Application of a Novel Brain Arteriovenous Malformation Endovascular Grading Scale for Transarterial Embolization.

BACKGROUND AND PURPOSE: The advent of modern neuroendovascular techniques has highlighted the need for a simple, effective, and reliable brain arteriovenous malformation endovascular grading scale. A novel scale of this type has recently been described. It incorporates the number of feeding arteries, eloquence, and the presence of an arteriovenous fistula component. Our aim is to assess the validity of this grading scale. MATERIALS AND METHODS: We retrospectively reviewed all suspected brain arteriovenous malformations at Massachusetts General Hospital from 2005 to 2013, identifying 126 patients who met the inclusion criteria. Spearman correlations between endovascular and Spetzler-Martin grading scales and long-term outcomes were performed. Median endovascular grades were compared between treatment modalities and endovascular outcomes. Binary regression analysis was performed with major endovascular complications as a dichotomized dependent variable. Intraclass correlation coefficients were calculated for interobserver reliability of the endovascular grading scale. RESULTS: A significant Spearman correlation between the endovascular grade and the Spetzler-Martin grade was demonstrated (ρ = 0.5, P < .01). Differences in the median endovascular grades between the endovascular cure (median = 2) and endovascular complication groups (median = 4) (P < .05) and between the endovascular cure and successful multimodal treatment groups (median = 3) (P < .05) were demonstrated. The endovascular grade was the only independent predictor of complications (OR = 0.5, P < .01). The intraclass correlation coefficient of the endovascular grade was 0.71 (P < .01). CONCLUSIONS: Validation of a brain arteriovenous malformation endovascular grading scale demonstrated that endovascular grades of ≤II were associated with endovascular cure, while endovascular grades of ≤III were associated with multimodal cure or significant lesion reduction and favorable outcome. The endovascular grade provides useful information to refine risk stratification for endovascular and multimodal treatment.

Functional magnetic resonance imaging and transcranial magnetic stimulation: complementary approaches in the evaluation of cortical motor function.

Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) represent different approaches to mapping the motor cortex. fMRI identifies areas of hemodynamic changes during task performance while TMS provides electrophysiologic data concerning the localization and density of cortical motoneurons. Here we define the spatial correlation between fMRI and TMS maps and compared them with direct electrical cortical stimulation (ECS). We performed fMRI at 1.5 T on 3 normal subjects and 2 patients with mass lesions near the central sulcus using a multislice, asymmetric, spin-echo, echo-planar pulse sequence during the performance of a motor task. We also performed focal TMS with surface EMG recordings from the muscles primarily involved in the fMRI task. We coregistered the stimulation sites in real time with the fMRI maps using a frameless stereotactic system. In both patients we also performed ECS of the cortex during surgery under local anesthesia. fMRI maps were validated by the electrophysiologic data both pre- and intraoperatively. Our results suggest that regions of fMRI activation correspond spatially to areas of highest motoneuron density as demonstrated by electrophysiologic techniques.

Reduction of post-traumatic brain injury and free radical production by inhibition of the caspase-1 cascade.

Necrotic and apoptotic cell death both play a role mediating tissue injury following brain trauma. Caspase-1 (interleukin-1beta converting enzyme) is activated and oligonucleosomal DNA fragmentation is detected in traumatized brain tissue. Reduction of tissue injury and free radical production following brain trauma was achieved in a transgenic mouse expressing a dominant negative inhibitor of caspase-1 in the brain. Neuroprotection was also conferred by pharmacological inhibition of caspase-1 by intracerebroventricular administration of the selective inhibitor of caspase-1, acetyl-Tyr-Val-Ala-Asp-chloromethyl-ketone or the non-selective caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone. These results indicate that inhibition of caspase-1-like caspases reduces trauma-mediated brain tissue injury. In addition, we demonstrate an in vivo functional interaction between interleukin-1beta converting enyzme-like caspases and free radical production pathways, implicating free radical production as a downstream mediator of the caspase cell death cascade.

Patients with polycystic kidney disease would benefit from routine magnetic resonance angiographic screening for intracerebral aneurysms: a decision analysis.

Autosomal dominant polycystic kidney disease (ADPKD) is associated with increased prevalence of cerebral aneurysms and increased risk of subarachnoid hemorrhage. A decision analysis by Levey et al. in 1983 demonstrated that patients with ADPKD would not significantly benefit from routine arteriographic screening for cerebral aneurysms. We reexamined this conclusion in light of new clinical data and the introduction of magnetic resonance imaging (MRI) as a screening method. We compared an MRI screening strategy with a nonscreening strategy. The screening strategy specified MRI screening and then neurosurgical management of detected aneurysms. The nonscreening strategy specified cerebrovascular care only in the event of subarachnoid hemorrhage. The decision tree incorporated estimates derived from the clinical literature for the prevalence of asymptomatic aneurysms in patients with ADPKD (15%), the annual incidence of aneurysmal rupture (1.6%), the morbidity and mortality rates associated with subarachnoid hemorrhage (70 and 56%, respectively), the risk of transfemoral arteriography (0.2%), the sensitivity and specificity of MRI, the morbidity and mortality rates associated with surgical treatment of an unruptured aneurysm (4.1 and 1.0%, respectively), and the life expectancy of patients with ADPKD. The model predicted that the screening strategy would provide 1.0 additional year of life without neurological disability to a 20-year-old patient with ADPKD. A sensitivity analysis showed that the model was most sensitive to estimates of the prevalence of aneurysms in ADPKD, the annual incidence of rupture, and the morbidity and mortality rates associated with rupture. A financial analysis showed that a screening strategy is likely to cost less than a nonscreening strategy. The model predicts that an MRI screening strategy would increase the life expectancy of young patients with ADPKD and reduce the financial impact on society of ADPKD.

Multimodality treatment of nongalenic arteriovenous malformations in pediatric patients.

OBJECTIVE: Previously reported series of arteriovenous malformations (AVMs) in pediatric patients have primarily used a single-modality treatment approach of either surgery, radiosurgery, or embolization, with significant treatment-related morbidity and mortality. At our institution, we have used a combined multidisciplinary team approach of all three treatment modalities, alone or in combination, to minimize complications and to maximize efficacy in the management of these lesions. METHODS: We retrospectively reviewed 40 consecutive pediatric patients with AVMs seen at our institution from 1991 to 1999. A multidisciplinary team planned the treatment for each AVM. The treatment modality consisted of the following approaches: surgery alone in 14 patients, a combination of endovascular embolization and surgery in 6 patients, radiosurgery alone in 11 patients, a combination of endovascular embolization and radiosurgery in 2 patients, and a combination of radiosurgery and surgery in 2 patients. Four patients are receiving ongoing multistaged treatment for reduction of the nidus size for eventual surgical resection or radiosurgical obliteration of large, complex lesions. In one patient, no treatment was recommended. RESULTS: The clinical outcomes for the overall series were 95.0% excellent or good (Glasgow Outcome Scale score 5 or 4), 2.5% fair (Glasgow Outcome Scale score 3), and 2.5% dead. Radiographic efficacy in the patients who have completed treatment was 92.9% complete obliteration of their AVMs and 7.1% incomplete obliteration. Of the 10 patients who had seizures, 9 are seizure-free. CONCLUSION: A combined multimodality approach of surgery, radiosurgery, and embolization in managing AVMs in pediatric patients can improve outcomes and minimize morbidity and mortality.

Thin and thick filament regulation of contractility in experimental cerebral vasospasm.

OBJECTIVE: Cerebral vasospasm is a potentially fatal consequence of aneurysmal subarachnoid hemorrhage and influences the prognosis of the patient. The purpose of this study was to evaluate the status of thin (actin) and thick (myosin) filament regulation of smooth muscle contraction in the double-subarachnoid hemorrhage canine model of cerebral vasospasm and to determine the effects of a kinase inhibitor reported to be effective in vasospasm, HA1077, on thin and thick filament regulation. METHODS: Cerebral vasospasm was assessed by vertebral angiography. Myosin regulatory light chain phosphorylation was measured using glycerol-urea gels, whereas protein levels of the thin filament-associated protein calponin were measured by Western blot. RESULTS: The basilar arteries of dogs in which subarachnoid hemorrhage was induced narrowed to 36% +/- 2.0% of their size on the first day (n = 12). The phosphorylation of the regulatory light chain tended to increase, but the change did not reach statistical significance (35% +/- 5.9% [n = 12] versus 25% +/- 4.8% [n = 10] in control arteries). In contrast to this increase, significant degradation of calponin was observed in the samples from vasospastic dogs (85.4% +/- 5.45% [n = 5] versus 15.2% +/- 6.21% [n = 5]; P < 0.01). Prophylactic treatment with intravenous injections of HA1077 at 0.67 mg/kg b.i.d. significantly inhibited vasospasm (diameters, 65% +/- 10.2% of Day 1 diameters [n = 5]; P < 0.05), and calponin degradation (57.8% +/- 13.9% [n = 4]) was substantially reduced. CONCLUSION: These data suggest that degradation of the thin filament-associated protein calponin plays a role in cerebral vasospasm and that the antivasospastic action of HA1077 is, at least in part, due to prevention of calponin degradation.

Stereotactic transcranial magnetic stimulation: correlation with direct electrical cortical stimulation.

OBJECTIVE: To evaluate stereotactic transcranial magnetic stimulation (TMS) as a tool for presurgical functional mapping of human motor cortex. METHODS: Transcranial magnetic stimulation using a frameless stereotactic system was performed in two patients with tumors near the central sulcus. TMS motor function maps were plotted on the patients' three-dimensional volumetric magnetic resonance imaging data and compared with direct electrical cortical stimulation at surgery with the patient under local anesthesia. RESULTS: Stereotactic TMS was well tolerated by both patients and was consistent with known somatotopic representation of human motor cortex. The results demonstrated a good correlation between the TMS and electrical cortical stimulation maps, with all TMS responses eliciting more than 75% of the maximum motor evoked potential falling within 1 cm of the electrical cortical stimulation site. CONCLUSIONS: Our findings indicate that stereotactic TMS is feasible and can provide accurate noninvasive localization of cortical motor function. It may prove to be a useful method for presurgical planning.

A mobile computed tomographic scanner with intraoperative and intensive care unit applications.

INTRODUCTION: A mobile computed tomographic scanner has been developed in which the scan plane is selected by means of gantry translation, rather than by translation of the patient table. This permits computed tomographic scanning in situ of any patient who is positioned on a radiolucent surface that fits within the inner diameter of the gantry. We report the design of and initial experience with this scanner as used with adapters for intraoperative and bedside computed tomography (CT). METHODS: The scanner is equipped with wheels, draws power from wall outlets (120 V, 20 A) in combination with batteries, and has a translating gantry. Preclinical studies of image quality were performed with phantoms. An operating table adapter was built for use with a radiolucent cranial fixation device. A bedside adapter was built that holds the head and shoulders of a patient in the intensive care unit. RESULTS: The preclinical phantom studies showed satisfactory image spatial resolution (0.8 mm) and low-contrast resolution signal-to-noise relative standard deviation (0.37%). Experience to date with 12 patients has confirmed the feasibility of intraoperative CT on demand. Experience to date with 26 patients has confirmed the feasibility of routine bedside CT in the intensive care unit. CONCLUSION: With these adaptations, mobile CT may increase the efficiency of intraoperative scanning by making it available to multiple operating rooms without committing it to any room for an entire operation and may increase the efficiency and safety of CT of critically ill patients who currently need to leave the intensive care unit to travel to a fixed CT installation and back.

Initial characterization of the dosimetry and radiology of a device for administering interstitial stereotactic radiosurgery.

OBJECTIVE: We report the design and initial characterization of the dosimetry and radiobiology of a novel device for interstitial stereotactic radiosurgery. INSTRUMENTATION: The device is lightweight, handheld, and battery-powered, and it emits x-ray radiation from the tip of a probe 3 mm in diameter by 10 cm in length. METHODS: The dosimetry was characterized by two independent methods: thermoluminescent dosimeters and radiochromic film. The radiobiology was characterized by in vivo irradiation of rat liver, dog liver, and dog brain. The animals were killed at varying intervals of time, and histological examinations were performed. Heat transfer from the probe to dog brain was studied in vivo by placing thermocouple sensors around the probe tip before irradiating. RESULTS: Both dosimetric methods showed a steep dose-distance fall-off relationship (proportional to the reciprocal of the cube of the distance from the probe tip). Rats and dogs that were killed weeks to months after liver irradiation tended to have sharply demarcated lesions. Liver enzyme levels, measured serially in the dogs, did not give evidence of chronic inflammation. Histological examination of the brains of dogs that were killed acutely after irradiation did not show evidence of inflammation, edema, or hemorrhage. The tissue temperature elevation 1 cm from the tip never exceeded 0.5 degree C, thereby excluding hyperthermia as a significant contributor to the formation of lesions. CONCLUSIONS: Because this device requires relatively few supporting resources, has sharp dosimetric properties, and seems to be safe, it may be useful as a clinical tool for interstitial stereotactic radiosurgery.

Temporal clustering of hemorrhages from untreated cavernous malformations of the central nervous system.

OBJECTIVE: Hemorrhages from cerebral cavernous malformations (CMs) sometimes seem to occur in closely spaced "clusters" interspersed with long hemorrhage-free intervals. Clustering of hemorrhages could affect retrospective assessments of radiosurgery efficacy in prevention of CM rehemorrhage. However, this empirical observation had not been tested quantitatively. To test whether CM hemorrhages tend to cluster, we reviewed pretreatment rebleeding rates after a first symptomatic hemorrhage in CM patients who later underwent surgery or radiosurgery. METHODS: We performed a retrospective review of 141 patients with CMs who presented with clinically overt hemorrhage, and who subsequently underwent surgery or proton beam radiosurgery during an 18-year period. Statistical models were used to analyze all events per person and identify potential variation in rebleeding risk with time after a previous hemorrhage. RESULTS: Sixty-three of 141 patients experienced a second hemorrhage before treatment; 16 had additional hemorrhages. Five hundred thirty-eight patient years elapsed between first hemorrhages and treatment. The cumulative incidence of a second hemorrhage after the first CM hemorrhage was 14% after 1 year and 56% after 5 years. During the first 2.5 years after a hemorrhage, the monthly rehemorrhage hazard was 2%. The risk then decreased spontaneously to less than 1% per month, which represents a 2.4-fold decline (P < 0.001). Rehemorrhage rates were higher in younger patients (P < 0.01), but not in females or in patients with deep lesions. Shorter intervals between successive hemorrhages did not predict higher subsequent rehemorrhage risk. CONCLUSION: The rehemorrhage rate from untreated CMs is high initially, and it decreases 2 to 3 years after a previous hemorrhage. This hazard pattern generates the observed temporal clustering of hemorrhages from untreated CMs.

Comparison of three methods of estimating confidence intervals for stereotactic error.

When planning a stereotactic procedure, it is clinically valuable to know the spatial confidence intervals of a particular stereotactic technique. To do this, the aggregate error distribution of the stereotactic technique must first be estimated. In a frame-based stereotactic procedure, there is an imaging step and a treatment delivery step. If error is introduced independently at these steps, then the error of a stereotactic procedure may be computed from the error distributions of the component steps. Three computational methods of doing this were compared: parametric, convolution, and Monte Carlo. To test these methods, the error distributions of an imaging technique, a delivery technique, and the corresponding stereotactic imaging-plus-delivery system were measured empirically using a phantom, computed tomography, and the CRW stereotactic system. The three methods gave concordant estimates of mean aggregate error (respectively 2.71 +/- 1.52, 2.45 +/- 2.30, 2.51 +/- 2.34, and 2.47 +/- 2.31 mm for the empiric, convolution, Monte Carlo, and parametric methods). However, the estimates of the confidence intervals differed between the parametric and the nonparametric methods. In particular, the parametric method gave significantly higher estimates of the 99% spatial confidence interval (6.40 mm versus 5.41 mm and 5.38 mm for the convolution and Monte Carlo methods). Knowledge of the confidence intervals allows a neurosurgeon to determine a priori whether a particular stereotactic technique is likely to satisfy a clinically defined error budget, and thereby achieve clinical success.

Upper limits on a stochastic background of gravitational waves.

The Laser Interferometer Gravitational-Wave Observatory has performed a third science run with much improved sensitivities of all three interferometers. We present an analysis of approximately 200 hours of data acquired during this run, used to search for a stochastic background of gravitational radiation. We place upper bounds on the energy density stored as gravitational radiation for three different spectral power laws. For the flat spectrum, our limit of omega0 < 8.4 x 10(-4) in the 69-156 Hz band is approximately 10(5) times lower than the previous result in this frequency range.

Limits on gravitational-wave emission from selected pulsars using LIGO data.

We place direct upper limits on the amplitude of gravitational waves from 28 isolated radio pulsars by a coherent multidetector analysis of the data collected during the second science run of the LIGO interferometric detectors. These are the first direct upper limits for 26 of the 28 pulsars. We use coordinated radio observations for the first time to build radio-guided phase templates for the expected gravitational-wave signals. The unprecedented sensitivity of the detectors allows us to set strain upper limits as low as a few times 10(-24). These strain limits translate into limits on the equatorial ellipticities of the pulsars, which are smaller than 10(-5) for the four closest pulsars.

The application of controlled intracranial hypertension in slit ventricle syndrome patients with obstructive hydrocephalus and shunt malfunction.

When a shunted patient with slit-ventricle syndrome (SVS) presents with a shunt malfunction or infection, the third ventricle may not be of sufficient caliber, despite the shunt malfunction, to allow atraumatic passage of an endoscope to the floor of the third ventricle. We describe four slit ventricle syndrome patients with respectively 24, 12, 18 and 2 prior shunt revisions who presented with shunt infection. In each patient the shunt was externalized and controlled intracranial hypertension (CIH) was applied over an average of 5.8 days by raising the height of the external ventricular drain (EVD) bag to a mean height of 18.8 cm above EAM. This increased the mean transverse third ventricular diameter from an average of 0.28 cm on admission to 1.13 cm after application of CIH. Endoscopic third ventriculocisternostomy (ETV) was satisfactorily performed in three of the four patients who remain shunt free after a mean follow-up of 21.3 months. CIH followed by ETV is an option in selected SVS patients who present with shunt malfunction or infection.

Measurement of the thermal contribution to the nonlinear refractive index of air at 1064nm.

The thermal contribution to the nonlinear refractive index of air at 1.064mum was measured with a high-finesse Fabry-Perot cavity and a 500-mW cw laser beam. At room temperature and pressure, the nonlinear refractive-index coefficient of air was found to be n(2)((th))=(-1.9+/-0.2)x10 (-14) cm(2)/W for a beam waist radius of 0.23 mm and was found to be independent of the relative humidity. The thermal nonlinearities of N(2) , O(2) , and CO(2) were also measured, and it was found that the dominant contribution to air is its O(2) content.

Spatial patterns induced in a laser beam by thermal nonlinearities.

Stable spatial laser patterns were observed in a high-finesse Fabry-Perot cavity containing up to 2 atm of CO(2) and O(2). The gases displayed the same sequence of patterns that obey a scaling law of the form P(beta)p(2), where P is the power stored in the cavity, p is the pressure of the gas, and beta is a material-dependent parameter.