Ralph G. Dacey

Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage A Statement for Healthcare Professionals From a Special Writing Group of the Stroke Council, American Heart Association

Subarachnoid hemorrhage (SAH) is a common and frequently devastating condition, accounting for ≈5% of all strokes and affecting as many as 30 000 Americans each year.1,2 The American Heart Association (AHA) previously published “Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage.”3 Since then, considerable advances have been made in endovascular techniques, diagnostic methods, and surgical and perioperative management paradigms. Nevertheless, outcome for patients with SAH remains poor, with population-based mortality rates as high as 45% and significant morbidity among survivors.4–9 Several multicenter, prospective, randomized trials and prospective cohort analyses have influenced treatment protocols for SAH. However, rapid evolution of newer treatment modalities, as well as other practical and ethical considerations, has meant that rigorous clinical scientific assessment of the treatment protocols has not been feasible in several important areas. To address these issues, the Stroke Council of the AHA formed a writing group to reevaluate the recommendations for management of aneurysmal SAH. A consensus committee reviewed existing data in this field and prepared the recommendations in 1994.3 In an effort to update those recommendations, a systematic literature review was conducted based on a search of MEDLINE to identify all relevant randomized clinical trials published between June 30, 1994, and November 1, 2006 (search terms: subarachnoid hemorrhage , cerebral aneurysm , trial ; Table 1). Each identified article was reviewed by at least 2 members of the writing group. Selected articles had to meet one of the following criteria to be included: randomized trial or nonrandomized concurrent cohort study. Case series and nonrandomized historical cohort studies were reviewed if no studies with a higher level of evidence were available for a particular topic covered in the initial guidelines. These were chosen on the basis of sample size and the relevance of the particular studies to subjects that …

Effect of Probenecid on Cerebrospinal Fluid Concentrations of Penicillin and Cephalosporin Derivatives

Probenecid may elevate the cerebrospinal fluid (CSF) concentration of penicillin G by inhibiting the excretion of organic acids from CSF. We have studied this phenomenon with various penicillin and cephalosporin derivatives. Penicillin concentrations were determined in rabbits under steady-state conditions before and after intravenous probenecid administration. With both low-dose and high-dose probenecid, CSF penicillin levels increased two to three times as did CSF concentration as a percentage of serum level. The same probenecid effect was consistently demonstrated in animals with experimental pneumococcal meningitis. Probenecid likewise increased the CSF concentration of ampicillin, carbenicillin, nafcillin, cephacatrile, and cefazolin. Probenecid may prove useful in certain bacterial infections where high CSF antibiotic levels are necessary.

Clinical Features and Outcome in North American Adults With Moyamoya Phenomenon

Background and Purpose— To describe baseline clinical features and outcomes of adults with moyamoya phenomenon treated at a single North American institution. Methods— We identified 34 adults with moyamoya phenomenon by review of angiographic records. Clinical presentation and baseline stroke risk factors were obtained by chart review. Follow-up was obtained prospectively. A 5-year Kaplan-Meier stroke risk was calculated. Results— The median age was 42 (range 20 to 79) years. Twenty-five were women. The initial symptom was ischemia, hemorrhage, or asymptomatic in 24, 7, and 3 patients, respectively. Twenty-two had bilateral involvement and 12 had unilateral moyamoya vessels. Baseline stroke risk factors were similar between groups. The median follow-up in 31 living patients was 5.1 (range 0.2 to 19.6) years. Fourteen patients were treated with surgical revascularization (20 total hemispheres). In medically treated symptomatic hemispheres, the 5-year risk of recurrent ipsilateral stroke was 65% after the initial symptom and 27% after angiographic diagnosis. Patients with bilateral involvement presenting with ischemic symptoms were at the highest risk of subsequent stroke (n=17, 5-year risk of stroke with medical treatment after first symptom of 82%). In surgically treated hemispheres, the 5-year risk of perioperative or subsequent ipsilateral stroke or death was 17%. This was significantly different compared with medical treatment after first symptom (P=0.02) but not after angiographic diagnosis. Conclusion— Moyamoya phenomenon in North American adults is associated with a high risk of recurrent stroke, particularly those with bilateral involvement and ischemic symptoms. These data suggest a potential benefit with surgery if diagnosis could be made earlier.

CRANIAL DURAL ARTERIOVENOUS FISTULAE: ASYMPTOMATIC CORTICAL VENOUS DRAINAGE PORTENDS LESS AGGRESSIVE CLINICAL COURSE

OBJECTIVECranial dural arteriovenous fistulae (dAVF) with cortical venous drainage (CVD) (Borden Types 2 and 3) are reported to carry a 15% annual risk of intracranial hemorrhage (ICH) or nonhemorrhagic neurological deficit (NHND). The purpose of this study was to compare the clinical course of Type 2 and 3 dAVFs that present with ICH or NHND with those that do not. METHODSTwenty-eight patients with Type 2 or 3 dAVFs were retrospectively evaluated. CVD was classified as asymptomatic (aCVD) if patients presented incidentally or with pulsatile tinnitus or orbital phenomena. CVD was classified as symptomatic (sCVD) if patients presented with ICH or NHND. Occurrence of new ICH or new or worsening NHND between diagnosis and disconnection of CVD or last follow-up (if not disconnected) was noted. Overall frequency of events was compared using Fishers exact test. Cumulative, event-free survival was compared using Kaplan-Meier analysis with log-rank testing. RESULTSOf 17 patients with aCVD, 1 (5.9%) developed ICH and none experienced NHND or death during the median 31.4-month follow-up period. Of 11 patients with sCVD, 2 (18.2%) developed ICH and 3 (27.3%) experienced new or worsened NHND over the median 9.7-month follow-up period. One of these patients subsequently died. Overall frequency of ICH or NHND was significantly lower in patients with aCVD versus sCVD (P = 0.022). Respective annual event rates were 1.4 versus 19.0%. aCVD patients had significantly higher cumulative event-free survival (P = 0.0016). CONCLUSIONCranial dAVFs with aCVD may have a less aggressive clinical course than those with sCVD.

Effect of antiplatelet therapy on thromboembolic complications of elective coil embolization of cerebral aneurysms.

BACKGROUND AND PURPOSE: Thromboembolic events are the most common complications of elective coil embolization of cerebral aneurysms. Administration of oral clopidogrel and/or aspirin could lower the thromboembolic complication rate. MATERIALS AND METHODS: Records over a 10-year period were reviewed in a retrospective cohort study. For 369 consecutive elective coil embolization procedures, 25 patients received no antiplatelet drugs, 86 received antiplatelet drugs only after embolization, and 258 received antiplatelet drugs before and after embolization. RESULTS: Symptomatic thromboembolic complications (transient ischemic attack or stroke within 60 days) occurred in 4 (16%) of 25 when no antiplatelet drugs were given, in 2 (2.3%) of 86 when antiplatelet drugs were administered only after embolization, and in 5 (1.9%) of 258 when antiplatelet drugs were administered before and after embolization. The lower symptomatic thromboembolic complication rate in the patients who received any antiplatelet therapy was statistically significant (P = .004). Clots were visible intraprocedurally in 5 (4.5%) of 111 when no antiplatelet drugs were administered before procedures and in 4 (1.6%) of 258 when they were (P value not significant). None of the 9 was symptomatic postprocedurally, but 7 were lysed or mechanically disrupted. Extracerebral hemorrhagic complications occurred in 0 (0%) of 25 when no antiplatelet drugs were given and in 11 (3.2%) of 344 when they were (P value not significant). CONCLUSION: Oral clopidogrel and/or aspirin significantly lowered the symptomatic thromboembolic complication rate of elective coil embolization of unruptured cerebral aneurysms. There were trends toward a lower rate of intraprocedural clot formation in patients given antiplatelet drugs before procedures and a higher hemorrhagic complication rate in patients given antiplatelet drugs. Benefits of antiplatelet therapy appear to outweigh risks.

Safety of Hypertensive Hypervolemic Therapy With Phenylephrine in the Treatment of Delayed Ischemic Deficits After Subarachnoid Hemorrhage

BACKGROUND AND PURPOSE Hypertensive hypervolemic therapy has been shown to reverse delayed ischemic deficits after aneurysmal subarachnoid hemorrhage. Concern has been raised about systemic complications of therapy, including pulmonary edema and myocardial ischemia, especially when high doses of vasopressors are used. Patients in whom delayed ischemic deficits were treated with hypervolemia and phenylephrine were prospectively evaluated for signs of systemic toxicity. METHODS Twenty-four consecutive patients treated with hypertensive hypervolemic therapy after aneurysmal subarachnoid hemorrhage were studied. Sixty-seven percent had underlying cardiac disease, vascular disease, or hypertension. No patient was excluded because of age or preexisting cardiac disease. Patients were closely monitored for signs of congestive heart failure (physical examination, chest x-ray films, arterial blood gases, cardiac index, pulmonary artery wedge pressure, and oxygen requirement). Indicators of cardiac ischemia and other extracerebral toxicity that were monitored included cardiac enzymes, electrocardiograms, serum creatinine, electrolyte and lactic acid levels, gastrointestinal motility, and urine output. RESULTS Volume expansion and phenylephrine infusion produced an increase in several hemodynamic parameters including pulmonary artery wedge pressure, which rose 28% (13 +/- 3.6 to 16 +/- 1.9 mm Hg), mean arterial blood pressure, which rose 25% (99 +/- 12.5 to 123 +/- 11.4 mm Hg), and systemic vascular resistance, which rose 46% (1234 +/- 294 to 1739 +/- 315 dyne.s-1.cm-5); however, there was no change in cardiac index (3.9 +/- 0.9 to 4.0 +/- 0.6 L.min-1.m-2). There were no clinically significant episodes of pulmonary edema requiring a change in vasopressor therapy and no myocardial infarctions. Phenylephrine was stopped in only one patient (incidence, 4%; 95% confidence interval, 0% to 12%), who developed an exacerbation of his preexisting bradycardia. There was no evidence of noncardiac organ system toxicity. Eighty-eight percent of the patients exhibited neurological improvement. CONCLUSIONS Hypertensive hypervolemic therapy with the use of high-dose phenylephrine can be administered with acceptable systemic toxicity, even in patients with previous cardiac disease, provided that close monitoring is performed. To minimize risk, aggressive treatment should probably be reserved for patients with signs of delayed ischemia rather than administered prophylactically.

Use of stimulation mapping and corticography in the excision of arteriovenous malformations in sensorimotor and language-related neocortex.

The excision of an arteriovenous malformation (AVM) located within eloquent neocortex presents a formidable neurosurgical challenge. Compromise of the vascular supply to normal surrounding brain or surgical trauma to essential neighboring neocortex may result in unacceptable postoperative neurological morbidity. In addition, successful removal of these lesions without the benefit of intraoperative corticography may leave in situ areas of highly epileptogenic brain, resulting in continued epilepsy. In this report, we describe eight patients who underwent craniotomy and excision of AVMs at our institutions. Six of these lesions were located in the dominant (left) hemisphere, and two were on the right. All patients underwent preoperative testing with Amytal administered via the carotid artery (Wada test). Subsequently, the patient was placed under local anesthesia, and we performed a craniotomy. Electrocorticography was used to identify epileptogenic brain in the region of the AVM and to establish after-discharge thresholds to electrical stimulation. Stimulation-mapping techniques were then used to delineate critical motor, sensory, and language areas. Trial occlusion of feeding vessels was also carried out to document postocclusion neurological deterioration, if any. At a later time, a second procedure was performed under general anesthesia to excise the lesion and any epileptogenic foci, using the cortical maps derived earlier. Using these techniques, it was possible to effect complete excision of these lesions in seven of eight patients without causing additional neurological deficits.

Mechanism of Extracellular K+-Induced Local and Conducted Responses in Cerebral Penetrating Arterioles

Background and Purpose— Extracellular concentration of potassium ion ([K+]o) may have a significant influence on the cerebral circulation in health and disease. Mechanisms of [K+]o-induced conducted vasomotor responses in cerebral arterioles, possibly linking microvascular regulation to neuronal activity, have not been examined. Methods— We analyzed vascular responses to small increases of [K+]o (up to 5 mmol/L) in isolated, cannulated, and pressurized rat cerebral arterioles (36.5±1.4 &mgr;m). [K+]o was elevated globally through extraluminal application or locally through micropipette, while arteriolar diameter was measured online. Results— Elevation of [K+]o (5 mmol/L) produced dilation that was inhibited by ouabain but not BaCl2. Locally applied [K+]o (3 to 5 mmol/L) produced a biphasic response (initial constriction followed by dilation), both of which were conducted to the remote site (distance 1142±68 &mgr;m). Endothelial impairment inhibited conducted but not local biphasic responses. Extraluminal ouabain attenuated local and conducted secondary dilation but not initial constriction. The local biphasic response was unaffected by extraluminal or intraluminal BaCl2. Extraluminal but not intraluminal BaCl2 impaired both conducted constriction and dilation. Conclusions— In rat penetrating arteriole, (1) [K+]o (3 to 5 mmol/L) strongly regulates arteriolar tone and causes conducted vasomotor responses; (2) local responses to elevated [K+]o are endothelium independent but conducted responses are dependent on an intact endothelium; (3) smooth muscle Na+-K+-ATPase activation is the generator of conducted dilation; and (4) smooth muscle inward rectifier potassium channels sustain conduction. Our findings suggest that potassium-induced conducted vasomotor responses may link local neuronal activity to microvascular regulation, which may be attenuated in pathological conditions.

Relative effects of brain and non-brain injuries on neuropsychological and psychosocial outcome

Based on the 242 consecutive surviving head injury cases and 132 general trauma cases, this study examined the contribution of brain and non-brain injuries to cognitive and psychosocial outcome 1 month postinjury. The study also examined the relationships among various head injury severity indices. The head injury severity indices were all correlated but patients with Glasgow Coma Scale scores in the mild range had broadly ranging scores on the other head injury severity indices (Abbreviated Injury Scale and time to follow commands). Neuropsychological outcome was related to brain injury severity, but was not independently influenced by severity of other systems injuries. Psychosocial outcome related to both brain and non-brain injuries independently. When evaluating trauma outcome, it is important to consider the contributions of both brain and other system injuries.

Combined endovascular embolization and stereotactic radiosurgery in the treatment of large arteriovenous malformations: Clinical article

OBJECT Large cerebral arteriovenous malformations (AVMs) are often not amenable to direct resection or stereotactic radiosurgery (SRS) treatment. An alternative treatment strategy is staged endovascular embolization followed by SRS (Embo/SRS). The object of this study was to examine the experience at Washington University in St. Louis with Embo/SRS for large AVMs and review the results in earlier case series. METHODS Twenty-one cases involving patients with large AVMs treated with Embo/SRS between 1994 and 2006 were retrospectively evaluated. The AVM size (before and after embolization), procedural complications, radiological outcome, and neurological outcome were examined. Radiological success was defined as AVM obliteration as demonstrated by catheter angiography, CT angiography, or MR angiography. Radiological failure was defined as residual AVM as demonstrated by catheter angiography, CT angiography, or MR angiography performed at least 3 years after SRS. RESULTS The maximum diameter of all AVMs in this series was > 3 cm (mean 4.2 cm); 12 (57%) were Spetzler-Martin Grade IV or V. Clinical follow-up was available in 20 of 21 cases; radiological follow-up was available in 19 of 21 cases (mean duration of follow-up 3.6 years). Forty-three embolization procedures were performed; 8 embolization-related complications occurred, leading to transient neurological deficits in 5 patients (24%), minor permanent neurological deficits in 3 patients (14%), and major permanent neurological deficits in none (0%). Twenty-one SRS procedures were performed; 1 radiation-induced complication occurred (5%), leading to a permanent minor neurological deficit. Of the 20 patients with clinical follow-up, none experienced cerebral hemorrhage. In the 19 patients with radiological follow-up, AVM obliteration was confirmed by catheter angiography in 13, MR angiography in 2, and CT angiography in 1. Residual nidus was found in 3 patients. In patients with follow-up catheter angiography, the AVM obliteration rate was 81% (13 of 16 cases). CONCLUSIONS Staged endovascular embolization followed by SRS provides an effective means of treating large AVMs not amenable to standard surgical or SRS treatment. The outcomes and complication rates reported in this series compare favorably to the results of other reported therapeutic strategies for this very challenging patient population.