✓ At 2, 10, and 60 min after intravenous injection of tritiated hydrocortisone into tumor-bearing mice, samples of brain and tumor were taken for autoradiography. Within 2 min of injection, large amounts of the steroid had left the bloodstream and had penetrated normal brain. By 60 min virtually all the drug had left the brain. The most radioactive structure was the choroid plexus. Within the normal and edematous brain, hydrocortisone was not found in cells alone but was spread randomly throughout the tissue. Edematous brain adjacent to implanted tumor contained much more steroid than normal brain. This difference was maximal at 10 min after injection. Edematous white matter adjacent to tumor was usually as radioactive as tumor. In the ependymoblastoma at 2 min after injection, neoplastic cells and interstitial tissue adjacent to blood vessels contained much hydrocortisone. At 10 min the drug was uniformly spread through the tumor tissue and by 60 min was largely gone. The uptake of the drug by the edematous brain suggests a direct local action. The high choroid plexus concentration may indicate a direct action there, perhaps to reduce cerebrospinal fluid production.
Michael L. Schwartz, Charles H. Tator, and Harold J. Hoffman
Charles H. Tator and Michael L. Schwartz
Jonathan P. S. Knisely, Rohan Ramakrishna, and Theodore H. Schwartz
Donald T. Stuss, Malcolm A. Binns, Fiona G. Carruth, Brian Levine, Clare E. Brandys, Richard J. Moulton, William G. Snow, and Michael L. Schwartz
Object. The goal of this study was to characterize more fully the cognitive changes that occur during the period of acute recovery after traumatic brain injury (TBI).
Methods. The pattern of performance recovery on attention and memory tests was compared with the results of the Galveston Orientation and Amnesia Test (GOAT). Tests of memory and attention were administered serially to a hospitalized group of patients with TBI of varying severity. The tests differed in their level of complexity and/or requirement for more effortful or strategic processing. The authors found a regular pattern to recovery. As expected, ability to perform on simpler tests was recovered before performance on more effortful ones. The ability to recall three words freely after a 24-hour delay (the operational definition in this study of return to continuous memory) was recovered last, later than normal performance on the GOAT. Ability to perform simple attentional tasks was recovered before the less demanding memory task (recognition); ability to perform more complex attentional tasks was recovered before the free recall of three words after a 24-hour delay. This recovery of attention before memory was most notable and distinct in the group with mild TBI.
Conclusions. The period of recovery after TBI, which is currently termed posttraumatic amnesia, appears to be primarily a confusional state and should be labeled as such. The authors propose a new definition for this acute recovery period and argue that the term posttraumatic confusional state should be used, because it more appropriately and completely characterizes the early period of recovery after TBI.
Ryan M. Jones, Shona Kamps, Yuexi Huang, Nadia Scantlebury, Nir Lipsman, Michael L. Schwartz, and Kullervo Hynynen
The object of this study was to correlate lesion size with accumulated thermal dose (ATD) in transcranial MRI-guided focused ultrasound (MRgFUS) treatments of essential tremor with focal temperatures limited to 50°C–54°C.
Seventy-five patients with medically refractory essential tremor underwent MRgFUS thalamotomy at the authors’ institution. Intraoperative MR thermometry was performed to measure the induced temperature and thermal dose distributions (proton resonance frequency shift coefficient = −0.00909 ppm/°C). In 19 patients, it was not possible to raise the focal temperature above 54°C because of unfavorable skull characteristics and/or the pain associated with cranial heating. In this patient subset, sonications with focal temperatures between 50°C and 54°C were repeated (5.1 ± 1.5, mean ± standard deviation) to accumulate a sufficient thermal dose for lesion formation. The ATD profile sizes (17, 40, 100, 200, and 240 cumulative equivalent minutes at 43°C [CEM43]) calculated by combining axial MR thermometry data from individual sonications were correlated with the corresponding lesion sizes measured on axial T1-weighted (T1w) and T2-weighted (T2w) MR images acquired 1 day posttreatment. Manual corrections were applied to the MR thermometry data prior to thermal dose accumulation to compensate for off-resonance–induced spatial-shifting artifacts.
Mean lesion sizes measured on T2w MRI (5.0 ± 1.4 mm) were, on average, 28% larger than those measured on T1w MRI (3.9 ± 1.4 mm). The ATD thresholds found to provide the best correlation with lesion sizes measured on T2w and T1w MRI were 100 CEM43 (regression slope = 0.97, R2 = 0.66) and 200 CEM43 (regression slope = 0.98, R2 = 0.89), respectively, consistent with data from a previous study of MRgFUS thalamotomy via repeated sonications at higher focal temperatures (≥ 55°C). Two-way linear mixed-effects analysis revealed that dominant tremor subscores on the Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (CRST) were statistically different from baseline at 3 months and 1 year posttreatment in both low-temperature (50°C–54°C) and high-temperature (≥ 55°C) patient cohorts. No significant fixed effect on the dominant tremor scores was found for the temperature cohort factor.
In transcranial MRgFUS thalamotomy for essential tremor, repeated sonications with focal temperatures between 50°C and 54°C can accumulate a sufficient thermal dose to generate lesions for clinically relevant tremor suppression up to 1 year posttreatment, and the ATD can be used to predict the size of the resulting ablation zones measured on MRI. These data will serve to guide future clinical MRgFUS brain procedures, particularly those in which focal temperatures are limited to below 55°C.
Michael L. Schwartz, Alan R. Hudson, Geoffrey R. Fernie, Ken Hayashi, and Allan A. Coleclough
✓ It is known that boxers suffer a characteristic cumulative brain injury from repeated blows to the head that correlates well with the number of bouts fought. Much less is known about full-contact karate (kickboxing), which is relatively new. In full-contact karate, punches and kicks are actually landed, rather than being focused to culminate just short of an opponent, as practiced in traditional karate. Although a combatant can win on points, the surest means of victory is a knockout. Consequently, fighters strive to land blows to the head.
To investigate the relative force of kicks and punches, a dummy head was mounted 175 cm above the floor (to simulate a 50th-percentile man standing erect) and 125 cm above the floor (to simulate the man in a crouched position) on a universal joint permitting motion about three axes. The mechanism was contrived to provide constant rotational stiffness, and springs provided constant restorative moments about the three axes. The texture of soft tissue was simulated by a mask of visco-elastic foamed materials. Fourteen karate experts punched and kicked the dummy. Accelerometer measurements in the 90- to 120-G range indicated that safety-chops (hand protectors) and safety-kicks (foot padding) did not reduce acceleration of the dummy. Ten-ounce boxing gloves mitigated peak acceleration to some extent. Kicks and punches produced accelerations in the same range.
Violent acceleration of the head by any means produces injury. The authors conclude that, if full-contact karate is widely practiced, cases of kickboxer's encephalopathy will soon be reported.
José Enrique Cohen, Howard J. Ginsberg, Eve C. Tsai, Michael L. Schwartz, and Sergio Petrocelli
Yuri M. Andrade-Souza, Gelareh Zadeh, Meera Ramani, Daryl Scora, May N. Tsao, and Michael L. Schwartz
Object. The aim of this study was to validate the radiosurgery-based arteriovenous malformation (AVM) score and the modified Spetzler—Martin grading system to predict radiosurgical outcome.
Methods. One hundred thirty-six patients with brain AVMs were randomly selected. These patients had undergone a linear accelerator radiosurgical procedure at a single center between 1989 and 2000. Patients were divided into four groups according to an AVM score, which was calculated from the lesion volume, lesion location, and patient age (Group 1, AVM score < 1; Group 2, AVM score 1–1.49; Group 3, AVM score 1.5–2; and Group 4, AVM score > 2). Patients with a Spetzler—Martin Grade III AVM were divided into Grades IIIA (lesion > 3 cm) and IIIB (lesion < 3 cm). Sixty-two female (45.6%) and 74 male (54.4%) patients with a median age of 37.5 years (mean 37.5 years, range 5–77 years) were followed up for a median of 40 months. The median tumor margin dose was 15 Gy (mean 17.23 Gy, range 15–25 Gy). The proportions of excellent outcomes according to the AVM score were as follows: 91.7% for Group 1, 74.1% for Group 2, 60% for Group 3, and 33.3% for Group 4 (chi-square test, degrees of freedom (df) = 3, p < 0.001). Based on the modified Spetzler—Martin system, Grade I lesions had 88.9% excellent results; Grade II, 69.6%; Grade IIIB, 61.5%; and Grades IIIA and IV, 44.8% (chi-square test, df = 3, p = 0.047).
Conclusions. The radiosurgery-based AVM score can be used accurately to predict excellent results following a single radiosurgical treatment for AVM. The modified Spetzler—Martin system can also predict radiosurgical results for AVMs, thus making it possible to use this system while deciding between surgery and radiosurgery.
Amir R. Dehdashti, Laurent Thines, Robert A. Willinsky, Karel G. terBrugge, Michael L. Schwartz, Michael Tymianski, and M. Christopher Wallace
In this study, the authors evaluated how an appropriate allocation of patients with occipital arteriovenous malformations (AVMs) who were treated according to different strategies would affect nonhemorrhagic headache, visual function, and hemorrhage risk levels.
Of the 712 patients with brain AVMs in the Toronto Western Hospital prospective database, 135 had occipital AVMs. The treatment decision was based on patients' characteristics, presentation, and morphology of the AVM. The management modalities were correlated with their outcomes.
The mean follow-up period was 6.78 years. Nonhemorrhagic headache was the most frequent symptom (82 [61%] of 135 patients). Ninety-four patients underwent treatment with one or a combination of embolization, surgery, or radiosurgery, and 41 were simply observed. Of the 40 nontreated patients with nonhemorrhagic headache, only 12 (30%) showed improvement. In the observation group 2 patients (22%) had worsening of visual symptoms, and 2 experienced hemorrhage, for an annual hemorrhage rate of 0.7% per year; 1 patient died. In the treatment group, the improvement in nonhemorrhagic headache in 35 patients (83%) was significant (p < 0.0001). Visual deficit at presentation worsened in 2 (8%), and there were 8 new visual field deficits (9%). The visual worsening was not significantly different. There were 2 other neurological deficits (2%) and 2 deaths (2%) related to the AVM treatment. One AVM hemorrhaged. The annual hemorrhage rate was 0.1% per year. The hemorrhage risk in the observation and treatment groups was lower than the observed hemorrhage risk of all patients with AVMs (4.6%) at the authors' institution.
Appropriate selection of patients with occipital AVMs for one or a combination of treatment modalities yields a significant decrease in nonhemorrhagic headache without significant visual worsening. The multidisciplinary care of occipital AVMs can aim for an apparent decrease in hemorrhage risk.