Benchmarking cytology support for ROSE during endoscopic and bronchoscopic procedures.

INTRODUCTION: There has been an increase in endoscopic and bronchoscopic biopsies as minimally invasive methods to obtain specimens from gastrointestinal (GI) or pancreatobiliary lesions and thoracic or mediastinal lesions, respectively. As hospitals undertake more of these procedures, it is important to consider the staffing implications that this has on cytopathology laboratories with respect to support for rapid on-site evaluation (ROSE). MATERIALS AND METHODS: Volume and time data from endoscopic ultrasound and bronchoscopic procedures (including endobronchial ultrasound-guided transbronchial needle aspirations and small biopsies with touch preparation) in the GI suite, bronchoscopy suite, or operating room were reviewed for 2 months at 2 different medical centers with ROSE services provided by cytologists or fellows physically present at the procedure and cytopathologists located remotely using telecytology. Statistical analysis was performed to investigate significant trends based on the location of the biopsies and other factors. RESULTS: A total of 16 proceduralists performed 159 procedures and submitted 276 different specimens during 16 total weeks at 2 institutions. The total ROSE time for the on-site personnel to cover these procedures was 109.3 hours (bronchoscopy, 62.3 hours [57%]; GI, 29.8 hours [27%]; OR, 17.2 hours [16%]), which represents an average of 0.69 hour (41.4 minutes) per procedure or 0.40 hour (24.0 minutes) per part, with the shortest procedure times per sample recorded during bronchoscopy. When stratified by practice volume for individual proceduralists, the average time per specimen sample submitted was shorter for proceduralists with high volume practices and was most pronounced during bronchoscopy procedures. CONCLUSIONS: Endoscopic and bronchoscopic procedures account for an increasing amount of the ROSE time for the cytology team. On average, each ROSE procedure takes 0.69 hour (41.4 minutes) or approximately 0.40 hour (24.0 minutes) per specimen, with shorter time requirements for specimens obtained in bronchoscopy procedures and for operators with high volume practices for endobronchial ultrasound-guided transbronchial needle aspirations. This provides important benchmarking data to calculate staffing needs for cytology to provide ROSE support for different proceduralists.

Practical applications of three-dimensional printing for process improvement in the cytopathology laboratory.

With the increased availability of three-dimensional (3D) printers, innovative teaching and training materials have been created in medical fields. For pathology, the use of 3D printing has been largely limited to anatomic representations of disease processes or the development of supplies during the coronavirus disease 2019 pandemic. Herein, an institution's 3D printing laboratory and staff with expertise in additive manufacturing illustrate how this can address design issues in cytopathology specimen collection and processing. The authors' institutional 3D printing laboratory, along with students and trainees, used computer-aided design and 3D printers to iterate on design, create prototypes, and generate final usable materials using additive manufacturing. The program Microsoft Forms was used to solicit qualitative and quantitative feedback. The 3D-printed models were created to assist with cytopreparation, rapid on-site evaluation, and storage of materials in the preanalytical phase of processing. These parts provided better organization of materials for cytology specimen collection and staining, in addition to optimizing storage of specimens with multiple sized containers to optimize patient safety. The apparatus also allowed liquids to be stabilized in transport and removed faster at the time of rapid on-site evaluation. Rectangular boxes were also created to optimally organize all components of a specimen in cytopreparation to simplify and expedite the processes of accessioning and processing, which can minimize errors. These practical applications of 3D printing in the cytopathology laboratory demonstrate the utility of the design and printing process on improving aspects of the workflow in cytopathology laboratories to maximize efficiency, organization, and patient safety.

Arachnoid webs causing rostral syrinx due to ball-valve effect: an illustrative report of two cases.

An arachnoid web is a pathological formation of the arachnoid membrane. It is a rare phenomenon but is known to lead to syrinx formation in the spinal cord along with pain and neurological deficits. On imaging, the 'scalpel sign' is pathognomonic for an arachnoid web. The etiology of syrinx formation from an arachnoid web is currently unknown. This report documents the only two cases of arachnoid webs with an extensive syrinx in which a likely pathophysiologic mechanism is identified. Both cases presented with motor deficits. The patients had no history of trauma or infection. After extensive workup in both patients and observation of the scalpel sign an arachnoid web was suspected. In both cases, the patients were treated surgically after an arachnoid web was suspected. Intra-operative ultrasound visualized in both cases demonstrates a fenestration in the web that allowed passage of cerebrospinal fluid in a rostral-caudal direction due to a ball-valve effect.

Pre-operative stereotactic radiosurgery for cerebral metastatic disease: A retrospective dose-volume study.

BACKGROUND AND PURPOSE: Stereotactic radiosurgery (SRS) after maximal safe resection is an accepted treatment strategy for patients with cerebral metastatic disease. Despite its high conformality profile, the incidence of radionecrosis (RN) remains high. SRS delivered pre-operatively could be associated with a reduced incidence of RN. We sought to evaluate whether neoadjuvant SRS could reduce radiotherapy doses in a cohort of patients treated with post-operative SRS. METHODS: A cohort of 47 brain metastases (BM) treated at 2 academic institutions was retrospectively analyzed. Subjects underwent surgical extirpation of BMs and subsequent SRS to surgical bed. Post-operative volumetric and dosimetric data was collected from records or recreations of delivered plans; pre-operative data were derived from hypothetical radiotherapy courses and compared using Wilcoxon signed-rank tests. RESULTS: Higher planned tumor volume post-operatively (median[IQR] 12.28 [6.54, 18.69]cc vs 10.20 [4.53, 21.70]cc respectively, p = 0.4150) was observed. The median prescribed radiotherapy dose (DRx) was 16 Gy pre-operatively and 24 Gy post-operatively (p < 0.0001). Further investigations revealed improved pre-operative conformity index (1.23[1.20, 1.29] vs 1.29[1.23, 1.39], p = 0.0098) and gradient index (2.72[2.59, 2.98] vs 2.94[2.69, 3.47], p = 0.0004). A significant difference was found in normal brain tissue exposed to 10 Gy (12.97[6.78, 25.54]cc vs 32.13[19.42, 48.40]cc, p < 0.0001), 12 Gy (9.31[4.56, 17.43]cc vs 23.80[14.74, 36.56]cc, p < 0.0001), and 14 Gy (5.62[3.23, 11.61]cc vs 17.47[9.00, 28.31]cc, p < 0.0001), favoring pre-operative SRS. CONCLUSIONS: Neoadjuvant SRS is associated reduced DRx, better conformality profile and decreased radiation to normal tissue. These findings could support the use of neoadjuvant SRS for the treatment of BMs.

Glioblastoma Adjacent to Radiosurgically Treated Arteriovenous Malformation: A Case Report and Review of the Literature.

Stereotactic radiosurgery (SRS) is a noninvasive therapy for patients suffering from both benign and malignant intracranial pathologies. While SRS allows for increased precision and efficacy, significant risks have been reported, such as radiation necrosis. Although traditional radiation therapies are associated with a well-understood risk of causing tumors or inducing malignancy, the risks associated with SRS are not well understood. Here, we present the case of a patient who underwent SRS post-Onyx embolization of a Spetzler-Martin grade 4 left parasagittal arteriovenous malformation. Four years later, the patient presented with a high-grade glioma adjacent to where the SRS was targeted. SRS has fundamentally altered the way we treat intracranial pathologies. While the risks for SRS-induced glioma appear to be extremely low, this case illustrates that they ought to be considered. Here, we discuss the details of our case and explore the currently available literature. Knowing these potential risks will further aid physicians and patients balance the associated benefits and risks.

Successful management of an intraluminal superior sagittal sinus meningioma causing elevated intracranial pressure using gamma knife radiosurgery in subacute setting: A case report.

BACKGROUND: Gamma Knife stereotactic radiosurgery (GKRS) facilitates precisely focused radiation to an intracranial target while minimizing substantial off-target radiation in the surrounding normal tissue. Meningiomas attached to or invading the superior sagittal sinus may result in sinus occlusion and are often impossible to completely resect safely. The authors describe successful management of a patient with a meningioma located completely inside the posterior aspect of the superior sagittal sinus. CASE DESCRIPTION: A 46-year-old woman presented to the emergency department with progressive generalized headaches accompanied by worsening vision. The patient underwent a diagnostic brain magnetic resonance imaging which showed a solitary a 7 × 6 × 10 mm homogeneously contrast-enhancing lesion within the lumen of the posterior aspect of superior sagittal sinus without ventricular enlargement or peritumoral edema. The lesion was thought to be a meningioma radiographically. To evaluate the suspected increased intracranial pressure, a lumbar puncture was subsequently performed and demonstrated an opening pressure of 30 cm H2O. After drainage of 40 cc of CSF, the spinal closing pressure was 9 cm H2O. After failure of conservative management with acetazolamide, and determination of surgical inoperability due to the critical intraluminal location of the mass lesion, the patient underwent Gamma Knife radiosurgery. The 0.36 cc tumor was treated as an outpatient in the Perfexion® model Gamma Knife with a highly conformal and selective plan that enclosed the 3D geometry of the tumor with a minimal margin tumor dose of 14 gy at the 50% isodose. Three months after GKRS, the patient reported continued reduction in the frequency and severity of both her headaches and her visual disturbance. Ophthalmological consultation noted progressive resolution of her optic disc edema confirmed by formal optical coherence tomography. The patient is now 3 years out from GKRS with complete resolution of headache symptoms along with persistent reduction in tumor size (3 × 1 × 4 mm) on serial period imaging and resolution of papilledema. CONCLUSION: Tumors located in such critical anatomic regions, as in our patient, should be considered for primary GKRS when the risks of biopsy or removal are too high. GKRS was able to provide great radiographic and clinical result in an intricately located meningioma.

Three decades of progress from surgery to medical therapy for isolated neuroaxis BRAF V600E-positive Langerhans cell histiocytosis management: illustrative case.

BACKGROUND: "Langerhans cell histiocytosis" (LCH) is a term that encompasses single-system or multisystem disorders traditionally characterized by a proliferation of clonal CD1a+/CD207+ myeloid-derived histiocytes. In most cases of LCH, mitogen-activated protein kinase (MAPK) pathway somatic mutations lead to near universal upregulation of phosphorylated extracellular signal-regulated kinase expression. The clinical manifestations of LCH are numerous, but bone involvement is common. Intracranial lesions, especially as isolated manifestations, are rare. OBSERVATIONS: The authors presented the case of a long-term survivor of exclusive intracranial LCH that manifested with isolated craniofacial bone and intraparenchymal central nervous system recurrences, which were managed with 3 decades of multimodal therapy. The patient was initially diagnosed with LCH at age 2 years, and the authors documented the manifestations of disease and treatment for 36 years. Most of the patient's treatment course occurred before the discovery of BRAF V600E. Treatments initially consisted of chemotherapy, radiosurgery, and open resections for granulomatous LCH lesions. Into young adulthood, the patient had a minimal disease burden but still required additional radiosurgical procedures and open resections. LESSONS: Surgical treatments alleviated the patient's immediate symptoms and allowed for tumor burden control. However, surgical interventions did not cure the underlying, aggressive disease. In the current era, access to systemic MAPK inhibitor therapy for histiocytic lesions may offer improved outcomes.

Pneumomyelia Secondary to Interlaminar Cervical Epidural Injection Causing Acute Cord Injury with Transient Quadriparesis.

BACKGROUND: Cervical radiculopathy and cervicalgia are commonly managed with spinal epidural steroid injections in the outpatient setting. Although cervical epidural injections are routinely performed, there is potential for significant complications if proper technique and safety measures are not followed. Spinal cord infarction and stroke following transforaminal injection have been described in the literature, whereas interlaminar injections have been associated with both epidural hematomas and direct cord injury. CASE DESCRIPTION: Here we describe a case of pneumomyelia after cervical interlaminar epidural steroid injection resulting in acute quadriparesis. The patient's symptoms were caused by an inadvertent puncture of the cervical cord and injection of air present in the needle or syringe via an interlaminar approach. The initial computed tomography imaging showed a slit-like lesion at C7-T2 with density consistent with air that migrated rostrally on a follow-up scan. CONCLUSIONS: Epidural steroid injections are often the treatment of choice in management of neck pain and cervical radiculopathy. Devastating complications can ensue if proper safety measures and technique are not used during the procedure regardless of the approach used.

Coronavirus Disease 2019 (COVID-19) and Neurosurgery Residency Action Plan: An Institutional Experience from the United States.

BACKGROUND: The current pandemic crisis, caused by a novel human coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), has forced a dramatic change in our society. A key portion of the medical work force on the frontline is composed of resident physicians. Thus, it becomes imperative to create an adequate and effective action plan to restructure this valuable human resource amid the SARS-CoV2 pandemic. We sought to describe a comprehensive approach taken by a Neurosurgery Department in quaternary care academic institution in the United States of America amid the SARS-CoV2 pandemic focused in resident training and support. OBJECTIVE: To describe a comprehensive approach taken by a Neurosurgery Department in quaternary care academic institution in the United States of America amid the SARS-CoV2 pandemic focused on resident training and support. RESULTS: A restructuring of the Neurosurgery Department at our academic institution was performed focused on decreasing their risk of infection/exposure and transmission to others, while minimizing negative consequences in the training experience. An online academic platform was built for resident education, guidance, and support, as well as continue channel for pandemic update by the department leadership. CONCLUSIONS: The SARS-CoV2 pandemic constitutes a global health emergency full of uncertainty. Treatment, scope, duration, and economic burden forced a major restructuring of our medical practice. In this regard, academic institutions must direct efforts to diminish further negative impact in the training and education of the upcoming generation of physicians, including those currently in medical school. Perhaps the only silver lining in this terrible disruption will be greater appreciation of the role of current health care providers and educators, whose contributions to our society are often neglected or unrecognized.

Near-resolution of persistent idiopathic facial pain with low-dose lumbar intrathecal ziconotide: a case report.

PURPOSE: Persistent idiopathic facial pain (PIFP) is a poorly defined and debilitating chronic pain state with a challenging and often inadequate treatment course. This is the first case report identifying the novel use of low-dose lumbar intrathecal ziconotide to successfully treat PIFP with nearly complete resolution of pain and minimal to no side effects. METHODS: The patient was a 37 year-old female whose PIFP was refractory to multimodal medication management and multiple neurovascular surgical interventions. A single-shot lumbar intrathecal trial of ziconotide (2.5 mL, equivalent 2.5 µg) was injected when she was at her baseline pain level - VAS 7/10. She received complete resolution of her pain for about 9 hours, concordant with ziconotide's half-life. She was subsequently implanted with a lumbar intrathecal delivery system. RESULTS: The patient experienced complete resolution of her facial pain with a single-shot intrathecal trial of ziconotide. The intrathecal pump system has provided nearly complete (VAS 1/10) pain relief. Two flares of pain occurred 10 and 18 months after pump placement, which subsequently resolved after increasing the ziconotide dose by 0.5 µg/day on each occasion. The patient is currently maintained on a dose of 2.0 µg/day and is pain-free. CONCLUSION: This is the first case report describing the use of a single-shot lumbar intrathecal trial of ziconotide and subsequent placement of lumbar (as opposed to thoracic) intrathecal ziconotide pump for PIFP. A single-injection intrathecal trial is a low-risk, viable option for patients with this debilitating and frustrating pain condition. Successful trials and subsequent intrathecal pump placement with ziconotide may supplant multimodal medication management and/or invasive orofacial surgical intervention for PIFP.

Seizure control after radiosurgery for cerebral arteriovenous malformations: a 25-year experience.

OBJECTIVE: Seizures are the second-most common presenting symptom in patients with lobar arteriovenous malformations (AVMs). However, few studies have assessed the long-term effect of stereotactic radiosurgery (SRS) on seizure control. The authors of this study assess the outcome of SRS for these patients to identify prognostic factors associated with seizure control. METHODS: Patients with AVM who presented with a history of seizure and underwent SRS at the authors' institution between 1987 and 2012 were retrospectively assessed. The total cohort included 155 patients with a mean follow-up of 86 months (range 6-295 months). Primary outcomes assessed were seizure frequency, antiepileptic drug regimen, and seizure freedom for 6 months prior to last follow-up. RESULTS: Seizure-free status was achieved in 108 patients (70%), with an additional 23 patients (15%) reporting improved seizure frequency as compared to their pre-SRS status. The median time to seizure-free status was estimated to be 12 months (95% CI 0-27 months) as evaluated via Kaplan-Meier survival analysis. The mean seizure frequency prior to SRS was 14.2 (95% CI 5.4-23.1) episodes per year. Although not all patients tried, the proportion of patients successfully weaned off all antiepileptic drugs was 18% (28/155 patients). On multivariate logistic regression, focal impaired awareness seizure type (also known as complex partial seizures) and superficial venous drainage were significantly associated with a decreased odds ratio for seizure-free status at last follow-up (OR 0.37 [95% CI 0.15-0.92] for focal impaired awareness seizures; OR 0.36 [95% CI 0.16-0.81] for superficial venous drainage). The effects of superficial venous drainage on seizure outcome were nonsignificant when excluding patients with < 2 years of follow-up. AVM obliteration did not correlate with long-term seizure freedom (p = 0.202, chi-square test). CONCLUSIONS: This study suggests that SRS improves long-term seizure control and increases the likelihood of being medication free, independently of AVM obliteration. Patients with focal impaired awareness seizures were less likely to obtain long-term seizure relief.

Defining Long-Term Clinical Outcomes and Risks of Stereotactic Radiosurgery for Brainstem Cavernous Malformations.

BACKGROUND: We evaluated clinical outcomes in patients with symptomatic brainstem cavernous malformations (CMs) treated by stereotactic radiosurgery (SRS). METHODS: Between 1988 and 2016, Gamma Knife SRS was performed in 76 evaluable patients with solitary symptomatic brainstem CMs. Forty-nine (66%) were intrinsic (not reaching a pial or ependymal surface). Most patients (91%) had experienced 2 or more hemorrhages associated with new neurologic deficits. Fourteen patients (18%) underwent resection before radiosurgery. The median CM volume was 0.66 cm3 (range, 0.05-6.8), and the median margin dose was 15.0 Gy. RESULTS: After SRS, 15 patients (20%) had an imaging confirmed new hemorrhage at a median follow-up of 48 months. The hemorrhage-free survival after SRS for brainstem CMs was 92% at 1 year, 87% at 3 years, and 85% at 5 years. The annual hemorrhage rate was 31% before and 4% after SRS. In univariate analysis, CM volume, previous surgical resection, and increased number of hemorrhages before SRS were significantly associated with a higher rate of hemorrhage after SRS. In multivariate analysis, only number of previous hemorrhages was significant (P < 0.0005; hazard ratio, 1.51, 95% confidence interval, 1.23-1.85). Symptomatic adverse radiation effects developed in 7 patients (9%). The rate of symptom deterioration related to hemorrhage or symptomatic adverse radiation effects was 10% at 1 year, 18% at 3 years, and 20% at 5 years. CONCLUSIONS: Patients with an increased rate of hemorrhage before SRS had an increased risk of repeat hemorrhage and symptom deterioration rate after SRS. Intrinsic CM location did not significantly affect rates of symptom deterioration or rebleeding.

Reconsidering an important subclass of high-risk dural arteriovenous fistulas for stereotactic radiosurgery.

OBJECTIVE: Aggressive dural arteriovenous fistulas (dAVFs) with cortical venous drainage (CVD) are known for their relatively high risk of recurrent neurological events or hemorrhage. However, recent natural history literature has indicated that nonaggressive dAVFs with CVD have a significantly lower prospective risk of hemorrhage. These nonaggressive dAVFs are typically diagnosed because of symptomatic headache, pulsatile tinnitus, or ocular symptoms, as in low-risk dAVFs. Therefore, the viability of stereotactic radiosurgery (SRS) as a treatment for this lesion subclass should be investigated. METHODS: The authors evaluated their institutional experience with SRS for dAVFs with CVD for the period from 1991 to 2016, assessing angiographic outcomes and posttreatment hemorrhage rates. They subsequently pooled their results with those published in the literature and stratified the results based on the mode of clinical presentation. RESULTS: In an institutional cohort of 42 dAVFs with CVD treated using SRS, there were no complications or hemorrhages after treatment in 19 patients with nonaggressive dAVFs, but there was 1 radiation-induced complication and 1 hemorrhage among the 23 patients with aggressive dAVFs. In pooling these cases with 155 additional cases from the literature, the authors found that the hemorrhage rate after SRS was significantly lower among the patients with nonaggressive dAVFs (0% vs 6.8%, p = 0.003). Similarly, the number of radiation-related complications was 0/124 in nonaggressive dAVF cases versus 6/73 in aggressive dAVF cases (p = 0.001). The annual rate of hemorrhage after SRS for aggressive fistulas was 3.0% over 164.5 patient-years, whereas none of the nonaggressive fistulas bled after radiosurgery over 279.4 patient-years of follow-up despite the presence of CVD. CONCLUSIONS: Cortical venous drainage is thought to be a significant risk factor in all dAVFs. In the institutional experience described here, SRS proved to be a low-risk strategy associated with a very low risk of subsequent hemorrhage or radiation-related complications in nonaggressive dAVFs with CVD.

Stereotactic Radiosurgery in the Multimodality Management of Residual or Recurrent Glioblastoma Multiforme.

Management options for residual or recurrent glioblastoma multiforme (GBM) are limited despite advances in surgical, chemotherapeutic, and radiotherapeutic techniques. Stereotactic radiosurgery (SRS) is often beneficial in such cases providing improved survival of patients, but still remains underutilized as part of the multimodality management of malignant gliomas. During the last 20 years, 297 patients with histologically proven residual or recurrent GBM underwent Gamma Knife surgery in the University of Pittsburgh. Retrospective analysis of outcomes revealed median survival after initial diagnosis of 18 months, and 1- and 2-year survival rates of 72.5 and 29.5%, respectively. Median survival from the time of SRS was 9 months. The use of modified RPA (recursive partitioning analysis) classification demonstrated superior survival in our series in comparison with historical data. Important prognostic variables include tumor volume <14 cm3, marginal radiation dose of ≥15 Gy, and younger age of the patients (<60 years). Adverse radiation effects (ARE) were noted in 23% of cases and were mainly controlled with corticosteroids. Combining SRS with bevacizumab resulted in further improvement of the overall and progression-free survival and decreased incidence of ARE. Nevertheless, for future application of SRS in patients with GBM, evaluation of its efficacy in a well-designed prospective controlled clinical trials seems mandatory.

Radiosurgical Thalamotomy.

Tremor is a common movement disorder that can be disabling, and its initial treatment is in the form of medical therapies. Often patients are refractory and seek surgical intervention. Treatment options for these patients include surgical radiofrequency thalamotomy and deep brain stimulation. There are a subset of patients who, for various reasons, are not candidates for open surgical procedures, or who opt to avoid them. For these patients, radiosurgical thalamotomy is a safe and useful alternative. Herein, we provide a review of the use of radiosurgical thalamotomy for the treatment of medically refractory tremor by discussing its history, defining the technique and its indications, evaluating its efficacy, and exploring its complications and shortcomings.

Is staged bilateral thalamic radiosurgery an option for otherwise surgically ineligible patients with medically refractory bilateral tremor?

OBJECTIVE Unilateral Gamma Knife thalamotomy (GKT) is a well-established treatment for patients with medically refractory tremor who are not eligible for invasive procedures due to increased risk of compications. The purpose of this study was to evaluate whether staged bilateral GKT provides benefit with acceptable risk to patients suffering from disabling medically refractory bilateral tremor. METHODS Eleven patients underwent staged bilateral GKT during a 17-year period (1999-2016). Eight patients had essential tremor (ET), 2 had Parkinson's disease (PD)-related tremor, and 1 had multiple-sclerosis (MS)-related tremor. For the first GKT, a median maximum dose of 140 Gy was delivered to the posterior-inferior region of the nucleus ventralis intermedius (VIM) through a single isocenter with 4-mm collimators. Patients who benefitted from unilateral GKT were eligible for a contralateral GKT 1-2 years later (median 22 months). For the second GKT, a median maximum dose of 130 Gy was delivered to the opposite VIM nucleus to a single 4-mm isocenter. The Fahn-Tolosa-Marin (FTM) clinical tremor rating scale was used to score tremor, drawing, and drinking before and after each GKT. The FTM writing score was assessed only for the dominant hand before and after the first GKT. The Karnofsky Performance Status (KPS) was used to assess quality of life and activities of daily living before and after the first and second GKT. RESULTS The median time to last follow-up after the first GKT was 35 months (range 11-70 months). All patients had improvement in at least 1 FTM score after the first GKT. Three patients (27.3%) had tremor arrest and complete restoration of function (noted via FTM tremor, writing, drawing, and drinking scores equaling zero). No patient had tremor recurrence or diminished tremor relief after the first GKT. One patient experienced new temporary neurological deficit (contralateral lower-extremity hemiparesis) from the first GKT. The median time to last follow-up after the second GKT was 12 months (range 2-70 months). Nine patients had improvement in at least 1 FTM score after the second GKT. Two patients had tremor arrest and complete restoration of function. No patient experienced tremor recurrence or diminished tremor relief after the second GKT. No patient experienced new neurological or radiological adverse effect from the second GKT. Statistically significant improvements were noted in the KPS score following the first and second GKT. CONCLUSIONS Staged bilateral GKT provided effective relief for medically refractory, disabling, bilateral tremor without increased risk of neurological complications. It is an appropriate strategy for carefully selected patients with medically refractory bilateral tremor who are not eligible for deep brain stimulation.

Stereotactic radiosurgery for medically refractory multiple sclerosis-related tremor.

OBJECTIVE Multiple sclerosis (MS) is a neurodegenerative disease that can lead to severe intention tremor in some patients. In several case reports, conventional radiotherapy has been reported to possibly exacerbate MS. Radiosurgery dramatically limits normal tissue irradiation to potentially avoid such a problem. Gamma Knife thalamotomy (GKT) has been established as a minimally invasive technique that is effective in treating essential tremor and Parkinson's disease-related tremor. The goal in this study was to analyze the outcomes of GKT in patients suffering from medically refractory MS-related tremor. METHODS The authors retrospectively studied the outcomes of 15 patients (mean age 46.5 years) who had undergone GKT over a 15-year period (1998-2012). Fourteen patients underwent GKT at a median maximum dose of 140 Gy (range 130-150 Gy) using a single 4-mm isocenter. One patient underwent GKT at a dose of 140 Gy delivered via two 4-mm isocenters (3 mm apart). The posteroinferior region of the nucleus ventralis intermedius (VIM) was the target for all GKTs. The Fahn-Tolosa-Marin clinical tremor rating scale was used to evaluate tremor, handwriting, drawing, and drinking. The median time to the last follow-up was 39 months. RESULTS After GKT, 13 patients experienced tremor improvement on the side contralateral to surgery. Four patients noted tremor arrest at a median of 4.5 months post-GKT. Seven patients had excellent tremor improvement and 6 had good tremor improvement. Four patients noted excellent functional improvement, 8 noted good functional improvement, and 1 noted satisfactory functional improvement. Three patients experienced diminished tremor relief at a median of 18 months after radiosurgery. Two patients experienced temporary adverse radiation effects. Another patient developed a large thalamic cyst 60 months after GKT, which was successfully managed with Ommaya reservoir placement. CONCLUSIONS Gamma Knife thalamotomy was found to be a minimally invasive and beneficial procedure for medically refractory MS tremor.

The benefit of radiosurgery for ARUBA-eligible arteriovenous malformations: a practical analysis over an appropriate follow-up period.

OBJECTIVE The authors of this study found that, given the latency period required for arteriovenous malformation (AVM) obliteration after stereotactic radiosurgery (SRS), a study with limited follow-up cannot assess the benefit of SRS for unruptured AVMs. METHODS The authors reviewed their institutional experience with "ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations)-eligible" AVMs treated with SRS between 1987 and 2016, with the primary outcome defined as stroke (ischemic or hemorrhagic) or death (AVM related or AVM unrelated). Patients with at least 3 years of follow-up in addition to those who experienced stroke or died during the latency period were included. Secondary outcome measures included obliteration rates, patients with new seizure disorders, and those with new focal deficits without stroke. RESULTS Of 233 patients included in this study, 32 had a stroke or died after SRS over the mean 8.4-year follow-up (14%). Utilizing the 10% stroke or death rate at a mean 2.8-year follow-up for untreated AVMs in ARUBA, the rate in the authors' study is significantly lower than that anticipated at the 8.4-year follow-up for an untreated cohort (14% vs 30%, p = 0.0003). Notwithstanding obliteration, in this study, annualized rates of hemorrhage and stroke or death after 3 years following SRS were 0.4% and 0.8%, respectively. The overall obliteration rate was 72%; new seizure disorders, temporary new focal deficits without stroke, and permanent new focal deficits without stroke occurred in 2% of patients each. CONCLUSIONS After a sensible follow-up period exceeding the latency period, there is a lower rate of stroke/death for patients with treated, unruptured AVMs with SRS than for patients with untreated AVMs.

A proposed plan for personalized radiosurgery in patients with trigeminal neuralgia.

OBJECTIVE During the last 25 years, more than 100,000 patients worldwide with trigeminal neuralgia (TN) have undergone stereotactic radiosurgery (SRS) with a standard dose of radiation. However, the radiobiological effect of radiation is determined by the amount of energy delivered to the tissue (integral dose [ID] = mean dose × target volume) and is directly associated with the nerve volume. Although the trigeminal nerve volume varies among patients with TN, the clinical impact of this variation in delivered energy is unknown. The objective of this study was to evaluate the effect of delivered ID on the outcome of TN radiosurgery. METHODS The authors evaluated 155 patients with unilateral TN who had undergone SRS as their initial surgical management over a 13-year period. The authors measured the postganglionic ID within the SRS target and retrospectively stratified patients into 3 groups: low (< 1.4 mJ), medium (1.4-2.7 mJ), and high (> 2.7 mJ) ID. Clinical outcomes, which included pain status (scored using the Barrow Neurological Institute Pain Scale) and sensory dysfunction (scored using the Barrow Neurological Institute Numbness Scale), were evaluated at a median follow-up of 71 months. RESULTS Patients who were treated with a medium ID had superior pain relief either with or without medications (p = 0.006). In the medium ID group, the rates of complete pain relief without medications at 1, 3, and 6 years after SRS were 67%, 54%, and 33%, respectively, while the rates in the rest of the cohort were 55%, 36%, and 19%, respectively. Patients given a high ID had a higher rate of post-SRS trigeminal sensory deterioration (p < 0.0001). At 1, 3, and 6 years after SRS, the high ID group had an estimated rate for developing sensory dysfunction of 35%, 45%, and 50%, respectively, while the rates in patients receiving low and medium IDs were 3%, 4%, and 9%, respectively. The optimal clinical outcome (maximum pain relief and minimal trigeminal sensory dysfunction) was obtained in patients who had received a medium ID. CONCLUSIONS With current dose selection methods, nerve volume affects long-term clinical outcomes in patients with TN who have undergone SRS. This study suggests that the prescribed SRS dose should be customized for each TN patient based on the nerve volume.

Stereotactic Radiosurgery for Intractable Tremor-Dominant Parkinson Disease: A Retrospective Analysis.

OBJECTIVE: The purpose of this study was to retrospectively analyze the outcomes of stereotactic radiosurgery for patients suffering from medically refractory Parkinson disease (PD) tremor. METHODS: We retrospectively studied the outcomes of 33 patients who were treated with gamma knife thalamotomy (GKT) over a 19-year period. Twelve patients were ≥80 years. A median dose of 140 Gy (range, 130-150 Gy) was delivered to the nucleus ventralis intermedius through a single 4-mm isocenter. We used the Fahn-Tolosa-Marin clinical tremor rating scale to score tremor, handwriting, drawing, and ability to drink fluids. The median time to the last follow-up was 23 months (range, 9-144 months). RESULTS: After GKT, 31 patients (93.9%) experienced improvement in tremor. Twenty-three patients (70.0%) had complete or nearly complete tremor arrest. Nine patients (27.2%) noted tremor arrest and resolution of impairment in writing, drawing, and ability to drink fluids. One patient (3%) improved in bradykinesia, 3 patients (9%) improved in rigidity, and 3 patients (9%) decreased their dosage of dopa after GKT. Tremor relief was fully maintained in the last follow-up for 96.8% of responding patients. Two patients (6%) experienced temporary adverse radiation effects. CONCLUSIONS: GKT is a safe and effective treatment for medically refractory PD tremor, especially for the elderly or those not suitable for deep brain stimulation or thermal thalamotomy.