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Biomedical subjects

W Koroshetz

Publications and source records attributed to W Koroshetz.

15 recordsLinked to original sources
PubMed2006

First-pass quantitative CT perfusion identifies thresholds for salvageable penumbra in acute stroke patients treated with intra-arterial therapy.

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether, in acute stroke patients treated with intra-arterial (IA) recanalization therapy, CT perfusion (CTP) can distinguish ischemic brain tissue destined to infarct from that which will survive. METHODS: Dynamic CTP was obtained in 14 patients within 8 hours of stroke onset, before IA therapy. Initial quantitative cerebral blood volume (CBV) and flow (CBF) values were visually segmented and normalized in the "infarct core" (region 1: reduced CBV and CBF, infarction on follow-up), "penumbra that infarcts" (region 2: normal CBV, reduced CBF, infarction on follow-up), and "penumbra that recovers" (region 3: normal CBV, reduced CBF, normal on follow-up). Normalization was accomplished by dividing the ischemic region of interest value by that of a corresponding, contralateral, uninvolved region, which resulted in CBV and CBF "ratios." Separate CBV and CBF values were obtained in gray matter (GM) and white matter (WM). RESULTS: Mean CBF ratios for regions 1, 2, and 3 were 0.19 +/- 0.06, 0.34 +/- 0.06, and 0.46 +/- 0.09, respectively (all P < .001). Mean CBV ratios for regions 1, 2, and 3 were similarly distinct (all P < .05). Absolute CBV and CBF values for regions 2 and 3 were not significantly different. All regions with CBF ratio <0.32, CBV ratio <0.68, CBF <12.7 mL/100 g/min, or CBV <2.2 mL/100 g infarcted. No region with CBF ratio >0.44 infarcted. GM versus WM CBF and CBV values were significantly different for region 2 compared with region 3 (P < .05). CONCLUSIONS: In acute stroke patients, quantitative CTP can distinguish ischemic tissue likely to infarct from that likely to survive.

Adult↗
PubMed2003

Establishment of primary stroke centers: a survey of physician attitudes and hospital resources.

OBJECTIVES: To survey US physicians involved in acute stroke care to determine the proportion of hospitals that currently meet the recommended Brain Attack Coalition (BAC) criteria for Primary Stroke Centers (PSC) and obtain opinions regarding the value of stroke centers. METHODS: A survey regarding the BAC guidelines for the establishment of stroke centers was mailed to 3,245 US neurologists, neurosurgeons, and emergency physicians. RESULTS: A total of 1,032 responses were received. Seventy-nine percent (range by specialty 58 to 98%) of respondents believed there was a need for stroke centers. If formal stroke center designation were established, 81% (range 72 to 90%) would like their hospital to become a PSC. Although 77% of respondents believed that their hospital currently met recommended criteria for a PSC, only 7% actually meet all recommended elements. However, 44% of hospitals already provide most acute stroke services. The BAC criteria most frequently lacking were continuing medical education for professional stroke center staff, stroke training for emergency department staff, formal establishment of a stroke unit, and designation of a stroke center director. CONCLUSIONS: The majority of emergency medicine and neuroscience physician respondents involved in acute stroke care support the designation of primary stroke centers. Although respondents globally overestimated the extent to which their facilities currently meet BAC recommended criteria for PSC, detailed responses suggested that over 40% of hospitals possess substantial existing acute stroke care resources and are poised to function as PSC with modest additional administrative and financial commitment.

Adult↗
PubMed2002

Small aneurysms as a cause of thromboembolic stroke.

OBJECTIVE AND IMPORTANCE: A small percentage of patients with intracranial aneurysms present with embolic stroke distal to the site of the aneurysm. Thromboembolism typically occurs in large or giant aneurysms where reduction of flow within the aneurysm is thought to increase the possibility of clot formation. Only a few examples are available in the literature of patients with smaller aneurysms who develop embolic infarction distal to the lesion. We have experience with two such patients with an apparent common pathophysiology. CLINICAL PRESENTATION: Patient 1 with a distal left middle cerebral artery infarct was found to have an 18 mm carotid artery bifurcation aneurysm (patient age 49 years). Patient 2 had a 7 mm right middle cerebral artery aneurysm with a small distal embolus (patient age 65 years). At surgery both patients were found to have atherosclerotic disease involving the aneurysm base and parent vessel. In each instance, the aneurysm was opened during temporary vessel occlusion and microendarterectomy was performed. Occlusion of one of the major arterial branches exiting the aneurysm was also present with anterior cerebral artery occlusion in the case of ICA bifurcation lesion and MCA branch occlusion in the case of the MCA aneurysm. Both patients made a good recovery following surgery. CONCLUSION: In small aneurysms with atherosclerotic disease distal thromboembolism may occur. Surgical treatment with microendarterectomy is appropriate to prevent further emboli and potential for subarachnoid hemorrhage. (Fig. 5, Ref. 16.)

Aged↗
PubMed2000

Spinocerebellar ataxia type 2 with parkinsonism in ethnic Chinese.

OBJECTIVE: To describe the clinical and molecular genetic analysis of a large family of northern Chinese descent with a mutation at the SCA2 locus causing carbidopa-levodopa-responsive parkinsonism. BACKGROUND: Most causes of parkinsonism remain unknown. However, molecular genetic analysis of families with parkinsonism has recently identified five distinct loci and pathogenic mutations in four of those. Additionally, some of the spinocerebellar ataxia syndromes (SCA), particularly Machado-Joseph syndrome (SCA3), are known to cause parkinsonism. Spinocerebellar ataxia type 2 (SCA2) has not previously been described as causing a typical dopamine-responsive asymmetric PD phenotype. METHODS: A large family was evaluated clinically and molecularly for apparent autosomal dominant parkinsonism. RESULTS: The phenotype includes presentation consistent with typical dopamine-responsive parkinsonism. Other presentations in this family include a parkinsonism/ataxia phenotype, which is classic for SCA2 and parkinsonism, resembling progressive supranuclear palsy. CONCLUSIONS: Patients presenting with a family history of parkinsonism, including familial progressive supranuclear palsy and PD, should be tested for the spinocerebellar ataxia type 2 expansion.

Adult↗
PubMed2000

Predictors of mortality in stroke patients admitted to an intensive care unit.

OBJECTIVE: Improved pathophysiologic insight and prognostic information regarding in-hospital risk of mortality among stroke patients admitted to an intensive care unit. DESIGN: Retrospective analysis. SETTING: Neurology/neurosurgery intensive care unit in a tertiary care university medical center. PATIENTS: A total of 63 consecutive ischemic stroke patients. INTERVENTIONS: Patients were classified according to in-hospital mortality. Charts were reviewed to retrospectively generate an admitting Acute Physiology and Chronic Health Evaluation (APACHE) II score. The APACHE II score and its individual components were assessed for predicting subsequent death. MEASUREMENTS AND MAIN RESULTS: Of 63 patients, 13 died and 50 survived to either discharge or surgical intervention. The mean admitting APACHE II score of survivors (6.9) was lower than that of patients who died (17.2; p < .0001). None of the 33 patients with a score <9 died, compared with 43% of those with a score > or =9. A score > or =18 was uniformly associated with fatal outcome (n = 8). Univariate analysis identified APACHE II total score, Glasgow Coma Scale score, temperature, pH, and white blood cell count as significant predictors of death. Among multivariate logistic regression models examining the components of the APACHE II score, the model containing white blood cells, temperature, and creatinine best predicted death. CONCLUSIONS: Several features of the APACHE II score are associated with risk of death in this patient population. The findings suggest particular physiologic derangements that are associated with, and may contribute to, increased mortality in critically ill patients with acute ischemic stroke.

APACHE↗
PubMed1999

Infarct volume as a surrogate or auxiliary outcome measure in ischemic stroke clinical trials. The RANTTAS Investigators.

BACKGROUND AND PURPOSE: Reduction in infarct volume is the standard measure of therapeutic success in animal stroke models. Reduction in infarct volume has been advocated as a biological surrogate or auxiliary outcome measure for human stroke clinical trials to replace or supplement deficit, disability, and global clinical scales. However, few studies have investigated correlations between infarct volume and clinical end points in acute ischemic stroke patients. METHODS: CT scans at days 6 to 11 were acquired prospectively in 191 fully eligible patients enrolled in the Randomized Trial of Tirilazad Mesylate in Patients With Acute Stroke (RANTTAS). Patients were enrolled within 6 hours of onset of stroke in any vessel distribution. Infarct volume was measured by operator-assisted computerized planimetry. RESULTS: One hundred thirty-two patients had visible new supratentorial infarcts, with median infarct volume of 28.0 cm3 (interquartile range, 9.0 to 93.0 cm3). Fifty-nine patients had no visible new infarct. Correlations with standard 3-month outcome scales and mortality were as follows: Barthel Index, r=0.43; Glasgow Outcome Scale, r=0.53; National Institutes of Health Stroke Scale, r=0.54; mortality, r=0.31. For visible infarcts alone, correlations were as follows: BI, r=0.46; GOS, r=0.59; NIHSS, r=0.56; mortality, r=0.32. CONCLUSIONS: Subacute CT infarct volume correlates moderately with 3-month clinical outcome as assessed by widely used neurological and functional assessment scales. The modesty of this linkage constrains the use of infarct volume as a surrogate end point in ischemic stroke clinical trials.

Acute Disease↗
PubMed1994

The neurogenetics genie: testing for the Huntington's disease mutation.

Even though the discovery of the HD gene will make genetic testing much easier to perform, until there is an effective treatment, it will be no easier for HD families to learn who among them carries the mutation. We believe that the standard of care for obtaining genetic testing for HD, as well as for other inherited neurodegenerative disorders, must continue to include extensive counseling, psychological assessment and support, a neurologic examination, and post-test follow-up. We advocate a flexible approach consistent with the individual's particular needs, but we emphasize that it is essential that these basic elements be adequately addressed.

DNA Mutational Analysis↗
PubMed1993

Do defects in mitochondrial energy metabolism underlie the pathology of neurodegenerative diseases?

The pathogenesis of nerve cell death in neurodegenerative diseases is unknown. An attractive hypothesis is that an impairment of energy metabolism may underlie slow excitotoxic neuronal death. Several studies have demonstrated mitochondrial or oxidative defects in neurodegenerative diseases. Impaired energy metabolism results in decreases in high-energy phosphate stores and a deteriorating membrane potential. Under these conditions, the voltage-sensitive Mg2+ block of NMDA receptors is relieved, allowing the receptors to be persistently activated by endogenous concentrations of glutamate. In this way, metabolic defects may lead to neuronal death by a slow 'excitotoxic' mechanism. Recent studies indicate that such a mechanism occurs in vivo, and it may play a role in animal models of Huntington's disease and Parkinson's disease. If a similar mechanism occurs in neurodegenerative diseases in humans it may be possible to use either excitatory amino acid antagonists or agents to improve neuronal bioenergetics as therapeutic treatments for these disorders.

Brain↗
PubMed1991

Aminooxyacetic acid results in excitotoxin lesions by a novel indirect mechanism.

Aminooxyacetic acid (AOAA) is an inhibitor of several pyridoxal phosphate-depedent enzymes in the brain. In the present experiments intrastriatal injections of AOAA produced dose-dependent excitotoxic lesions. The lesions were dependent on a pyridoxal phosphate mechanisms because pyridoxine blocked them. The lesions were blocked by the noncompetitive N-methyl-D-aspartate (NMDA) antagonist MK-801 and by coinjection of kynurenate, a result indicating an NMDA receptor-mediated excitotoxic process. Electrophysiologic studies showed that AOAA does not directly activate ligand-gated ion channels in cultured cortical or striatal neurons. Pentobarbital anesthesia attenuated the lesions. AOAA injections resulted in significant increases in lactate content and depletions of ATP levels. AOAA striatal lesions closely resemble Huntington's disease both neurochemically and histologically because they show striking sparing of NADPH-diaphorase and large neurons within the lesioned area. AOAA produces excitotoxic lesions by a novel indirect mechanism, which appears to be due to impairment of intracellular energy metabolism, secondary to its ability to block the mitochondrial malate-aspartate shunt. These results raise the possibility that a regional impairment of intracellular energy metabolism may secondarily result in excitotoxic neuronal death in chronic neurodegenerative illnesses, such as Huntington's disease.

Aminooxyacetic Acid↗
PubMed1981

Ion transport mediated by the valinomycin analogue cyclo(L-Lac-L-Val-D-Pro-D-Val)3 in lipid bilayer membranes.

Cyclo(L-Lac-L-Val-D-Pro-D-Val)3 (PV-Lac) a structural analogue of the ion-carrier valinomycin, increases the cation permeability of lipid bilayer membranes by forming a 1:1 ion-carrier complex. The selectively sequence for PV-Lac is identical to that of valinomycin; i.e., Rb+ greater than K+ greater than Cs+ greater than or equal to NH+4 greater than Na+ greater than Li+. The steady-state zero-voltage conductance, G(0), is a saturating function of KCl concentration. A similar behavior was found for Rb+, Cs+, and NH+4. However, the ion concentration at which G(0) reaches a plateau strongly depends on membrane composition. The current-voltage curves present saturating characteristics, except at low ion concentrations of Rb+, K+, or Cs+. The ion concentration at which the saturating characteristics appear depends on membrane composition. These and other results presented in this paper agree with a model that assumes complexation between carrier and ion at the membrane-water interface. Current relaxation after voltage-jump studies were also performed for PV-Lac. Both the time constant and the amplitude of the current after a voltage jump strongly depend on ion concentration and membrane composition. These results, together with the stationary conductance data, were used to evaluate the rate constants of the PV-Lac-mediated K+ transport. In glycerolmonooleate they are: association rate constant, 2 x 10(6) M-1 s-1; dissociation rate constant, 4 x 10(5) s-1; translocation rate constant for complex, 5 x 10(4) s-1; and the rate of translocation of the free carrier (ks), 55 s-1. ks is much smaller for PV-Lac than for valinomycin and thus limits the efficiency with which the carrier is able to translocate cations across the membrane.

Biological Transport↗