Risk factors for the development of post-traumatic cerebral vasospasm.

BACKGROUND: Post-traumatic vasospasm is a well-recognized sequela of head injury. The risk factors associated with post-traumatic vasospasm have not been well defined. We studied 119 consecutive patients with head injury to determine the risk factors for post-traumatic vasospasm. METHODS: Twenty-nine (27.1%) patients were excluded from the study because of poor insonation (n = 12) or a hospital stay of less than 72 hours (n = 17). Seventy (77.8%) of 90 patients suffered severe head injury. Sixteen (17.8%) patients sustained moderate head injury and four (4.4%) patients sustained mild head injury. All patients were monitored with transcranial Doppler (TCD) ultrasonography daily. RESULTS: Post-traumatic vasospasm was detected in 32 (35.6%) of 90 patients. Among these patients, 29 (90.6%) had severe head injury, and three (9.4%) had moderate head injury. None of the patients with mild head injury suffered post-traumatic vasospasm. In most cases, the onset of post-traumatic vasospasm began on the fifth day and lasted 1 to 9 days. In 8 (25%) patients, post-traumatic vasospasm began within the first three days of the head injury. Among 32 patients with post-traumatic vasospasm, 10 (31.2%) patients had mild vasospasm, 20 (65.5%) had moderate vasospasm, and 2 (6.3%) had severe post-traumatic vasospasm. Clinical deterioration was documented in two (2.5%) patients. CONCLUSIONS: Development of post-traumatic vasospasm correlated only with severe subarachnoid hemorrhage on initial computed tomographic scan. There was an increased incidence of post-traumatic vasospasm in patients with epidural hematomas, subdural hematomas, and intracerebral hemorrhages. The Glasgow Coma Scale (GCS) score on admission was inversely related to the development of post-traumatic vasospasm. In most cases, the period of vasospasm was short and clinical deterioration was rare. Probably, two varieties of post-traumatic vasospasm exist, one that lasts a shorter time and does not correlate with the presence of SAH, and a second that correlates with the presence of SAH, lasts longer, and resembles aneurysmal vasospasm.

Pure sylvian fissure arteriovenous malformations.

OBJECT: Pure sylvian fissure arteriovenous malformations (AVMs) are vascular malformations confined to the sylvian fissure without parenchymal involvement. Because the branches of the middle cerebral artery are arteries of passage and the margins between the AVM and the insula cortex may be ill defined, many surgeons regard pure sylvian fissure AVMs as inoperable. The authors reviewed their surgical experience with eight patients harboring pure sylvian fissure AVMs to determine the incidence of operative morbidity. METHODS: All eight patients experienced seizures, five (63%) had headaches, and three (38%) experienced hemorrhages. Preoperatively, six patients (75%) were normal neurologically and two (25%) had neurological deficits. Five (63%) of eight sylvian fissure AVMs were located in the dominant hemisphere. The size of the nidus ranged from 6 to 27 cm3 (mean 14 cm3). Complete removal of the AVM was documented by postoperative angiography in every case. Seizures were reduced or eliminated and headaches were relieved in all affected patients. Transient neurological deficits, which included aphasia, short-term memory loss, and hemiparesis, occurred in four patients (50%). Within 3 months, all patients were functioning independently with no new neurological deficits. The status of two patients who had had preoperative neurological deficits improved postoperatively. Neuropsychological testing showed no new cognitive deficits. CONCLUSIONS: With appreciation for transient instances of postoperative morbidity, the outcome was excellent in all patients. The authors thus advocate microsurgery as the primary treatment for pure sylvian fissure AVMs.

Endoscopic treatment of symptomatic septum pellucidum cysts: with some preliminary observations on the ultrastructure of the cyst wall: two technical case reports.

OBJECTIVE AND IMPORTANCE: We describe two patients with symptomatic septum pellucidum cysts managed by endoscopic fenestration. In each case, tissue from the cyst wall was studied to define the origin of the cyst wall and fluid. CLINICAL PRESENTATION: The patients, a 6-year-old boy and a 42-year-old man, each presented with headaches and a syncopal episode. Imaging studies demonstrated large septum pellucidum cysts with obstruction of the foramina of Monro. INTERVENTION: The patients underwent endoscopic transventricular cyst fenestration with a 4-mm steerable fiberscope. The fenestrations were created to allow communication with the right and left lateral ventricles. In one patient, adhesions between the cyst wall and the foramen of Monro were lysed with endoscopic monopolar cautery. Tissue from the cyst walls was removed for examination by electron microscopy. Postoperatively, the headaches and syncopal episodes resolved in both patients. CONCLUSION: Endoscopic fenestration of symptomatic septum pellucidum cysts produces immediate relief of the mass effect of the cyst and resolution of associated symptoms. Cannulation of the lateral ventricle before cyst fenestration prevents inadvertent injury to the fornices, thalamus, internal capsule, caudate nucleus, and septal and thalamostriate veins. The endoscopic approach allows the surgeon to ensure communication within the ventricular system, thus avoiding placement of a shunt. Preliminary ultrastructural analysis indicates that the cyst walls derive from the septum pellucidum rather than the choroid plexus or arachnoid. The cellular machinery necessary for fluid secretion was identified in some specimens.

Bloody cerebrospinal fluid alters contractility of cultured arteries.

The pathogenesis of cerebral vasospasm that follows aneurysmal subarachnoid hemorrhage (SAH) is poorly understood. Multiple methods have been used to clarify the mechanism of spasmogen-induced vasospasm, however, each method has its own limitations. Cultured cells lose their phenotype and inter-cellular interactions, and animal models are expensive and can be used only in some established centers. Isolated cerebral arteries have been used extensively to study the contractility by transient exposure to spasmogens that, however, can hardly represent cerebral vasospasm that occurs 2-4 days after SAH. In this study, we cultured arteries with bloody cerebrospinal fluid (CSF) from patients of cerebral vasospasm and studied the contractility of the arteries 1, 3 and 4 days later. This method preserves artery wall structure, prolongs exposure of artery to bloody CSF, and is simple and inexpensive. Cultured rat aorta showed enhanced contractile response to 5-HT (p < 0.001) but reduced response to KCl (p < 0.05) 4 days after culturing with bloody CSF. We concluded that the contractility of arteries was modified by prolonged incubation with bloody CSF. Our observations in this study could be important and may explain some aspects of pathogenesis of cerebral vasospasm.

Oxyhemoglobin-induced apoptosis in cultured endothelial cells.

OBJECT: Oxyhemoglobin (OxyHb) is one of the most important spasmogens for cerebral vasospasm that follows aneurysmal subarachnoid hemorrhage. The cytotoxic effect of OxyHb has been documented in endothelial and smooth-muscle cells; however, the pattern of cell death--necrosis or apoptosis--as the final stage of cell damage has not been demonstrated. This study was undertaken to determine if OxyHb induces apoptotic changes in cultured bovine aortic endothelial cells. METHODS: Confluent bovine aortic endothelial cells were treated with OxyHb in a concentration- and time-dependent manner. Cell density was assayed by counting the number of cells that attached to culture dishes after exposure to OxyHb. To identify apoptotic changes, the investigators used three specific methods: DNA fragmentation (electrophoreses), the apoptotic body (transmission electron microscopy), and cleavage of poly (adenosine diphosphate ribose) polymerase (PARP [Western blotting]). CONCLUSIONS: Oxyhemoglobin decreased cell density in a concentration- and time-dependent manner. Analysis of DNA showed a pattern of internucleosomal cleavage characteristic of apoptosis (DNA ladder). Transmission electron microscopy demonstrated condensation of nuclei and apoptotic bodies in OxyHb-treated endothelial cells. Western blotting with the PARP antibody revealed that the 116-kD PARP was cleaved to the 85-kD apoptosis-related fragment. These results for the first time demonstrated that the OxyHb induces apoptosis in cultured endothelial cells.

Mitogen-activated protein kinase mediation of hemolysate-induced contraction in rabbit basilar artery.

OBJECT: Mitogen-activated protein kinase (MAPK) is an important signaling factor in vascular proliferation and contraction, which are the two features of cerebral vasospasm that follow subarachnoid hemorrhage. The authors studied the possible involvement of MAPK in hemolysate-induced signal transduction and contraction in rabbit basilar artery (BA). METHODS: Isometric tension was used to record the contractile response of rabbit BA to hemolysate, and Western blots were obtained using antibodies for MAPK. The following results are reported. 1) Hemolysate produced a concentration-dependent contraction of rabbit BA; however, preincubation of arteries with the MAPK kinase (MEK) inhibitor PD-98059 markedly reduced this contraction. The administration of PD-98059 also relaxed, in a concentration-dependent fashion, the sustained contraction induced by 10% hemolysate. 2) The Janus tyrosine kinase 2 inhibitor AG-490, preincubated with arterial rings, reduced the contractile response to hemolysate but failed to relax the sustained contraction induced by this agent. The Src-tyrosine kinase inhibitor damnacanthal and the phosphatidylinositol 3-kinase inhibitor wortmannin failed to reduce hemolysate-induced contraction. 3) Hemolysate produced a time-dependent elevation of MAPK immunoreactivity as seen on Western blots of rabbit BA. The MAPK was enhanced 1 minute after hemolysate exposure and the effect reached maximum levels at 5 minutes. The immunoreactivity of MAPK decayed slowly over time, but the level of this kinase was still higher than the basal level, even at 2 hours after exposure to hemolysate. Preincubation of arteries with the MEK inhibitor PD-98059 abolished the effect of hemolysate on MAPK immunoreactivity. CONCLUSIONS: Hemolysate produced contraction of rabbit BA, possibly by activation of MAPK, and therefore MAPK inhibitors may be useful in the treatment of cerebral vasospasm.

Morphological changes after percutaneous transluminal angioplasty.

BACKGROUND: Percutaneous transluminal angioplasty (PTA) dilates constricted arteries at the circle of Willis to reverse cerebral ischemia caused by cerebral vasospasm. Although 90% of the patients show angiographic improvement after PTA, only 70% show clinical improvement. Why some patients do not improve after PTA is unknown. We report on a 48-year-old woman who failed to improve after PTA and died from aneurysm rerupture. Pathologic studies were performed to determine why PTA failed to reverse the symptoms of cerebral ischemia. METHODS: The arteries of the brain were studied by light microscopy using Gomori's trichrome stain. The arteries were also studied by scanning and transmission electron microscopy. RESULTS: The arteries that were dilated with PTA showed compression of the connective tissue, stretching of the internal elastic lamina, and a combination of compression and stretching of the smooth muscle. The small arteries and arterioles that had been treated with an infusion of intraarterial papaverine were constricted with a thickened intimal layer. CONCLUSION: The persistence of cerebral vasospasm in small and perforating arteries may contribute to the failure of cerebral ischemia to reverse after PTA.

Spontaneous dural sinus thrombosis in children.

The clinical course of spontaneous dural sinus thrombosis in children varies from indolent to fulminant. Although many different etiologies for the development of dural sinus thrombosis have been described, a full recovery can be anticipated in most children following rehydration and the administration of systemic antibiotics. Steroids, systemic anticoagulation and intrasinus thrombolysis may be beneficial in selected patients, although the efficacy of these therapies has not been established prospectively in children. We reviewed 12 pediatric patients with spontaneous dural sinus thrombosis (1978-1998) to determine the etiology, clinical course and best treatment options. In the absence of a hypercoagulable state, pediatric patients generally recover well with rehydration and antibiotics and do not require anticoagulation.

Transluminal angioplasty and intra-arterial papaverine for the treatment of cerebral vasospasm after ruptured arteriovenous malformations.

BACKGROUND: This is the first report on the use of intra-arterial papaverine and percutaneous transluminal angioplasty in two patients with severe, symptomatic cerebral vasospasm who suffered ruptured arteriovenous malformations (AVMs). CASE DESCRIPTIONS: The source of hemorrhage was a venous aneurysm in the first case and a pedicular aneurysm of the distal posterior inferior cerebellar artery in the second case. In both cases, the AVMs were located in the superior vermis and there was minimal subarachnoid hemorrhage. The first patient underwent removal of the AVM before the period of cerebral vasospasm and the second patient underwent removal of the AVM after the cerebral vasospasm had resolved. The outcome was excellent in the first patient and poor in the second patient. CONCLUSION: Arteriovenous malformation with ruptured aneurysms may be at high risk for cerebral vasospasm even when there is minimal subarachnoid hemorrhage. We recommend early treatment of AVMs with ruptured pedicular, intranidal, or venous aneurysms to avoid rebleeding and to allow for aggressive treatment of cerebral vasospasm. The management of cerebral vasospasm after AVM rupture is discussed.

Combined interventional and surgical treatment of arteriovenous malformations.

This article describes the combined interventional and surgical treatment of arteriovenous malformations. The development of embolization as an adjunct to microsurgical resection of arteriovenous malformations has expanded the therapeutic armamentarium in the treatment of these lesions. Patient selection, indications, technical aspects as well as avoidance and treatment of complications with regard to endovascular embolization are discussed. Four individual cases are presented to show how embolization can be combined with microsurgery to achieve optimal treatment results.

Surgical management of deep-seated dural arteriovenous malformations.

The best treatment for deep-seated dural arteriovenous malformations (AVMs) remains controversial. Therapeutic options include transarterial and transvenous embolization, surgical excision of the dural nidus, ligation of draining veins, and stereotactically guided radiation treatment. The authors report on their experience with the application and technique of skull base surgical approaches for deep-seated dural AVMs. Their series includes six patients who were surgically treated for five tentorial dural AVMs and one inferior petrosal sinus dural AVM between 1991 and 1995. Three patients presented with progressive brainstem dysfunction, one had progressive myelopathy, and two suffered subarachnoid hemorrhage. Venous hypertension caused progressive neurological deterioration in four patients and ruptured venous aneurysms caused hemorrhage in two patients. Four of the five tentorial dural AVMs received bilateral arterial supply from the internal carotid arteries and external carotid arteries (ECAs). The dural AVM of the inferior petrosal sinus was fed from both vertebral arteries and ECAs. In this series, all dural AVMs drained into deep cerebral veins. Intra- and postoperative angiographic studies were used to document complete obliteration in each case. After surgery, three patients developed transient, delayed (24-72 hours) neurological worsening. One month postsurgery, all six patients showed improvement from their preoperative neurological function. Surgical resection of these deep-seated dural AVMs was accomplished by eliminating the arterial supply rather than ligating the draining veins to avoid aggravating the underlying venous hypertension. This study demonstrates an important role for skull base surgical approaches in the management of patients with deep-seated dural AVMs that have hemorrhaged, are not obliterated by embolization, and for which stereotactically guided radiation therapy is an unsuitable option.

Long-term results in direct carotid-cavernous fistulas after treatment with detachable balloons.

Transarterial embolization of direct carotid-cavernous fistulas (CCFs) using detachable balloons is the best initial option for occlusion of the fistula and preservation of the internal carotid artery. However, the long-term safety and efficacy of this treatment is unknown. The authors reviewed the long-term outcome of 87 patients with 88 direct CCFs occluded by detachable balloons. Clinical follow up was obtained in 48 (83%) of 58 patients treated with latex balloons (mean follow-up period 10 years, range 5.9-15.5 years) and 28 (97%) of 29 patients treated with silicone balloons (mean follow-up period 4 years, range 1-6.6 years). Two patients were treated with both balloon types. There were no late recurrent symptoms of cranial bruit, proptosis, chemosis, or arterialized conjunctiva in patients treated with either latex or silicone balloons. Diplopia improved in all patients; however, five patients required shortening of the lateral rectus muscle. Delayed ischemia occurred in three patients: one patient had a transient ischemic episode 5 years after treatment with latex balloons and two patients (85 and 90 years old) who had ruptured spontaneous intracavernous aneurysms suffered cerebral infarctions 6 weeks and 4 months, respectively, after treatment with silicone balloons. There were five deaths in the series unrelated to balloon treatment. These results show that after transarterial embolization of direct CCFs using either silicone or latex detachable balloons, the long-term risks are low for fistula recurrence, symptomatic foreign body reaction, symptomatic pseudoaneurysm formation, and cerebral ischemia.

Prevention of subarachnoid hemorrhage-induced cerebral vasospasm by oral administration of endothelin receptor antagonists.

The purpose of this study was to investigate the effectiveness of oral treatment with the endothelin (ET) A/B receptor antagonist Ro 47-0203, 4-tert-butyl-N-[6-(hydroxy- ethoxy)-5-(2-methoxy-phenoxy)-2'-bipyrimidin-4-yl]-benzenesulfonam ide (bosentan), and the ET A receptor antagonist 2-benzo[1,3]dioxol-5-yl-3-benzyl-4-(4-methoxy- phenyl)-4-oxo-but-2-enoic acid monosodium salt (PD155080), in the prevention of subarachnoid hemorrhage (SAH)-induced delayed cerebral vasospasm. Double hemorrhage in the rabbit constricted the basilar artery to 34% if control as determined by angiography. Oral bosentan and PD155080 administration after the initial SAH decreased the magnitude of constriction to 9% and 16% of control, respectively. Plasma and cerebrospinal fluid bosentan levels and plasma PD155808 levels were consistent with concentrations reported to inhibit ET-1 constriction of blood vessels in vitro. These results support the use of oral administration of ET A/B and ET A receptor antagonists as potential specific treatment for vasospasm resulting from SAH in humans.

Relaxation of subarachnoid hemorrhage-induced spasm of rabbit basilar artery by the K+ channel activator cromakalim.

BACKGROUND AND PURPOSE: Cerebral vasospasm resulting from subarachnoid hemorrhage (SAH) is refractory to most vasodilators. However, despite evidence that a mechanism underlying the vasospasm may be smooth muscle cell membrane depolarization resulting from decreased K+ conductance, the ability of K+ channel activators to relax the spasm has not been thoroughly investigated. The purpose of this study, therefore, was to investigate whether K+ channel activation selectively relaxes SAH-induced vasospasm. METHODS: Three days after SAH in the rabbit, relaxation of the basilar artery in response to the K+ channel activator cromakalim as well as to staurosporine (protein kinase C antagonist), forskolin (adenylate cyclase activator), and sodium nitroprusside (guanylate cyclase activator) was measured in situ with the use of a cranial window. Relaxation in response to these agents was also investigated in control vessels contracted with serotonin. Membrane potential of the smooth muscle cells of the basilar artery from SAH and control rabbit was measured in vitro with the use of intracellular microelectrodes. RESULTS: Cromakalim completely relaxed the SAH-induced spastic basilar artery, while staurosporine, forskolin, and sodium nitroprusside were significantly less efficacious. In contrast, sodium nitroprusside and forskolin were more efficacious relaxants in serotonin-contracted control vessels than in SAH vessels. The K+ channel blocker glyburide and high [K+] prevented cromakalim-induced relaxation. Glyburide did not inhibit forskolin-induced relaxation of serotonin-contracted control vessels. Cromakalim concentration-dependently repolarized spastic basilar artery smooth muscle cells, and the repolarization was prevented by glyburide. CONCLUSIONS: These results suggest that K+ channel activation selectively relaxes SAH-induced vasospasm. We speculate that the ability of K+ channel activators to selectively relax the spasm may be due, at least in part, to the underlying inhibition of K+ channels after SAH.

Immunohistochemical localization of endothelial nitric oxide synthase in vessels of the dura mater of the Sprague-Dawley rat.

Nitric oxide (NO) and the dura mater are implicated in the pathogenesis of vascular headache. Many studies have demonstrated the participation of NO in headache; however, few studies have identified NO in the dura mater. In this study, nine Sprague-Dawley rats were examined with immunohistochemistry using two different endothelial nitric oxide synthase (eNOS) monoclonal antibodies, H32 and ECNOS. eNOS was successfully localized to the endothelium of the middle meningeal artery. To the best of our knowledge, this is the first study to report NOS immunopositive endothelial cells in the blood vessels of the rat dura mater. The authors propose that NO plays an active role in dural vasodilation, contributing to the pathogenesis of vascular headache; in the future, NO inhibitors could serve as pharmacological agents to treat vascular headache.

Management strategies and surgical techniques for deep-seated supratentorial arteriovenous malformations.

The therapeutic options for arteriovenous malformations (AVMs) of the thalamus and the basal ganglia have expanded to include preoperative embolization, stereotactic radiation, and microsurgery. Adjuncts to surgery such as stereotactic guidance, electrophysiological monitoring, intraoperative ultrasound, intraoperative angiography, and induced hypotension have significantly reduced postoperative morbidity. We review the management and outcome of 65 consecutive patients who were treated for deep-seated supratentorial vascular malformations; 45 patients (69%) were treated surgically, 10 patients (15%) were treated conservatively, and 10 patients (15%) underwent radiosurgery. This retrospective study (1976-1993) includes 51 AVMs (78%), 14 cavernous angiomas (22%), and 10 associated vascular anomalies (15%). Initially, 59 (91%) of 65 patients presented with hemorrhage; 23 patients (39%) suffered recurrent hemorrhages. Malformations ranged in size from 1 to 7.5 cm (mean, 2.8 cm). AVMs were fed principally by the anterior and posterior choroidal, thalamoperforate, and lenticulostriate arteries. Venous drainage was uniform via the deep venous system. Among 39 patients who underwent surgery for AVMs, 26 (67%) improved, 7 (18%) remained unchanged, 5 (13%) worsened, and 1 (3%) died. Among six patients who underwent surgery for cavernous angiomas, four (66%) improved, one (17%) remained unchanged, and one (17%) worsened. Operative complications included transient neurological deficits in seven patients (16%), permanent neurological deficits in six patients (13%), and new bleeding from residual AVMs in four patients (9%). Among 10 patients treated conservatively, 3 (30%) had repeat hemorrhages, 2 (20%) had progressive neurological deficits, and 1 (10%) died.(ABSTRACT TRUNCATED AT 250 WORDS)

Endoscopic treatment of loculated hydrocephalus.

Loculated hydrocephalus remains a difficult neurosurgical problem and endoscopes designed to navigate through the ventricular system provide a new option for treatment. The authors review their experience, during the period March 1990 to June 1993, using a steerable fiberscope in 34 cases of loculated hydrocephalus to evaluate the efficacy of endoscopic cyst fenestration. The goals of treatment were to control hydrocephalus, simplify preexisting shunt systems, and reduce operative morbidity. Endoscopic cyst fenestrations reduced the shunt revision rate from 3.04 per year prior to endoscopy to 0.25 per year after the procedure, during a follow-up period ranging from 8 to 45 months, mean 26 months. However, eight patients (23.5%) required 14 repeat operations to control loculated hydrocephalus. After endoscopy, patients with multiloculated hydrocephalus had a nearly fivefold increased risk (relative risk 4.85) for shunt malfunction and more than a twofold increased risk (relative risk 2.43) for cyst recurrence versus patients with uniloculated hydrocephalus. Similarly, six (50%) of 12 patients shunted prior to endoscopy required a repeat endoscopic procedure (relative risk 5.56). Although repeat endoscopic procedures may be required to control hydrocephalus, endoscopic cyst fenestration avoided placement of a shunt in seven (33%) of 21 patients with uniloculated hydrocephalus. One patient, encountered early in the authors' experience, required a craniotomy for fenestration of multiple ventricular cysts. Endoscopic complications included cerebrospinal fluid leakage in one case and ventriculitis in another. The authors conclude that endoscopic treatment of loculated hydrocephalus is a safe, minimally invasive technique that should be considered as the initial treatment option.