[Juvenile stroke - what is important?] / Juveniler Schlaganfall ­ was gibt es zu beachten?

Stroke in young adults is a diagnostic and therapeutic challenge for all persons involved. Approximately 15% of ischemic strokes occur in young adults. Lack of awareness of the symptoms in emergency departments often results in delayed diagnosis and access to specific therapeutic options, such as revascularization. The causes are often heterogeneous and necessitate specific investigations. The etiology of juvenile stroke includes drug abuse, vasculitis and arteriopathies, such as reversible vasoconstriction syndrome and posterior reversible encephalopathy syndrome, although the prevalence of classical vascular risk factors is high. The most frequent causes of ischemic stroke in young adults are cardioembolism and microangiopathy; furthermore, dissection of vessels of the neck are more frequent compared to older patients. According to the results of currently available studies reperfusion strategies, such as intravenous fibrinolysis and mechanical thrombectomy are efficacious and safe in young patients.

[Cerebral amyloid angiopathy associated with inflammation]. / Zerebrale Amyloidangiopathie assoziiert mit Inflammation.

Cerebral amyloid angiopathy (CAA) associated with inflammation is a rare form of a potentially reversible encephalopathy in a subgroup of patients with CAA. The cerebral amyloid deposition can in isolated cases induce an inflammation predominantly of the cerebral blood vessels and a multifocal edema of the cerebral white matter. The courses can occur as monophasic, relapsing remitting and primarily progressive forms. We present seven cases with different courses of the disease and give an overview of the pathophysiology, clinical aspects and treatment of the disease with reference to the current literature. The cases presented show a very different and often difficult differential diagnostic clinical picture and all showed a significant improvement under steroid medication without signs of recurrence of the disease during the course. The recognition and early consistent treatment of inflammatory forms of CAA with and without direct inflammatory involvement of vessels can be decisive for successful treatment.

Glycoprotein IIb/IIIa Inhibitor Bridging and Subsequent Endovascular Therapy in Vertebrobasilar Occlusion in 120 Patients.

PURPOSE: The treatment mode in acute vertebrobasilar occlusion (VBO) remains uncertain. We analyzed efficacy and safety of intravenous glycoprotein IIb/IIIa inhibitor (IV GPI) plus subsequent intra-arterial thrombolysis with or without additional endovascular mechanical therapy (percutaneous transluminal angioplasty/stenting or thrombus aspiration) and sought treatment factors that predict good clinical outcome. METHODS: We retrospectively analyzed 120 cases of patients with angiographically proven acute VBO. Multivariate logistic regression was used to identify independent predictors for clinical outcome and included level of consciousness, age, sex, time to angiography, GPI agent, admission mode, occlusion type, recanalization success, and endovascular treatment mode. Clinical follow-up was dichotomized in no to moderate disability (modified Rankin scale (mRS) 0-3) vs. severe disability or death (mRS 4-6). RESULTS: Median National Institutes of Health stroke scale (NIHSS) score on admission was 32, and mean NIHSS score was 24. A total of 49 patients (41 %) developed no to moderate disability (mRS 0-3), and 39 patients (33 %) died. Thrombolysis in myocardial infarction 2/3 recanalization success was achieved in 97 patients (80.8 %). Symptomatic intracerebral hemorrhages occurred in 11 patients (9 %). Mild impairment of consciousness (p < 0.001) and embolic occlusion type (p = 0.01) were significant predictors of favorable outcome. Clinical outcome in recanalized patients was better, but not statistically significant (p = 0.055). CONCLUSIONS: Our results indicate that combined therapy with IV GPI and subsequent endovascular therapy may be a valid treatment strategy in acute VBO. With this treatment approach, a preserved vigilance before treatment and an embolic occlusion type are associated with no to moderate disability.

[Not Available]. / IQWiG Arbeitspapier GA15-02: "Stents zur Behandlung intrakranieller Stenosen: VISSIT Studie und Akutbehandlung in Deutschland". Kommentar des Berufsverbandes der Neuroradiologen (BDNR), der Deutschen Gesellschaft für Neuroradiologie (DGNR), der Deutschen Gesellschaft für Neurologie (DGN) und der Deutschen Schlaganfall-Gesellschaft (DSG).

There is an ongoing discussion about reimbursement of stent-angioplasty for the treatment of intracranial stenoses in Germany. The discussion was initiated by the statutory health insurance companies after publication of the SAMMPRIS study results, which were in favor for medical management compared to stent-angioplasty with the Wingspan® stent system. A report (Rapid report N14-01) mainly based on SAMMPRIS was written by the German Institute for Quality and Efficiency in Health Care (IQWiG) and serves as a basis for the decision-making process. This report was previously commented by the medical societies involved. Limitations of the SAMMPRIS trial and vital indications for intracranial stenting were outlined in this comment (acute vessel occlusion, hemodynamic impairment, recurrent symptoms under medical treatment). Currently also emergency stent procedures are a matter of debate. In this context a second IQWiG report was commissioned (GA 15 - 02) addressing the results of the VISSIT trial, the transferability of the results of the first report to emergency treatments and the practice of emergency intracranial stent treatment in Germany. Regarding transferability of results the main conclusion was that there was no evidence that the results of the studies analyzed for the first report (mainly SAMMPRIS) could not be transferred to emergency treatments. From a medical professional and scientific standpoint it is inacceptable to compare outcomes of a secondary prophylactic treatment with emergency procedures. The analysis of emergency treatments in Germany based on retrospective case series with a cumulative number of 31 patients. Since most emergency procedures are performed in a clinical context and are not necessarily subject to scientific evaluation, this does not reflect current practice in Germany. The first part of this statement briefly outlines the design of SAMMPRIS and VISSIT and the interpretation of the trial results from a professional perspective. The current state of discussion regarding reimbursement of intracranial stenting is summarized. The second section contains a detailed comment on the current IQWiG report GA15-02 "Stents for the treatment of intracranial artery stenosis: VISSIT study and acute treatment in Germany".

IQWiG Arbeitspapier GA15-02: "Stents zur Behandlung intrakranieller Stenosen: VISSIT Studie und Akutbehandlung in Deutschland" : Kommentar des Berufsverbandes der Neuroradiologen (BDNR), der Deutschen Gesellschaft für Neuroradiologie (DGNR), der Deutschen Gesellschaft für Neurologie (DGN) und der Deutschen Schlaganfall-Gesellschaft (DSG).

There is an ongoing discussion about reimbursement of stent-angioplasty for the treatment of intracranial stenoses in Germany. The discussion was initiated by the statutory health insurance companies after publication of the SAMMPRIS study results, which were in favor for medical management compared to stent-angioplasty with the Wingspan® stent system. A report (Rapid report N14-01) mainly based on SAMMPRIS was written by the German Institute for Quality and Efficiency in Health Care (IQWiG) and serves as a basis for the decision-making process. This report was previously commented by the medical societies involved. Limitations of the SAMMPRIS trial and vital indications for intracranial stenting were outlined in this comment (acute vessel occlusion, hemodynamic impairment, recurrent symptoms under medical treatment).Currently also emergency stent procedures are a matter of debate. In this context a second IQWiG report was commissioned (GA 15 - 02) addressing the results of the VISSIT trial, the transferability of the results of the first report to emergency treatments and the practice of emergency intracranial stent treatment in Germany6. Regarding transferability of results the main conclusion was that there was no evidence that the results of the studies analyzed for the first report (mainly SAMMPRIS) could not be transferred to emergency treatments. From a medical professional and scientific standpoint it is inacceptable to compare outcomes of a secondary prophylactic treatment with emergency procedures. The analysis of emergency treatments in Germany based on retrospective case series with a cumulative number of 31 patients. Since most emergency procedures are performed in a clinical context and are not necessarily subject to scientific evaluation, this does not reflect current practice in Germany.The first part of this statement briefly outlines the design of SAMMPRIS and VISSIT and the interpretation of the trial results from a professional perspective. The current state of discussion regarding reimbursement of intracranial stenting is summarized. The second section contains a detailed comment on the current IQWiG report GA15-02 "Stents for the treatment of intracranial artery stenosis: VISSIT study and acute treatment in Germany".

Clopidogrel Resistance in Neurovascular Stenting: Correlations between Light Transmission Aggregometry, VerifyNow, and the Multiplate.

BACKGROUND AND PURPOSE: Clopidogrel resistance is blamed for thromboembolic complications in neurovascular stent placement. Platelet-function assays are weakly standardized. The aim of this study was to correlate the results of 3 different platelet-inhibition measurements (from light transmission aggregometry, the VerifyNow P2Y12 test, and the Multiplate analyzer) and their relation to periprocedural thromboembolic complications in elective neurovascular stent placement. MATERIALS AND METHODS: Clopidogrel resistance was determined on the day of the intervention according to predefined platelet reactivity cutoff values. All 3 tests were performed in 103 consecutive neurovascular stent-placement procedures in 97 patients (extracranial, n = 77; intracranial, n = 26). RESULTS: The clopidogrel resistance rates were 47.6% (light transmission aggregometry), 50.5% (VerifyNow), and 35.9% (Multiplate). In 67% of the patients, clopidogrel resistance was present according to at least one method. The correlations of qualitative results that classified a patient as responsive or resistant to clopidogrel were 67.9% for light transmission aggregometry with VerifyNow, 77.7% for light transmission aggregometry with the Multiplate, and 66% for VerifyNow with the Multiplate. Periprocedural thromboembolic complications (n = 9) occurred more frequently in patients who were determined by all 3 methods to be clopidogrel resistant. The difference was most pronounced with light transmission aggregometry (complication rates, 14.4% [clopidogrel-resistant patients] vs 3.7% [clopidogrel-responsive patients]). Sensitivity and specificity rates of clopidogrel resistance in relation to embolic complications were, respectively, 78% and 55% for light transmission aggregometry, 67% and 51% for VerifyNow, and 44% and 67% for the Multiplate. CONCLUSIONS: Clopidogrel resistance is a frequent finding in patients who undergo neurovascular stent placement. The correlations among the different testing methods are only modest and differ considerably. Light transmission aggregometry results seem to correlate with thromboembolic complications more accurately than with VerifyNow and Multiplate point-of-care methods.

Cerebral magnetic resonance imaging findings in adults with haemolytic uraemic syndrome following an infection with Escherichia coli, subtype O104:H4.

PURPOSE: Infections with Enterohaemorrhagic Escherichia coli typically occur in children causing haemolytic uraemic syndrome (HUS) and neurological symptoms in 20-50 %. Little information is available on the morphology of brain manifestations in adults. The purpose of this study was to identify a characteristic magnetic resonance imaging (MRI) pattern during the outbreak of a novel mutation of Escherichia coli O104:H4. METHODS: Patients were recruited from two hospitals between May and July 2011. The MRI protocol included standard anatomical, diffusion-weighted, and susceptibility-sensitive sequences. RESULTS: A total of 104 MRIs of 57 (32 female, 25 male) patients (mean 45.5 ± 18.4 years) showed abnormal signal intensity on 51 MRIs (49 %). Bilateral thalamus (39 %), bilateral pons (35 %), centrum semiovale and splenium of corpus callosum (33 %) were most often involved. Acute lesions were reversible in 81 % of cases. There was no statistically significant association between symptom onset and the MRI findings (P = 0.2). CONCLUSIONS: Neuroimaging findings in this adult patient cohort were non-specific and similar to previous findings in children. A characteristic neuroimaging pattern of an infection with Escherichia coli O104:H4 was not identified. However, bilateral symmetric T2 hyperintense lesions of the thalami and dorsal pons characterized by restricted diffusion suggest a metabolic toxic effect of the disease on the brain.

Cloning, and Molecular Characterization of Polymorphic Iranian Isolate Theileria annulata Surface Protein (Tasp).

BACKGROUND: Because of the strong immunologic responses of surface protein TaSp in Theileria annulata infected host, we tried to characterize this protein in a T. annulata isolate from Iran. METHODS: The RNA prepared from T. annulata infected cells was used to produce SMART-DS-cDNA. The Double strand cDNA was then amplified with primers derived from TaSp mRNA sequences. The PCR product was cloned in pTZ57R/T vector, sequenced and registered under accession no. JQ003240 in GenBank. RESULTS: The sequence analysis showed 90%-94% nucleotide sequence identity and 68%-94% amino acid homology to the corresponding sequences of TaSp gene by T. annulata, T. sp. china I, T. sp. china and T. lestoquardi and three T. annulata reported from Iran respectively. Interestingly, the sequence analysis also showed small nucleotide sequence region near the 5' end in which the presented TaSp protein differed very strongly from the other known TaSp sequences. For the preparation of the recombinant protein, the cDNA was cloned in pQE-32 vector, the recombinant protein was prepared and assayed by Theileria infected bovine serum. CONCLUSION: The polymorphism in TaSp gene could be detected in intra- as well as inter species. The different characterized TaSp proteins had a common identic region, which may be helpful for development of broad band vaccine based on the recombinant proteins. The polymorphism in this gene, make this protein also interesting for the diagnostic purposes.

Development of a Reverse Line Blot Hybridization method for Detection of some Streptococcal/Lactococcal Species, the causative agents of Zoonotic Streptococosis/Lactococosis in farmed fish.

BACKGROUND AND OBJECTIVE: Streptococcosis/lactococcosis is the cause of high morbidity and mortality in aquaculture sector and to date a number of species of Streptococcus and Lactococcus genera including S. iniae, S. agalactiae, S. dysagalactiae, S. parauberis, S. feacalis, L. garvieae and L. lactis have been discriminated as the cause of disease in aquatic animals. Despite the use of diagnostic molecular methods for each of these bacterial species, no data is available on a suitable, rapid and simple simultaneous detection tool for these pathogens. This paper describes a simultaneous detection method which is PCR based on a reverse line blot (RLB) for rapid detection and differentiation of four species of genera of Streptococcus and Lactococcus genera consisting of S. iniae, S. agalactiae, S. parauberis and L. garvieae the most important agents of the disease in fish. MATERIALS AND METHODS: A reverse line blot (RLB) assay was developed for the simultaneously identification of four species of Streptococcus/lactococcusconsisting of S. iniae, S. parauberis, S. agalactiaeand Lactococcusgarvieae. The assay employs one set of primer pair for specific amplification of the 16S rRNA gene. These were designed based on the nucleotide sequences of 16S rRNA gene sharing a homology region with Streptococcus spp. and Lactococcus spp. DNA was extracted from the pure bacterial colonies and amplified. A membrane was prepared with specific oligonucleotide for each bacterial species. PCR products were then hybridized to a membrane. RESULTS AND CONCLUSION: The amplification resulted in PCR product of 241 bp in length. No cross-reactions were observed between any of the tested bacterial species, and mixed DNAs from these four bacterial species were correctly identified. This RLB method is a suitable technique for a simultaneous detection of these species of bacterial fish pathogens that are some of the main causes of streptococcal/lactococcal infections in both freshwater and marine aquatic animals, and so we recommend its use for integrated epidemiological monitoring of streptococcosis/lactococcis in aquaculture industry.

Annualized relapse rate of first-line treatments for multiple sclerosis: a meta-analysis, including indirect comparisons versus fingolimod.

OBJECTIVES: Previous systematic reviews and meta-analyses of treatments in relapsing-remitting multiple sclerosis (RRMS) derived their findings from either placebo-controlled studies only or separately from head-to-head and comparative studies. The purpose of this study is to compare annualized relapse rates (ARR) of fingolimod versus all of the commonly used first-line treatments in RRMS using evidence from both placebo-controlled and head-to-head studies. In absence of the head-to-head data between fingolimod and the other treatments, these comparisons were formed using meta-analysis techniques for indirect treatment comparisons. METHODS: A systematic literature review was conducted by searching MEDLINE, EMBASE, and the Cochrane Library with no limitations applied on publication language or dates. Included studies were randomized controlled trials evaluating one or more of fingolimod, interferon beta-1a, interferon beta-1b, or glatiramer acetate in RRMS populations. Primary outcome was ARR. Data extraction included author, year, treatment, dosage, mean age, percentage females, duration of disease, Expanded Disability Status Scale (EDSS) score at baseline, relapses in 2 years prior to baseline, trial duration, relapse-related outcome, and definition of relapse. The indirect treatment comparisons were performed using a mixed-treatment comparison framework. ARR was analyzed as a Poisson outcome. RESULTS: The relative ARRs, for each treatment versus fingolimod, estimated from our meta-analyses were 1.43 (glatiramer acetate 20 mg), 1.51 (interferon beta-1b 250 mcg), 1.55 (interferon beta-1a 44 mcg), 1.67 (interferon beta-1a 22 mcg), 1.93 (interferon beta-1a 30 mcg), and 2.32 (placebo). None of the 95% confidence intervals for these estimates overlapped unity, implying statistical significance of these findings. LIMITATIONS: The key limitations of this study are the persisting heterogeneity even after adjusting for covariates and the variability in outcome definition across the included trials. CONCLUSIONS: Our study demonstrated that fingolimod significantly reduces relapse frequency in patients with RRMS compared with current first-line disease-modifying therapies.

Oral fingolimod (FTY720) in relapsing multiple sclerosis: impact on health-related quality of life in a phase II study.

BACKGROUND: Health-related quality of life (HRQoL) worsens with multiple sclerosis (MS) relapses and disease progression. Common symptoms including depression and fatigue may contribute to poor HRQoL. OBJECTIVES: To report exploratory analyses assessing the impact of fingolimod (FTY720) on HRQoL and depression in a phase II study of relapsing MS. METHODS: The Hamburg Quality of Life Questionnaire in MS (HAQUAMS) and Beck Depression Inventory second edition (BDI-II) scores were assessed during a 6-month, placebo-controlled study and optional extension. RESULTS: HAQUAMS total score improved with fingolimod and worsened with placebo. Mean score change from baseline to month 6 was -0.02 with fingolimod 1.25 mg (p < 0.05 versus placebo), -0.01 with fingolimod 5.0 mg and + 0.12 with placebo. Categorical data supported a clinically important effect of fingolimod on HRQoL. Fingolimod 1.25 mg was also beneficial over placebo in the fatigue/thinking HAQUAMS sub-domain (p < 0.05 versus placebo). Change in mean BDI-II scores from baseline to month 6 and the proportion of patients with BDI-II scores indicative of clinical depression favored fingolimod 1.25 mg over placebo (p < 0.05 for both). At month 4, mean BDI-II and HAQUAMS total scores appeared to be maintained in fingolimod-treated patients. CONCLUSION: Fingolimod 1.25 mg may improve HRQoL and depression at 6 months compared with placebo in patients with relapsing MS.

Carotidynia: magnetic resonance imaging and ultrasonographic imaging of a self-limiting disease.

This article describes the characteristic symptoms of carotidynia and the diagnostic options for this rare and not yet officially recognized disease entity. Based on a case report the findings of magnetic resonance imaging (MRI) and ultrasound scanning are presented.

Molecular study of sheep malignant theileriosis at barka region in the sultanate of oman.

BACKGROUND: We used the PCR technique based on the abovementioned primer pair and sequencing to demonstrate the Theileria infection in the sheep samples collected from Sultanate of Oman. METHODS: According to the frame work of "integrated control of ticks and tick borne diseases in globalized world managed by EU-ICTTD-3 project, the samples from blood, liver, spleen, lymph node and lung were sent to the laboratory of Iranian Research Center for Ticks and Tick-borne Diseases (IRCTTD). Samples from blood smear and impression smears from liver, spleen, lymph node, and lung were analyzed by Geimsa staining. The DNA was extracted from the abovementioned samples and analyzed by PCR technique using specific primers derived from the nucleotide sequences of 18S rRNA gene of T. lestoquardi, which can amplify the common region in other Theileria and Babesia spp. Subsequently the amplified DNA was sequenced. RESULTS: The analysis of blood smears of the sheep was negative for piroplasmosis performed through the Giemsa staining. The impression smears prepared from liver, spleen, lymph node, and lung showed suspicious structures mimicking Theileria schizonts in some cells. The results showed an expected PCR product of 428 bp in length, which is specific for Theileria spp. The PCR products were subsequently sequenced. The corresponding nucleotide sequence is registered under accession number JF309152 in GenBank. The sequence alignment in GenBank showed that the PCR products had 99% homology to the known T. lestoquardi registered under accession number AF081135 in the GenBank. CONCLUSION: Oman sheep are highly susceptible for Theileria infection and the infected sheep mostly die before the microschizonts or erythrocytic form of Theileria appears in the nucleated or erytrocytic cells respectively.

Successful treatment of shrinking lung syndrome with rituximab in a patient with systemic lupus erythematosus.

Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus (SLE). We report the case of a 27-year-old woman with SLE presenting with a 2-year history of chest pain and progressive dyspnea. Respiratory function tests demonstrated severe restrictive ventilatory impairment. Chest x-ray demonstrated elevated hemi diaphragms and chest computed tomography showed no evidence of interstitial fibrosis, significant pleural disease or pulmonary emboli. Based on a diagnosis of SLS the patient received 4 months of high dose corticosteroids, mycophenolate and pain management with opiates. Her condition deteriorated and she was given a trial of rituximab. This resulted in marked improvement of the clinical condition and respiratory function tests that was maintained for 18 months. Subsequently, the patient represented with a similar clinical picture and another course of rituximab again produced remission. This is the first case report of reproducible remission of SLS in SLE treated with rituximab.

The development and validation of the Unidimensional Fatigue Impact Scale (U-FIS).

BACKGROUND: The multidimensional assessment of fatigue is complicated by the interrelation of its multiple causes and effects. OBJECTIVE: The purpose of the research was to develop a unidimensional assessment of fatigue (U-FIS). METHODS: Data collected with the Fatigue Impact Scale (FIS) were subjected to Rasch analysis to identify potential problems with the scale. Additional items for the U-FIS were generated from interviews with UK MS patients. The U-FIS was tested for face and content validity in patient interviews and included in a validation survey to determine dimensionality (Rasch model), reliability and validity. RESULTS: The original FIS was not unidimensional when subscale items were combined. The modification of the FIS and addition of a number of items allowed the development of a 22-item unidimensional scale (U-FIS) that was reliable (Cronbach Alpha = 0.96; test-retest = 0.86,) and valid given correlations with the Nottingham Health Profile and ability to distinguish between MS severity groups. There was no significant difference in U-FIS scores according to MS type. CONCLUSION: It is valid to conceptualize the functional impact of fatigue as unidimensional. The U-FIS is a reliable and valid questionnaire that will allow the measurement of this construct in clinical studies.