Therapy of basilar artery occlusion: a systematic analysis comparing intra-arterial and intravenous thrombolysis

BACKGROUND AND PURPOSE: Basilar artery occlusion (BAO) is an infrequent form of acute stroke, which invariably leads to death or long-term disability if not recanalized. A traditional recanalization approach based on historical controls and pathophysiological consideration is local intra-arterial thrombolysis (IAT) in eligible patients. This necessitates diagnostic evaluation and treatment in stroke centers equipped with an interventional neuroradiological service on a 24-hour basis, but its superiority to the technically simple intravenous thrombolysis (IVT) remains unproven. METHODS: We analyzed systematically published case series of substantial size reporting the outcome of BAO after IAT or IVT. RESULTS: In 420 BAO patients treated with IVT (76) and IAT (344), death or dependency were equally common: 78% (59 of 76) and 76% (260 of 344), respectively (P=0.82). Recanalization was achieved more frequently with IAT (225 of 344; 65%) than with IVT (40 of 76; 53%; P=0.05), but survival rates after IVT (38 of 76; 50%) and IAT (154 of 344; 45%) were equal (P=0.48). A total of 24% of patients treated with IAT and 22% treated with IVT reached good outcomes (P=0.82). Without recanalization, the likelihood of good outcome was close to nil (2%). CONCLUSIONS: Recanalization occurs in more than half of BAO patients treated with IAT or IVT, and 45% to 55% of survivors regain functional independence. Although improved therapy forms for BAO are necessary, hospitals not equipped for IAT may set up IVT protocols. The effect of IVT is probably not much different from the effect of IAT. IVT represents probably the best treatment that can be offered to victims of acute BAO in such hospitals.

Outcome of stroke with mild or rapidly improving symptoms

BACKGROUND AND PURPOSE: Acute ischemic stroke with mild or rapidly improving symptoms is expected to result in good functional outcome, whether treated or not. Therefore, thrombolysis with its potential risks does not seem to be justified in such patients. However, recent studies indicate that the outcome is not invariably benign. METHODS: We analyzed clinical and radiological data of patients with stroke who presented within 6 hours of stroke onset and did not receive thrombolysis because of mild or rapidly improving symptoms. Univariate and logistic regression analyses were performed to define predictors of clinical outcome. RESULTS: One hundred sixty-two consecutive patients (110 men and 52 women) aged 63+/-13 years were included. The median National Institutes of Health Stroke Scale score on admission was 2 (range, 1 to 14). All patients presented within 6 hours of symptom onset. After 3 months, modified Rankin Scale score was of Health Stroke Scale score >/=10 points increased the odds of unfavorable outcome or death 16.9-fold (95% CI: 1.8 to 159.5; P<0.013), and proximal vessel occlusion increased the odds 7.13-fold (95% CI: 1.1 to 45.5; P<0.038). CONCLUSIONS: Seventy-five percent of patients with mild or rapidly improving symptoms will have a favorable outcome after 3 months. Therefore, a decision against thrombolysis seems to be justified in the majority of patients. However, selected patients, especially those with proximal vessel occlusions and baseline National Institutes of Health Stroke Scale scores >/=10 points, might derive a benefit from thrombolysis.

Quality of life in stroke survivors after local intra-arterial thrombolysis

Background: We aimed to assess quality of life (QOL) and its predictors in stroke survivors after local intra-arterial thrombolysis (IAT) as well as to measure QOL according to the site of pretreatment vessel occlusion. Methods: From January 2000 to April 2004, 175 consecutive patients underwent IAT for acute ischemic stroke. Clinical and radiological data were collected prospectively. We contacted 135 stroke survivors after a mean of 923 (+/-431) days, 132 responded. QOL, assessed with EuroQol (EQ-5D), and functional abilities, measured with the modified Rankin Scale (mRS) and the Barthel Index, were compared, and predictors of QOL were analyzed. Results: Measured with EQ-5D, 56% of the patients reported a good QOL (EQ-5D Index >/=70). Low mRS and high Barthel Index scores at follow-up were associated with better overall QOL (Kendall's tau >0.5). Nevertheless, 25% of the functionally independent patients (mRS 0-2) indicated a markedly impaired QOL (EQ-5D Index <70) and 10% of disabled patients indicated good QOL. QOL was significantly lower in patients with occlusion of the internal carotid artery compared to patients with occlusion of the basilar artery or the M1, M2 or M3/4 segment of the middle cerebral artery (EQ-5D Index: p = 0.005). A high National Institute of Health Stroke Scale score on admission and occlusion of the internal carotid artery were independent predictors of impaired QOL (p < 0.05). Conclusion: More than half of the stroke survivors treated with IAT reported a good QOL, mostly survivors with mild disabilities. QOL assessment gives information that is not provided by traditional outcome scores. Our results support guidelines to measure QOL in stroke research. Copyright (c) 2008 S. Karger AG, Basel.

Effect of interferon-beta and atorvastatin on Th1/Th2 cytokines in multiple sclerosis

Beneficial effects by both interferon-beta and statin treatment in patients with multiple sclerosis (MS) may be linked to interference with the Th1/Th2 cytokine balance. We determined patterns of Th1/Th2 cytokines (interleukin (IL)-1beta, IL-2, IL-6, IL-12p70, tumor-necrosis factor (TNF)-alpha and interferon-gamma, and IL-4, IL-5 and IL-10, respectively) in the serum of patients with relapsing-remitting MS treated with 250microg interferon-beta 1b or with interferon-beta plus 40mg atorvastatin. In treatment naïve patients with MS, a trend for lower TNF-alpha serum levels compared to controls was detected (P=0.08). Interferon-beta treatment increased TNF-alpha levels, while a trend for lowering of IL-5 serum levels was found (P=0.07). Addition of atorvastatin raised IL-12p70 serum levels (P<0.05). Mean levels of two Th2 cytokines (IL-4, IL-10) showed a non-significant increase after addition of atorvastatin. We conclude that interferon-beta and atorvastatin exert divergent action on Th1/Th2 serum cytokines levels in MS. Supplemental atorvastatin might promote a Th1-type response by raising IL-12p70. Further studies are required to support a Th2 cytokine shift by atorvastatin in patients with MS.

Aspekte der strukturellen Organisation der Basalmembran und der Mauscornea

Thin and ultrathin cryosections of mouse cornea were labeled with affinity-purified antibodies directed against either laminin, its central segments (domain 1), the end of its long arm (domain 3), the end of one of its short arms (domain 4), nidogen, or low density heparan sulfate proteoglycan. All basement membrane proteins are detected by indirect immunofluorescence exclusively in the epithelial basement membrane, in Descemet's membrane, and in small amorphous plaques located in the stroma. Immunoelectron microscopy using the protein A-gold technique demonstrated laminin domain 1 and nidogen in a narrow segment of the lamina densa at the junction to the lamina lucida within the epithelial basement membrane. Domain 3 shows three preferred locations at both the cellular and stromal boundaries of the epithelial basement membrane and in its center. Domain 4 is located predominantly in the lamina lucida and the adjacent half of the lamina densa. The low density heparan sulfate proteoglycan is found all across the basement membrane showing a similar uniform distribution as with antibodies against the whole laminin molecule. In Descemet's membrane an even distribution was found with all these antibodies. It is concluded that within the epithelial basement membrane the center of the laminin molecule is located near the lamina densa/lamina lucida junction and that its long arm favors three major orientations. One is close to the cell surface indicating binding to a cell receptor, while the other two are directed to internal matrix structures. The apparent codistribution of laminin domain 1 and nidogen agrees with biochemical evidence that nidogen binds to this domain.

The effect of seasonal temperature variation on behaviour and metabolism in the freshwater mussel (Unio tumidus)

Temperature plays a critical role in determining the biology of ectotherms. Many animals have evolved mechanisms that allow them to compensate biological rates, i.e. adjust biological rates to overcome thermodynamic effects. For low energy-organisms, such as bivalves, the costs of thermal compensation may be greater than the benefits, and thus prohibitive. To examine this, two experiments were designed to explore thermal compensation in Unio tumidus. Experiment 1 examined seasonal changes in behaviour in U. tumidus throughout a year. Temperature had a clear effect on burrowing rate with no evidence of compensation. Valve closure duration and frequency were also strongly affected by seasonal temperature change, but there was slight evidence of partial compensation. Experiment 2 examined oxygen consumption during burrowing, immediately following valve opening and at rest in summer (24 °C), autumn (14 °C), winter (4 °C), and spring (14 °C) acclimatized U. tumidus. Again, there was little evidence of burrowing rate compensation, but some evidence of partial compensation of valve closure duration and frequency. None of the oxygen compensation rates showed any evidence of thermal compensation. Thus, in general, there was only very limited evidence of thermal compensation of behaviour and no evidence of thermal compensation of oxygen compensation rates. Based upon this evidence, we argue that there is no evolutionary pressure for these bivalves to compensate these biological rates. Any pressure may be to maintain or even lower oxygen consumption as their only defence against predation is to close their valves and wait. An increase in oxygen consumption will be detrimental in this regard so the cost of thermal compensation may outweigh the benefits.

What is new in the pathology of pancreatic neuroendocrine tumors?

The diagnostics of pancreatic neuroendocrine tumors (PanNEN) have changed in recent years especially concerning the World Health Organization (WHO) classification, TNM staging and grading. Furthermore, some new prognostic and predictive immunohistochemical markers have been introduced. Most progress, however, has been made in the molecular pathogenesis of these neoplasms. Using next generation sequencing techniques, the mammalian target of rapamycin (mTOR) pathway, hypoxia and epigenetic changes were identified as key players in tumorigenesis. In this article the most important developments of morphological as well as immunohistochemical diagnostics together with the molecular background of PanNEN are summarized.

The role of seasonality of mineral dust concentration and size on glacial/interglacial dust changes in the EPICA Dronning Maud Land ice core

We present a record of particulate dust concentration and size distribution in subannual resolution measured on the European Project for Ice Coring in Antarctica (EPICA) Dronning Maud Land (EDML) ice core drilled in the Atlantic sector of the East Antarctic plateau. The record reaches from present day back to the penultimate glacial until 145,000 years B.P. with subannual resolution from 60,000 years B.P. to the present. Mean dust concentrations are a factor of 46 higher during the glacial (~850–4600 ng/mL) compared to the Holocene (~16–112 ng/mL) with slightly smaller dust particles during the glacial comparedto the Holocene and with an absolute minimum in the dust size at 16,000 years B.P. The changes in dust concentration are mainly attributed to changes in source conditions in southern South America. An increase in the modal value of the dust size suggests that at 16,000 years B.P. a major change in atmospheric circulation apparently allowed more direct transport of dust particles to the EDML drill site. We find a clear in-phase relation of the seasonal variation in dust mass concentration and dust size during the glacial (r(conc,size) = 0.8) but no clear phase relationship during the Holocene (0 of the dust to the ice sheet using the size as an indicator for transport intensity, we find that the effect of the changes in the seasonality of the source emission strength and the transport intensity on the dust decrease over Transition 1 can significantly contribute to the large decrease of dust concentration from the glacial to the Holocene.