Headache and spontaneous glabellar ecchymosis: More than a self-injury behavior?

A33-YEAR-OLD MAN PRESENTED to our outpatient clinic for evaluation of severe headaches located at the left eye and forehead and multiple episodes of discoloration of the superior glabella. The pain was described as throbbing lasting for 30–45 min about 2–3 times per month with minimal nausea, photophobia, left eye tearing, redness, and ptosis. The erythema-like lesion developed after a severe headache episode and gradually resolved over the next few days. The patient disclosed habitually rubbing the forehead or face during pain episodes, making an ‘artificial’ post-traumatic skin ecchymosis unlikely

Erythropoietin for stroke treatment: dead or alive?

Endothelial progenitor cell (EPC) mobilization from the bone marrow was considered to improve outcome after ischemic stroke. Erythropoietin (EPO) might be a potential candidate stroke drug that increases the number of circulating EPCs. In the previous issue of Critical Care, Yip and colleagues investigated the effect of EPO in stroke patients on both clinical outcome and EPC stimulation. Although beneficial effects of EPO were observed, several issues regarding EPO's suitability as a stroke drug remain

Intracarotid administration of human bone marrow mononuclear cells in rat photothrombotic ischemia

Background: Increasing evidence suggests that cell therapy improves functional recovery in experimental models of stroke and myocardial infarction. So far only small pilot trials tested the effects of cell therapy in stroke patients, whereas large clinical trials were conducted in patients with ischemic heart disease. To investigate the therapeutic benefit of cell therapy to improve the recovery after stroke, we determined the efficacy of bone marrow derived mononuclear cells, which were shown to improve the recovery in experimental and clinical acute myocardial infarction studies, in a rat stroke model. Methods: Adult male Wistar rats were randomly assigned to receive either five million human bone marrow mononuclear cells (hBMC) or placebo intraarterially 3 days after photothrombotic ischemia. For immunosuppression the animals received daily injections of cyclosporine throughout the experiment, commencing 24 hours before the cell transplantation. A battery of behavioural tests was performed before and up to 4 weeks after ischemia. Results: Body temperature and body weight revealed no difference between groups. Neurological deficits measured by the Rotarod test, the adhesive-removal test and the cylinder test were not improved by hBMC transplantation compared to placebo. Conclusions: This study demonstrates that hBMC do not improve functional recovery when transplanted intraaterially 3 days after the onset of focal cerebral ischemia. A possible reason for the failed neurological improvement after cell therapy might be the delayed treatment initiation compared to other experimental stroke studies that showed efficacy of bone marrow mononuclear cells

The hematopoietic factor GM-CSF (Granulocyte-macrophage colony-stimulating factor) promotes neuronal differentiation of adult neural stem cells in vitro

BACKGROUND: Granulocyte-macrophage colony stimulating factor (GM-CSF) is a hematopoietic growth factor involved in the generation of granulocytes, macrophages, and dendritic cells from hematopoietic progenitor cells. We have recently demonstrated that GM-CSF has anti-apoptotic functions on neurons, and is neuroprotective in animal stroke models. RESULTS: The GM-CSF receptor α is expressed on adult neural stem cells in the rodent brain, and in culture. Addition of GM-CSF to NSCs in vitro increased neuronal differentiation in a dose-dependent manner as determined by quantitative PCR, reporter gene assays, and FACS analysis. CONCLUSION: Similar to the hematopoietic factor Granulocyte-colony stimulating factor (G-CSF), GM-CSF stimulates neuronal differentiation of adult NSCs. These data highlight the astonishingly similar functions of major hematopoietic factors in the brain, and raise the clinical attractiveness of GM-CSF as a novel drug for neurological disorders

Monocyte Chemoattractant Protein-1-Deficiency Impairs the Expression of IL-6, IL-1β and G-CSF after Transient Focal Ischemia in Mice

Monocyte chemoattractant protein-1 (MCP-1), a chemokine secreted by neurons and astrocytes following stroke is known to aggravate ischemia-related damage. Previous studies revealed that MCP-1-deficient mice develop smaller infarcts and have an improved neurological outcome, whereas mice overexpressing MCP-1 show worsened brain damage and impaired neurological function. The aim of the present study was to elucidate the molecular background of the enhanced recovery in MCP-1-deficient mice after stroke. For this purpose, we (1) performed expression analyses on crucial post-stroke related inflammatory genes in MCP-1-deficient mice compared to wildtype controls, (2) analyzed a possible impact of MCP-1 on astrocyte activation (3) investigated the cellular origin of respective inflammatory cytokines and (4) analyzed the impact of MCP-1 secretion on the migration of both neutrophil granulocytes and T-cells. Here we report that MCP-1-deficiency leads to a shift towards a less inflammatory state following experimental occlusion of the middle cerebral artery including an impaired induction of interleukin-6, interleukin-1β and granulocyte-colony stimulating factor expression as well as a subsequent diminished influx of hematogenous cells. Additionally, MCP-1-deficient mice developed smaller infarcts 36 hours after experimental stroke. Investigations revealed no differences in transcription of tumor necrosis factor-α and astrogliosis 12 and 36 hours after onset of ischemia. These novel results help to understand post ischemic, inflammatory mechanisms and might give further arguments towards therapeutical interventions by modulation of MCP-1 expression in post stroke inflammation

Late Onset Postpartum Eclampsia: It is Really Never Too Late—A Case of Eclampsia 8 Weeks after Delivery

Introduction. Eclampsia is the combination of preeclampsia and seizures. Approximately one-half of all cases of eclampsia occur postpartum. Thereby late onset postpartum eclampsia is defined by its onset more than 48 hours after delivery. Summary of Case. We report a postpartum eclampsia occurring 8 weeks after delivery, which is the latest onset ever described. The course was complicated by an intracerebral hemorrhage (ICH). Conclusion. A late onset postpartum eclampsia even several weeks after delivery should be considered as possible diagnosis, since early treatment initiation with magnesium sulphate and antihypertensive medication prevents severe complications and reduces mortality

Bone marrow-derived mononuclear cells do not exert acute neuroprotection after stroke in spontaneously hypertensive rats

Bone marrow-derived mononuclear cells (BM-MNCs) were shown to improve the outcome in animal stroke models and clinical pilot studies on BM-MNCs for stroke patients were already conducted. However, relevant aspects of pre-clinical evaluation, such as the use of animals with comorbidities and dose-response studies, were not thoroughly addressed so far. We therefore investigated different BM-MNC doses in the clinical meaningful stroke model of spontaneously hypertensive (SH) rats. Three hours after the onset of transient middle cerebral artery occlusion (MCAO) animals received either one of three syngeneic BM-MNC doses or placebo intravenously. The primary endpoint was the infarct size. Secondary endpoints included functional outcome, mortality, inflammatory processes, and the dose-response relationship. In contrast to previous studies which used healthy animals no beneficial effect of BM-MNCs was found. Infarct volumes, mortality, behavioral outcomes, and the extent of the inflammatory response to cerebral ischemia were comparable in all groups. In conclusion, we could not demonstrate that early BM-MNC treatment improves the outcome after stroke in SH rats. Whether BM-MNCs improve neurological recovery after delayed treatment initiation was not investigated in the present study, but our data indicates that this should be determined in co-morbid animal stroke models before moving to large-scale clinical studies. Future preclinical stroke studies on co-morbid animals should also include groups of healthy animals in order to determine whether negative results can be attributed to the comorbid condition