Leukoencephalopathy after whole-brain radiation therapy plus radiosurgery versus radiosurgery alone for metastatic lung cancer.

BACKGROUND: As systemic therapies improve and patients live longer, concerns mount about the toxicity of whole-brain radiation therapy (WBRT) for treatment of brain metastases. Development of delayed white matter abnormalities indicative of leukoencephalopathy have been correlated with cognitive dysfunction. This study assesses the risk of imaging-defined leukoencephalopathy in patients whose management included WBRT in addition to stereotactic radiosurgery (SRS). This risk is compared to patients who only underwent SRS. METHODS: We retrospectively compared 37 patients with non-small cell lung cancer who underwent WBRT plus SRS to 31 patients who underwent only SRS. All patients survived at least 1 year after treatment. We graded the development of delayed white matter changes on magnetic resonance imaging using a scale to evaluate T(2) /FLAIR (fluid attenuated image recovery) images: grade 1 = little or no white matter hyperintensity; grade 2 = limited periventricular hyperintensity; and grade 3 = diffuse white matter hyperintensity. RESULTS: Patients treated with WBRT and SRS had a significantly greater incidence of delayed white matter leukoencephalopathy compared to patients who underwent SRS alone (P < .001). On final imaging, 36 of 37 patients (97.3%) treated by WBRT developed leukoencephalopathy (25% with grade 2; 70.8% with grade 3). Only 1 patient treated with SRS alone developed leukoencephalopathy. CONCLUSIONS: Risk of leukoencephalopathy in patients treated with SRS alone for brain metastases was significantly lower than that for patients treated with WBRT plus SRS. A prospective study is necessary to correlate these findings with neurocognition and quality of life. These data supplement existing reports regarding the differential effects of WBRT and SRS on normal brain structure and function.

Long term delay in onset of prevertebral hematoma following anterior cervical discectomy and fusion: A case report.

Post-operative hematoma following anterior cervical discectomy and fusion (ACDF) is an uncommon but feared complication. Typically, these complications present in the immediate post-operative period. We present a case of a 51 year-old woman who underwent a C4-5 ACDF for left sided radicular pain. Her immediate post-operative course was uncomplicated, but she presented 6 weeks subsequently to the emergency department with neck swelling, difficulty swallowing, cough, and shortness of breath. She was found to have a 4.5 cm anterior neck hematoma with settling of the instrumentation and a new C4 vertebral fragment protruding anteriorly. She underwent evacuation of hematoma without clear evidence of a bleeding source. After several days of observation, she was discharged home and ultimately had resolution of her presenting symptoms. Most hematomas resulting in airway compromise appear in the immediate post-operative period, but a high index of suspicion must remain high in any patient with a prior anterior cervical surgery presenting with symptoms of pre-vertebral compression or respiratory compromise.

Utility of the Aspirin and P2Y12 Response Assays to Determine the Effect of Antiplatelet Agents on Platelet Reactivity in Traumatic Brain Injury.

BACKGROUND: Premorbid antithrombotic medication may worsen intracranial injury and outcome after traumatic brain injury (TBI). Routine laboratory tests are insufficient to evaluate platelet activity. OBJECTIVE: To profile the spectrum of platelet inhibition, as measured by aspirin and P2Y12 response unit assays, in a TBI population on antiplatelet therapy. METHODS: This single-center, prospective cohort study included patients presenting to our institution between November 2010 and January 2015 with a clinical history of TBI. Serum platelet reactivity levels were determined immediately on admission and analyzed using the aspirin and P2Y12 response unit assays; test results were reported as aspirin response units and P2Y12 response units. We report congruence between assay results and clinical history as well as differences in assay results between types of antiplatelet therapy. RESULTS: A sample of 317 patients was available for analysis, of which 87% had experienced mild TBI, 7% moderate, and 6% severe; the mean age was 71.5 years. The mean aspirin response units in patients with a history of any aspirin use was 456 ± 67 (range, 350-659), with 88% demonstrating therapeutic platelet inhibition. For clopidogrel, the mean P2Y12 response unit was 191 ± 70 (range, 51-351); 77% showed therapeutic response. CONCLUSION: Rapid measurement of antiplatelet function using the aspirin and P2Y12 response assays indicated as many as one fourth of patients on antiplatelet therapy do not have platelet dysfunction. Further research is required to develop guidelines for the use of these assays to guide platelet transfusion in the setting of TBI.

Use of Aspirin and P2Y12 Response Assays in Detecting Reversal of Platelet Inhibition With Platelet Transfusion in Patients With Traumatic Brain Injury on Antiplatelet Therapy.

BACKGROUND: At present, guidelines are lacking on platelet transfusion in patients with a traumatic intracranial bleed and history of antiplatelet therapy. The aspirin and P2Y 12 response unit (ARU and PRU, respectively) assays detect the effect of aspirin and P2Y 12 inhibitors in the cardiac population. OBJECTIVE: To describe the reversal of platelet inhibition after platelet transfusion using the ARU and PRU assays in patients with traumatic brain injury. METHODS: Between 2010 and 2015, we conducted a prospective comparative cohort study of patients presenting with a positive head computed tomography and a history of antiplatelet therapy. ARU and PRU assays were performed on admission and 6 hours after transfusion, with a primary end point of detection of disinhibition after platelet transfusion. RESULTS: One hundred seven patients were available for analysis. Seven percent of patients taking aspirin and 27% of patients taking clopidogrel were not therapeutic on admission per the ARU and PRU, respectively. After platelet transfusion, 51% of patients on any aspirin and 67% of patients on any clopidogrel failed to be reversed. ARU increased by 71 ± 76 per unit of apheresis platelets for patients taking any aspirin, and PRU increased by 48 ± 46 per unit of apheresis platelets for patients taking any clopidogrel. CONCLUSION: A significant percentage of patients taking aspirin or clopidogrel were not therapeutic and thus would be unlikely to benefit from a platelet transfusion. In patients with measured platelet inhibition, a single platelet transfusion was not sufficient to reverse platelet inhibition in almost half.

Total Hip Arthroplasty Complicated by a Gluteal Hematoma Resulting in Acute Foot Drop.

Total hip arthroplasty is a prevalent orthopedic intervention in the United States. Massive postoperative hematomas are a rare albeit serious complication of the procedure. Sequelae of these hematomas can include lower extremity paralysis from compression of the sciatic nerve. A 66-year-old woman taking aspirin and clopidogrel for coronary stents presented with a complete foot drop, paresthesias, and lower extremity pain 10 days after a total hip arthroplasty. The patient was initially seen by a neurology service at another hospital and thought to have lateral recess stenosis. At the authors' center, magnetic resonance imaging of the lumbar spine failed to show lateral recess stenosis. Urgent pelvic computed tomography showed a large hematoma and raised suspicion of sciatic nerve compression. Hip magnetic resonance imaging showed a right gluteal hematoma compressing the sciatic nerve. The patient was then taken to the operating room for the clot to be evacuated and was later referred for rehabilitation. Massive hematomas after total hip arthroplasty are an important consideration in the differential diagnosis of nontraumatic acute foot drop. Prompt diagnosis may correlate with improved neurological outcome and help reduce overall morbidity.

The accuracy of predicting survival in individual patients with cancer.

OBJECT: Estimating survival time in cancer patients is crucial for clinicians, patients, families, and payers. To provide appropriate and cost-effective care, various data sources are used to provide rational, reliable, and reproducible estimates. The accuracy of such estimates is unknown. METHODS: The authors prospectively estimated survival in 150 consecutive cancer patients (median age 62 years) with brain metastases undergoing radiosurgery. They recorded cancer type, number of brain metastases, neurological presentation, extracranial disease status, Karnofsky Performance Scale score, Recursive Partitioning Analysis class, prior whole-brain radiotherapy, and synchronous or metachronous presentation. Finally, the authors asked 18 medical, radiation, or surgical oncologists to predict survival from the time of treatment. RESULTS: The actual median patient survival was 10.3 months (95% CI 6.4-14). The median physician-predicted survival was 9.7 months (neurosurgeons = 11.8 months, radiation oncologists = 11.0 months, and medical oncologist = 7.2 months). For patients who died before 10 months, both neurosurgeons and radiation oncologists generally predicted survivals that were more optimistic and medical oncologists that were less so, although no group could accurately predict survivors alive at 14 months. All physicians had individual patient survival predictions that were incorrect by as much as 12-18 months, and 14 of 18 physicians had individual predictions that were in error by more than 18 months. Of the 2700 predictions, 1226 (45%) were off by more than 6 months and 488 (18%) were off by more than 12 months. CONCLUSIONS: Although crucial, predicting the survival of cancer patients is difficult. In this study all physicians were unable to accurately predict longer-term survivors. Despite valuable clinical data and predictive scoring techniques, brain and systemic management often led to patient survivals well beyond estimated survivals.

Multistaged volumetric management of large arteriovenous malformations.

We sought to define the long-term outcomes and risks of arteriovenous malformation (AVM) management using 2 or more stages of stereotactic radiosurgery (SRS) for symptomatic large-volume AVMs unsuitable for surgery. Two decades ago, we prospectively began to stage anatomical components in order to deliver higher single doses to AVMs>10 cm3 in volume. Forty-seven patients with large AVMs underwent volume-staged SRS. The median interval between the two SRS procedures was 4.9 months (range, 3-14 months). The median nidus volume was 11.5 cm3 (range, 4.0-26 cm3) in the first stage of SRS and 9.5 cm3 in the second. The median margin dose was 16 Gy (range, 13-18 Gy) for both SRS stages. The actuarial rates of total obliteration after 2-staged SRS were 7, 20, 28 and 36% at 3, 4, 5 and 10 years, respectively. Sixteen patients needed additional SRS at a median interval of 61 months (range, 33-113 months) after the 2-staged SRS. After repeat procedure(s), the eventual obliteration rate was 66% at 10 years. The cumulative rates of AVM hemorrhage after SRS were 4.3, 8.6, 13.5 and 36.0% at 1, 2, 5 and 10 years, respectively. Symptomatic adverse radiation effects were detected in 13% of patients. Successful prospective volume-staged SRS for large AVMs unsuitable for surgery requires 2 or more procedures to complete the obliteration process. Patients remain at risk for hemorrhage if the AVM persists.

Future perspectives on brain metastasis management.

Brain metastases are the most common intracranial tumors encountered by physicians. Historically, the mainstays of therapy were limited to surgery and whole brain radiation. Surgery is typically reserved for safely accessible and symptomatic tumors in patients well enough to tolerate a procedure. Whole-brain radiation therapy has proven to have limited efficacy and concerns have arisen regarding its toxicity. Advances in the treatment of systemic cancers have yielded improved long-term survival and quality of life for patients. To parallel these efforts in systemic treatment, continual improvement of the treatment of brain metastases is a must. The last two decades have seen a paradigm shift in the thinking about metastatic brain tumor treatment as a result of the advent of stereotactic radiosurgery. Radiosurgery has proven to be an efficacious, minimally invasive, and highly selective treatment for metastatic brain tumors. In this review, we discuss the evolution of metastatic brain tumor management, the appropriately diminished role for reflexive whole brain radiation, and the growing importance of stereotactic radiosurgery as an upfront treatment modality in conjunction with surgery and subsequent salvage radiosurgery.

Stereotactic radiosurgery for arteriovenous malformations, Part 6: multistaged volumetric management of large arteriovenous malformations.

OBJECT: The object of this study was to define the long-term outcomes and risks of arteriovenous malformation (AVM) management using 2 or more stages of stereotactic radiosurgery (SRS) for symptomatic large-volume lesions unsuitable for surgery. METHODS: In 1992, the authors prospectively began to stage the treatment of anatomical components to deliver higher single doses to AVMs with a volume of more than 10 cm(3). Forty-seven patients with such AVMs underwent volume-staged SRS. In this series, 18 patients (38%) had a prior hemorrhage and 21 patients (45%) underwent prior embolization. The median interval between the first-stage SRS and the second-stage SRS was 4.9 months (range 2.8-13.8 months). The median target volume was 11.5 cm(3) (range 4.0-26 cm(3)) in the first-stage SRS and 9.5 cm(3) in the second-stage SRS. The median margin dose was 16 Gy (range 13-18 Gy) for both stages. RESULTS: In 17 patients, AVM obliteration was confirmed after 2-4 SRS procedures at a median follow-up of 87 months (range 0.4-209 months). Five patients had near-total obliteration (volume reduction > 75% but residual AVM). The actuarial rates of total obliteration after 2-stage SRS were 7%, 20%, 28%, and 36% at 3, 4, 5, and 10 years, respectively. The 5-year total obliteration rate after the initial staged volumetric SRS with a margin dose of 17 Gy or more was 62% (p = 0.001). Sixteen patients underwent additional SRS at a median interval of 61 months (range 33-113 months) after the initial 2-stage SRS. The overall rates of total obliteration after staged and repeat SRS were 18%, 45%, and 56% at 5, 7, and 10 years, respectively. Ten patients sustained hemorrhage after staged SRS, and 5 of these patients died. Three of 16 patients who underwent repeat SRS sustained hemorrhage after the procedure and died. Based on Kaplan-Meier analysis (excluding the second hemorrhage in the patient who had 2 hemorrhages), the cumulative rates of AVM hemorrhage after SRS were 4.3%, 8.6%, 13.5%, and 36.0% at 1, 2, 5, and 10 years, respectively. This corresponded to annual hemorrhage risks of 4.3%, 2.3%, and 5.6% for Years 0-1, 1-5, and 5-10 after SRS. Multiple hemorrhages before SRS correlated with a significantly higher risk of hemorrhage after SRS. Symptomatic adverse radiation effects were detected in 13% of patients, but no patient died as a result of an adverse radiation effect. Delayed cyst formation did not occur in any patient after SRS. CONCLUSIONS: Prospective volume-staged SRS for large AVMs unsuitable for surgery has potential benefit but often requires more than 2 procedures to complete the obliteration process. To have a reasonable chance of benefit, the minimum margin dose should be 17 Gy or greater, depending on the AVM location. In the future, prospective volume-staged SRS followed by embolization (to reduce flow, obliterate fistulas, and occlude associated aneurysms) may improve obliteration results and further reduce the risk of hemorrhage after SRS.

Image-guided frameless stereotactic needle biopsy in awake patients without the use of rigid head fixation.

OBJECT: Image-guided frameless stereotactic techniques provide an alternative to traditional head-frame fixation in the performance of fine-needle biopsies. However, these techniques still require rigid head fixation, usually in the form of a head holder. The authors report on a series of fine-needle biopsies and brain abscess aspirations in which a frameless technique was used with a patient's head supported on a horseshoe headholder. To validate this technique, they performed an in vitro accuracy study. METHODS: Forty-eight patients underwent fine-needle biopsy of intracranial lesions that ranged in size from 0.9 to more than 107.7 ml; a fiducial-less, frameless, image-guided technique was used without rigid head fixation. In 1 of the 48 patients a cerebral abscess was drained. The accuracy study was performed with a skull phantom that was imaged with a CT scanner and tracked with a registration mask containing light-emitting diodes. The objective was a skin fiducial marker with a 4-mm circular target to accommodate the 2.5-mm biopsy needle. A series of 50 trials was conducted. RESULTS: Diagnostic tissue was obtained on the first attempt in 47 of 48 brain biopsy cases. In 2 cases small hemorrhages at the biopsy site were noted as a complication on the postoperative CT scan. One of these hemorrhages resulted in hand and arm weakness. The accuracy study demonstrated a 98% success rate of the biopsy needle passing through the 4-mm circular target using the registration mask as the registration and tracking device. This demonstrates a ± 0.75-mm tolerance on the targeting method. CONCLUSIONS: The accuracy study demonstrated the ability of the mask to actively track the target and allow navigation to a 4-mm-diameter circular target with a 98% success rate. The frameless, pinless, fiducial-less technique described herein will likely be another safe, fast alternative to frame-based stereotactic techniques for fine-needle biopsy that avoids the potential morbidity of rigid head-pin fixation. Furthermore, it should lend itself to other image-guided applications such as the placement of ventricular catheters for shunting or Ommaya reservoirs.

Long-term outcomes after gamma knife stereotactic radiosurgery for nonfunctional pituitary adenomas.

BACKGROUND: Nonfunctional pituitary adenomas (NFPAs) represent approximately 50% of all pituitary tumors. OBJECTIVE: To evaluate the long-term outcomes of stereotactic radiosurgery for NFPAs. METHODS: We evaluated the management outcomes of Gamma Knife radiosurgery in 125 patients with NFPAs over an interval of 22 years. The median patient age was 54 years (range, 16-88 years). One hundred ten patients (88%) had residual or recurrent tumors after ≥ 1 surgical procedures, and 17 (14%) had undergone prior fractionated radiation therapy. The median target volume was 3.5 cm3 (range, 0.4-28.1 cm3), and the median tumor margin dose was 13.0 Gy (range, 10-25 Gy). RESULTS: Tumor volume decreased in 66 patients (53%), remained stable in 46 (37%), and increased in 13 (10.4%) during a median of 62 months (maximum, 19 years) of imaging follow-up. The actuarial tumor control rates at 1, 5, and 10 years were 99%, 94%, and 76%, respectively. Factors associated with a reduced progression-free survival included larger tumor volume (≥ 4.5 cm3) and ≥ 2 prior recurrences. Of 88 patients with residual pituitary function, 21 (24%) suffered new hormonal deficits at a median of 24 months (range, 3-114 months). Prior radiation therapy increased the risk of developing new pituitary hormonal deficits. One patient (0.8%) had a decline in visual function, and 2 (1.6%) developed new cranial neuropathies without tumor progression. CONCLUSION: Stereotactic radiosurgery can provide effective management for patients with newly diagnosed NFPAs and for those after prior resection and/or radiation therapy.

Importance of the C1 anterior tubercle depth and lateral mass geometry when placing C1 lateral mass screws.

OBJECTIVE: We measured the variability in the size of the anterior tubercle of C1 and the optimal depth and angle of placement of C1 lateral mass screws using axial and sagittal reconstructed computed tomographic scans to determine the utility of these parameters for preoperative planning and intraoperative guidance. METHODS: One hundred consecutive cervical spine computed tomographic scans were reviewed (mean patient age, 44.6 years; age range, 7-96 years). The size of the anterior tubercle of C1, bilateral depths of optimal screw placement in the axial and sagittal planes, and optimal angles of placement in the axial and sagittal planes were measured in a standardized manner using the measuring tool included in our radiology server software. These measurements were correlated with age and sex. RESULTS: The mean depth of the C1 tubercle was 6.9 mm (range, 2.7-11.2 mm; standard deviation, 1.7 mm). The depth of the C1 tubercle tended to increase with age, but the relationship was not significant. The optimal screw depth in the sagittal plane was significantly greater than in the axial plane (right 2.09 versus 1.93 cm; left 2.07 versus 1.91 cm). The depth of the right lateral mass increased significantly with age. No other relationships reached significance. CONCLUSION: The depth of the anterior tubercle of C1 varies considerably and should be studied carefully before using lateral fluoroscopy of this structure to guide depth of C1 lateral mass screw placement. Optimal angles and depths of placement of C1 lateral mass screws vary widely and should be examined preoperatively to plan appropriate depth and trajectory.