✓ The accuracy of a novel frameless stereotactic system was determined during 10 surgeries performed to resect brain tumors. An array of three charge-coupled device cameras tracked the locations of infrared light-emitting diodes on a hand-held stylus and on a reference frame attached to the patient's skull with a single bone screw. Patient—image registration was achieved retrospectively by digitizing randomly chosen scalp points with the system and fitting them to a scalp surface model derived from magnetic resonance (MR) images. The reference frame enabled continual correction for patient head movements so that registration was maintained even when the patient's head was not immobilized in a surgical clamp. The location of the stylus was displayed in real-time on cross-sectional and three-dimensional MR images of the head; this information was used to predict the locations of small intracranial lesions. The average distance (and standard deviation) between the actual position of the mass and its stereotactically predicted location was 4.8 ± 3.5 mm. The authors conclude that frameless stereotaxy can be used for accurate localization of intracranial masses without resorting to using fiducial markers during presurgical imaging and without immobilizing the patient's head during surgery.
Martin J. Ryan, Robert K. Erickson, David N. Levin, Charles A. Pelizzari, R. Loch Macdonald and George J. Dohrmann
Ryan C. Turner, Michael J. Seminerio, Zachary J. Naser, J. Neal Ford, Samantha J. Martin, Rae R. Matsumoto, Charles L. Rosen and Jason D. Huber
Despite the role of aging in development of neurological and neurodegenerative diseases, the effects of age are often disregarded in experimental design of preclinical studies. Functional assessment increases the clinical relevance of animal models of neurological disease and adds value beyond traditional histological measures. However, the relationship between age and functional impairment has not been systematically assessed through a battery of functional tests.
In this study, various sensorimotor and behavioral tests were used to evaluate effects of aging on functional performance in naive animals. Sensorimotor measures included locomotor activity; Rotarod, inclined plane, and grip-strength testing; and modified Neurological Severity Score. The Morris water maze was used to examine differences in learning and memory, and the elevated plus maze and forced swim test were used to assess anxiety-like and depressive-like behaviors, respectively.
Older Sprague-Dawley rats (18–20 months) were found to perform significantly worse on the inclined plane tests, and they exhibited alterations in elevated-plus maze and forced swim test compared with young adult rats (3–4 months). Specifically, older rats exhibited reduced exploration of open arms in elevated plus maze and higher immobility time in forced swim test. Spatial acquisition and reference memory were diminished in older rats compared with those in young adult rats.
This study demonstrates clear differences between naive young adult and older animals, which may have implications in functional assessment for preclinical models of neurological disease.
Ryan M. Martin, Matthew J. Wright, Evan S. Lutkenhoff, Benjamin M. Ellingson, John D. Van Horn, Meral Tubi, Jeffry R. Alger, David L. McArthur and Paul M. Vespa
Hemorrhagic contusions are often the most visible lesions following traumatic brain injury. However, the incidence, location, and natural history of traumatic parenchymal hemorrhage and its impact on neurological outcome have been understudied. The authors sought to examine the location and longitudinal evolution of traumatic parenchymal hemorrhage and its association with cognitive outcome.
Sixteen patients with hemorrhagic contusions due to acceleration-deceleration injuries underwent MRI in the acute (mean 6.3 days postinjury) and chronic (mean 192.9 days postinjury) phases. ImageJ was used to generate GRE and FLAIR volumes. To account for the effect of head-size variability across individuals, the authors calculated each patient's total brain tissue volume using SIENAX. GRE and FLAIR volumes were normalized to the total brain tissue volume, and values for absolute and percent lesion volume and total brain volume change were generated. Spearman's rank correlations were computed to determine associations between neuroimaging and 6-month postinjury neuropsychological testing of attention (Symbol Digit Modalities Test [SDMT], oral [O] and written [W] versions), memory (Selective Reminding Test, total learning and delayed recall), and executive function (Trail Making Test Part B [TMT-B]).
The patients' mean age was 31.4 ± 14.0 years and their mean Glasgow Coma Scale score at admission was 7.9 ± 2.8. Lesions were predominantly localized to the frontal (11 lesions) and temporal (9 lesions) lobes. The average percent reductions in GRE and FLAIR volumes were 44.2% ± 46.1% and 80.5% ± 26.3%, respectively. While total brain and frontal lesion volumes did not correlate with brain atrophy, larger temporal lobe GRE and FLAIR volumes were associated with larger volumes of atrophy (GRE: acute, −0.87, p < 0.01, chronic, −0.78, p < 0.01; FLAIR: acute, −0.81, p < 0.01, chronic, −0.88, p < 0.01). Total percent volume change of GRE lesions correlated with TMT-B (0.53, p < 0.05) and SDMT-O (0.62, p < 0.05) scores. Frontal lobe lesion volume did not correlate with neuropsychological outcome. However, robust relationships were seen in the temporal lobe, with larger acute temporal lobe GRE volumes were associated with worse scores on both oral and written versions of the SDMT (SDMT-W, −0.85, p < 0.01; SDMT-O, −0.73, p < 0.05). Larger absolute change in temporal GRE volume was strongly associated with worse SDMT scores (SDMT-W, 0.88, p < 0.01; SDMT-O, 0.75, p < 0.05). The same relationships were also seen between temporal FLAIR lesion volumes and neuropsychological outcome.
Traumatic parenchymal hemorrhages are largely clustered in the frontal and temporal lobes, and significant residual blood products are present at 6 months postinjury, a potential source of ongoing secondary brain injury. Neuropsychological outcome is closely tied to lesion volume size, particularly in the temporal lobe, where larger GRE and FLAIR volumes are associated with more brain atrophy and worse SDMT scores. Interestingly, larger volumes of hemorrhage resorption were associated with worse SDMT and TMT-B scores, suggesting that the initial tissue damage had a lasting impact on attention and executive function.
Martin J. Rutkowski, Ryan M. Alward, Rebecca Chen, Jeffrey Wagner, Arman Jahangiri, Derek G. Southwell, Sandeep Kunwar, Lewis Blevins, Han Lee and Manish K. Aghi
In 2004, the WHO classified atypical pituitary adenoma as a distinct adenoma subtype. However, the clinical significance of this distinction remains undetermined. The authors sought to define patient characteristics, tumor features, and treatment outcomes associated with atypical pituitary adenoma.
The authors reviewed records of patients who underwent resection of pituitary adenoma at the University of California, San Francisco, between 2007 and 2014. Per institutional protocol, adenomas exhibiting mitotic activity underwent evaluation for all 3 markers of atypicality (mitotic index, extensive p53 staining, and MIB-1 index ≥ 3%). Statistical analyses were performed using χ2, Fisher’s exact test, t-test, log-rank, and logistic regression.
Between 2007 and 2014, 701 patients underwent resection for pituitary adenoma. Among these patients, 122 adenomas exhibited mitotic activity and therefore were evaluated for all 3 markers of atypicality, with 36 tumors (5%) proving to be atypical. There were 21 female patients (58%) and 15 male patients (42%) in the atypical cohort, and 313 female patients (47%) and 352 male patients (53%) in the nonatypical cohort (p = 0.231). The mean age of patients in the atypical cohort was 37 years (range 10–65 years), which was significantly lower than the mean age of 49 years (range 10–93 years) for patients in the nonatypical cohort (p < 0.001). The most common presenting symptoms for patients with atypical adenomas were headaches (42%) and visual changes (33%). Atypical adenomas were more likely to be functional (78%) than nonatypical adenomas (42%; p < 0.001). Functional atypical adenomas were significantly larger than functional nonatypical adenomas (mean diameter 2.2 vs 1.4 cm; p = 0.009), as were nonfunctional atypical adenomas compared with nonfunctional nonatypical adenomas (mean diameter 3.3 vs 2.3 cm; p = 0.01). Among the entire adenoma cohort, larger presenting tumor size was associated with cavernous sinus invasion (p < 0.001), and subtotal resection was associated with cavernous sinus invasion (p < 0.001) and larger size (p < 0.001) on binomial multivariate regression. The median time until recurrence was 56 months for atypical adenomas, 129 months for functional nonatypical adenomas, and 204 months for nonfunctional nonatypical adenomas (p < 0.001). Functional atypical adenomas recurred more frequently and significantly earlier than functional nonatypical adenomas (p < 0.001). When accounting for extent of resection, cavernous sinus invasion, size, age, sex, and functional subtype, atypicality remained a significant predictor of earlier recurrence among functional adenomas (p = 0.002).
When compared with nonatypical pituitary adenomas, atypical adenomas are more likely to present in younger patients at a larger size, are more often hormonally hypersecretory, and are associated with earlier recurrence. These features lend credence to atypical pituitary adenomas being a distinct clinical entity in addition to a discrete pathological diagnosis.