Michael Karsy, Jian Guan and L. Eric Huang
Gliomas are one of the most common types of primary brain tumors. Recent studies have supported the importance of key genetic alterations, including isocitrate dehydrogenase (IDH) mutations and 1p19q codeletion, in glioma prognosis. Mutant IDH produces 2-hydroxyglutarate from α-ketoglutarate, a key metabolite of the Krebs cycle. The mitochondrial pyruvate carrier (MPC) is composed of MPC1 and MPC2 subunits and is functionally essential for the Krebs cycle. The authors sought to explore the impact of MPC1 and MPC2 expression on patient prognosis.
Genomic and clinical data in patients with lower-grade glioma (WHO grades II and III) from The Cancer Genome Atlas (TCGA) were evaluated using Kaplan-Meier analysis and hazards modeling. Validation was conducted with additional data sets, including glioblastoma.
A total of 286 patients with lower-grade glioma (mean age 42.7 ± 13.5 years, 55.6% males) included 54 cases of IDH–wild type (18.9%); 140 cases of IDH-mutant, 1p19q-intact (49.0%); and 85 cases of IDH-mutant, 1p19q-codeleted (29.7%) tumors. Kaplan-Meier analysis showed that an MPC1 z-score > 0 distinguished better survival, particularly in IDH-mutant (p < 0.01) but not IDH–wild type tumors. Conversely, an MPC2 z-score > 0 identified worsened survival, particularly in IDH-mutant (p < 0.01) but not IDH–wild type tumors. Consistently, neither MPC1 nor MPC2 was predictive in a glioblastoma data set containing 5% IDH-mutant cases. Within the IDH-stratified lower-grade glioma data set, MPC1 status distinguished improved survival in 1p19q-codeleted tumors (p < 0.05), whereas MPC2 expression delineated worsened survival in 1p19q-intact tumors (p < 0.01). A hazards model identified IDH and 1p19q status, age (p = 0.01, HR = 1.03), Karnofsky Performance Scale (KPS) score (p = 0.03, HR = 0.97), and MPC1 (p = 0.003, HR = 0.52) but not MPC2 (p = 0.38) as key variables affecting overall survival. Further validation confirmed MPC1 as an independent predictor of lower-grade glioma. A clinical risk score using IDH and 1p19q status, age, KPS score, and MPC1 and MPC2 z-scores defined 4 risk categories for lower-grade glioma; this score was validated using a secondary glioma data set.
These results support the importance of MPC, especially MPC1, in improving prognostication of IDH-mutant tumors. The generation of a risk score system directly translates this finding to clinical application; however, further research to improve the molecular understanding of the role of MPC in the metabologenomic regulation of gliomas is warranted.
Spencer Twitchell, Michael Karsy, Jian Guan, William T. Couldwell and Philipp Taussky
The term “radiation vasculopathy” defines a heterogeneous and poorly defined complex of vessel injury due to radiation. Radiation vasculopathy remains underrecognized and poorly treated with respect to head and neck radiotherapy. Distinct injury patterns to small (≤ 100-μm), medium (> 100-μm), and large (> 500-μm) vessels can occur, resulting in carotid stenosis, intracranial stenosis, and vascular anomalies (e.g., cavernous malformations, aneurysms). Because of the lack of clinical evidence and guidelines, treatment plans involve medical management, carotid endarterectomy, and carotid artery stenting and are developed on a patient-by-patient basis. In this review, the authors discuss the current pathophysiology, imaging, clinical impact, and potential treatment strategies of radiation vasculopathy with clinical pertinence to practicing neurosurgeons and neurologists. A review of 4 patients with prior head and neck tumors in whom delayed radiation vasculopathy developed after radiotherapy demonstrates the application of various treatment options in a case-by-case manner. Earlier recognition of radiation vasculopathy disease patterns may enable earlier initiation of treatment and monitoring for complications. Standardized terminology and treatments may assist with improving clinical outcomes.
Michael Karsy, Daxa M. Patel, Kyle Halvorson, Vance Mortimer and Robert J. Bollo
Anterior two-thirds corpus callosotomy is a common palliative surgical intervention most commonly employed in patients with atonic or drop seizures. Recently, stereotactic laser ablation of the corpus callosum without a craniotomy has shown promise in achieving similar outcomes with fewer side effects and shorter hospitalizations. The authors demonstrate ablation of the anterior two-thirds corpus callosum in a patient with Lennox-Gastaut syndrome and drug-resistant drop seizures. Technical nuances of laser ablation with 3 laser fibers are described. Postoperatively, the patient showed a significant reduction in seizure frequency and severity over a 9-month follow-up period.
The video can be found here: https://youtu.be/3-mMq5-PLiM.
Hussam Abou-Al-Shaar, Michael Karsy, Vijay Ravindra, Evan Joyce and Mark A. Mahan
Particularly challenging after complete brachial plexus avulsion is reestablishing effective hand function, due to limited neurological donors to reanimate the arm. Acute repair of avulsion injuries may enable reinnervation strategies for achieving hand function. This patient presented with pan–brachial plexus injury. Given its irreparable nature, the authors recommended multistage reconstruction, including contralateral C-7 transfer for hand function, multiple intercostal nerves for shoulder/triceps function, shoulder fusion, and spinal accessory nerve–to–musculocutaneous nerve transfer for elbow flexion. The video demonstrates distal contraction from electrical stimulation of the avulsed roots. Single neurorrhaphy of the contralateral C-7 transfer was performed along with a retrosternocleidomastoid approach.
The video can be found here: https://youtu.be/GMPfno8sK0U.
Michael Karsy, Daxa M. Patel and Robert J. Bollo
Magnetic resonance imaging–guided stereotactic laser ablation of intracranial targets, including brain tumors, has expanded dramatically over the past decade, but there have been few reports of complications, especially those occurring in a delayed fashion. Laser ablation of subependymal giant cell astrocytomas (SEGAs) is an attractive alternative to maintenance immunotherapy in some children with tuberous sclerosis complex (TSC); however, the effect of treatment on disease progression and the nature and frequency of potential complications remains largely unknown. The authors report the case of a 5-year-old boy with TSC who underwent stereotactic laser ablation of a SEGA at the right foramen of Monro on 2 separate occasions. After the second ablation, immediate posttreatment MRI revealed gadolinium extravasation from the tumor into the lateral ventricle. Nine months later, the patient presented with papilledema and delayed obstructive hydrocephalus secondary to intraventricular adhesions causing a trapped right lateral ventricle. This was successfully treated with endoscopic septostomy. The authors discuss the potential cause and clinical management of a delayed complication not previously reported after a relatively novel surgical therapy.
Al-Wala Awad, Craig Kilburg, Michael Karsy, William T. Couldwell and Philipp Taussky
The Pipeline embolization device (PED) is a self-expanding mesh stent that diverts blood flow away from an aneurysm; it has been successfully used to treat aneurysms of the proximal internal carotid artery (ICA). PEDs have a remarkable ability to alter regional blood flow along the tortuous segments of the ICA and were incidentally found to alter the angle of the anterior genu after treatment. The authors quantified these changes and explored their implications as they relate to treatment effect.
The authors retrospectively reviewed cases of aneurysms treated with a PED between the ophthalmic and posterior communicating arteries from 2012 through 2015. The angles of the anterior genu were measured on the lateral projections of cerebral angiograms obtained before and after treatment with a PED. The angles of the anterior genu of patients without aneurysms were used as normal controls.
Thirty-eight patients were identified who had been treated with a PED; 34 (89.5%) had complete obliteration and 4 (10.5%) had persistence of their aneurysm at last follow-up (mean 11.3 months). After treatment, 32 patients had an increase, 3 had a decrease, and 3 had no change in the angle of the anterior genu. The average measured angle of the anterior genu was 36.7° before treatment and 44.3° after treatment (p < 0.0001). The average angle of the anterior genu of control patients was 43.32° (vs 36.7° for the preoperative angle in the patients with aneurysms, p < 0.057). The average change in the angle of patients with postoperative Raymond scores of 1 was 9.10°, as compared with 1.25° in patients with postoperative Raymond scores > 1 (p < 0.001).
Treatment with a PED significantly changes the angle of the anterior genu. An average change of 9.1° was associated with complete obliteration of treated aneurysms. These findings have important implications for the treatment and management of cerebral aneurysm.
Michael Karsy, Philipp Taussky and Ramesh Grandhi
Spencer Twitchell, Michael Karsy, Jared Reese, Jian Guan, William T. Couldwell, Andrew Dailey and Erica F. Bisson
Efforts to examine the value of care—combining both costs and quality—are gaining importance in the current health care climate. This thrust is particularly evident in treating common spinal disease where both incidences and costs are generally high and practice patterns are variable. It is often challenging to obtain direct surgical costs for these analyses, which hinders the understanding of cost drivers and cost variation. Using a novel tool, the authors sought to understand the costs of posterior lumbar arthrodesis with interbody devices.
The Value Driven Outcomes (VDO) database at the University of Utah was used to evaluate the care of patients who underwent open or minimally invasive surgery (MIS), 1- and 2-level lumbar spine fusion (Current Procedural Terminology code 22263). Patients treated from January 2012 through June 2017 were included.
A total of 276 patients (mean age 58.9 ± 12.4 years) were identified; 46.7% of patients were men. Most patients (82.2%) underwent 1-level fusion. Thirteen patients (4.7%) had major complications and 11 (4.1%) had minor complications. MIS (β = 0.16, p = 0.002), length of stay (β = 0.47, p = 0.0001), and number of operated levels (β = 0.37, p = 0.0001) predicted costs in a multivariable analysis. Supplies and implants (55%) and facility cost (36%) accounted for most of the expenditure. Other costs included pharmacy (7%), laboratory (1%), and imaging (1%).
These results provide direct cost accounting for lumbar fusion procedures using the VDO database. Efforts to improve the value of lumbar surgery should focus on high cost areas, i.e., facility and supplies/implant.
Michael Karsy, Jian Guan, Walavan Sivakumar, Jayson A. Neil, Meic H. Schmidt and Mark A. Mahan
Genetic alterations in the cells of intradural spinal tumors can have a significant impact on the treatment options, counseling, and prognosis for patients. Although surgery is the primary therapy for most intradural tumors, radiochemothera-peutic modalities and targeted interventions play an ever-evolving role in treating aggressive cancers and in addressing cancer recurrence in long-term survivors. Recent studies have helped delineate specific genetic and molecular differences between intradural spinal tumors and their intracranial counterparts and have also identified significant variation in therapeutic effects on these tumors. This review discusses the genetic and molecular alterations in the most common intradural spinal tumors in both adult and pediatrie patients, including nerve sheath tumors (that is, neurofibroma and schwannoma), meningioma, ependymoma, astrocytoma (that is, low-grade glioma, anaplastic astrocytoma, and glioblastoma), hemangioblastoma, and medulloblastoma. It also examines the genetics of metastatic tumors to the spinal cord, arising either from the CNS or from systemic sources. Importantly, the impact of this knowledge on therapeutic options and its application to clinical practice are discussed.