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Turkish expresses adverbial subordination predominantly by means of converb clauses. These are headed by nonfinite verbs, i.e. converbs, which have a converb suffix attached to the stem. The different converbs express different aspectual relations between the subordinate and the superordinate clause, and they can be modifying or non-modifying. We analyse data from speakers of Turkish as a heritage language in Germany and the U.S. as well as monolingual speakers of Turkish in Turkey. The data come from two age groups: adults and adolescents. We show that unlike in canonical Turkish, converbs in heritage Turkish can be multifunctional, meaning that they can express both simultaneity and causality, for example. Furthermore, we show that converbs in heritage Turkish can be both modifying and non-modifying. As possible factors which might be responsible for such variation, we discuss language contact, sociolinguistic differences between the speaker communities (Germany vs. the U.S.) and age of the speakers.

Turkish is a language described as relying predominantly on non-finite subordination in the domain of clause combining. However, there are also strategies of finite subordination, as well as means of syndetic and asyndetic paratactic clause combining, especially in the informal settings. Clause combining is and has been one of the focal points of research on heritage Turkish (h-Turkish). One point is particularly clear: In comparison with the monolingual setting, finite means of clause combining are more frequent in h-Turkish in Germany, the U.S., and the Netherlands, while non-finite means of clause combining are less frequent. Overall, our results confirm the findings of earlier studies: heritage speakers in Germany and the U.S. prefer paratactic means of clause combining using connectors, as opposed to monolingual speakers. Our results also reveal that age (adolescents vs. adults) and register (informal vs. formal) significantly modulate the use of connectors. Moreover, we find that the shift in preferences in means of clause combining triggers an expansion in the system of connectors and leads to the development of new narrative connectors, such as o zaman and derken. The system of syndetic paratactic clause combining is expanding in heritage Turkish. This expansion calls for multifaceted modeling of change in heritage languages, which integrates language-internal factors (register), dynamics of convergence with the contact languages, and extra-linguistic factors (age and language use).

Summary L3 acquisition has begun to attract the attention of many scholars in recent years. Heritage contexts are especially fruitful areas to understand how linguistic and nonlinguistic mechanisms interact with one another. The current study focuses on L3 English acquisition of object pronouns with L1 Turkish, L2 German speakers. We seek to find out whether the speakers could produce object pronouns accurately, whether L3 English proficiency has any effects on their acquisition, and finally, whether all object pronouns are acquired in the same way. Data for this study come from a corpus consisting of written and oral productions of 167 participants, who were students in four distinct grades, namely 5th, 7th, 10th and 12th graders at different schools in Berlin, Germany. The results reveal that participants were highly meticulous in their object pronoun use. Also, no clear L1 effect was observed, while L2 impact is implied. Lastly, proficiency and linguistic features are noted as significant factors that have an impact on L3 acquisition.

This article presents an empirical study on selected aspects of the orthographic performance of mono- and bilingual students in German. Particular attention is paid to the question whether a connection can be drawn between the orthographic performance of the bilingual students in German and their first language. For this purpose, a corpus is analyzed with data from approx. 800 test students. One group is monolingual in German, one is bilingual German–Turkish and one is bilingual German–Russian. A highly significant influence of Russian resp. Turkish on the performance to differentiate between tense and lax vowels is found. This corresponds to expectations insofar as in opposition to German, neither in Turkish nor in Russian, tense and lax vowels are distinguished phonologically. In other areas of orthography, this influence of the first language is not measurable or not to the same extent.

Every anticoagulation decision has in inherent risk of hemorrhage; intracerebral hemorrhage (ICH) is the most devastating hemorrhagic complication. We examined whether combining ischemic and hemorrhagic stroke risk in individual patients might provide a meaningful paradigm for risk stratification. We enrolled consecutive patients with anticoagulation-associated ICH in 15 tertiary centers in the USA, Europe and Asia between 2015 and 2017. Each patient was assigned baseline ischemic stroke and hemorrhage risk based on their CHA2DS2-VASc and HAS-BLED scores. We computed a net risk by subtracting hemorrhagic from ischemic risk. If the sum was positive the patient was assigned a “Favorable” indication for anticoagulation; if negative, “Unfavorable”. We enrolled 357 patients [59% men, median age 76 (68–82) years]. 31% used non-vitamin K antagonist (NOAC). 191 (53.5%) patients had a favorable indication for anticoagulation prior to their ICH; 166 (46.5%) unfavorable. Those with unfavorable indication were younger [72 (66–80) vs 78 (73–84) years, p = 0.001], with lower CHA2DS2-VASc score [3(3–4) vs 5(4–6), p

Reporting of new or unexpected adverse drug reactions of medicines that are subject to additional monitoring (“black triangle” label), such as the antipsychotic drug cariprazine, is of paramount importance to improve pharmacotherapy safety.

Prior studies suggest an association between Vitamin K antagonists (VKA) and cerebral microbleeds (CMBs); less is known about nonvitamin K oral anticoagulants (NOACs). In this observational study we describe CMB profiles in a multicenter cohort of 89 anticoagulation‐related intracerebral hemorrhage (ICH) patients. CMB prevalence was 51% (52% in VKA‐ICH, 48% in NOAC‐ICH). NOAC‐ICH patients had lower median CMB count [2(IQR:1–3) vs. 7(4–11); P

High-dose-rate brachytherapy (HDR-BT) for dose escalation in localized prostate cancer has been established as one standard treatment option. However, long-term results at followup (FU) ≥5 years are usually needed to ensure robustness of reported outcomes. Potential benefit of salvage therapy is, nevertheless, higher when relapse is diagnosed early. This study aimed to solve this dilemma by evaluating the prostate-specific antigen (PSA) nadir for early prediction of long-term biochemical control.Combined pelvis-external beam radiation/HDR-BT boost to EQD2100 Gy (α/β = 3) was performed in 459 consecutively treated patients. These patients with an FU ≥ 24 months were analyzed and stratified in PSA nadir (nPSA)-groups by PSA nadir within 18 months after radiotherapy (nPSA18). Kaplan-Meier/log-rank tests and Cox-regression models were used to compare the study endpoints.The mean FU was 77 months. A PSA nadir within 18 months (nPSA18)0.5 ng/mL was achieved in 222 patients with median time to reach nPSA18 of 7 months. The 5-year American Society of Therapeutic Radiology and Oncology (ASTRO) biochemical control (prostate-specific antigen disease-free survival) for the nPSA18 group0.5 ng/mL was 89% and for the group ≥ 0.5 ng/mL, it was 78.6% (p = 0.011). nPSA18 was an independent predictor of cancer-specific survival, distant metastasis-free survival, and biochemical control (ASTRO) (p = 0.026, p = 0.020, and p = 0.01, respectively).The present results suggest that the PSA nadir level within 18 months after radiotherapy may serve as an early parameter for long-term biochemical control according to ASTRO definitions following radical dose escalation by HDR-BT for prostate cancer. Excellent outcomes were associated with nPSA18 0.5 ng/mL.

BACKGROUND AND PURPOSE Progressive multifocal leukoencephalopathy (PML), an opportunistic infection of the central nervous system from the John Cunningham virus (JCV), is a side effect of natalizumab (NTZ) treatment for relapsing-remitting multiple sclerosis (RRMS), potentially leading to a substantial increase of physical and mental disability. Nevertheless, data of neuropsychological impairment during the NTZ-PML disease course are missing. Our objective was to evaluate the neuropsychological disease course of NTZ-PML patients and to compare neuropsychological deficits of NTZ-PML patients with two different non-PML multiple sclerosis (MS) cohorts. METHODS Neuropsychological examinations of 28 NTZ-PML patients performed during different phases of the disease ([i] at PML diagnosis, [ii] during immune reconstitution inflammatory syndrome [IRIS], and [iii] post-IRIS/PML) were retrospectively analyzed and compared to those of NTZ-treated RRMS or secondary progressive MS patients with and without immunotherapy. RESULTS Compared to controls, NTZ-PML patients performed worse in neuropsychological examinations during all stages of disease, mainly affecting visuospatial ability and working memory. Furthermore, failure to eliminate the JCV from the central nervous system was associated with a progredient decline of cognition, especially working memory. CONCLUSIONS Working memory and visuospatial abilities are the core neuropsychological deficits of NTZ-PML patients in long-term follow-up. Our findings should be implemented in neurorehabilitation strategies.

Die deutschsprachigen Lander sind mehrsprachig, in mehrerer Hinsicht. Sie sind es einerseits im Sinne der regionalen Varietaten des plurizentrischen Deutschen; es gibt Gebiete, in denen die informellen Register sehr stark von Dialekten gepragt sind, die neben dem schriftsprachlich orientierten formalen Register bestehen, bis hin zu den (binnen-)diglossischen Verhaltnissen der deutschsprachigen Schweiz. Sie sind es auch, weil neben dem Deutschen anerkannte Minderheitensprachen bestehen, meist regional gebunden, aber im Falle des Romanes auch regional ungebunden; ebenso ist die deutsche Gebardensprache als eigenstandige Sprache anerkannt.

The paper investigates Turkish texts from heritage speakers of Turkish in Germany in a pseudo-longitudinal setting, looking at pupils’ texts from the 5th, 7th, 10th and 12th grades. Two types of dynamics are identified in the advanced acquisition1 of Turkish orthography in the heritage context. One is the dynamic of language contact, where in certain areas of the orthography, we find a re-interpretation of Turkish principles according to the German model. However, this changes as the pupils grow up. The second dynamic is the heritage situation. The heritage situation on one side leads to the establishment of new practices, and it also leads to a higher degree of variability of spelling solutions in those areas, where the orthographic system of Turkish poses challenges to every writer, whether monolingual and growing up in Turkey or heritage speaker.2

We thank Dr. Chen for his comment. We included neuromyelitis optica spectrum disorder (NMOSD) patients with longitudinal visual-evoked potential (VEP) data covering ≥3 months. We calculated the changes per year using regression analysis. For eyes with

Introduction: With more widespread anticoagulant use, anticoagulation-associated intracerebral hemorrhage (ICH) represents an increasing proportion of all ICH. We hypothesized that c ombining ischemic and hemorrhagic stroke risk estimation can guide treatment decisions, with more precision than ischemic risk estimation alone. Methods: We enrolled consecutive patients with anticoagulation-associated ICH in 15 centers in USA, Europe and Asia from 2015-2017. Each patient was assigned annual baseline ischemic stroke and hemorrhage risk based on their CHA 2 DS 2 -VASc and HAS-BLED scores without and with index ICH taken into account. We computed a net risk by subtracting the hemorrhagic from the ischemic risk. If the sum was positive the patient was assigned a “Favorable” indication for anticoagulation; if negative an “Unfavorable”. We compared clinical and neuroimaging characteristics between the two groups. Results: Our cohort comprised 357 patients (59% male, median age 76 [68-82] years). 69% used vitamin-K antagonists (VKA), 31 % Non vitamin K antagonist (NOAC). 191 (53.5%) of patients had a favorable indication for anticoagulation prior to their ICH event; the rest 166 (46.5%) had an unfavorable indication. Those with an unfavorable indication were younger (72[66-80] vs 78[73-84] years, p=0.001, had a lower CHA 2 DS 2 -VASc score (3[3-4] vs 5[4-6], p Conclusions: In this anticoagulation-associated ICH cohort, baseline hemorrhage risk exceeded ischemic risk in ~50% of patients. This finding highlights the need for careful consideration of risk/benefit ratio prior to anticoagulation decisions. The remaining ~ 50% suffered an ICH although their baseline risk of ischemia exceeded that of hemorrhage which stresses the need for imaging, serum or other biomarkers to allow more precise estimation of hemorrhagic complication risk.

ObjectiveTo determine the prevalence of antibodies to Epstein-Barr virus (EBV) in a large cohort of patients with early multiple sclerosis (MS).MethodsSerum samples were collected from 901 patients with a clinically isolated syndrome (CIS) or early relapsing–remitting multiple sclerosis (RRMS) participating in the German National MS cohort, a prospective cohort of patients with early MS with stringent inclusion criteria. Epstein-Barr nuclear antigen (EBNA)-1 and viral capsid antigen (VCA) antibodies were measured in diluted sera by chemiluminescence immunoassays (CLIAs). Sera of EBNA-1 and VCA antibody-negative patients were retested undiluted by an EBV IgG immunoblot. For comparison, we retrospectively analysed the EBV seroprevalence across different age cohorts, ranging from 0 to >80 years, in a large hospital population (N=16 163) from Berlin/Northern Germany.ResultsEBNA-1 antibodies were detected by CLIA in 839 of 901 patients with CIS/RRMS. Of the 62 patients without EBNA-1 antibodies, 45 had antibodies to VCA as detected by CLIA. In all of the remaining 17 patients, antibodies to EBV were detected by immunoblot. Altogether, 901 of 901 (100%) patients with CIS/RRMS were EBV-seropositive. EBV seropositivity increased with age in the hospital population but did not reach 100% in any of the investigated age cohorts.ConclusionThe complete EBV seropositivity in this large cohort of patients with early MS strengthens the evidence for a role of EBV in MS. It also suggests that a negative EBV serology in patients with suspected inflammatory central nervous system disease should alert clinicians to consider diagnoses other than MS.

Background and Purpose— The aim of this study was to prospectively validate our prior findings of smaller hematoma volume and lesser neurological deficit in nonvitamin K oral anticoagulant (NOAC) compared with Vitamin K antagonist (VKA)-related intracerebral hemorrhage (ICH). Methods— Prospective 12-month observational study in 15 tertiary stroke centers in the United States, Europe, and Asia. Consecutive patients with premorbid modified Rankin Scale score of 33%] increase), neurological severity measured by National Institutes of Health Stroke Scale score, 90-day mortality, and functional status (modified Rankin Scale score). Results— Our cohort comprised 196 patients, 62 NOAC related (mean age, 75.0±11.4 years; 54.8% men) and 134 VKA related (mean age, 72.3±10.5; 73.1% men). There were no differences in vascular comorbidities, antiplatelet, and statin use; NOAC-related ICH patients had lower median baseline hematoma volume (13.8 [2.5–37.6] versus 19.5 [6.6–52.0] mL; P =0.026) and were less likely to have severe neurological deficits (National Institutes of Health Stroke Scale score of >10 points) on admission (37% versus 55.3%, P =0.025). VKA-ICH were more likely to have significant hematoma expansion (37.4% versus 17%, P =0.008). NOAC pretreatment was independently associated with smaller baseline hematoma volume (standardized linear regression coefficient:−0.415 [95% CI, −0.780 to −0.051]) resulting in lower likelihood of severe neurological deficit (odds ratio, 0.44; 95% CI, 0.22−0.85) in multivariable-adjusted models. Conclusions— Patients with NOAC-related ICH have smaller baseline hematoma volumes and lower odds of severe neurological deficit compared with VKA-related ICH. These findings are important for practicing clinicians making anticoagulation choices.

Background and purpose To date, normal values for optic nerve diameter (OND) and optic nerve sheath diameter (ONSD) for transorbital sonography (TOS) have only been reported by individual small-scale studies, exposing a great variability in the measurement of the OND and ONSD. Methods We performed a systematic review and metanalysis of available to date studies on TOS evaluation of adults without elevated intracranial pressure to provide an overview of the published literature, measuring methods and further specify normal values for OND and ONSD. Results In total, we included 39 studies with 2,927 healthy volunteers (mean age 36.1 years, 44.4% female), so that a total of 5,854 eyes were examined. All pooled analyses were based on random effect models. Mean values for OND were provided in 13 studies. Calculated mean pooled OND value was 3.08 mm (95% confidence interval [CI], 2.9-3.25), with low heterogeneity across studies (I2 = 12.7%). Thirty-four studies provided mean values for ONSD measurement. The pool of mean ONSD measurements was 4.78 mm (95% CI, 4.63-4.94), with evidence of substantial heterogeneity between estimates ONSD (I2 = 50.6%). There were no significant differences (P = .139) in the subsequent subgroup analysis for the different geographic continents. Also, no significant differences could be recorded for the effect of age (P = .824) or gender (P = .093). Conclusions TOS is a frequently described and widely used method. We provide reference values of OND and ONSD that are based on metanalytical analysis. Different measuring methods of ONSD result in higher heterogeneity. Subgroup analysis revealed no significant correlation between ONSD and age, gender, or geographic origin.

BACKGROUND AND PURPOSE Early prognostication of the outcome in resuscitated post cardiac arrest (CA) patients remains challenging especially if treated with therapeutic hypothermia. Brain edema caused by hypoxic-ischemic encephalopathy (HIE) can indirectly be estimated by transorbital sonography (TOS) taking in account the optic nerve sheath diameter (ONSD). The prognostic value of this easy, safe, and reproducible technique was investigated in this study. METHODS A total of 49 patients, initially unconscious (Glasgow Coma Scale ≤6) after successful resuscitation, were enrolled into this prospective observational study. Sonographic ONSD measurements were performed twice on day of admission (day 0) and once on days 1 and 2 after CA. Beyond ONSD, established prognostic parameters like neuron specific enolase and gray-white matter ratios were assessed. Cerebral Performance Category (CPC) score served as outcome parameter. RESULTS A total of 15 (31.3%) patients had a good outcome (CPC-score 1-2), 8 patients (14.6%) had severe disability (CPC-score 3-4), and 26 (54.2%) had a fatal outcome (CPC-score 5). Already in the first measurement on day 0, nonsurvivors showed significantly higher ONSD values (P < .001). For predicting mortality, a threshold of 5.75 mm was calculated with a specificity of 100%. ONSD did not differ significantly depending on hypothermia (P = .7009). CONCLUSION Early and reliable prognostication of outcomes in patients with HIE can be simplified by ONSD values gathered with the use of TOS. Main advantages compared to other established markers are prognostication within the first 24 hours and independence from therapy with hypothermia. A higher level of accuracy can be reached by combining computed tomography (gray-to-white matter ratio values) and ONSD values.

Background and purpose Vascular aspects like global cerebral hypoperfusion are frequently reported in patients with multiple sclerosis (MS). Although mechanistic question remains unanswered, this hemodynamic impairment may be caused by a widespread endothelial dysfunction. Furthermore, impaired cerebrovascular reactivity (CVR) has been described in patients with MS by means of hypercapnic perfusion magnetic resonance imaging (MRI). We sought to further evaluate potential hemodynamic restriction in patients with MS using functional sonographic methods. Methods We evaluated consecutive patients with MS and healthy controls with adequate bilateral transtemporal window. CVR was assessed by bilateral transcranial Doppler monitoring of proximal middle cerebral arteries. Mean flow velocities were recorded before and after 30 seconds of breath holding. Vasomotor response was quantified by breath holding index (BHI). Results A total of 42 patients with MS (mean age 39 ± 12 years; 69% women) were compared to 31 healthy controls (mean age 35 ± 11 years; 71% women). BHI was lower in patients with MS compared to healthy controls (.70 ± .43 vs. .93 ± .55; P = .006), documenting a lower cerebrovascular response to hypercapnia. There was no correlation between patient age (r = .1254; P = .277), expanded disability status scale (r = .1838; P = .109), and disease duration (r = .1882; P = .101) with BHI in patients with MS. Conclusions These preliminary sonographic findings appear to independently corroborate the previously reported observation of impaired CVR on brain MRI in patients with MS. However, the underlying pathophysiological mechanisms as well as the clinical impact of this observation remain elusive.

ObjectiveTo investigate if patients with neuromyelitis optica spectrum disorder (NMOSD) develop subclinical visual pathway impairment independent of acute attacks.MethodsA total of 548 longitudinally assessed full-field visual evoked potentials (VEP) of 167 patients with NMOSD from 16 centers were retrospectively evaluated for changes of P100 latencies and P100-N140 amplitudes. Rates of change in latencies (RCL) and amplitudes (RCA) over time were analyzed for each individual eye using linear regression and compared using generalized estimating equation models.ResultsThe rates of change in the absence of optic neuritis (ON) for minimal VEP intervals of ≥3 months between baseline and last follow-up were +1.951 ms/y (n = 101 eyes; SD = 6.274; p = 0.012) for the P100 latencies and −2.149 µV/y (n = 64 eyes; SD = 5.013; p = 0.005) for the P100-N140 amplitudes. For minimal VEP intervals of ≥12 months, the RCL was +1.768 ms/y (n = 59 eyes; SD = 4.558; p = 0.024) and the RCA was −0.527 µV/y (n = 44 eyes; SD = 2.123; p = 0.111). The history of a previous ON >6 months before baseline VEP had no influence on RCL and RCA. ONs during the observational period led to mean RCL and RCA of +11.689 ms/y (n = 16 eyes; SD = 17.593; p = 0.003) and −1.238 µV/y (n = 11 eyes; SD = 3.708; p = 0.308), respectively.ConclusionThis first longitudinal VEP study of patients with NMOSD provides evidence of progressive VEP latency delay occurring independently of acute ON. Prospective longitudinal studies are needed to corroborate these findings and help to interpret the clinical relevance.

Congenital diaphragmatic hernia (CDH) occurs in similar to 1:2,000 pregnancies and is associated with substantial morbidity and mortality. Fetal tracheal occlusion (TO) is an emerging therapy that improves lung growth and reduces mortality, although substantial respiratory compromise persists in survivors. In this study, we used tracheal fluid in a fetal sheep model of CDH with TO for proteomic analysis with subsequent validation of findings in sheep lung tissue. We found that the proteomic profiles of CDH tracheal fluid was most similar to control lung and CDH/TO lung most similar to TO lung. Among 118 proteins altered in CDH, only 11 were reciprocally regulated in CDH/TO. The most significantly altered pathways and processes were cell proliferation, phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling, inflammation, and microtubule dynamics. CDH suppressed and TO promoted cell proliferation and AKT-related signaling cascades. By Western blot analysis and immunohistochemistry, epithelial PCNA and phosphorylated AKT were decreased in CDH and increased in TO and CDH/TO lungs. The Wnt target Axin2 was decreased threefold in CDH lung compared with control without a significant increase in CDH/TO lung. Cilia-related pathways were among the most dysregulated with CDH lung having a nearly twofold increase in acetylated alpha-tubulin and a relative increase in the number of ciliated cells. While TO improves lung growth and patient survival in CDH, the procedure substantially alters many processes important in lung development and cell differentiation. Further elucidation of these changes will be critical to improving lung health in infants with CDH treated with TO., National Heart, Lung, and Blood Institute; Spanish Health Institute Carlos III Economy and Development Ministry; Parker B. Francis Fellowship Award; Cincinnati Children’s Hospital Research Foundation Procter Award

The hyperechogenicity of the substania nigra (SN) has been established as a valid finding in patients with Parkinson&acute, s disease (PD), probably caused by an increased tissue iron concentration in the SN. The application of transcranial sonography (TCS) has been investigated for further echogenic basal ganglia alterations in patients with extrapyramidal movement disorders. Compared to PD, a hyperechogenic nucleus lentiformis (LN) has been reported to appear more frequently in atypical parkinsonian syndromes (aPS) such as the parkinsonian phenotype of multiple system atrophy (MSA-P) or the progressive supranuclear palsy (PSP). As the evidence providing study sizes are small, we conduct the first meta-analysis of the prevalence of LN hyperechogenicity in PD and aPS. We search for available studies providing prevalence of LN hyperechogenicity in patients with PD and aPS (MSA-P and PSP) detected by TCS in MEDLINE and SCOPUS databases. We calculate the prevalence rates of LN hyperechogenicity detection in patients with clinical diagnosis of PD vs. aPS under the random-effects model. We include a total of 1330 patients, 1091 PD and 239 aPS (MSA-P and PSP). We find a significantly higher prevalence of LN hyperechogenicity in aPS (76%, 95% CI: 0.62-0.88) compared to PD (16%, 95% CI: 0.10-0.23). After proving a higher prevalence of LN hyperechogenicity in aPS compared to PD, its histopathological cause needs to be investigated. Furthermore, its full diagnostic accuracy and the qualification to serve as a risk factor for MSA-P and PSP should also be questioned in future studies.

Der Band thematisiert die besonderen Bedingungen des deutsch-polnischen Sprachkontakts auf deutscher und polnischer Seite. Dieser Spezifik entsprechend ist das Buch gegliedert in die thematischen Schwerpunkte «Potenzial von Zweisprachigkeit und Einstellungen zur Zweisprachigkeit, Linguistische Untersuchungen zur Zweisprachigkeit und Grenzregion und Mehrsprachigkeit».Das Buchprojekt ist in Kooperation deutscher und polnischer Linguisten entstanden und geht auf eine Sektionentagung der Gesellschaft für Angewandte Linguistik (GAL) zurück. Dass die Autorinnen und Autoren ihre Beiträge auf Deutsch und Polnisch verfasst haben, steht programmatisch für die Intention dieser Publikation: Interesse zu wecken für die Spezifik des (zu) wenig beachteten deutsch-polnischen Sprachkontakts.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired, chronic progressive or relapsing immune mediated disorder of the peripheral nervous system. Thickening of cranial nerves as a sign of central nerve involvement is increasingly reported in the last years. Our aim was to assess systematically for the first time the frequency of optic nerve hypertrophy in patients with CIDP by means of transorbital sonography (TOS). Thirty-four optic nerves of 17 patients with CIDP (age=60.8±13.3y, range=39-82y; 7 female) were examined by TOS. The diameter of Optic nerve (OND) as well as the intern and extern diameters of the sheath (ONDSi, ONSDe) was measured 3mm behind the optic disc. Findings were compared to the data of 15 healthy controls. CIDP-patients showed a mean OND of 2.8±0.4mm, an ONSDi of 4.7±0.7mm, and an ONSDe of 6.3±0.9mm. No papilledema was detectable. There was no significant difference to the healthy control group. Our study revealed no evidence for a frequent optic nerve involvement in CIDP. Reported cases seem to represent exceptions. Transorbital sonography could be a useful tool in these rare cases with optic nerve hypertrophy.

After its discovery, anti-N-methyl-d-aspartate receptor encephalitis is now an established neuroinflammatory disorder, for which various immune-suppressive strategies have been successfully proposed. The most commonly applied therapy includes high dose cortico-steroids, as well as plasma exchange procedures (PLEX), and subsequently either oral immunosuppressants, such as azathioprine or B-cell depletion by the anti- CD20 monoclonal antibody rituximab. However, in rare cases we are faced with patients who do not respond to either oral immunosuppressants, or rituximab. Hence, we have recently described bortezomib, a proteasome inhibitor as a potentially effective treatment in patients not responding to first-line immune-therapies. Particularly, plasma cells as mature, non-dividing antibody secreting cells are highly sensitive to proteasome inhibitors. Here, we report of a patient with severe, and prolonged anti-NMDAR encephalitis despite PLEX and repeatedly applied high dose rituximab. As documented in the accompanying video that shows the different stages before, and immediately after bortezomib therapy the patient recovered swiftly.

Publicado em: Schroeder, Christoph. Zum Sprachverstandnis in der Migrationsdebattein Deutschland. In: Ekinci, Yuksel; Montanari, Elke; Selmani, Lirim (Hrsg.). Grammatik und Variation. Festschrift fur Ludger Hoffmann zum 65. Geburtstag. Heidelberg: Synchron, 2017. p. 361-367.

Objective:To compare the neuroimaging profile and clinical outcomes among patients with intracerebral hemorrhage (ICH) related to use of vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF).Methods:We evaluated consecutive patients with NVAF with nontraumatic, anticoagulant-related ICH admitted at 13 tertiary stroke care centers over a 12-month period. We also performed a systematic review and meta-analysis of eligible observational studies reporting baseline characteristics and outcomes among patients with VKA- or DOAC-related ICH.Results:We prospectively evaluated 161 patients with anticoagulation-related ICH (mean age 75.6 ± 9.8 years, 57.8% men, median admission NIH Stroke Scale [NIHSSadm] score 13 points, interquartile range 6–21). DOAC-related (n = 47) and VKA-related (n = 114) ICH did not differ in demographics, vascular risk factors, HAS-BLED and CHA2DS2-VASc scores, and antiplatelet pretreatment except for a higher prevalence of chronic kidney disease in VKA-related ICH. Patients with DOAC-related ICH had lower median NIHSSadm scores (8 [3–14] vs 15 [7–25] points, p = 0.003), median baseline hematoma volume (12.8 [4–40] vs 24.3 [11–58.8] cm3, p = 0.007), and median ICH score (1 [0–2] vs 2 [1–3] points, p = 0.049). Severe ICH (>2 points) was less prevalent in DOAC-related ICH (17.0% vs 36.8%, p = 0.013). In multivariable analyses, DOAC-related ICH was independently associated with lower baseline hematoma volume (p = 0.006), lower NIHSSadm scores (p = 0.022), and lower likelihood of severe ICH (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.13–0.87, p = 0.025). In meta-analysis of eligible studies, DOAC-related ICH was associated with lower baseline hematoma volumes on admission CT (standardized mean difference = −0.57, 95% CI −1.02 to −0.12, p = 0.010) and lower in-hospital mortality rates (OR = 0.44, 95% CI 0.21–0.91, p = 0.030).Conclusions:DOAC-related ICH is associated with smaller baseline hematoma volume and lesser neurologic deficit at hospital admission compared to VKA-related ICH.