Waldo R. Guerrero

Sigma-1 receptor activation prevents intracellular calcium dysregulation in cortical neurons during in vitro ischemia.

Sigma receptors are putative targets for neuroprotection following ischemia; however, little is known on their mechanism of action. One of the key components in the demise of neurons following ischemic injury is the disruption of intracellular calcium homeostasis. Fluorometric calcium imaging was used to examine the effects of sigma receptor activation on changes in intracellular calcium concentrations ([Ca2+]i) evoked by in vitro ischemia in cultured cortical neurons from embryonic rats. The sigma receptor agonist, 1,3-di-o-tolyl-guanidine (DTG), was shown to depress [Ca2+]i elevations observed in response to ischemia induced by sodium azide and glucose deprivation. Two sigma receptor antagonists, metaphit [1-(1-(3-isothiocyanatophenyl)-cyclohexyl)-piperidine] and BD-1047 (N-[2–3,4-dichlorophenyl)-ethyl]-N-methyl-2-(dimethylamino)ethylamine), were shown to blunt the ability of DTG to inhibit ischemia-evoked increases in [Ca2+]i, revealing that the effects are mediated by activation of sigma receptors and not via the actions of DTG on nonspecific targets such as N-methyl-d-aspartate receptors. DTG inhibition of ischemia-induced increases in [Ca2+]i was mimicked by the σ-1 receptor-selective agonists, carbetapentane, (+)-pentazocine and PRE-084 [2-(4-morpholinethyl) 1-phenylcyclohexanecarboxylate hydrochloride], but not by the sigma-2-selective agonist, ibogaine, showing that activation of sigma-1 receptors is responsible for the effects. In contrast, DTG, carbetapentane, and ibogaine blocked spontaneous, synchronous calcium transients observed in our preparation at concentrations consistent with sigma receptor-mediated effects, indicating that both sigma-1 and sigma-2 receptors regulate events that affect [Ca2+]i in cortical neurons. Our studies show that activation of sigma receptors can ameliorate [Ca2+]i dysregulation associated with ischemia in cortical neurons and, thus, identify one of the mechanisms by which these receptors may exert their neuroprotective properties.

Hemorrhagic stroke following use of the synthetic marijuana “spice”

The association between the street drug spice (K-2 or herbal incense), a synthetic marijuana, and intracranial hemorrhage (ICH) has not yet been described, but it has with acute ischemic stroke (AIS),1 seizure, and myocardial infarction.2 Two young patients (31 and 25 years old) independently presented to our hospital with subarachnoid hemorrhage (SAH) after spice inhalation. The first also had 2 large intraparenchymal hemorrhages (IPH); the other also had AIS. Both were previously healthy without hypertension, coagulopathy, bleeding diathesis, thrombocytopenia, intracranial aneurysm, arteriovenous malformation, connective tissue disease, or anticoagulant/antiplatelet medication use.

ASPECTS decay during inter-facility transfer in patients with large vessel occlusion strokes

Background Favorable imaging profile according to the Alberta Stroke Program Early CT Score (ASPECTS) on non-contrast head CT is a key criterion for the selection of patients with ischemic stroke from large vessel occlusion (LVO) for IA revascularization therapies. Objective To analyze factors associated with changes in ASPECTS during inter-hospital transfer and to determine how deterioration of ASPECTS affects eligibility for endovascular procedures. Methods We analyzed factors associated with changes in ASPECTS during inter-hospital transfer and their potential impact on eligibility for IA stroke therapies in patients with anterior circulation ischemic strokes. Clinical and demographic characteristics between patients with favorable (ASPECTS ≥6) and unfavorable (ASPECTS <6) imaging on repeat CT were compared. Results Stroke evolution towards unfavorable ASPECTS occurred in 13/42 (31%) patients who initially had a favorable imaging profile at outside hospitals. A higher National Institutes of Health Stroke Scale (NIHSS) score was the only significant predictor of ASPECTS decay, whereas other clinical characteristics, such as the use of IV thrombolysis and site of LVO, were similar between the two groups. Conclusions In our cohort, one out of three patients became ineligible for IA thrombectomy because of unfavorable ASPECTS ‘decay’ following inter-hospital transfer. Except for NIHSS severity, baseline clinical factors could not identify which patients were at risk for ASPECTS deterioration.

Hemiparesis, encephalopathy, and extrapontine osmotic myelinolysis in the setting of hyperosmolar hyperglycemia

Osmotic demyelination syndrome (ODS) is a recognized complication of rapid correction of hyponatremia. However, other medical conditions have been associated recently with the development of ODS in the absence of changes in serum sodium. We present a 23-year-old man who developed left hemiparesis and encephalopathy after treatment of hyperglycemia. MRI demonstrated changes in the splenium of the corpus callosum and the posterior limb of the right internal capsule. This report, together with others, suggests that the full spectrum of lesions of ODS, pontine and extrapontine, can occur in the setting of any rapid change in osmolar state.

Vessel wall enhancement in herpes simplex virus central nervous system vasculitis.

Infection is a well-known cause of cerebral vasculopathy and vasculitis. We report a 36-year-old woman with cerebral vasculitis and ischemic stroke secondary to herpes simplex virus (HSV). MRI studies revealed a pontine stroke with basilar artery stenosis and vessel wall gadolinium enhancement. This case demonstrates the ability of HSV to cause a focal brainstem vasculitis and the utility of enhanced MRI in the diagnosis of stroke related to HSV central nervous system vasculitis.

Tissue-Type Plasminogen Activator for Stroke Mimics: Continuing to Be Swift Rather Than Delaying Treatment to Be Sure

In the April issue of Stroke , we have yet another study on the safety of tissue-type plasminogen activator (tPA) for patients with stroke mimics (SM). Zinkstok et al1 conducted a multicenter retrospective analysis of patients with SM treated with tPA at primary and community hospitals. With 100 patients reported in the largest series to date, the authors found, like all the previous cohort studies, a low rate of symptomatic intracerebral hemorrhage and death.2,3 There were no instances of orolingual edema or fatal intracerebral hemorrhages. The incidence of SM in their cohort among all tPA-treated patients was on the lower end of other reports: 2% to 31%.2,4–6 This rate is also much lower than the 7% misdiagnosis rate reported for emergency departments in which tPA was administered without a stroke team evaluation.7 In fact, …

Management of tandem occlusion stroke with endovascular therapy

OBJECT Approximately 25% of patients with middle cerebral artery (MCA) occlusion will have a concomitant internal carotid artery (ICA) occlusion, and 50% of patients with an ICA occlusion will have a proximal MCA occlusion. Cervical ICA occlusion with MCA embolic occlusion is associated with a low rate of recanalization and poor outcome after intravenous thrombolysis. The authors report their experience with acute ischemic stroke patients who suffered tandem ICA/MCA (TIM) occlusions and underwent intravenous thrombolysis followed by extracranial ICA angioplasty and intracranial MCA mechanical thrombectomy. METHODS In a retrospective analysis of their stroke database (2008-2011), the authors identified 2 patients with TIM occlusion treated with intravenous thrombolysis followed by extracranial ICA angioplasty and intracranial mechanical thrombectomy. They examined early neurological improvement defined by a greater than 10-point reduction of National Institutes of Health Stroke Scale (NIHSS) score and an improved modified Rankin Scale (mRS) score at 60 days. Successful recanalization based on thrombolysis in cerebral infarction (TICI) score of 2 or 3 was also evaluated. RESULTS In both patients a TICI score of 2b or 3 was achieved, signifying successful recanalization. In addition, both patients had a reduction in the NIHSS score by greater than 10 points and an mRS score of 0 at 60 days. CONCLUSIONS Tandem occlusions of the cervical ICA and MCA may be successfully treated using the multimodality approach of intravenous thrombolysis followed by extracranial ICA angioplasty and intracranial mechanical thrombectomy.

Observation of Mean Transit Time (Mtt) Perfusion Maps on a 320-Detector Row Ct Scanner and its Potential Application in Acute Ischemic Stroke

Background and Purpose: We present three patients with acute ischemic stroke who underwent computed tomography perfusion (CTP) imaging utilizing an Aquilion ONE (Toshiba Medical Systems, Nasu, Japan) 320-dectector row CT scanner using a Singular Value Decomposition Plus (SVD+) algorithm to generate perfusion maps. These MTT maps may prove to be a sensitive and specific predictor of ischemic penumbra (IP) and infarct core (IC). Methods: Patients, who presented with an acute ischemic stroke, received high quality whole-brain CTP scans and a follow up MRI or non-contrast CT (NCCT) scan, and underwent successful pharmacological and/ or interventional reperfusion procedures were selected for evaluation. A neuroradiologist utilizing Vitrea FX 3.1 software reviewed images, and the IC volumes were calculated. Results: A comparison was made between the volumes of infarct core utilizing SVD+ MTT maps and DWI MR sequences or a sub-acute NCCT. There was a correlation between the infarct core volume measured on MTT and final infarct volume on follow up imaging. However due to limitations associated with a small sample size, a statistical correlation cannot be definitively calculated from this data set. Conclusions: Utilization of the SVD+ MTT map may allow for a more accurate assessment of the infarct core and surrounding salvageable tissue as compared to cerebral blood flow/cerebral blood volume (CBF/CBV) mismatch though further studies are required to validate this observation.

The role of perfusion CT in identifying stroke mimics in the emergency room: a case of status epilepticus presenting with perfusion CT alterations

Emergency medicine physicians are often faced with the challenging task of differentiating true acute ischemic strokes from stroke mimics. We present a case that was initially diagnosed as acute stroke. However, perfusion CT and EEG eventually led to the final diagnosis of status epilepticus. This case further asserts the role of CT perfusion in the evaluation of patients with stroke mimics in the emergency room setting.

Defining Intravenous Recombinant Tissue Plasminogen Activator Failure

Although the 2 National Institute of Neurological Disorders and Stroke (NINDS) trials1 and subsequent studies from Europe (ECASS-3, IST-3)2,3 established intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (rtPA) within 4.5 hours of symptom onset as an effective treatment for acute ischemic stroke, the ability of IV rtPA to predictably result in an excellent outcome is still limited; in most cases, IV rtPA treatment is not enough to produce complete recanalization.4,5 Intraarterial (endovascular) treatment (IAT) is superior to IV rtPA in opening arteries, particularly when coupled with mechanical thrombectomy, with recanalization rates up to 87%.6,7 There is increasing evidence that IAT has a therapeutic role in large artery occlusions.8,9 In addition, faster time to angiographic reperfusion is a predictor of good clinical outcome with IAT.10 Thus, there is a need for a quick and accurate strategy to identify IV rtPA nonresponders with large artery occlusion to select those patients who would benefit from IAT. Mechanical Embolus Removal in Cerebral Ischemia (MERCI), Multi MERCI, and Solitaire With the Intention For Thrombectomy (SWIFT) are just a few of the studies that have used the concept of IV rtPA failure as inclusion criteria to enroll subjects in their studies. But what exactly is the definition of IV tPA nonresponder or failure? To date, there is no clear and consistent designation for this subgroup in the stroke literature. How do the characteristics of the clot influence response to IV rtPA? Is there a time window that should define IV rtPA failure? Should imaging modalities to assess vessel recanalization be used to define IV rtPA failure? Should early clinical change be criteria to differentiate IV rtPA responders from nonresponders? Accurate and rapid identification …