Search Results

You are looking at 1 - 10 of 19 items for

  • Author or Editor: Stephen Johnson x
Clear All Modify Search
Full access

Stephen L. Fedder

Restricted access

Stephen R. Marano, Peter C. Johnson and Robert F. Spetzler

✓ A case of recurrent Lhermitte-Duclos disease (dysplastic gangliocytoma of the cerebellum) in a child is described with a summary of the clinical presentation and associated malformations, and a review of other cases reported in the literature. The histological examination and electron microscopic findings, with special reference to the cytological changes found during evaluation of the recurrence, are presented. Theories regarding the pathogenesis of Lhermitte-Duclos disease are reviewed.

Full access

Brian J. Karlovits, Matthew R. Quigley, Stephen M. Karlovits, Lindsay Miller, Mark Johnson, Olivier Gayou and Russell Fuhrer

Object

Whole-brain radiation therapy (WBRT) has been the traditional approach to minimize the risk of intracranial recurrence following resection of brain metastases, despite its potential for late neurotoxicity. In 2007, the authors demonstrated an equivalent local recurrence rate to WBRT by using stereotactic radiosurgery (SRS) to the operative bed, sparing 72% of their patients WBRT. They now update their initial experience with additional patients and more mature follow-up.

Methods

The authors performed a retrospective review of all cases involving patients with limited intracranial metastatic disease (≤ 4 lesions) treated at their institution with SRS to the operative bed following resection. No patient had prior cranial radiation and WBRT was used only for salvage.

Results

From November 2000 to June 2009, 52 patients with a median age of 61 years met inclusion criteria. A single metastasis was resected in each patient. Thirty-four of the patients each had 1 lesion, 13 had 2 lesions, 3 had 3 lesions, and 2 had 4 lesions. A median dose of 1500 cGy (range 800–1800 cGy) was delivered to the resection bed targeting a median volume of 3.85 cm3 (range 0.08–22 cm3). With a median follow-up of 13 months, the median survival was 15.0 months. Four patients (7.7%) had a local recurrence within the surgical site. Twenty-three patients (44%) ultimately developed distant brain recurrences at a median of 16 months postresection, and 16 (30.7%) received salvage WBRT (8 for diffuse disease [> 3 lesions], 4 for local recurrence, and 4 for diffuse progression following salvage SRS). The median time to WBRT administration postresection was 8.7 months (range 2–43 months). On univariate analysis, patient factors of a solitary tumor (19.0 vs 12 months, p = 0.02), a recursive partitioning analysis (RPA) Class I (21 vs 13 months, p = 0.03), and no extracranial disease on presentation (22 vs 13 months, p = 0.01) were significantly associated with longer survival. Cox multivariate analysis showed a significant association with longer survival for the patient factors of no extracranial disease on presentation (p = 0.01) and solitary intracranial metastasis (p = 0.02). Among patients with no extracranial disease, a solitary intracranial metastasis conferred significant additional survival advantage (43 vs 10.5 months, p = 0.05, log-rank test). No factor (age, RPA class, tumor size or histological type, disease burden, extent of resection, or SRS dose or volume) was related to the need for salvage WBRT.

Conclusions

Adjuvant SRS to the metastatic intracranial operative bed results in a local recurrence rate equivalent to adjuvant WBRT. In combination with SRS for unresected lesions and routine imaging surveillance, this approach achieves robust overall survival (median 15 months) while sparing 70% of the patients WBRT and its potential acute and chronic toxicity.

Restricted access

Robert Kellogg, Philip Lee, Christopher P. Deibert, Zachary Tempel, Nathan T. Zwagerman, Christopher M. Bonfield, Stephen Johnson and Stephanie Greene

OBJECTIVE

The authors reviewed 20 years’ experience with the surgical management of open myelomeningocele in a well-defined retrospective cohort from a single large academic medical center. Their goal was to define the characteristics of a modern cohort of children with myelomeningocele to allow for evidence-based decision-making for the treatment of these patients.

METHODS

After IRB approval was obtained, the authors queried an operative database maintained by the Department of Neurological Surgery at Children’s Hospital of Pittsburgh for patients who underwent closure of a myelomeningocele between 1995 and 2015. They identified 153 infants, and a retrospective chart review was performed.

RESULTS

Eighty-eight percent of the patients required placement of a ventriculoperitoneal shunt, and 15% of these patients acquired shunt-related infections. Eighteen percent of patients underwent Chiari malformation type II (CM-II) decompression. Sixteen percent of patients underwent a tethered cord release. Three percent of patients died within the 1st year of life. Predictors of an early demise included poor Apgar scores, large head circumference, and need for early CM-II decompression. Functional motor outcome was slightly better than predicted by anatomical level of defect.

CONCLUSIONS

Myelomeningoceles represent a severe birth defect with life-threatening complications. The authors provide long-term follow-up data and insight into factors that contribute to early death.

Restricted access

Michael M. McDowell, Nitin Agarwal, Gordon Mao, Stephen Johnson, Hideyuki Kano, L. Dade Lunsford and Stephanie Greene

OBJECTIVE

The study of pediatric arteriovenous malformations (pAVMs) is complicated by the rarity of the entity. Treatment choice has often been affected by the availability of different modalities and the experience of the providers present. The University of Pittsburgh experience of multimodality treatment of pAVMs is presented.

METHODS

The authors conducted a retrospective cohort study examining 212 patients with pAVM presenting to the University of Pittsburgh between 1988 and 2018, during which patients had access to surgical, endovascular, and radiosurgical options. Univariate analysis was performed comparing good and poor outcomes. A poor outcome was defined as a modified Rankin Scale (mRS) score of ≥ 3. Multivariate analysis via logistic regression was performed on appropriate variables with a p value of ≤ 0.2. Seventy-five percent of the cohort had at least 3 years of follow-up.

RESULTS

Five patients (2.4%) did not receive any intervention, 131 (61.8%) had GKRS alone, 14 (6.6%) had craniotomies alone, and 2 (0.9%) had embolization alone. Twenty-two (10.4%) had embolization and Gamma Knife radiosurgery (GKRS); 20 (9.4%) had craniotomies and GKRS; 8 (3.8%) had embolization and craniotomies; and 10 (4.7%) had embolization, craniotomies, and GKRS. Thirty-one patients (14.6%) were found to have poor outcome on follow-up. The multivariate analysis performed in patients with poor outcomes was notable for associations with no treatment (OR 18.9, p = 0.02), hemorrhage requiring craniotomy for decompression alone (OR 6, p = 0.03), preoperative mRS score (OR 2.1, p = 0.004), and Spetzler-Martin score (OR 1.8, p = 0.0005). The mean follow-up was 79.7 ± 62.1 months. The confirmed radiographic obliteration rate was 79.4% and there were 5 recurrences found on average 9.5 years after treatment.

CONCLUSIONS

High rates of long-term functional independence (mRS score of ≤ 2) can be achieved with comprehensive multimodality treatment of pAVMs. At this center there was no difference in outcome based on treatment choice when accounting for factors such as Spetzler-Martin grade and presenting morbidity. Recurrences are rare but frequently occur years after treatment, emphasizing the need for long-term screening after obliteration.

Restricted access

Stephen Johnson, Hideyuki Kano, Andrew Faramand, Ajay Niranjan, John C. Flickinger and L. Dade Lunsford

OBJECTIVE

Optimizing outcomes in the management of patients with vestibular schwannomas (VSs) requires consideration of the patient’s goals. Earlier recognition of VS by imaging has led to an evolution in management. Stereotactic radiosurgery (SRS) has emerged as a frequently used strategy designed to reduce management risks, obtain long-term tumor control, and preserve current neurological function. The authors analyzed features that impact hearing preservation rates in patients with serviceable hearing prior to SRS.

METHODS

The study included 307 patients who had serviceable hearing (Gardner-Robertson hearing scale [GR] grade 1 or 2, speech discrimination score ≥ 50%, pure tone average ≤ 50 dB) at the time of SRS. The authors evaluated parameters that included age, tumor volume, hearing status, disequilibrium, tinnitus, Koos class, sex, and tumor margin dose. The Pittsburgh Hearing Prediction Score (PHPS) was evaluated as a method to predict long-term hearing outcomes in these cases.

RESULTS

At a median of 7.6 years after SRS (range 1–23 years), tumor control was achieved in 95% of patients. The overall serviceable hearing preservation rate was 77.8% at 3 years, 68.8% at 5 years, and 51.8% at 10 years. The PHPS assigns a total of 5 points based on patient age (1 point if < 45 years, 2 points if 45–59 years, and 3 points if ≥ 60 years), tumor volume (0 points if < 1.2 cm3, 1 point if ≥ 1.2 cm3), and GR grade (0 points if grade 1 hearing, 1 point if grade 2 hearing) The serviceable hearing preservation rate was 92.3% at 10 years in patients whose score total was 1. In contrast, none of the patients whose PHPS was 5 maintained serviceable hearing at 10 years (p < 0.001).

CONCLUSIONS

SRS resulted in a high rate of long-term tumor control and cranial nerve preservation. The PHPS helped to predict long-term hearing preservation rates in patients who underwent SRS when they still had serviceable hearing. The best long-term hearing preservation rates were found in younger patients with smaller tumor volumes.

Full access

William G. B. Singleton, Alison S. Bienemann, Max Woolley, David Johnson, Owen Lewis, Marcella J. Wyatt, Stephen J. P. Damment, Lisa J. Boulter, Clare L. Killick-Cole, Daniel J. Asby and Steven S. Gill

OBJECTIVE

The pan–histone deacetylase inhibitor panobinostat has preclinical efficacy against diffuse intrinsic pontine glioma (DIPG), and the oral formulation has entered a Phase I clinical trial. However, panobinostat does not cross the blood-brain barrier in humans. Convection-enhanced delivery (CED) is a novel neurosurgical drug delivery technique that bypasses the blood-brain barrier and is of considerable clinical interest in the treatment of DIPG.

METHODS

The authors investigated the toxicity, distribution, and clearance of a water-soluble formulation of panobinostat (MTX110) in a small- and large-animal model of CED. Juvenile male Wistar rats (n = 24) received panobinostat administered to the pons by CED at increasing concentrations and findings were compared to those in animals that received vehicle alone (n = 12). Clinical observation continued for 2 weeks. Animals were sacrificed at 72 hours or 2 weeks following treatment, and the brains were subjected to neuropathological analysis. A further 8 animals received panobinostat by CED to the striatum and were sacrificed 0, 2, 6, or 24 hours after infusion, and their brains explanted and snap-frozen. Tissue-drug concentration was determined by liquid chromatography tandem mass spectrometry (LC-MS/MS). Large-animal toxicity was investigated using a clinically relevant MRI-guided translational porcine model of CED in which a drug delivery system designed for humans was used. Panobinostat was administered at 30 μM to the ventral pons of 2 juvenile Large White–Landrace cross pigs. The animals were subjected to clinical and neuropathological analysis, and findings were compared to those obtained in controls after either 1 or 2 weeks. Drug distribution was determined by LC-MS/MS in porcine white and gray matter immediately after CED.

RESULTS

There were no clinical or neuropathological signs of toxicity up to an infused concentration of 30 μM in both small- and large-animal models. The half-life of panobinostat in rat brain after CED was 2.9 hours, and the drug was observed to be distributed in porcine white and gray matter with a volume infusion/distribution ratio of 2 and 3, respectively.

CONCLUSIONS

CED of water-soluble panobinostat, up to a concentration of 30 μM, was not toxic and was distributed effectively in normal brain. CED of panobinostat warrants clinical investigation in patients with DIPG.

Restricted access

Visish M. Srinivasan, Joy Gumin, Kevin M. Camstra, Stephen R. Chen, Jeremiah N. Johnson, Yuzaburo Shimizu, Brittany C. Parker Kerrigan, Elizabeth J. Shpall, Frederick F. Lang and Peter Kan

OBJECTIVE

Bone marrow–derived human mesenchymal stem cells (BM-hMSCs) have been used in clinical trials for the treatment of several neurological disorders. MSCs have been explored as a delivery modality for targeted viral therapeutic agents in the treatment of intracranial pathologies. Delta-24-RGD, a tumor-selective oncolytic adenovirus designed to target malignant glioma cells, has been shown to be effective in animal models and in a recent clinical trial. However, the most efficient strategy for delivering oncolytic therapies remains unclear. BM-hMSCs have been shown to home toward glioma xenografts after intracarotid delivery. The feasibility of selective intraarterial infusion of BM-hMSCs loaded with Delta-24-RGD (BM-hMSC-Delta-24) to deliver the virus to the tumor is being investigated. To evaluate the feasibility of endovascular intraarterial delivery, the authors tested in vitro the compatibility of BM-hMSC-Delta-24 with a variety of commercially available, clinically common microcatheters.

METHODS

BM-hMSCs were cultured, transfected with Delta-24-RGD, and resuspended in 1% human serum albumin. The solution was then injected via 4 common neuroendovascular microcatheters of different inner diameters (Marathon, Echelon-14, Marksman, and SL-10). Cell count and viability after injection through the microcatheters were assessed, including tests of injection velocity and catheter configuration. Transwell assays were performed with the injected cells to test the efficacy of BM-hMSC-Delta-24 activity against U87 glioma cells. BM-hMSC-Delta-24 compatibility was also tested with common neuroendovascular medications: Omnipaque, verapamil, and heparin.

RESULTS

The preinfusion BM-hMSC-Delta-24 cell count was 1.2 × 105 cells/ml, with 98.7% viability. There was no significant difference in postinfusion cell count or viability for any of the catheters. Increasing the injection velocity from 1.0 ml/min to 73.2 ml/min, or modifying the catheter shape from straight to tortuous, did not significantly reduce cell count or viability. Cell count and viability remained stable for up to 5 hours when the cell solution was stored on ice. Mixing BM-hMSC-Delta-24 with clinical concentrations of Omnipaque, verapamil, and heparin prior to infusion did not alter cell count or viability. Transwell experiments demonstrated that the antiglioma activity of BM-hMSC-Delta-24 was maintained after infusion.

CONCLUSIONS

BM-hMSC-Delta-24 is compatible with a wide variety of microcatheters and medications commonly used in neuroendovascular therapy. Stem cell viability and viral agent activity do not appear to be affected by catheter configuration or injection velocity. Commercially available microcatheters can be used to deliver stem cell neurotherapeutics via intraarterial routes.

Restricted access

Kathryn Wagner, Aditya Srivatsan, Alina Mohanty, Visish M. Srinivasan, Yasir Saleem, Jacob Cherian, Robert F. James, Stephen Chen, Jan-Karl Burkhardt, Jeremiah Johnson and Peter Kan

OBJECTIVE

Flow diversion is increasingly used to treat a variety of intracranial aneurysms with good safety and efficacy; however, there is some evidence that this treatment is associated with a larger postoperative ischemic burden on imaging than that with other traditional endovascular modalities. These findings typically do not manifest as neurological deficits, but any subtle effects on cognition remain unknown. In this study, the authors describe the neurocognitive performance of a cohort of patients with unruptured intracranial aneurysms (UIAs) before and after treatment with flow diversion. This is the first report of cognitive outcomes following aneurysm treatment with flow diversion.

METHODS

The authors prospectively collected data on cognitive function using the Montreal Cognitive Assessment (MoCA) tool in patients with UIAs who were undergoing endovascular aneurysm treatment with flow diversion between June 2017 and July 2019. Patients completed the MoCA prior to intervention, at the 1-month follow-up after treatment, and again at 6 months after the procedure. All patients with UIAs treated with flow diversion were included regardless of age, aneurysm location, or morphology, unless their functional status precluded completion of the MoCA instrument. A repeated-measures linear mixed-effects model was used to compare preintervention and postintervention cognitive status at the time intervals outlined.

RESULTS

Fifty-one patients with 61 aneurysms underwent endovascular aneurysm treatment with flow diversion (mean age 52.5 years, 90.2% females). There was no difference between baseline and postprocedure MoCA scores at any time interval (p > 0.05). The MoCA scores at baseline, 1 month postprocedure, and 6 months postprocedure were 26.1, 26.2, and 26.6, respectively. There was also no difference between pre- and postprocedure scores on any individual domain of the instrument (visuospatial, naming, attention, language, abstraction, delayed recall, and orientation) at any time interval (p > 0.05). Thirty-four patients had follow-up MRI or CT imaging, 5 of whom showed radiographic changes or ischemia. All patients with follow-up clinical evaluation had a 6-month modified Rankin Scale score ≤ 2.

CONCLUSIONS

Flow diversion is increasingly used in the treatment of intracranial aneurysms. This study suggests that this treatment may not alter neurocognitive function. Larger patient samples and longer follow-ups with other tests of cognitive functions are needed to confirm these findings.

Full access

Mario Teo, Jeremiah N. Johnson, Teresa E. Bell-Stephens, Michael P. Marks, Huy M. Do, Robert L. Dodd, Michael B. Bober and Gary K. Steinberg

OBJECTIVE

Majewski osteodysplastic primordial dwarfism Type II (MOPD II) is a rare genetic disorder. Features of it include extremely small stature, severe microcephaly, and normal or near-normal intelligence. Previous studies have found that more than 50% of patients with MOPD II have intracranial vascular anomalies, but few successful surgical revascularization or aneurysm-clipping cases have been reported because of the diminutive arteries and narrow surgical corridors in these patients. Here, the authors report on a large series of patients with MOPD II who underwent surgery for an intracranial vascular anomaly.

METHODS

In conjunction with an approved prospective registry of patients with MOPD II, a prospectively collected institutional surgical database of children with MOPD II and intracranial vascular anomalies who underwent surgery was analyzed retrospectively to establish long-term outcomes.

RESULTS

Ten patients with MOPD II underwent surgery between 2005 and 2012; 5 patients had moyamoya disease (MMD), 2 had intracranial aneurysms, and 3 had both MMD and aneurysms. Patients presented with transient ischemic attack (TIA) (n = 2), ischemic stroke (n = 2), intraparenchymal hemorrhage from MMD (n = 1), and aneurysmal subarachnoid hemorrhage (n = 1), and 4 were diagnosed on screening. The mean age of the 8 patients with MMD, all of whom underwent extracranial-intracranial revascularization (14 indirect, 1 direct) was 9 years (range 1–17 years). The mean age of the 5 patients with aneurysms was 15.5 years (range 9–18 years). Two patients experienced postoperative complications (1 transient weakness after clipping, 1 femoral thrombosis that required surgical repair). During a mean follow-up of 5.9 years (range 3–10 years), 3 patients died (1 of subarachnoid hemorrhage, 1 of myocardial infarct, and 1 of respiratory failure), and 1 patient had continued TIAs. All of the surviving patients recovered to their neurological baseline.

CONCLUSIONS

Patients with MMD presented at a younger age than those in whom aneurysms were more prevalent. Microneurosurgery with either intracranial bypass or aneurysm clipping is extremely challenging but feasible at expert centers in patients with MOPD II, and good long-term outcomes are possible.