Neuroscience. Journal. Management of low-grade gliomas. New stroke guidelines extend the window for mechanical thrombectomy pg. 8. pg.

Transcription

1 Neuroscience P A L M E T T O H E A L T H Vol. 4 Issue 2 Spring 2018 Journal Management of low-grade gliomas pg. 4 New stroke guidelines extend the window for mechanical thrombectomy pg. 8

2 As physician co-leaders of Palmetto Health s neuroscience service, we share a vision to provide the most advanced neurology and neurological surgery treatments available to the residents of South Carolina. We are excited to share this latest edition of our neuroscience journal featuring articles about management of low-grade gliomas and the new stroke guidelines that resulted from the DEFUSE 3 trial and have extended the window for mechanical thrombectomy. Souvik Sen, MD, MS, MPH Chair of Neurology, Palmetto Health-USC Neurology Professor of Neurology, University of South Carolina School of Medicine Roham Moftakhar, MD Chief of Neurosurgery, Palmetto Health Richland Medical Director, Palmetto Health-USC Neurosurgery Associate Professor of Clinical Surgery, University of South Carolina School of Medicine 2

3 Palmetto Health s 4-BRAIN phone line for neurosurgical transfers Because seconds matter. Providers now can call BRAIN to transfer urgent and emergent neurosurgical and neurological patients easily and efficiently. Studies have shown that one of the challenges faced by emergency room providers and referring physicians is fast and efficient access to neurological and neurosurgical physicians in tertiary medical centers. Palmetto Health s 4-BRAIN line allows emergency room providers and referring physicians to speak directly with a neurosurgeon or neurologist without going through an operator or long waits on the phone. Neurological problems that the 4-BRAIN line may be used for include intracerebral hemorrhages, subarachnoid hemorrhage, aneurysms, vascular malformations and brain tumors. The 4-BRAIN line is answered 24 hours a day, seven days a week. Call BRAIN (27246) for emergent neurosurgical transfers. Call for brain and spine tumor referrals. Our sub-specialized service offers: Patients seen within two business days following referral Each case reviewed by our multidisciplinary brain and spine tumor board Cutting-edge technology Prompt development of individualized treatment plan

4 Management of low-grade gliomas by David C. Straus, MD, Palmetto Health-USC Neurosurgery Tumor classifications and epidemiology Gliomas are intrinsic brain tumors arising from the glial cell lines, including astrocytes, ependymal cells, and oligodendrocytes. The current World Health Organization (WHO) classification uses histology to classify tumors and determine grade. The tumors are grouped by the most commonly encountered cell type and graded by the presence or absence of necrosis, mitotic activity, nuclear atypia, and endothelial cell proliferation. Low-grade gliomas are classified as those with WHO grade I or II. While both WHO grades I and II are considered low grade, the natural history and, therefore, the management of each group of lesions varies greatly. Intracranial WHO grade I gliomas include pilocytic astrocytomas, subependymal giant cell astrocytomas, gangliogliomas and subependymomas. These lesions may be diffuse but usually are well defined with a benign clinical course. Patients with these lesions often are cured with a successful resection alone. We will focus primarily on the management of WHO grade II astrocytomas, pleomorphic xanthoastrocytomas, oligodendrogliomas and oligoastrocytomas as these tumors are common in adults and present the greatest clinical challenges. WHO grade II gliomas have an incidence of 1 to 2 per 100,000 people per year and are most likely to affect young adults. The vast majority of patients, up to 80 percent, present with seizures. Lesions may be either welldefined, involving two or fewer lobes with clear margins on FLAIR, or diffuse, with poorly defined FLAIR borders or involving more than two lobes. Indications for surgical intervention Biopsy When a patient is found to have a lesion consistent with a low-grade glioma, a decision must be made between surgical intervention and observation. In cases where a tissue diagnosis is thought to be useful to direct therapy, stereotactic or open biopsy may be performed. As more and more evidence argues for resection first, biopsy of low grade gliomas is used in limited scenarios such as when a tumor is inaccessible or diffuse, or when there is a poor functional status or uncertain pathology. Open biopsy with image guidance is appropriate in cases where the lesion approaches or reaches the cortical surface in a safe, accessible area. Stereotactic biopsy is most appropriate for deep-seated or small lesions (Figure 2). Based on the surgeon s experience and comfort with each technique, frame-based or frameless stereotactic biopsy can be performed. Frameless stereotaxy has gained popularity as its reliability has been shown in large series. Stereotactic biopsies often use a blunt cannulated needle. The most common complications encountered with this procedure include new neurological deficit due to hemorrhage or cerebral edema. The complication rate for stereotactic biopsies has repeatedly been quoted with a morbidity rate of percent and mortality of percent. A series of 270 consecutive stereotactic biopsies of varying pathologies reported by McGirt et al demonstrated a 5 percent morbidity and 1 percent mortality with a diagnostic accuracy of 93 percent. 4

5 figure 1 Left-sided low grade insular glioma. a) Nonenhancing post-contrast, with T1 hypointesity b) hyperintense FLAIR seen in left insular region, with sharp borders c) mild-mass effect seen as encroachment on ventricular system on the left-side d) perfusion imaging showing elevated perfusion in lesion, consistent with neoplasm. Resection The indications for surgical resection include: diagnosis, relief of neurological deficits, medically uncontrolled epilepsy, relief of mass effect and possibly improvement in progressionfree survival (PFS) or overall survival (OS). The usefulness of surgical resection for diagnosis and relief of mass effect are self-evident. If mass effect is causing neurological deficits, removing the majority of the mass is likely to aid in relief of neurological deficits. If the tumor is infiltrative of demonstrably functional areas, but does not cause mass effect, surgical resection is unlikely to relieve symptoms and may bring a high risk of postoperative deficit. Surgical resection of a low-grade glioma in a patient who has medically intractable epilepsy related to the 5

6 glioma is a common indication for surgery. In patients with low-grade glioma-associated seizures, surgical resection results in seizure improvements in almost all patients: Engel class 1 outcome (seizure-free) in percent of patients and improvement in seizure frequency in another percent. Moreover, increased extent of tumor resection was found to be an important factor in multivariate analysis of seizure outcome in low-grade glioma. There has been significant historical discussion regarding the influence of the extent of resection (EOR) and overall survival in the treatment of low grade gliomas. Arguments for biopsy alone or radiographic monitoring have been purported since the advent of CT and MRI technologies. Similarly, as our ability to detect these lesions has grown with increasingly sensitive neuroimaging modalities, we have been forced to scrutinize our management approaches to these lesions. Our diagnostic and surgical treatment algorithm has been outlined above. Older retrospective studies comparing subjective EOR parameters (e.g., gross total resection versus subtotal resection versus biopsy ) have yielded variable results. However, recent literature examining volumetric EOR data has identified consistent associations between increased EOR and increased patient PFS and OS. On the basis of these data, a strategy of maximal resection of low-grade gliomas is preferred, where it can be done without excess perioperative morbidity. In cases without mass effect and where the expected volumetric resection of tumor is less than 50 percent, it may be appropriate to consider biopsy or radiologic monitoring as outlined above. While minor transient deficits are common after surgery for eloquent low-grade glioma, most resolve over the first several months postoperatively and thus yield a low rate of permanent neurologic morbidity and consequent functional impairment. Advanced imaging and surgical techniques The most critical factor in surgical planning for resective surgery in low-grade gliomas is the neuroanatomic milieu within which the neoplastic lesion exists. Lesions can be categorized into three groups based on anatomic location: presumed eloquent location, neareloquent location and non-eloquent location. Regions presumed to be eloquent include the primary sensorimotor cortex of the pre- and postcentral gyri, Wernicke s area (posterior figure 2 Advanced imaging techniques in low-grade glioma. a) Composite diffusion tensor imaging (DTI) representation, depicting subcortical white matter tracts b) anatomic overlay of DTI images, enable live neuronavigation around critical white matter pathways c) functional MRI (fmri) to identify critical cortical speech and motor regions of the brain and their relation to the tumor. 6

7 portion of the superior temporal gyrus and the inferior parietal lobule), Broca s area (inferior dominant frontal lobe), the calcarine visual cortex, the basal ganglia, internal capsule, thalamus, brainstem and the white matter paths of each. If any part of the lesion is found to infiltrate these regions, it is regarded as being located in presumed eloquent brain; if it approaches, but does not clearly involve these regions, it is considered near-eloquent; and if it is situated in a separate anatomic location, it is considered non-eloquent. In many cases of eloquent or near-eloquent tumors, preoperative functional imaging may be an important adjunct. This includes diffusor tensor tractography to define white matter tracts (e.g., the posterior limb of the internal capsule), and functional MRI (fmri) to localize primary speech and motor cortices. The use of fmri allows the surgeon to better assess the relationship of a lesion to eloquent cortex, there are considerable limitations, especially when mapping language areas. Studies show relatively reliable motor mapping using fmri techniques. However, fmri does not allow for precise localization of language, which is reflected by the wide range of reported results in the literature. A review of five studies showed language mapping sensitivity from percent and specificity from 0 97 percent when compared to intraoperative stimulation. Various authors have used newer non-invasive technologies for anatomic mapping, such as magnetoencephalography (MEG) and transcranial magnetic stimulation (TMS). Advanced preoperative functional imaging may serve two important purposes: (1) neuroplasticity may induce migration of functional activity to other neighboring regions in tumor-infiltrated brain, thus providing a better understanding of the true functional eloquence of the anatomically eloquent region under investigation; and (2) it enables the surgeon to understand the most dangerous regions of the figure 3 Intraoperative mapping. During either awake or asleep craniotomy for tumor resection, advanced neurophysiologic techniques of motor and speech mapping may be used to enhance the safety and extent of surgical resection. Here, electrical stimulation of critical regions is used to identify, in real time, the precise regions of the brain where speech and motor functions reside. tumor with regard to neurological morbidity and to estimate the extent of safe resection prior to the operation, further informing both discussions with the patient and multidisciplinary care providers considering adjuvant and neoadjuvant treatment options. In eloquent and near-eloquent tumors advanced neurophysiologic techniques and awake craniotomy with direct motor and speech mapping allows the surgeon to maximize the extent of resection and safety of the operation. With these advanced techniques including both awake and asleep, cortical and subcortical mapping of motor tracts and awake mapping of the speech region active monitoring and precise localization of the functional neural tissue in the operative region is achieved. Conclusion A growing body of evidence shows that aggressive surgical resection of low-grade gliomas may improve symptoms, extend PFS, and even cure a select few patients. With the application of preoperative functional imaging, intraoperative navigation, and cortical stimulation, neurosurgeons are able to perform more complete resections while limiting the risk to patients. While the treatment paradigm has moved away from biopsy and observation, there is still a role when the patient has a poor status or when the tumor is unresectable. t 7

8 New stroke guidelines extend the window for mechanical thrombectomy by Kolby T. Redd, PhD, MHA, assistant research professor, director of research, Palmetto Health-USC Neurology After an exhilarating presentation at the International Stroke Conference in Los Angeles, California in late January, the new stroke guidelines were presented and discussed at the South Carolina Neurological Association s annual meeting in early March. William J. Powers, MD, FAHA, lead author on the 2018 Guidelines for the Early Management of Patients with Acute Ischemic Stroke, presented the most pertinent changes within the guidelines to the state s leading neurology professionals during the introductory night of the conference. This presentation was well attended and spurred a large amount of intellectual discussion around the decisions most pressing to provide datadriven stroke care in the pre-hospital, acute and rehabilitative stages of care. The guidelines for health care professionals from the American Heart Association/American Stroke Association are updated every five years to ensure that the most recent clinical research is reviewed and integrated into current treatment. The guidelines are all-inclusive and cover the entire spectrum of care. They are divided into six distinct content areas that are further broken into individual guidelines for the categories as displayed in the table below. Each is evaluated on its strength and quality and given a class of recommendation and level of evidence which assists the clinician in giving treatment options. Special to this year s publication is the inclusion of secondary prevention measures that are appropriately instituted within the first two weeks of treatment. Topic area Pre-hospital stroke management and systems of care Emergency evaluation and treatment General supportive care and emergency treatment In-hospital management of acute ischemic stroke (AIS): general supportive care In-hospital management AIS: treatment of acute complications In-hospital institution of secondary prevention: evaluation Categorical breakdown Pre-hospital systems, EMS assessment and management, EMS systems, hospital stroke capabilities, hospital stroke teams, telemedicine, organization and integration components, establishment of data repositories, and stroke system care quality improvement processes Stroke scales, brain imaging, and other diagnostic tests Airway, breathing, and oxygenation, blood pressure, temperature, blood glucose, IV Alteplase, other IV thrombolytics and sonothrombolysis, mechanical thrombectomy, other EVTs, antiplatelet treatment, anticoagulants, volume expansion/hemodilution, vasodilators, and hemodynamic augmentation, neuroprotective agents, emergency CEA, carotid angioplasty and stenting without intracranial clot, and other Stroke units, supplemental oxygen, blood pressure, temperature, glucose, dysphasia screening, nutrition, deep vein thrombosis prophylaxis, depression screening, rehabilitation and other Cerebellar and cerebral edema, and seizures Brain imaging, vascular imaging, cardiac evaluation, glucose, cholesterol, other test for secondary prevention, antithrombotic treatment, statins, carotid revascularization, smoking cessation intervention, and stroke evaluation 8

9 There are various new and dissimilar aspects within each topic area. Most notable is in relation to mechanical thrombectomy. Thanks to the DAWN and DEFUSE 3 clinical trials, there is a new recommendation that extends the window for mechanical thrombectomy up to 24 hours from last known normal. Specifically, it states that for patients with AIS within 6 16 hours of last known normal who have large vessel occlusions in the anterior circulation and meet other DAWN or DEFUSE 3 eligibility criteria, mechanical thrombectomy is recommended (I, A). Furthermore, in patients with AIS within hours of last known normal who have large vessel occlusion in the anterior circulation and meet other DAWN eligibility criteria, mechanical thrombectomy is reasonable (IIa, B-R). Souvik Sen, MD, MPH, FAHA, chair of neurology at Palmetto Health-USC Neurology, served as a principal investigator for the DEFUSE-3 clinical trial, which was crucial in determining these guidelines. Based on current evidence, another prominent guideline addition resulted within the regional systems category. There is a new IIb-B-NR recommendation stating that when several IV alteplase-capable hospital options exist within a defined geographical location, the benefit to bypassing the closest to bring the patient to the one that offers a higher level of stroke care is uncertain. Even with this uncertainty, due to lack of current data, the state of South Carolina currently is working to pass a Stroke System of Care regulation in partnership with the American Heart Association/American Stroke Association and the Stroke Advisory Council within the Department of Health and Environmental Control. In March, this regulation received its second reading unanimously by the full Senate and is expected to pass the body by a unanimous vote in the coming weeks. The regulation passed unanimously out of the House Regulations and Administrative Procedures Committee and is now heading to the full House for a vote. This is proof of the magnificent work that is happening within the state to ensure that all patients who have stroke-like symptoms receive the best care, within the quickest timeframe, for improved outcomes. t 9

10 2018 SCNA annual meeting in Hilton Head offered enlightenment and fun by Kolby T. Redd, PhD, MHA, assistant research professor, director of research, Palmetto Health-USC Neurology The South Carolina Neurological Association s (SCNA) annual meeting was held March at the Hilton Head Marriot Resort and Spa on Hilton Head Island, South Carolina. The meeting drew attendees from South Carolina, North Carolina and Georgia, and included neurologists, nurses, physician assistants, physical/occupational/speech therapists, researchers, stroke management and other health care professionals. Across three days, attendees learned about the latest clinical advances and research within the field of neurology. The meeting kicked off on Friday evening with a welcome reception that included exhibits from various health care sponsors and the fifth annual scientific poster competition. This was followed by the Neuro Bowl competition between neurology residents from Palmetto Health/USC and the Medical University of South Carolina. After 25 grueling questions, the Palmetto Health/ USC team was proclaimed the winner of this year s Neuro Bowl. Congratulations to both teams for their preparation and effort. After a brief welcome from the new president of SCNA, Souvik Sen, MD, professor and chair of clinical neurology, Palmetto Health-USC Neurology and USC School of Medicine, presentations began during dinner on Friday night, allowing the audience to hear from William J. Powers, MD, chair and professor of neurology, UNC School of Medicine, and lead author of the 2018 Guidelines for the Early Management of Patients with Acute Ischemic Stroke. He presented the most pertinent changes within the guidelines to the state s leading neurology professionals. The presentation was well attended and spurred a large amount of intellectual discussion around the decisions most pressing to provide data driven stroke care in the pre-hospital, acute and rehabilitative stages of care. The attendees also heard an update from Swamy Venkatesh, MD, residency director and professor of neurology at Palmetto Health/USC SOM, and from Suzanne McDermott, PhD, professor and director of USC Arnold School of Public Health Disability, Research and Dissemination Center, regarding MD STARnet. MD STARnet is a multi-site surveillance system that was established in response to the Muscular Dystrophy Community Assistance, Research and Education (MD CARE Act) legislation in 2001 and re-authorized in 2008 and Saturday s activities kicked off with Justin Martello, MD, neurologist from Christiana Care Health System in Delaware, presenting on the American Academy of Neurology (AAN) quality measures. The AAN quality measures allow for quality improvements efforts at the provider or practice level and accountability for merit-based incentive payment systems and private payers. Following this was an engaging presentation from Bradley Vaughn, MD, FACS, professor of neurology and chief of sleep medicine and epilepsy at UNC. He discussed, in detail, the evaluation for epilepsy, the types of patients that need treatment, medication regimen highlights, and closed with intractable epilepsy and status epilepticus updates. The audience also heard 10

11 from Fredy Revilla, MD, professor of neurology at GHS Patewood Memorial, who spoke about the different classes of drugs recommended for Parkinson s disease patients, treatment options for both motor and non-motor symptoms, and the role of surgery in PD treatment. The presentations continued with Roham Moftakhar, MD, chief of neurosurgery, Palmetto Health, associate professor of clinical surgery, USC School of Medicine, who provided the audience with a very informative lecture on the management of intracerebral hemorrhage. He walked the attendees through the classification process (lobar versus non-lobar), interventions, current recommendations for the management of hypertension, reversal of coagulopathy, the management of intraventricular hemorrhage and hydrocephalus, and finished with surgical intervention techniques. Subsequently, Myriam Sollman, PhD, neuropsychologist at Palmetto Health Richland, presented on neuropsychological perspectives of cognitive decline. Specifically, she went into the multitude of different evaluations that can be conducted to aid neurology clinicians in the plan management and treatment of their patients. neuroanesthesiology to create a dedicated unit that can address the complex needs and treatment of stroke patients. The meeting wrapped up with R. Scott Turner, MD, PhD, spelling out a call to action for neurologists to open the window of opportunity for patients with early Alzheimer s Disease. Dr. Turner is professor of neurology and director of the Memory Disorders Program at Georgetown University Medical Center in Washington, D.C. He described the importance of early recognition of mild cognitive impairment and early cognitive decline. This meeting covered a multitude of topics that were of interest to neurology professionals. The next SCNA meeting will be just as informative and is scheduled for Spring 2019 in Asheville, North Carolina. We hope to see you there. t Later in the afternoon, the attendees heard Aljoeson Walker, MD, neurologist at MUSC, as he described the diagnosis and treatment of headaches (specifically migraine) and how to evaluate new agents that are on the market for migraine treatment. He highlighted the new upcoming treatment of migraine including monoclonal antibody to calcitonin generelated peptide (CGRP), which is believed to be the mediator for the final common pathway of migraine. After this presentation, Rodney Leacock, MD, neurointensivist at Palmetto Health-USC Medical Group, presented on neurocritical care in the 21st century. He went into detail regarding how neurocritical care evolved from neurosurgery and 11

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