RESUMO
Deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in idiopathic Parkinson's disease, yet the mechanism of action remains unclear. Previous studies indicate that STN DBS increases regional cerebral blood flow (rCBF) in immediate downstream targets but does not reveal which brain regions may have functional changes associated with improved motor manifestations. We studied 48 patients with STN DBS who withheld medication overnight and underwent PET scans to measure rCBF responses to bilateral STN DBS. PET scans were performed with bilateral DBS OFF and ON in a counterbalanced order followed by clinical ratings of motor manifestations using Unified Parkinson Disease Rating Scale 3 (UPDRS 3). We investigated whether improvement in UPDRS 3 scores in rigidity, bradykinesia, postural stability and gait correlate with rCBF responses in a priori determined regions. These regions were selected based on a previous study showing significant STN DBS-induced rCBF change in the thalamus, midbrain and supplementary motor area (SMA). We also chose the pedunculopontine nucleus region (PPN) due to mounting evidence of its involvement in locomotion. In the current study, bilateral STN DBS improved rigidity (62%), bradykinesia (44%), gait (49%) and postural stability (56%) (paired t-tests: P < 0.001). As expected, bilateral STN DBS also increased rCBF in the bilateral thalami, right midbrain, and decreased rCBF in the right premotor cortex (P < 0.05, corrected). There were significant correlations between improvement of rigidity and decreased rCBF in the SMA (r(s) = -0.4, P < 0.02) and between improvement in bradykinesia and increased rCBF in the thalamus (r(s) = 0.31, P < 0.05). In addition, improved postural reflexes correlated with decreased rCBF in the PPN (r(s) = -0.38, P < 0.03). These modest correlations between selective motor manifestations and rCBF in specific regions suggest possible regional selectivity for improvement of different motor signs of Parkinson's disease.
Assuntos
Estimulação Encefálica Profunda/métodos , Doença de Parkinson/terapia , Núcleo Subtalâmico/fisiopatologia , Idoso , Circulação Cerebrovascular , Eletromiografia , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/fisiopatologia , Núcleo Tegmental Pedunculopontino/diagnóstico por imagem , Núcleo Tegmental Pedunculopontino/fisiopatologia , Tomografia por Emissão de Pósitrons , Núcleo Subtalâmico/diagnóstico por imagemRESUMO
Recent antecedent hypoglycemia has been found to shift glycemic thresholds for autonomic (including adrenomedullary epinephrine), symptomatic, and other responses to subsequent hypoglycemia to lower plasma glucose concentrations. This change in threshold is the basis of the clinical syndromes of hypoglycemia unawareness and, in part, defective glucose counterregulation and the unifying concept of hypoglycemia-associated autonomic failure in type 1 diabetes. We tested in healthy young adults the hypothesis that recent antecedent hypoglycemia increases blood-to-brain glucose transport, a plausible mechanism of this phenomenon. Eight subjects were studied after euglycemia, and nine were studied after approximately 24 h of interprandial hypoglycemia ( approximately 55 mg/dl, approximately 3.0 mmol/l). The latter were shown to have reduced plasma epinephrine (P = 0.009), neurogenic symptoms (P = 0.009), and other responses to subsequent hypoglycemia. Global bihemispheric blood-to-brain glucose transport and cerebral glucose metabolism were calculated from rate constants derived from blood and brain time-activity curves-the latter determined by positron emission tomography (PET)-after intravenous injection of [1-(11)C]glucose at clamped plasma glucose concentrations of 65 mg/dl (3.6 mmol/l). For these calculations, a model was used that includes a fourth rate constant to account for egress of [(11)C] metabolites. Cerebral blood flow was measured with intravenous [(15)O]water using PET. After euglycemia and after hypoglycemia, rates of blood-to-brain glucose transport (24.6 +/- 2.3 and 22.4 +/- 2.4 micromol. 100 g(-1). min(-1), respectively), cerebral glucose metabolism (16.8 +/- 0.9 and 15.9 +/- 0.9 micromol. 100 g(-1). min(-1), respectively) and cerebral blood flow (56.8 +/- 3.9 and 53.3 +/- 4.4 ml. 100 g(-1). min(-1), respectively) were virtually identical. These data do not support the hypothesis that recent antecedent hypoglycemia increases blood-to-brain glucose transport during subsequent hypoglycemia. They do not exclude regional increments in blood-to-brain glucose transport. Alternatively, the fundamental alteration might lie beyond the blood-brain barrier.
Assuntos
Glicemia/metabolismo , Barreira Hematoencefálica/fisiologia , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Circulação Cerebrovascular/fisiologia , Glucose/metabolismo , Hipoglicemia/fisiopatologia , Adulto , Radioisótopos de Carbono , Epinefrina/sangue , Feminino , Glucagon/sangue , Técnica Clamp de Glucose , Hormônio do Crescimento Humano/sangue , Humanos , Hidrocortisona/sangue , Hipoglicemia/sangue , Cinética , Masculino , Norepinefrina/sangue , Radioisótopos de Oxigênio , Polipeptídeo Pancreático/sangue , Valores de Referência , Fluxo Sanguíneo Regional , Tomografia Computadorizada de Emissão , ÁguaRESUMO
To test the hypothesis that blood-to-brain glucose transport is reduced in poorly controlled type 1 diabetes, we studied seven patients with a mean (+/- SD) HbA1c level of 10.1 +/- 1.2% and nine nondiabetic subjects during hyperinsulinemic, mildly hypoglycemic (approximately 3.6 mmol/l, approximately 65 mg/dl) glucose clamps. Blood-to-brain glucose transport and cerebral glucose metabolism were calculated from rate constants derived from blood and brain time-activity curves--the latter determined by positron emission tomography (PET)--after intravenous injection of [1-(11)C]glucose using a model that includes a fourth rate constant to account for regional egress of 11C metabolites. Cerebral blood flow and cerebral blood volume were determined with intravenous H2(15)O and inhaled C(15)O, respectively, also by PET. At plateau plasma glucose concentrations of 3.6 +/- 0.0 and 3.7 +/- 0.1 mmol/l, rates of blood-to-brain glucose transport were similar in the two groups (23.7 +/- 2.2 and 21.6 +/- 2.9 micromol x 100 g(-1) x min(-1), P = 0.569, in the control subjects and the patients, respectively). There were also no differences in the rates of cerebral glucose metabolism (16.8 +/- 0.8 and 16.3 +/- 1.2 micromol x 100 g(-1) x min(-1), P = 0.693, respectively). Plasma epinephrine (1,380 +/- 340 vs. 450 +/- 170 pmol/l, P = 0.0440) and glucagon (26 +/- 5 vs. 12 +/- 1 pmol/l, P = 0.0300) responses to mild hypoglycemia were reduced in the patients with type 1 diabetes. We conclude that neither blood-to-brain glucose transport nor cerebral glucose metabolism is measurably reduced in people with poorly controlled type 1 diabetes.
Assuntos
Glicemia/metabolismo , Barreira Hematoencefálica , Diabetes Mellitus Tipo 1/metabolismo , Glucose/metabolismo , Adulto , Pressão Sanguínea , Radioisótopos de Carbono/farmacocinética , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Ácidos Graxos não Esterificados/sangue , Feminino , Glucagon/sangue , Técnica Clamp de Glucose , Hemoglobinas Glicadas/análise , Frequência Cardíaca , Hormônio do Crescimento Humano/sangue , Humanos , Hidrocortisona/sangue , Insulina/sangue , Masculino , Norepinefrina/sangue , Polipeptídeo Pancreático/sangue , Valores de Referência , Tomografia Computadorizada de EmissãoRESUMO
We have revised our methods for calculating regional blood volume, flow, oxygen extraction, and oxygen utilization from positron emission tomography data obtained using 15O-labeled radiotracers. These revisions include radioactive decay explicitly within the model equations instead of requiring all measured activity to be corrected for decay prior to incorporation in the equations. The revised equations yield small but significant differences in the computed values.
Assuntos
Volume Sanguíneo , Encéfalo/metabolismo , Circulação Cerebrovascular , Oxigênio/metabolismo , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Matemática , Radioisótopos de Oxigênio , Tomografia Computadorizada de EmissãoRESUMO
Given the low spatial resolution of positron emission tomography (PET), regional measurements of neural tissue are often inaccurate because of the presence of non-neural elements and to mixtures of different tissue types within the volume of space influencing the measurements. These effects are significant in scans of brains both with and without atrophy, but are particularly significant when comparing measurements of brains with atrophy with those of normals, as is typically done in studies of aging and dementia. Previous attempts to correct for cerebral atrophy have been limited to global measurements. Using computer simulations, we illustrate the effects of atrophy and describe a method for correcting regional PET data to represent units of actual neural tissue volume.
Assuntos
Encéfalo/diagnóstico por imagem , Tomografia Computadorizada de Emissão , Atrofia , Encéfalo/patologia , HumanosRESUMO
Few data regarding early developmental changes in cerebral (blood-to-brain) glucose transport (CTXglc) and CMRglc are available for humans. We measured CBF, CTXglc, and CMRglc with positron emission tomography at 4 to 7 days of life in six preterm human infants whose estimated gestational age was 25 to 34 weeks. The Michaelis-Menten constants Kt and Tmax were estimated from CTXglc and the calculated cerebral capillary plasma glucose concentration. Mean CMRglc was 8.8 mumol 100 g-1 min-1. The CMRglc did not correlate with plasma glucose concentration (r = .315, P = .543), whereas CTXglc showed a significant correlation with plasma glucose concentration (r = .836, P = .038). Estimation of the Michaelis-Menten constants from the best fit to the measured data produced values of Kt = 6.0 mumol mL-1 and Tmax = 32.6 mumol 100 g-1 min-1. These values for Kt in the developing human brain are similar to those that have been reported for the mature brain of adolescent and adult humans and adult nonhuman primates, indicating the affinity of the glucose transport protein for D-glucose is similar. However, Tmax is approximately one third to one half of the comparable values for mature brain, indicating a reduced number of available luminal transporters.
Assuntos
Encéfalo/metabolismo , Glucose/metabolismo , Recém-Nascido Prematuro/metabolismo , Transporte Biológico , Glicemia/metabolismo , Barreira Hematoencefálica , Capilares , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Terapia Intensiva Neonatal , Cinética , Masculino , Tomografia Computadorizada de EmissãoRESUMO
A zone of hypoperfusion surrounding acute intracerebral hemorrhage (ICH) has been interpreted as regional ischemia. To determine if ischemia is present in the periclot area, the authors measured cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and oxygen extraction fraction (OEF) with positron emission tomography (PET) in 19 patients 5 to 22 hours after hemorrhage onset. Periclot CBF, CMRO2, and OEF were determined in a 1-cm-wide area around the clot. In the 16 patients without midline shift, periclot data were compared with mirror contralateral regions. All PET images were masked to exclude noncerebral structures, and all PET measurements were corrected for partial volume effect due to clot and ventricles. Both periclot CBF and CMRO2 were significantly reduced compared with contralateral values (CBF: 20.9 +/- 7.6 vs. 37.0 +/- 13.9 mL 100 g(-1) min(-1), P = 0.0004; CMRO2: 1.4 +/- 0.5 vs. 2.9 +/- 0.9 mL 100 g(-1) min(-1), P = 0.00001). Periclot OEF was less than both hemispheric OEF (0.42 +/- 0.15 vs. 0.47 +/- 0.13, P = 0.05; n = 19) and contralateral regional OEF (0.44 +/- 0.16 vs. 0.51 +/- 0.13, P = 0.05; n = 16). In conclusion, CMRO2 was reduced to a greater degree than CBF in the periclot region in acute ICH, resulting in reduced OEF rather than the increased OEF that occurs in ischemia. Thus, the authors found no evidence for ischemia in the periclot zone of hypoperfusion in acute ICH patients studied 5 to 22 hours after hemorrhage onset.
Assuntos
Isquemia Encefálica/fisiopatologia , Encéfalo/irrigação sanguínea , Hemorragia Cerebral/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/administração & dosagem , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Feminino , Humanos , Labetalol/administração & dosagem , Masculino , Manitol/administração & dosagem , Pessoa de Meia-Idade , Consumo de Oxigênio , Fatores de Tempo , Tomografia Computadorizada de Emissão , Tomografia Computadorizada por Raios XRESUMO
We evaluated the sensitivity and specificity of positron emission tomography for diagnosis of probable Alzheimer's disease under conditions similar to those encountered in the routine clinical practice of nuclear medicine. We obtained tomographic images of regional cerebral blood flow from three groups of subjects: (1) 13 subjects, ages 69 to 84, who had probable Alzheimer's disease diagnosed by validated clinical criteria; (2) 15 subjects, ages 57 to 77, who had Parkinson's disease without dementia; and (3) 11 subjects, ages 65 to 83, who were normal. Three blinded reviewers, who had not previously seen the images, categorized them as normal, bilateral temporoparietal flow defects typical of Alzheimer's disease, or other abnormality. Consensus interpretation demonstrated sensitivity of 0.38 (5/13) and specificity of 0.88 (23/26) for identifying patients with probable Alzheimer's disease. Thus, the criterion of bilateral temporoparietal reduction in cerebral blood flow used in this study did not have sufficient sensitivity to be of clinical value. While other criteria may be developed to improve diagnostic accuracy, clinical utility can be established only by testing for validity in patients with a full spectrum of complicating neurologic and psychiatric conditions for whom diagnosis is uncertain and who are then followed longitudinally to determine clinical outcome or pathologic findings.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/psicologia , Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular , Humanos , Pessoa de Meia-Idade , Variações Dependentes do Observador , Sensibilidade e Especificidade , Tomografia Computadorizada de EmissãoRESUMO
OBJECTIVE: To determine whether welding-related parkinsonism differs from idiopathic PD. BACKGROUND: Welding is considered a cause of parkinsonism, but little information is available about the clinical features exhibited by patients or whether this is a distinct disorder. METHODS: The authors performed a case-control study that compared the clinical features of 15 career welders, who were ascertained through an academic movement disorders center and compared to two control groups with idiopathic PD. One control group was ascertained sequentially to compare the frequency of clinical features, and the second control group was sex- and age-matched to compare the frequency of motor fluctuations. RESULTS: Welders were exposed to a mean of 47,144 welding hours. Welders had a younger age at onset (46 years) of PD compared with sequentially ascertained controls (63 years; p < 0.0001). There was no difference in frequency of tremor, bradykinesia, rigidity, asymmetric onset, postural instability, family history, clinical depression, dementia, or drug-induced psychosis between the welders and the two control groups. All treated welders responded to levodopa. Motor fluctuations and dyskinesias occurred at a similar frequency in welders and the two control groups. PET with 6-[18F]fluorodopa obtained in two of the welders showed findings typical of idiopathic PD, with greatest loss in posterior putamen. CONCLUSIONS: Parkinsonism in welders is distinguished clinically only by age at onset, suggesting welding may be a risk factor for PD. These preliminary data cannot exclude a genetic contribution to susceptibility in these exposed individuals.
Assuntos
Doenças Profissionais/epidemiologia , Doença de Parkinson/epidemiologia , Soldagem , Adulto , Idade de Início , Idoso , Estudos de Casos e Controles , Di-Hidroxifenilalanina/análogos & derivados , Feminino , Humanos , Masculino , Manganês/efeitos adversos , Pessoa de Meia-Idade , Neostriado/patologia , Doenças Profissionais/patologia , Doenças Profissionais/terapia , Exposição Ocupacional , Doença de Parkinson/patologia , Doença de Parkinson/terapia , Fatores de Risco , Tomografia Computadorizada de EmissãoRESUMO
BACKGROUND: Arterial hypertension is common in the first 24 hours after acute intracerebral hemorrhage (ICH). Although increased blood pressure usually declines to baseline values within several days, the appropriate treatment during the acute period has remained controversial. Arguments against treatment of hypertension in patients with acute ICH are based primarily on the concern that reducing arterial blood pressure will reduce cerebral blood flow (CBF). The authors undertook this study to provide further information on the changes in whole-brain and periclot regional CBF that occur with pharmacologic reductions in mean arterial pressure (MAP) in patients with acute ICH. METHODS: Fourteen patients with acute supratentorial ICH 1 to 45 mL in size were studied 6 to 22 hours after onset. CBF was measured with PET and (15)O-water. After completion of the first CBF measurement, patients were randomized to receive either nicardipine or labetalol to reduce MAP by 15%, and the CBF study was repeated. RESULTS: MAP was lowered by -16.7 +/- 5.4% from 143 +/- 10 to 119 +/- 11 mm Hg. There was no significant change in either global CBF or periclot CBF. Calculation of the 95% CI demonstrated that there is less than a 5% chance that global or periclot CBF fell by more than -2.7 mL x 100 g(-1) x min(-1). CONCLUSION: In patients with small- to medium-sized acute ICH, autoregulation of CBF was preserved with arterial blood pressure reductions in the range studied.
Assuntos
Anti-Hipertensivos/uso terapêutico , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/fisiopatologia , Circulação Cerebrovascular/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Labetalol/uso terapêutico , Nicardipino/uso terapêutico , Doença Aguda , Adulto , Idoso , Pressão Sanguínea/efeitos dos fármacos , Hemorragia Cerebral/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
Changes in brain tissue volume in six patients who had acute complete middle cerebral artery (MCA) infarctions and CT evidence of midline shift were measured using the brain boundary shift integral (BBSI) on sequential T1-weighted MR images acquired before and after a 1.5-g/kg bolus infusion of mannitol. At 50 to 55 minutes after the baseline scan, total brain volume decreased by 8.1 +/- 2.8 mL (0.6%, p < 0.005). Brain in the noninfarcted hemisphere shrank more (0.8 +/- 0.4%) than in the infarcted hemisphere (0.0 +/- 0.5%, p < 0.05).
Assuntos
Edema Encefálico/tratamento farmacológico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Imageamento por Ressonância Magnética , Manitol/efeitos adversos , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Atrofia , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Edema Encefálico/diagnóstico , Mapeamento Encefálico , Progressão da Doença , Dominância Cerebral/efeitos dos fármacos , Dominância Cerebral/fisiologia , Feminino , Humanos , Infarto da Artéria Cerebral Média/diagnóstico , Infusões Intravenosas , Masculino , Manitol/administração & dosagem , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND OBJECTIVE: Deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus (VIM) provides remarkable relief of tremor in the limbs contralateral to the side of the brain stimulated. The benefits have been sufficiently dramatic that this is now an accepted clinical treatment of essential as well as other forms of tremor. Despite this clinical benefit, the mechanism of action of DBS remains unknown. In this investigation, we sought to determine the effects of VIM DBS on neuronal function. METHODS: The authors used PET measurements of qualitative regional cerebral blood flow in patients with essential tremor to determine the effects of DBS in the left VIM. Each subject had four to six scans with the arms at rest and DBS turned either on or off during alternate scans. Continuous physiologic monitoring revealed no tremor during any of the scans. The PET images from each subject were aligned, averaged, and coregistered to a standard image oriented in stereotactic space. RESULTS: The authors used subtraction image analysis with statistical parametric mapping methods and a restricted volume search to identify a significantly increased flow response at the site of stimulation in thalamus. An exploratory analysis revealed increased flow in ipsilateral supplementary motor area, a region that receives afferents from VIM. CONCLUSIONS: The increased blood flow at terminal fields of thalamocortical projections suggests that DBS stimulates and does not inactivate projection neurons in VIM thalamus.
Assuntos
Encéfalo/irrigação sanguínea , Encéfalo/fisiopatologia , Terapia por Estimulação Elétrica , Tremor Essencial/fisiopatologia , Tremor Essencial/terapia , Idoso , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Circulação Cerebrovascular , Terapia por Estimulação Elétrica/métodos , Eletromiografia , Feminino , Análise de Fourier , Lobo Frontal/irrigação sanguínea , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiopatologia , Neurônios/fisiologia , Técnica de Subtração , Tálamo/irrigação sanguínea , Tálamo/diagnóstico por imagem , Tálamo/fisiopatologia , Tomografia Computadorizada de Emissão , Núcleos Ventrais do Tálamo/irrigação sanguínea , Núcleos Ventrais do Tálamo/diagnóstico por imagem , Núcleos Ventrais do Tálamo/fisiopatologiaRESUMO
OBJECTIVE: To determine the prognosis of asymptomatic carotid artery occlusion. BACKGROUND: As opposed to symptomatic carotid occlusion, little information is available on the prognosis of asymptomatic carotid occlusion. METHOD: Thirty never-symptomatic and 81 symptomatic patients with carotid occlusion underwent baseline assessment of 15 risk factors together with PET measurements of oxygen extraction fraction (OEF). Every 6-month telephone contact recorded interval medical treatment and subsequent stroke occurrence during an average follow-up of 32 months. Patients, treating physicians, and an end point adjudicator were blinded to PET results. RESULTS: Ischemic stroke occurred in 1 of 30 of never-symptomatic patients (3.3%) and 15 of 81 of symptomatic patients (18.5%; p = 0.03). No strokes in the carotid territory distal to the occluded vessel occurred in the never-symptomatic patients. Multivariate analysis of baseline risk factors for all 111 patients revealed that age, plasma fibrinogen level, and PET findings of high OEF distal to the occluded carotid artery were the only independent predictors of subsequent stroke (p < 0.05). Previous ipsilateral hemispheric or retinal symptoms was not a significant predictive variable. The lower risk of stroke in never-symptomatic patients was associated with a lower incidence of high OEF (4 of 30) as opposed to symptomatic patients (39 of 81; p = 0.002), but there was no significant difference in age or fibrinogen level. CONCLUSIONS: Never-symptomatic carotid occlusion carries a very low risk of subsequent ischemic stroke. This benign prognosis is associated with a low incidence of cerebral hemodynamic compromise in these patients. These data support further the importance of hemodynamic factors in the pathogenesis of ischemic stroke in patients with carotid occlusion.
Assuntos
Arteriopatias Oclusivas/fisiopatologia , Doenças das Artérias Carótidas/fisiopatologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
UNLABELLED: PET measurement of increased oxygen extraction fraction (OEF) identifies patients at high risk for subsequent stroke. OEF methodology remains controversial. In this study we compare the sensitivity and specificity of absolute OEF measurements with ipsilateral-to-contralateral ratios of absolute OEF and count-based OEF estimates. METHODS: Multivariate analyses of OEF methods were performed using data from patients with symptomatic carotid artery occlusion (n = 68). Outcome and receiver operating characteristic (ROC) curve analyses were performed. RESULTS: All 3 methods were predictive of stroke risk in univariate analysis. Only the count-based method remained significant in multivariate analysis. The area under the ROC curve was greatest for the count-based ratio: 0.815 versus 0.769 (absolute) and 0.737 (ratios of absolute). CONCLUSION: All 3 methods are predictive of stroke risk in patients with unilateral carotid artery occlusion. ROC curve analysis is useful for selecting optimal thresholds for maximal sensitivity and specificity.
Assuntos
Consumo de Oxigênio/fisiologia , Acidente Vascular Cerebral/diagnóstico por imagem , Tomografia Computadorizada de Emissão/métodos , Arteriosclerose/complicações , Arteriosclerose/diagnóstico por imagem , Química Encefálica , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/mortalidade , Humanos , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Acidente Vascular Cerebral/etiologia , Resultado do TratamentoRESUMO
Epileptiform activity was induced in the visual cortex with penicillin to test whether it would prevent the ocular dominance shift that normally occurs in monocularly deprived kittens. The eyelids of one eye of 5-week-old kittens were sutured shut for several days. During this period, whenever the kittens were in the light, aqueous penicillin in artificial cerebrospinal fluid (CSF) or just CSF was applied in a cylinder mounted over the visual cortex. Electroencephalograms monitored during the period of deprivation indicated nearly continuous interictal spiking in the visual cortex. Extracellular recordings were made of cells in the region directly under the position of the cylinder. 14C-labeled 2-deoxyglucose autoradiography in a control kitten showed that this area had considerably increased metabolism during epileptiform activity. The majority of cortical cells were dominated by the non-deprived eye in both epileptic and control kittens, with no noticeable difference between them. These preliminary observations indicate that the disruption of cortical activity that occurs during interictal epileptiform activity does not prevent the ocular dominance shift in monocularly deprived kittens.
Assuntos
Dominância Cerebral/fisiologia , Epilepsia/fisiopatologia , Privação Sensorial/fisiologia , Visão Ocular , Córtex Visual/fisiopatologia , Animais , Autorradiografia , Gatos , Modelos Animais de Doenças , Eletroencefalografia , Epilepsia/induzido quimicamente , Glucose/metabolismo , Penicilina GRESUMO
BACKGROUND AND PURPOSE: Deep white matter may be the location of an internal arterial border zone. The purpose of this study was to determine whether the deep white matter was subject to a greater degree of ischemia than was the cortex among patients with chronic carotid occlusion. METHODS: Thirty-six patients with carotid occlusion and structurally normal deep white matter were studied with positron emission tomography. Measurements of oxygen extraction fraction were made in superficial (cortical and subcortical) regions in the middle cerebral artery territory and in deep white matter (internal border zone) regions. The presence of selective ischemia of the deep white matter was assessed by the ratio of deep white matter:superficial oxygen extraction fraction. Ipsilateral hemispheric ratios among patients were assessed as a group as compared with contralateral hemispheric ratios and as compared with normal hemispheric ratios from 15 control volunteers. RESULTS: Mean deep white matter to superficial oxygen extraction fraction ratios (+/-95% confidence limits) were 0.99 (+/-0.07), 1.01 (+/-0.06), and 1.02 (+/-0.08) for ipsilateral, contralateral, and normal hemispheres, respectively. No statistically significant difference was found between ipsilateral and contralateral (P = .691) or normal hemispheres (P = .68), nor was any statistically significant difference found when the analysis was limited to patients with increased superficial oxygen extraction fraction (n = 9). Individual deep white matter:superficial ratios were within the normal range for all patients. CONCLUSION: Normal deep white matter among patients with carotid occlusion is not subject to a greater degree of ischemia than is the overlying cortex. It is unlikely that deep white matter infarctions observed among patients with carotid occlusion are owing to chronic selective hemodynamic compromise occurring at an internal arterial border zone.
Assuntos
Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/metabolismo , Estenose das Carótidas/complicações , Oxigênio/metabolismo , Tomografia Computadorizada de Emissão , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/etiologia , Circulação Cerebrovascular , Doença Crônica , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECT: Hyperventilation has been used for many years in the management of patients with traumatic brain injury (TBI). Concern has been raised that hyperventilation could lead to cerebral ischemia; these concerns have been magnified by reports of reduced cerebral blood flow (CBF) early after severe TBI. The authors tested the hypothesis that moderate hyperventilation induced early after TBI would not produce a reduction in CBF severe enough to cause cerebral energy failure (CBF that is insufficient to meet metabolic needs). METHODS: Nine patients were studied a mean of 11.2+/-1.6 hours (range 8-14 hours) after TBI occurred. The patients' mean Glasgow Coma Scale score was 5.6+/-1.8 and their mean age 27+/-9 years; eight of the patients were male. Intracranial pressure (ICP), mean arterial blood pressure, and jugular venous oxygen content were monitored and cerebral perfusion pressure was maintained at a level higher than 70 mm Hg by using vasopressors when needed. Measurements of CBF, cerebral blood volume (CBV), cerebral metabolic rate for oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral venous oxygen content (CvO2) were made before and after 30 minutes of hyperventilation to a PaCO2 of 30+/-2 mm Hg. Ten age-matched healthy volunteers were used as normocapnic controls. Global CBF, CBV, and CvO2 did not differ between the two groups, but in the TBI patients CMRO2 and OEF were reduced (1.59+/-0.44 ml/100 g/minute [p < 0.01] and 0.31+/-0.06 [p < 0.0001], respectively). During hyperventilation, global CBF decreased to 25.5+/-8.7 ml/100 g/minute (p < 0.0009), CBV fell to 2.8+/-0.56 ml/100 g (p < 0.001), OEF rose to 0.45+/-0.13 (p < 0.02), and CvO2 fell to 8.3+/-3 vol% (p < 0.02); CMRO2 remained unchanged. CONCLUSIONS: The authors conclude that early, brief, moderate hyperventilation does not impair global cerebral metabolism in patients with severe TBI and, thus, is unlikely to cause further neurological injury. Additional studies are needed to assess focal changes, the effects of more severe hyperventilation, and the effects of hyperventilation in the setting of increased ICP.
Assuntos
Lesões Encefálicas/metabolismo , Lesões Encefálicas/terapia , Isquemia Encefálica/metabolismo , Encéfalo/metabolismo , Circulação Cerebrovascular , Hiperventilação/metabolismo , Pressão Intracraniana , Oxigênio/metabolismo , Adulto , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Lesões Encefálicas/complicações , Lesões Encefálicas/diagnóstico por imagem , Lesões Encefálicas/fisiopatologia , Isquemia Encefálica/etiologia , Isquemia Encefálica/prevenção & controle , Estudos de Casos e Controles , Feminino , Escala de Coma de Glasgow , Humanos , Hiperventilação/fisiopatologia , Masculino , Seleção de Pacientes , Fatores de Tempo , Tomografia Computadorizada de EmissãoRESUMO
OBJECTIVES: The effects of subthalamic nucleus (STN) deep brain stimulation (DBS) on gait and balance vary and the underlying mechanisms remain unclear. DBS location may alter motor benefit due to anatomical heterogeneity in STN. The purposes of this study were to (1) compare the effects of DBS of dorsal (D-STN) versus ventral (V-STN) regions on gait, balance and regional cerebral blood flow (rCBF) and (2) examine the relationships between changes in rCBF and changes in gait and balance induced by D-STN or V-STN DBS. METHODS: We used a validated atlas registration to locate and stimulate through electrode contacts in D-STN and V-STN regions of 37 people with Parkinson's disease. In a within-subjects, double-blind and counterbalanced design controlled for DBS settings, we measured PET rCBF responses in a priori regions of interest and quantified gait and balance during DBS Off, unilateral D-STN DBS and unilateral V-STN DBS. RESULTS: DBS of either site increased stride length without producing significant group-level changes in gait velocity, cadence or balance. Both sites increased rCBF in subcortical regions and produced variable changes in cortical and cerebellar regions. DBS-induced changes in gait velocity are related to premotor cortex rCBF changes during V-STN DBS (r=-0.40, p=0.03) and to rCBF changes in the cerebellum anterior lobe during D-STN DBS (r=-0.43, p=0.02). CONCLUSIONS: DBS-induced changes in gait corresponded to rCBF responses in selected cortical and cerebellar regions. These relationships differed during D-STN versus V-STN DBS, suggesting DBS acts through distinct neuronal pathways dependent on DBS location.
Assuntos
Córtex Cerebral/irrigação sanguínea , Estimulação Encefálica Profunda/métodos , Transtornos Neurológicos da Marcha/terapia , Equilíbrio Postural/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Transtornos de Sensação/terapia , Núcleo Subtalâmico/fisiologia , Idoso , Córtex Cerebral/diagnóstico por imagem , Feminino , Lateralidade Funcional/fisiologia , Transtornos Neurológicos da Marcha/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/patologia , Doença de Parkinson/terapia , Tomografia por Emissão de Pósitrons , Transtornos de Sensação/etiologia , Índice de Gravidade de Doença , Estatística como AssuntoRESUMO
OBJECTIVE: To determine whether unihemispheral hemodynamic failure is independently associated with cognitive impairment among participants in the National Institute of Neurological Disorders and Stroke-sponsored, multicenter, randomized clinical trial, Randomized Evaluation of Carotid Occlusion and Neurocognition (RECON). METHODS: Forty-three patients were randomized into RECON after recent symptomatic carotid artery occlusion and asymmetrically increased oxygen extraction fraction (OEF) by PET (OEF ratio >1.13), indicating stage II hemodynamic failure on the side of occlusion. The PET-positive patients were compared with 28 RECON-enrolled patients who met all clinical and radiographic inclusion/exclusion criteria but had no OEF asymmetry. A multivariable regression compared patients with PET OEF >1.13 or ≤1.13, stratifying by TIA vs. stroke as the qualifying event. The dependent variable was a composite neurocognitive score derived from averaging age-normalized z scores on a test battery that included global and internal carotid artery (ICA) side-relevant hemisphere-specific tests. RESULTS: There were no differences in demographic, clinical, or radiologic characteristics between the PET-positive and PET-negative patients except for PET OEF asymmetry. The unadjusted average neurocognitive z score was -1.45 for the PET-positive and -1.25 for the PET-negative patients, indicating cognitive impairment in both groups but no difference between them (p = 0.641). After adjustment for age, education, side of occlusion, depression, and previous stroke, there was a significant difference between PET-positive and PET-negative patients among those with TIA as a qualifying event (average z score = -1.41 vs. -0.76, p = 0.040). Older age and right ICA side were also significant in this model. CONCLUSION: Hemodynamic failure is independently associated with cognitive impairment in patients with carotid occlusion. This finding establishes the physiologic parameter upon which the extracranial-intracranial bypass will be tested.
Assuntos
Circulação Cerebrovascular , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Idoso , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/fisiopatologia , Doenças das Artérias Carótidas/psicologia , Transtornos Cognitivos/diagnóstico por imagem , Estudos de Coortes , Escolaridade , Feminino , Lateralidade Funcional , Humanos , Ataque Isquêmico Transitório/diagnóstico por imagem , Ataque Isquêmico Transitório/fisiopatologia , Ataque Isquêmico Transitório/psicologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Destreza Motora , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/psicologia , Teste de Sequência Alfanumérica , Percepção Visual , Testes de Associação de PalavrasRESUMO
BACKGROUND: Welding exposes workers to manganese (Mn) fumes, but it is unclear if this exposure damages dopaminergic neurons in the basal ganglia and predisposes individuals to develop parkinsonism. PET imaging with 6-[(18)F]fluoro-l-dopa (FDOPA) is a noninvasive measure of nigrostriatal dopaminergic neuron integrity. The purpose of this study is to determine whether welding exposure is associated with damage to nigrostriatal neurons in asymptomatic workers. METHODS: We imaged 20 asymptomatic welders exposed to Mn fumes, 20 subjects with idiopathic Parkinson disease (IPD), and 20 normal controls using FDOPA PET. All subjects were examined by a movement disorders specialist. Basal ganglia volumes of interest were identified for each subject. The specific uptake of FDOPA, K(i), was generated for each region using graphical analysis method. RESULTS: Repeated measures general linear model (GLM) analysis demonstrated a strong interaction between diagnostic group and region (F(4,112) = 15.36, p < 0.001). Caudate K(i)s were lower in asymptomatic welders (0.0098 + 0.0013 minutes(-1)) compared to control subjects (0.0111 + 0.0012 minutes(-1), p = 0.002). The regional pattern of uptake in welders was most affected in the caudate > anterior putamen > posterior putamen. This uptake pattern was anatomically reversed from the pattern found in subjects with IPD. CONCLUSIONS: Active, asymptomatic welders with Mn exposure demonstrate reduced FDOPA PET uptake indicating dysfunction in the nigrostriatal dopamine system. The caudate K(i) reduction in welders may represent an early (asymptomatic) marker of Mn neurotoxicity and appears to be distinct from the pattern of dysfunction found in symptomatic IPD.