RESUMEN
BACKGROUND/OBJECTIVES: Hypothalamic obesity (HO) occurs in 50% of patients with the pituitary tumor craniopharyngioma (CP). Attempts have been made to predict the risk of HO based on hypothalamic (HT) damage on magnetic resonance imaging (MRI), but none have included volumetry. We performed qualitative and quantitative volumetric analyses of HT damage. The results were explored in relation to feeding related peptides and body fat. SUBJECTS/METHODS: A cross-sectional study of childhood onset CPs involving 3 Tesla MRI, was performed at median 22 years after first operation; 41 CPs, median age 35 (range: 17-56), of whom 23 had HT damage, were compared to 32 controls. After exclusions, 35 patients and 31 controls remained in the MRI study. Main outcome measures were the relation of metabolic parameters to HT volume and qualitative analyses of HT damage. RESULTS: Metabolic parameters scored persistently very high in vascular risk particularly among HT damaged patients. Patients had smaller HT volumes compared to controls 769 (35-1168) mm3 vs. 879 (775-1086) mm3; P < 0.001. HT volume correlated negatively with fat mass and leptin among CP patients (rs = -0.67; P < .001; rs = -0.53; P = 0.001), and explained 39% of the variation in fat mass. For every 100 mm3 increase in HT volume fat mass decreased by 2.7 kg (95% CI: 1.5-3.9; P < 0.001). Qualitative assessments revealed HT damage in three out of six patients with normal volumetry, but HT damage according to operation records. CONCLUSIONS: A decrease in HT volume was associated with an increase in fat mass and leptin. We present a method with a high inter-rater reliability (0.94) that can be applied by nonradiologists for the assessment of HT damage. The method may be valuable in the risk assessment of diseases involving the HT.
Asunto(s)
Craneofaringioma , Hipotálamo , Obesidad/complicaciones , Neoplasias Hipofisarias , Adolescente , Adulto , Craneofaringioma/complicaciones , Craneofaringioma/diagnóstico por imagen , Craneofaringioma/epidemiología , Craneofaringioma/patología , Estudios Transversales , Femenino , Humanos , Hipotálamo/diagnóstico por imagen , Hipotálamo/patología , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/diagnóstico por imagen , Neoplasias Hipofisarias/epidemiología , Neoplasias Hipofisarias/patología , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Cerebral mitochondrial dysfunction is prominent in the pathophysiology of severe bacterial meningitis. In the present study, we hypothesize that the metabolic changes seen after intracisternal lipopolysaccharide (LPS) injection in a piglet model of meningitis is compatible with mitochondrial dysfunction and resembles the metabolic patterns seen in patients with bacterial meningitis. METHODS: Eight pigs received LPS injection in cisterna magna, and four pigs received NaCl in cisterna magna as a control. Biochemical variables related to energy metabolism were monitored by intracerebral microdialysis technique and included interstitial glucose, lactate, pyruvate, glutamate, and glycerol. The intracranial pressure (ICP) and brain tissue oxygen tension (PbtO2) were also monitored along with physiological variables including mean arterial pressure, blood glucose, lactate, and partial pressure of O2 and CO2. Pigs were monitored for 60 min at baseline and 240 min after LPS/NaCl injection. RESULTS: After LPS injection, a significant increase in cerebral lactate/pyruvate ratio (LPR) compared to control group was registered (p = 0.01). This increase was due to a significant increased lactate with stable and normal values of pyruvate. No significant change in PbtO2 or ICP was registered. No changes in physiological variables were observed. CONCLUSIONS: The metabolic changes after intracisternal LPS injection is compatible with disturbance in the oxidative metabolism and partly due to mitochondrial dysfunction with increasing cerebral LPR due to increased lactate and normal pyruvate, PbtO2, and ICP. The metabolic pattern resembles the one observed in patients with bacterial meningitis. Metabolic monitoring in these patients is feasible to monitor for cerebral metabolic derangements otherwise missed by conventional intensive care monitoring.
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Cerebro/metabolismo , Ácido Láctico/metabolismo , Lipopolisacáridos/farmacología , Meningitis Bacterianas/metabolismo , Enfermedades Mitocondriales/metabolismo , Ácido Pirúvico/metabolismo , Animales , Modelos Animales de Enfermedad , Femenino , Lipopolisacáridos/administración & dosificación , Microdiálisis , Monitorización Neurofisiológica , PorcinosRESUMEN
OBJECTIVES: Aneurysmal subarachnoid hemorrhage (SAH) is frequently associated with delayed neurological deterioration (DND). Several studies have shown that DND is not always related to vasospasm and ischemia. Experimental and clinical studies have recently documented that it is possible to diagnose and separate cerebral ischemia and mitochondrial dysfunction bedside. The study explores whether cerebral biochemical variables in SAH patients most frequently exhibit a pattern indicating ischemia or mitochondrial dysfunction. METHODS: In 55 patients with severe SAH, intracerebral microdialysis was performed during neurocritical care with bedside analysis and display of glucose, pyruvate, lactate, glutamate, and glycerol. The biochemical patterns observed were compared to those previously described in animal studies of induced mitochondrial dysfunction as well as the pattern obtained in patients with recirculated cerebral infarcts. RESULTS: In 29 patients, the biochemical pattern indicated mitochondrial dysfunction while 10 patients showed a pattern of cerebral ischemia, six of which also exhibited periods of mitochondrial dysfunction. Mitochondrial dysfunction was observed during 5162 h. An ischemic pattern was obtained during 688 h. Four of the patients (40%) with biochemical signs of ischemia died at the neurosurgical department as compared with three patients (10%) in the group of mitochondrial dysfunction. CONCLUSIONS: The study documents that mitochondrial dysfunction is a common cause of disturbed cerebral energy metabolism in patients with SAH. Mitochondrial dysfunction may increase tissue sensitivity to secondary adverse events such as vasospasm and decreased cerebral blood flow. The separation of ischemia and mitochondrial dysfunction bedside by utilizing microdialysis offers a possibility to evaluate new therapies.
Asunto(s)
Biomarcadores/líquido cefalorraquídeo , Aneurisma Intracraneal/complicaciones , Microdiálisis/métodos , Mitocondrias/patología , Hemorragia Subaracnoidea/líquido cefalorraquídeo , Hemorragia Subaracnoidea/diagnóstico , Anciano , Isquemia Encefálica/líquido cefalorraquídeo , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiología , Metabolismo Energético/fisiología , Femenino , Glucosa/líquido cefalorraquídeo , Ácido Glutámico/líquido cefalorraquídeo , Glicerol/líquido cefalorraquídeo , Humanos , Ácido Láctico/líquido cefalorraquídeo , Masculino , Persona de Mediana Edad , Ácido Pirúvico , Hemorragia Subaracnoidea/complicacionesRESUMEN
BACKGROUND: The study explores whether the cerebral biochemical pattern in patients treated with hemicraniectomy after large middle cerebral artery infarcts reflects ongoing ischemia or non-ischemic mitochondrial dysfunction. METHODS: The study includes 44 patients treated with decompressive hemicraniectomy (DCH) due to malignant middle cerebral artery infarctions. Chemical variables related to energy metabolism obtained by microdialysis were analyzed in the infarcted tissue and in the contralateral hemisphere from the time of DCH until 96 h after DCH. RESULTS: Reperfusion of the infarcted tissue was documented in a previous report. Cerebral lactate/pyruvate ratio (L/P) and lactate were significantly elevated in the infarcted tissue compared to the non-infarcted hemisphere (p < 0.05). From 12 to 96 h after DCH the pyruvate level was significantly higher in the infarcted tissue than in the non-infarcted hemisphere (p < 0.05). CONCLUSION: After a prolonged period of ischemia and subsequent reperfusion, cerebral tissue shows signs of protracted mitochondrial dysfunction, characterized by a marked increase in cerebral lactate level with a normal or increased cerebral pyruvate level resulting in an increased LP-ratio. This biochemical pattern contrasts to cerebral ischemia, which is characterized by a marked decrease in cerebral pyruvate. The study supports the hypothesis that it is possible to diagnose cerebral mitochondrial dysfunction and to separate it from cerebral ischemia by microdialysis and bed-side biochemical analysis.
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Isquemia Encefálica/metabolismo , Cerebro/metabolismo , Infarto de la Arteria Cerebral Media/complicaciones , Enfermedades Mitocondriales , Ácido Pirúvico/metabolismo , Adolescente , Adulto , Anciano , Craniectomía Descompresiva , Femenino , Humanos , Infarto de la Arteria Cerebral Media/cirugía , Masculino , Microdiálisis , Persona de Mediana Edad , Enfermedades Mitocondriales/diagnóstico , Enfermedades Mitocondriales/etiología , Enfermedades Mitocondriales/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Mitochondrial dysfunction is an important factor contributing to tissue damage in both severe traumatic brain injury and ischemic stroke. This experimental study explores the possibility to diagnose the condition bedside by utilising intracerebral microdialysis and analysis of chemical variables related to energy metabolism. METHODS: Mitochondrial dysfunction was induced in piglets and evaluated by monitoring brain tissue oxygen tension (PbtO2 ) and cerebral levels of glucose, lactate, pyruvate, glutamate, and glycerol bilaterally. The biochemical variables were obtained by microdialysis and immediate enzymatic analysis. Mitochondrial function was blocked by unilateral infusion of NaCN/KCN (0.5 mol/L) through the microdialysis catheter (N = 5). As a reference, NaCl (0.5 mol/L) was infused by intracerebral microdialysis in one group of animals (N = 3). RESULTS: PbtO2 increased during cyanide infusion and returned to baseline afterwards. The lactate/pyruvate (LP) ratio increased significantly following cyanide infusion because of a marked increase in lactate level while pyruvate remained within normal limits. Glutamate and glycerol increased after cyanide infusion indicating insufficient energy metabolism and degradation of cellular membranes, respectively. CONCLUSION: Mitochondrial dysfunction is characterised by an increased LP ratio signifying a shift in cytoplasmatic redox state at normal or elevated PbtO2 . The condition is biochemically characterised by a marked increase in cerebral lactate with a normal or elevated pyruvate level. The metabolic pattern is different from cerebral ischemia, which is characterised by simultaneous decreases in intracerebral pyruvate and PbtO2 . The study supports the hypothesis that cerebral ischemia and mitochondrial dysfunction may be identified and separated at the bedside by utilising intracerebral microdialysis.
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Encéfalo/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Cianuro de Potasio/toxicidad , Cianuro de Sodio/toxicidad , Animales , Presión Sanguínea/efectos de los fármacos , Encéfalo/metabolismo , Química Encefálica , Dióxido de Carbono/sangre , Complejo IV de Transporte de Electrones/antagonistas & inhibidores , Femenino , Glucosa/análisis , Ácido Glutámico/análisis , Glucólisis/efectos de los fármacos , Concentración de Iones de Hidrógeno , Presión Intracraneal/efectos de los fármacos , Lactatos/análisis , Microdiálisis , Oximetría , Oxígeno/sangre , Piruvatos/análisis , Sus scrofa , PorcinosRESUMEN
BACKGROUND: In patients with traumatic brain injury as well as stroke, impaired cerebral oxidative energy metabolism may be an important factor contributing to the ultimate degree of tissue damage. We hypothesize that mitochondrial dysfunction can be diagnosed bedside by comparing the simultaneous changes in brain tissue oxygen tension (PbtO(2)) and cerebral cytoplasmatic redox state. The study describes cerebral energy metabolism during mitochondrial dysfunction induced by sevoflurane in piglets. METHODS: Ten piglets were included, seven in the experimental group (anesthetized with sevoflurane) and three in the control group (anesthetized with midazolam). PbtO(2) and cerebral levels of glucose, lactate, and pyruvate were monitored bilaterally. The biochemical variables were obtained by intracerebral microdialysis. RESULTS: All global variables were within normal range and did not differ significantly between the groups except for blood lactate that was slightly higher in the experimental group. Mitochondrial dysfunction was observed in the group of animals initially anesthetized with sevoflurane. Cerebral glucose was significantly lower in the experimental group than in the control group whereas lactate and lactate/pyruvate ratio were significantly higher. Pyruvate and tissue oxygen tension remained within normal range in both groups. Changes of intracerebral variables indicating mitochondrial dysfunction were present already from the very start of the monitoring period. CONCLUSION: Intracerebral microdialysis revealed mitochondrial dysfunction by marked increases in cerebral lactate and lactate/pyruvate ratio simultaneously with normal levels of pyruvate and a normal PbtO(2). This metabolic pattern is distinctively different from cerebral ischemia, which is characterized by simultaneous decreases in PbtO(2) and intracerebral pyruvate.
Asunto(s)
Química Encefálica/fisiología , Metabolismo Energético/fisiología , Enfermedades Mitocondriales/metabolismo , Anestesia por Inhalación , Anestésicos por Inhalación , Animales , Análisis de los Gases de la Sangre , Presión Sanguínea/fisiología , Temperatura Corporal , Citoplasma/metabolismo , Femenino , Glucosa/metabolismo , Presión Intracraneal/fisiología , Ácido Láctico/metabolismo , Éteres Metílicos , Oxidación-Reducción , Consumo de Oxígeno , Ácido Pirúvico/metabolismo , Sevoflurano , PorcinosRESUMEN
OBJECTIVES: In patients with large middle cerebral artery (MCA) infarcts, maximum brain swelling leading to cerebral herniation and death usually occurs 2-5 days after onset of stroke. The study aimed at exploring the pattern of compounds related to cerebral energy metabolism in infarcted brain tissue. METHODS: Forty-four patients with malignant MCA infarcts were included after decision to perform decompressive hemicraniectomy (DHC). Cerebral energy metabolism was in all patients monitored bedside by 1-3 microdialysis catheters inserted into the infarcted hemisphere during DHC. In 29 of the patients, one microdialysis catheter was also placed in the non-infarcted hemisphere. MCA blood-flow velocity was monitored bilaterally by transcranial Doppler ultrasound. RESULTS: The interstitial glucose levels were in both sides within normal limits throughout the monitoring period. Mean lactate/pyruvate (LP) ratio was very high in infarcted tissue immediately after DHC. The ratio slowly decreased but did not reach normal level during the study period. In the infarcted hemisphere, MCA blood-flow velocities increased from approximately 42 cm/s 1 day prior to DHC (nine of nine patients) to approximately 60 cm/s at day 4. CONCLUSIONS: Normal interstitial glucose level in the infarcted hemisphere in combination with substantial MCA blood-flow velocities bilaterally even before DHC was performed indicates that malignant brain swelling usually commences when the embolus/thrombosis has been largely resolved and recirculation of the infarcted area has started. The protracted increase of the LP ratio in infarcted tissue might indicate mitochondrial dysfunction.
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Edema Encefálico/etiología , Edema Encefálico/metabolismo , Encéfalo/irrigación sanguínea , Infarto de la Arteria Cerebral Media/complicaciones , Infarto de la Arteria Cerebral Media/metabolismo , Adolescente , Adulto , Anciano , Encéfalo/metabolismo , Química Encefálica , Edema Encefálico/fisiopatología , Circulación Cerebrovascular/fisiología , Femenino , Humanos , Infarto de la Arteria Cerebral Media/fisiopatología , Masculino , Microdiálisis , Persona de Mediana Edad , Daño por Reperfusión/complicaciones , Daño por Reperfusión/metabolismo , Daño por Reperfusión/fisiopatología , Ultrasonografía Doppler Transcraneal , Adulto JovenRESUMEN
BACKGROUND: Tumefactive demyelinating disease (TDD) is a rare primary demyelinating disease with diagnostic and therapeutic challenges. METHODS AND RESULTS: We report a 50-year old woman with TDD successfully treated with decompressive craniectomy and corticosteroids. The patient presented with seizures, subacute progressive hemispheric syndrome, and a tumourlike abnormality on MRI. Demyelinating disease was initially considered unlikely. Due to a rapidly evolving herniation syndrome hemicraniectomy was performed. Outcome was favourable with only very mild neurological deficits 6 weeks later. CONCLUSION: TDD should be considered as a differential diagnosis in tumour-like presentations, and appears to have distinctive neuroimaging features. In the advent of treatement failure from high dose corticosteroids and plasmapheresis and development of severe mass effect, decompressive hemicraniectomy is an important treatment option.
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Encéfalo/patología , Encéfalo/cirugía , Enfermedades Desmielinizantes/patología , Enfermedades Desmielinizantes/cirugía , Corticoesteroides/uso terapéutico , Encéfalo/efectos de los fármacos , Craneotomía , Descompresión Quirúrgica , Enfermedades Desmielinizantes/fisiopatología , Diagnóstico Diferencial , Femenino , Humanos , Neuroborreliosis de Lyme , Imagen por Resonancia Magnética , Persona de Mediana EdadRESUMEN
The optimal therapy of sustained increase in intracranial pressure (ICP) is still controversial. The "Lund concept" is based on the physiological volume regulation of the intracranial compartments. In addition to its other functions the blood-brain barrier (BBB) is the most important regulator of brain volume. Water exchange across the intact BBB is counteracted by the low permeability to crystalloids (mainly Na+ and Cl-) combined with the high osmotic pressure (5,700 mmHg) on both sides of the BBB. If the BBB is disrupted transcapillary water transport will be determined by the differences in hydrostatic and colloid osmotic pressure between the intra- and extracapillary compartments. Under pathological conditions pressure autoregulation of cerebral blood flow is often impaired and intracapillary hydrostatic pressure will depend on variations in systemic blood pressure. The "Lund concept" can be summarized in four paragraphs: I. Reduction of stress response and cerebral energy metabolism; II. Reduction of capillary hydrostatic pressure; III. Maintenance of colloid osmotic pressure and control of fluid balance; IV. Reduction of cerebral blood volume. The efficacy of the treatment protocol has been evaluated in experimental and clinical studies regarding the physiological and biochemical (utilizing intracerebral microdialysis) effects. The clinical experiences have been favourable.
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Volumen Sanguíneo , Barrera Hematoencefálica , Hipertensión Intracraneal/fisiopatología , Hipertensión Intracraneal/terapia , Presión Intracraneal , Modelos Biológicos , Guías de Práctica Clínica como Asunto , Animales , Encéfalo/irrigación sanguínea , Encéfalo/fisiopatología , Permeabilidad Capilar , Circulación Cerebrovascular , Metabolismo Energético , Humanos , Presión Hidrostática , Presión Osmótica , Pautas de la Práctica en Medicina , Equilibrio HidroelectrolíticoRESUMEN
Specific causes of death, survival, and recurrence rates were assessed in a cohort of 60 patients who had undergone surgery for craniopharyngioma between 1951 and 1988. Compared to the general population, the standardized mortality ratio (SMR) was increased [5.55; 95% confidence interval (CI), 3.68-8.22], and it was higher among females (SMR, 11.4) than males (SMR, 4.79). The risk of cardio- and cerebrovascular mortality (SMR, 3.21; 95% CI, 1.29-6.61) was also enhanced. The cumulative survival rates 10 and 15 yr after the initial operation were 68% (95% CI 54-78) and 59% (95% CI 30-63), respectively. A multivariate survival analysis adjusting for age showed a protective effect of radiotherapy (hazard ratio, 0.3; 95% CI, 0.1-0.8) and an increased risk of death after recurrence (hazard ratio, 4.4; 95% CI, 1.4-14), but no obvious effect of radicality at surgery. However, when patients who had died within 6 months after surgery were excluded, no significant protective effect of radiotherapy remained. The cumulative frequency of recurrence after 10 yr was 33% (95% CI, 22-48%), and that after 15 yr was 40% (95% CI, 28-56%). The incidence of recurrence did not differ significantly with respect to age, radicality at surgery, or postoperative radiotherapy. The determinants for long term outcome in patients with craniopharyngioma are interrelated in a complex way, which calls for strict selection criteria in follow-up studies and the use of multivariate statistical models.
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Enfermedades Cardiovasculares/mortalidad , Craneofaringioma/cirugía , Recurrencia Local de Neoplasia/mortalidad , Neoplasias Hipofisarias/cirugía , Enfermedades Cardiovasculares/etiología , Terapia Combinada , Craneofaringioma/complicaciones , Craneofaringioma/mortalidad , Femenino , Humanos , Incidencia , Masculino , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/mortalidad , Periodo Posoperatorio , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
The influence of brain and body temperature on ischemic brain damage, notably on the density and distribution of selective neuronal vulnerability, was studied in SPF-Wistar rats subjected to 15 min of forebrain ischemia induced by bilateral occlusion of the common carotid arteries combined with arterial hypotension (50 mm Hg) in a room air environment. In one group of animals, the body temperature was maintained at 37 degrees C but no attempt was made to prevent heat losses from the ischemic brain; i.e., the head was not heated during ischemia. Under those conditions the temperature of the caudoputamen and at a subcutaneous site over the skull bone spontaneously fell to approximately 32 degrees C. In four other groups, both the rectal and the subcutaneous skull temperatures were maintained at 38, 37, 35, and 33 degrees C during the ischemia. Our results confirm those recently reported when brain temperature was varied during 20 min of ischemia, with body temperature kept constant. Thus, the histopathological outcome of the brain damage, as assessed after 7 days of recovery, was strongly temperature dependent. Whereas ischemia at 37-38 degrees C consistently caused neuronal necrosis in the hippocampus, neocortex, and caudoputamen, spontaneous cooling of the brain during ischemia at a rectal temperature of 37 degrees C significantly reduced the ischemic damage. Intentional lowering of temperature to 35 degrees C markedly reduced and to 33 degrees C virtually prevented neuronal necrosis in some but not all of the regions studied. While damage to the caudoputamen was extremely temperature sensitive, that affecting the CA1 sector of the hippocampus, and particularly the lateral reticular nucleus of the thalamus, was less so. Our results suggest that whatever biochemical events are responsible for selective neuronal vulnerability, they are temperature sensitive; however, since there are differences in sensitivity between different parts of the brain, more than one mechanism may be involved.
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Temperatura Corporal , Isquemia Encefálica/fisiopatología , Animales , Presión Sanguínea , Isquemia Encefálica/sangre , Corteza Cerebral/fisiopatología , Circulación Cerebrovascular , Masculino , Ratas , Ratas Endogámicas , Recto/fisiopatologíaRESUMEN
OBJECTIVE: To evaluate a new therapy of posttraumatic brain oedema, with the main concept that opening of the blood-brain barrier upsets the normal brain volume regulation, inducing oedema formation. This means that transcapillary fluid fluxes will be controlled by hydrostatic capillary and colloid osmotic pressures, rather than by crystalloid osmotic pressure. If so, brain oedema therapy should include reduction of hydrostatic capillary pressure and preservation of normal colloid osmotic pressure. PATIENTS: 11 severely head injured comatose patients with brain swelling, raised intracranial pressure (ICP), and impaired cerebrovascular response to hyperventilation. INTERVENTIONS: To reduce capillary hydrostatic pressure the patients were given hypotensive therapy (beta 1-antagonist, metoprolol and alpha 2-agonist, clonidine) and a potential precapillary vasoconstrictor (dihydroergotamine). The latter may also decrease cerebral blood volume through venous capacitance constriction. Colloid osmotic pressure was maintained by albumin infusions. The concept implies the need of a negative fluid balance with preserved normovolaemia. RESULTS: ICP decreased significantly within a few hours of treatment with unaltered perfusion pressure in spite of lowered blood pressure. Of 11 patients 9 survived with good recovery/moderate disability, 2 died. This was compared to outcome in a historical control group with identical entry criteria, given conventional brain oedema therapy, where mortality/vegetativity/severe disability was 100%. CONCLUSION: The results indicate that the therapy should focus on extracellular rather than intracellular oedema and that ischemia is not the main triggering mechanism behind oedema formation. We suggest that our therapy is superior to conventional therapy by preventing herniation during the healing period of the blood-brain barrier.
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Edema Encefálico/terapia , Lesiones Encefálicas/terapia , Adolescente , Adulto , Barrera Hematoencefálica , Edema Encefálico/etiología , Edema Encefálico/fisiopatología , Lesiones Encefálicas/complicaciones , Lesiones Encefálicas/fisiopatología , Preescolar , Coma/etiología , Coma/fisiopatología , Coma/terapia , Terapia Combinada/métodos , Femenino , Hemodinámica , Humanos , Presión Intracraneal , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: To study cerebral biochemical markers with intracerebral microdialysis and bedside analysis in patients with severe head injuries treated with a controlled reduction of cerebral perfusion pressure (CPP). DESIGN: Prospective observational study. SETTING: Neurological intensive care unit in a university hospital. PATIENTS: A consecutive series of 48 patients with severe head injuries and intracranial pressure (ICP) above 20 mmHg after conventional treatment. INTERVENTIONS: Reduction of CPP was attained with i. v. infusion of beta1-antagonist (metoprolol) and an alpha2-agonist (clonidine). One microdialysis catheter was inserted via a burr hole frontally to that used for the intraventricular catheter ("better" position). In 27 patients one or more catheters were inserted into cerebral cortex surrounding an evacuated focal contusion or underlying an evacuated haematoma ("worse" position). Perfusion rate was 0.3 microl/min and samples were taken every 30 or 60 min. The levels of glucose, pyruvate, lactate, glycerol and glutamate were analysed and displayed bedside. RESULTS: After initiation of treatment mean CPP decreased from 73 to 62 mmHg. During the first 96 h CPP was less than 60 mmHg and less than 50 mmHg during 30% and 8% of the time, respectively. The treatment was associated with a gradual normalisation of all biochemical markers in the "better" as well as the "worse" catheter position. CONCLUSION: The study shows that pharmacological decrease in CPP according to the "Lund concept" is associated with a normalisation of cerebral metabolism. The study also indicates that intracerebral microdialysis can be used for evaluation of new treatment strategies.
Asunto(s)
Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/terapia , Circulación Cerebrovascular , Metabolismo Energético , Presión Intracraneal , Adolescente , Adulto , Anciano , Biomarcadores , Niño , Preescolar , Femenino , Glucosa/metabolismo , Ácido Glutámico/metabolismo , Glicerol/metabolismo , Hemodinámica , Humanos , Lactante , Ácido Láctico/metabolismo , Masculino , Microdiálisis , Persona de Mediana Edad , Estudios Prospectivos , Ácido Pirúvico/metabolismoRESUMEN
Brain levels of tyrosine, dopamine (DA), noradrenaline (NA), tryptophan, 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were measured after 30, 60 and 120 min of sustained seizure activity, induced in paralyzed, artificially ventilated and anaesthetized (70% N2O) rats by administration of bicuculline (1.2 mg/kg i.v.). In separate animals the rates of accumulation of DOPA and 5-hydroxytryptophan (5-HTP) were estimated in three different brain regions after blockage of the aromatic L-amino acid decarboxylase with NSD 1015 (100 mg/kg). The tissue level of NA was markedly reduced at 30 min and remained low during 120 min of sustained epileptic seizures. In contrast, the DA concentration, being essentially unaffected at 30 min, continuously increased during the following 90 min. 5-HT decreased significantly after 30 min but returned to control levels following 60 and 120 min of seizure activity. The 5-HIAA concentration progressively increased. In all three brain regions (striatum, limbic forebrain and hemispheres) the rate of tyrosine hydroxylation increased. Tryptophan hydroxylation showed a significant increase only in the limbic forebrain. The results suggest that bicuculline-induced seizures lead to an increased functional activity in NA neurons and, at least initially, also in 5-HT neurons. In contrast, DA neurons appear to be inhibited.
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Aminoácidos/metabolismo , Encéfalo/metabolismo , Catecolaminas/metabolismo , Convulsiones/metabolismo , 5-Hidroxitriptófano/metabolismo , Animales , Bicuculina , Cerebelo/metabolismo , Cuerpo Estriado/metabolismo , Dihidroxifenilalanina/metabolismo , Dopamina/metabolismo , Ácido Hidroxiindolacético/metabolismo , Sistema Límbico/metabolismo , Masculino , Norepinefrina/metabolismo , Ratas , Receptores Adrenérgicos/metabolismo , Receptores Dopaminérgicos/metabolismo , Receptores de Serotonina/metabolismo , Convulsiones/inducido químicamente , Serotonina/metabolismo , Triptófano/metabolismo , Tirosina/metabolismoRESUMEN
Cerebral ischemia was induced in normothermic, artificially ventilated rats, anesthetized with 70% N2O or 150 mg/kg of phenobarbitone, by bilateral occlusion of the common carotid arteries and by simultaneous depression of the mean arterial blood pressure to 50 mm Hg. The levels of tyrosine, dopamine (DA), noradrenaline (NA), tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were measured after 15 min of ischemia as well as after 30 min of recirculation. In separate experiments (70% N2O) the rate of accumulation of DOPA and 5-hydroxytryptophan (5-HTP) was determined in three different brain regions (striatum, limbic forebrain and hemispheres) during recirculation. During ischemia, the monoamine pattern was unaffected. Following recirculation, increases in DA, 5-HIAA, tyrosine and tryptophan were found irrespective of the type of anesthesia used. Pronounced postischemic decreases in NA and 5-HT were observed in animals anesthetized with nitrous oxide but not in those given phenobarbitone. During recirculation the rate of tyrosine hydroxylation increased in all three brain regions while tryptophan hydroxylation was reduced. It is tentatively concluded that following transient, global cerebral ischemia, neuronal activity is low or eliminated in dopaminergic and serotoninergic neurons and high in noradrenergic neurons.
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Anestesia por Inhalación , Anestesia Intravenosa , Encéfalo/metabolismo , Catecolaminas/metabolismo , Ataque Isquémico Transitorio/metabolismo , Óxido Nitroso/farmacología , Fenobarbital/farmacología , 5-Hidroxitriptófano/metabolismo , Animales , Cerebelo/metabolismo , Circulación Cerebrovascular , Cuerpo Estriado/metabolismo , Dihidroxifenilalanina/metabolismo , Dopamina/metabolismo , Ácido Hidroxiindolacético/metabolismo , Sistema Límbico/metabolismo , Masculino , Norepinefrina/metabolismo , Ratas , Serotonina/metabolismo , Triptófano/metabolismo , Tirosina/metabolismoRESUMEN
Recent laboratory results have indicated that the ischemic brain is very sensitive to minor variations in temperature. This has created new interest in hypothermia and brain temperature. There is, however, very little information available regarding human intracerebral temperature and its relation to body core temperature during normal and pathological circumstances. We therefore made continuous measurements of the temperature of the lateral ventricle in 15 neurosurgical patients utilizing a newly developed technique with copper-constantan thermocouples introduced through a plastic catheter also used for monitoring intracranial pressure. The intraventricular temperature was higher than the rectal temperature during approximately 90% of all measurements. The largest temperature gradient measured was 2.3 degrees C. Usually the difference between the temperature of the rectum and the brain was much smaller, the mean value being 0.33 degrees C. For the patients in the most severe condition, the rectal temperature was sufficiently close to the brain temperature to afford a reliable basis for adequate clinical judgment.
Asunto(s)
Temperatura Corporal/fisiología , Encéfalo/fisiología , Adolescente , Adulto , Anciano , Encéfalo/cirugía , Encefalopatías/cirugía , Isquemia Encefálica/fisiopatología , Humanos , Hipotermia/fisiopatología , Presión Intracraneal , Persona de Mediana Edad , Monitoreo FisiológicoRESUMEN
Current interest in brain temperature and selective brain cooling makes a method allowing for continuous monitoring of intracerebral temperature in humans desirable. The authors describe a safe, simple, and reliable technique using a thermocouple of copper and constantan in combination with intraventricular monitoring of intracranial pressure for measurement of brain temperature in neurosurgical patients.
Asunto(s)
Temperatura Corporal , Encéfalo/fisiopatología , Monitoreo Fisiológico/métodos , Neurocirugia/métodos , Humanos , Presión Intracraneal , Monitoreo Fisiológico/efectos adversos , Monitoreo Fisiológico/instrumentaciónRESUMEN
OBJECTIVE: The study was undertaken to measure baseline values for chemical markers in human subjects during wakefulness, anesthesia, and neurosurgery, using intracerebral microdialysis. METHODS: Microdialysis catheters were inserted into normal posterior frontal cerebral cortex in nine patients who were undergoing surgery to treat benign lesions of the posterior fossa. The perfusion rate was 1.0 microl/min during anesthesia/neurosurgery and the early postoperative course and 0.3 microl/min during the later course. Bedside biochemical analyses of glucose, pyruvate, lactate, glycerol, glutamate, and urea were performed before, during, and after neurosurgery. After the bedside analyses, all samples were frozen for subsequent high-performance liquid chromatographic analyses of amino acids. RESULTS: The following baseline values were obtained during wakefulness (perfusion rate, 0.3 microl/min): glucose, 1.7+/-0.9 mmol/L; lactate, 2.9+/-0.9 mmol/L; pyruvate, 166+/-47 micromol/L; lactate/pyruvate ratio, 23+/-4; glycerol, 82+/-44 micromol/L; glutamate, 16+/-16 mmol/L; urea, 4.4+/-1.7 mmol/L. Marked increases in the levels of all chemical markers were observed at the beginning and end of anesthesia/surgery. CONCLUSION: The study provides human baseline levels for biochemical markers that can presently be measured at the bedside during neurointensive care. In addition, some changes that occurred under varying physiological conditions are described.
Asunto(s)
Anestesia General , Metabolismo Energético/fisiología , Neoplasias Meníngeas/cirugía , Meningioma/cirugía , Microdiálisis/métodos , Monitoreo Intraoperatorio , Neuroma Acústico/cirugía , Vigilia/fisiología , Adulto , Aminoácidos/metabolismo , Glucemia/metabolismo , Femenino , Lóbulo Frontal/fisiopatología , Ácido Glutámico/metabolismo , Glicerol/metabolismo , Humanos , Ácido Láctico/metabolismo , Masculino , Neoplasias Meníngeas/fisiopatología , Meningioma/fisiopatología , Persona de Mediana Edad , Neuroma Acústico/fisiopatología , Ácido Pirúvico/metabolismo , Valores de Referencia , Urea/metabolismoRESUMEN
Cerebral blood flow (CBF) and oxygen consumption (CMRO2) were determined during timmediate posttraumatic period in rats subjected to concussive impact acceleration. According to previous studies an impact of 9 m/sec velocity elicited typical and marked symptoms of experimental concussion and often a prolonged comatose state, accompanied by cerebral metabolic signs of energy failure. During the immediate concussive response there was an increase of the CBF, followed within the next few minutes by a decrease to about one-third of normal flow, and then by a tendency toward normalization of flow 20 to 40 minutes posttrauma. Simultaneous measurements of cerebral oxygen extraction indicated an increase of the CMRO2 during the first minute. During the ischemic phase oxygen extraction increased but the lowest CBF values were only partially compensated for, and normal oxygen availability could not be maintained. The combined data, including cerebrospinal fluid pressure measurements, indicated primary cerebrovascular effects of the concussive trauma. These vasomotor effects may induce critical cerebral ischemia and thus profoundly influence posttraumatic cerebral function, and cause irreversible damage.
Asunto(s)
Conmoción Encefálica/fisiopatología , Encéfalo/metabolismo , Circulación Cerebrovascular , Consumo de Oxígeno , Animales , Presión Sanguínea , Conmoción Encefálica/metabolismo , Líquido Cefalorraquídeo , Masculino , Presión , RatasRESUMEN
The metabolic rate was determined in the rat brain during the immediate concussive response to standardized impact accelerations of 7 and 9 m/sec velocity. In one series, the metabolic state was determined in freeze-clamped cortical and brain-stem tissue 20 seconds after the impact. The metabolic rate was calculated from the rate of energy depletion in the adjacent unclamped tissue during 10 seconds of total ischemia. The freeze-clamping procedure per se was shown to enhance the metabolic rate probably by inducing mechanical excitation. In another series, in situ freezing was used for tissue sampling in the same situation. A 10-second period of heart standstill induced a standardized period of ischemia. During the acute concussive response to impact acceleration at 7 m/sec velocity, there was an increase of the metabolic rate in the brain stem. A more intense concussive impact at 9 m/sec velocity further enhanced this reaction and also involved the cortex. It is concluded that the basis of the immediate concussive response is a mechanically elicited neuronal excitation. This may lead to energy depletion unless the increased metabolic demands are met.