Transcranial Doppler ultrasound criteria for hemodynamically significant internal carotid artery stenosis based on residual lumen diameter calculated from en bloc endarterectomy specimens.

Background And Purpose: Transcranial Doppler (TCD) is often used in conjunction with carotid duplex ultrasonography (CDUS) to evaluate the hemodynamic significance of internal carotid artery (ICA) stenosis. We examined the sensitivity and specificity of TCD criteria for detection of a hemodynamically significant stenosis (residual lumen diameter < 1.5 mm) at the origin of the ICA.

A Neural Dissociation within Language: Evidence that the Mental Dictionary Is Part of Declarative Memory, and that Grammatical Rules Are Processed by the Procedural System.

Language comprises a lexicon for storing words and a grammar for generating rule-governed forms. Evidence is presented that the lexicon is part of a temporal-parietalhnedial-temporal "declarative memory" system and that granlmatical rules are processed by a frontamasal-ganglia "procedural" system. Patients produced past tenses of regular and novel verbs (looked and plagged), which require an -ed-suffixation rule, and irregular verbs (dug), which are retrieved from memory.

Energy metabolism defects in Huntington's disease and effects of coenzyme Q10.

We investigated whether the Huntington's disease (HD) gene mutation may produce either primary or secondary effects on energy metabolism. 31P magnetic resonance spectroscopy demonstrated a significant decrease in the phosphocreatine to inorganic phosphate ratio in resting muscle of 8 patients as compared with 8 control subjects. The cerebrospinal fluid lactate-pyruvate ratio was significantly increased in 15 patients as compared with 13 control subjects.

Increased levels of plasma cholesteryl ester hydroperoxides in patients with subarachnoid hemorrhage.

The pathophysiology of subarachnoid hemorrhage (SAH) may involve free radical production and lipid peroxidation. We examined plasma levels of cholesteryl ester hydroperoxides (CEOOH) and antioxidants in 25 patients with SAH, and 10 neurologic controls with lacunar stroke. Patients with SAH had significantly increased plasma levels of CEOOH, which peaked on day 5 after the ictus.

Carotid Doppler ultrasound criteria for internal carotid artery stenosis based on residual lumen diameter calculated from en bloc carotid endarterectomy specimens.

Background And Purpose: Carotid duplex ultrasound is widely used to screen patients for carotid endarterectomy and if combined with MR angiography and transcranial Doppler may be an alternative to conventional angiography in the preoperative assessment. We have examined the correlation between Doppler velocities and the residual lumen diameters of internal carotid arteries from surgical pathological specimens to establish Doppler criteria for residual lumen diameter independent of percent stenosis.

Methods: Ninety-one patients who underwent 99 carotid endarterectomies for internal carotid artery stenosis within 6 months of their carotid duplex ultrasound evaluation were studied.

Emerging treatments for stroke in humans.

Ischaemic stroke causes loss of brain function in millions of people worldwide each year. Despite the enormity of the problem, no currently approved therapy reduces stroke size or neurological disability. This contrasts with a number of recently developed agents, reviewed here by Walter Koroshetz and Michael Moskowitz, which limit infarct size in animal stroke models.

Hyperacute stroke: evaluation with combined multisection diffusion-weighted and hemodynamically weighted echo-planar MR imaging.

Purpose: To evaluate acute stroke with conventional, multisection diffusion-weighted (DW), and hemodynamically weighted (HW) magnetic resonance (MR) imaging.

Materials And Methods: The three MR imaging techniques were performed in 11 patients within 10 hours of the onset of acute hemiparesis. The volume of DW and HW abnormalities were compared with infarct volumes depicted at initial and/or follow-up MR or computed tomography (CT).

Cocaine-associated cerebral vasculitis.

Cocaine use is associated with a variety of serious neurological complications, including cerebral infarction, intracerebral and subarachnoid hemorrhage, transient ischemic attacks, migraines, and seizures. We report two cases of intracerebral hemorrhage with biopsy-proven cerebral vasculitis associated with the use of cocaine. The first case involved a 32-year-old man who presented with headache, left-sided hemiparesis, and severe hypertension and who was found to have a large right putaminal hemorrhage on cranial tomographic (CT) scan.

Glutamate stably enhances the activity of two cytosolic forms of phospholipase A2 in brain cortical cultures.

The mechanisms by which glutamatergic neurotransmitters modulate neuronal lipid metabolism are not well established. We have directly measured phospholipase A2 (PLA2) enzymic activity in cell-free extracts from cortical neuronal cultures from rat brain and have found that the PLA2 activity is up-regulated after cells are exposed to glutamate. Brief exposure to a calcium ionophore or phorbol 12-myristate 13-acetate (PMA) stably enhanced PLA2 activity.

Heat shock response in the central nervous system.

The heat shock response is induced in nervous tissue in a variety of clinically significant experimental models including ischemic brain injury (stroke), trauma, thermal stress and status epilepticus. Excessive excitatory neurotransmission or the inability to metabolically support normal levels of excitatory neurotransmission may contribute to neuronal death in the nervous system in many of the same pathophysiologic circumstances. We demonstrated that in vitro glutamate-neurotransmitter induced excitotoxicity is attenuated by the prior induction of the heat shock response.

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.

Evidence for impairment of energy metabolism in vivo in Huntington's disease using localized 1H NMR spectroscopy.

The Huntington's disease (HD) gene mutation has recently been found; however, the biochemical defect that leads to neurodegeneration is still unknown. A progressive impairment of neuronal energy metabolism is a possible etiologic factor. We tested this possibility using localized proton nuclear magnetic resonance (NMR) spectroscopy in 18 patients at high risk for, or suffering from, HD as compared with normal controls.

De novo expansion of a (CAG)n repeat in sporadic Huntington's disease.

Huntington's disease (HD) chromosomes contain an expanded unstable (CAG)n repeat in chromosome 4p16.3. We have examined nine families with potential de novo expression of the disease.

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.

Phospholipase A2 (PLA2) activity in gerbil brain: characterization of cytosolic and membrane-associated forms and effects of ischemia and reperfusion on enzymatic activity.

Phospholipases A2 comprise a family of enzymes that hydrolyze the acyl bond at the sn-2 position of phospholipids to generate free fatty acids and lysophospholipids. In the central nervous system products of PLA2 regulate neurotransmission. In addition, the lysophospholipids, free fatty acids, eicosanoids, platelet activating factor and reactive oxygen species, generated by enhanced PLA2 activity and arachidonic acid metabolism, may be responsible for many destructive cellular processes in neuronal tissue.

Evidence of presymptomatic cognitive decline in Huntington's disease.

Asymptomatic persons at risk for Huntington's disease (HD) (N = 28) were assessed with neuropsychological, psychiatric, and neurologic tests while undergoing genetic linkage studies to determine their probability of carrying the HD gene. Those participants who were subsequently identified as probable gene carriers did not differ on neurologic or psychiatric examination from those subsequently identified as probable noncarriers. Neuropsychological data are presented for a subset of participants free of other conditions (such as alcoholism) putting them at risk for cognitive deficits.

Competitive antagonism of glutamate receptor channels by substituted benzazepines in cultured cortical neurons.

Whole-cell recordings from rat cortical neurons in dissociated cell culture were used to study the antagonism of glutamate receptors by several lipophilic benzazepine analogues of 2,5-dihydro-2,5-dioxo-3-hydroxy-1H-benzazepine (DDHB). DDHB and three substituted derivatives, 4-bromo-, 7-methyl-, and 8-methyl-DDHB, inhibited the activation of N-methyl-D-aspartate (NMDA) receptors at both the NMDA recognition site and the glycine allosteric site. In addition, all four compounds blocked the activation of non-NMDA receptors by kainate and L-glutamate.

Heat shock protects cultured neurons from glutamate toxicity.

Expression of heat shock proteins (HSPs) occurs in brain after ischemia and status epilepticus. We report that induction of the heat shock response in cortical cultures protects neurons from glutamate-induced excitotoxicity. Cultures heated to 42.

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.

Factors associated with slow progression in Huntington's disease.

The rate of disease progression was assessed for 42 persons affected by Huntington's disease who had been neurologically examined at least six times and followed up for at least 3 years. Disease progression was assessed by a disability rating scale administered at each examination. Slow progression was associated with older age at onset of disease and with heavier weight (body mass index) at the first examination.