Depresiones corticales propagadas y su posible rol en la fisiopatología del daño neuronal subsecuente a la hemorragia subaracnoidea / Cortical spreading depressions and their role in the pathophysiology of neuronal damage subsequent to aneurysmal subarachnoid hemorrhage

El vasoespasmo cerebral es la principal causa potencialmente tratable de mortalidad e incapacidad en pacientes que sufren hemorragia subaracnoidea aneurismática (HSA). Sin embargo, a la fecha no existe un tratamiento eficaz para el mismo. La reciente demostración de la falta de respuesta clínica a la reversión farmacológica del espasmo arterial a consecuencia de HSA ha obligado un replanteo de los fundamentos fisiopatológicos de los déficits neurológicos isquémicos tardíos (“delayed ischemic neurologic déficit”, DIND) a consecuencia de HSA, los cuales se creían en relación al espasmo arterial observado en pacientes con HSA. Desde la demostración de hallazgos electrocorticográficos de depresión cortical propagada (“cortical spreading depression”, CSD) en pacientes con HSA, un interés creciente se ha despertado respecto del rol de estos fenómenos en la fisiopatología de los DIND observados en pacientes con HSA. Cuando inducidas en un cerebro saludable, las CSD se asocian con un aumento del flujo sanguíneo cerebral, facilitando la entrega del cerebro de los sustratos energéticos necesarios. En un cerebro que ha sido lesionado, sin embargo, la CSD se asocia con una reducción en flujo sanguíneo cerebral, lo cual, en el contexto de un aumento de las necesidades de energía, conduce a la insuficiencia energética y la hipoxia, empeorando así el daño cerebral. Estas observaciones sugieren que el déficit de energía producida por la CSD es un factor clave en la patogénesis de los DIND observados a consecuencia de HSA. Este resumen detalla características sobresalientes de las CSD y su potencial relevancia en la fisiopatología del vasoespasmo.

Cerebral vasospasm is the leading potentially treatable cause of mortality and disability in patients with aneurysmatic subarachnoid hemorrhage (SAH). However, to date there is no effective treatment for this entity. The recently demonstrated lack of clinical response to pharmacologic reversal of arterial spasm as a result of SAH has spurred a reassessment of the pathophysiological concepts on delayed ischemic neurologic deficits (DIND) that follow SAH, which were long believed the effect of the arterial spasm observed in patients with SAH. Since the discovery of electrocorticographic cortical spreading depressions (CSD) in patients with SAH, increasing interest has been shown on the role of these phenomena in the pathophysiology of DIND observed in patients with HSA. When induced in a healthy brain, CSD are associated with an increase in cerebral blood flow by facilitating the delivery of the necessary energy substrates. In a brain that has been injured, however, CSD are associated with a reduction in cerebral blood flow, which, in the context of increased energy requirements leads to energy shortage and hypoxia, thus worsening brain damage. These observations suggest that the energetic deficit produced by the CSD is a key factor in the pathogenesis of DIND observed as a result of HSA. This review details striking characteristics of CSD and their potential relevance in the pathophysiology of vasospasm.

Hemorragia subaracnoídea por aneurisma cerebral roto: guías de manejo clínico actualizadas 2010: una propuesta al capítulo vascular de la FLANC / Cortical spreading depressions and their role in the pathophysiology of neuronal damage subsequent to aneurysmal subarachnoid hemorrhage

El vasoespasmo cerebral es la principal causa potencialmente tratable de mortalidad e incapacidad en pacientes que sufren hemorragia subaracnoidea aneurismática (HSA). Sin embargo, a la fecha no existe un tratamiento eficaz para el mismo. La reciente demostración de la falta de respuesta clínica a la reversión farmacológica del espasmo arterial a consecuencia de HSA ha obligado un replanteo de los fundamentos fisiopatológicos de los déficits neurológicos isquémicos tardíos (“delayed ischemic neurologic déficit”, DIND) a consecuencia de HSA, los cuales se creían en relación al espasmo arterial observado en pacientes con HSA. Desde la demostración de hallazgos electrocorticográficos de depresión cortical propagada (“cortical spreading depression”, CSD) en pacientes con HSA, un interés creciente se ha despertado respecto del rol de estos fenómenos en la fisiopatologíade los DIND observados en pacientes con HSA. Cuando inducidas en un cerebro saludable, las CSD se asocian con un aumento del flujo sanguíneo cerebral, facilitando la entrega del cerebro de los sustratos energéticos necesarios. En un cerebro que ha sido lesionado, sin embargo, la CSD se asocia con una reducción en flujo sanguíneo cerebral, lo cual, en el contexto deun aumento de las necesidades de energía, conduce a la insuficiencia energética y la hipoxia, empeorando así el daño cerebral. Estas observaciones sugieren que el déficit de energía producida por la CSD es un factor clave en la patogénesis de los DINDobservados a consecuencia de HSA. Este resumen detalla características sobresalientes de las CSD y su potencial relevancia en la fisiopatología del vasoespasmo.

Cerebral vasospasm is the leading potentially treatable cause of mortality and disability in patients with aneurysmatic subarachnoid hemorrhage (SAH). However, to date there is no effective treatment for this entity. The recently demonstrated lack of clinical response to pharmacologic reversal of arterial spasm as a result of SAH has spurred a reassessment of the pathophysiological concepts on delayed ischemic neurologic deficits (DIND) that follow SAH, which were long believed the effect of the arterial spasm observed in patients with SAH. Since the discovery of electrocorticographic cortical spreading depressions (CSD) in patients with SAH, increasing interest has been shown on the role of these phenomena in the pathophysiology of DIND observed in patients with HSA. When induced in a healthy brain, CSD are associated with an increase in cerebral blood flow by facilitating the delivery of the necessary energy substrates. In a brain that has been injured, however, CSD are associated with a reduction in cerebral blood flow, which, in the context of increased energy requirements leads to energy shortage and hypoxia, thus worsening brain damage. These observations suggest that the energetic deficit produced by the CSD is a key factor inthe pathogenesis of DIND observed as a result of HSA. This review details striking characteristics of CSD and their potential relevance in the pathophysiology of vasospasm.

Hypervolemic Versus Normovolemic Therapy in Patients with Ruptured Cerebral Aneurysm

BACKGROUND: Postoperative triple H therapy is regarded as a mainstay for prophylaxis and treatment of delayed ischemic neurologic deficit (DIND) after subarachnoid hemorrhage (SAH). However, there are doubts about its effectiveness. This study was performed to assess hypervolemic dynamic fluid therapy in patients with ruptured cerebral aneurysms. METHODS: The authors retrospectively studied a total of 393 patients with ruptured cerebral aneurysms, consisting of early surgery with or without intraoperative ventriculostomy during a recent 5 year period (July 1998~June 2003). Hypervolemic dynamic fluid therapy was initiated postoperatively in patients with DIND. Since January 2001, however, patients were maintained in normovolemia and normotension, and when DIND had manifested, low molecular weight dextran was only added. The incidence of DIND and outcome according to Glasgow Outcome Scale at 6 months of the normovolemic group were compared with the hypervolemic group. All patients were followed for at least 14 days after the admission including clinical assessment, TCD recording, CT scanning, CVP measurements, and nimodipine infusion. RESULTS: Subjects in the two treatment groups were similar with regard to age, sex, Fisher grade, Hunt-Hess grade, aneurysm location, and aneurysm size. No differences were found between the two groups regarding the incidence of DIND (29/182: 15.9% vs 29/211: 13.7%). Surgical outcome in the normovolemic group (good, 171/211: 81.0%) was comparable to the hypervolemic group (good, 154/182: 84.6%). CONCLUSIONS: Although careful fluid management to avoid hypovolemia may reduce the risk of DIND after SAH, prophylactic hypervolemic dynamic fluid therapy is unlikely to confer an additional benefit.

Clinical Analysis of Factors Influencing the Development of Delayed Ischemic Neurologic Deficit after Aneurysm Surgery

OBJECTIVE: This study shows the factors influencing the development of postoperative delayed ischemic neurologic deficit. METHODS: The authors analyzed 120 patients had performed aneurysmal neck clipping. Eleven variables were examined as to relationship to delayed ischemic neurologic deficit and classified as non- surgical and surgical variables. Data were analyzed by the univariate analysis and significant variables were entered into multiple logistic regression model in order to draw out Odds ratio. RESULTS: Delayed ischemic neurologic deficit after aneurysm surgery developed in 23 patients(19.2%). Significant non-surgical variables were clinical grade at admission(p=0.032), CT grade(p=0.005), and degree of preoperative angiographic vasospasm. Surgical variables were timing of surgery, brain retraction time, and duration of temporary clip application. The application time of temporary clip was significant (p=0.032) in development of delayed ischemic neurologic deficit. However, in multiple logistic regression analysis, duration of temporary clip application was excluded. With the clinical grade I - II and the CT grade I - II as the reference, the Odds ratio were 2.358(95% CI 0.87-6.37) and 4.041(95% CI 1.06-15.37), respectively. CONCLUSION: Delayed ischemic neurologic deficit after aneurysm surgery developed in poor clinical grade and high CT grade with high risk. The effect of surgery on the development of post-operative vasospasm was not significant.

Aneurysm Surgery Influences the Development of Delayed Ischemic Neurologic Deficit

The authors recently reported that over the years, the outcome of aneurysm surgery improved, and that surgical complications importantly affected this change. The present study was conducted to determine whether the incidence of symptomatic vasospasm in fact changed during the period under review, and the factors contributing to any changes. Between 1990 and 1995, 219 Hunt-Hess grade I to III patients with ruptured intracranial aneurysm underwent surgery within 3 days of subarachnoid hemorrhage ; all operations were performed by the same surgeon. Age, Hunt-Hess grade on admission, Fisher grade, hypertension, and hydrocephalus were analyzed to determine which factors were significant for syptomatic vasospasm, and for the periods 1990 to 1993, and 1994 to 1995, the distribution of each significant factor was then examined. Syptomatic vasospasm decreased significantly (p<0.05), but was seen in 28 of 124 patients(22.6%) treated beween 1990 and 1993 and 11 of 95(11.6%) treated between 1994 and 1995 ; no significant reduction of syptomatic vasospasm as a cause of mortality and morbidity (irreversible vasospasm) was seen, however, Fisher grade(p<0.05) and Hunt-Hess grade(p<0.05) significantly contributed to the development of symptomatic vasospasm, though the distribution of these two biologically significant factors was not statistically different. The question of whether or not surgery aggravates symptomatic vasospasm is controversial, and symptomatic vasospasm is, in addition, still an ill-defined disease entity. Except for the occurrence of fewer surgical complication and the fact that the incidence of reversible symptomatic vasospasm was less during the second period of treatment, no differences were found in the distribution of factors which significantly influenced symptomatic vasospasm, and this suggests that surgery affects the development of reversible symptomatic vasospasm. On the basis of increased risk of cerebral ischemia associated with surgery in vulnerable ischemic brain resulting from subarachnoid hemorrhage, the use of the term 'delayed ischemic neurologic deficit' after such hemorrhage appears to be more suitable than 'symptomatic vasospasm'.