated three groups of patients. Group 1 received TCP + BG, group 2 received BG alone and group 3 received no augmentation. Bone stability was assessed 1 and 2 years after non-union revision surgery through analysis of radiographs using the Lane Sandhu Score. Scores ≥ 3 were rated as stable Other influencing factors were collected from the electronic medical record.Results: In 224 non-unions, bone defects were filled with autologous bone and TCP (TCP+BG). In 137 non-unions, bone defects were filled with autologous bone (BG), and in 43 non-unions presenting non-relevant defects, neither autologous bone nor TCP were used (NBG). After 2 years, 72.7% of the TCP+BG patients, 90.1% of the BG patients and 84.4% of the NBG patients achieved a consolidation score ≥ 3. Advanced age, presence of comorbidities and longer treatment period had a significantly negative effect on consolidation 1 year after surgery. Longer treatment periods also showed a negative significant effect after 2 years. It is notable that larger defects, mainly treated with the combination of autologous bone and TCP, showed similar healing rates to that of smaller defects after 2 years.Conclusion: The combination of TCP and autologous bone-grafts shows good results in the reconstruction of complicated bone-defects, but patience is required since the healing period exceeds 1 year in most patients.Keywords: non-unions, bone substitute, Lane Sandhu Score, tricalcium phosphate

Background: The treatment of large-sized bone defects remains a major challenge in trauma and orthopaedic surgery. Although there are many treatment options, there is still no clear guidance on surgical management, and the influence of defect size on radiological and clinical outcome remains unclear due to the small number of affected patients. The aim of the present study was to determine the influence of defect size on the outcome of atrophic and infected nonunions of the tibia or the femur based on the diamond concept in order to provide recommendations for treatment guidance. Patients and Methods: All medical records, surgical reports, laboratory data and radiological images of patients treated surgically for atrophic or infected nonunions of the lower limbs (femur or tibia) between 1 January 2010 and 31 December 2020 were examined. Patients with proximal, diaphyseal or distal nonunions of the femur or tibia who were surgically treated at our institution according to the “diamond concept” and attended our standardised follow-up program were included in a database. Surgical treatment was performed as a one- or two-step procedure, depending on the type of nonunion. Patients with a segmental bone defect ≥5 cm were matched with patients suffering a bone defect

Fragestellung: Ein zentraler Aspekt der Therapie von Pseudarthrosen ist die Auffüllung von Knochendefekten. Die Verfügbarkeit von autologem Knochen ist limitiert. Alternativ oder additiv werden Knochenersatzstoffe eingesetzt. Ziel der retrospektiven, single-zentrischen Studie mit 425 Patienten, [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Obtaining pilot data regarding the AQ scale and potential score variability among CSUF psychology department participants, as well as how those scores may relate to basic cognitive task performances.

Bowel dysfunction after spinal surgery is often underestimated and if not treated in a timely manner can lead to undesirable surgical interventions or fatal complications. The current medical literature primarily focuses on bowel dysfunction as a result of spinal injury. The purpose of this review is to explore this topic in evaluating current evidence regarding the causes of acute bowel dysfunction after elective spinal surgery, primarily the thoracolumbar spine. Since available evidence for recommendations of treatment is scarce, an interdisciplinary management approach for treatment of bowel dysfunction following spinal surgery is also formulated. An extensive literature search was carried out on PubMed. Keywords that were used in the search included bowel dysfunction, obstruction, postoperative ileus, spinal surgery, spinal fusion, constipation, opioid-induced constipation, colonic pseudo-obstruction, ischemic colitis, immobility-induced bowel changes, epidural anesthesia and diet. Relevant studies were chosen and included in the review. The treatment approach used in the spine center of a university hospital was included. Current research mainly focuses on investigating the nature and symptomatology of chronic bowel dysfunction after spinal cord injury. Emphasis on the acute phase of bowel dysfunction in patients after elective spinal surgery is lacking. The comorbidities that exacerbate bowel dysfunction postoperatively are well-defined. There has been refinement and expansion of the pharmacological and nonpharmacological treatment that could be implemented. Enough evidence exists to provide sufficient care. Management of acute bowel dysfunction after spinal surgery requires a comprehensive and individualized approach, encompassing comorbidities, behavioral changes, medications and surgery. Close supervision and timely treatment could minimize further complications. Research is required to identify patients who are at a higher risk of developing bowel dysfunction after specific spinal procedures.

Background:Intraoperative femoral fractures (IFF) during primary total hip arthroplasty (THA) pose a major clinical challenge, and data on mid-term implant performance, functional outcome and patient satisfaction is limited.Methods:50 patients who sustained IFFs during primary THA were retrospectively reviewed. A control group of patients who received a primary THA without complications was matched according to gender, age, body mass index and indication for THA. Both groups were followed-up for a minimum duration of 2 years. Average follow-up duration was 5.6 years (range 2–11.8 years) for the fracture group and 6 years (range 4.1–8.3 years) for the control group respectively. The following parameters were assessed and compared: stem revision, Harris Hip Score improvement, pain scale improvement, WOMAC, Tegner Score, UCLA, SF-36, forgotten joint score and patient satisfaction.Results:There were no stem revisions in the fracture group and 1 stem revision in the control group. Stem survival was 100% and 98.1% respectively ( p = 0.447). The mean improvement in Harris hip score was 35.3 and 44.8 respectively. Significantly lower Harris Hip score improvement ( p = 0.021) and patient satisfaction ( p = 0.01) were observed in the fracture group. All other acquired parameters did not show significant differences.Conclusion:Intraoperative fractures of the proximal femur are a relevant complication that does not lead to higher revision rates but might worsen the functional outcome and negatively impact patient satisfaction in mid-term follow-up even if treated appropriately.

Clinical investigations of brain death are supposed to prove absence of cerebral perfusion. However, only limited data are available documenting intracranial pressure (ICP) and cerebral perfusion pressure (CPP) during the development of brain death. Our study presents additional data to understand the course of ICP and CPP in patients developing brain death.We analyzed retrospective data of 18 patients with ICP monitoring during the development of brain death due to primary brain lesions. ICP and CPP values were continuously measured between two clinically defined time points: 1. non-reactive and widened pupils, 2. brain death determination. We analyzed ICP and CPP at the above-mentioned end points. Additionally, we investigated maximum ICP and minimal CPP values between these time points.Patients developed fixed and dilated pupils with a median of 38 h before brain death determination. During brain death determination median ICP and median CPP were 103.5 and -2.5 mmHg, respectively. Maximum ICP before brain death determination was significantly higher and minimal CPP values were significantly lower compared to the time point of brain death. During the investigation period all patients experienced ICP values95 mmHg and CPP 10 mmHg. All but one patient had documented CPP values of ≤0 mmHg. This single patient had a minimum CPP of 8 mmHg with a maximum ICP of 145 mmHg.Cerebral perfusion pressure during brain death determination may be positive in some patients. Our results showed variable values of ICP and CPP. However, extremely elevated ICP values before or during brain death in combination with low CPP values suggest absence of cerebral perfusion. The occurrence of positive CPP values during brain death determination therefore depends on the time point at which brain death determination is performed.

ZusammenfassungDie Neurografie des N. suralis hat große Bedeutung in der Diagnose von Polyneuropathien. Dieser Artikel stellt unterschiedliche Untersuchungstechniken mit ihren Vor- und Nachteilen vor, bespricht Messergebnisse und Normalwerte und nennt Anhaltspunkte für die Unterscheidung des axonalen und demyelinisierenden Läsionstyps. Letztlich wird ein Standard für die neurografische Untersuchung und deren Bewertung vorgeschlagen.

Hereditary neuropathies are a group of diseases of which the most prevalent is Charcot Marie Tooth disease (CMT). From the clinical point of view pes cavus is a typical yet not specific sign for CMT. Motor signs like bilateral foot drop are dominant over sensory signs. Mutations in some 80 genes can lead to CMT. Whereas clinical sign can hardly differentiate between these genotypes, there is a clear differentiation by classical neurography: median nerve conduction velocity of less or more than 38 m / s differentiates between CMT type 1 and CMT type 2. The two most common forms are CMT1A induced by duplication of the PMP22 gene and hereditary neuropathy with liability to pressure palsy (HNPP) induced by deletion of the PMP22 gene.Polyneuropathien zählen zu den häufigsten neurologischen Erkrankungen. Die Charcot-Marie-Tooth Erkrankung (CMT) ist ihre häufigste erblich bedingte Form. Orthopädische Symptome wie ein Hohlfuß oder Krallenzehen können ein erstes Anzeichen der Krankheit sein. Verdachtsfälle können mithilfe elektrophysiologischer und sonografischer Methoden abgeklärt und ggf. molekulargenetisch genau charakterisiert werden.

Altered autophagy accompanied by abnormal autophagic (rimmed) vacuoles detectable by light and electron microscopy is a common denominator of many familial and sporadic non‐inflammatory muscle diseases. Even in the era of next generation sequencing (NGS), late‐onset vacuolar myopathies remain a diagnostic challenge. We identified 32 adult vacuolar myopathy patients from 30 unrelated families, studied their clinical, histopathological and ultrastructural characteristics and performed genetic testing in index patients and relatives using Sanger sequencing and NGS including whole exome sequencing (WES). We established a molecular genetic diagnosis in 17 patients. Pathogenic mutations were found in genes typically linked to vacuolar myopathy (GNE, LDB3/ZASP, MYOT, DES and GAA), but also in genes not regularly associated with severely altered autophagy (FKRP, DYSF, CAV3, COL6A2, GYG1 and TRIM32) and in the digenic facioscapulohumeral muscular dystrophy 2. Characteristic histopathological features including distinct patterns of myofibrillar disarray and evidence of exocytosis proved to be helpful to distinguish causes of vacuolar myopathies. Biopsy validated the pathogenicity of the novel mutations p.(Phe55*) and p.(Arg216*) in GYG1 and of the p.(Leu156Pro) TRIM32 mutation combined with compound heterozygous deletion of exon 2 of TRIM32 and expanded the phenotype of Ala93Thr‐caveolinopathy and of limb‐girdle muscular dystrophy 2i caused by FKRP mutation. In 15 patients no causal variants were detected by Sanger sequencing and NGS panel analysis. In 12 of these cases, WES was performed, but did not yield any definite mutation or likely candidate gene. In one of these patients with a family history of muscle weakness, the vacuolar myopathy was eventually linked to chloroquine therapy. Our study illustrates the wide phenotypic and genotypic heterogeneity of vacuolar myopathies and validates the role of histopathology in assessing the pathogenicity of novel mutations detected by NGS. In a sizable portion of vacuolar myopathy cases, it remains to be shown whether the cause is hereditary or degenerative.

Background Treatment of non-union remains challenging and often necessitates augmentation of the resulting defect with an autologous bone graft (ABG). ABG is limited in quantity and its harvesting incurs an additional surgical intervention leaving the risk for associated complications and morbidities. Therefore, artificial bone graft substitutes that might replace autologous bone are needed. S53P4-type bioactive glass (BaG) is a promising material which might be used as bone graft substitute due to its osteostimulative, conductive and antimicrobial properties. In this study, we plan to examine the clinical effectiveness of BaG as a bone graft substitute in Masquelet therapy in comparison with present standard Masquelet therapy using an ABG with tricalciumphosphate to fill the bone defect. Methods/design This randomized controlled, clinical non-inferiority trial will be carried out at the Department of Orthopedics and Traumatology at Heidelberg University. Patients who suffer from tibial or femoral non-unions with a segmental bone defect of 2–5 cm and who are receiving Masquelet treatment will be included in the study. The resulting bone defect will either be filled with autologous bone and tricalciumphosphate (control group, N = 25) or BaG (S53P4) (study group, N = 25). Subsequent to operative therapy, all patients will receive the same standardized follow-up procedures. The primary endpoint of the study is union achieved 1year after surgery. Discussion The results from the current study will help evaluate the clinical effectiveness of this promising biomaterial in non-union therapy. In addition, this randomized trial will help to identify potential benefits and limitations regarding the use of BaG in Masquelet therapy. Data from the study will increase the knowledge about BaG as a bone graft substitute as well as identify patients possibly benefiting from Masquelet therapy using BaG and those who are more likely to fail, thereby improving the quality of non-union treatment. Trial registration German Clinical Trials Register (DRKS), ID: DRKS00013882. Registered on 22 January 2018. Electronic supplementary material The online version of this article (10.1186/s13063-018-2681-9) contains supplementary material, which is available to authorized users.

Neuroinflammation presumably has an important impact on the secondary phase of spinal cord injury and is regulated by pro- and anti-inflammatory cytokines. We analyzed serum levels of three different cytokines (insulin-like-growth-factor [IGF]-1, tumor growth factor [TGF]-β1, and soluble CD 95 ligand [sCD95L]), in blood samples of 23 patients admitted with acute traumatic spinal cord injury between November 2010 and July 2013 with a follow-up period of 12 weeks. Quantification was performed using Human Quantikine Immunoassays, classification of neurological impairment was performed using the American Spinal Cord Injury Impairment Scale at time of admission and after 12 weeks. After an initial drop of all three cytokine serum levels, IGF-1, TGF-β1, and sCD95L showed significantly increased serum levels during the acute and sub-acute phases. For IGF-1 and sCD95L, we could also observe significantly higher serum levels in patients without neurological improvement compared with patients who had improvement after 12 weeks. In this study, we were able to show differences in cytokine serum levels in patients with different neurological outcome. Measuring the serum level patterns of IGF-1, TGF-β1, and sCD95L might be a useful tool for prognosis in patients with neurological improvement and tracking the pathophysiology in further studies. Further, our observations might link promising therapeutic efforts in numerous animal studies and future studies in human patients.

Objectives Percutaneous tracheostomy (PT) is common on ICUs. An increase of intracranial pressure (ICP) can be observed in patients with acute cerebral diseases. Factors determining ICP increase remain unclear. Patients and methods Data for all PTs were collected prospectively. ICP, cerebral perfusion pressure (CPP), mean arterial pressure (MAP), peripheral oxygen saturation (SpO2), and heart rate (HR) were monitored continuously every minute. Primary outcome parameter was an increase of ICP during PT (ICP > 20 mmHg). Influencing factors were evaluated by the means of logistic regression analysis: Body mass index (BMI), age, gender, physician performing the procedure (neurologist vs. neurosurgeon), duration of the procedure, underlying disease, duration of mechanical ventilation, and baseline ICP value before the procedure. Results A total of 175 PTs were performed during the observation period between 2010 and 2013. Of these, 54 received ICP monitoring and were included into this study. Median initial ICP value was 10.4 mmHg and rose significantly to a median value of 18.4 mmHg (p Conclusion Percutaneous tracheostomies in patients with cerebral injury leads to a significant increase of ICP during the procedure. Patients with a baseline ICP > 15 mmHg are at risk to develop harmful ICP crises.

Background Studies investigating multimodal cerebral monitoring including partial brain tissue oxygen monitoring (ptiO2) in neuro-intensive care patients during physiotherapy are completely lacking in the literature. Materials and Methods We performed a post hoc analysis of prospectively collected data of patients on multimodal cerebral monitoring by intracranial pressure (ICP) and cerebral perfusion pressure (CPP) measurement as well as ptiO2. Patients with severe brain diseases were treated with passive range of motion (PROM). We recorded ICP, CPP, and ptiO2 continuously every minute at baseline (15 minutes), during treatment (26 minutes), and 15 minutes after treatment with PROM. Results Overall, 25 treatment units with PROM in 10 patients with combined ICP/CPP and ptiO2 monitoring were evaluated. Median ICP, CPP, and ptiO2 at baseline were 12 ± 6.1 mm Hg, 86 ± 17.1 mm Hg, and 27 ± 14.3 mm Hg, respectively. Values for ICP, CPP, and ptiO2 did not change significantly when comparing mean values before, during, and after therapy. Conclusions Based on ptiO2 measurements, our data provide new information about the feasibility and safety of physiotherapy in patients with severe brain diseases.

Background Linkage analyses of families with primary familial brain calcification (formerly idiopathic basal ganglia calcification [IBGC]) identified 3 candidate loci (IBGC1-3). Recently, SLC20A2 mutations were found in the IBGC1 and IBGC3 families, merging these 2 loci. We here elucidate the genetic cause of primary familial brain calcification in the 'IBGC2' kindred. Methods We sequenced known primary familial brain calcification genes and quantified SLC20A2 and PDGFB. Moreover, CT scans of affected and unaffected family members were evaluated by 2 blinded neuroradiologists for distribution of brain calcification. Results A heterozygous multiexonic SLC20A2 deletion was detected in several affected family members. A reevaluation of neuroimaging data revealed a subset of mutation-negative individuals with only mild and/or unilateral calcification. Conclusions The identified SLC20A2 mutation resolves the genetic cause of primary familial brain calcification in the 'IBGC2' kindred, collapsing 'IBGC2' into IBGC1. We suggest an algorithm for predicting the chances of finding genetic mutations that has to be validated in further studies. Our study enhances criteria for the evaluation of neuroimaging data, contributing further to the much needed harmonization of diagnostic and research data collection in primary familial brain calcification. © 2016 International Parkinson and Movement Disorder Society.

Spontaneous intracranial hypotension is the most common complication in patients undergoing a lumbar puncture. A much rarer entity is headaches attributed to spontaneous (or idiopathic) low cerebrospinal fluid (CSF) pressure but the combination with a connective tissue disorder is even rarer. The first case of a patient with spontaneous intracranial hypotension and genetically established Marfan syndrome was published in 1995. This article describes the cases of two female patients who presented with postural headache. Magnetic resonance imaging revealed multiple leakages of CSF and both patients had a genetically confirmed diagnosis of Marfan syndrome. The initial symptomatic treatment did not result in a significant relief of the headaches. Epidural blood patching was performed and the intervention was successful in both patients. Finally, the most important epidemiological, diagnostic and pathophysiological aspects are demonstrated and the therapeutic procedures are presented.

Intrahospital transport is associated with a high rate of complications. Investigations of this problem using neuromonitoring remain scarce. This is a monocentric, prospective observational study. Patients with severe brain diseases and intracranial pressure (ICP) monitoring were included. Continuous monitoring of ICP, cerebral perfusion pressure (CPP), oxygen saturation (SpO2), heart rate, and mean arterial pressure was measured during seven different periods of intrahospital transport (baseline for 30 min, I = preparation, II = transport I, III = CT scan, IV = transport II, V = postprocessing, and follow-up for another 30 min). All complications were documented. Between July 2013 and December 2013, a total number of 56 intrahospital transports of 43 patients were performed from ICU to CT. Data recording was incomplete in six cases. Fifty transports have been taken into account for statistical analysis. Forty-two percent were emergency transports. Mean duration of the procedure was 17′ (preparation), 6′ (transport I), 9′ (CT scan), 6′ (transport II), and 15′ (postprocessing), respectively. Mean ICP at baseline was 8.53 mmHg. Comparing all periods of intrahospital transport and the follow-up period to the baseline showed a significant increase of ICP only during CT scan (15.83 mmHg, p

ZusammenfassungGemeinsam mit der Vierten Fortschreibung der Richtlinie der Bundesärztekammer zur Feststellung des irreversiblen Hirnfunktionsausfalls („Hirntod“) im Jahr 2015 erfolgte eine Revision der Empfehlungen der Deutschen Gesellschaft für Klinische Neurophysiologie und Funktionelle Bildgebung (DGKN) zu den ergänzenden elektrophysiologischen (Elektroenzephalografie, frühe akustisch evozierte Potenziale, somatosensorisch evozierte Potenziale) und neurovaskulären (Dopplersonografie, Duplexsonografie) Untersuchungen.Die Empfehlungen der DGKN wurden 2018 in einigen Punkten aktualisiert. Neben redaktionellen Änderungen (u. a. Ersetzen des Begriffs „Eichsignal“ durch „Kalibriersignal“, präzisere Formulierung der zu setzenden Elektroden für die Elektroenzephalografie) wurden Vorgaben zur Bildanzeige bei digitaler Elektroenzephalografie und altersbezogene Mindestgrößen des arteriellen Mitteldruckes bei Kindern für die Doppler- und Duplexsonografie neu aufgenommen. Diese hier präsentierten Empfehlungen stellen die Indikationen, Limitationen, Voraussetzungen und die Durchführung dieser Zusatzverfahren in der Diagnostik des irreversiblen Hirnfunktionsausfalls bei Kindern und Erwachsenen dar.

Principally, in the fourth update of the rules for the procedure to finally determine the irreversible cessation of function of the cerebrum, the cerebellum and the brainstem, the importance of an electroencephalogram (EEG), somatosensory evoked potentials (SEP) and brainstem auditory evoked potentials (BAEP) are confirmed. This paper presents the reliability and validity of the electrophysiological diagnosis, discusses the amendments in the fourth version of the guidelines and introduces the practical application, problems and sources of error.An EEG is the best established supplementary diagnostic method for determining the irreversibility of clinical brain death syndrome. It should be noted that residual brain activity can often persist for many hours after the onset of brain death syndrome, particularly in patients with primary brainstem lesions. The derivation and analysis of an EEG requires a high level of expertise to be able to safely distinguish artefacts from primary brain activity. The registration of EEGs to demonstrate the irreversibility of clinical brain death syndrome is extremely time consuming.The BAEPs can only be used to confirm the irreversibility of brain death syndrome in serial examinations or in the rare cases of a sustained wave I or sustained waves I and II. Very often, an investigation cannot be reliably performed because of existing sound conduction disturbances or failure of all potentials even before the onset of clinical brain death syndrome. This explains why BAEPs are only used in exceptional cases.The SEPs of the median nerve can be very reliably derived, are technically simple and with few sources of error. A serial investigation is not required and the time needed for examination is short. For these reasons SEPs are given preference over EEGs and BAEPs for establishing the irreversibility of clinical brain death syndrome.

Hintergrund: Der irreversible Hirnfunktionsausfall ist ein sicheres Todeszeichen. In Deutschland wird hierfur der dauerhafte Nachweis des Funktionsausfalls von Groshirn, Kleinhirn und Hirnstamm gefordert. Die Kriterien zur Feststellung des Hirntods variieren weltweit. Anhand eines Fallberichts werden die aktuellen Richtlinien der Bundesarztekammer vorgestellt. Fallbericht: Wir berichten vom Fall eines 41-jahrigen Patienten, der aufgrund einer Subarachnoidalblutung (SAB) bei einem Aneurysma der A. cerebelli inferior posterior (PICA) in unsere Klinik eingeliefert wurde. Trotz Koma, ausgefallener Hirnstammfunktion, fehlender Apnoe sowie ausgefallener fruher akustisch evozierter Potenziale (FAEP) und kortikaler Potenziale der somatosensibel medianusevozierten Potenziale konnte eine Alpha-Aktivitat im EEG als Zeichen einer kortikalen Restfunktion am 3. Behandlungstag nachgewiesen werden. Wir stellten die Diagnose eines isolierten Hirnstammtods. Am Folgetag wurde das EEG wiederholt und zeigte eine Nulllinie. Somit konnte dann der irreversible Hirnfunktionsausfall diagnostiziert werden, und damit der Tod des Patienten. Diskussion: In Deutschland ist die Diagnose des isolierten Hirnstammtods kein sicheres Todeszeichen, sondern vielmehr der irreversible Hirnfunktionsausfall des gesamten Gehirns. Umso wichtiger ist die Kenntnis der Art der Hirnschadigung. In diesem Fall handelte es sich um eine primare infratentorielle Schadigung, die fur den Irreversibilitatsnachweis obligat eine geeignete Zusatzuntersuchung erforderlich macht.

Background: The first specific antidote for non-vitamin K antagonist oral anticoagulants (NOAC) has recently been approved. NOAC antidotes will allow specific treatment for 2 hitherto problematic patient groups: patients with oral anticoagulant therapy (OAT)-associated intracerebral hemorrhage (ICH) and maybe also thrombolysis candidates presenting on oral anticoagulation (OAT). We aimed to estimate the frequency of these events and hence the quantitative demand of antidote doses on a stroke unit. Methods: We extracted data of patients with acute ischemic stroke and ICH (Results: Eighteen percent of ICH patients within 6 h of symptom onset or an unknown symptom onset were on OAT. Given a NOAC share at admission of 40%, about 7% of all ICH patients may qualify for NOAC reversal therapy. Thirteen percent of ischemic stroke patients admitted within 4 h presented on anticoagulation. Given the availability of an appropriate antidote, a NOAC share of 50% could lead to a 6.1% increase in thrombolysis rate. Conclusions: Stroke units serving populations with a comparable demographic structure should prepare to treat up to 1% of all acute ischemic stroke patients and 7% of all acute ICH patients with NOAC antidotes. These numbers may increase with the mounting prevalence of atrial fibrillation and an increasing use of NOAC.

Objectives: Total hip arthroplasty (THA) offers a highly successful treatment option for patients with end stage hip osteoarthritis. The occurrence of an intraoperative fracture (IFF) at the proximal femur during primary THA has been frequently documented in the literature with an incidence of 0.1%[for full text, please go to the a.m. URL], Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2018)

[Background] The role of ANO3 variants as a monogenic cause of dystonia is still under debate because of its relatively high frequency also in controls., [Objective] To screen >1000 patients with movement disorders for rare ANO3 variants., [Methods] We searched for rare ANO3 variants in 729 dystonia and 294 Parkinson's disease (PD) patients using a gene panel. Variants were validated by Sanger sequencing. For one variant carrier, family members were available for segregation analysis., [Results] Nine carriers (seven with dystonia [1.0%], two with PD [0.7%]) of seven different rare, protein-changing variants were identified. None of these variants has been previously reported in dystonia patients. Two of the variants in dystonia patients were found recurrently: p.Arg328Cys was detected in two Korean and p.Arg969Gln in two German patients. The frequency of these two variants in our sample seemed to be higher as in ethnically matched samples from the Genome Aggregation Database (GnomAD). Further, we identified a patient with early-onset, generalized dystonia with a de-novo variant in ANO3 (p.Val561Glu). Of note, she benefitted from deep brain stimulation., [Conclusion] This study confirms the relatively high frequency of rare, protein-changing ANO3 variants in both dystonia and non-dystonia patients indicating that not all variants contribute to the disease. Thus, disease relevance of novel variants remains difficult to interpret and functional studies are warranted for a better understanding of the role of ANO3 variants in dystonia. In contrast, de-novo variants in childhood-onset, generalized dystonia seem to represent an as yet underestimated phenotypic expression of changes in ANO3., This work was supported by the German Ministry of Education and Research (BMBF, DYSTRACT consortium, 01GM1514B, to C.K. and K.L.).

Einleitung: Im Irreversiblen Hirnfunktionsausfall (Hirntod) wird ein zerebraler Zirkulationsstillstand postuliert mit einem Anstieg des intrakraniellen Druckes (ICP) über den mittleren arteriellen Druck (MAP). Studien zu ICP und cerebralen Perfusionsdruck (CPP) zum Zeitpunkt des irreversiblen Hirnfunktionsausfalles[zum vollständigen Text gelangen Sie über die oben angegebene URL], 69. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Mexikanischen und Kolumbianischen Gesellschaft für Neurochirurgie

Background Familial hemiplegic migraine (FHM) is a rare monogenic form of migraine with aura with three distinct genetic subtypes (FHM1-3). Imaging studies during acute FHM attacks are scarce in the literature. This is particularly true for the FHM2 subtype. Patients and methods In this monocentric study, we retrospectively evaluated imaging data of four different patients with genetically confirmed FHM2. Analysis comprised a total of eight cMRI and two CT perfusion studies, which were obtained during a total of six different attacks. Results cMRI investigations at all available time-points were without evidence of cytotoxic edema. The most prominent finding (four attacks in three patients) was swelling and/or cortical hyperintensity of the affected cerebral hemisphere on T2/FLAIR-weighted MRI. Further changes, encountered only in a few patients, included increased perfusion of the affected hemisphere (as assessed by perfusion CT) as well as dilatation of the middle cerebral artery. Conclusion Our data from a sizeable cohort of FHM2 patients highlight that swelling / cortical hyperintensity of the clinically affected cerebral hemisphere - which has been previously reported mainly in FHM1 - can be observed also in FHM2. Further, they suggest that these changes, which tend to be present not in the very beginning, but rather later on during attacks, may be a possible correlate of the prolonged attack duration in our patients.

Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Checklist: recommended items to address in a clinical trial protocol and related documents. (DOC 119Â kb)

Background and purpose Some authors have suggested a rise of intracranial pressure (ICP) during apnoea testing and the possibility of harm to patients. Data, however, have yet to be obtained. Methods Between October 2012 and May 2014 an observational study was performed on patients who received ICP measurements and who underwent brain death diagnosis. ICP, cerebral perfusion pressure (CPP), mean arterial blood pressure (MAP) and heart rate were recorded continuously from 15 min before the start of brain death diagnosis (baseline), during clinical examination including apnoea testing, until 15 min after this procedure. Results A total of 16 clinical examinations for brain death including apnoea testing were performed on 13 patients. All patients had primary brain lesions. Mean ICP and mean CPP during the examination were 95 ± 27.7 mmHg and 13.5 ± 20.7 mmHg, respectively. ICP and MAP showed a strong and statistically significant correlation, with Pearson's correlation coefficients of more than +0.6 or less than -0.6 in 13 of the 15 examinations. Conclusion Mean ICP even before brain death determination is increased excessively. Changes of ICP during apnoea show a clear correlation to the changes of MAP. Furthermore, CPP during the condition of brain death may not equal zero but may be positive thereby indicating some minor net influx of blood into the brain in some patients.

Serum levels of interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α) were measured over a 12-week period in 23 patients with spinal cord injury (SCI) with and without neurological improvement.To determine the course of IL-1β and TNF-α in patients with SCI and observe a possible relationship between improvements in neurological functioning and cytokine levels.All patients were treated at the BG Trauma Centre, Ludwigshafen, Germany. All lab work was done at the University Hospital, Heidelberg.Spinal cord injury was classified according to the American Spinal Injury Association (ASIA) impairment scale (AIS) in 23 patients. TNF-α and IL-1β levels were measured upon arrival at the hospital, after 4 h, 9 h and 12 h, on days 1 and 3 and at the end of weeks 1, 2, 4, 8 and 12.Temporal changes in TNF-α and IL-1β in SCI patients were seen. Patients with AIS improvement (Group 1) had significantly lower TNF-α levels at 9 h compared with patients without AIS improvement (Group 2; P0.01). The course of IL-1β fluctuated greatly between 4 h and week 1 in the groups; however, between 2 and 12 weeks post trauma, there was an overall decline in both groups.Measuring serum levels of TNF-α and IL-1β over time could be useful in tracking the course of SCI. Our data show differences in measured cytokines over a 12-week period for SCI patients with and without neurological improvement.

Objective To determine serum concentrations of soluble CD95 ligand (sCD95L) in patients with traumatic spinal cord injury. Methods Patients with traumatic spinal cord injury were recruited. Blood was collected on admission to hospital and at 4 h, 9 h, 12 h, 24 h, 3 days, 7 days, and 2, 4, 8 and 12 weeks postadmission. Serum concentrations of sCD95L were determined via immunoassay. Result The study included 23 patients. Mean sCD95L concentrations were significantly lower at 4 h, 9 h, 12 h and 24 h than at admission, and were significantly higher at 8 and 12 weeks, compared with admission. Conclusion The serum sCD95L concentration fell significantly during the first 24 h after traumatic spinal cord injury. Concentrations then rose, becoming significantly higher than admission levels at 8 weeks. sCD95L may represent a possible therapeutic target for traumatic spinal cord injury.

Background: Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)–defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). Methods: An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. Results: A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52–1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor. Conclusions: Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01994720.

Hereditary neuropathies comprise a wide variety of chronic diseases associated to more than 80 genes identified to date. We herein examined 612 index patients with either a Charcot-Marie-Tooth phenotype, hereditary sensory neuropathy, familial amyloid neuropathy, or small fiber neuropathy using a customized multigene panel based on the next generation sequencing technique. In 121 cases (19.8%), we identified at least one putative pathogenic mutation. Of these, 54.4% showed an autosomal dominant, 33.9% an autosomal recessive, and 11.6% an X-linked inheritance. The most frequently affected genes were PMP22 (16.4%), GJB1 (10.7%), MPZ, and SH3TC2 (both 9.9%), and MFN2 (8.3%). We further detected likely or known pathogenic variants in HINT1, HSPB1, NEFL, PRX, IGHMBP2, NDRG1, TTR, EGR2, FIG4, GDAP1, LMNA, LRSAM1, POLG, TRPV4, AARS, BIC2, DHTKD1, FGD4, HK1, INF2, KIF5A, PDK3, REEP1, SBF1, SBF2, SCN9A, and SPTLC2 with a declining frequency. Thirty-four novel variants were considered likely pathogenic not having previously been described in association with any disorder in the literature. In one patient, two homozygous mutations in HK1 were detected in the multigene panel, but not by whole exome sequencing. A novel missense mutation in KIF5A was considered pathogenic because of the highly compatible phenotype. In one patient, the plasma sphingolipid profile could functionally prove the pathogenicity of a mutation in SPTLC2. One pathogenic mutation in MPZ was identified after being previously missed by Sanger sequencing. We conclude that panel based next generation sequencing is a useful, time- and cost-effective approach to assist clinicians in identifying the correct diagnosis and enable causative treatment considerations.

Orphanet journal of rare diseases : OJRD 12(1), 86 (2017). doi:10.1186/s13023-017-0640-2, Published by BioMed Central, London

Genetic variants identified in patients with SLONM using NGS and a panel of 283 genes. (DOC 72 kb)

Genetic variants identified in patients with SLONM using NGS and a panel of 283 genes. (DOC 72 kb)

The objective of our trial was to obtain more comprehensive data on the risks and benefits of kinetic therapy in intensive care patients with intracerebral pathology.Standardized data of prone positioning in our NeuroIntensive Care Unit were collected from 2007 onward. A post hoc analysis of all available data was undertaken, with special consideration given to values of intracranial pressure (ICP), cerebral perfusion pressure (CPP) and oxygenation in correlation to prone (PP), or supine positioning (SP) of patients. Cases were considered eligible if kinetic therapy and ICP were documented. Prone positioning was performed in a 135° position for 8 h per treatment unit.A total of 115 patients treated with prone positioning from 2007 to 2013 were identified in our medical records. Of these, 29 patients received ICP monitoring. Overall, 119 treatment units of prone positioning with a mean duration of 2.5 days per patient were performed. The mean baseline ICP in SP was 9.5 ± 5.9 mmHg and was increased significantly during PP (p0.0001). There was no significant difference between CPP in SP (82 ± 14.5 mmHg) compared to PP (p0.05). ICP values20 mmHg occurred more often during PP than SP (p0.0001) and were associated with significantly more episodes of decreased CPP70 mmHg (p0.0022). The mean paO(2)/FiO(2) ratio (P/F ratio) was increased significantly in prone positioning of patients (p0.0001).The analyzed data allow a more precise understanding of changes in ICP and oxygenation during prone positioning in patients with acute brain injury and almost normal baseline ICP. Our study shows a moderate, yet significant elevation of ICP during prone positioning. However, the achieved increase of oxygenation by far exceeded the changes in ICP. It is evident that continuous monitoring of cerebral pressure is required in this patient group.

Cerebral cavernous malformations (CCM) are prevalent vascular malformations occurring in familial autosomal dominantly inherited or isolated forms. Once CCM are diagnosed by magnetic resonance imaging, the indication for genetic testing requires either a positive family history of cavernous lesions or clinical symptoms such as chronic headaches, epilepsy, neurological deficits, and hemorrhagic stroke or the occurrence of multiple lesions in an isolated case. Following these inclusion criteria, the mutation detection rates in a consecutive series of 105 probands were 87% for familial and 57% for isolated cases. Thirty-one novel mutations were identified with a slight shift towards proportionally more CCM3 mutations carriers than previously published (CCM1: 60%, CCM2: 18%, CCM3: 22%). In-frame deletions and exonic missense variants requiring functional analyses to establish their pathogenicity were rare: An in-frame deletion within the C-terminal FERM domain of CCM1 resulted in decreased protein expression and impaired binding to the transmembrane protein heart of glass (HEG1). Notably, 20% of index cases carrying a CCM mutation were below age 10 and 33% below age 18 when referred for genetic testing. Since fulminant disease courses during the first years of life were observed in CCM1 and CCM3 mutation carriers, predictive testing of minor siblings became an issue. peerReviewed