Recurrent Hemispheric Stroke Syndromes in Symptomatic Atherosclerotic Internal Carotid Artery Occlusions: The Carotid Occlusion Surgery Study Randomized Trial.

Background: There are limited data on outcomes of extracranial-intracranial (EC-IC) bypass in patients with recurrent hemispheric syndromes due to atherosclerotic internal carotid artery occlusion (AICAO).

Objective: To compare clinical outcomes and efficacy of EC-IC bypass surgery in patients with and without recurrent hemispheric syndromes associated with AICAO in the Carotid Occlusion Surgery Study (COSS).

Methods: In patients enrolled in the COSS trial, we compared baseline characteristics and clinical outcomes for participants with (rHEMI+) and without recurrent hemispheric ischemia (rHEMI-) prior to randomization into surgical vs medical groups.

Relative Mean Transit Time Predicts Subsequent Stroke in Symptomatic Carotid Occlusion.

Background: Mean transit time (MTT) measurements to assess cerebral hemodynamics are easily obtained by computed tomography and magnetic resonance imaging. We reviewed hemodynamic and clinical outcome data from the St. Louis Carotid Occlusion Study to determine if increased MTT was associated with an increased risk of stroke in patients with symptomatic complete carotid artery occlusion.

Lower stroke risk with lower blood pressure in hemodynamic cerebral ischemia.

Objective: To determine whether strict blood pressure (BP) control is the best medical management for patients with symptomatic carotid artery occlusion and hemodynamic cerebral ischemia.

Methods: In this prospective observational cohort study, we analyzed data from 91 participants in the nonsurgical group of the Carotid Occlusion Surgery Study (COSS) who had recent symptomatic internal carotid artery occlusion and hemodynamic cerebral ischemia manifested by ipsilateral increased oxygen extraction fraction. The target BP goal in COSS was ≤130/85 mm Hg.

Randomized Evaluation of Carotid Occlusion and Neurocognition (RECON) trial: main results.

Objective: To determine whether extracranial-intracranial (EC-IC) bypass can improve cognition over 2 years compared to best medical therapy alone in patients with symptomatic internal carotid artery (ICA) occlusion and increased oxygen extraction fraction (OEF) on PET.

Methods: Patients underwent (15)O PET and were randomized if OEF ratio was >1.13 on the occluded side.

Striatal dopamine D1-like receptor binding is unchanged in primary focal dystonia.

Background: Multiple studies have demonstrated decreases in striatal D2-like (D2, D3) radioligand binding in primary focal dystonias. Although most investigations have focused on D2-specific receptors (D2R), a recent study suggests that the decreased D2-like binding may be due to a D3-specific (D3R) abnormality. However, only limited data exist on the role of D1-specific receptors (D1R) and the D1R-mediated pathways within basal ganglia in dystonia.

Principal component analysis of PiB distribution in Parkinson and Alzheimer diseases.

Objective: To use principal component analyses (PCA) of Pittsburgh compound B (PiB) PET imaging to determine whether the pattern of in vivo β-amyloid (Aβ) in Parkinson disease (PD) with cognitive impairment is similar to the pattern found in symptomatic Alzheimer disease (AD).

Methods: PiB PET scans were obtained from participants with PD with cognitive impairment (n = 53), participants with symptomatic AD (n = 35), and age-matched controls (n = 67). All were assessed using the Clinical Dementia Rating and APOE genotype was determined in 137 participants.

Validation of nigrostriatal positron emission tomography measures: critical limits.

Objective: Molecular imaging and clinical endpoints are frequently discordant in Parkinson disease clinical trials, raising questions about validity of these imaging measures to reflect disease severity. We compared striatal uptake for 3 positron emission tomography (PET) tracers with in vitro measures of nigral cell counts and striatal dopamine in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys.

Methods: Sixteen macaques had magnetic resonance imaging and baseline PETs using 6-[18F]fluorodopa (FD), [11C]dihydrotetrabenazine (DTBZ), and 2beta-[11 C]carbomethoxy-3beta-(4-fluorophenyl)tropane (CFT).

Surgical results of the Carotid Occlusion Surgery Study.

Object: The Carotid Occlusion Surgery Study (COSS) was conducted to determine if superficial temporal artery-middle cerebral artery (STA-MCA) bypass, when added to the best medical therapy, would reduce subsequent ipsilateral stroke in patients with complete internal carotid artery (ICA) occlusion and an elevated oxygen extraction fraction (OEF) in the cerebral hemisphere distal to the occlusion. A recent publication documented the methodology of the COSS in detail and briefly outlined the major findings of the trial. The surgical results of the COSS are described in detail in this report.

Thalamic activation during slightly subphysiological glycemia in humans.

Objective: The central nervous system mechanisms of defenses against falling plasma glucose concentrations, and how they go awry and result in iatrogenic hypoglycemia in diabetes, are not known. Hypoglycemic plasma glucose concentrations of 55 mg/dL (3.0 mmol/L) cause symptoms, activate glucose counterregulatory systems, and increase synaptic activity in a network of brain regions including the dorsal midline thalamus in humans.

Characterization of extrastriatal D2 in vivo specific binding of [¹⁸F](N-methyl)benperidol using PET.

PET imaging studies of the role of the dopamine D2 receptor family in movement and neuropsychiatric disorders are limited by the use of radioligands that have near-equal affinities for D2 and D3 receptor subtypes and are susceptible to competition with endogenous dopamine. By contrast, the radioligand [¹⁸F]N-methylbenperidol ([¹⁸F]NMB) has high selectivity and affinity for the D2 receptor subtype (D2R) and is not sensitive to endogenous dopamine. Although [¹⁸F]NMB has high binding levels in striatum, its utility for measuring D2R in extrastriatal regions is unknown.

Mood response to deep brain stimulation of the subthalamic nucleus in Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus (STN DBS) in Parkinson's disease (PD) improves motor functioning but has variable effects on mood. Little is known about the relationship between electrode contact location and mood response. The authors identified the anatomical location of electrode contacts and measured mood response to stimulation with the Visual Analog Scale in 24 STN DBS PD patients.

Reduced uptake of FDOPA PET in end-stage liver disease with elevated manganese levels.

Objective: To investigate whether manganese toxicity secondary to end-state liver disease is associated with nigrastriatal dysfunction as measured by 6-[(18)F]fluoro-L-DOPA (FDOPA) positron emission tomographic (PET) imaging.

Design: Observational case report.

Setting: The Movement Disorder Center at Washington University, St Louis, Missouri.

Effect of osmotic agents on regional cerebral blood flow in traumatic brain injury.

Purpose: Cerebral blood flow (CBF) is reduced after severe traumatic brain injury (TBI) with considerable regional variation. Osmotic agents are used to reduce elevated intracranial pressure (ICP), improve cerebral perfusion pressure, and presumably improve CBF. Yet, osmotic agents have other physiologic effects that can influence CBF.

Comparison of induced hypertension, fluid bolus, and blood transfusion to augment cerebral oxygen delivery after subarachnoid hemorrhage.

Object: Critical reductions in oxygen delivery (DO(2)) underlie the development of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). If DO(2) is not promptly restored, then irreversible injury (that is, cerebral infarction) may result. Hemodynamic therapies for DCI (that is, induced hypertension [IH] and hypervolemia) aim to improve DO(2) by raising cerebral blood flow (CBF).

Effect of mannitol on cerebral blood volume in patients with head injury.

Background: Mannitol has traditionally been the mainstay of medical therapy for intracranial hypertension in patients with head injury. We previously demonstrated that mannitol reduces brain volume in patients with cerebral edema, although whether this occurs because of a reduction in brain water, blood volume, or both remains poorly understood.

Objective: To test the hypothesis that mannitol acts by lowering blood viscosity leading to reflex vasoconstriction and a fall in cerebral blood volume (CBV).

Extracranial-intracranial bypass surgery for stroke prevention in hemodynamic cerebral ischemia: the Carotid Occlusion Surgery Study randomized trial.

Context: Patients with symptomatic atherosclerotic internal carotid artery occlusion (AICAO) and hemodynamic cerebral ischemia are at high risk for subsequent stroke when treated medically.

Objective: To test the hypothesis that extracranial-intracranial (EC-IC) bypass surgery, added to best medical therapy, reduces subsequent ipsilateral ischemic stroke in patients with recently symptomatic AICAO and hemodynamic cerebral ischemia.

Design: Parallel-group, randomized, open-label, blinded-adjudication clinical treatment trial conducted from 2002 to 2010.

Poor correlation between perihematomal MRI hyperintensity and brain swelling after intracerebral hemorrhage.

Background And Purpose: The perihematomal hyperintensity (PHH) is commonly interpreted to represent cerebral edema following intracerebral hemorrhage (ICH), but the accuracy of this interpretation is unknown. We therefore investigated the relationship between the changes in PHH and the changes in hemispheric brain volume as a measure of edema during the first week after ICH.

Methods: Fifteen individuals aged 66 ± 13 with baseline hematoma size of 13.

Metabolic control of resting hemispheric cerebral blood flow is oxidative, not glycolytic.

Although the close regional coupling of resting cerebral blood flow (CBF) with both cerebral metabolic rate of oxygen (CMRO(2)) and cerebral metabolic rate of glucose (CMRglc) within individuals is well documented, there are few data regarding the coupling between whole brain flow and metabolism among different subjects. To investigate the metabolic control of resting whole brain CBF, we performed multivariate analysis of hemispheric CMRO(2), CMRglc, and other covariates as predictors of resting CBF among 23 normal humans. The univariate analysis showed that only CMRO(2) was a significant predictor of CBF.

Cerebral hemodynamic and metabolic effects of equi-osmolar doses mannitol and 23.4% saline in patients with edema following large ischemic stroke.

Introduction: Cerebral edema after ischemic stroke is frequently treated with mannitol and hypertonic saline (HS); however, their relative cerebrovascular and metabolic effects are incompletely understood, and may operate independent of their ability to lower intracranial pressure.

Methods: We compared the effects of 20% mannitol and 23.4% saline on cerebral blood flow (CBF), blood volume (CBV), oxygen extraction fraction (OEF), and oxygen metabolism (CMRO(2)), in nine ischemic stroke patients who deteriorated and had >2 mm midline shift on imaging.

Decreased striatal dopamine receptor binding in primary focal dystonia: a D2 or D3 defect?

Dystonia is an involuntary movement disorder characterized by repetitive patterned or sustained muscle contractions causing twisting or abnormal postures. Several lines of evidence suggest that abnormalities of dopaminergic pathways contribute to the pathophysiology of dystonia. In particular, dysfunction of D2-like receptors that mediate function of the indirect pathway in the basal ganglia may play a key role.

Platelet mitochondrial complex I and I+III activities do not correlate with cerebral mitochondrial oxidative metabolism.

Assays of mitochondrial electron transport system (ETS) activity in circulating blood platelets have been used to investigate the cause of neurodegenerative diseases. However, the correspondence between platelet ETS function and cerebral mitochondrial metabolism is not well characterized. To assess the validity of using platelet ETS activity to infer cerebral mitochondrial metabolism, we measured platelet ETS activity (complex I and complex I+III), cerebral metabolic rate of oxygen (CMRO(2)), and the CMRO(2)/cerebral metabolic rate for glucose ratio in 40 subjects: 7 with never-medicated Parkinson's disease, 13 with genetically proved Huntington's disease, and 20 normal controls.

Mapping Go-No-Go performance within the subthalamic nucleus region.

The basal ganglia are thought to be important in the selection of wanted and the suppression of unwanted motor patterns according to explicit rules (i.e. response inhibition).

Autoregulation of cerebral blood flow to changes in arterial pressure in mild Alzheimer's disease.

Studies in transgenic mice overexpressing amyloid precursor protein (APP) demonstrate impaired autoregulation of cerebral blood flow (CBF) to changes in arterial pressure and suggest that cerebrovascular dysfunction may be critically important in the development of pathological Alzheimer's disease (AD). Given the relevance of such a finding for guiding hypertension treatment in the elderly, we assessed autoregulation in individuals with AD. Twenty persons aged 75±6 years with very mild or mild symptomatic AD (Clinical Dementia Rating 0.

Dynamic susceptibility contrast MRI with localized arterial input functions.

Compared to gold-standard measurements of cerebral perfusion with positron emission tomography using H(2)[(15)O] tracers, measurements with dynamic susceptibility contrast MR are more accessible, less expensive, and less invasive. However, existing methods for analyzing and interpreting data from dynamic susceptibility contrast MR have characteristic disadvantages that include sensitivity to incorrectly modeled delay and dispersion in a single, global arterial input function. We describe a model of tissue microcirculation derived from tracer kinetics that estimates for each voxel a unique, localized arterial input function.

Cerebellum as the normal reference for the detection of increased cerebral oxygen extraction.

Hemispheric ratios of oxygen extraction fraction (OEF), a proven methodology for the detection of severe hemodynamic impairment and stroke risk, are not sensitive for detecting bilateral hemispheric increases in OEF. The aim of this study was to investigate the use of cerebellum as the reference normal. We analyzed positron emission tomographic (PET) measurements of count-based OEF and clinical data from 57 patients with unilateral atherosclerotic carotid occlusion and 13 controls enrolled in a prospective study of stroke risk.