Rudolph J. Schrot

Fluorescence lifetime imaging microscopy for brain tumor image-guided surgery

We demonstrate for the first time the application of an endoscopic fluorescence lifetime imaging microscopy (FLIM) system to the intraoperative diagnosis of glioblastoma multiforme (GBM). The clinically compatible FLIM prototype integrates a gated (down to 0.2 ns) intensifier imaging system with a fiber-bundle (fiber image guide of 0.5 mm diameter, 10,000 fibers with a gradient index lens objective 0.5 NA, and 4 mm field of view) to provide intraoperative access to the surgical field. Experiments conducted in three patients undergoing craniotomy for tumor resection demonstrate that FLIM-derived parameters allow for delineation of tumor from normal cortex. For example, at 460±25-nm wavelength band emission corresponding to NADH/NADPH fluorescence, GBM exhibited a weaker fluorescence intensity (35% less, p-value<0.05) and a longer lifetime τGBM-Amean=1.59±0.24 ns than normal cortex τNC-Amean=1.28±0.04 ns (p-value<0.005). Current results demonstrate the potential use of FLIM as a tool for image-guided surgery of brain tumors.

The Efficacy of Factor VIIa in Emergency Department Patients With Warfarin Use and Traumatic Intracranial Hemorrhage

OBJECTIVES The objective was to compare outcomes in emergency department (ED) patients with preinjury warfarin use and traumatic intracranial hemorrhage (tICH) who did and did not receive recombinant activated factor VIIa (rFVIIa) for international normalized ratio (INR) reversal. METHODS This was a retrospective before-and-after study conducted at a Level 1 trauma center, with data from 1999 to 2009. Eligible patients had preinjury warfarin use and tICH on cranial computed tomography (CT) scan. Patients before (standard cohort) and after (rFVIIa cohort) implementation of a protocol for administering 1.2 mg of rFVIIa in the ED were reviewed. Glasgow Coma Scale (GCS) score, Revised Trauma Score (RTS), Injury Severity Score (ISS), INR, and Marshall score were collected. Outcome measures included mortality, thromboembolic complications, and INR normalization. RESULTS Forty patients (median age=80.5 years, interquartile range [IQR]=63.5-85) were included (20 in each cohort). Age, GCS score, ISS, RTS, initial INR, and Marshall score were similar (p>0.05) between the two cohorts. Survival was identical between cohorts (13 of 20, or 65.0%, 95% confidence interval [CI]=40.8% to 84.6%). There were no differences in rate of thromboembolic complications in the standard cohort (1 of 20, 5.0%, 95% CI=0.1% to 24.9%) than the rFVIIa cohort (4 of 20, 20.0%, 95% CI=5.7% to 43.7%; p=0.34). Time to normal INR was earlier in the rFVIIa cohort (mean=4.8 hours, 95% CI=3.0 to 6.7 hours) than in the standard cohort (mean=17.5 hours, 95% CI=12.5 to 22.6; p<0.001). CONCLUSIONS In patients with preinjury warfarin and tICH, use of rFVIIa was associated with a decreased time to normal INR. However, no difference in mortality was identified. Use of rFVIIa in patients on warfarin and tICH requires further study to demonstrate important patient-oriented outcomes.

Coccygectomy for chronic refractory coccygodynia: clinical case series and literature review: Clinical article

OBJECT Coccygodynia is disabling pain in the coccyx and is usually provoked by sitting or rising from sitting. The diagnosis can be missed by neurosurgeons likely to encounter the disorder, and surgical treatment for coccygodynia has historically been viewed with caution. The authors conducted a retrospective review of 62 successive coccygectomy surgeries for coccygodynia performed at their institution. METHODS Sixty-two consecutive cases of coccygectomy for coccygodynia in 61 unique patients were identified from the surgical database; they had been treated between 1997 and 2009. The authors succeeded in contacting 26 patients for follow-up (42.6%). A retrospective chart review was performed, and a telephone questionnaire was administered to these patients. Data collected included cause, pre- and postoperative visual analog scale, a graded outcome measure, and patient satisfaction. The median follow-up time was 37 months (range 2-133 months). RESULTS The clinical results among the 26 patients with follow-up were as follows: 13 excellent, 9 good, 2 fair, and 2 poor. The overall favorable (excellent and good) outcome after coccygectomy was 84.6%. There were 3 wound infections (11.5%). There were no rectal injuries. An overwhelming majority of patients were satisfied with the procedure. CONCLUSIONS The authors report the results of their clinical case series, which to date is the largest in North America. The results closely concur with previously published case series from Europe. Coccygectomy for chronic intractable coccygodynia is simple and effective, with a low complication rate. A comprehensive literature review and discussion of coccygectomy is provided.

Organotypic distribution of stem cell markers in formalin-fixed brain harboring glioblastoma multiforme.

The role of stem cells in the origin, growth patterns, and infiltration of glioblastoma multiforme is a subject of intense investigation. One possibility is that glioblastoma may arise from transformed stem cells in the ventricular zone. To explore this hypothesis, we examined the distribution of two stem cell markers, activating transcription factor 5 (ATF5) and CD133, in an autopsy brain specimen from an individual with glioblastoma multiforme. A 41-year-old male with a right posterior temporal glioblastoma had undergone surgery, radiation, and chemotherapy. The brain was harvested within several hours after death. After formalin fixation, sectioning, and mapping of tumor location in the gross specimen, histologic specimens were prepared from tumor-bearing and grossly normal hemispheres. Fluorescence immunohistochemistry and colorimetric staining were performed for ATF5 and CD133. Both markers co-localized to the ependymal and subependymal zones on the side of the tumor, but not in the normal hemisphere or more rostrally in the affected hemisphere. ATF5 staining was especially robust within the diseased hemisphere in histologically normal ependyma. To our knowledge, this is the first in situ demonstration of stem cell markers in whole human brain. These preliminary results support the hypothesis that some glioblastomas may arise from the neurogenic zone of the lateral ventricle. The robust staining for ATF5 and CD133 in histologically normal ventricular zone suggests that an increase in periventricular stem cell activity occurred in this patient on the side of the tumor, either as a localized response to brain injury or as an integral component of oncogenesis and tumor recurrence.

Incidence of first primary central nervous system tumors in California, 2001-2005

We examined the incidence of first primary central nervous system tumors (PCNST) in California from 2001–2005. This study period represents the first five years of data collection of benign PCNST by the California Cancer Registry. California’s age-adjusted incidence rates (AAIR) for malignant and benign PCNST (5.5 and 8.5 per 100,000, respectively). Malignant PCNST were highest among non-Hispanic white males (7.8 per 100,000). Benign PCNST were highest among African American females (10.5 per 100,000). Hispanics, those with the lowest socioeconomic status, and those who lived in rural California were found to be significantly younger at diagnosis. Glioblastoma was the most frequent malignant histology, while meningioma had the highest incidence among benign histologies (2.6 and 4.5 per 100,000, respectively). This study is the first in the US to compare malignant to benign PCNST using a population-based data source. It illustrates the importance of PCNST surveillance in California and in diverse communities.

Decompressive craniectomy using gelatin film and future bone flap replacement

OBJECT Decompressive craniectomy plays an important role in the management of patients with traumatic brain injury (TBI) and stroke. Risks of decompressive craniectomy include those associated with cranioplasty, and may be related to adhesions that develop between the brain surface and overlying scalp and temporalis muscle. The authors report their institutional experience using a multilayered technique (collagen and gelatin film barriers) to facilitate safe and rapid cranioplasty following decompressive craniectomy. METHODS The authors conducted a retrospective chart review of 62 consecutive adult and pediatric patients who underwent decompressive craniectomy and subsequent cranioplasty between December 2007 and January 2011. Diagnoses included TBI, ischemic stroke, intraparenchymal hemorrhage, or subarachnoid hemorrhage. A detailed review of clinical charts was performed, including anesthesia records and radiographic study results. RESULTS The majority of patients underwent unilateral hemicraniectomy (n = 56), with indications for surgery including midline shift (n = 37) or elevated intracranial pressure (n = 25). Multilayered decompressive craniectomy was safe and easy to perform, and was associated with a low complication rate, minimal operative time, and limited blood loss. CONCLUSIONS Decompressive craniectomy repair using an absorbable gelatin film barrier facilitates subsequent cranioplasty by preventing adhesions between intracranial contents and the overlying galea aponeurotica and temporalis muscle fascia. This technique makes cranioplasty dissection faster and potentially safer, which may improve clinical outcomes. The indications for gelatin film should be expanded to include placement in the epidural space after craniectomy.

Breast‐Related CSF Shunt Complications: Literature Review with Illustrative Case

Abstract:  In this article, we discuss and classify breast‐related ventriculoperitoneal (VP) cerebrospinal fluid (CSF) shunt complications, and provide a literature review. Shunt complications related to pre‐existing breast implants comprise nearly half of the breast‐related shunt complications reported thus far. We present a complication of shunt failure in a 61‐year‐old woman who had previously undergone mastectomies for breast cancer with implant reconstruction. Following shunting, she developed headaches, fever, and right‐sided breast swelling and erythma consequent to breast implant rupture, distal shunt migration, and CSF pseudocyst. This case is unique in that it involved rupture of a breast implant from VP shunt insertion. For complication avoidance, neurosurgeons should be aware of the potential pitfalls in shunting patients with breast implants.

Giant intracranial medullary thyroid carcinoma metastasis presenting as apoplexy

We present a case of a giant sellar and suprasellar skull base-invasive metastasis from a medullary carcinoma of the thyroid gland. Radiographic features were similar to atypical/malignant meningioma or pituitary macroadenoma. Intracranial metastases from medullary thyroid carcinoma are very rare. Unusual features of our case are discussed.

Acute deterioration in occult Chiari malformation following missile spinal trauma : Case report

Patients with Chiari malformation (CM) Type I typically experience chronic, slowly progressive symptoms. Rarely, however, do they suffer acute neurological deterioration following an iatrogenic decrease in caudal cerebrospinal fluid pressure due to, for example, a lumbar puncture. To our knowledge, acute neurological deterioration following missile spinal injury in CM has not been previously described. The authors report on a 16-year-old girl who was shot in the abdomen and lumbar spine. Although neurologically intact on initial workup, she developed precipitous quadriplegia and apnea in a delayed fashion. Tonsillar herniation with medullary compression and cerebellar infarction was diagnosed on magnetic resonance imaging. Suboccipital decompression resulted in significant neurological improvement. Well-formed tonsillar ectopia diagnosed at surgery suggested a preexisting CM. The authors conclude that missile spinal trauma can precipitate medullary compression and acute neurological decline, especially in patients with preexisting tonsillar ectopia. Immediate operative decompression to relieve impaction at the cervicomedullary junction can result in significant neurological recovery.

Headache relief after anterior cervical discectomy: post hoc analysis of a randomized investigational device exemption trial: clinical article.

OBJECT The authors analyzed headache relief after anterior cervical discectomy. Headache may be relieved after anterior cervical discectomy, but the mechanism is unknown. If headaches were directly referred from upper cervical pathology, more headache relief would be expected from surgery performed at higher cervical levels. If spinal kinesthetics were the mechanism, then headache relief may differ between arthroplasty and fusion. Headache relief after anterior cervical discectomy was quantified by the operated disc level and by the method of operation (arthroplasty vs arthrodesis). METHODS The authors performed a post hoc analysis of an artificial disc trial. Data on headache pain were extracted from the Neck Disability Index (NDI) questionnaire. RESULTS A total of 260 patients underwent single-level arthroplasty or arthodesis. Preoperatively, 52% reported NDI headache scores of 3 or greater, compared with only 13%-17% postoperatively. The model-based mean NDI headache score at baseline was 2.5 (95% CI 2.3-2.7) and was reduced by 1.3 points after surgery (95% CI 1.2-1.4, p < 0.001). Higher cervical levels were associated with a greater degree of preoperative headache, but there was no association with headache relief. There was no significant difference in headache relief between arthroplasty and arthrodesis. CONCLUSIONS Most patients with symptomatic cervical spondylosis have headache as a preoperative symptom (88%). Anterior cervical discectomy with both arthroplasty and arthrodesis is associated with a durable decrease in headache. Headache relief is not related to the level of operation. The mechanism for headache reduction remains unclear.