Surgical Management of Giant Intracranial Arteriovenous Malformations: A Single Center Experience over 32 years.

OBJECTIVE: Treatment of giant intracranial arteriovenous malformations (gAVMs) is a formidable challenge for neurosurgeons and carries significant morbidity and mortality rates for patients compared with smaller AVMs. In this study, we reviewed the treatments, angiographic results, and clinical outcomes in 64 patients with gAVMs who were treated at Henry Ford Hospital between 1980 and 2012. METHODS: The arteriovenous malformation (AVM) database at our institution was queried for patients with gAVMs (≥ 6 cm) and data regarding patient demographics, presentation, AVM angioarchitecture, and treatments were collected. Functional outcomes as well as complications were analyzed. RESULTS: Of the 64 patients, 33 (51.6%) were female and 31 (48.4%) were male, with an average age of 45.7 years (SD ± 15.5). The most common symptoms on presentation were headaches (50%), seizures (50%), and hemorrhage (41%). The mean AVM size was 6.65 cm (range, 6-9 cm). Only 6 AVMs (9.4%) were located in the posterior fossa. The most common Spetzler-Martin grade was V, seen in 64% of patients. Of the 64 patients, 42 (66%) underwent surgical excision, 10 (15.5%) declined any treatment, 8 (12.5%) were deemed inoperable and followed conservatively, 2 (3%) had stand-alone embolization, 1 (1.5%) had embolization before stereotactic radiosurgery, and 1 (1.5%) received stereotactic radiosurgery only. Complete obliteration was achieved in 90% of the surgical patients. Mortality rate was 19% in the surgical cohort compared with 22% in the observation cohort (P = 0.770). CONCLUSIONS: Treatment of gAVMs carries significant morbidity and mortality; however, good outcomes are attainable with a multimodal treatment approach in carefully selected patients.

Bedside external ventricular drain placement: can multiple passes be predicted on the computed tomography scan before the procedure?

OBJECTIVE: Bedside external ventricular drain (EVD) placement is less than perfect and often requires multiple passes to achieve cerebrospinal fluid flow. We conducted this prospective study to understand why multiple passes are necessary and whether this affects the incidence of hemorrhage. METHODS: We compared the number of passes in 47 EVD placement procedures to the incidence of hemorrhage after the procedure. We also analyzed computed tomography scans before the procedure to identify variables that correlate with multiple passes. RESULTS: Of the procedures analyzed, 72% (34/47) were single pass whereas 28% (13/47) required multiple passes. Average number of passes was 1.85 (± 1.8), but average number of passes when multiple passes were made was 4.1 (± 2.29; range, 2-9). Incidence of tract hemorrhage was 10.6% (5/47). Of those, 11.8% (4/34) were in the single-pass group and 7.7% (1/13) from the multiple-pass group. There was no statistical relationship between the number of passes and hemorrhage (P > 0.99). Subarachnoid hemorrhage, intraventricular hemorrhage, and midline shift were not found to be statistically significant in relation to the number of passes. The presence of midline rostral hematoma significantly correlated with multiple passes. One of 34 patients (2.9%) needed a single pass and 5/13 (38.5%) needed multiple passes in the presence of midline rostral hematoma (P = 0.0011). The average targeted frontal horn volume was larger in patients who needed single pass EVD (12.4 ± 6.3 cm(2) vs. 8.0 ± 4.7 cm(2); P = 0.035). CONCLUSIONS: Multiple passes are inherent to the bedside EVD procedure, but did not increase the rate of intracranial hemorrhage.

Civamide cream 0.075% in patients with osteoarthritis of the knee: a 12-week randomized controlled clinical trial with a longterm extension.

OBJECTIVE: To evaluate the safety and efficacy of civamide cream 0.075% for the treatment of osteoarthritis (OA) of the knee. METHODS: We conducted a 12-week, multicenter, randomized, double-blind study with a 52-week open-label extension. Patients with OA of the knee received either civamide cream 0.075% or a lower dose of civamide cream, 0.01%, as the control. The 3 co-primary endpoints in the double-blind study were the time-weighted average (TWA) of change from baseline to Day 84 in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale, the WOMAC physical function subscale, and the Subject Global Evaluation (SGE). In the 52-week open-label extension study, the Osteoarthritis Pain Score and SGE were assessed. RESULTS: A total of 695 patients were randomized to receive civamide cream 0.075% (n = 351) or civamide cream 0.01% (control; n = 344) in the double-blind study. Significance in favor of civamide cream 0.075% was achieved for the TWA for all 3 co-primary efficacy variables: WOMAC pain (p = 0.009), WOMAC physical function (p < 0.001), and SGE (p = 0.008); and at Day 84 for these 3 variables (p = 0.013, p < 0.001, and p = 0.049, respectively). These analyses accounted for significant baseline-by-treatment interactions. In the 52-week open-label extension, efficacy was maintained. Civamide cream 0.075% was well tolerated throughout the studies. CONCLUSION: These studies demonstrate the efficacy of civamide cream for up to 1 year of continuous use. Civamide cream, with its lack of systemic absorption, does not have the potential for serious systemic toxicity, in contrast to several other OA treatments.

Strategic placement of bedside ventriculostomies using ultrasound image guidance: report of three cases.

BACKGROUND: The blind free-hand technique for external ventricular drain (EVD) placement sometimes requires multiple attempts, and catheter location is often less than ideal. Our institution has adapted an intraoperative ultrasound-guided ventriculostomy technique for the placement of EVDs at the bedside. Our experience with ultrasound at the bedside has proven to be invaluable in certain circumstances. We present three cases of strategic EVD catheter trajectories that were made possible at the bedside with the use of ultrasound. METHODS: Illustrative cases were chosen from a larger prospective study investigating the ultrasound-guided EVD technique. A portable ultrasound with a "burr hole" probe was used with modification of the standard surgical technique for placement of EVDs at the bedside. RESULTS: Case 1 describes an unexpected re-hemorrhage that was first realized by the ultrasound image obtained during the bedside EVD placement procedure. The catheter was purposefully directed across midline to the more prominent ventricle on the contralateral side based on this real-time finding. Case 2 describes how ultrasound was used to salvage the failed free-hand procedure and cannulate an extremely small ventricular space at the bedside. Case 3 describes an unconventionally placed burr hole that provided a customized trajectory in which the EVD catheter was placed just laterally and inferior to a large frontal hematoma. CONCLUSION: Ultrasound-guided bedside EVD placement allows EVD trajectories to be customized based on real-time information to accommodate for distorted and dynamic anatomy of the brain and its ventricles.

Effects of opioid antagonists on unconditioned and conditioned hyperactivity to morphine.

In a series of experiments, the ability of selective mu- (beta-funaltrexamine, beta-FNA), delta- (naltrindole, nalt) and kappa- (nor-binaltorphimine, nor-BNI) opioid receptor antagonists to attenuate the unconditioned and conditioned hyperactive effects of morphine was examined. For comparison, the nonselective opioid receptor antagonist naloxone (nalx) was also examined. Locomotor activity served as the behavioral measure. Experiment 1 found that doses of 1 and 4, but not 16 mg/kg, of morphine effectively produced conditioned hyperactivity (CH). Experiments 2a-d found that beta-FNA, nalt, nor-BNI and nalx, respectively, attenuated unconditioned morphine-induced hyperactivity. Experiments 3a-c, however, found that none of the selective antagonists, given individually, attenuated CH. In contrast, nalx did attenuate CH (Experiment 3d). Collectively results suggest that the unconditioned and conditioned hyperactive responses to morphine are mediated by different receptor systems and that activation of multiple opioid-receptor subtypes mediate expression of CH.

Intranasal civamide for the treatment of episodic cluster headaches.

OBJECTIVE: To evaluate the safety and efficacy of intranasal civamide solution for preventive treatment during an episodic cluster headache period. SUBJECTS AND METHODS: This was a multicenter, double-blind, randomized, vehicle-controlled study with a 7-day treatment period and a 20-day posttreatment period performed at 14 headache/neurology centers in the United States. Twenty-eight subjects were randomized to receive civamide or its vehicle in a 2:1 ratio; 18 received civamide and 10 received the vehicle. Subjects received 100 microL of 0.025% civamide (25 microg) or 100 microL of the vehicle to each nostril via dropper once daily for 7 days. The total daily dose of civamide was 50 microg. MAIN OUTCOME MEASURES: The number of cluster headaches per week during the treatment and posttreatment periods, pain intensity, presence of associated symptoms, and the incidence of adverse events were assessed. RESULTS: Subjects in the civamide group had a significantly greater percent decrease in the number of headaches from baseline to posttreatment during days 1 through 7 (-55.5% vs -25.9%; P =.03) and a trend toward significance during days 8 through 14 (-66.9% vs -32.3%; P =.07) and days 15 through 20 (-70.6% vs -34.9%; P =.07), as well as a near-significant decrease during the entire posttreatment period (days 1 through 20 [P =.054]) compared with the vehicle group. There were larger decreases in the number of headaches per week during the posttreatment period in the civamide-treated group, with trends toward significance during posttreatment days 8 through 14 (-8.6 vs -3.6; P =.09) and days 15 through 20 (-8.9 vs -3.6; P =.07). There were no significant differences between groups in cluster headache pain intensity, number of severe headaches, or associated symptoms. The most common adverse events included nasal burning (14 of 18 civamide-treated subjects, 1 of 10 vehicle-treated subjects; P =.001) and lacrimation (9 of 18 civamide-treated subjects, 0 of 10 vehicle-treated subjects; P =.01). CONCLUSION: Intranasal civamide solution at a dose of 50 microg may be modestly effective in the preventive treatment of episodic cluster headache.