Thrombolytic therapy of acute ischemic stroke during pregnancy.

The authors report eight pregnant women with acute ischemic stroke treated with thrombolysis (rt-PA [recombinant human tissue plasminogen activator] or urokinase). Seven women recovered. Two extracranial and two asymptomatic intracranial hemorrhages complicated treatment; one woman died of arterial dissection complicating angiography. Three patients had therapeutic abortions, two fetuses were miscarried, and two babies were delivered healthy. Although pregnant women may be treated safely with thrombolytics, risks and benefits to mother and fetus must be carefully weighed.

Haptoglobin and the development of cerebral artery vasospasm after subarachnoid hemorrhage.

BACKGROUND: Vasospasm is a prolonged constriction of a cerebral artery that is induced by hemoglobin after subarachnoid hemorrhage (SAH). The subarachnoid blood clot also contains the protein haptoglobin, which acts to neutralize hemoglobin. Because the haptoglobin alpha gene is dimorphic, a person can expresses only one of three types of haptoglobin (alpha1-alpha1, alpha1-alpha2, or alpha2-alpha2) depending on the alpha subunit genes he or she inherits. Each of these three haptoglobin types has different antihemoglobin activities; therefore, haptoglobin may influence the development of vasospasm differently in various patients with SAH. OBJECTIVE: To determine whether SAH patients who have haptoglobin containing the alpha2 subunit would be more likely to develop vasospasm than would be SAH patients who have haptoglobin alpha1-alpha1. METHODS AND RESULTS: A total of 32 patients with Fisher Grade 3 SAH were enrolled in this study. Haptoglobin type was determined by polyacrylamide gel electrophoresis. The primary measure for vasospasm was increased blood flow velocities as detected by daily transcranial Doppler ultrasonography (TCD). The authors found that only 2 of 9 patients with haptoglobin alpha1-alpha1 (22%) had development of "possible" vasospasm as measured by TCD, whereas 20 of 23 patients with the haptoglobin alpha2 subunit (either the alpha1-alpha2 or alpha2-alpha2 haptoglobin types) had development of "possible" vasospasm (87%). The secondary measure for vasospasm was cerebral angiography performed between 3 and 14 days after SAH. Similar results (17% vs 56%) were seen between these groups in those patients who underwent cerebral angiography, although its inconsistent use limited the strength of the statistical comparison. CONCLUSIONS: Haptoglobins containing the alpha2 subunit seem to be associated with a higher rate of vasospasm than is haptoglobin alpha1-alpha1.

Measurement of free fatty acids in cerebrospinal fluid from patients with hemorrhagic and ischemic stroke.

Free fatty acid (FFA) concentrations in cerebrospinal fluid (CSF) from patients with ischemic and hemorrhagic stroke (n=25) and in contemporary controls (n=73) were examined using HPLC. Concentrations of CSF FFAs from ischemic and hemorrhagic stroke patients obtained within 48 h of the insult were significantly greater than in control patients. Higher concentrations of polyunsaturated fatty acids (PUFAs) in CSF obtained within 48 h of insult were associated with significantly lower (P<0.05) admission Glasgow Coma Scale scores and worse outcome at the time of hospital discharge, using the Glasgow Outcome Scale (P<0.01).

Intra-arterial urokinase for acute ischemic stroke: factors associated with complications.

The authors abstracted the records of 43 patients treated with intra-arterial urokinase for acute ischemic stroke to identify predictors of serious complications. Sixteen (37%) had such a complication. Higher urokinase dose (>1.5 x 10(6) U), higher mean arterial blood pressure before treatment (>130 mm Hg), basilar occlusive strokes, and severe strokes were most predictive of these complications. Although urokinase is no longer manufactured, these findings identify patients at risk for complications from other intra-arterial thrombolytics.

Safety and feasibility of craniectomy with duraplasty as the initial surgical intervention for severe traumatic brain injury.

BACKGROUND: Decompressive craniectomy has historically served as a salvage procedure to control intracranial pressure after severe traumatic brain injury. We assessed the safety and feasibility of performing craniectomy as the initial surgical intervention. METHODS: Of 29 consecutive patients undergoing emergent decompression for severe traumatic brain injury with horizontal midline shift greater than explained by a removable hematoma, 17 had traditional craniotomy with or without brain resection and 12 underwent craniectomy. RESULTS: The craniectomy group had lower Glasgow Coma Scale scores at surgery (median, 4 vs. 7; p = 0.04) and more severe radiographic injuries (using specific measures). Mortality, Glasgow Outcome Scale scores, Functional Independence Measures, and length of stay in both the acute care setting and the rehabilitation phase were similar between the surgical groups. CONCLUSION: Despite more severe injury severity, patients undergoing initial craniectomy had outcomes similar to those undergoing traditional surgery. A randomized evaluation of the effect of early craniectomy on outcome is warranted.

Stroke after bone marrow transplantation: frequency, aetiology and outcome.

Few data exist on the frequency, aetiology and outcome of cerebrovascular complications of bone marrow transplantation (BMT). We reviewed all patients undergoing BMT at the Fred Hutchinson Cancer Research Center, Seattle, Wash., USA (a large referral institution) over 3 years. We reviewed ICD-9 (International Classification of Diseases) codes for ischaemic stroke, seizure, intracranial haemorrhage and brain infection. Using standardized forms, we paid detailed attention to clinical features and demographics, oncological diagnosis, conditioning regimens, neurological history, comorbidities, time from BMT to ictus, stroke subtype, radiological and pathological features, and outcomes. We identified 36 patients with stroke from 1245 patients who had BMT (2.9%) over 3 years. These patients' median age was 35 (range 5-60, interquartile range 25-45) years. The most common causes of stroke were intracranial haemorrhage related to thrombocytopenia (38.9%) and infarction or haemorrhage secondary to fungal infection (30.6%). Twenty-five patients (69.4%) died from their stroke; none survived without disability. Using a logistic regression model, we found that neither demographic (e.g. age, gender) nor clinical (e.g. oncological diagnosis, type of BMT, time of stroke after BMT) factors predicted outcome. Stroke occurs relatively frequently (incidence almost 3%) after BMT, has a relatively high frequency of infection-triggered events, has a neurological outcome not easily predicted from available data and is often fatal.

Intracranial pressure and surgical decompression for traumatic brain injury: biological rationale and protocol for a randomized clinical trial.

Commonly, severe traumatic brain injury (TBI) patients undergo amputation of contused brain; the rationale being that edema in presumed unsalvageable cerebrum increases intracranial pressure (ICP). Neuro-critical care expends great effort to control ICP and prevent secondary injury. Non-randomized investigations have employed hemicraniectomy with duraplasty after developing refractory ICP. We undertook a randomized pilot of hemicraniectomy with duraplasty as the initial surgery for severe TBI patients. Goals included reduced ICP therapeutic intensity and return to the operating room, and improved neurological outcome. Upon hospital presentation, the study was to randomize 92 patients with midline shift greater than the size of a surgically removable hematoma. One group was to receive standardized hemicraniectomy and duraplasty; the other would undergo 'traditional' craniotomy (with brain amputation at the neurosurgeon's discretion). A standardized medical protocol followed. The six-month Glasgow Outcome Scale was the primary outcome, with secondary measures including quality of life one year after TBI, duration and frequency of elevated ICP, intensive care unit (ICU) therapeutic intensity, operating room return, and ICU and hospital lengths-of-stay. This article presents the biological rationale and the evidence-based standardized protocols of the study and its outcome measures. The study has stopped and a phase III outcome trial is being organized.

Poor prognosis of acute stroke patients denied thrombolysis due to early CT findings.

OBJECTIVES: Whether acute stroke patients with major early infarct signs on computed tomography (CT) should be treated with intravenous (i.v.) thrombolysis remains controversial. The authors sought to define the outcomes in 5 consecutive patients who were not treated with i.v. thrombolysis, according to established guidelines. METHODS: The authors retrospectively analyzed the outcomes of a consecutive series of 5 patients evaluated by an acute stroke team at a university medical center and who were denied i.v. tissue plasminogen activator due to early CT changes. RESULTS: Five patients with a median National Institutes of Health Stroke Scale score of 22 (range 20-28) were evaluated. Despite aggressive care (e.g., hemicraniectomy), 2 patients died owing to herniation, 1 patient died of cardiac causes, and neither of the 2 surviving patients achieved a 3-month Rankin score below 4 (moderately severe disability). CONCLUSIONS: Given the poor prognosis of patients with hemispheric stroke and early CT changes, alternative treatment modalities such as intra-arterial thrombolysis, early hemicraniectomy, and neuroprotective therapy should be vigorously pursued.

Quantification of free fatty acids in human cerebrospinal fluid.

Free fatty acids (FFA) in cerebrospinal fluid (CSF) are well-recognized markers of brain damage in animal studies. Information is limited regarding human CSF in both normal and pathological conditions. Samples of CSF from 73 patients, who had undergone lumbar puncture for medically indicated reasons, came from a core laboratory upon completion of ordered tests. Using high performance liquid chromatography, mean FFA concentrations (microg/L +/- SEM) were: arachidonic 26.14 +/- 3.44; docosahexaenoic 60.74 +/- 5.70; linoleic 105.07 +/- 10.98; myristic 160.38 +/- 16.17; oleic 127.91 +/- 10.13; and palmitic 638.34 +/- 37.27. No differences in FFA concentrations were seen with gender, race, age, and/or indication for lumbar puncture. This is the first study to document normal human CSF FFA concentrations in a large series. Further characterization of FFA in pathological conditions may provide markers for evaluating clinical treatments and assisting in prognostication of neurological disease.

Nimodipine-induced acute hypoxemia: case report.

OBJECTIVE AND IMPORTANCE: Nimodipine is commonly used to improve neurological outcomes after subarachnoid hemorrhage. Although nimodipine reportedly has high specificity for the cerebral vasculature, adverse systemic effects such as hypotension have been described. This case report describes a patient with traumatic subarachnoid hemorrhage who experienced two episodes of previously undescribed, life-threatening hypoxemia that was directly related to nimodipine therapy. CLINICAL PRESENTATION: The patient experienced acute hypoxemia (partial pressures of oxygen of 32.9 and 58.7 mm Hg), on two separate occasions (3 d apart), that was temporally related to single doses of nimodipine therapy for traumatic subarachnoid hemorrhage. Other disease- and medication-related causes did not explain these episodes. INTERVENTION: After the inspired oxygen concentration was increased to 100% (both episodes) and the positive end expiratory pressure was increased to 7.5 mm Hg (first episode), the arterial oxygen saturation of the patient returned to baseline levels (>99%) within 40 minutes in each instance. Nimodipine therapy was discontinued after each episode. CONCLUSION: It is hypothesized that, in the presence of concomitant adult respiratory distress syndrome, nimodipine increased ventilation/perfusion ratio mismatch, through its direct vasodilatory effects on the pulmonary artery, and possibly interfered with the reflex hypoxic pulmonary vasoconstriction necessary to maintain adequate oxygenation for this patient. Clinicians should carefully monitor the oxygenation status of patients when nimodipine therapy is initiated.

Infection related to intracranial pressure monitors in adults: analysis of risk factors and antibiotic prophylaxis.

OBJECTIVE: Infection is a complication related to intracranial pressure monitoring devices. The timing, duration, and role of prophylactic antimicrobial agents against intracranial pressure monitor (ICPM) related infection have not previously been well defined. Risk factors and selection, duration, and timing of antibiotic prophylaxis in patients with ICPMs were evaluated. METHODS: Records of all consecutive patients who underwent ICPM insertion between 1993 and 1996 were reviewed. Patients included were older than 12 years with an ICPM placed for at least 24 hours. Exclusion criteria consisted of ICPM placed before admission or documented CSF infection before or at the time of insertion. Standard criteria were applied to all patients for diagnosis of CSF infection. RESULTS: A total of 215 patients were included, 16 (7.4%) of whom developed CSF infection. Antibiotic prophylaxis for ICPM placement was administered to 63% of infected and 59% of non-infected patients. Vancomycin (60%) and cefazolin (34%) were used most often. Sixty per cent (6/16) of patients who developed infection and 45% (53/199) of those without CSF infection received their first antibiotic dose within the 2 hours before ICPM insertion. Risk factors for CSF infection included duration of monitoring greater than 5 days (RR 4.0 (1.3-11.9)); presence of ventriculostomy (RR 3.4 (1.0-10.7)); CSF leak (RR 6.3 (1.5-27.4)); concurrent systemic infection (RR 3.4 (1.2-9.5)); or serial ICPM (RR 4.9 (1. 7-13.8)). CONCLUSIONS: Administration of antibiotics to patients before or at the time of ICPM placement did not decrease the incidence of CSF infection. Patients found to be at greater risk for infection at our institution included duration of ICPM greater than 5 days, use of ventricular catheter, CSF leak, concurrent systemic infection, or serial ICPM.

Anticonvulsant prophylaxis and timing of seizures after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: There is no evidence that seizure prophylaxis is indicated after aneurysmal subarachnoid hemorrhage (SAH). This study examines prophylactic antiepileptic drug (AED) prescription and the occurrence of seizures within a single university-affiliated institution. METHODS: The authors reviewed 95 SAH patient charts using standardized forms. Variables included prophylaxis duration, seizure incidence and timing, CT findings, AED adverse events, and 1-year patient follow-up. RESULTS: Prehospital seizures occurred in 17.9% (17/95) of patients; another 7.4% (7/95) had a questionable prehospital seizure. In-hospital seizures occurred in 4.1% (4/95) of patients, a mean of 14.5 +/- 13.7 days from ictus; three of these four patients were receiving an AED at the time of seizure. Inpatient AED were prescribed to 99% of the cohort for a median of 12 (range 1 to 68) days. Approximately 8% of the cohort had posthospital discharge seizures; this included the patients who had prehospital or in-hospital seizures, 50% of whom were receiving AED therapy at the time of the seizure. Adverse effects occurred in 4. 1%; none were serious. The thickness of cisternal clot was associated with having a seizure; no other clinical predictors were identified. Having a seizure at any time did not adversely affect outcome. CONCLUSIONS: In this SAH population, the majority of seizures happened before medical presentation. In-hospital seizures were rare and occurred more than 7 days postictus for patients receiving AED prophylaxis. The vast majority of putative clinical predictors did not help predict the occurrence of seizures; only the thickness of the cisternal clot was of value in predicting seizures. Patient selection for and the efficacy and timing of AED prophylaxis after SAH deserve prospective evaluation.

Implications of extubation delay in brain-injured patients meeting standard weaning criteria.

We hypothesized that variation in extubating brain injured patients would affect the incidence of nosocomial pneumonia, length of stay, and hospital charges. In a prospective cohort of consecutive, intubated brain-injured patients, we evaluated daily: intubation status, spontaneous ventilatory parameters, gas exchange, neurologic status, and specific outcomes listed above. Of 136 patients, 99 (73%) were extubated within 48 h of meeting defined readiness criteria. The other 37 patients (27%) remained intubated for a median 3 d (range, 2 to 19). Patients with delayed extubation developed more pneumonias (38 versus 21%, p < 0.05) and had longer intensive care unit (median, 8.6 versus 3.8 d; p < 0.001) and hospital (median, 19.9 versus 13.2 d; p = 0.009) stays. Practice variation existed after stratifying for differences in Glasgow Coma Scale scores (10 versus 7, p < 0.001) at time of meeting readiness criteria, particularly for comatose patients. There was a similar reintubation rate. Median hospital charges were $29,057.00 higher for extubation delay patients (p < 0.001). This study does not support delaying extubating patients when impaired neurologic status is the only concern prolonging intubation. A randomized trial of extubation at the time brain-injured patients fulfill standard weaning criteria is justifiable.

Safety and feasibility of continuous infusion of remifentanil in the neurosurgical intensive care unit.

OBJECTIVE: Remifentanil is a selective mu-opioid agonist with a context-sensitive half-time of 3 to 5 minutes, independent of dose or administration duration. Other desirable effects include decreased cerebral metabolism and intracranial pressure (ICP) with minimal cerebral perfusion pressure changes. We present six cases illustrating indications for the use of remifentanil in the neurosurgical intensive care unit. METHODS: Patients received bolus doses of remifentanil of 0.05 to 1.0 microg/kg, followed by continuous infusions of 0.03 to 0.26 microg/kg/min, titrated to effect. When infusions were discontinued for neurological examinations, another bolus dose preceded infusion reinstitution. Indications for the use of remifentanil included mean arterial pressure and cerebral perfusion pressure decreases with the use of other agents (e.g., codeine or propofol) for ICP control, elevated ICP that was refractory to propofol/mannitol treatment, agitation that was unresponsive to standard therapies, and coughing that caused ICP increases after subarachnoid hemorrhage. RESULTS: Three patients experienced spontaneous intracranial bleeding (two cases of subarachnoid hemorrhage and one case of intraventricular hemorrhage), and three patients exhibited severe traumatic subdural hemorrhage. All patients recovered from the effects of remifentanil within 3 minutes after discontinuation of infusion, which allowed frequent rapid neurological assessments. Procedures for pulmonary toilet (i.e., endotracheal suctioning, postural drainage, and bronchoscopy) were performed without deleterious ICP increases or mean arterial pressure or cerebral perfusion pressure decreases during remifentanil infusions. CONCLUSION: The ultrashort duration of action of remifentanil allowed easy performance of frequent neurological examinations in the neurosurgical intensive care unit. No patient experienced deleterious hemodynamic or neurological effects as a result of remifentanil use.

Tissue plasminogen activator for acute ischemic stroke in patients with unruptured cerebral aneurysms.

Intracranial hemorrhage (ICH) is the most feared complication of thrombolytic therapy for acute ischemic stroke. There are limited data on the risks of thrombolysis in patients with asymptomatic intracranial aneurysm. We report 2 adults with signs of hemispheric ischemia who were successfully treated with intravenous tissue plasminogen activator (t-PA), despite the presence of asymptomatic intracranial aneurysm. The presence of an asymptomatic intracranial aneurysm may not necessarily preclude a good outcome from acute ischemic stroke treated with rt-PA. Selected patients harboring incidental, unruptured intracranial aneurysm may benefit from thrombolytics.

Cerebrospinal fluid creatine kinase-BB isoenzyme activity and outcome after subarachnoid hemorrhage.

BACKGROUND: The brain is rich in creatine kinase-BB isoenzyme activity (CK-BB), which is not normally present in cerebrospinal fluid (CSF). Results of previous studies have shown that CK-BB can be detected in the CSF of patients with aneurysmal subarachnoid hemorrhage (SAH), but whether CK-BB levels correlate with patients' neurologic outcomes is unknown. OBJECTIVE: To evaluate the relationship between CSF CK-BB level and outcome after SAH. DESIGN: Prospective observational cohort. SETTING: University-affiliated tertiary care center. PATIENTS: Convenience sample of 30 patients seen for cerebral aneurysm clipping. INTERVENTIONS: We sampled and assayed CSF for CK isoenzymes a median of 3 days after SAH in 27 patients, and at the time of unruptured aneurysm clipping in 3 patients. MAIN OUTCOME MEASURES: Without knowledge of CK results, we assigned the Glasgow Outcome Scale score early (approximately 1 week) and late (approximately 2 months) after surgery. RESULTS: Higher CSF CK-BB levels were associated with higher Hunt and Hess grades at hospital admission (Spearman rank correlation, p = 0.69; P<.001), lower Glasgow Coma Scale scores at hospital admission (p = -0.72; P<.001), and worse early outcomes on the Glasgow Outcome Scale (p = -0.64; P<.001). For patients with a favorable early outcome (Glasgow Outcome Scale score, 3-5), all CK-BB levels were less than 40 U/L. With a cutoff value of 40 U/L, CK-BB had a sensitivity of 70% and a specificity of 100% for predicting unfavorable early outcome (Glasgow Outcome Scale score, 1-2). Having a CK-BB level greater than 40 U/L increased the chance of an unfavorable early outcome, from 33% (previous probability) to 100%, whereas a CK-BB level of 40 U/L or less decreased it to 13%. Similar findings were obtained when considering late outcomes. CONCLUSION: The level of CSF CK-BB may help predict neurologic outcome after SAH.

Urokinase activity after freezing: implications for thrombolysis in intraventricular hemorrhage.

The retention of urokinase activity after frozen storage was studied. Urokinase powder was reconstituted aseptically in sterile water for injection or preservative-free 0.9% sodium chloride injection to a final concentration of 5000 IU/mL. Samples were stored in 5-mL plastic syringes at -20 or -70 degrees C for up to six months. Samples containing urokinase 25,000 IU/mL were similarly prepared by using sodium chloride injection as the diluent and were stored frozen at the same temperatures for up to 93 days. Urokinase activity was measured with a chromogenic assay at each test interval. Samples were also cultured after thawing to evaluate their potential to support microbial growth. The activity of urokinase at either concentration did not change appreciably during the study period. The method of thawing-at room temperature or in a refrigerator-had no effect on urokinase activity. No microbial growth was observed. Urokinase 5000 IU/mL did not show any changes in activity when reconstituted with sterile water for injection or 0.9% sodium chloride injection and frozen for up to six months. Urokinase 25,000 IU/mL in sodium chloride injection was also stable after 93 days of frozen storage.