PubMed Health⌕ Search

Biomedical subjects

Sean I Savitz

Publications and source records attributed to Sean I Savitz.

13 recordsLinked to original sources
PubMed2007

Pitfalls in the diagnosis of cerebellar infarction.

BACKGROUND: Cerebellar infarctions are an important cause of neurologic disease. Failure to recognize and rapidly diagnose cerebellar infarction may lead to serious morbidity and mortality due to hydrocephalus and brain stem infarction. OBJECTIVES: To identify sources of preventable medical errors, the authors obtained pilot data on cerebellar ischemic strokes that were initially misdiagnosed in the emergency department. METHODS: Fifteen cases of misdiagnosed cerebellar infarctions were collected, all seen, or reviewed by the authors during a five-year period. For each patient, they report the presenting symptoms, the findings on neurologic examination performed in the emergency department, specific areas of the examination not performed or documented, diagnostic testing, the follow-up course after misdiagnosis, and outcome. The different types of errors leading to misdiagnosis are categorized. RESULTS: Half of the patients were younger than 50 years and presented with headache and dizziness. All patients had either incomplete or poorly documented neurologic examinations. Almost all patients had a computed tomographic scan of the head interpreted as normal, and most of these patients underwent subsequent magnetic resonance imaging showing cerebellar infarction. The initial incorrect diagnoses included migraine, toxic encephalopathy, gastritis, meningitis, myocardial infarction, and polyneuropathy. The overall mortality in this patient cohort was 40%. Among the survivors, about 50% had disabling deficits. Pitfalls leading to misdiagnosis involved the clinical evaluation, diagnostic testing, and establishing a diagnosis and disposition. CONCLUSIONS: This study demonstrates how the diagnosis of cerebellar infarction can be missed or delayed in patients presenting to the emergency department.

Adult↗
PubMed2006

EDG receptors as a potential therapeutic target in retinal ischemia-reperfusion injury.

LPA (lysophosphatidic acid) specific endothelial differentiation gene (EDG) receptors have been implicated in various anti-apoptotic pathways. Ischemia of the brain and retina causes neuronal apoptosis, which raises the possibility that EDG receptors participate in anti-apoptotic signaling in ischemic injury. We examined the expression of EDG receptors in a model of retinal ischemia-reperfusion injury and also tested LXR-1035, a novel analogue of LPA, in the rat following global retinal ischemic injury. Rats were subjected to 45 or 60 min of raised intraocular pressure. Animals were sacrificed at 24 h post-ischemia and retinal tissue was stained for EDG receptors. In separate experiments, animals were randomized to receive LXR or saline vehicle by intravitreal injection 24 h prior to ischemia. The degree of retinal damage was assessed morphologically by measuring the thickness of the inner retinal layers as well as functionally by electroretinography (ERG). We found that the normal retina has a baseline expression of the LPA receptors, EDG-2 and EDG-4, which are significantly upregulated in the inner layers in response to ischemia. Animals pretreated with LXR-1035 had dose-dependent, significant reductions in histopathologic damage and significant improvement in functional deficits compared with corresponding vehicle-controls, after 45 and 60 min of ischemia. These results suggest that LPA receptor signaling may play an important role in neuroprotection in retinal ischemia-reperfusion injury.

Animals↗
PubMed2006

Vertebral artery compression of the medulla.

BACKGROUND: Intracranial arteries in the subarachnoid space may compress the brain parenchyma and cranial nerves. Most arterial compressive lesions have been attributed to dolichoectasia in the vertebral-basilar system, and prior reports have concentrated on the pressure effects of basilar artery ectasia. Much less is known about vertebral artery compression of the medulla. OBJECTIVE: To describe a series of patients with vertebral arteries compressing the medulla oblongata. DESIGN: Prospective case studies. SETTING: Tertiary care center. PATIENTS: Nine symptomatic patients, 4 men and 5 women, between the ages of 32 and 79 years. MAIN OUTCOME MEASURES: Clinical phenomena, radiographic findings, treatment, and outcomes. RESULTS: We found that compression most commonly occurs at the ventrolateral surface. The clinical features can be transient or permanent and are predominantly motor and cerebellar or vestibular, but a poor correlation exists between the clinical findings and the severity or extent of impingement. The vertebral arteries were angulated, tortuous, or dilated but not necessarily dolichoectatic to cause obvious indentation. Seven patients were treated with antiplatelets and anticoagulants or analgesics, whereas 2 underwent microvascular decompression, resulting in temporary or no relief. One surgical patient developed cranial nerve complications. Among the medically treated patients, none had progression of deficits, and those with single episodes had no recurrence of symptoms. CONCLUSION: This study is the largest collection, to our knowledge, of patients with medullary vascular compression. Further studies are needed to estimate its frequency, natural course, and preferred management.

Adult↗
PubMed2006

Ischemic preconditioning is mediated by erythropoietin through PI-3 kinase signaling in an animal model of transient ischemic attack.

Ischemic preconditioning (IP) protects the brain from subsequent, prolonged, and lethal ischemia in experimental studies. Erythropoietin (EPO) participates in the brain's intrinsic response to injury and may play a role in preconditioning. By using a middle cerebral artery occlusion (MCAo) model of transient ischemic attack (TIA), we sought to determine whether EPO is required for IP in the protective response against focal ischemic stroke. Rats underwent three 10-min MCA occlusions or sham surgery. Three days later, animals underwent 2 hr of MCAo and 22 hr of reperfusion. Experimental TIAs reduced infarct volumes by 55% (P < 0.05), inhibited DNA fragmentation, and improved neurological outcome by 50% (P < 0.05) after ischemic stroke. EPO and its receptor were up-regulated by IP in the ipsilateral hemisphere by 24 hr after IP, before ischemic stroke and soluble EPO receptor attenuated neuroprotection by IP (88% reduction, P < 0.05). Pretreatment with the PI-3 kinase inhibitor wortmannin abolished the protective effect of IP against ischemic injury (P < 0.05). IP may be mediated in part by EPO through a PI-3 kinase pathway.

Animals↗
PubMed2005

Neurotransplantation of fetal porcine cells in patients with basal ganglia infarcts: a preliminary safety and feasibility study.

BACKGROUND: Cell transplantation is safe in animal models and enhances recovery from stroke in rats. METHODS: We studied the safety and feasibility of fetal porcine transplantation in 5 patients with basal ganglia infarcts and stable neurological deficits. To prevent rejection, cells were pretreated with an anti-MHC1 antibody and no immunosuppressive drugs were given to the patients. RESULTS: The first 3 patients had no adverse cell, procedure, or imaging-defined effects. The fourth patient had temporary worsening of motor deficits 3 weeks after transplantation, and the fifth patient developed seizures 1 week after transplantation. MRI in both patients demonstrated areas of enhancement remote from the transplant site, which resolved on subsequent imaging. Two patients showed improvement in speech, language, and/or motor impairments over several months and persisted at 4 years. The study was terminated by the FDA after the inclusion of 5 patients. CONCLUSION: This is the first report on the transplantation of nontumor cells in ischemic stroke patients.

Adult↗
PubMed2005

Arterial occlusive lesions recanalize more frequently in women than in men after intravenous tissue plasminogen activator administration for acute stroke.

BACKGROUND AND PURPOSE: Previous reports suggest that women achieve better outcome than men after intravenous thrombolysis for ischemic stroke. Coagulation and fibrinolysis differ between sexes. These findings prompted us to investigate possible gender differences in arterial recanalization after intravenous tissue plasminogen activator (IV tPA). METHODS: We identified 100 consecutive patients who presented with acute ischemic stroke and received IV tPA within 6 hours of onset. Only patients with large artery anterior circulation strokes, as determined by MRI/MRA or CT/CTA before treatment, who had follow-up vascular study within 72 hour after treatment were included. We compared demographics, clinical features, admission medications, symptom-to-needle and treatment-to-repeat vascular imaging times, baseline National Institutes of Health Stroke Severity score, radiological and laboratory data, stroke mechanism, and outcome between the sexes. RESULTS: 39 patients met all inclusion/exclusion criteria (22 men and 17 women). The recanalization rate was significantly higher in women (94% versus 59%; P=0.02). This difference remained statistically significant after excluding patients whose strokes were attributed to internal carotid artery occlusive lesions, and when the analysis was limited to those treated within 3 hours of stroke onset. All other confounding variables did not differ significantly between the sexes. CONCLUSIONS: In our cohort, vascular occlusive lesions were more likely to recanalize in women than men in response to IV tPA. These preliminary findings need to be validated in larger prospective studies.

Aged↗
PubMed2004

Cell therapy for stroke.

Increasing experimental evidence suggests that cell transplantation can enhance recovery from stroke in animal models of focal cerebral ischemia. Clinical trials have been investigating the effects of a human immortalized neuronal cell line and porcine fetal neurons in stroke victims with persistent and stable deficits. Preclinical studies are focusing on the effects of human stem cells from various sources including brain, bone marrow, umbilical cord, and adipose tissue. This review presents an overview of preclinical and clinical studies on cell therapy for stroke. We emphasize the current, limited knowledge about the biology of implant sources and discuss special conditions in stroke that will impact the potential success of neurotransplantation in clinical trials.

Cell Transplantation↗
PubMed2002

Erythropoietin administration protects retinal neurons from acute ischemia-reperfusion injury.

Erythropoietin (EPO) plays an important role in the brain's response to neuronal injury. Systemic administration of recombinant human EPO (rhEPO) protects neurons from injury after middle cerebral artery occlusion, traumatic brain injury, neuroinflammation, and excitotoxicity. Protection is in part mediated by antiapoptotic mechanisms. We conducted parallel studies of rhEPO in a model of transient global retinal ischemia induced by raising intraocular pressure, which is a clinically relevant model for retinal diseases. We observed abundant expression of EPO receptor (EPO-R) throughout the ischemic retina. Neutralization of endogenous EPO with soluble EPO-R exacerbated ischemic injury, which supports a crucial role for an endogenous EPO/EPO-R system in the survival and recovery of neurons after an ischemic insult. Systemic administration of rhEPO before or immediately after retinal ischemia not only reduced histopathological damage but also promoted functional recovery as assessed by electroretinography. Exogenous EPO also significantly diminished terminal deoxynucleotidyltransferase-mediated dUTP end labeling labeling of neurons in the ischemic retina, implying an antiapoptotic mechanism of action. These results further establish EPO as a neuroprotective agent in acute neuronal ischemic injury.

Animals↗
PubMed2002

Cell transplantation for stroke.

Cell transplantation has emerged as an experimental approach to restore brain function after stroke. Various cell types including porcine fetal cells, stem cells, immortalized cell lines, and marrow stromal cells are under investigation in experimental and clinical stroke trials. This review discusses the unique advantages and limitations of the different graft sources and emphasizes the current, limited knowledge about their biology. The survival, integration, and efficacy of neural transplants in stroke patients will depend on the type, severity, chronicity, adequacy of circulation, and location of the stroke lesion.

Bone Marrow Transplantation↗