Biomedical subjects
K M Welch
Publications and source records attributed to K M Welch.
A 47-year-old woman with tension-type headaches.
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Age and carotid artery occlusive disease are important determinants of cerebral blood flow changes after antihypertensive therapy.
STUDY OBJECTIVE: To determine the short-term effects of antihypertensive therapy on cerebral blood flow (CBF). DESIGN: Prospective, observational study. SETTING: A university-affiliated teaching hospital. PATIENTS: Twenty-four patients (age range 53-85 yrs) with chronic hypertension, nine of whom had carotid artery occlusive disease (CAOD). INTERVENTIONS: The CBF (xenon-133 inhalation technique) and blood pressure were measured before and at 60 minutes after administration of antihypertensive therapy. MEASUREMENTS AND MAIN RESULTS: Age was inversely related to the change in CBF in patients with CAOD (p < 0.01). In all patients, the change in CBF after taking antihypertensive drugs was significantly inversely associated with baseline CBF (p < 0.01). Changes in regional CBF, measured by asymmetry scores, were significantly greater in patients with CAOD than in those without CAOD (p < 0.05). CONCLUSIONS: Elderly patients with occlusive extracranial cerebrovascular disease are at risk of drug-induced changes in both mean and regional CBF, and may benefit from a CBF assessment before being prescribed antihypertensive therapy.
Assessment of magnesium concentrations by 31P NMR in vivo.
31P NMR spectra obtained in vivo reveal the presence of a few reasonably well defined chemical species, namely, ATP, orthophosphate (Pi), and, in brain, phosphocreatine. The chemical shifts of these resonances respond to changes in concentrations of ions such as H+ and Mg2+ in a manner that depends on both the chemical shifts intrinsic to individual complexes and the formation or binding constants for the several complexes. Values of the appropriate formation constants are well established in the literature. We have derived estimates of the chemical shifts intrinsic to the individual complexes by analyzing high resolution spectra of solutions whose composition brackets the domain of physiological relevance. This provides information sufficient to estimate intracellular concentrations of H+ and Mg2+ from chemical shifts seen with in vivo spectra. The primary finding is an estimate of 0.3 mM for the concentration of free magnesium in human brain. Differing values are obtained from other tissues.
The occipital cortex is hyperexcitable in migraine: experimental evidence.
OBJECTIVES: Threshold for generation of magnetophosphenes has been reported to be lower in migraine. We compared the threshold for eliciting phosphenes by transcranial magnetic stimulation and the ability to visually trigger headache in a select group of individuals with migraine with and without aura to normal controls. METHODS: Transcranial magnetic stimulation was performed using the Cadwell MES-10 stimulator. A circular coil, 9.5 cm in diameter, was applied to the occipital scalp (7 cm above the inion). Stimulator intensity was increased in 10% increments until subjects reported visual phenomena or 100% intensity was reached. Stimulator intensity was then fine-tuned to determine the threshold at which phosphenes were seen. In the same subjects, visual stimulation was given in 3.0 T MRI and if a headache occurred the response was recorded. RESULTS: Fifteen subjects with migraine were compared to 8 controls. A significant proportion of the migraineurs (86.7%) developed phosphenes compared to the controls (25%) (P = .006). The probability of triggering a headache was also higher in the migraineurs (53%); no headache was triggered in the controls (P = .019). A significant correlation was found between the threshold for phosphenes on transcranial magnetic stimulation and visually triggered headache (P = .002). When only migraine was considered, there was again a significant trend (P = .084). CONCLUSIONS: There is a difference in threshold for excitability of occipital cortex in migraineurs and controls. The hyperexcitable visual cortex in migraine is predisposed to visually triggered headache.
Periaqueductal gray matter dysfunction in migraine: cause or the burden of illness?
OBJECTIVE: The periaqueductal gray matter (PAG) is at the center of a powerful descending antinociceptive neuronal network. We studied iron homeostasis in the PAG as an indicator of function in patients with episodic migraine (EM) between attacks and patients with chronic daily headache (CDH) during headache. High-resolution magnetic resonance techniques were used to map the transverse relaxation rates R2, R2*, and R2' in the PAG, red nucleus (RN), and substantia nigra (SN). R2' is a measure of non-heme iron in tissues. METHODS: Seventeen patients diagnosed with EM with and without aura, 17 patients diagnosed with CDH and medication overuse, and 17 normal adults (N) were imaged with a 3.0-tesla magnetic resonance imaging system. For each subject, mean values of the relaxation rates, R2 (1/T2), R2* (1/T2*), and R2' (R2* - R2) were obtained for the PAG, RN, and SN. R2, R2*, and R2' values of the EM, CDH, and N groups were compared using analysis of variance, Student t test, and correlation analysis. RESULTS: In the PAG, there was a significant increase in mean R2' and R2* values in both the EM and CDH groups (P<.05) compared with the N group, but no significant difference in these values was demonstrated between the EM and CDH groups, or between those with migraine with or without aura in the EM group. Positive correlations were found for duration of illness with R2' in the EM and CDH groups. A decrease in mean R2' and R2* values also was observed in the RN and SN of the CDH group compared with the N and EM groups (P<.05), explained best by flow activation due to head pain. CONCLUSIONS: Iron homeostasis in the PAG was selectively, persistently, and progressively impaired in the EM and CDH groups, possibly caused by repeated migraine attacks. These results support and emphasize the role of the PAG as a possible "generator" of migraine attacks, potentially by dysfunctional control of the trigeminovascular nociceptive system.
Magnetic resonance assessment of acute and chronic stroke.
This article describes the important role of magnetic resonance imaging (MRI) in noninvasively assessing human focal ischemic stroke. Conventional MRI, diffusion-weighted and/or perfusion-weighted imaging have been used to facilitate both the qualitative and quantitative evaluation of heterogeneity of ischemic brain tissue. Further, by combining 2 or more magnetic resonance parameters, tissue-signature models have been developed that may be used as surrogate markers of tissue histopathology to characterize ischemic tissue as salvageable, necrotic, or tissue in transition to necrosis. Magnetic resonance tissue-signature models and results are presented. Dynamic changes in the evolution of ischemic tissue to infarction are also discussed. Recovery from acute stroke was studied with blood oxygenation level-dependent functional MRI to investigate the neural mechanisms for recovery from aphasia after stroke.
In vivo 31-P NMR of photoactivated hematoporphyrin derivative in cat brain.
In vivo 31-P nuclear magnetic resonance (NMR) spectroscopy was performed on cat brains injected with hematoporphyrin derivative (HpD). A 2-cm-diam region of the right parietal lobe was photoactivated with red light. The 31-P NMR spectra of the photoactivated hemisphere revealed increased inorganic phosphate and decreased phosphocreatine and adenosine triphosphate (ATP) levels, compared to spectra obtained from the control hemisphere. In the absence of drug, no difference in spectra was observed between the photoradiated and control lobes. Our studies suggest that in vivo 31-P NMR spectroscopy may be used to monitor the effects of phototherapy on tissue high-energy phosphate metabolism.
Viewing stroke pathophysiology: an analysis of contemporary methods.
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Cerebrovascular ischemia associated with lupus anticoagulant.
The lupus anticoagulant, an acquired circulating serum gamma-globulin, prolongs all phospholipid-dependent coagulation tests. Recent associations of the lupus anticoagulant and focal cerebral and/or ocular ischemia have been made. We present 5 cases of lupus anticoagulant-associated cerebrovascular ischemia and review all reported cases for the first time. Clinical spectra, cerebral angiographic findings, associated conditions, and response to therapy are presented. Typical features include a relatively young age (mean 39 years), female preponderance, transient ischemic attacks (including amaurosis fugax) or stroke, and normal or large vessel occlusions on angiography. Commonly associated conditions were systemic lupus erythematosus (34%), noncerebral venous thrombosis (31%), hypertension (28%), false-positive VDRL (28%), and spontaneous abortions (22%). Four of our 5 patients (all without systemic lupus erythematosus) and 11 of the 20 (55%) patients in the literature without systemic lupus erythematosus had other definite stroke risk factors coexisting. Response to therapy was highly variable, with no clear beneficial effect of corticosteroids.
Cerebral venous thrombosis with lupus anticoagulants. Report of two cases.
Lupus anticoagulants are circulating autoantibodies, primarily directed against phospholipids, that prolong the partial thromboplastin time. They have been previously associated with systemic arterial and venous thrombosis and arterial stroke, but not with cerebral venous thrombosis. We describe 2 young patients with cerebral venous thrombosis documented by intravenous digital subtraction angiography in whom a lupus anticoagulant was demonstrated. Both patients improved with corticosteroid and anticoagulant therapy.
Intracellular acidosis during and after cerebral ischemia: in vivo nuclear magnetic resonance study of hyperglycemia in cats.
In vivo 31P nuclear magnetic resonance spectroscopy was used to monitor the time course of intracellular pH in cat cerebral cortex subjected to global cerebral ischemia under control and hyperglycemic pretreatment conditions. Transient (16 minutes) global cerebral ischemia was induced in 14 cats using an inflatable cervical cuff combined with systemic arterial hypotension. Six cats were pretreated with infusion of 1.5 g/kg glucose prior to ischemia. Relative concentrations of high-energy phosphate metabolites and intracellular pH were continuously monitored before, during, and for 2 hours after cerebral reperfusion. During ischemia, intracellular pH fell to the same level and followed a similar time course in both groups. However, during initial reperfusion in the hyperglycemic group, there was a severe further decline (p less than 0.003) in intracellular pH. We suggest that the increased neurologic deficit and mortality found in hyperglycemic animals subjected to cerebral ischemia may be attributed to this transient severe tissue acidosis.
Ischemic stroke associated with anticardiolipin antibodies.
Anticardiolipin antibodies are a group of antiphospholipid autoantibodies seen primarily in patients with systemic lupus erythematosus and other autoimmune diseases. We report 3 patients, 2 without systemic lupus, who suffered ischemic brain infarction associated with these antibodies in the absence of detectable lupus anticoagulant activity. Anticardiolipin antibodies, possibly associated with a lupus anticoagulant-like thrombotic tendency, may be a newly recognized cause of ischemic stroke.
Cerebral blood flow asymmetries in headache-free migraineurs.
Regional cerebral blood flow (rCBF) asymmetries were studied in controls and patients with common and classic/complicated migraine using 133Xe inhalation with 8 homologously situated external collimators over each cerebral hemisphere. Migraine patients as a group more frequently had posterior rCBF asymmetries than controls (p less than 0.03). Although there were no differences in the number of anterior rCBF asymmetries, migraine patients had 2 or more asymmetric probe pairs more often than controls (p less than 0.02). The posterior rCBF asymmetries, consistent with the site of activation of many migraine attacks, may be related to more labile control of the cerebral circulation.
Influence of adrenergic receptor blockade on circulatory and metabolic effects of disordered neurotransmitter function in stroke patients.
Cerebral hemispheric blood flow and metabolism were measured before and after therapy with intracarotid infusion of combined PBZ and PPL in 15 patients with recent cerebral infarction. HBF was unaltered despite decrease in cerebral perfusion pressure. Cerebral hemispheric oxygen comsumption and carbon dioxide production decreased while cerebral hemispheric lactate production increased. Biphasic cerebral uptake of tyrosine was observed during and immediately after PBZ and PPL infusion. CSF HVA increased, indicating altered DA turnover. CSF 5HIAA levels also increased, suggesting altered 5HT turnover after PBZ and PPL. Release of cyclic AMP from ischemic brain into cerebral venous blood seen in the steady state was abolished after therapy. Cerebral hemodynamic studies suggest a functional balance between monaminergic neurogenic influences in the control of cerebral circulation. Imbalance of such controlling factors in ischemic brain may lead to paradoxical vascular responses to induced hypertension and hypotension. PBZ and PPL enhance such responses perhaps by increasing central neurotransmitter turnover and release. Further shift toward cerebral anaerobic metabolism may occur in ischemic brain following the use of phenoxybenzamine and propranolol. Worsening of neurological deficit occurred in four cases. Combined therapy with PBZ and PPL does not appear beneficial in the therapy of patients with recent stroke.
Effect of cerebrospinal fluid removal on cerebral blood flow and metabolism in patients with Alzheimer's disease versus recent stroke.
Cerebral hemispheric blood flow (HBF) and metabolism were measured before and after withdrawal of 20 to 30 ml of cerebrospinal fluid (CSF) over a 10-minute interval in eight patients with recent cerebral infarction and in four patients with Alzheimer's disease (AD). Immediately after CSF removal HBF decreased significantly in the AD group (-14%) but showed no significant change in the stroke group (-5%). There was rapid reduction in cerebral venous O2 content and some increase in cerebral venous PCO2 appearing within 60 seconds of CSF withdrawal, interpreted as a rapid reduction of cerebral blood flow (CBF) as judged by cerebral A-VO2 differences. The reduction in CBF was confirmed by the hydrogen clearance method. Reduction of CBF in response to lowering CSF pressure is presumably of neurogenic origin since it was rapid and occurred without changes in PaCO2 or MABP. Furthermore, measurement of HBF demonstrated that cerebral metabolism constant after CSF removal. It is postulated that in AD, reduction of HBF following CSF withdrawal is mediated by a disordered neurogenic veno-arterial vasoconstriction reflex which is stimulated by rapid reduction in CSF pressure (CSFP). In patients with stroke, when cerebral perfusion pressure is increased by lowering CSFP, CBF is maintained constant most likely by a physiological cerebral veno-arterial vasoconstrictive reflex. Apparently, this vasocontrictive reflex becomes excessive in Alzheimer's disease, possibly due to cerebral neurogenic imbalance.