Endovascular therapy outcome in isolated posterior cerebral artery occlusion strokes: A multicenter analysis of the Swiss Stroke Registry.

PURPOSE: There is little data on the safety and efficacy of endovascular treatment (EVT) in comparison with intravenous thrombolysis (IVT) in acute ischemic stroke due to isolated posterior cerebral artery occlusion (IPCAO). We aimed to investigate the functional and safety outcomes of stroke patients with acute IPCAO treated with EVT (with or without prior bridging IVT) compared to IVT alone. METHODS: We did a multicenter retrospective analysis of data from the Swiss Stroke Registry. The primary endpoint was overall functional outcome at 3 months in patients undergoing EVT alone or as part of bridging, compared with IVT alone (shift analysis). Safety endpoints were mortality and symptomatic intracranial hemorrhage. EVT and IVT patients were matched 1:1 using propensity scores. Differences in outcomes were examined using ordinal and logistic regression models. FINDINGS: Out of 17,968 patients, 268 met the inclusion criteria and 136 were matched by propensity scores. The overall functional outcome at 3 months was comparable between the two groups (EVT vs IVT as reference category: OR = 1.42 for higher mRS, 95% CI = 0.78-2.57, p = 0.254). The proportion of patients independent at 3 months was 63.2% in EVT and 72.1% in IVT (OR = 0.67, 95% CI = 0.32-1.37, p = 0.272). Symptomatic intracranial hemorrhages were overall rare and present only in the IVT group (IVT = 5.9% vs EVT = 0%). Mortality at 3 months was also similar between the two groups (IVT = 0% vs EVT = 1.5%). CONCLUSION: In this multicenter nested analysis, EVT and IVT in patients with acute ischemic stroke due to IPCAO were associated with similar overall good functional outcome and safety. Randomized studies are warranted.

Outcomes after reperfusion therapies in patients with ACA stroke: A multicenter cohort study from the EVATRISP collaboration.

BACKGROUND: Patients with stroke secondary to occlusions of the anterior cerebral artery (ACA) often have poor outcomes. The optimal acute therapeutic intervention for these patients remains unknown. METHODS: Patients with isolated ACA-stroke were identified from 10 centers participating in the EndoVascular treatment And ThRombolysis in Ischemic Stroke Patients (EVATRISP) prospective registry. Patients treated with endovascular thrombectomy (EVT) were compared to those treated with intravenous thrombolysis (IVT). Odds ratios with 95% confidence intervals (OR; 95%CI) were calculated using multivariate regression analysis. RESULTS: Included were 92 patients with ACA-stroke. Of the 92 ACA patients, 55 (60%) were treated with IVT only and 37 (40%) with EVT (±bridging IVT). ACA patients treated with EVT had more often wake-up stroke (24% vs. 6%, p = 0.044) and proximal ACA occlusions (43% vs. 24%, p = 0.047) and tended to have higher stroke severity on admission [NIHSS: 10.0 vs 7.0, p = 0.054). However, odds for favorable outcome, mortality or symptomatic intracranial hemorrhage did not differ significantly between both groups. Exploration of the effect of clot location inside the ACA showed that in patients with A1 or A2/A3 ACA occlusions the chances of favorable outcome were not influenced by treatment allocation to IVT or EVT. DISCUSSION: Treatment with either IVT or EVT could be safe with similar effect in patients with ACA-strokes and these effects may be independent of clot location within the occluded ACA.

Investigating the Association of Wallerian Degeneration and Diaschisis After Ischemic Stroke With BOLD Cerebrovascular Reactivity.

INTRODUCTION: Wallerian degeneration and diaschisis are considered separate remote entities following ischemic stroke. They may, however, share common neurophysiological denominators, since they are both related to disruption of fiber tracts and brain atrophy over time. Therefore, with advanced multimodal neuroimaging, we investigate Wallerian degeneration and its association with diaschisis. METHODS: In order to determine different characteristics of Wallerian degeneration, we conducted examinations on seventeen patients with chronic unilateral ischemic stroke and persisting large vessel occlusion, conducting high-resolution anatomical magnetic resonance imaging (MRI) and blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) tests, as well as Diamox 15(O)-H2O-PET hemodynamic examinations. Wallerian degeneration was determined using a cerebral peduncle asymmetry index (% difference of volume of ipsilateral and contralateral cerebral peduncle) of more than two standard deviations away from the average of age-matched, healthy subjects (Here a cerebral peduncle asymmetry index > 11%). Diaschisis was derived from BOLD-CVR to assess the presence of ipsilateral thalamus diaschisis and/or crossed cerebellar diaschisis. RESULTS: Wallerian degeneration, found in 8 (47%) subjects, had a strong association with ipsilateral thalamic volume reduction (r 2 = 0.60) and corticospinal-tract involvement of stroke (p < 0.001). It was also associated with ipsilateral thalamic diaschisis (p = 0.021), No cerebral peduncular hemodynamic differences were found in patients with Wallerian degeneration. In particular, no CBF decrease or BOLD-CVR impairment was found. CONCLUSION: We show a strong association between Wallerian degeneration and ipsilateral thalamic diaschisis, indicating a structural pathophysiological relationship.

Predictors for affected stroke territory and outcome of acute stroke treatments are different for posterior versus anterior circulation stroke.

Distinct patient characteristics have been proposed for ischaemic stroke in the anterior versus posterior circulation. However, data on functional outcome according to stroke territory in patients with acute stroke treatment are conflicting and information on outcome predictors is scarce. In this retrospective study, we analysed functional outcome in 517 patients with stroke and thrombolysis and/or thrombectomy treated at the University Hospital Zurich. We compared clinical factors and performed multivariate logistic regression analyses investigating the effect of outcome predictors according to stroke territory. Of the 517 patients included, 80 (15.5%) suffered a posterior circulation stroke (PCS). PCS patients were less often female (32.5% vs. 45.5%, p = 0.031), received thrombectomy less often (28.7% vs. 48.3%, p = 0.001), and had lower median admission NIHSS scores (5 vs. 10, p < 0.001) as well as a better median three months functional outcome (mRS 1 vs. 2, p = 0.010). Predictors for functional outcome were admission NIHSS (OR 0.864, 95% CI 0.790-0.944, p = 0.001) in PCS and age (OR 0.952, 95% CI 0.935-0.970, p < 0.001), known symptom onset (OR 1.869, 95% CI 1.111-3.144, p = 0.018) and admission NIHSS (OR 0.840, 95% CI 0.806-0.876, p < 0.001) in ACS. Acutely treated PCS and ACS patients differed in their baseline and treatment characteristics. We identified specific functional outcome predictors of thrombolysis and/or thrombectomy success for each stroke territory.

Embolization of tumor cells is rare in patients with systemic cancer and cerebral large vessel occlusion.

BACKGROUND AND PURPOSE: Stroke is a dreaded complication in patients with cancer. Besides paraneoplastic coagulopathy, chemotherapy, radiotherapy and tumor-directed invasive procedures, circulating cancer cells may contribute to thrombus formation and embolic stroke. However, the incidence of tumor cells within the blood clots of cancer patients with stroke is unknown and the role of circulating tumor cells in the formation of cerebrovascular thrombi remains unclear. METHODS: All patients who had undergone cerebrovascular thrombectomy at the University Hospital Zurich between 2014 and 2017 were screened for history of cancer. Clinical information was retrieved from the local stroke registry and the electronic charts and thrombi underwent a thorough histopathological re-review. RESULTS: Thirty-two of 182 patients (18%) with thrombectomy had a history of cancer. The majority of patients had advanced stage cancer. However, even after extensive histopathological re-review, only one specimen revealed tumor cells in the thrombus: a 75-year-old patient with acute occlusion of the middle cerebral artery who had been diagnosed with non-small-cell lung cancer 8.1 months prior to stroke. CONCLUSIONS: The presence of cancer cells in clots from cerebrovascular thrombectomy, indicative of a direct involvement of circulating tumor cells in the causation of stroke, is rare.

Task-Specific Motor Rehabilitation Therapy After Stroke Improves Performance in a Different Motor Task: Translational Evidence.

While the stroke survivor with a motor deficit strives for recovery of all aspects of daily life movements, neurorehabilitation training is often task specific and does not generalize to movements other than the ones trained. In rodent models of post-stroke recovery, this problem is poorly investigated as the training task is often the same as the one that measures motor function. The present study investigated whether motor training by pellet reaching translates into enhancement of different motor functions in rats after stroke. Adult rats were subjected to 60-min middle cerebral artery occlusion (MCAO). Five days after stroke, animals received either training consisting of 7 days of pellet reaching with the affected forelimb (n = 18) or no training (n = 18). Sensorimotor deficits were assessed using the sticky tape test and a composite neuroscore. Infarct volumes were measured by T2-weighted MRI on day 28. Both groups of rats showed similar lesion volume and forelimb impairment after stroke. Trained animals improved in the sticky tape test after day 7 post-stroke reaching peak performance on day 14. More reaching attempts during rehabilitation were associated with a better performance in the sticky tape removal time. Task-oriented motor training generalizes to other motor functions after experimental stroke. Training intensity correlates with recovery.

[Cognitive deficits and dementia in patients with multiple sclerosis: status quo and open questions]. / Kognitive Teilleistungsstörungen und Demenz bei Patienten mit Multipler Sklerose: Status quo und offene Fragen.

Multiple sclerosis (MS) is the most common chronic immune-mediated disease which goes along with serious somatic and psychic symptoms. Whereas recent research rather focussed on the neurological symptoms of MS, there is nowadays an increasing interest among researchers in psychological symptoms of the disease. It is known that about half of the MS patients suffer from cognitive deficits, and that cognitive decline has a disadvantageous impact on lifestyle and quality of life in affected persons. So far, cognitive deficits in subjects with MS have been described as rather isolated, specific cognitive disturbances with otherwise intact intellectual abilities, while global deterioration of mental skills in terms of dementia is considered as being rather rare. In the present article, we describe cognitive domains which are typically impaired in subjects with MS and reflect on the question if the diagnosis of dementia might be underrepresented in MS patients due to several reasons (e.g., progression of cognitive deficits in the course of the disorder, adhering very closely to memory deficits as cardinal symptom of dementia, lack of longitudinal studies of cognitive performance levels). Furthermore, we recommend a multistage neuropsychological diagnostic procedure for clinical practice which aims at diagnosing cognitive deficits already in early stages of the illness. In so doing, practitioners may be able to offer adequate therapies to affected persons in all stages of the disorder in order to improve psychosocial functional levels.

[Laparoscopic resection of gastric diverticula: two case reports]. / Die laparoskopische Resektion von Magendivertikeln: zwei Fallberichte.

Gastric diverticula are rare. In the literature the mentioned incidences vary between 0.01 % and 2.6 % depending on the method of detection. Until now the laparoscopic treatment of gastric diverticula is reported worldwide by eight authors (eight laparoscopic resections and one laparoscopic invagination with oversewing). Between September 2000 and November 2004 we have operated upon two patients laparoscopically for a gastric diverticulum. In two case reports we describe our operative and perioperative procedure. In both cases the gastric diverticulum was resected with a linear stapling device. In the second patient we did simultaneously a laparoscopic 360 degrees -Nissen-fundoplicatio plus dorsal hiatorrhaphy and fundopexy because of reflux disease based on a cardia insufficiency. The dates of the literature concerning incidence, localisation, classifications, symptoms, diagnostic and therapy are summarized and discussed. Our two case reports show, like the cases mentioned in the literature, that symptomatic gastric diverticula can be treated by laparoscopic resection with very good results.

[From hedgehogs to men. Zoophilic dermatophytosis caused by Trichophyton erinacei in eight patients]. / Von Igeln auf Menschen. Zoophile Dermatomykose durch Trichophyton erinacei bei 8 Patienten.

The hedgehog is an in Germany previously unrecognized source of human ringworm. Eight hedgehog caretakers from Göttingen and the surrounding area developed dermatophytosis caused by Trichophyton erinacei. Four patients who handled the animals without gloves developed lesions on the hands that were more in keeping with hand eczema, leading to a delay in diagnosis. The other caretakers who wore gloves presented with typical ringworm on the arms, the big toe, the back, the abdomen, and the thighs. Their typical clinical features led to an early diagnosis and treatment.

U-HO1, a new cell line derived from a primary refractory classical Hodgkin lymphoma.

The Hodgkin cell line U-HO1 was established from a malignant pleural effusion of a 23-year-old male patient during the end stage of refractory nodular sclerosing classical Hodgkin lymphoma (cHL). Since its establishment in 2005, U-HO1 has maintained stable characteristics in vitro and has a doubling time of about 4 days under standard culture conditions. U-HO1 forms typical Reed-Sternberg cells in suspension, is EBV negative, lacks HLA-A, -B, -C but expresses HLA-D proteins/CD74 and exposes CD15 together with CD30 in the absence of CD19 and CD20 on the cell surface. Karyotype analysis of U-HO1 revealed a hyperdiploid karyotype with multiple clonal aberrations. Most significant is an elongated chromosome 2, der(2)t(2;10)(q35; q16.1)add(2)(p13). CGH analysis revealed the following imbalances: ish cgh dim(1)(p13p31)(p12q21), enh(2)(p13p23), dim(4)(q31.3qter), enh(6)(q22q27), enh(12), enh(18), enh(20) (q13.1pter). FISH analysis showed about six-fold amplification of REL and BCL11A, thus, U-HO1 is prototypical for cHL in every aspect tested so far. As an outstanding feature compared to the existing HL cell lines, U-HO1 has high levels of microRNA transcripts of MIRN216 and MIRN217 located in the amplicon 2p16. Compared to other HL cell lines, U-HO1 proved far less genetically aberrant suggesting that U-HO1's imbalances suffice to cause the full-blown phenotype of primary refractory cHL.

Mutations of the tumor suppressor gene SOCS-1 in classical Hodgkin lymphoma are frequent and associated with nuclear phospho-STAT5 accumulation.

The suppressors of cytokine signaling (SOCS) are critically involved in the regulation of cellular proliferation, survival, and apoptosis via cytokine-induced JAK/STAT signaling. SOCS-1 silencing by aberrant DNA methylation contributes to oncogenesis in various B-cell neoplasias and carcinomas. Recently, we showed an alternative loss of SOCS-1 function due to deleterious SOCS-1 mutations in a major subset of primary mediastinal B-cell lymphoma (PMBL) and in the PMBL line MedB-1, and a biallelic SOCS-1 deletion in PMBL line Karpas1106P. For both cell lines our previous data demonstrated retarded JAK2 degradation and sustained phospho-JAK2 action leading to enhanced DNA binding of phospho-STAT5. Here, we analysed SOCS-1 in laser-microdissected Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL). We detected SOCS-1 mutations in HRS cells of eight of 19 cHL samples and in three of five Hodgkin lymphoma (HL)-derived cell lines by sequencing analysis. Moreover, we found a significant association between mutated SOCS-1 of isolated HRS cells and nuclear phospho-STAT5 accumulation in HRS cells of cHL tumor tissue (P < 0.01). Collectively, these findings support the concept that PMBL and cHL share many overlapping features, and that defective tumor suppressor gene SOCS-1 triggers an oncogenic pathway operative in both lymphomas.

[Mutations of the tumor suppressor gene SOCS-1 in classical Hodgkin lymphoma are frequent and associated with nuclear phospho-STAT5 accumulation]. / Mutationen des Tumorsuppressorgens SOCS-1 treten im klassichen Hodgkin Lymphom häufig auf und sind assoziiert mit einer Kernakkumulation des phospho-STAT5 Proteins.

AIMS: Suppressors of cytokine signaling (SOCS) negatively regulate Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling involved in proliferation, survival, and apoptosis. We previously showed a loss of SOCS-1 function due to deleterious mutations in a major subset of mediastinal B-cell lymphoma (MBL). In MBL cell lines this leads to retarded JAK2 degradation and sustained phospho-STAT5 action results in enhanced DNA binding of phospho-STAT5. METHODS: To investigate the SOCS-1 gene we laser-microdissected Hodgkin-and Reed-Sternberg (HRS) cells of 19 classical Hodgkin lymphoma (cHL) and performed sequencing analysis. To assess phospho-STAT5 status immunohistochemistry on the corresponding paraffin-embedded cHL tumor tissue was done. RESULTS: We detected mutations of the SOCS-1 gene in HRS cells of 8 of 19 cHL samples and in 3 of 5 cHL-derived cell lines. Moreover, we found a significant association between mutated SOCS-1 of isolated HRS cells and nuclear phospho-STAT5 accumulation in HRS cells (P <0.01). CONCLUSIONS: In conclusion, these findings support the concept that MBL and cHL share overlapping features and that defective tumor suppressor gene SOCS-1 triggers an oncogenic pathway operative in both lymphomas.

[Biallelic mutation of SOCS-1 impairs JAK2 degradation and sustains phospho-JAK2 action in MedB-1 mediastinal lymphoma line]. / Die biallelische Mutation von SOCS-1 verhindert den Abbau von JAK2 und prolongiert die Wirkung von phospho-JAK2 in der mediastinalen B-Zell Lymphomlinie MedB-1.

Primary mediastinal B-cell lymphoma (PMBL) is a well-defined subtype of diffuse large B-cell lymphoma. Molecular cytogenetics revealed frequent gains of 9 p24. JAK2, mapping in this region, is presently regarded as a candidate oncogene since expression profiling showed high JAK2 transcript levels and JAK2 was found to be constitutively phosphorylated in mediastinal B-cell lymphomas. We confirm that in the MedB-1 mediastinal B-cell line, harbouring a trisomy 9, JAK2 transcription is elevated and the product is highly phosphorylated. However, JAK2 is not over-expressed at the protein level. On top, JAK2 protein turnover is even delayed. This unexpected finding coincides with a biallelic mutation of the SOCS-1 gene in this cell, which abrogates SOCS box function of the protein. Ectopic expression of wt-SOCS-1 in MedB-1 leads to growth arrest, dramatic reduction of phospho-JAK2 and its downstream partner phospho-STAT5. We conclude that, in MedB-1, action of phospho-JAK2 is sustained due to defective SOCS-1. Hence, SOCS-1 qualifies as a novel tumor suppressor. Of note, the SOCS-1 mutations are also present in the parental tumor of MedB-1 and were detected in 9 of 20 PMBL.

Sulfonylurea drugs do not influence initial stroke severity and in-hospital outcome in stroke patients with diabetes.

BACKGROUND AND PURPOSE: Sulfonylurea drugs inhibit ATP-dependent potassium channels and may increase mortality after myocardial infarction. Sulfonylurea drugs also inhibit ischemic preconditioning in experimental models of brain ischemia and in clinical studies in the human heart. METHODS: In the present study we examined the impact of sulfonylurea drugs on in-hospital mortality and the immediate neurological deficit of diabetic stroke patients. From a larger stroke data bank, we studied 146 diabetic patients with acute hemispheric ischemic stroke. Sixty patients were using sulfonylurea drugs. RESULTS: Major baseline characteristics such as age, blood pressure, admission glucose level, HbA(1c), distribution of cardiovascular risk factors, and presumed stroke etiology (Trial of Org 10172 in Acute Stroke Treatment [TOAST] criteria) were not different. Mortality (15% versus 14%; P=0.86) and initial stroke severity (Canadian Neurological Scale score, 7.4 versus 7.5; P=0.79) were not significantly different between patients with and without sulfonylurea drugs. Further end points such as Rankin Scale score, deteriorating stroke, duration of hospital stay, type of infarcts on CT/MRI, requirement of intensive care, and complications were not different. In a stepwise logistic regression model, sulfonylurea drugs were not independent predictors for increased mortality, deteriorating stroke, or stroke severity. CONCLUSIONS: In the present hospital-based study, sulfonylurea drugs in patients with diabetes and stroke are not associated with increased stroke severity, mortality, or a worse in-hospital outcome.

A gene related to yeast HOS2 histone deacetylase affects extracellular depolymerase expression and virulence in a plant pathogenic fungus.

A gene, HDC1, related to the Saccharomyces cerevisiae histone deacetylase (HDAC) gene HOS2, was isolated from the filamentous fungus Cochliobolus carbonum, a pathogen of maize that makes the HDAC inhibitor HC-toxin. Engineered mutants of HDC1 had smaller and less septate conidia and exhibited an approximately 50% reduction in total HDAC activity. Mutants were strongly reduced in virulence as a result of reduced penetration efficiency. Growth of hdc1 mutants in vitro was normal on glucose, slightly decreased on sucrose, and reduced by 30 to 73% on other simple and complex carbohydrates. Extracellular depolymerase activities and expression of the corresponding genes were downregulated in hdc1 mutant strains. Except for altered conidial morphology, the phenotypes of hdc1 mutants were similar to those of C. carbonum strains mutated in ccSNF1 encoding a protein kinase necessary for expression of glucose-repressed genes. These results show that HDC1 has multiple functions in a filamentous fungus and is required for full virulence of C. carbonum on maize.

Penicillin-resistant streptococcus pneumoniae: review of moxifloxacin activity.

Streptococcus pneumoniae is a significant pathogen of respiratory tract infections such as pneumonia, sinusitis, meningitis, and acute otitis media. Rising incidences of antimicrobial resistance among pneumococcal strains reported worldwide have led to research into and development of advanced antibacterials with improved gram-positive activity. Moxifloxacin, a new 8-methoxy quinolone, has been tested against a variety of S. pneumoniae strains, including penicillin-sensitive, intermediately resistant to penicillin, and penicillin-resistant strains. We review the preclinical data corroborated by the available clinical experience to demonstrate moxifloxacin's activity against S. pneumoniae strains, irrespective of penicillin susceptibility.

Laparoscopic management of traumatic ruptures of the diaphragm.

INTRODUCTION: As a result of the relatively high frequency of high-speed accidents, diaphragmatic rupture is a diagnosis that is increasingly being established. Not all of these, usually multi-traumatized, patients are diagnosed as having diaphragmatic rupture immediately following the traumatic event--rather, an appreciable number of these injuries are not detected until some time later--often after a considerable delay. Most of the cases involve rupture of the left diaphragm, with most defects occurring in the region of the central tendon. METHODS: During the course of the second half of the year 1998, we operated on three patients with left diaphragmatic rupture. Two of these patients were treated immediately following traumatization, while the third case was a 10-year-old rupture originally misdiagnosed as a para-esophageal hernia. In all three cases, we were able to reduce the hernia and close the diaphragmatic defect laparoscopically. In the case of the two patients with a fresh rupture, the post-operative course was unremarkable, while in the patient with the missed rupture, a serous pleural effusion requiring drainage occurred on the left side. CONCLUSION: Overall, it would appear that in the case of an acute traumatic diaphragmatic rupture in particular, laparoscopic management, with its low level of traumatization and excellent access, offers a favorable alternative to conventional surgery. A point to be considered, however, is the fact that probably not every hospital will have the facilities for laparoscopic management available on a 24-h basis. In the case of longstanding ruptures, reduction of herniated bowel and treatment of the rupture will make considerable demands on the surgeon.