Neuropsychology of late-onset epilepsies.

In an increasingly ageing society, patients ageing with epilepsy and those with late-onset epilepsies (LOE) represent a challenge for epilepsy care and treatment. Senescence itself bears risks of pathologies which in the form of acute focal damage (e.g. stroke) or slowly progressive degenerative damage can cause seizures and substantial cognitive impairment. There is converging evidence from studies in LOE that cognitive impairments are present from epilepsy onset before treatment is initiated and may even precede the emergence of seizures. This suggests that these impairments (like the seizures) are expressions of the underlying disease. Indeed, both seizures and cognitive impairments can be early indicators of disease conditions which lead to mental decline. Cognitive decline over time poses the challenge of disentangling the interrelation between seizures, treatment effects and underlying disease. This issue must be considered as some of the etiologies for causing neuropsychological decline can be addressed. Medication and active epilepsy can contribute to impairments and their impact may be reversible. Dementia is rare if seizures are what has brought the person to attention, and if this is not accompanied by other slowly developing features (such as cognitive of psychiatric changes). From a neuropsychological point of view choosing the right screening tools or assessments, obtaining the history and timeline of impairments in relation to epilepsy, and most importantly longitudinally following the patients regardless of whether epilepsy is ultimately controlled or not appear essential.

Keratin films for ocular surface reconstruction: Wound healing in an in-vivo model.

The most commonly used tissue substitute for ocular surface reconstruction is human amniotic membrane (AM). Because of its low biomechanical strength and intransparency there is a need to search for alternatives of consistent quality. This study, further explored the biocompatibility of Keratin Film (KF) and its ability to sustain corneal epithelial wound healing. In three equal groups of 5 New Zeeland white rabbits a 4 mm superficial keratectomy was created in the right eye. Five eyes received a KF, five a human AM graft and the remaining five no implant. All eyes were treated with ofloxacin and dexamethasone eye drops and followed up for 10 days. Corneal fluorescein staining, vascularization, and transparency were assessed using slit lamp biomicroscopy according to a standardized grading score during and at the end of follow-up. The corneal-scleral-button was excised and processed for histology. After 10 days all eyes which had received a KF showed complete epithelial healing and no signs of neovascularization. In the AM group 1 eye showed a persistent epithelial defect at day 10 and 2 eyes showed neovascularization at day 7 resolving at day 10. Transparency improved progressively both in the KF group as well as in the AM group towards the end of the follow. Histology showed a multilayer epithelium firmly adherent to the KF with no evidence of keratocyte migration or inflammatory reaction in the corneal stroma. In this study on rabbit eyes KF better supported corneal epithelial wound healing than amniotic membrane.

Cost-effectiveness of varying degrees and models of therapist-assisted transdiagnostic internet-delivered cognitive behaviour therapy: Evidence from a randomized controlled trial.

In routine care, Internet-delivered Cognitive Behaviour Therapy (ICBT) is often delivered with therapist support via emails/phone calls, but the cost-effectiveness of varying amounts of therapist support or having therapists specialized in ICBT is not known. This study compared the cost-effectiveness of specialized therapists providing ICBT support once-weekly (1WS) versus providing support once-weekly supplemented with a one-business-day response to patient emails (1W/1BD-S). We further compared the cost-effectiveness of 1W support offered by therapists employed in a specialized clinic (1WS) versus community clinics where therapists primarily deliver face-to-face therapy (1WC). Patients were randomly allocated to groups: 1WS group (n = 216), 1W/1BD-S group (n = 233), and 1WC group (n = 226). At baseline, 12, 24 and 52-week follow-up, patients completed the Treatment Inventory of Costs in Patients with Psychiatric Disorders questionnaire (TiC-P) adapted for use in Canada to assess healthcare use and productivity losses. Additionally, to assess Quality Adjusted Life Years (QALYs) gained, patients completed the EQ-5D-5L at the same time periods. We quantified uncertainties by one-way and probabilistic sensitivity analysis and reported Incremental cost-effectiveness ratios (ICER), cost-effectiveness planes and acceptability curves. Cost-effectiveness over 52 weeks was CAD 3072/QALY for 1WC, CAD 3244/QALY for 1W/1BD-S, and CAD 3528/QALY for 1WS. Our model suggests that 1WS is the best strategy since the incremental cost per QALY is below the $50,000 threshold (ICER is CAD 42,328/QALY compared to the next most effective, 1WC). 1W/1BD-S is dominated by the other strategies. The cost-effectiveness acceptability curves suggest that the 1WS group has a higher probability for cost-effectiveness (38 %) than 1W/1BD-S (30 %) and 1WC (32 %) when the willingness to pay is $50,000 per QALY. These results have important implications for health policymakers deciding on delivery of ICBT for the treatment of anxiety and/depressive disorders.

[Beyond esthetics-Regenerative medicine for severe diseases of the adnexa oculi]. / Jenseits von Ästhetik ­ Regenerative Medizin bei schweren Erkrankungen der okulären Adnexe.

BACKGROUND: Restoration of eyelid and lacrimal functions are important steps on the way to an intact ocular surface. Clinically available substitute tissues or therapeutic options for eyelid reconstruction and lacrimal gland regeneration often reach their limits in patients with severe diseases of the adnexa oculi. Several approaches in regenerative medicine have been intensively researched and clinically tested in recent years. These range from reconstructive approaches with novel tissue matrices in the field of eyelid surgery to stem cell therapies to regenerate lacrimal gland function. MATERIAL AND METHODS: The state of the art in the current literature is presented and an overview of clinically applied or currently researched tissues for eyelid reconstruction is given. Furthermore, approaches in stem cell therapy of the lacrimal gland as well as own results are presented. RESULTS: Acellular dermis has been successfully used for eyelid reconstruction and represents a viable option in cases of limited availability of autologous tissue. In vitro grown cellular constructs or tissues with genetically modified cells have already been successfully applied in dermatology for the treatment of burns or severe genodermatoses. First studies on stem cell therapy for severe dry eye in Sjögren syndrome showed a safe and effective application of mesenchymal stem cells by injection into the lacrimal gland. CONCLUSION: Due to the limitations of currently available replacement tissues, there is a clinical need for the development of new materials for adnexa oculi reconstruction. Constructs grown in vitro with allogeneic and/or genetically engineered cells are slowly making their way into clinical practice. The efficacy and mode of action of stem cells in severe dry eye are subject matters of current clinical trials.

Multiple model triangulation to identify factors associated with lameness in British sheep flocks.

Identification of factors associated with an outcome can be challenging when the number of explanatory variables is large in relation to the number of observations. Multiple model triangulation, where results from several model types are combined, improves the likelihood of identifying true predictor variables. The aim of this study was to use triangulation to identify covariates likely to be truly associated with the prevalence of lameness in sheep flocks in Great Britain. Data were collected using a questionnaire sent to 3200 sheep farmers in Great Britain in 2018. The useable response rate was 14.1 %. The geometric mean prevalence of lameness was 1.4 % (95 % CI 1.2-1.7) for ewes, and 0.6 % (95 % CI 0.5-0.9) for lambs, however, approximately 60 % flocks had >2% prevalence of lameness in ewes. Four model types were investigated, two generalised linear models (negative binomial and quasi-Poisson) built using stepwise selection, and two elastic net models (Poisson and Gaussian distributions) refined with selection stability estimation. Triangulated covariates were those selected in three or all four models - 10 for ewes and 12 for lambs. Higher prevalence of lameness in ewes was associated with 5-100% feet bleeding during routine foot trimming compared with not foot trimming, footbathing the flock to treat severe footrot (SFR) and always using formalin in footbaths, both compared with not footbathing, using FootVax™ for <1 year compared with not using FootVax™, and never quarantining new or returning sheep to the farm for >3 weeks compared with always. Lower prevalence of lameness in ewes was associated with vaccinating with FootVax™ for >5 years compared with not vaccinating, peat soil compared with no peat soil, and having no lame ewes to treat. Higher prevalence of lameness in lambs was associated with 5-100% feet bleeding during routine foot trimming, always foot trimming ewes with SFR, not knowingly selecting replacement ewes from ewes that were never lame compared with always, replacement sheep purchased and homebred compared with only homebred, treating lambs >3 days after recognition of lameness compared with 0-3 days and footbathing the flock to treat interdigital dermatitis compared with not footbathing at all. Lower prevalence of lameness in lambs was associated with peat soil, flocks in Scotland versus England, an altitude of >230-500 m compared with ≤230 m, never using antibiotic injection to treat lambs with SFR compared with always, and having no lame lambs to treat. We conclude triangulation identified reliable management practices for farmers to implement to minimise lameness in sheep.

From open simple to robotic-assisted simple prostatectomy (RASP) for large benign prostate hyperplasia: the time has come.

PURPOSE: Robotic-assisted simple prostatectomy (RASP) has recently been studied as an alternative to open simple prostatectomy or endoscopic treatment options. At present, there is no defined recommendation for a robotic procedure as a standard surgical technique to treat large benign prostate hyperplasia. METHODS: Several robotic techniques have been described since 2007. Contemporaneously, multiple endoscopic enucleation techniques have been proposed. Nevertheless, open simple prostatectomy still remains a mainstay of therapy. We aimed to evaluate the development of robotic-assisted prostatectomy for large benign prostatic obstruction, thus comparing the technical aspects and clinical outcomes with open and endoscopic enucleation. RESULTS: Robotic-assisted simple prostatectomy provides significantly less blood loss and shorter hospital stay but longer operative time compared to open simple prostatectomy. Compared to endoscopic treatments, robotic approaches have a similar perioperative outcome, but cause less urethral trauma or potential bladder neck strictures. Moreover, concomitant bladder pathologies can be treated within the same setting. CONCLUSION: Robotic-assisted simple prostatectomy is an effective and safe technique, and can hence be considered to become the preferred first-line therapy to treat patients with obstructive large prostate glands.

[Multicenter comparison of complications after robot-assisted and open simple prostatectomy]. / Multizentrischer Vergleich von Komplikationen nach roboterassistierter und offen chirurgischer Prostataadenomenukleation.

INTRODUCTION: Robot-assisted simple prostatectomy (RASP) is a relatively new minimally invasive procedure for surgical treatment to manage symptomatic, therapy-refractory benign prostate hyperplasia (BPH) in prostate volumes >80 cm3. Thus, postoperative morbidity based on Clavien-Dindo and hematological parameters in RASP and open simple prostatectomy (OSP) procedures are examined. PATIENTS AND METHODS: We retrospectively reviewed a total of 78 patients: 39 patients underwent RAPS and 39 OSP. The following parameters were statistically evaluated and compared: age, PSA value, prostate volume, ASA score, duration of hospital stay, operative time, Hb decrease on postoperative (po) day 1 and in the 5 five po days, CRP peak in the first 5 po days and transfusion rate. RESULTS: The comparison between RASP and standard OSP showed no significant differences regarding the mean patient age (73 vs. 74 years; p =0.54), PSA values (7.7 vs. 10.7 ng/ml; p =0.17), ASA score (2.2 vs. 2.3; p =0.26) and prostate volume (130 vs. 113 cm3; p =0.07). Patients in the RAPAE group had statistically significant longer surgery (178 vs. 110 min; p =<0.01) with a significantly smaller decrease in Hb on po day 1 (1.9 vs. 3.3 g/dl; p ≤0.01) and in the first 5 po days (2.4 vs. 4.2 g/dl; p ≤0.01), lower need for preserved blood (3% vs. 26%; p =0.01) and number of blood bags (0.1 vs. 1.3; p =0.01), a lower po Clavien-Dindo score (0.44 vs. 1.23; p =0.003) and lower CRP values (52 vs. 104 mg/l; p ≤0.01) in the first 5 po days. CONCLUSION: RASP is a safe procedure that offers the advantage of reduced blood loss and blood bag consumption and rare complications due to the minimally invasive surgical method. The OSP group showed an increased occurrence of complications due to bleeding, leading to prolonged hospitalization and significantly increased need for blood transfusion. The lesser increase of CRP in RASP group is a result of the lower invasiveness of the robot-assisted procedure.

Eye Socket Regeneration and Reconstruction.

Purpose: When an eye has become irreversibly blind or painful it is removed by enucleation or evisceration. The resulting anophthalmic socket usually receives a volume replacing implant and is subsequently fitted with a prosthetic shell for adequate cosmesis. Trauma, tumour or immunological pathomechanisms can induce loss of bone, orbital soft tissue volume, and conjunctival contraction or implant exposure, which result in difficult or impossible prosthesis wear. In this situation as well as in numerous diseases limited to the conjunctiva (e.g. Pterygium, or cicatrizing conjunctivitis) strategies to substitute the lost tissue are required.Methods: A review of the literature search using various electronic databases (PubMed and MEDLINE) was performed on indications, surgical techniques and materials used to restore the ocular socket.Results: Amniotic membrane and oral mucosa are still the most commonly used substitutes for the reconstruction of larger conjunctival defects and ocular socket reconstruction. However, due to limitations of clinical available grafts, synthetic scaffolds, biomaterials or tissue-engineered grafts have been described in preclinical studies but most of them have not been investigated adequately in clinical studies yet. In orbital volume replacement, porous and nonporous spheres are used and both show acceptable results. However, more clinical studies are required that directly compare the outcomes in patients with similar conditions. Dermofat graft remains a good option in case of sockets with significant orbital volume and conjunctival surface loss.Conclusion: Beyond established techniques using autologous or allogeneic tissue, various approaches of engineering tissue based on scaffolds and stem cell expansion techniques are currently under investigation and may become alternatives in socket reconstruction in the not too far future.

Intraoperative verification of resection margins of maxillary malignancies by cone-beam computed tomography.

Resection of maxillary cancer often results in incomplete excision because of the tumour's proximity to important structures such as the orbit. To deal with this problem we prospectively investigated the feasibility of intraoperative imaging during maxillectomy to verify the planned resection margins. In total, six patients diagnosed with maxillary cancer listed for maxillectomy were included, irrespective of the histological type of tumour. Before resection, an accurate intended resection volume was delineated on diagnostic images. At the end of the operation we took a cone-beam computed tomographic (CT) scan of the treated maxilla, after which the accuracy of the resection was quantitatively evaluated by comparing the preoperative resection plan and the images acquired intraoperatively, based on the anatomy. Further resection was then done if necessary and quantitatively evaluated with a second cone-beam CT scan. Postoperatively we compared the results of the scan with those of the histological examination. Of the six, two resections were reported pathologically as less than radical, each of which was detected by intraoperative CT and resulted in extensions of the original resections. The mean (SD) distance between the planned and the actual resection was 1.49 (2.78)mm. This suggests that intraoperative cone-beam CT imaging is a promising way to make an adequate intraoperative assessment of planned surgical margins of maxillary tumours. This allows for intraoperative resection margins to be improved, possibly leading to a better prognosis for the patient.

[Stereotactic laser thermocoagulation in epilepsy surgery]. / Stereotaktische Laserthermokoagulation in der Epilepsiechirurgie.

In common with other stereotactic procedures, stereotactic laser thermocoagulation (SLT) promises gentle destruction of pathological tissue, which might become especially relevant for epilepsy surgery in the future. Compared to standard resection, no large craniotomy is necessary, cortical damage during access to deep-seated lesions can be avoided and interventions close to eloquent brain areas become possible. We describe the history and rationale of laser neurosurgery as well as the two available SLT systems (Visualase® and NeuroBlate®; CE marks pending). Both systems are coupled with magnetic resonance imaging (MRI) and MR thermometry, thereby increasing patient safety. We report the published clinical experiences with SLT in epilepsy surgery (altogether approximately 200 cases) with respect to complications, brain structural alterations, seizure outcome, neuropsychological findings and treatment costs. The rate of seizure-free patients seems to be slightly lower than for resection surgery. Due to the inadequate quality of studies, the neuropsychological superiority of SLT has not yet been unambiguously demonstrated.

Minimally invasive periacetabular osteotomy using a modified Smith-Petersen approach: technique and early outcomes.

AIMS: Periacetabular osteotomy is an effective way of treating symptomatic hip dysplasia. We describe a new minimally invasive technique using a modification of the Smith-Peterson approach. We performed a prospective, longitudinal cohort study to assess for any compromise in acetabular correction when using this approach, and to see if the procedure would have a higher complication rate than that quoted in the literature for other approaches. We also assessed for any improvement in functional outcome. PATIENTS AND METHODS: From 168 consecutive patients (189 hips) who underwent acetabular correction between March 2010 and March 2013 we excluded those who had undergone previous pelvic surgery for DDH and those being treated for acetabular retroversion. The remaining 151 patients (15 men, 136 women) (166 hips) had a mean age of 32 years (15 to 56) and the mean duration of follow-up was 2.8 years (1.2 to 4.5). In all 90% of cases were Tönnis grade 0 or 1. Functional outcomes were assessed using the Non Arthritic Hip Score (NAHS), University of California, Los Angeles (UCLA) and Tegner activity scores. RESULTS: The mean pre-operative lateral centre-edge angle was 14.2° (-5° to 30°) and the mean acetabular index was 18.4° (4° to 40°). Post-operatively these were 31° (18° to 46°) and 3° (-7° to 29°), respectively, a significant improvement in both (p < 0.001). Allogenic blood transfusion was required in two patients (1.2%). There were no major nerve or vascular complications, and no wound infections. At the time of last follow-up, we noted a significant improvement in functional outcome scores: UCLA improved by 2.31 points, Tegner improved by 1.08 points, and the NAHS improved by 25.4 points (p < 0.001 for each). Hypermobility and longer duration of surgery were significant negative predictors for a good post-operative UCLA score, while residual retroversion was a positive predictor of post-operative UCLA score. CONCLUSION: We have found this approach to be safe and effective, facilitating early recovery from surgery. Cite this article: Bone Joint J 2017;99-B:22-8.

Probing the spiral magnetic phase in 6 nm textured erbium using polarised neutron reflectometry.

We characterise the magnetic state of highly-textured, sputter deposited erbium for a film of thickness 6 nm. Using polarised neutron reflectometry it is found that the film has a high degree of magnetic disorder, and we present some evidence that the film's local magnetic state is consistent with bulk-like spiral magnetism. This, combined with complementary characterisation techniques, show that thin film erbium is a strong candidate material for incorporation into device structures.

Magnetic Phases of Sputter Deposited Thin-Film Erbium.

We present a detailed structural and magnetic characterization of sputter deposited thin film erbium, determined by x-ray diffraction, transport measurements, magnetometry and neutron diffraction. This provides information on the onset and change of the magnetic state as a function of temperature and applied magnetic field. Many of the features of bulk material are reproduced. Also of interest is the identification of a conical magnetic state which repeats with a wavevector parallel to the c axis τc = 4/17 in units of the reciprocal lattice parameter c*, which is a state not observed in any other thin film or bulk measurements. The data from the various techniques are combined to construct magnetic field, temperature (H, T)-phase diagrams for the 200 nm-thick Er sample that serves as a foundation for future exploitation of this complex magnetic thin film system.

Seizure control and cognitive improvement via immunotherapy in late onset epilepsy patients with paraneoplastic versus GAD65 autoantibody-associated limbic encephalitis.

OBJECTIVE: To determine the efficacy of immunotherapy in limbic encephalitis (LE) associated epilepsies with autoantibodies against intracellular antigens in the forms of paraneoplastic autoantibodies versus glutamic acid decarboxylase 65 (GAD)-autoantibodies. METHODS: Eleven paraneoplastic-antibodies+ and eleven age- and gender-matched GAD-antibodies+ patients with LE were compared regarding EEG, seizure frequency, MRI volumetry of the brain, and cognition. All patients received immunotherapy with corticosteroids add-on to antiepileptic therapy. A few patients underwent additional interventions like immunoglobulins or immunoadsorption. RESULTS: Immunotherapy led to a significantly greater proportion of seizure-free patients in the paraneoplastic antibodies+(55%) as compared to GAD-antibodies+(18%) patients (p<0.05). Impaired cognition was evident initially (total cognitive performance score based on attentional-executive function, figural/verbal memory and word fluency) in 100% of the paraneoplastic-antibodies+ and 73% of the GAD-antibodies+ group. After therapy, cognition improved significantly in the paraneoplastic-antibodies+, but not in the GAD-antibodies+ patients (p<0.05). Cognitive change did not correlate with the change in the number of antiepileptic drugs over time. MRI showed larger and unchanged volumes of the amygdala, presubiculum and subiculum in GAD-antibodies+as compared to paraneoplastic-antibodies+patients (p<0.05) over time. CONCLUSIONS: Our data provide evidence of a beneficial effect of immunotherapy added to antiepileptic drugs on seizure frequency and cognition only in the paraneoplastic-antibodies+ subgroup of LE presenting autoantibodies against intracellular antigens.

The effects of downscaling method on the variability of simulated watershed response to climate change in five U.S. basins.

Simulations of future climate change impacts on water resources are subject to multiple and cascading uncertainties associated with different modeling and methodological choices. A key facet of this uncertainty is the coarse spatial resolution of GCM output compared to the finer-resolution information needed by water managers. To address this issue, it is now common practice to apply spatial downscaling techniques, using either higher-resolution regional climate models or statistical approaches applied to GCM output to develop finer-resolution information for use in water resources impacts assessments. Downscaling, however, can also introduce its own uncertainties into water resources impacts assessments. This study uses watershed simulations in five U.S. basins to quantify the sources of variability in streamflow, nitrogen, phosphorus, and sediment loads associated with the underlying GCM compared to the choice of downscaling method (both statistically and dynamically downscaled GCM output). We also assess the specific, incremental effects of downscaling by comparing watershed simulations based on downscaled and non-downscaled GCM model output. Results show that the underlying GCM and the downscaling method each contribute to the variability of simulated watershed responses. The relative contribution of GCM and downscaling method to the variability of simulated responses varies by watershed and season of the year. Results illustrate the potential implications of one key methodological choice in conducting climate change impacts assessments for water - the selection of downscaled climate change information.