Drug addiction represents a significant public health concern that has high rates of relapse despite optimal medical therapy and rehabilitation support. New therapies are needed, and deep brain stimulation (DBS) may be an effective treatment. The past 15 years have seen numerous animal DBS studies for addiction to various drugs of abuse, with most reporting decreases in drug-seeking behavior with stimulation. The most common target for stimulation has been the nucleus accumbens, a key structure in the mesolimbic reward pathway. In addiction, the mesolimbic reward pathway undergoes a series of neuroplastic changes. Chief among them is a relative hypofunctioning of the prefrontal cortex, which is thought to lead to the diminished impulse control that is characteristic of drug addiction. The prefrontal cortex, as well as other targets involved in drug addiction such as the lateral habenula, hypothalamus, insula, and subthalamic nucleus have also been stimulated in animals, with encouraging results. Although animal studies have largely shown promising results, current DBS studies for drug addiction primarily use stimulation during active drug use. More data are needed on the effect of DBS during withdrawal in preventing future relapse. The published human experience for DBS for drug addiction is currently limited to several promising case series or case reports that are not controlled. Further animal and human work is needed to determine what role DBS can play in the treatment of drug addiction.
Tony R. Wang, Shayan Moosa, Robert F. Dallapiazza, W. Jeffrey Elias and Wendy J. Lynch
Kenneth C. Liu, Robert M. Starke, Christopher R. Durst, Tony R. Wang, Dale Ding, R. Webster Crowley and Steven A. Newman
Idiopathic intracranial hypertension (IIH) may cause blindness due to elevated intracranial pressure (ICP). Venous sinus stenosis has been identified in select patients, leading to stenting as a potential treatment, but its effects on global ICP have not been completely defined. The purpose of this pilot study was to assess the effects of venous sinus stenting on ICP in a small group of patients with IIH.
Ten patients for whom medical therapy had failed were prospectively followed. Ophthalmological examinations were assessed, and patients with venous sinus stenosis on MR angiography proceeded to catheter angiography, venography with assessment of pressure gradient, and ICP monitoring. Patients with elevated ICP measurements and an elevated pressure gradient across the stenosis were treated with stent placement.
All patients had elevated venous pressure (mean 39.5 ± 14.9 mm Hg), an elevated gradient across the venous sinus stenosis (30.0 ± 13.2 mm Hg), and elevated ICP (42.2 ± 15.9 mm Hg). Following stent placement, all patients had resolution of the stenosis and gradient (1 ± 1 mm Hg). The ICP values showed an immediate decrease (to a mean of 17.0 ± 8.3 mm Hg), and further decreased overnight (to a mean of 8 ± 4.2 mm Hg). All patients had subjective and objective improvement, and all but one improved during follow-up (median 23.4 months; range 15.7–31.6 months). Two patients developed stent-adjacent stenosis; retreatment abolished the stenosis and gradient in both cases. Patients presenting with papilledema had resolution on follow-up funduscopic imaging and optical coherence tomography (OCT) and improvement on visual field testing. Patients presenting with optic atrophy had optic nerve thinning on follow-up OCT, but improved visual fields.
For selected patients with IIH and venous sinus stenosis with an elevated pressure gradient and elevated ICP, venous sinus stenting results in resolution of the venous pressure gradient, reduction in ICP, and functional, neurological, and ophthalmological improvement. As patients are at risk for stent-adjacent stenosis, further follow-up is necessary to determine long-term outcomes and gain an understanding of venous sinus stenosis as a primary or secondary pathological process behind elevated ICP.
Adeel Ilyas, Ching-Jen Chen, Dale Ding, Andrew Romeo, Thomas J. Buell, Tony R. Wang, M. Yashar S. Kalani and Min S. Park
Stroke is one of the leading causes of death worldwide and a significant source of long-term morbidity. Unfortunately, a substantial number of stroke patients either are ineligible or do not significantly benefit from contemporary medical and interventional therapies. To address this void, investigators recently made technological advances to render transcranial MR-guided, high-intensity focused ultrasound (MRg-HIFU) sonolysis a potential therapeutic option for both acute ischemic stroke (AIS)—as an alternative for patients with emergent large-vessel occlusion (ELVO) who are ineligible for endovascular mechanical thrombectomy (EMT) or as salvage therapy for patients in whom EMT fails—and intracerebral hemorrhage (ICH)—as a neoadjuvant means of clot lysis prior to surgical evacuation. Herein, the authors review the technological principles behind MRg-HIFU sonolysis, its results in in vitro and in vivo stroke models, and its potential clinical applications. As a noninvasive transcranial technique that affords rapid clot lysis, MRg-HIFU thrombolysis may develop into a therapeutic option for patients with AIS or ICH. However, additional studies of transcranial MRg-HIFU are necessary to ascertain the merit of this treatment approach for thrombolysis in both AIS and ICH, as well as its technical limitations and risks.
James H. Nguyen, Thomas J. Buell, Tony R. Wang, Jeffrey P. Mullin, Marcus D. Mazur, Juanita Garces, Davis G. Taylor, Chun-Po Yen, Christopher I. Shaffrey and Justin S. Smith
Recent literature describing complications associated with spinopelvic fixation with iliac screws in adult patients has been limited but has suggested high complication rates. The authors’ objective was to report their experience with iliac screw fixation in a large series of patients with a 2-year minimum follow-up.
Of 327 adult patients undergoing spinopelvic fixation with iliac screws at the authors’ institution between 2010 and 2015, 260 met the study inclusion criteria (age ≥ 18 years, first-time iliac screw placement, and 2-year minimum follow-up). Patients with active spinal infection were excluded. All iliac screws were placed via a posterior midline approach using fluoroscopic guidance. Iliac screw heads were deeply recessed into the posterior superior iliac spine. Clinical and radiographic data were obtained and analyzed.
Twenty patients (7.7%) had iliac screw–related complication, which included fracture (12, 4.6%) and/or screw loosening (9, 3.5%). No patients had iliac screw head prominence that required revision surgery or resulted in pain, wound dehiscence, or poor cosmesis. Eleven patients (4.2%) had rod or connector fracture below S1. Overall, 23 patients (8.8%) had L5–S1 pseudarthrosis. Four patients (1.5%) had fracture of the S1 screw. Seven patients (2.7%) had wound dehiscence (unrelated to the iliac screw head) or infection. The rate of reoperation (excluding proximal junctional kyphosis) was 17.7%. On univariate analysis, an iliac screw–related complication rate was significantly associated with revision fusion (70.0% vs 41.2%, p = 0.013), a greater number of instrumented vertebrae (mean 12.6 vs 10.3, p = 0.014), and greater postoperative pelvic tilt (mean 27.7° vs 23.2°, p = 0.04). Lumbosacral junction–related complications were associated with a greater mean number of instrumented vertebrae (12.6 vs 10.3, p = 0.014). Reoperation was associated with a younger mean age at surgery (61.8 vs 65.8 years, p = 0.014), a greater mean number of instrumented vertebrae (12.2 vs 10.2, p = 0.001), and longer clinical and radiological mean follow-up duration (55.8 vs 44.5 months, p < 0.001; 55.8 vs 44.6 months, p < 0.001, respectively). On multivariate analysis, reoperation was associated with longer clinical follow-up (p < 0.001).
Previous studies on iliac screw fixation have reported very high rates of complications and reoperation (as high as 53.6%). In this large, single-center series of adult patients, iliac screws were an effective method of spinopelvic fixation that had high rates of lumbosacral fusion and far lower complication rates than previously reported. Collectively, these findings argue that iliac screw fixation should remain a favored technique for spinopelvic fixation.
Davis G. Taylor, Thomas J. Buell, Tony R. Wang, Matthew J. Shepard, Dominic Maggio, Ching-Jen Chen, Min S. Park and Mark E. Shaffrey
Tony R. Wang, Aaron E. Bond, Robert F. Dallapiazza, Aaron Blanke, David Tilden, Thomas E. Huerta, Shayan Moosa, Francesco U. Prada and W. Jeffrey Elias
Although the use of focused ultrasound (FUS) in neurosurgery dates to the 1950s, its clinical utility was limited by the need for a craniotomy to create an acoustic window. Recent technological advances have enabled efficient transcranial delivery of US. Moreover, US is now coupled with MRI to ensure precise energy delivery and monitoring. Thus, MRI-guided transcranial FUS lesioning is now being investigated for myriad neurological and psychiatric disorders. Among the first transcranial FUS treatments is thalamotomy for the treatment of various tremors. The authors provide a technical overview of FUS thalamotomy for tremor as well as important lessons learned during their experience with this emerging technology.
Tony Wang, David Yu-Te Chou, Jamie Y. Ding, Vance Fredrickson, Changya Peng, Steven Schafer, Murali Guthikonda, Christian Kreipke, José A. Rafols and Yuchuan Ding
Previous studies have demonstrated that traumatic brain injury (TBI) causes brain edema by allowing excessive water passage through aquaporin (AQP) proteins. To establish the potential neuroprotective properties of ethanol as a post-TBI therapy, in the present study the authors determined the effect of ethanol on brain edema, AQP expression, and functional outcomes in a post-TBI setting.
Adult male Sprague-Dawley rats weighing between 425 and 475 g received a closed head TBI in which Maramarou's impact-acceleration method was used. Animals were given a subsequent intraperitoneal injection of 0.5 g/kg or 1.5 g/kg ethanol at 60 minutes post-TBI and were killed 24 hours after TBI. Brains were subsequently examined for edema along with AQP mRNA and protein expression. Additional animals treated with either 0.5 g/kg or 1.5 g/kg ethanol at 60 minutes post-TBI were designated for cognitive and motor testing for 3 weeks.
Ethanol administration post-TBI led to significantly (p < 0.05) lower levels of brain edema as measured by brain water content. This downregulation in brain edema was associated with significantly (p < 0.05) reduced levels of AQP mRNA and protein expression as compared with TBI without treatment. These findings concur with cognitive studies in which ethanol-treated animals exhibited significantly (p < 0.05) faster radial maze completion times. Motor behavioral testing additionally demonstrated significant (p < 0.05) beneficial effects of ethanol, with treated animals displaying improved motor coordination when compared with untreated animals.
The present findings suggest that acute ethanol administration after a TBI decreases AQP expression, which may lead to reduced cerebral edema. Ethanol-treated animals additionally showed improved cognitive and motor outcomes compared with untreated animals.
Randy S. D'Amico, Matei A. Banu, Petros Petridis, Alexandra S. Bercow, Hani Malone, Moshe Praver, Tony J. C. Wang, Steven R. Isaacson and Michael B. Sisti
Advanced microsurgical techniques contribute to reduced morbidity and improved surgical management of meningiomas arising within the cerebellopontine angle (CPA). However, the goal of surgery has evolved to preserve the quality of the patient's life, even if it means leaving residual tumor. Concurrently, Gamma Knife radiosurgery (GKRS) has become an acceptable and effective treatment modality for newly diagnosed, recurrent, or progressive meningiomas of the CPA. The authors review their institutional experience with CPA meningiomas treated with GKRS, surgery, or a combination of surgery and GKRS. They specifically focus on rates of facial nerve preservation and characterize specific anatomical features of tumor location with respect to the internal auditory canal (IAC).
Medical records of 76 patients with radiographic evidence or a postoperative diagnosis of CPA meningioma, treated by a single surgeon between 1992 and 2016, were retrospectively reviewed. Patients with CPA meningiomas smaller than 2.5 cm in greatest dimension were treated with GKRS, while patients with tumors 2.5 cm or larger underwent facial nerve–sparing microsurgical resection where appropriate. Various patient, clinical, and tumor data were gathered. Anatomical features of the tumor origin as seen on preoperative imaging confirmed by intraoperative investigation were evaluated for prognostic significance. Facial nerve preservation rates were evaluated.
According to our treatment paradigm, 51 (67.1%) patients underwent microsurgical resection and 25 (32.9%) patients underwent GKRS. Gross-total resection (GTR) was achieved in 34 (66.7%) patients, and subtotal resection (STR) in 17 (33.3%) patients. Tumors recurred in 12 (23.5%) patients initially treated surgically, requiring additional surgery and/or GKRS. Facial nerve function was unchanged or improved in 68 (89.5%) patients. Worsening facial nerve function occurred in 8 (10.5%) patients, all of whom had undergone microsurgical resection. Upfront treatment with GKRS for CPA meningiomas smaller than 2.5 cm was associated with preservation of facial nerve function in all patients over a median follow-up of 46 months, regardless of IAC invasion and tumor origin. Anatomical origin was associated with extent of resection but did not correlate with postoperative facial nerve function. Tumor size, extent of resection, and the presence of an arachnoid plane separating the tumor and the contents of the IAC were associated with postoperative facial nerve outcomes.
CPA meningiomas remain challenging lesions to treat, given their proximity to critical neurovascular structures. GKRS is a safe and effective option for managing CPA meningiomas smaller than 2.5 cm without associated mass effect or acute neurological symptoms. Maximal safe resection with preservation of neurological function can be performed for tumors 2.5 cm or larger without significant risk of facial nerve dysfunction, and, when combined with GKRS for recurrence and/or progression, provides excellent disease control. Anatomical features of the tumor origin offer critical insights for optimizing facial nerve preservation in this cohort.
Randy S. D'Amico, George Zanazzi, Gunnar Hargus, Timothy Dyster, Shirley Chan, Angela Lignelli-Dipple, Tony J. C. Wang, Phyllis L. Faust and Guy M. McKhann II
Tufted angioma (TA) is a rare, slow-growing, vascular lesion that commonly presents as a solitary macule, papule, or nodule arising in the soft tissues of the torso, extremities, and head and neck in children and young adults. Adult-onset cases have been infrequently reported. While typically benign, TAs may be locally aggressive. Complete physical examination and hematological workup are recommended in patients with TA to exclude the presence of Kasabach-Merritt phenomenon (KMP). The authors describe the case of a 69-year-old man with a contrast-enhancing frontal lobe lesion, with surrounding vasogenic edema, which was treated by gross-total resection. Characteristic histological features of a TA were demonstrated, with multiple cannonball-like tufts of densely packed capillaries emanating from intraparenchymal vessels in cerebral cortex and adjacent white matter. Tumor recurrence was detected after 4 months and treated with adjuvant Gamma Knife radiosurgery. To the extent of the authors' knowledge, this case illustrates the first report of TA presenting in an adult as an intracranial intraaxial tumor without associated KMP. The fairly rapid regrowth of this tumor, requiring adjuvant treatment after resection, is consistent with a potential for locally aggressive growth in a TA occurring in the brain.