Chemical Angioplasty with Nitroglycerin for Vasospasm after Subarachnoid Hemorrhage: Case Series and Review

Introduction Vasospasm is a common and potentially devastating complication in patients with subarachnoid hemorrhage, causing high morbidity and mortality. There is no effective and consistent way to prevent or treat cerebral vasospasm capable of altering the morbidity and mortality of this complication. Animal and human studies have attempted to show improvement in aneurysmal vasospasm. Some sought their prevention; others, the treatment of already installed vasospasm. Some achieved only angiographic improvement without clinical correlation, others achieved both, but with ephemeral duration or at the expense of very harmful associated effects. Endovascular techniques allow immediate and aggressive treatment of cerebral vasospasm and include methods such as mechanical and chemical angioplasty. These methods have risks and benefits. Objectives To analyze the results of chemical angioplasty using nitroglycerin (GTN). In addition, to performa comprehensive review and analysis of aneurysmal vasospasm. Methods We describe our series of 77 patients treated for 8 years with angioplasty for vasospasm, either mechanical (with balloon), chemical (with GTN) or both. Results Eleven patients received only balloon; 37 received only GTN; 29 received both. Forty-four patients (70.1%) evolved with delayed cerebral ischemia and 19 died (mortality of 24.7%). Two deaths were causally related to the rupture of the vessel by the balloon. The only predictors of poor outcome were the need for external ventricular drainage in the first hours of admission, and isolated mechanical angioplasty. Conclusions Balloon angioplasty has excellent results, but it is restricted to proximal vessels and is not without complications. Chemical angioplasty using nitroglycerin has reasonable but short-lived results and further research is needed about it. It is restricted to vasospasm angioplasties only in hospitals, like ours, where better and more potent vasodilator agents are not available.

Fatal reversible cerebral vasoconstriction syndrome: A systematic review of case series and case reports.

OBJECTIVE: To describe patient characteristics, radiological findings and the clinical course of adults with fatal reversible cerebral vasoconstriction syndrome (RCVS). METHODS: A systematic literature search from January 1, 2000, until December 31, 2018, was performed using PubMed, EMBASE, Scopus, Cochrane reviews, LILACS and Scielo. Studies reporting RCVS in adult patients with fatal outcomes were included. RESULTS: 430 studies were initially identified, 179 full-text articles were reviewed, and 9 publications describing 12 subjects were included. The vast majority of the reports were from the U.S. Most of the female cases occurred during postpartum. All patients had a headache on initial presentation, although only 42% had thunderclap headache. A CT scan was performed on 67% of the patients. Imaging results were diverse, with a tendency toward cerebral hemorrhage followed by mixed cases. The main course of treatment included steroids (58% of the patients), with only 42% receiving nimodipine. The time to death ranged from 4 to 14 days, with a median of 9.2 days (SD ±â€¯3.2). CONCLUSION: We found that the majority of fatal cases reported in the literature are most likely related to postpartum angiopathy. We established a tendency in the onset of brain hemorrhage and the combination of infarction and brain hemorrhage. We described various markers for poor prognosis, including focal signs, the presence of hemorrhage and infarct in the first diagnostic image obtained and the need for invasive interventions. The majority of fatal cases in our report occurred in women, with over half of those cases during the puerperium period.

Taurine and aneurysmal subarachnoid hemorrhage prognosis.

Despite its beneficial effects for the cardiovascular system, taurine remains a controversial substance. Taurine increases cardiac muscle strength and prevents arrhythmias, but its benefits go beyond this. Determining taurine levels may become an issue of life or death. In aneurysmal subarachnoid hemorrhage, taurine may be a warning signal informing of the risk of death in a patient. High plasma taurine levels may identify those patients at a high risk for death or a vegetative state at discharge from the hospital; thus, taurine may be a vital marker for the prognosis of this disorder. This is even more relevant considering that the result occurred in patients with a good neurological grade at admission that would usually receive a good prognosis but, despite this, one out of four died or remained in a vegetative state. Maybe taurine is key to explain this apparent paradox.

Descripción de los cambios en la velocidad media de flujo sanguíneo cerebral en posición supino y sedente, en pacientes con hemorragia subaracnoidea aneurismática con vasoespasmo asintomático o sin vasoespasmo: Serie de casos / Changes in cerebral blood flow velocity in supine and sitting position in patients with aneurysmal subarachnoid hemorrhage

Background: Early mobilization in intensive care units (ICU) provides respiratory, neurological and cardiovascular benefits in hospitalized patients. However, the orthostatic effects of changing from a supine to a sitting position may interfere with cerebral hemodynamics of patients with aneurysmal subarachnoid hemorrhage (aSAH). Aim: To describe the changes in mean cerebral blood flow velocity (MCBFV) in supine and sitting position, in adult patients with aSAH, with asymptomatic vasospasm (AVS) or without vasospasm (VS) at a neurosurgical ICU. Material and Methods: Descriptive case series study in 21 patients with aSAH, both with and without VS. They were positioned in a supine 30° position and then seated at the edge of bed for six minutes. MCBFV was measured by transcranial Doppler (TCD), and hemodynamic variables in both positions were registered. After this basal assessment and for 21 days after the episode of SAH, patients were seated once a day and signs of VS were recorded. Results: No significant changes in MCBFV or hemodynamic variables were detected during position changes, except for an increase in heart rate in the sitting position. No patient with AVS at the onset, had symptomatic VS during the 21 days of follow up when patients were seated. Among patients with a normal MCBFV at baseline, five patients (24%) had VS at a mean of three days after the first time that they were seated on the edge of bed. Conclusions: Sitting patients at the edge of the bed is a safe mobilization alternative for patients who suffered aSAH who did not have VS or had AVS.

Erythropoietin in vasospasm. From bench to bedside? / Eritropoietina no vasoespasmo. Da bancada do laboratório para a beira do leito?

Aneurysmal subarachnoid haemorrhage is one of the most deleterious acute neurological diseases. The cerebral ischemia secondary to arterial vasospasm occurring after aneurysmal subarachnoid haemorrhage is still responsible for the considerable morbidity and mortality in these patients. Besides the knowledge of basic mechanisms of cerebral vasoespasm following aneurysmal subarachnoid haemorrhage, the prophylaxis and treatment of this pathology however still remain suboptimal. There issome evidence that acute erythropoietin treatment may reduce the severity of cerebral vasospasm and eventually improve outcome in aneurysmal subarachnoid haemorrhage patients. There are underlying mechanisms extend far beyond erythropoiesis: like enhancing neurogenesis, decreasing inflammation and apoptosis inhibition. In this review the authors describe many of the biologic effects, especially experimental studies and clinical studies that reported why the erythropoietin could be beneficial topatients with aneurysmal subarachnoid haemorrhage.

A hemorragia subaracnóidea é uma das doenças neurológicas agudas mais graves. A isquemia cerebral secundária ao vasoespasmo arterial após a hemorragia ainda é responsável por considerável morbidade e mortalidade nesses pacientes. Ao lado do conhecimento dos mecanismos básicos do vasoespasmo na hemorragia subaracnóidea, a profilaxia e o tratamento dessa entidade ainda são insuficientes. Há evidências de que o uso da eritropoietina na fase aguda pode reduzir a gravidade do vasoespasmo e,eventualmente, melhorar o prognóstico desses pacientes. Há mecanismos de ação da eritropoietina que vão além da eritropoiese como neurogênese, redução da inflamação e inibição da apoptose. Nesta revisão, os autores elucidam inúmeros efeitos biológicos, principalmente aqueles demonstrados nos estudos experimentais e clínicos que descrevem por que a eritropoietina pode ser benéfica em pacientes com hemorragia subaracnóidea.

[Changes in cerebral blood flow velocity in supine and sitting position in patients with aneurysmal subarachnoid hemorrhage]. / Descripción de los cambios en la velocidad media de flujo sanguíneo cerebral en posición supino y sedente, en pacientes con hemorragia subaracnoidea aneurismática con vasoespasmo asintomático o sin vasoespasmo. Serie de casos.

BACKGROUND: Early mobilization in intensive care units (ICU) provides respiratory, neurological and cardiovascular benefits in hospitalized patients. However, the orthostatic effects of changing from a supine to a sitting position may interfere with cerebral hemodynamics of patients with aneurysmal subarachnoid hemorrhage (aSAH). AIM: To describe the changes in mean cerebral blood flow velocity (MCBFV) in supine and sitting position, in adult patients with aSAH, with asymptomatic vasospasm (AVS) or without vasospasm (VS) at a neurosurgical ICU. MATERIAL AND METHODS: Descriptive case series study in 21 patients with aSAH, both with and without VS. They were positioned in a supine 30° position and then seated at the edge of bed for six minutes. MCBFV was measured by transcranial Doppler (TCD), and hemodynamic variables in both positions were registered. After this basal assessment and for 21 days after the episode of SAH, patients were seated once a day and signs of VS were recorded. RESULTS: No significant changes in MCBFV or hemodynamic variables were detected during position changes, except for an increase in heart rate in the sitting position. No patient with AVS at the onset, had symptomatic VS during the 21 days of follow up when patients were seated. Among patients with a normal MCBFV at baseline, five patients (24%) had VS at a mean of three days after the first time that they were seated on the edge of bed. CONCLUSIONS: Sitting patients at the edge of the bed is a safe mobilization alternative for patients who suffered aSAH who did not have VS or had AVS.

Fisher revised scale for assessment of prognosis in patients with subarachnoid hemorrhage / Avaliação prognóstica com escala de Fisher modificada em pacientes com hemorragia subaracnóidea

The Fisher revised scale (FRS) presents an alternative for evaluating patients with subarachnoid hemorrhage (SAH). In this study, we compared the prognosis of patients with SAH and vasospasms (VSP). METHOD: This was a prospective study on patients with a diagnosis of aneurysmal SAH, 72 hours after the initial event. Sequential neurological examinations and Hunt and Hess (HaH) score were performed on the 1st, 7th and 14th days. Transcranial Doppler was used to assess vasospasms. RESULTS: Out of the 24 patients studied, ten (41.66 percent) presented a delayed neurological deficit, such as diminished consciousness, decreased HaH score or death. The single patient classified as FS-1 did not have any delayed neurological deficit, while such deficits evolved in one patient out of five with FS-2 (20 percent); two out of seven with FS-3 (28.57 percent) and seven out of 11 with FS-4 (63.63 percent). CONCLUSION: Level three of the FS and FRS seemed to be compatible with regard to predicting the likelihood of progression to severe VSP.

A escala revisada de Fisher (FRS) representa uma alternativa para avaliação de pacientes com hemorragia subaracnóidea (HSA). Neste estudo comparamos a evolução prognóstica referente ao vasoespasmo (VSP) nos pacientes com HSA. MÉTODO: Estudo prospectivo em pacientes com diagnóstico de HSA, com 72 horas após o evento inicial. Escala de Hunt e Hess (HeH) foi realizada no 1º, 7º, 14º dia. Utilizamos Doppler transcraniano para avaliação de VSP. RESULTADOS: Dos 24 pacientes estudados dez (41,66 por cento) tiveram déficit neurológico tardio (DNT), como diminuição da consciência, grau de HeH ou morte. Um paciente de cinco classificados como FS-2 (20 por cento), dois de sete pacientes com FS-3 (28,57 por cento) e sete de 11 pacientes com FS-4 (63,63 por cento) evoluíram com DNT. Para o FRS não encontramos piora neurológica precoce no paciente com FRS-0. CONCLUSÃO: O nível três da FS e FRS parecem ser comparáveis, quando se trata de predizer a probabilidade de progressão para VSP grave.

[Symptomatic vasospasm. Clinical manifestations]. / Vasoepasmo sintomático. Caracterización clínica.

INTRODUCTION: Symptomatic vasospasm in the setting of a subarachnoid hemorrhage is a complication of difficult diagnosis in some clinical situations. Objectives. Describe the clinical characteristics of cerebral vasospasm demonstrated by neurovascular studies in patients with ruptured saccular aneurysm. PATIENTS AND METHODS: 19 consecutive patients with symptomatic vasospasm, evaluated with TCD and any variant of neurovascular study with contrast injection. All these cases were in degrees between 1 and 3 of the World Federation of Neurological Surgeons Scale. RESULTS: The cognitive and behavioral manifestations were the most frequent (53%), followed by neurological focal deficits (26%). Clinical vasospasm occurred most frequently between day 9 and 10. Vasospasm is predominant in the arteries of the anterior circulation. The high mortality (42%) and the antecedent of arterial hypertension characterized the group with symptomatic vasospasm. There was no statistical relationship between the result of the scale of Fisher and the symptomatic vasospasm. All the TCD parameters had statistical significance. CONCLUSIONS: The clinical manifestations more frequently associated with symptomatic vasospasm were cognitive and behavioral. This group of patients is characterized by a high mortality. The TCD is a test of great value to predict cerebral ischemia due to vasospasm.

Fisher revised scale for assessment of prognosis in patients with subarachnoid hemorrhage.

UNLABELLED: The Fisher revised scale (FRS) presents an alternative for evaluating patients with subarachnoid hemorrhage (SAH). In this study, we compared the prognosis of patients with SAH and vasospasms (VSP). METHOD: This was a prospective study on patients with a diagnosis of aneurysmal SAH, 72 hours after the initial event. Sequential neurological examinations and Hunt and Hess (HaH) score were performed on the 1(st), 7(th) and 14(th) days. Transcranial Doppler was used to assess vasospasms. RESULTS: Out of the 24 patients studied, ten (41.66%) presented a delayed neurological deficit, such as diminished consciousness, decreased HaH score or death. The single patient classified as FS-1 did not have any delayed neurological deficit, while such deficits evolved in one patient out of five with FS-2 (20%); two out of seven with FS-3 (28.57%) and seven out of 11 with FS-4 (63.63%). CONCLUSION: Level three of the FS and FRS seemed to be compatible with regard to predicting the likelihood of progression to severe VSP.

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.

Hemodinâmica do vasoespasmo: [revisão] / Cerebral hemodynamic alterations due to vasospasm: [review]

Os autores descrevem as alterações hemodinâmicas encefálicas que ocorrem na vigência do vasoespasmo após a hemorragia subaracnoidea por aneurismas. O conhecimento dessas alterações facilita o entendimento das medidas terapêuticas.

The authors describe the hemodynamic encephalic alterations that occur during the vasospasm after aneurysmal subarachnoid hemorrhage. The knowledge of these alterations promotes better understanding of the therapeutic procedures.

Milrinone as a rescue therapy for symptomatic refractory cerebral vasospasm in aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Delayed ischemic neurological deficit associated to cerebral vasospasm is the most common cause of sequelae and death that follows the rupture of an aneurysm. The objective of this study was to evaluate the safety and efficacy of intra-arterial Milrinone in patients with symptomatic refractory cerebral vasospasm. PATIENTS AND METHOD: Eight patients diagnosed with aneurysmal subarachnoid hemorrhage who developed symptomatic cerebral vasospasm refractory to conventional medical therapy were enrolled. They received an intra-arterial infusion of Milrinone at a rate of 0.25 mg/min, with a total dose of 10-15 mg. Qualitative evaluation of angiographic response, neurological and systemic complications as well as functional outcome at 3 months were documented. RESULTS: All patients had a significant angiographic response. This was evidenced by a pre-treatment vessel stenosis greater than 70%, that improved to less than 50% after the intra-arterial Milrinone infusion. Three patients developed recurrent vasospasm that improved after a second intra-arterial Milrinone infusion. None of the patients developed neurologic or systemic complications attributed to the intervention. At 3 months follow-up all patients were alive and had a mean modified Rankin scale of 2 +/- 1 and a Barthel index of 83 +/- 10. CONCLUSION: Intra-arterial Milrinone infusion seems to be a safe and effective treatment for patients who develop refractory symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

Endothelin-1 levels in plasma and cerebrospinal fluid of patients with cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Plasma and cerebrospinal fluid (CSF) concentrations of endothelin-1 (ET-1) were measured in patients with subarachnoid hemorrhage (SAH) after aneurysmal rupture and compared with levels of ET-1 in volunteers. We analyze the relationship between levels of ET-1 in both CSF and plasma with the risk of developing cerebral vasospasm (CVS). METHODS: Cerebrospinal fluid and blood samples were collected from 30 selected patients after SAH and from 10 healthy volunteers who were used as control. All samples were stored at -70 degrees C and the levels of ET-1 in CSF and blood were measured by using enzyme-linked immunosorbent assay and Western blot. All patients were submitted to angiography to confirm vasospasm. RESULTS: From the 30 patients admitted at different days of SAH, 18 (60%) developed clinical CVS and 10 (33%) presented angiographic CVS. The levels of ET-1 in the CSF were significantly higher (P = .0001) in patients (1.618 +/- 1.05 fmol/mL) than in controls (0.365 +/- 0.328 fmol/mL). There was statistical difference (P < .05) in CSF levels of ET-1 between each group of the Hunt-Hess scale and controls. The mean plasma concentration of ET-1 was similar (P > .05) in the control group (1.531 +/- 0.753 fmol/mL) and in patients with SAH (1.920 +/- 1.15 fmol/mL). CONCLUSIONS: These findings indicate that a significant rise in ET-1 levels in the CSF, but not in the plasma, occurs in patients who develop CVS after SAH. Our observation suggests that ET-1 might be involved in the pathogenesis of SAH-associated CVS.

Cerebral vasospasm and headache during sexual intercourse and masturbatory orgasms.

BACKGROUND: The pathophysiology of the explosive type of headache associated with sexual activity is not completely understood. Five reported cases of patients with thunderclap headache, precipitated by sexual activity, in association with concomitant cerebral arterial narrowing, were found in the literature. METHODS: A 44-year-old woman with both coital and masturbatory headaches during orgasm associated with segmental reversible cerebral artery vasospasm was investigated. Cerebral anatomy and eventual spasm was documented by magnetic resonance imaging or digital angiography before, during, and after resolution of the orgasmic headache-vasospasm clinical manifestation. CONCLUSION: Findings of cerebral arterial narrowing, presented by some patients shortly after orgasmic headache attacks, support the hypothesis that segmental vasospasm may exert a role in the pathogenesis of this uncommon type of headache. The literature is reviewed, and possible mechanisms underlying the development of orgasmic headache are discussed.

Vasoespasmo cerebral en la hemorragia subaracnoide aneurismática: bases fisiopatológicas y tratamiento / Cerebral vasospasm during aneurysmal subarachnoid hemorrhage: physiopathological bases and treatment

El vasoespasmo cerebral es una complicación devastadora de la hemorragia subaracnoídea aneurismática, a pesar de la gran cantidad de investigaciones experimentales y clínicas que se han llevado a cabo en un esfuerzo para encontrar el camino para prevenir esta complicación. La primera parte de esta revisión delinea los estudios experimentales más importantes y recientes que han contribuido a la base en la comprensión de los mecanismos que llevan al vasoespasmo cerebral. La segunda parte trata sobre los intentos terapéuticos, basados en este conocimiento fisiopatológico. La prevención y tratamiento del vasoespasmo o estrechamiento de las grandes arterias de la base del cerebro, y de la prevención y tratamiento de la consecuencia de este estrechamiento arterial, el déficit isquémico retrasado, con los tratamientos médicos más aceptados. (AU)