Biomedical subjects

Brian-Fred Fitzsimmons

Publications and source records attributed to Brian-Fred Fitzsimmons.

10 recordsLinked to original sources

PubMed2006

Recent steps toward a reconstructive endovascular solution for the orphaned, complex-neck aneurysm.

OBJECTIVE: The purposes of this article are to summarize recent developments and concerns in endovascular aneurysm therapy leading to the adjunctive use of endoluminal devices, to review the published literature on stent-supported coil embolization of cerebral aneurysms, and to describe our experience with this technique in a limited subgroup of problematic complex aneurysms over a medium-term follow-up period. METHODS: Between January 2003 and June 2004, 28 individuals among 157 patients with cerebral aneurysms we evaluated were identified as harboring aneurysms with exceptionally broad necks. Out of these 28 patients, 16 were treated with a combination of stents and detachable coils, preserving the parent artery. Recorded data included patient demographics, the clinical presentation, aneurysm location and characteristics, procedural details, and clinical and angiographic outcome. RESULTS: Over an 18-month period, 16 patients with large cerebral aneurysms additionally characterized by neck sizes between 7 and 14 mm were treated, using combined coil embolization of the aneurysm with stent reconstruction of the aneurysm neck. Thirteen out of the 16 aneurysms were occluded at angiographic reevaluation between 11 and 24 months (mean angiographic follow-up, 17.5 mo). There were no treatment-related deaths or clinically evident neurological complications. Thirteen patients experienced excellent clinical outcomes, with good outcomes in two patients and a poor visual outcome in one patient (mean clinical follow-up, 29 mo). A single technical complication occurred, involving transient nonocclusive stent-associated thrombus, which was treated uneventfully with abciximab. CONCLUSION: Stent-supported coil embolization of large, complex-neck cerebral aneurysms seems to provide superior medium-term anatomic reconstruction of the parent artery compared with historic series of aneurysms treated exclusively with endosaccular coils. In the near future, increasingly sophisticated endoluminal devices offering higher coverage of the neck defect will likely enable more definitive endovascular treatment of complex cerebral aneurysms and further expand our ability to manipulate the vascular biology of the parent artery.

Blood Vessel Prosthesis↗

PubMed2005

Predictors and impact of aneurysm rebleeding after subarachnoid hemorrhage.

BACKGROUND: Aneurysm rebleeding has historically been an important cause of mortality after subarachnoid hemorrhage (SAH). OBJECTIVE: To describe the frequency and impact of rebleeding in the modern era of aneurysm care, which emphasizes early surgical or endovascular treatment. DESIGN: Inception cohort. SETTING: Tertiary care medical center. PATIENTS: A total of 574 patients enrolled in the Columbia University SAH Outcomes Project between August 1996 and June 2002. Early aneurysm repair was performed whenever feasible. MAIN OUTCOME MEASURES: Rebleeding was defined by prespecified clinical and radiographic criteria, excluding prehospital, intraprocedural, and postrepair events. Functional outcome was assessed at 3 months with the modified Rankin Scale. Multiple logistic regression was used to identify predictors of rebleeding, poor functional outcome, and mortality. RESULTS: Rebleeding occurred in 40 (6.9%) of the 574 patients; most cases (73%) occurred within 3 days of ictus. Hunt-Hess grade on admission (odds ratio [OR], 1.92 per grade; 95% confidence interval [CI], 1.33-2.75; P<.001) and maximal aneurysm diameter (OR, 1.07/mm; 95% CI, 1.01-1.13; P = .005) were independent predictors of rebleeding. After controlling for Hunt-Hess grade and aneurysm size, rebleeding was associated with a markedly reduced chance of survival with functional independence (modified Rankin Scale score, </=4; OR, 0.08; 95% CI, 0.02-0.34) at 3 months. CONCLUSIONS: Despite an aggressive management strategy, rebleeding still occurred in 6.9% of patients and was associated with a dismal outcome. Poor Hunt-Hess grade and larger aneurysm size are related to rebleeding. Pharmacologic therapy to reduce the risk of rebleeding before aneurysm repair, particularly in patients with poor grade neurologic status and large aneurysms, deserves renewed attention.

Aged↗

PubMed2005

Dobutamine versus milrinone after subarachnoid hemorrhage.

OBJECTIVE: Neurogenic stunned myocardium is a well-recognized complication of subarachnoid hemorrhage. Dobutamine and milrinone are both used for neurogenic stunned myocardium, but there are few data comparing them after subarachnoid hemorrhage. METHODS: We compared the physiological dose response of dobutamine and milrinone in patients with subarachnoid hemorrhage requiring a pulmonary artery catheter. We located 11 patients who received either inotrope. Physiological data were fitted to a mixed model accounting for drug, dose, and between-patient variation. RESULTS: There were 11 patients who had 152 pulmonary artery catheter measurements. Two received both inotropes (but not within 4 h of each other), 2 only milrinone, and 7 only dobutamine. The groups had similar clinical and physiological characteristics. After adjustment for vasopressin, milrinone was significantly more potent in increasing cardiac output (P <0.0001) and stroke volume (P=0.03), while decreasing vascular resistance (P <0.0001) and systolic blood pressure (P=0.008), than dobutamine. CONCLUSION: These data suggest that milrinone and dobutamine should be used in different clinical situations. Milrinone may be more effective in patients with severely depressed systolic function but who have at least normal vascular resistance and blood pressure and in whom raising cardiac output is the primary goal. Dobutamine may be superior when vascular resistance or blood pressure is low.

Adrenergic beta-Agonists↗

PubMed2004

Clinical trial of a novel surface cooling system for fever control in neurocritical care patients.

OBJECTIVE: To compare the efficacy of a novel water-circulating surface cooling system with conventional measures for treating fever in neuro-intensive care unit patients. DESIGN: Prospective, unblinded, randomized controlled trial. SETTING: Neurologic intensive care unit in an urban teaching hospital. PATIENTS: Forty-seven patients, the majority of whom were mechanically ventilated and sedated, with fever > or =38.3 degrees C for >2 consecutive hours after receiving 650 mg of acetaminophen. INTERVENTIONS: Subjects were randomly assigned to 24 hrs of treatment with a conventional water-circulating cooling blanket placed over the patient (Cincinnati SubZero, Cincinnati OH) or the Arctic Sun Temperature Management System (Medivance, Louisville CO), which employs hydrogel-coated water-circulating energy transfer pads applied directly to the trunk and thighs. MEASUREMENTS AND MAIN RESULTS: Diagnoses included subarachnoid hemorrhage (60%), cerebral infarction (23%), intracerebral hemorrhage (11%), and traumatic brain injury (4%). The groups were matched in terms of baseline variables, although mean temperature was slightly higher at baseline in the Arctic Sun group (38.8 vs. 38.3 degrees C, p = .046). Compared with patients treated with the SubZero blanket (n = 24), Arctic Sun-treated patients (n = 23) experienced a 75% reduction in fever burden (median 4.1 vs. 16.1 C degrees -hrs, p = .001). Arctic Sun-treated patients also spent less percent time febrile (T > or =38.3 degrees C, 8% vs. 42%, p < .001), spent more percent time normothermic (T < or =37.2 degrees C, 59% vs. 3%, p < .001), and attained normothermia faster than the SubZero group median (2.4 vs. 8.9 hrs, p = .008). Shivering occurred more frequently in the Arctic Sun group (39% vs. 8%, p = .013). CONCLUSION: The Arctic Sun Temperature Management System is superior to conventional cooling-blanket therapy for controlling fever in critically ill neurologic patients.

Adult↗

PubMed2004

Chemical meningitis after cerebral aneurysm treatment using two second-generation aneurysm coils: report of two cases.

OBJECTIVE AND IMPORTANCE: In the quest for effective and durable endovascular aneurysm treatment, second-generation aneurysm coils endeavor to increase the biological healing response to the implanted material. We report two cases of large cerebral aneurysms treated concurrently with both available second-generation aneurysm coils and the subsequent development of symptomatic nonbacterial meningitis. CLINICAL PRESENTATION: Two previously healthy patients underwent endovascular treatment for large (>=2 cm) cerebral aneurysms. Both aneurysms were treated using multiple Hydrogel coils (MicroVention, Inc., Aliso Viejo, CA) and Matrix coils (Boston Scientific/Target, Fremont, CA). Careful aseptic technique was observed throughout each procedure, and prophylactic intravenous antibiotics were administered during the perioperative period to both patients. Treatment proceeded uneventfully in both cases with excellent aneurysm occlusion and no immediate postoperative neurological deficits. INTERVENTION: In both cases, the patients were discharged from hospital but quickly were readmitted with stigmata of meningitis. Imaging demonstrated durable occlusion of the aneurysms in both patients and also abnormalities indicative of perianeurysmal and diffuse intracranial inflammatory response. Complete septic workup failed to identify an organism in either patient. Both patients responded to treatment with corticosteroid medication used to modulate the inflammatory response induced by the coil implants. CONCLUSION: Second-generation aneurysm coils were developed to promote more durable occlusion of cerebral aneurysms by promoting more complete volumetric aneurysm occlusion or by eliciting a more prolific inflammatory response. The concurrent use of Hydrogel and Matrix coil systems in large aneurysms may cause an exuberant inflammatory response with both local and systemic manifestations. Although vigilant evaluation and treatment for presumptive bacterial meningitis is required in all such cases, patients respond to immunomodulatory therapy with corticosteroids. More information to understand better the interaction of Hydrogel and Matrix coils is needed.

Embolization, Therapeutic↗

PubMed2003

Midazolam challenge reinduces neurological deficits after transient ischemic attack.

BACKGROUND AND PURPOSE: A transient ischemic attack (TIA) in the brain is classically considered a syndrome lasting <24 hours. Having previously shown that an experimental challenge with the GABAA agonist midazolam in recovered stroke patients can reinduce the acute clinical state, we determined whether TIA patients would demonstrate a similar effect. METHODS: Four right-handed patients participated: 3 with clinical TIA presumed to have affected the left hemisphere within the previous 24 to 72 hours and no evidence of a new lesion on diffusion-weighted and fluid-attenuated inversion recovery imaging, and 1 patient with an asymptomatic temporal arteriovenous malformation. The TIA duration ranged from 30 minutes to 3 hours. Each patient underwent baseline testing for motor function and aphasia, after which intravenous midazolam was delivered until mild drowsiness was detected. Patients were tested during the peak drug effect and again after 2 hours when sedation had dissipated. RESULTS: No patient showed weakness or aphasia at baseline. After administration of midazolam, all 3 TIA patients demonstrated re-emergence of features that characterized their recent transient neurological syndromes (right-sided weakness and/or aphasia) but no left-sided findings. The arteriovenous malformation patient who had never been symptomatic showed no drug effect. Two hours later, all TIA patients returned to their normal clinical state. CONCLUSIONS: Patients who had suffered recent transient cerebral ischemic episodes and were neurologically intact with negative diffusion-weighted imaging showed re-emergence of prior focal deficits after administration of a benzodiazepine in a dose that produces light sedation. These findings suggest that presumed TIA may produce neuronal dysfunction beyond the symptomatic period.

Adult↗

PubMed2002

Refractory status epilepticus: frequency, risk factors, and impact on outcome.

BACKGROUND: Refractory status epilepticus (RSE) is a life-threatening condition in which seizures do not respond to first- and second-line anticonvulsant drug therapy. How often RSE occurs, risk factors that predispose to this condition, and the effect of failure to control seizures on clinical outcome are poorly defined. OBJECTIVE: To determine the frequency, risk factors, and impact on outcome of RSE. DESIGN: Retrospective cohort study. SETTING: Large academic teaching hospital. PATIENTS: Consecutive sample of 83 episodes of status epilepticus in 74 patients (mean age, 63 years). MAIN OUTCOME MEASURES: Refractory status epilepticus was defined as seizures lasting longer than 60 minutes despite treatment with a benzodiazepine and an adequate loading dose of a standard intravenous anticonvulsant drug. Factors associated with RSE were identified using univariate and backward stepwiselogistic regression analyses. RESULTS: In 57 episodes (69%), seizures occurred after treatment with a benzodiazepine, and in 26 (31%), seizures occurred after treatment with a second-line anticonvulsant drug (usually phenytoin), fulfilling our criteria for RSE. Nonconvulsive SE (P=.03) and focal motor seizures at onset (P=.04) were identified as independent risk factors for RSE. Eleven (42%) of 26 patients with RSE had seizures after receiving a third-line agent (usually phenobarbital). Although mortality was not increased (17% overall), RSE was associated with prolonged hospital length of stay (P<.001) and more frequent functional deterioration at discharge (P=.02). CONCLUSIONS: Refractory status epilepticus occurs in approximately 30% of patients with SE and is associated with increased hospital length of stay and functional disability. Nonconvulsive SE and focal motor seizures at onset are risk factors for RSE. Randomized controlled trials are needed to define the optimal treatment of RSE.

Adult↗

PubMed2002

Reemergence of stroke deficits with midazolam challenge.

BACKGROUND AND PURPOSE: Patients who have sustained a neurological injury and then improved may experience transient reemergence of their syndromes when given benzodiazepines. As a step toward assessing whether neurotransmitter systems underlie poststroke clinical improvement, we selected midazolam, a gamma-aminobutyric acid(A) (GABA(A)) agonist, for systemic administration to measure general or stroke-specific effects in patients. METHODS: Eight patients with image-verified stroke (5 with left-sided and 3 with right-sided cerebral lesions) participated. The strokes had occurred from 7 days to 6 years earlier, with patients showing clinical improvement from their initial syndromes. Each patient underwent baseline testing for motor function, aphasia, and left hemispatial neglect, after which intravenous midazolam was delivered until mild drowsiness was detected. Patients were tested during this period and again after 2 hours when sedation had dissipated. RESULTS: After the administration of midazolam, the 5 patients with left hemisphere stroke demonstrated reemergence or worsening of their initial right hemiparesis and aphasia but showed no left neglect. The 3 patients with right cerebral stroke showed reemergence of left hemiparesis and left visual field neglect but no aphasia. All patients returned to baseline after 2 hours. CONCLUSIONS: Under conditions of light sedation, patients whose initial stroke syndrome had substantially improved clinically showed transient reemergence of their initial focal syndrome. These data suggest a possible role for GABA(A)-mediated neurochemical mechanisms in poststroke improvement and sensitivity to medication effects.

Adult↗

PubMed2002

Intraarterially administered verapamil as adjunct therapy for cerebral vasospasm: safety and 2-year experience.

BACKGROUND AND PURPOSE: Despite the widespread use of angioplasty, adjunct chemical therapy is often needed to treat patients with cerebral vasospasm. In this study, we examined the safety of intraarterial administration of verapamil to patients with cerebral vasospasm. We herein summarize our 2-year experience with this treatment. METHODS: We retrospectively reviewed the procedure reports, anesthesia records, clinical charts, and brain images of 29 patients who received intraarterially administered verapamil in 34 procedures for the treatment of vasospasm after subarachnoid hemorrhage from July 1998 to June 2000. The average changes in mean arterial pressure and heart rate were used to measure cardiovascular side effects. The neurologic effects were assessed by angiographic findings, the results of neurologic examinations performed before and after the procedure, and findings of CT of the head. RESULTS: The average dose of verapamil per patient was 3 +/- 0 mg or 44 +/- 5 mcg/kg. The average changes in mean arterial pressure at 10 and 20 minutes were -5 +/- 1 mm Hg and -2 +/- 1 mm Hg or -3.8 +/- 1.0% and -1.7 +/- 1.1%, respectively. No significant change of heart rate was observed at 10 minutes. The patients showed no sign of increased intracranial pressure by hemodynamic parameters, neurologic examination, or CT of the head. On 10 occasions, when the effect of verapamil infusion was assessed angiographically, there was 44 +/- 9% increase of vessel diameter in the spastic segment. Neurologic improvement was noted after five of 17 procedures when verapamil was used as the sole treatment. CONCLUSION: Low dose verapamil is safe when administered intraarterially to patients with cerebral vasospasm. Beneficial effects are achieved in some patients, prompting further study of its efficacy.

Calcium Channel Blockers↗

PubMedDate not supplied

A phase 2 study of tramiprosate for cerebral amyloid angiopathy.

BACKGROUND AND PURPOSE: No treatments have been identified to lower the risk of intracerebral hemorrhage due to cerebral amyloid angiopathy (CAA). A potential approach to prevention is the use of agents that interfere with the pathogenic cascade initiated by the beta-amyloid peptide (Abeta). Tramiprosate (3-amino-1-propanesulfonic acid) is a candidate molecule shown in preclinical studies to reduce CAA in a transgenic mouse model. METHODS: We performed a 5-center phase 2 double-blinded trial to evaluate the safety, tolerability, and pharmacokinetics of tramiprosate in subjects with lobar intracerebral hemorrhage. Twenty-four subjects age > or =55 years with possible or probable CAA were randomized to receive 12 weeks of tramiprosate at 1 of 3 oral doses (50, 100, or 150 mg twice daily). Subjects were followed for clinical adverse effects, laboratory, vital sign, electrocardiogram, cognitive, or functional changes, appearance of new symptomatic or asymptomatic hemorrhages, and pharmacokinetic parameters. RESULTS: Enrolled subjects were younger (mean age 70.8+/-5.4, range 61 to 78) and had more advanced baseline disease (measured by number of previous hemorrhages) than consecutive subjects in a CAA natural history cohort. No concerning safety issues were encountered with treatment. Nausea and vomiting were the most common adverse events and were more frequent at high doses. Nine subjects had new symptomatic or asymptomatic hemorrhages during treatment; all occurred in subjects with advanced baseline disease, with no apparent effect of drug dosing assignment. CONCLUSIONS: These data suggest that tramiprosate can be given safely to subjects with suspected CAA and support future efficacy trials.

Aged↗