Spinal manipulative therapy is an independent risk factor for vertebral artery dissection.

OBJECTIVE: To determine whether spinal manipulative therapy (SMT) is an independent risk factor for cervical artery dissection. METHODS: Using a nested case-control design, the authors reviewed all patients under age 60 with cervical arterial dissection (n = 151) and ischemic stroke or TIA from between 1995 and 2000 at two academic stroke centers. Controls (n = 306) were selected to match cases by sex and within age strata. Cases and controls were solicited by mail, and respondents were interviewed using a structured questionnaire. The medical records of interviewed patients were reviewed by two blinded neurologists to confirm that the patient had stroke or TIA and to determine whether there was evidence of arterial dissection. RESULTS: After interview and blinded chart review, 51 patients with dissection (mean age 41 +/- 10 years; 59% female) and 100 control patients (44 +/- 9 years; 58% female) were studied. In univariate analysis, patients with dissection were more likely to have had SMT within 30 days (14% vs 3%, p = 0.032), to have had neck or head pain preceding stroke or TIA (76% vs 40%, p < 0.001), and to be current consumers of alcohol (76% vs 57%, p = 0.021). In multivariate analysis, vertebral artery dissections were independently associated with SMT within 30 days (OR 6.62, 95% CI 1.4 to 30) and pain before stroke/TIA (OR 3.76, 95% CI 1.3 to 11). CONCLUSIONS: This case-controlled study of the influence of SMT and cervical arterial dissection shows that SMT is independently associated with vertebral arterial dissection, even after controlling for neck pain. Patients undergoing SMT should be consented for risk of stroke or vascular injury from the procedure. A significant increase in neck pain following spinal manipulative therapy warrants immediate medical evaluation.

Dural arteriovenous fistula associated with prothrombin gene mutation.

An association between dural arteriovenous fistula and cerebral sinus thrombosis is reported. It is clear in several cases that thrombosis precedes the development of the fistula while it is unclear that it occurs in every case. The authors report a case of a woman with sinus thrombosis and presence of prothrombin gene mutation who subsequently developed a large dural arteriovenous fistula. Various possible factors involved in the pathogenesis of a dural fistula are discussed, with emphasis on underlying thrombophilia and oral contraceptive use in this patient.

Treatment of unruptured cerebral aneurysms in California.

BACKGROUND AND PURPOSE: The impact of endovascular therapy on treatment outcomes of unruptured cerebral aneurysms has not been studied in a defined geographic area. METHODS: All primary diagnoses of unruptured aneurysms were retrieved from a statewide database of hospital discharges in California from January 1990 through December 1998. Admissions for initial treatment and all follow-up care were combined to reflect the entire course of therapy. An adverse outcome was defined as an in-hospital death or discharge to nursing home or rehabilitation hospital at any point during the treatment course. Multivariable analyses were performed with generalized estimating equations with adjustment for age, sex, ethnicity, source of admission, year of treatment, hospital volume, and clustering of observations at institutions. RESULTS: A total of 2069 patients were treated for unruptured aneurysms. Adverse outcomes were more frequent in the 1699 patients treated with surgery (25%) than in those treated with endovascular therapy (10%; P:<0.001). The difference persisted after multivariable adjustment (surgery versus endovascular therapy: odds ratio for adverse outcomes, 3.1; 95% CI, 2.5 to 4.0; P:<0.001). Adverse outcomes declined from 1991 to 1998 in patients treated with endovascular therapy (P:<0.005) but not for surgery. In-hospital deaths occurred in 3.5% of surgical cases and 0.5% of endovascular cases (P:=0.003), and the difference remained significant after adjustment (odds ratio, 6.3; 95% CI, 3.5 to 11.4; P:<0.001). Total length of stay and hospital charges were greater in surgical cases (both P:<0.001). Results were similar in a confirmatory analysis focusing on treatment differences between institutions. Institutional treatment volume was also associated with outcome but did not account for the differences between surgery and endovascular therapy. CONCLUSIONS: In California, endovascular therapy of unruptured aneurysms is associated with less risk of adverse outcomes and in-hospital death, lower hospital charges, and shorter hospital stays compared with surgery. Differences between therapies became more distinct through the years. Uncontrolled differences in prognosis of patients receiving endovascular therapy and surgery cannot be ruled out in this study of discharge abstracts.

Endovascular and surgical treatment of unruptured cerebral aneurysms: comparison of risks.

Unruptured cerebral aneurysms are commonly treated by surgical clipping, but endovascular coil embolization is increasingly employed as an alternative. In a blinded review of unruptured aneurysms treated at our institution since 1990, we identified patients whose aneurysms were judged to be treatable by both neurosurgeons and neurointerventional radiologists. A change in Rankin Scale score of 2 or more from hospital admission to discharge, indicating a new moderate disability or worse, was predefined as the primary outcome measure. Long-term follow-up was obtained by mailed questionnaire and telephone interview. Length of stay and hospital charges were totaled for all hospitalizations, including follow-up. Sixty-eight patients treated surgically and 62 patients treated with endovascular coil embolization were considered candidates for either procedure on blinded review, and overall anticipated procedure risk was rated as identical. A larger proportion of patients in the surgical group developed a change in Rankin Scale score of 2 or more (25% of surgical patients vs 8% of endovascular patients). Total length of stay was longer (mean days: 7.7 for surgical patients vs 5.0 for endovascular patients) and hospital charges were greater (mean, $38,000 for surgical patients vs $33,400 for endovascular patients) for the surgical patients. At follow-up, an average of 3.9 years after the procedure, surgical patients were more likely to report persistent new symptoms or disability since treatment (34% of surgical patients vs 8% of endovascular patients) and a longer period for recovery to normal (50% returning to normal in 1 year for surgery and in 27 days for coil embolization). Coil embolization of unruptured cerebral aneurysms seems to be associated with significantly fewer complications than surgical clipping. More long-term data on aneurysm rupture rates are required to confirm efficacy.

Subclavian arteritis and pseudoaneurysm formation secondary to stent infection.

Technically uncomplicated percutaneous angioplasty and stent placement of a left subclavian artery stenosis was performed in a 56-year-old man for treatment of subclavian steal syndrome and vertebrobasilar insufficiency. Six days later the patient was readmitted with Staphylococcus aureus bacteremia and stigmata of septic emboli isolated to the ipsilateral hand. Nine days later he had computed tomography (CT) evidence of a contrast-enhancing phlegmon surrounding the stent. Despite clinical improvement and resolution of bacteremia on intravenous antibiotic therapy, the phlegmon progressed, and at day 21 a pseudoaneurysm was angiographically confirmed. The patient underwent surgical removal of the stented arterial segment and successful autogenous arterial reconstruction. The possible contributory factors leading to stent infection were prolonged right femoral artery access and an infected left arm venous access. Although the role of prophylactic antibiotics remains to be defined, it may be important in cases where the vascular access sheath remains in place for a prolonged period of time.

Short-term prognosis after emergency department diagnosis of TIA.

CONTEXT: Management of patients with acute transient ischemic attack (TIA) varies widely, with some institutions admitting all patients and others proceeding with outpatient evaluations. Defining the short-term prognosis and risk factors for stroke after TIA may provide guidance in determining which patients need rapid evaluation. OBJECTIVE: To determine the short-term risk of stroke and other adverse events after emergency department (ED) diagnosis of TIA. DESIGN AND SETTING: Cohort study conducted from March 1997 through February 1998 in 16 hospitals in a health maintenance organization in northern California. Patients A total of 1707 patients (mean age, 72 years) identified by ED physicians as having presented with TIA. MAIN OUTCOME MEASURES: Risk of stroke during the 90 days after index TIA; other events, including death, recurrent TIA, and hospitalization for cardiovascular events. RESULTS: During the 90 days after index TIA, 180 patients (10.5%) returned to the ED with a stroke, 91 of which occurred in the first 2 days. Five factors were independently associated with stroke: age greater than 60 years (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1-2.7; P=.01), diabetes mellitus (OR, 2.0; 95% CI, 1.4-2.9; P<.001), symptom duration longer than 10 minutes (OR, 2.3; 95% CI, 1.3-4.2; P=.005), weakness (OR, 1.9; 95% CI, 1.4-2.6; P<.001), and speech impairment (OR, 1.5; 95% CI, 1.1-2.1; P=.01). Stroke or other adverse events occurred in 428 patients (25.1%) in the 90 days after the TIA and included 44 hospitalizations for cardiovascular events (2.6%), 45 deaths (2.6%), and 216 recurrent TIAs (12.7%). CONCLUSIONS: Our results indicate that the short-term risk of stroke and other adverse events among patients who present to an ED with a TIA is substantial. Characteristics of the patient and the TIA may be useful for identifying patients who may benefit from expeditious evaluation and treatment.

Endovascular therapy of traumatic injuries of the intracranial cerebral arteries.

Traumatic intracranial arterial injuries represent uncommon complications of both closed-head injury and penetrating head trauma. These injuries include arterial dissections, pseudoaneurysms, and fistulas, both direct and indirect. Although these lesions may be identified while still asymptomatic, they usually present in a delayed fashion with intracranial hemorrhage, focal cerebral ischemia, or, occasionally, severe epistaxis. Endovascular therapy has assumed a major role in the management of this diverse group of lesions. Embolization of pseudoaneurysms with balloons or detachable coils, the use of embolic particles for small arterial injuries, and large vessel occlusion with detachable balloons represent current treatment strategies that have evolved over the past three decades. Angioplasty and stent deployment may have a future role to play in the management of arterial dissection. Principles of neurologic critical care that minimize secondary brain injury are essential adjuncts in the management of these patients before, during, and after endovascular treatment.

Stroke prevention.

This article reviews the causes of stroke and emphasizes the underlying vascular pathology. The risk factors associated with the pathologic processes are examined, with emphasis on the beneficial impact on stroke risk through the risk factor modification. Risk factor modification is a powerful tool in stroke prevention and can lead to a marked decrease in the burden of stroke. The majority of strokes could be eliminated with an organized prevention strategy.

Treatment of posterior circulation ischemia with extracranial percutaneous balloon angioplasty and stent placement.

BACKGROUND AND PURPOSE: Vertebrobasilar territory ischemia (VBI) leads to disabling neurological symptoms and poses a risk for stroke by an embolic or flow-related mechanism. We present our clinical experience in the endovascular treatment of patients with symptomatic VBI from severe atherosclerosis or dissection of the vertebral and subclavian arteries that was unresponsive to medical therapy. METHODS: Twenty-one patients (9 female, 12 male) with a mean age of 65.7 years (range 47 to 81 years) underwent treatment with percutaneous endovascular balloon angioplasty and stent placement. Sixteen patients (76.2%) had evidence of contralateral involvement, and 9 (42.8%) demonstrated severe anterior-circulation atherosclerosis. Nine patients had a previous infarct in the occipital lobe, cerebellum, or pons before treatment. Follow-up was available for all patients. RESULTS: Balloon angioplasty with intravascular stent placement was performed in 13 vertebral artery lesions (10 at the origin, 3 in the cervical segment) and in 8 subclavian lesions. The prestenting stenosis was 75% (50% to 100%) and was reduced to 4.5% (0% to 20%) after stenting. Six of the patients with proximal subclavian stenosis demonstrated angiographic evidence of subclavian steal, which resolved in all cases after treatment. All patients showed improvement in symptoms after the procedure except for 1 who developed a hemispheric stroke after thrombotic occlusion of an untreated cavernous carotid artery stenosis (rate of major stroke and mortality=4.8%). One patient (4.8%) had a periprocedural transient ischemic attack (TIA), and none had minor stroke. At long-term follow-up (mean=20.7+/-3.6 months) of the surviving 20 patients, 12 (57.1%) remained symptom-free, 4 (19%) had at most 1 TIA over a 3-month period, 2 (9.5%) had at most 1 TIA per month, and 2 (9.5%) had persistent symptoms. There were no clinically evident infarcts during the follow-up period. CONCLUSIONS: Endovascular treatment using balloon angioplasty with intravascular stent placement for symptomatic stenotic lesions resulting in VBI that is unresponsive to medical therapy appears to be of benefit in this high-risk subset of patients with poor collateral flow.

Surgical and endovascular treatment of unruptured cerebral aneurysms at university hospitals.

OBJECTIVE: To compare complications of surgical clipping and coil embolization in the treatment of unruptured aneurysms. BACKGROUND: Surgical clipping has been the preferred treatment for unruptured cerebral aneurysms but endovascular coil embolization is an increasingly employed alternative. No direct comparisons of the techniques are available to guide clinical decision making. METHODS: We performed a cohort study of patients treated for unruptured cerebral aneurysms at 60 university hospitals from January 1994 through June 1997 using the University HealthSystem Consortium database. The database was validated by chart review from one of the participant universities. The main outcome measures were in-hospital mortality and adverse outcomes, defined as in-hospital deaths and discharges to nursing homes or rehabilitation hospitals. RESULTS: The primary treatment modality was surgical in 2,357 cases and endovascular in 255 cases. Adverse outcomes were significantly more common in surgical cases (18.5%) compared to endovascular cases (10.6%) (p = 0.002), and the difference was not altered after adjusting for age, sex, race, transfer admissions, emergency room admissions, and year of treatment (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.4 to 3.3; p = 0.001). In-hospital mortality was also increased in surgical cases (2.3% versus 0.4%; p = 0.039), but the difference was not significant in the multivariable model (OR 6.3, 95% CI 0.9 to 46.1; p = 0.07). Length of stay and hospital charges were significantly greater for surgical cases (p < 0.0001 for each), and these differences were not affected by risk adjustment. CONCLUSION: Endovascular coil embolization resulted in fewer adverse outcomes than surgery for unruptured cerebral aneurysms treated at the university hospitals studied. Although these results should be seen as preliminary, the magnitude of difference and current predominance of surgery appear to justify a randomized trial.

Which unruptured cerebral aneurysms should be treated? A cost-utility analysis.

OBJECTIVE: To determine which unruptured cerebral aneurysms should be treated considering the risks. benefits, and costs. BACKGROUND: Asymptomatic unruptured cerebral aneurysms are commonly treated by surgical clipping or endovascular coil embolization to prevent subarachnoid hemorrhage (SAH). METHODS: We performed a cost-utility analysis comparing surgical clipping and endovascular coil embolization with no treatment for unruptured aneurysms. Eight clinical scenarios were defined based on aneurysm size, symptoms, and history of SAH from a different aneurysm. Health outcomes of a hypothetical cohort of 50-year-old women were modeled over the projected lifetime of the cohort. Costs were assessed from the societal perspective. We compared net quality-adjusted life years (QALYs) and cost per QALY of each therapy to no treatment. RESULTS: For an asymptomatic unruptured aneurysm less than 10 mm in diameter in patients with no history of SAH from a different aneurysm, both procedures resulted in a net loss in QALYs, and confidence intervals (CI) were not compatible with a benefit from treatment (clipping, loss of 1.6 QALY [95% CI 1.1 to 2.1]; coiling, loss of 0.6 QALY [95% CI 0.2 to 0.8]). For larger aneurysms (> or = 10 mm), those producing symptoms by compressing neighboring nerves and brain structures, or in patients with a history of SAH from a different aneurysm, treatment was cost-effective. Coiling appeared more effective and cost-effective than clipping but these differences depended on relatively uncertain model parameters. CONCLUSIONS: Treatment of small, asymptomatic, unruptured cerebral aneurysms in patients without a history of SAH worsens clinical outcomes, and thus is neither effective nor cost-effective. For aneurysms that are > or = 10 mm or symptomatic, or in patients with a history of SAH, treatment appears to be cost-effective.

Oral contraceptives and the risk of subarachnoid hemorrhage: a meta-analysis.

OBJECTIVE: The objective of this study is to estimate the risk of subarachnoid hemorrhage produced by oral contraceptive use. METHODS: Studies published since 1960 were identified using MEDLINE, Cumulated Index Medicus, Dissertation Abstracts On-line, and bibliographies of pertinent articles. Two independent reviewers screened published cohort and case-control studies that evaluated the risk of subarachnoid hemorrhage associated with oral contraceptives. Eleven of 21 pertinent studies met predefined quality criteria for inclusion in the meta-analysis. Relative risk (RR) estimations evaluating subarachnoid hemorrhage risk in oral contraceptive users compared with nonusers were extracted from each study by two independent reviewers. Study heterogeneity was assessed by design type, outcome measure (mortality versus incidence), exposure measure (current versus ever use), prevailing estrogen dose used, and control for smoking and hypertension. RESULTS: The overall summary RR of subarachnoid hemorrhage due to oral contraceptive use was 1.42 (95% CI, 1.12 to 1.80; p = 0.004). When the two study results failing to control for smoking were excluded from the analysis, a slightly greater effect was seen, with an RR of 1.55 (95% CI, 1.26 to 1.91; p < 0.0001). In the six studies controlling for smoking and hypertension the RR was 1.49 (95% CI, 1.20 to 1.85; p = 0.0003). High-estrogen oral contraceptives appeared to impart a greater risk than low-dose preparations in studies controlling for smoking, but the difference was not significant (high-dose RR, 1.94; 95% CI, 1.06 to 3.56; low-dose RR, 1.51; 95% CI, 1.18 to 1.92). CONCLUSIONS: This meta-analysis of observational studies suggests that oral contraceptive use produces a small increase in the risk of subarachnoid hemorrhage.

PIP: Both case-control and cohort studies have evaluated the risk of subarachnoid hemorrhage (SAH) among oral contraceptive (OC) users and identified relative risks as low as 0.5 and as high as 6.5. To determine whether OC use is indeed a risk factor for SAH after accounting for the variability in study designs and results, a meta-analysis was conducted of the 11 salient independent studies included in the research literature. The summary estimate of effect for all studies was a relative risk (RR) of 1.42 (95% confidence interval (CI), 1.12-1.80). There was a trend toward smaller RRs in the most recent studies, presumably as a result of decreases in the estrogen dose of modern OCs. In the 6 studies that controlled for both smoking and hypertension, the summary RR was 1.49 (95% CI, 1.20-1.85). Only 2 of the 11 studies found a protective effect of current OC use on SAH risk, and it was nonsignificant. Taken together, these studies support a weak positive association between OC use and SAH risk. In the US, an additional 430 patients each year with OC-related SAH would be expected. For most women, the SAH risk is inconsequential in evaluating the decision about OC use. However, for women at high risk of SAH due to unruptured aneurysms, a strong positive family history, smoking, or hypertension, it may be advisable to consider alternative contraceptive methods until more data are available.

The burden, trends, and demographics of mortality from subarachnoid hemorrhage.

OBJECTIVE: The objective of this study was to describe the recent epidemiology of mortality from subarachnoid hemorrhage in the United States. BACKGROUND: Subarachnoid hemorrhage is distinct from other forms of stroke in its risk factors, demographics, and treatment. However, it is often clustered with other stroke subtypes, obscuring its unique epidemiology. METHODS: We analyzed subarachnoid hemorrhage mortality data from the National Center for Health Statistics of the United States for the years 1979 to 1994 and compared it with other stroke subtypes. RESULTS: Age-adjusted mortality rates of subarachnoid hemorrhage were 62% greater in females than in males and 57% greater in blacks than in whites. The median age of death from subarachnoid hemorrhage was 59 years compared with 73 years for intracerebral hemorrhage and 81 years for ischemic stroke. Mortality rates of subarachnoid hemorrhage have decreased by approximately 1% per year since 1979, and the mean age of death has steadily increased from 57 years in 1979 to 60 years in 1994. Subarachnoid hemorrhage accounted for 4.4% of stroke mortality but 27.3% of all stroke-related years of potential life lost before age 65, a measure of premature mortality. The proportion of years of potential life lost due to subarachnoid hemorrhage was comparable with ischemic stroke (38.5%) and intracranial hemorrhage (34.2%). CONCLUSIONS: Subarachnoid hemorrhage is an uncommon cause of stroke mortality but occurs at a young age, producing a relatively large burden of premature mortality, comparable with ischemic stroke.

Rapid development of giant fusiform cerebral aneurysms in angiographically normal vessels.

Several reports have mentioned formation of new saccular aneurysms in previously normal-appearing vessels, but de novo fusiform aneurysms have not been reported. We describe three children who initially presented with giant fusiform aneurysms involving the cervical and petrous portions of the internal carotid artery and were treated with balloon occlusion. Between 2 and 6 years later, they were found to have new giant fusiform aneurysms in the vertebrobasilar system.

Effects of induced hypertension on transcranial Doppler ultrasound velocities in patients after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Transcranial doppler ultrasound (TCD) is used after subarachnoid hemorrhage to detect cerebral vasospasm and is often treated with induced hypertension. Cerebral autoregulation, however, may be disturbed in this population, raising the possibility that TCD velocities may be elevated by induced hypertension. To study this possibility, we performed continuous TCD monitoring of the middle cerebral artery during the induction and withdrawal of induced hypertension in patients after subarachnoid hemorrhage. METHODS: Twenty-eight patients were studied during the induction and withdrawal of hypertension using primarily phenylephrine. Continuous monitoring was performed on the middle cerebral artery with the highest flow velocity. Treatment was based on rising TCD velocities or clinical evidence for cerebral vasospasm. Mean arterial pressure and mean TCD velocities were recorded every minute. A change of > 15% from starting TCD values was considered significant. Cerebral autoregulation was calculated as a percentage of intact autoregulation. Patients were subsequently divided into groups of disturbed and intact autoregulation. RESULTS: In 10 of 19 patients (53%), TCD velocities changed by > 15% and paralleled changes in mean arterial pressure. This directly altered the TCD interpretation of the grade of vasospasm in 7 of 19 patients (36%). Three additional patients had smaller absolute changes in TCD velocities. No clinical difference could be identified between patients with disturbed and intact autoregulation. CONCLUSIONS: In patients with disturbed autoregulation after subarachnoid hemorrhage, induced hypertension can alter cerebral blood flow velocities. The level of autoregulation needs to be considered when interpreting TCD velocities in patients after subarachnoid hemorrhage.

The safety and efficacy of cyclosporine A in the prevention of vasospasm in patients with Fisher grade 3 subarachnoid hemorrhages: a pilot study.

OBJECTIVE: To evaluate the safety and any potential effect of cyclosporine A (CycA) in preventing cerebral vasospasm. METHODS: Nine patients with Fisher Grade 3 subarachnoid hemorrhages were studied. After a loading dose of 7.5 mg/kg of CycA was administered every 12 hours for two doses, enteral treatment with CycA was started within 72 hours of the onset of the subarachnoid hemorrhage. Whole blood CycA levels were titrated to maintain levels of 50 to 400 ng/kg. Transcranial doppler ultrasonography was performed daily. Middle cerebral artery velocities were used to assess the degree of vasospasm. Angiography was performed to confirm the vasospasm in symptomatic patients, or it was performed if transcranial doppler ultrasonograms were unobtainable. Patients were treated with a standard pharmacological regimen of nimodipine. Induced hypertension, hemodilution, and hypervolemia were instituted at the discretion of the neurosurgical team. Intra-arterial papaverine was infused into the vasospastic vessels of three recalcitrant patients. Outcome was assessed at 6 months with the Glasgow Outcome Scale. RESULTS: All the patients displayed evidence of vessel narrowing, which was disclosed by transcranial doppler ultrasonography or angiography. Five patients developed ischemic deficits, two were treated with intra-arterial papaverine, and three died of complications secondary to vasospasm. No significant hepatic, renal, or infectious complication developed as a result of the administration of CycA. CONCLUSIONS: CycA proved safe to use but failed to prevent the development of cerebral vasospasm or delayed ischemic deficits in patients considered at high risk.