Comprehensive CT Evaluation in Acute Ischemic Stroke: Impact on Diagnosis and Treatment Decisions

Background. With modern CT imaging a comprehensive overview of cerebral macro- and microcirculation can be obtained within minutes in acute ischemic stroke. This opens for patient stratification and individualized treatment. Methods. Four patients with acute ischemic stroke of different aetiologies and/or treatments were chosen for illustration of the comprehensive CT protocol and its value in subsequent treatment decisions. The patients were clinically evaluated according to the NIHSS-scale, examined with the comprehensive CT protocol including both CT angiography and CT perfusion, and followed up by MRI. Results. The comprehensive CT examination protocol increased the examination time but did not delay treatment initiation. In some cases CT angiography revealed the cause of stroke while CT perfusion located and graded the perfusion defect with reasonable accuracy, confirmed by follow-up MR-diffusion. In the presented cases findings of the comprehensive CT examination influenced the treatment strategy. Conclusions. The comprehensive CT examination is a fast and safe method allowing accurate diagnosis and making way for individualized treatment in acute ischemic stroke

Experimental Stroke and Neurotrophins: Regulation, function and gene transfer of neurotrophins in rat and mouse models of focal cerebral ischemia

Stroke caused by focal cerebral ischemia is a major cause of death and neurological disability in humans. The forebrain region most commonly affected by ischemic incidents is that supplied by the middle cerebral artery. In this thesis, neuronal cell death has been investigated using immunohistochemistry for identification of specific neurons and unbiased counting methods after transient occlusion of the middle cerebral artery (MCAO). Our studies show that striatal projection neurons and parvalbumin-containing interneurons are vulnerable, whereas cholinergic and NOS-containing interneurons are highly resistant to MCAO. The high potency of the neurotrophin family of neurotrophic factors to inhibit neuronal death in immature cell systems and the widespread expression of these factors throughout the adult brain, suggest that the neurotrophins might be critical regulators of neuronal survival. Rapid and profound increase of BDNF gene expression has been shown in the frontal and cingulate cortices after MCAO. We show here that also the BDNF protein levels are elevated in the same cortical regions after the ischemic insult, but also further dynamic changes in subcortical regions strongly suggesting anterograde transport of BDNF in forebrain neurons. In our further studies, the ability of the neurotrophins to change the vulnerability of striatal neurons to ischemic damage was investigated in the MCAO model. First, the resistant cholinergic interneurons in striatum respond to MCAO with expression of the p75 neurotrophin receptor (p75NTR). However, the vulnerability of the cholinergic interneurons to MCAO was not increased in a mice strain mutant for the P75NTR, which strongly argue against a major role of this receptor for the prominent resistance of these interneurons to ischemic insults. In order to directly investigate the neuroprotective properties of the neurotrophins, the vulnerability of striatal neurons to focal cerebral ischemia was determined after increasing the levels of BDNF and NGF by gene transfer to the striatum. Increased survival of striatal projection neurons was found after intrastriatal grafting of NGF-secreting genetically modified neural stem cells and after direct transfer of the BDNF gene to striatal cells using an adenoassociated viral (AAV) vector. Furthermore, viral transfer of the BDNF or NGF gene to striatal cells increased survival of parvalbumin-containing interneurons after MCAO. Our data support a role for the neurotrophins as a protective factor against ischemic damage. To assess the functional significance of increased neuronal survival in striatum after focal cerebral ischemia, we utilized different behavioral tests for striatal motor function. We found a strong correlation between scores from these behavioral tests and the extent of striatal damage, and in particular skilled forelimb use in the staircase paradigm was the best predictor of damage. Viral delivery of the neurotrophins lead to improvements in ischemia-induced motor impairments, which appeared to be due to increase in the survival of striatal neurons treated with BDNF. In conclusion, this thesis shows that focal cerebral ischemia causes dynamic changes of the BDNF and p75NTR levels. Gene transfer-induced elevation of neurotrophin levels increases the survival of striatal neurons to ischemic damage, which indicates a neuroprotective role for these factors in the mature brain

Upregulation of p75 neurotrophin receptor after stroke in mice does not contribute to differential vulnerability of striatal neurons

The survival of different neuron types and the expression of the p75 neurotrophin receptor (p75(NTR)) after focal cerebral ischemia were studied in the mouse striatum using immunocytochemical and histochemical techniques and stereological procedures. As assessed at 1 week after 30 min of middle cerebral artery occlusion, the order of vulnerability was projection neurons > parvalbumin-expressing interneurons > nitric oxide synthase-containing interneurons > cholinergic interneurons. Within the ischemic lesion, projection neurons were almost completely lost whereas cholinergic interneurons were spared. Calretinin-immunoreactive interneurons also seemed resistant to the insult. Expression of p75(NTR) was induced in cholinergic interneurons within the lesioned area, raising the possibility of a protective action. However, the number of cholinergic interneurons was unaffected in p75(NTR) knockout mice subjected to the same ischemic insult. These quantitative data demonstrate that striatal neurons in the mouse are differentially susceptible to ischemic damage and argue against a significant role of p75(NTR) for the high resistance of cholinergic interneurons

Multiplicity of Risk Factors in Ischemic Stroke Patients: Relations to Age, Sex, and Subtype - A Study of 2,505 Patients from the Lund Stroke Register.

Background: The prevalence of risk factors for ischemic stroke may vary between different groups of stroke patients. We examined the distribution of individual well-established risk factors as well as the multiplicity of risk factors in different age groups and among subtypes. Methods: In the Lund Stroke Register, we consecutively enrolled 2,505 patients with first-ever ischemic stroke from 2001 to 2009 and registered hypertension, diabetes mellitus, heart disease, current smoking, hypercholesterolemia as well as stroke subtype. Results: Among young patients (<55 years), at least 50% had ≥2 risk factors and 20-25% had ≥3 risk factors. In patients aged 55 years or older, the proportion with ≥2 risk factors was 70-80% and with ≥3 risk factors 35-45%. Men and women had a similar burden of risk factors. Approximately 50% of the cases classified as cardioembolism (CE) and large artery atherosclerosis (LAA) had ≥3 risk factors, which was significantly more than the other TOAST (Trial of Org 10172 in Acute Stroke Treatment) subtypes (CE p < 0.001, LAA p = 0.001). Conclusions: The prevalence of well-established risk factors is similar among young and old stroke patients with large proportions (50-80%) having ≥2 risk factors. Even though the prevalence of well-established risk factors differs between pathogenetic subtypes, these risk factors as well as the multiplicity of risk factors seem to be of clinical importance in all major subtypes of ischemic stroke. © 2014 S. Karger AG, Basel

PreHospital Ambulance Stroke Test - pilot study of a novel stroke test

Abstract Background There is a need for a prehospital stroke test that in addition to high sensitivity for stroke, also is able to communicate stroke severity similar to the National Institute of Health Stroke Scale (NIHSS). Methods The PreHospital Ambulance Stroke Test (PreHAST), an eight item test based on NIHSS, which scores stroke severity from 0–19 points, was designed and adapted for the ambulance services. In the pilot study the ambulance nurses used PreHAST to assess patients with suspected stroke in the prehospital setting. Regardless of the results after PreHAST testing the patients were triaged with a provisional stroke diagnosis. The PreHAST scores were compared with the final diagnosis and the ability to differentiate stroke and transient ischemic attacks (TIA) with ongoing symptoms at evaluation from non-stroke patients was analysed. Results 69 patients were included in the study, 26 had stroke/TIA and 43 other diagnoses. All stroke/TIA patients were identified by PreHAST (sensitivity 100% (95% CI; 87-100%)). The specificity increased with higher PreHAST scores and the discriminative capacity for PreHAST for different cut off values showed an area under the curve of 0.77 (95%CI; 0.66-0.88) in the receiver operating characteristic (ROC) analysis. Discussion PreHAST is designed for high sensitivity, screening for a broad range of stroke symptoms including most key components of NIHSS. The promising sensitivity between 87 and 100% in our study has to be confirmed in a larger study also including multiple centres. Higher PreHAST scores implied more typical patterns of stroke and accordingly the proportion of stroke mimics decrease with higher scores. However, also stroke mimics with epilepsy/seizure and patients with deficit after prior stroke could show higher PreHAST scores. Other prehospital stroke tests that evaluate stroke severity have been designed with the main purpose to screen for large vessel occlusion. The advantage of PreHAST is the dual purpose not only to evaluate stroke severity but also to screen for stroke in general. Conclusions PreHAST is a new screening test of stroke adapted for ambulance services that in addition to high sensitivity for stroke, provides a grading system with increasing specificity with higher scores

Subacute vessel wall imaging at 7-T MRI in post-thrombectomy stroke patients

PurposeReports from 3-T vessel wall MRI imaging have shown contrast enhancement following thrombectomy for acute stroke, suggesting potential intimal damage. Comparisons have shown higher SNR and more lesions detected by vessel wall imaging when using 7 T compared with 3 T. The aim of this study was to investigate the vessel walls after stent retriever thrombectomy using high-resolution vessel wall imaging at 7 T.MethodsSeven patients with acute stroke caused by occlusion of the distal internal carotid artery (T-occlusion), or proximal medial cerebral artery, and treated by stent retriever thrombectomy with complete recanalization were included and examined by 7-T MRI within 2 days. The MRI protocol included a high-resolution black blood sequence with prospective motion correction (iMOCO), acquired before and after contrast injection. Flow measurements were performed in the treated and untreated M1 segments.ResultsAll subjects completed the MRI examination. Image quality was independently rated as excellent by two neuroradiologists for all cases, and the level of motion artifacts did not impair diagnostic quality, despite severe motion in some cases. Contrast enhancement correlated with the deployment location of the stent retrievers. Flow data showed complete restoration of flow after treatment.ConclusionVessel wall imaging with prospective motion correction can be performed in patients following thrombectomy with excellent imaging quality at 7 T. We show that vessel wall contrast enhancement is the normal post-operative state and corresponds to the deployment location of the stent retriever