Low-dose recombinant tissue-type plasminogen activator enhances clot resolution in brain hemorrhage: the intraventricular hemorrhage thrombolysis trial.

BACKGROUND AND PURPOSE: Patients with intracerebral hemorrhage and intraventricular hemorrhage have a reported mortality of 50% to 80%. We evaluated a clot lytic treatment strategy for these patients in terms of mortality, ventricular infection, and bleeding safety events, and for its effect on the rate of intraventricular clot lysis. METHODS: Forty-eight patients were enrolled at 14 centers and randomized to treatment with 3 mg recombinant tissue-type plasminogen activator (rtPA) or placebo. Demographic characteristics, severity factors, safety outcomes (mortality, infection, bleeding), and clot resolution rates were compared in the 2 groups. RESULTS: Severity factors, including admission Glasgow Coma Scale, intracerebral hemorrhage volume, intraventricular hemorrhage volume, and blood pressure were evenly distributed, as were adverse events, except for an increased frequency of respiratory system events in the placebo-treated group. Neither intracranial pressure nor cerebral perfusion pressure differed substantially between treatment groups on presentation, with external ventricular device closure, or during the active treatment phase. Frequency of death and ventriculitis was substantially lower than expected and bleeding events remained below the prespecified threshold for mortality (18% rtPA; 23% placebo), ventriculitis (8% rtPA; 9% placebo), symptomatic bleeding (23% rtPA; 5% placebo, which approached statistical significance; P=0.1). The median duration of dosing was 7.5 days for rtPA and 12 days for placebo. There was a significant beneficial effect of rtPA on rate of clot resolution. CONCLUSIONS: Low-dose rtPA for the treatment of intracerebral hemorrhage with intraventricular hemorrhage has an acceptable safety profile compared to placebo and historical controls. Data from a well-designed phase III clinical trial, such as CLEAR III, will be needed to fully evaluate this treatment.

Frequency of sustained intracranial pressure elevation during treatment of severe intraventricular hemorrhage.

BACKGROUND: Elevated intracranial pressure (ICP) is an important marker of neurological deterioration. The occurrence and significance of elevated ICP and low cerebral perfusion pressure (CPP) in aggressively treated spontaneous intraventricular hemorrhage (IVH) are not defined. METHODS: We performed a secondary longitudinal exploratory data analysis of a randomized multicenter trial of urokinase (UK) versus placebo (Pcb) as a treatment for IVH. Eleven IVH patients who required an external ventricular drain (EVD) were randomized to receive either intraventricular UK or Pcb every 12 h until clinical response permitted EVD removal. ICP and CPP were recorded every 4 or 6 h, as well as before and 1 h after EVD closure for administration of study agent. ICP, CPP and the proportion of ICP readings above 20, 30, 40 and 50 mm Hg were analyzed. RESULTS: Six UK and 5 Pcb patients aged 39-74 years (mean +/- standard deviation; 53 +/- 11 years) were enrolled. Initial ICP ranged from 0 to 38 mm Hg (10.9 +/- 11.0), initial CPP from 65 to 133 mm Hg (100.5 +/- 17.7). We recorded 472 ICP readings over the entire monitoring period. Of these 65 (14%) were >20 mm Hg, 23 (5%) >30 mm Hg, 9 (2%) >40 mm Hg and 3 (<1%) >50 mm Hg. Only 2 of 141 intraventricular injections of study agent with EVD closure were not tolerated and required reopening of the EVD. CONCLUSIONS: In the intensive care unit, initial ICP measured with an EVD was uncommonly elevated (1/11 patients) in this group of severe IVH patients despite acute obstructive hydrocephalus. Frequent monitoring reveals ICP elevation >20 mm Hg in 14% of observations during use of EVD. ICP elevation, though it can occur, is not routinely associated with EVD closure for thrombolytic treatment with UK.

Frameless stereotaxy-assisted clipping of distal anterior cerebral artery aneurysm: technical note and case series.

OBJECTIVE: Microsurgery for the clipping of cerebral aneurysms requires a working knowledge of the anatomy of the cerebral vasculature and its relationship to landmarks on the surface of the brain and along the skull base. However, for more distally located aneurysms of the anterior cerebral artery (ACA), locating the lesion can prove frustrating and may require much more extensive interhemispheric dissection than is otherwise needed for proximal control, exposure of the aneurysm, and clip application. We report a case series of five patients in which frameless stereotaxy and CT angiographic data sets were used to minimize the extent of surgery required to clip distal ACA aneurysms. CLINICAL PRESENTATIONS: Five patients were found to have distal ACA aneurysms during the work-up of subarachnoid hemorrhage or other neurologic symptoms. The patients comprised two with subarachnoid hemorrhage, one with dizziness, one with stroke, and one with migraines and polycystic kidney disease. Each patient was found to have an aneurysm at the pericallosal/callosal marginal junction. INTERVENTION: All five patients underwent a right parasagittal craniotomy and clipping of a distal ACA aneurysm. The location of the craniotomy and subsequent interhemispheric dissection were guided by CT angiographic data sets and computer-assisted frameless stereotaxy. CONCLUSION: Frameless stereotaxy using a CT angiographic data set is a useful adjunct to routine microsurgery in the clipping of distal ACA aneurysms. Its use obviates the need for extensive interhemispheric dissection, allows the surgeon to gain proximal control and expose the aneurysm more efficiently, and should minimize complications related to unwitting aneurysm exposure.

Preventing Distal Catheter Obstruction in Laparoscopic Ventriculoperitoneal Shunt Placement in Adults: The "Falciform Technique".

BACKGROUND: Distal obstruction of ventriculoperitoneal (VP) shunts is a major problem in the treatment of hydrocephalus. To avoid this complication, we describe a simple method using the falciform ligament to place and hold the distal catheter in the right subdiaphragmatic space, preventing catheter migration and distal obstruction. MATERIALS AND METHODS: We retrospectively collected data of all VP shunt insertion and revision for adults with idiopathic normal-pressure hydrocephalus between November 2011 and September 2013. All of these were done using the "falciform technique," with the distal catheter portion performed laparoscopically. No exclusion criteria were applied. A neurosurgeon and a laparoscopic surgeon were involved in each case. The falciform ligament was used to tether the distal catheter above the liver, with the distal tip of the catheter reaching the hepatic flexure to allow for drainage directly into the right paracolic gutter. Baseline, operative, and postoperative data were collected and analyzed. RESULTS: In total, 58 patients underwent a shunt procedure during the period of study. The majority (74%) underwent new VP shunt placement, and 26% underwent revision and replacement for catheter obstruction. The female to male ratio was 1.14:1. Mean age was 67.3±17.5 years. Revisions due to distal catheter obstruction were subsequent to previous surgery placement. Median follow-up was 329 days. Three patients (5%) had proximal catheter obstruction requiring shunt revision. None of the patients (0%) was found to have distal obstruction at the end of the study period at the most recent follow-up. CONCLUSIONS: The faparoscopic falciform technique significantly reduces the rate of distal VP shunt obstruction in adults with idiopathic normal-pressure hydrocephalus. Continued follow-up is needed to confirm long-term patency of the catheter.

Intraventricular thrombolysis speeds blood clot resolution: results of a pilot, prospective, randomized, double-blind, controlled trial.

OBJECTIVE: Animal models and clinical studies suggest that intraventricular thrombolysis improves clot resolution and clinical outcomes among patients with intraventricular hemorrhage. However, this intervention may increase the rates of rebleeding and infection. To assess the safety and efficacy of intraventricular thrombolysis, we conducted a pilot, randomized, double-blind, controlled, multicenter study. METHODS: Patients with intraventricular hemorrhage requiring ventriculostomy were randomized to receive intraventricular injections of normal saline solution or urokinase (25000 international units) at 12-hour intervals. Injections continued until ventricular drainage was discontinued according to prespecified clinical criteria. Head computed tomographic scans were obtained daily, for quantitative determinations of intraventricular hemorrhage volumes. The rate of clot resolution was estimated for each group. RESULTS: Twelve subjects were enrolled (urokinase, seven patients; placebo, five patients). Commercial withdrawal of urokinase precluded additional enrollment. The urokinase and placebo groups were similar with respect to age (49.6 versus 55.2 yr, P = 0.43) and presenting Glasgow Coma Scale scores (7.14 versus 8.00, P = 0.72). Randomization to the urokinase treatment arm (P = 0.02) and female sex (P = 0.008) favorably affected the clot resolution rate. The sex-adjusted clot half-life for the urokinase-treated group was reduced 44.6%, compared with the value for the placebo group (4.69 versus 8.48 d). CONCLUSION: Intraventricular thrombolysis with urokinase speeds the resolution of intraventricular blood clots, compared with treatment with ventricular drainage alone.

The management of neuropathic pain.

Although the definitive treatment for neuropathic pain remains elusive, scientific investigation continues to provide the field with better and better therapies. As our understanding of the neurophysiologic mechanisms of pain improves, pharmaceutic therapies have become more effective even as side effects are minimized. Surgical therapies have become more precise and less invasive. Advances in neurophysiology have given rise to new advances in the field of neuro-modulation. As this therapy continues to emerge, ablative procedures recede as therapies offering minimal invasiveness, reversible mechanisms, and long-standing relief emerge to the forefront of treatment for neuropathic pain.

Gold fiducials are a unique marker for localization in the thoracic spine: a cost comparison with percutaneous vertebroplasty.

We present a unique application of the gold fiducial as a preoperative, radiographic marker placed in the thoracic spine and used for intraoperative localization. In comparison to percutaneous vertebroplasty marking of thoracic spinal levels with polymethyl methacrylate (PMMA) cement, implantation of the gold fiducial is technically facile with a minimal learning curve. The fiducial markers are also associated with significantly less financial resources. Following 2013 Current Procedural Terminology (CPT) coding, the cost of vertebroplasty under fluoroscopic guidance, $3195·43, or under computed tomography (CT) guidance, $3232·54, is more than double the cost of the gold fiducial implantation - $1237·55 and $1267·03, under similar imaging techniques, respectively. In the first description of gold fiducials in the thoracic spine, we conclude that the marker is a safe and cost-effective method for preoperative localization of the thoracic levels.

Predictors of outcome in civilian gunshot wounds to the head.

OBJECT: Civilian gunshot wounds to the head (GSWH) are often deadly, but some patients with open cranial wounds need medical and surgical management and are potentially good candidates for acceptable functional recovery. The authors analyzed predictors of favorable clinical outcome (Glasgow Outcome Scale scores of 4 and 5) after GSWH over a 24-month period. METHODS: The authors posited 2 questions: First, what percentage of civilians with GSWH died in the state of Maryland in a given period of time? Second, what were the predictors of favorable outcome after GSWH? The authors examined demographic, clinical, imaging, and acute care data for 786 civilians who sustained GSWH. Univariate and logistic regression analyses were used to analyze the data. RESULTS: Of the 786 patients in this series, 712 (91%) died and 74 (9%) completed acute care in 9 trauma centers. Of the 69 patients admitted to one Maryland center, 46 (67%) eventually died. In 48 patients who were resuscitated, the Injury Severity Score was 26.2, Glasgow Coma Scale (GCS) score was 7.8, and an abnormal pupillary response (APR) to light was present in 41% of patients. Computed tomography indicated midline shift in 17%, obliteration of basal cisterns in 41.3%, intracranial hematomas in 34.8%, and intraventricular hemorrhage in 49% of cases. When analyzed for trajectory, 57.5% of bullet slugs crossed midcoronal, midsagittal, or both planes. Two subsets of admissions were studied: 27 patients (65%) who had poor outcome (25 patients who died and 2 who had severe disability) and 15 patients (35%) who had a favorable outcome when followed for a mean period of 40.6 months. Six patients were lost to follow-up. Univariate analysis indicated that admission GCS score (p < 0.001), missile trajectory (p < 0.001), surgery (p < 0.001), APR to light (p = 0.002), patency of basal cisterns (p = 0.01), age (p = 0.01), and intraventricular bleed (p = 0.03) had a significant relationship to outcome. Multivariable logistic regression analysis indicated that GCS score and patency of the basal cistern were significant determinants of outcome. Exclusion of GCS score from the regression models indicated missile trajectory and APR to light were significant in determining outcome. CONCLUSIONS: Admission GCS score, trajectory of the missile track, APR to light, and patency of basal cisterns were significant determinants of outcome in civilian GSWH.

Delivery of stereotactic radiosurgery: a cross-platform comparison.

Stereotactic radiosurgery is a modern addition to the armamentarium of treatment options for intracranial and extracranial lesions. It is increasingly being used as an adjuvant to surgery, conventional radiation therapy, and chemotherapy as well as being used as primary treatment. Since the introduction of the Gamma Knife (Elekta, Stockholm, Sweden) system, many more stereotactic radiosurgery machines have become available. The objective of this review is to compare and contrast the various currently available stereotactic radiosurgery platforms.