Zihao Wang and Bing Xing
Prashant Chittiboina, John D. Heiss and Russell R. Lonser
An intraoperative MRI (iMRI)–compatible system has been developed for direct placement of convection-enhanced delivery (CED) cannulae using real-time imaging. To establish the precision and feasibility of this technology, the authors analyzed findings in patients who underwent direct iMRI CED cannula placement.
Three consecutive patients underwent iMRI-guided placement of CED infusion cannulae (6 cannulae) for treatment of diffuse intrinsic brainstem glioma (2 patients) or Parkinson's disease (1 patient). Convective infusion cannulae were guided to the target using the ClearPoint iMRI-based navigation platform (MRI Interventions, Inc.). Placement accuracy was analyzed.
Real-time iMRI during infusion cannula insertion allowed for monitoring of trajectory accuracy during placement. During cannula insertion, no reinsertions or changes due to errors in targeting were necessary. The mean radial error was 1.0 ± 0.5 mm (± SD). There was no correlation between the total length of the planned trajectory and the radial error (Pearson's coefficient: −0.40; p = 0.5). The mean anteroposterior and lateral errors were 0.9 ± 0.5 and 0.3 ± 0.2 mm, respectively. The mean in-plane distance error was 1.0 ± 0.4 mm. The mean tip error (scalar distance between the planned target and actual tip) was 1.9 ± 0.9 mm. There was no correlation between the length of the planned trajectory and any of the measured errors. No complications were associated with cannula placement.
Real-time iMRI-based targeting and monitoring of infusion cannula placement is a safe, effective, and accurate technique that should enable more selective perfusion of brain regions.
Prashant Chittiboina, David E. Connor Jr. and Anil Nanda
Every neurosurgeon develops his or her own standard approach to common intracranial pathologies in terms of the order in which different stages are performed and which instruments are used to perform individual tasks. The majority of the basic steps in performing a craniotomy are learned through repetition and practice during residency training. Significant amounts of energy are devoted to mastering technical skills and developing an operative rhythm. What often receives little attention is the historical origin of the instruments that make the work possible. The Freer elevator represents a particularly interesting example. To people unfamiliar with the accomplishments of turn-of-the-century laryngologist Otto “Tiger” Freer, it can be assumed that the name of the instrument in one's hand is simply named for what it can do, that is, to “free” the nasal mucosa from the bony and cartilaginous septum during the transsphenoidal approach. The technique this master surgeon spent his life and career perfecting is now repeated almost daily by skull base neurosurgeons approaching pathologies from the inferior frontal lobe to the foramen magnum. In reviewing his life and work, the authors of this paper discovered an interesting creative process that led to the design of the eponymous instrument. Additionally, they discovered important advances toward the development of the transnasal approach and in our understanding of the anterior skull base. They present a historical perspective on the life and accomplishments of Dr. Freer and the ubiquitous surgical instrument that he invented and popularized.
Mark M. Souweidane
David E. Connor Jr., Prashant Chittiboina and Anil Nanda
The authors trace the etymology and historical significance of galea or epicranial aponeurosis. In ancient Greece, galea referred to a helmet worn by soldiers, typically made of animal hide or leather. Throughout antiquity, physicians referred to all soft tissue between the skin and the skull as panniculus, a standard established by Galen of Pergamon. A manual of surgery in the Middle Ages referred to the entire scalp as a “great panicle that is called pericranium.” During the early Renaissance, Leonardo da Vinci famously and stylistically analogized the dissection of the cranium with the peeling of an onion. Not until 1724 would the tendinous sheath connecting the frontalis and occipitalis muscles be defined as “Galea tendinosa cranii.” By 1741, the convention of referring to the galea as an aponeurosis was well established.
Harvey Cushing's wartime experiences at Army Base Hospital No. 5 reinforced the surgical significance of the galea. Operative mortality was significantly diminished due to “closure of the wounds with buried sutures in the galea.” This operative nuance was then passed from teacher to pupil and has now become one of the tenets of modern neurosurgical practice.
Gautam U. Mehta, Michael J. Feldman, Herui Wang, Dale Ding and Prashant Chittiboina
The presence of vestibular schwannomas has long been considered an exclusion criterion for the diagnosis of schwannomatosis. Recently, 2 cases of vestibular schwannoma were reported in patients with schwannomatosis, leading to a revision of the diagnostic criteria for this genetic disorder. Overall, the relative infrequency of vestibular schwannomas in schwannomatosis is unexplained, and the genetics of this uncommon phenomenon have not been described. The authors report on a family with clinical manifestations consistent with schwannomatosis, including 4 affected members, that was identified as having an affected member harboring a unilateral cerebellopontine angle mass with extension into the internal auditory canal. Radiologically, this mass was consistent with a vestibular schwannoma and resulted in a symptomatic change in ipsilateral hearing (word recognition 86% at 52 dB) and increased latency of the wave I–V interval on auditory brainstem response testing. The patient was found to be negative for a germline mutation of NF2 and LZTR1, and her affected mother was found to harbor neither NF2 nor SMARCB1 mutations on genetic testing. Although vestibular schwannomas have been classically considered to not occur in the setting of schwannomatosis, this patient with schwannomatosis and a vestibular schwannoma further confirms that schwannomas can occur on the vestibular nerve in this syndrome. Further, this is the first such case found to be negative for a mutation on the LZTR1 gene.
Prashant Chittiboina, John D. Heiss, Katherine E. Warren and Russell R. Lonser
Coinfused surrogate imaging tracers can provide direct insight into the properties of convection-enhanced delivery (CED) in the nervous system. To better understand the distributive properties of CED in a clinical circumstance, the authors analyzed the imaging findings in pediatric diffuse intrinsic pontine glioma (DIPG) patients undergoing coinfusion of Gd-DTPA and interleukin-13–Pseudomonas exotoxin (IL13-PE).
Consecutive patients undergoing CED (maximal rates of 5 or 10 μl/minute) of Gd-DTPA (1 or 5 mM) and IL13-PE (0.125 μg/ml or 0.25 μg/ml) for DIPG were included. Real-time MRI was performed during infusions, and imaging results were analyzed.
Four patients (2 males, 2 females; mean age at initial infusion 13.0 ± 5.3 years; range 5–17 years) underwent 5 infusions into DIPGs. Brainstem infusions were clearly identified on T1-weighted MR images at 1-mM (1 infusion) and 5-mM (4 infusions) coinfused Gd-DTPA concentrations. While the volume of distribution (Vd) increased progressively with volume of infusion (Vi) (mean volume 2.5 ± 0.9 ml; range 1.1–3.7 ml), final Vd:Vi ratios were significantly reduced with lower Gd-DTPA concentration (Vd:Vi for 1 mM of 1.6 compared with a mean Vd:Vi ratio for 5 mM of 3.3 ± 1.0) (p = 0.04). Similarly, anatomical distribution patterns were affected by preferential flow along parallel axial fiber tracts, into prior infusion cannula tracts and intraparenchymal air pockets, and leak back around the infusion cannula at the highest rate of infusion.
Magnetic resonance imaging of a coinfused Gd-DTPA surrogate tracer provided direct insight into the properties of CED in a clinical application. While clinically relevant Vds can be achieved by convective delivery, specific tissue properties can affect distribution volume and pattern, including Gd-DTPA concentration, preferential flow patterns, and infusion rate. Understanding of these properties of CED can enhance its clinical application. Part of clinical trial no. NCT00880061 (ClinicalTrials.gov).
Prashant Chittiboina, Blake K. Montgomery, Corina Millo, Peter Herscovitch and Russell R. Lonser
High-resolution PET (hrPET) performed using a high-resolution research tomograph is reported as having a resolution of 2 mm and could be used to detect corticotroph adenomas through uptake of18F-fluorodeoxyglucose (18F-FDG). To determine the sensitivity of this imaging modality, the authors compared18F-FDG hrPET and MRI detection of pituitary adenomas in Cushing disease (CD).
Consecutive patients with CD who underwent preoperative18F-FDG hrPET and MRI (spin echo [SE] and spoiled gradient recalled [SPGR] sequences) were prospectively analyzed. Standardized uptake values (SUVs) were calculated from hrPET and were compared with MRI findings. Imaging findings were correlated to operative and histological findings.
Ten patients (7 females and 3 males) were included (mean age 30.8 ± 19.3 years; range 11–59 years). MRI revealed a pituitary adenoma in 4 patients (40% of patients) on SE and 7 patients (70%) on SPGR sequences.18F-FDG hrPET demonstrated increased18F-FDG uptake consistent with an adenoma in 4 patients (40%; adenoma size range 3–14 mm). Maximum SUV was significantly higher for18F-FDG hrPET–positive tumors (difference = 5.1, 95% CI 2.1–8.1; p = 0.004) than for18F-FDG hrPET–negative tumors.18F-FDG hrPET positivity was not associated with tumor volume (p = 0.2) or dural invasion (p = 0.5). Midnight and morning ACTH levels were associated with18F-FDG hrPET positivity (p = 0.01 and 0.04, respectively) and correlated with the maximum SUV (R = 0.9; p = 0.001) and average SUV (R = 0.8; p = 0.01). All18F-FDG hrPET–positive adenomas had a less than a 180% ACTH increase and18F-FDG hrPET–negative adenomas had a greater than 180% ACTH increase after CRH stimulation (p = 0.03). Three adenomas were detected on SPGR MRI sequences that were not detected by18F-FDG hrPET imaging. Two adenomas not detected on SE (but no adenomas not detected on SPGR) were detected on18F-FDG hrPET.
While18F-FDG hrPET imaging can detect small functioning corticotroph adenomas and is more sensitive than SE MRI, SPGR MRI is more sensitive than18F-FDG hrPET and SE MRI in the detection of CD-associated pituitary adenomas. Response to CRH stimulation can predict18F-FDG hrPET–positive adenomas in CD.
David E. Connor Jr., Prashant Chittiboina, Gloria Caldito and Anil Nanda
Spinal epidural abscess (SEA), once considered a rare occurrence, has showed a rapid increase in incidence over the past 20–30 years. Recent reports have advocated for conservative, nonoperative management of this devastating disorder with appropriate risk stratification. Crucial to a successful management strategy are decisive diagnosis, prompt intervention, and consistent follow-up care. The authors present a review of their institutional experience with operative and nonoperative management of SEA to assess morbidity and mortality and the accuracy of microbiological diagnosis.
A retrospective analysis of patient charts, microbiology reports, operative records, and radiology reports was performed on all cases involving patients admitted with the diagnosis of SEA between July 1998 and May 2009.
Seventy-seven cases were reviewed (median patient age 51.4 years, range 17–78 years). Axial pain was the most common presenting symptom (67.5% of cases). Presenting signs included focal weakness (55.8%), radiculopathy (28.6%), and myelopathy (5.2%). Abscesses were localized to the lumbar, thoracic, and cervical spine, respectively, in 39 (50.6%), 20 (26.0%), and 18 (23.4%) of the patients. Peripheral blood cultures were negative in 32 (45.1%) of 71 patients. Surgical site or interventional biopsy cultures were diagnostic in 52 cases (78.8%), with concordant blood culture results in 36 (60.0%). Methicillin-resistant Staphylococcus aureus (MRSA) was the most frequent isolate in 24 cases (31.2%). The mean time from admission to surgery was 5.5 days (range 0–42 days; within 72 hours in 66.7% of cases). Outcome data were available in 72 cases. At discharge, patient condition had improved or resolved in 57 cases (79.2%), improved minimally in 6 (8.3%), and showed no improvement or worsening in 9 (12.5%). Patient age and premorbid weakness were the only factors found to be significantly associated with outcome (p = 0.04 and 0.012, respectively).
These results strongly support immediate surgical decompression combined with appropriately tailored antibiotic therapy for the treatment of symptomatic SEA presenting with focal neurological deficit. The nonsuperiority discovered in other patient subsets may be due to allocation biases between surgically treated and nonsurgically treated cohorts. The present data demonstrate the accuracy of peripheral blood culture for the prediction of causative organisms and confirm patient age as a predictor of outcomes.
Ali Nourbakhsh, Prashant Chittiboina, Prasad Vannemreddy, Anil Nanda and Bharat Guthikonda
Transpedicular thoracic vertebrectomy (TTV) is a safe alternative to the more standard transthoracic approach. A TTV is most commonly used to address vertebral body fractures due to tumor or trauma.
Transpedicular reconstruction of the anterior column with cage/bone traditionally requires unilateral thoracic nerve root sacrifice. In a cadaveric model, the authors evaluated the feasibility of transpedicular anterior column reconstruction without nerve root sacrifice. If feasible, this may be a reasonable approach that could be extended to the lumbar spine where nerve root sacrifice is not an option.
A TTV was performed in 8 fixed cadaveric specimens. In each specimen, an alternate vertebra (either odd or even) was removed so that single-level reconstruction could be evaluated. The vertebrectomy included facetectomy, adjacent discectomies, and laminectomy; however, the nerve roots were preserved. The authors then evaluated the feasibility of inserting a titanium mesh cage (Medtronic Sofamor Danek) without neural sacrifice.
Transpedicular anterior cage reconstruction could be safely performed at all levels of the thoracic spine without nerve root sacrifice. The internerve root space varied from 18 mm at T2–3 to 27 mm at T11–12; thus, the size of the cage that was used also varied with level.
Cage reconstruction of the anterior column could be safely performed via the transpedicular approach without nerve root sacrifice in this cadaveric study. Removal of the proximal part of the rib in addition to a standard laminectomy with transpedicular vertebrectomy provided an excellent corridor for anterior cage reconstruction at all levels of the thoracic spine without nerve root sacrifice.