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Neurology and Neurosurgery

Outcomes and Research

Our bench-to-bedside approach

creates a dynamic academic healthcare

environment where scientific discoveries

and clinical excellence go hand in hand,

making for better patient outcomes.

‘‘

’’

A.M. Rostami, MD, PhD, and Robert H. Rosenwasser, MD

Dear Colleague,

We are pleased to present our latest Neuroscience Outcomes and Research report. The many findings in the pages ahead reflect the innovative and dedicated work of clinicians, researchers and other staff at Jefferson Hospital for Neuroscience (JHN), part of Thomas Jefferson University Hospitals. JHN is the Philadelphia region’s only hospital dedicated to the treatment of neurologic conditions.

We chose the theme “Making the Connection: From Laboratory Science to Clinical Care” because it sums up what we do every day. We continually strive to apply research findings learned in the laboratory to clinical care, and, in turn, we take insights from patient care back to the laboratory to further explore the origins of neurologic diseases. That bench-to-bedside approach creates a dynamic academic healthcare environment where scientific discoveries and clinical excellence go hand in hand, making for better patient outcomes.

Thomas Jefferson University Hospital was recently named to the Best Hospitals 2013–14 Honor Roll by U.S.News & World Report, ranking it among the most outstanding hospitals in the country. Jefferson was also singled out for exemplary care across 12 specialties, including neurology and neurosurgery.

The JHN staff is committed to connecting patients with the right clinicians to receive high quality and compassionate care. JHN includes multiple centers and programs of expertise specifically dedicated to brain tumors, headache, epilepsy, multiple sclerosis, Parkinson’s disease and other movement disorders, cognitive impairment and Alzheimer’s, spine and neuromuscular disorders. Jefferson is recognized as one of the most advanced centers in the U.S. for stroke and is one of only 14 Model Spinal Cord Injury Centers in the country. Neurocritical care is a specialty that spans all those areas, and patients in acute situations benefit from being in a dedicated neurointensive care unit staffed by neurointensivists.

Some patients come to us in a moment of crisis; others rely on us to manage a lifetime of disease. No matter the circumstances, the goal is to connect patients with the services they need, optimize their treatment plan and promote a high quality of life, even in the most difficult of cases.

On a daily basis, our clinicians connect patients with state-of-the-art clinical trials that evaluate new therapies to treat disease or extend life. Jefferson doctors lead many of those clinical trials, sometimes collaborating with researchers in this country and abroad. Through the publication of scholarly articles, community-based research projects and a telemedicine consulting network for stroke, the reach of our specialists is vast.

Leading-edge technology is adding an exciting dimension to our understanding of the brain and the nervous system. Not only can we visualize the structure of the brain in greater detail, but can now also marvel as we watch the brain at work. Advanced imaging techniques are lending clarity to the diagnosis and treatment of a variety of complex neurologic conditions.

New discoveries are made in Jefferson labs every day. Neuroscientists are in pursuit of new genes involved in neurologic diseases and studying the molecular basis of disease. An overarching goal is to make the connection between laboratory findings and real-time patient needs. When scientists identify a new target for therapy, they are laying the critical groundwork for the development of safe and effective therapeutics that will relieve symptoms or, better yet, slow the course of relentless neurodegenerative diseases.

We invite you to review this report to learn how JHN clinicians and researchers are improving patient outcomes through forward-thinking clinical care and research. More information about the services available at Jefferson can be found on our website at JeffersonHospital.org/neuroscience. To refer a patient, please call Jefferson’s physician referral line at 215-503-8888 or have your patient call 1-800-JEFF-NOW (1-800-533-3669). The staff will be happy to assist you in accessing care for your patients.

Sincerely,

A MESSAGE FROM thE ChAiRS

A.M. Rostami, MD, PhDProfessor and Chair, Department of NeurologyJefferson Hospital for NeuroscienceJefferson Medical College ofThomas Jefferson University

Robert H. Rosenwasser, MDChair, Department of Neurological SurgeryJewall L. Osterholm, MD ProfessorJefferson Hospital for NeuroscienceJefferson Medical College ofThomas Jefferson University

05 OVERVIEW: NEuROscIENcE AT THOMAs JEFFERsON uNIVERsITY HOsPITALs

NeuroscieNce sPeciALTies

09 NEuROVAscuLAR dIsEAsE

15 EPILEPsY

21 bRAIN TuMOR

25 sPINE

29 NEuROMuscuLAR dIsEAsE

31 MOVEMENT dIsORdERs

35 HEAdAcHE

41 cOgNITIVE IMPAIRMENT/ALzHEIMER’s dIsEAsE

45 MuLTIPLE scLEROsIs

49 NEuROcRITIcAL cARE

52 AcTIVE REsEARcH PROJEcTs

CONtENtS

Making theConnectionA N o V e r V i e W

At Jefferson Hospital for Neuroscience, the extraordinary happens every day.

There has never been a more exciting time to study the brain and the intricate neural network that enable us to think, move, feel and carry out all the functions so vital to life.

Likewise, caring for patients with neurologic diseases is more rewarding than ever, thanks to new scientific findings, advanced imaging and diagnostic tests, improved treatments and comprehensive supportive therapies.

Jefferson Hospital for Neuroscience (JHN), part of Thomas Jefferson University Hospitals, is recognized as a leader in neurologic care and research. Jefferson clinicians and scientists make important genetic and molecular discoveries, develop and evaluate new drugs and connect patients with the right combination of services to ensure high quality and efficient care. Whether the patient is a young adult recovering from a life-altering accident or an older patient with early signs of disease, the JHN staff treats every patient encounter with a commitment to patient-centered, researched-informed care.

JHN has one of the busiest neurological surgery and neurology programs in the region. Research has shown a connection between large-volume centers and better outcomes. Recognized for its clinical excellence, JHN offers a comprehensive range of services in neurologic subspecialties, including epilepsy, cerebrovascular disease, headache, MS/neuroimmunology, spinal cord injury and brain tumors. But no disease exists in a bubble. With multiple disciplines under the umbrella of JHN, clinicians are able to reach across specialties to provide the latest in surgical techniques, medical approaches, imaging technology, clinical trials, rehabilitation therapies and preventive measures to meet their patients’ needs.

The demand for leading-edge neurologic services is great and will continue to increase as the baby-boomer generation grows older. Experts predict coming waves of Alzheimer’s disease and neurodegenerative disorders such as Parkinson’s disease. Treatment isn’t just about taking care of the patient in the moment. Staying cognitively fit and

51-800-JEFF-NOW | JeffersonHospital.org/neuroscience | transfers: 1-800-JEFF-121 | physician referrals: 215-503-8888

Jefferson Hospital for Neuroscience | Neuroscience Outcomes and Research 5

Overview

6

neurologically intact are the means to a long and productive life, and helping patients reach that goal is essential at JHN.

The JHN team also is deep into basic science that is leading to a better understanding of the biochemistry of the brain and the genetic and molecular roots of disease. In the areas of multiple sclerosis, for instance, researchers are studying the role of specific immune cells in the disease process, and the findings could pay off for other autoimmune diseases.

Laboratory findings are helping to elucidate rare conditions as well as more common illnesses.

Headache researchers, for example, identified a molecule in alcohol that could be the culprit in hangover headache – a discovery that could lead to new treatments for migraine. Functional MRI is being used in multiple disciplines to examine the brain at work. This mapping of the brain is leading to more precise treatments in fields such as epilepsy surgery and new ways to think about preventing neurologic decline.

At the bedside, research clinicians are identifying factors that lead to fewer complications and better recovery from brain surgery, spinal cord injury, head trauma and stroke. Researchers also are studying

Department of Neurology – FY 2013 New and Established Patient Visits

Patient Type

Cognitive Disorders

Epilepsy

General Neurology

Headache

Movement Disorders

Multiple Sclerosis

Neuromuscular

Stroke

Grand Total

New

246

357

273

633

301

67

248

185

2,310

Established

769

8,287

287

22,629

4,753

4,627

1,285

3,982

46,619

Grand Total

1,015

8,644

560

23,262

5,054

4,694

1,533

4,167

48,929

Department of Neurological Surgery – FY 2013 Volumes

Patient Type

Spine

Tumor

Vascular

Total

Initial Outpatient Visits

2,706

1,478

785

4,969

Total Outpatient Visits

10,176

8,240

2,681

21,097

Surgical/Interventional Procedures

1,637

1,273

1,864

4,774

Source: Jefferson Internal Data


DiseAses AND DisorDers• Acoustic Neuroma

• Alzheimer’s Disease

• Amyotrophic Lateral Sclerosis

• Aneurysm

• Arteriovenous malformation (AVM)

• Ataxia

• Bell’s Palsy

• Brain Tumors

• Chiari Malformation

• Chronic Headache and Migraine

• Chronic Pain

• Degenerative Disc Diseases

• Dural Arteriovenous Fistula (DAVF)

• Encephalitis

• Epilepsy and Seizures

• Guillain-Barré Syndrome

• Head Injury

• Hemorrhagic Stroke

• Hydrocephalus

• Ischemic Stroke

• Meningitis

• Multiple Sclerosis

• Muscular Dystrophy

• Myasthenia Gravis

• Neurocutaneous Syndromes

• Neuromuscular Diseases

• Parkinson’s Disease

• Pituitary Tumors

• Retinoblastoma

• Scoliosis

• Spinal Cord Injury

• Spinal Fractures

• Spinal Tumors

• Stroke

• Vertebral Dislocation

factors beyond the hospital walls, such as cultural attitudes and societal beliefs, that influence whether patients seek out care for problems such as dementia and headache.

Jefferson’s large research portfolio includes:

• Drug development – Brain tumor researchers have devised a novel therapeutic to prime the body’s immune system to attack gliomas, aggressive brain tumors that often defy standard treatment. Early testing in a small number of patients looks promising.

• Clinical research – Jefferson researchers conducted a study to determine what factors put patients at added risk for pulmonary embolism after spinal fusion. The findings will help clinicians and patients weigh the risks and benefits of surgery based on the patient’s medical status and history.

• Patient outcomes – A new telemedicine consulting service that connects JHN stroke specialists to emergency departments at outlying hospitals is allowing stroke patients throughout the Philadelphia region to benefit from state-of-the-art treatment. A preliminary analysis of outcomes data for the stroke network found that 97 percent of stroke patients who met the criteria for intravenous tissue plasminogen activator (IV tPA) went on to receive the therapy.

The pages ahead provide more details on how Jefferson clinicians and scientists are utilizing research findings to optimize the care of patients with neurologic conditions. The findings illustrate why JHN leads the way in “Making the Connection: From Laboratory Science to Clinical Care.”

Neuroscience Patient Admissions FY 2013

Neurology 2,351

Neurological Surgery 4,258

Total Admissions 6,609

TesTs AND ProceDures• Corpectomy

• Craniotomy

• CT Scan of the Brain

• Deep Brain Stimulation

• Electroencephalogram (EEG)

• Electromyography (EMG)

• Endoscopic Resection

• Endovascular Embolization

• Evoked Potentials Studies

• Foraminotomy

• Intra-Arterial Chemotherapy (IAC)

• Intrathecal Pump Implantation

• Ketogenic Diet Therapy

• Laminectomy

• Lumbar Puncture (Spinal Tap)

• Magnetic Resonance Imaging (MRI)

• Medical and Radiation Therapy for Brain Tumors

• Microsurgical Resection

• Muscle Biopsy

• Nerve Conduction Velocity (NCV)

• Neurostimulator Implant

• Shunt Placement

• Spinal Decompression

• Spinal Fusion

• Spondylectomy

• Stereotactic Radiosurgery

• Stereotactic Surgery

• Surgical Clipping

• Vagus Nerve Stimulation

Source: Jefferson Internal Data

NeurovascularDisease

Jefferson’s Division of Neurovascular and Endovascular Surgery is built on an integrated approach to patient care that flows from the collective expertise of neurosurgeons, vascular neurologists and neurointensivists. Clinicians evaluate patients through a lens that is not technique focused but rather disease focused. The patient benefits because the resulting treatment plan is not based on a bias toward any particular surgical intervention or medical therapy.

Among the busiest in the region, Jefferson’s Division of Neurovascular and Endovascular Surgery is setting standards in the surgical and medical management of stroke, aneurysm, carotid artery disease and arteriovenous malformations. Last year, for instance, clinicians handled more than 400 brain aneurysm cases, including 95 open-brain surgeries and more than 300 endovascular procedures. Additionally, the program offers stereotactic radio-surgery using the Gamma Knife or linear accelerator (LINAC), based on the patient’s specific needs.

A specially designed hybrid operating suite allows neurosurgeons to combine open and endovascular procedures in the same OR, without needing to

move the patient to a different location. Also, two dedicated neurointensive care units, a total of 66 beds, are staffed by neurointensivists trained to manage complex surgical and medical cases.

More than 1,500 patients were cared for in 2012 at the Jefferson Acute Stroke Center. The Center offers advanced care for cerebrovascular emergencies. Patients living in a vast geographical area within Pennsylvania, New Jersey and Delaware can benefit from Jefferson’s stroke expertise through a telemedicine program that links outlying emergency departments with Jefferson stroke experts. The robotic consulting service allows for timely evaluations and interventions such as intravenous tPA (IV tPA), as well as the triaging of patients who require advanced interventions such as intra-arterial tPA, mechanical thrombolysis and aneurysm coiling.

The Division of Neurovascular and Endovascular Surgery is also a busy medical training and research center. Fellows from across the country train at Jefferson in cerebrovascular surgery, and attending neurosurgeons receive dual training in cerebrovascular and endovascular surgery.

Clinicians evaluate patients through a lens that is not technique focused but

rather disease focused.



Clinicians in the division published more than 40 academic papers last year. Here is a closer look at some of that research:

eNDoVAscuLAr TreATmeNT of BAsiLAr TiP ANeurysms By coiLiNg, WiTh AND WiThouT sTeNT AssisTANce Basilar tip aneurysms (BTA) account for approximately five percent of intracranial aneurysms and 50 percent of aneurysms in the posterior circulation. Posterior circulation artery aneurysms have a higher potential for rupture than anterior circulation aneurysms, making intervention often a better choice than observation, though surgery can be a challenge.

Endovascular treatment options have emerged as alternatives to surgery. Jefferson researchers headed by Stavropoula I. Tjoumakaris, MD, Assistant Professor of Neurological Surgery, conducted a retrospective review that included 235 patients with BTAs who underwent endovascular treatment – 147 with coil embolization and 88 patients with stent-assisted coiling (72 single stents and 16 Y stents).

They found that:

• Thromboembolic complications occurred in 6.8 percent of patients in each of the two groups.

• Stented patients had significantly lower recanalization rates than non-stent patients, 17.2 percent versus 38.9 percent, as well as lower retreatment rates, 7.8 percent versus 27.8 percent.

• Four rehemorrhages occurred in the coiled group (2.7 percent) and none in the stented group.

The review, published in Neurosurgery, found overall that stent-assisted techniques for BTA treatment are associated with significantly lower recurrence, retreatment and rehemorrhage rates compared to coiling alone. Y stenting is especially efficacious.

The question arises as to whether stent-assisted techniques should be systematically used for all BTAs regardless of their morphology. Although these findings point in that direction, randomized controlled trials with long-term follow-up are needed to answer that question.

eNDoVAscuLAr mANAgemeNT of AcuTe ischemic sTroke iN eLDerLy PATieNTsAs more people live longer, there is a corresponding increase in the prevalence of stroke in the elderly. More attention is now given to the potential benefits of intra-arterial and mechanical thrombolysis for even the most elderly patients. Clinicians have begun to perform endovascular recanalization of acute ischemic stroke in septuagenarians and above, though there is not much in the medical literature on how very elderly patients fare with such an intervention. Existing medical comorbidities such as diabetes, hypertension, cardiac problems and renal insufficiency increase perioperative patient risk. In addition, vascular anatomical limitations – such as atherosclerosis, vessel tortuosity and peripheral vascular disease – pose additional surgical risks for the elderly.

To help elucidate the safety and efficacy of endovascular intervention for elderly patients, Jefferson researchers headed by Dr. Tjoumakaris conducted a systematic review of medical charts for 51 stroke patients over age 75 who underwent a procedure at Jefferson between 2000 and 2011.

The patients, 35 women and 16 men, were 81.4 years old on average, and the oldest patient was 90. Of the 51 total patients, 23 received intravenous tissue plasminogen activator (IV tPA) prior to admission. Eight underwent stent placement after intra-arterial thrombolysis, 10 underwent balloon angioplasty and seven had both angioplasty and stent placement. A total of 21 required intra-arterial chemical thrombolysis alone. At baseline, 46 patients (90.2 percent) had a complete arterial occlusion before intervention.

Outcomes, reported in the Journal of NeuroInterventional Surgery, include:

• Thirty-four patients (67 percent) had significant revascularization of the affected vessel.

• Thirteen patients (25.4 percent) showed some degree of intracranial hemorrhage on post-operative imaging.

• Three patients (6 percent) had symptomatic intracranial hemorrhage, though none required surgical intervention.

• One patient (1.9 percent) had a postoperative retroperitoneal hematoma, which was managed conservatively.

Neurovascular Disease

10


• Two patients (3.9 percent), both of whom had balloon angioplasty of the distal cervical internal carotid artery, died from intraoperative vessel rupture.

• The all-cause mortality rate was 21.6 percent.

• At the time of discharge, 33 percent of patients had a favorable outcome, indicated by either a 4 (moderate disability) or 5 (good recovery) rating on the Glasgow Outcome Scale.

Restoring function after stroke is a key goal for all stroke patients, regardless of age. Multimodal endovascular recanalization of acute ischemic stroke is a safe treatment option in patients older than 75. That said, careful patient selection by clinical and radiographic criteria is necessary for the successful management of stroke in this age group.

TreATiNg sTroke iN The roBoTic erAStroke is the second leading cause of death worldwide and the third leading cause in the U.S. New drug and endovascular treatments are helping to save the lives and function of stroke patients, but not all patients have immediate access to these life-saving therapies. Many stroke patients are taken to hospitals without a neurovascular team to do assessments 24/7 and administer intravenous plasminogen activator (IV tPA) or an intra-arterial procedure. As a result, many stroke patients do not receive the latest care or they are immediately transferred to another facility without a proper evaluation.

To overcome barriers to stroke care, Jefferson Hospital for Neuroscience established the Jefferson Neuroscience Network, which provides a 24/7 telemedicine stroke consulting service for participating community hospitals. Unlike more passive telemedicine systems used in some ICUs, this robotic system allows the Jefferson stroke expert on service to be virtually at the bedside and direct treatment by remotely maneuvering a robotic system in the outlying emergency department (ED). The Jefferson physician can manipulate the robot to conduct a visual exam, view monitors and talk with the patient, family and ED staff.

The Jefferson Neuroscience Network – which includes 29 community hospitals in Pennsylvania, New Jersey and Delaware – provided 1,643 stroke consults between January 2011 and June 2012.

A systematic review, led by Dr. Tjoumakaris, of the stroke consults provided over that period found that:

• A total of 237 patients (14.4 percent) were determined to be eligible for IV tPA; of those, 97 percent received it.

• The average time from consultation request to telemedicine response was 12 minutes.

• All hospitals within the telemedicine network reported an increased use of IV tPA. The overall rate of use was 14 percent among all consultations.

L. Fernando Gonzalez, MD

Jefferson Hospitals for Neuroscience | Neuroscience Outcomes and Research 510

Stavropoula I. Tjoumakaris, MD


• The proportion of patients transferred to a primary stroke center after telemedicine consultation decreased from 44 percent in the first two quarters of 2011 to 19 percent in the first two quarters of 2012.

These data were accepted for publication in Neurosurgery, the official journal of the Congress of Neurological Surgeons. The encouraging results provide a strong rationale for the establishment of robotic stroke consulting networks. Patients in remote or medically under served regions can benefit from the expertise of stroke specialists at tertiary centers.

PeArLs AND PiTfALLs of iNTrA-ArTeriAL chemoTherAPy for reTiNoBLAsTomARetinoblastoma is the most common primary intraocular malignancy in children. Advances in the detection and management of the potentially fatal cancer have led to a cure rate approaching 96 percent in the U.S. In the developing world, however, the outlook for children with retinoblastoma is still bleak, with estimated death rates ranging from 50 to 70 percent.

Intravenous chemotherapy has become the mainstay of treatment for retinoblastoma, helping to avoid removal of the affected eye and spare vision in some cases. Over the past several years, intra-arterial chemotherapy (IAC) has emerged as a promising treatment alternative for advanced and refractory retinoblastoma. The targeted delivery technique – which involves installation under fluoroscopic guidance of chemotherapy into the ophthalmic artery branch of the internal carotid artery on the side of the involved eye – is designed to avoid systemic complications. Jefferson and other centers using IAC have reported dramatic regression of advanced tumors in cases in which other treatment modalities have failed, along with impressive declines in the rate of enucleation in children with retinoblastoma.

Despite promising early results, IAC has limitations and there are concerns related to the chemotherapy and infusion techniques. To assess the effectiveness and use of IAC in treating retinoblastoma, a Jefferson research team headed by Pascal Jabbour, MD, Associate Professor of Neurology, reviewed the existing body of data. The findings, published in the Journal of Neurosurgery: Pediatrics, include:

• IAC seems to work best in cases involving less-advanced tumors. In one study, for instance, Jefferson researchers reported on their two-

year experience with IAC in 17 patients with retinoblastoma, 13 of them treated with primary IAC and the four others with secondary IAC after failure of other methods. Complete tumor regression was noted in 88 percent of the patients, all of whom remained recurrence-free at follow-up. Another Jefferson study found that only one or two cycles of IAC can be sufficient to treat tumors classified as either Group C or D, with 100 percent of tumor control. Some patients need only one treatment for complete cure.

• The targeted technique does not offer assurance against the potential for metastatic disease. Any systemic dose that happens to result from the targeted therapy may be inadequate to eliminate extraocular tumors.

• Complications to the eye include eyelid edema, forehead erythema, thinning or loss of eyelashes, blepharoptosis and transient ocular dysmotility, but those side effects usually disappear within a few months. A much more serious concern is the risk of vasculopathy in the ophthalmic, retinal and choroidal vessels.

IAC requires specialized expertise and experience on the part of the treating physician. It also requires sophisticated instrumentation, which is not available in all areas of the world, in particular Asia and Africa, where the need is greatest. Another concern is the cumulative effect from repeated exposure to ionizing radiation, especially in children.

While a number of studies have shown that IAC holds promise for the treatment of retinoblastoma, the evidence is still preliminary. Clinicians need to counsel patients and their families on the pros and cons of the technique. As research continues, IAC should be used only with great caution.

Neurovascular Disease


Rodney D. Bell, MD

Epilepsy

The Jefferson Comprehensive Epilepsy Center is a tertiary referral center that offers the latest in diagnostic testing and treatment options, including medical therapy, epilepsy surgery, ketogenic diet, neurostimulation, surgical implantation of electrodes, advanced functional magnetic resonance imaging (fMRI), counseling and neuropsychological evaluation and treatment. The Center is one of the most experienced and highest-volume epilepsy surgery programs in the country. It has a dedicated eight-bed inpatient video-EEG monitoring unit that evaluates approximately 400 people each year for diagnosis, pre-surgical assessment and management of uncontrolled seizures.

The Center’s strength comes from a deep bench of experts in neurology, neurosurgery, neuropsychology and radiology, coupled with a rigorous research agenda that extends from basic science to clinical trials. Clinicians and researchers share the goal of improving the lives of people with epilepsy.

Active research projects include: investigational therapeutics, predictors of outcomes after epilepsy surgery, metabolic effects of antiepileptic drugs, genetics of epilepsy, use of functional MRI to assess cognitive function and to explore the pathophysiology of epilepsy, cognitive electrophysiology and cardiac

electrophysiology in epilepsy. The Center is also leading a new multicenter study to assess the use of MRI-guided thermal ablation for refractory epilepsy, using a new form of laser technology.

The Jefferson Comprehensive Epilepsy Center attracts patients from around the globe. It also provides specialty training in epilepsy for physicians from multiple countries, including Argentina, Iran and Nigeria. The Center’s experts deliver eight to 10 international lectures a year on the clinical and research work performed at Jefferson.

It is the combination of clinical volume, vast experience, team approach, and a commitment to research and publications that makes the Center a leader in epilepsy treatment and research.

Here is a look at some recently published research:

usiNg eeg To PreDicT surgicAL ouTcome iN froNTAL LoBe ePiLePsyPatients with frontal lobe epilepsy (FLE) are especially difficult to diagnose and treat, and surgical treatment of FLE is less likely than anterior temporal lobectomy to alleviate seizures. To better select those FLE patients most likely to benefit from surgical intervention, it is important to identify

The Jefferson Comprehensive Epilepsy Center attracts patients from around the globe.



which preoperative features are predictors of seizure freedom or recurrence.

Jefferson researchers Michael R. Sperling, MD, and Ashwini D. Sharan, MD, and Martin Holtkamp, MD, of Charité – Universitätsmedizin Berlin, performed a study assessing 25 FLE patients who had recently undergone frontal lobe surgery to determine which interictal and ictal intracranial EEG findings, along with clinical features and scalp EEG data, predict good seizure control postoperatively. The patients were 32.3 years old on average and had epilepsy an average of 16 years. The study, which involved a review of EEG test results and other medical records, found that:

• Fifteen patients (60 percent) were free of seizures 19 to 24 months after surgery.

• Ten patients (40 percent) continued to have seizures, and most were improved.

• Lack of seizure freedom following surgery was more likely in patients who had surgery on the left frontal lobe. Why left hemisphere surgery is less likely than right-sided resection to lead to seizure freedom is not clear, but may be related to the tendency to perform more restrictive surgery in the language-dominant hemisphere.

• Sex, age at surgery, duration of epilepsy and presence of an MRI lesion in the frontal lobe or extrafrontal structures were not predictors of seizure freedom or recurrence.

• EEG findings were good predictors. Specifically, rapid seizure spread in intracranial EEG recordings predicted seizure recurrence after surgery. Rapid seizure propagation likely indicates an extended area of increased epileptogenicity beyond the actual seizure-onset zone, and thus failure to remove brain tissue that is involved in propagation of ictal activity could result in seizure relapse. It is also possible that rapid spread could be a marker of defective network inhibitory mechanisms and indicates a more widely distributed pathology in cortical and subcortical structures.

These findings, published in Epilepsia, should help in the selection of FLE patients for surgery and help doctors improve surgical outcome.

effecT of eNzyme-iNDuciNg ANTiePiLePTic Drugs oN cArDioVAscuLAr risk fAcTorsPeople with epilepsy have higher cardiovascular morbidity than those without epilepsy. That could be in part due to the medications they take. Antiepileptic drugs (AEDs) that induce the cytochrome P450 system alter lipid metabolism and metabolism of hormones and other molecules in the body. A better understanding of the metabolic profile of AEDs could help inform physicians in the selection of medications for their patients and, in turn, perhaps reduce risk of developing cardiovascular disease.

In a series of clinical studies, Jefferson researchers led by Scott Mintzer, MD, assessed lipid levels, C-active protein and homocysteine in people being switched from enzyme-inducing AEDs, including phenytoin and carbamazepine, to non-inducers, including levetiracetam, lamotrigine and topiramate. They found that total cholesterol, LDL, C-reactive protein and homocysteine significantly dropped in most patients after being taken off an enzyme-

Epilepsy

16


inducing drug. The findings, published in Annals of Neurology, Epilepsy & Behavior, and Epilepsy Research, have the potential to change medical practice. More research is needed to determine the long-term cardiovascular risks of various AEDs, but these findings strongly suggest that non-inducing medications may have the edge because they can offer seizure control without creating unwanted metabolic effects.

surgery for meDicALLy iNTrAcTABLe ePiLePsy: sooNer BeTTer ThAN LATer?Temporal lobe epilepsy (TLE) is the most common cause of drug-resistant seizures. The American Academy of Neurology practice parameter recommends surgery as the treatment of choice for medically intractable TLE. But surgical treatment for epilepsy is delayed and underutilized because it is seen as a last resort. Patients who are referred for surgery typically have had epilepsy for more than 20 years and failed many antiepileptic medications.

The time lag to surgery is often too long to avoid significant disability, and can result in premature death.

Jefferson participated in a multicenter clinical trial – called Early Randomized Surgical Epilepsy Trial – to determine whether surgery soon after failure to respond to two AEDs is superior to continued medical management in controlling seizures and improving quality of life. Michael R. Sperling, MD, Professor of Neurology, participated in overall trial design and led the effort at Jefferson.

The study enrolled 38 participants, 18 men and 20 women, who were at least 12 years old. All had mesial temporal lobe epilepsy and disabling seizures for no more than two consecutive years after trials of two AEDS. Twenty-three of the study participants continued on medical management, while 15 underwent anterior temporal lobe resection. The primary outcome measure was freedom from disabling seizures during two years of follow-up. The study, published in the Journal of the American

Michael R. Sperling, MD

Thomas Jefferson University Hospitals | Neuroscience Outcomes and Research 5

Epilepsy

14

Ashwini D. Sharan, MD


Medical Association, found that none of the 23 medically managed patients was seizure free, but eleven of the 15 surgery patients were, a significant result. Surgery also improved quality of life, as measured by a standardized scale, and the ability to drive and socialize. Adverse events included a transient neurologic deficit attributed to an MRI-identified postoperative stroke in one of the surgery patients and three cases of status epilepticus in the medical group.

The data reinforce the view that referral for surgery soon after the failure of two AEDs offers the best chance for preventing a lifetime of disability.

emPLoymeNT AfTer ePiLePsy surgeryPeople with epilepsy have higher unemployment than the general population. Cognitive, behavioral and psychiatric impairments, along with social barriers associated with epilepsy, all likely contribute to this high rate of unemployment. Patients with uncontrolled seizures are more apt to be unemployed than patients with controlled seizures. Up to now, there have been conflicting findings on whether surgery improves the chances for employment.

Jefferson researchers, headed by Dr. Sperling, undertook a study to determine employment status following anterior temporal lobectomy. A total of 369 patients were evaluated, the largest published series in the world literature. The study, published in Epilepsia, found that employment levels were higher and unemployment levels lower after surgery, supporting the concept that epilepsy surgery reverses the disability of epilepsy. The major factors influencing employment after surgery were becoming seizure free and working prior to surgery.

Specifically:

• Of the 131 patients who were unemployed or homemakers before surgery, 67 (51 percent) became employed postoperatively. Factors associated with gaining employment were becoming seizure free, a younger age at surgery and driving a motor vehicle.

• Of the 172 patients who were working before surgery, 27 (15.7 percent) became unemployed or homemakers after surgery. Women were more

Graph illustrating change in employment status after anterior temporal lobectomy in relation to seizure outcome group. The number of patients with a change in employment category (full time, part time, homemaker, unemployed) after surgery is shown for each seizure control group. Group 1 = seizure-free in each year following surgery; Group 2 = majority of seizure-free years (>50%) following surgery; and Group 3 = minority of seizure-free years (≤50%) following surgery. After surgery, the change in employment classification is significant for Groups 1 and 2, whereas there is no significant change in employment in Group 3.

Source: Reproduced with permission Wiley Periodicals, Inc. © 2011 International League Against Epilepsy; Employment After Anterior Temporal Lobectomy; Epliepsia © ILAE

52(5): 925-931, 2011 doi:10/1111/j.1528-1167.2011.03098x

Katherine Zarroli, Joseph I. Tracy, Maromi Nei, Ashwini D. Sharan and Michael R. Sperling

likely than men not to hold a job before they transitioned to the position of homemaker.

• Most students ultimately became employed after surgery, with seizure control determining whether they became employed.

Employment is a valuable measure of surgical success because it tends to enhance financial and psychosocial well-being. It has benefits for society as well, since gainful employment adds to general economic activity. This research provides important information for physicians and patients contemplating surgery for intractable epilepsy. The findings help define reasonable expectations and provide objective evidence of benefit beyond purely medical outcomes.

Change in Employment Status and Postoperative Seizure Control

Seizure Control Group

n Full Time n Part Time n Homemaker n Unemployed

Num

ber

of

Pat

ient

s

40

20

0

-20

-40

Group 1 Group 3Group 2

Brain Tumor

The Jefferson Kimmel Cancer Center Brain Tumor Center is among the most comprehensive programs in the country, performing more than 1,100 surgeries annually of benign and malignant tumors. Patients benefit from a multidisciplinary team of specialists experienced in delivering the latest surgical, radiological and chemotherapy techniques.

The Center’s specialists – including neurosurgeons, neuropathologists, neuro-oncologists, radiation oncologists and neuroimmunologists – routinely handle complex cases, and many patients come to the program after receiving confusing and sometimes discouraging reports elsewhere. The program’s patient-centered approach means that while the emphasis is on treatment, maximizing patients’ quality of life throughout the course of their disease is also important.

The program’s strong focus on basic research and participation in clinical trials allows patients to personally benefit from new approaches to fighting tumors. The program is a leader in developing the use of stereotactic radiosurgery and new immune-boosting therapies to target even the most persistent brain tumors. As part of its commitment to research,

Jefferson participates in a national tumor bank, The Cancer Genome Atlas, that analyzes the genetic makeup of tumors. Jefferson clinicians also regularly participate in NIH-funded trials that investigate the optimal use of surgery, radiotherapy and chemo-therapy in the treatment of brain tumors.

Here is a summary of some of those research efforts:

immuNe-BoosTiNg TherAPy for gLiomAsGliomas can be among the most aggressive and relentless brain tumors, often resulting in a grim prognosis for patients. Surgery and radiotherapy are effective treatment tools, but gliomas often recur, presenting challenges for both patients and clinicians.

Jefferson researchers under the direction of David W. Andrews, MD, Professor of Neurosurgery, Jefferson Medical College of Thomas Jefferson University, are exploring the potential of immunotherapy as an adjunct treatment for malignant gliomas. In laboratory studies and a Phase I clinical trial designed for 12 patients, researchers have demonstrated the safety of the approach and have achieved some promising biological results.


Jefferson’s multidisciplinary team of specialists delivers the latest surgical, radiological and

chemotherapy techniques.


The immunotherapy works like this:

A patient’s tumor cells are harvested at surgery, and the cells are then treated with an investigational new drug called an antisense molecule that is designed to shut down a targeted surface receptor protein on the tumor cells. The tumor cells treated with the antisense molecule are encapsulated in a small diffusion chamber less than the size of a dime. The device is implanted in the patient’s abdomen, between the rectus sheath and muscle, within 24 hours of surgery.

The loss of the surface receptor causes the tumor cells in the diffusion chamber to die, and as they do the cells release small particles called exosomes that are filled with tumor antigens. Researchers hypothesize that the exosomes and the antisense molecule work together to activate the immune system as they slowly diffuse out of the imbedded chamber device. Immune cells are immediately available for activation because they recognize in the diffusion chamber a foreign body that must be eliminated. Over a period of 24 hours, various

waves of immune cells are activated, including the all-critical T cells, which are now primed to attack and eliminate the tumor. The patient is also protected over time because the T cells serve as a surveillance system, ready to pounce should the tumor recur.

In addition to a favorable safety profile, the Phase I trial also shows some positive clinical responses to the immunotherapy, as measured by MRI scans and objective measures of an immune response. In one case, for instance, after a patient with advanced disease underwent treatment, a series of MRI scans revealed a large inflammatory response with only a small residual tumor in the temporal lobe. This patient continues to do well as he approaches his one-year anniversary.

Compared to treatment alternatives for recurrence of gliomas, including additional radiation and chemotherapy, this immunotherapy could potentially provide a greater benefit with fewer risks and side effects for the patient. It is hoped that further investigation will result in a viable treatment against tumors that often defy the very best of surgical and medical care.

usiNg fuNcTioNAL mri To sTuDy The effecTs of BrAiN meTAsTAsesNearly 40 percent of cancer patients develop brain metastases as a result of another cancer. The standard palliative treatment for such tumors is whole brain radiotherapy (WBRT), which can extend life but also can cause changes in cognitive function.

Previous randomized trials have evaluated the added survival benefit of either surgery or stereotactic radiosurgery (SRS) combined with WBRT in comparison with WBRT alone. Regardless of the particular radiotherapy approach chosen, nearly all patients will experience some degree of neurocognitive impairment either because of the brain tumor itself or as a consequence of radiation treatment to the brain.

Jefferson is conducting an observational MRI study of neurocognitive function in patients with brain metastases who are scheduled to undergo WBRT

Brain tumor

22

A B

C D

This patient was treated with the antisense vaccine a month prior to the images in the panels (A: contrast enhanced axial image; C: contrast enhanced coronal image). Six days later a scan was obtained, which revealed dramatic improvement in the contrast-enhancing tumor volume (panels B and D).


or SRS treatment. The goal is to use fMRI to observe neurocognitive changes that may result from intracranial disease burden, radiation or both. Scans conducted before and after radiotherapy will be evaluated for changes over time. Brain scans conducted on age and gender-matched controls will be used for comparison.

This study is expected to yield new information about human neurocognition and, in particular, shed light on how the brain works while in a “resting state”– the so-called default mode network. The fMRI study will provide insight into what impact brain metastases

and radiation have on the default mode network and certain neurocognitive tasks, such as executive function and short-term memory.

The ultimate goal is to fine-tune treatment approaches so that the most beneficial irradiation of metastatic tumors can be achieved while preserving neurocognitive function as much as possible. Quality of life for patients is an important measure of success.

David W. Andrews, MD

Jefferson spine specialists are leaders in the treatment of a wide array of spine problems, including herniated disc, degenerative disc disease, spine deformity, spinal cord injury, fractures and tumors. Neurosurgeons on the team collaborate with specialists throughout the Jefferson system, including orthopedic surgeons, neurologists, pain management specialists, traumatologists and rehabilitation practitioners, to arrive at the optimal treatment plan for each patient, whether it’s a surgical or nonsurgical approach.

Each year, the neurosurgical team performs more than 1,500 spine procedures, making Jefferson among the busiest spine programs in the Northeast. Jefferson is also a designated Level 1 Regional Resource Trauma Center and a federally designated Regional Spinal Cord Injury Center. About 1,000 patients are treated annually for spinal and spinal cord injuries, many of them transferred to Jefferson because of our experience with complex injuries.

Spine specialists are also involved in basic science research and clinical studies that are helping to reduce complications and improve outcomes in

spinal surgery. Here is a look at several recently published studies:

iNciDeNce of PuLmoNAry emBoLism AfTer sPiNAL fusioNPulmonary embolism (PE) is a rare but serious event that may occur after spinal surgery. While there have been significant advances over the past two decades in the understanding and use of venous thromboembolism prophylaxis, it is not clear whether those preventive measures have translated into fewer complications for spinal fusion patients.

Jefferson researchers used a national database to study trends in PE over time in spinal fusion patients and to identify under what specific surgical circumstances PE is more likely to occur. The findings, published in Clinical Neurology and Neurosurgery, should help inform clinicians and patients on the benefits and risks of surgery.

The research team led by James S. Harrop, MD, Professor, Department of Neurosurgery, Jefferson Medical College of Thomas Jefferson University,


Each year, the neurosurgical team performs more than 1,500 spine procedures, making Jefferson

among the busiest spine programs in the Northeast.


Spine

26

used a database called the Nationwide Inpatient Sample to identify patients who underwent spinal fusion procedures between 1998 and 2008. The data were further analyzed for surgical approach (anterior, posterior or combination) region of the spine operated on (cervical, thoracic or lumbar) and surgical indication (intervertebral disc degeneration, scoliosis, vertebral fracture or spinal cord injury [SCI] with concurrent vertebral fracture).

The analysis found:

• Of the 4,505,556 patients identified, 9,530 had PE — an incidence of 0.2 percent. The incidence of PE remained fairly stable over the two decades.

• While the mortality rate for spinal fusion was very low, patients with PE were almost 12 times more likely to die than patients without PE.

• The number of patients undergoing spinal fusion increased dramatically, from 75,600 in 1988 to 404,475 in 2008.

• The average age of patients for all surgical interventions increased during the two decades. For instance, it went from 44.1 years to 54.3 years for intervertebral disc degeneration. The chance of PE went up with age.

• Patients whose surgery involved a combined anterior-posterior approach were nearly twice as likely to have PE than patients with a posterior approach.

• Patients who had an anterior approach had a 25 percent greater chance of PE than those with a posterior approach.

• Patients whose fusion involved the thoracic region of the spine were 2.5 times more likely to have a PE than patients with cervical or lumbar fusion.

• PE incidence remained stable over the 21 years for patients with intevertebral disc degeneration and scoliosis. The incidence increased for patients with vertebral fracture and SCI with vertebral fracture.

Further research is needed to determine why the incidence of PE has not decreased for spinal fusion, despite the evolution of minimally invasive surgical techniques and the development of clinical guidelines aimed at reducing DVT and PE through the use of postoperative anticoagulation therapy, compression devices and elastic stockings. The question of why PE risk has increased for trauma patients warrants particular research attention.

The cosT of comorBiDiTies AND comPLicATioNs AfTer sPiNAL surgeryIn today’s healthcare environment, clinicians and hospitals must be attentive to the cost of the care they render. Increasingly, well-managed costs are being equated with higher quality, and new reimbursement measures are aimed at both improving care and holding the line on costs by minimizing medical and surgical complications and cutting down on readmissions. Reducing hospital-acquired conditions (HAC) such as pneumonia and “never events” such as central venous catheter infections are seen as critical to the goal of slowing rising healthcare costs. Despite efforts to reduce adverse events related to spinal surgery, complications are still common and are significantly increased by patient comorbidities. Busy urban academic centers tend to have an especially broad mix of patients, many of them with comorbidities that put them at risk for surgical complications.

With all that in mind, Jefferson researchers undertook a study to quantify how patient comorbidities and perioperative complications associated with spinal surgery affect healthcare costs to society. A total of 226 patients who underwent spinal surgery at Jefferson from May 2008 to December 2008 were prospectively followed. Researchers calculated the direct healthcare cost for each case by adding up the national Medicare reimbursement payments associated with each Diagnosis-Related Group (DRG) and Current Procedural Terminology (CPT).

Among the findings:

• About 57 percent of patients had some complication, though most of them were minor.

• Patients on average had two comorbidities, and 25 percent of patients had four to seven comorbidities.

• Systemic malignancy increased the cost of care by $7,919 on average and preoperative neurological comorbidity increased the cost by $5,508.

• Spinal surgery cases with a complication cost $13,518 more per average than cases without a complication. Specifically, a pulmonary complication increased the cost by $7,233 and wound infection pushed up cost by $4,067.

This study, published in Spine, underestimates the true cost of spinal surgery to the nation’s healthcare bill because it does not include loss of productivity,


out-of-pocket expenses and the cost of outpatient

services. But it does illustrate the impact that comorbidities and surgery-related complications have on the direct cost of care. Government and private insurers’ reimbursement formulas need to take into consideration the added cost of caring for patients with comorbidities. At the same time, hospitals and clinicians need to be attentive to the fact that reducing postoperative complications will ease the burden on patients and society as a whole.

eArLy DecomPressioN for sPiNAL corD iNjury Given the life-altering effects of SCI on patients and their families and the high costs for acute and long-term care, there is a pressing need for better treatments. While preclinical evidence suggests that early decompression for SCI improves neurologic outcome, many surgeons still take the traditional approach of waiting at least 24 hours before intervening. Jefferson was part of a key study to evaluate the advantages of early-versus-later decompression for SCI.

The multicenter prospective study included 313 patients with acute SCI – 182 underwent early decompressive surgery, at an average of 14 hours post-injury, and 131 had surgery after 24 hours (on average at 48 hours) following injury. The degree of neurologic improvement postoperatively was measured by change in the American Spinal Injury Association Impairment Scale (AIS) at six months’ follow-up.

A total of 222 patients were followed to six months after surgery. The findings, published in the open-access journal PLOS ONE, were:

• Nearly 20 percent of patients who underwent early decompression had an improvement of 2 or more in their AIS score compared to 8.8 percent of the late decompression group. An improvement of 2 or more can be the difference between walking and not walking.

• Complications occurred in 24.2 percent of the early surgery patients compared to 30.5 percent of the latter group.

• There was one mortality in each group in the 30 days following surgery.

The findings suggest that clinicians caring for SCI patients should give careful consideration to performing decompressive surgery sooner than the usual waiting period of 24 hours or more.

Outcomes after Decompression for Spinal Cord Injury

AIS Grade Change at Six Months

No improvement

One grade improvement

Two grade improvement

One grade worsening

Early Intervention

42.7%

36.6%

16.8%

00.8%

Later (after 24 hours)

50.6%

40.7%

08.8%

No one worsened

Source: Alexander Vaccaro, MD, PhD, Thomas Jefferson University Hospitals

James S. Harrop, MD

muscularNeuroDisease


muscularJefferson’s program offers specialized evaluation and ongoing treatment options for various autoimmune neuromuscular conditions, such as myasthenia gravis, stiff-person syndrome, inflammatory neuropathies and myopathies, chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, multifocal motor neuropathy, and other demyelinating conditions. It also provides expertise in the diagnosis of muscular dystrophies, motor neuron disorders such as post- polio syndrome and amyotrophic lateral sclerosis, and various hereditary neuropathies, including Charcot-Marie-Tooth disease.

Under the leadership of Marinos Dalakas, MD, who came to Jefferson after serving as Chief of the Neuromuscular Diseases Section at the National Institute of Neurological Disorders and Stroke for 20 years, the program is focused on developing a strong research emphasis on the immune pathogenesis of various neuromuscular disorders and the application of novel immunotherapies. The program is exploring new antibodies in autoimmune neuropathies, neuromyelitis optica, inflammatory myopathies and stiff-person syndrome in connection with Dr. Dalakas’ laboratory at the University of Athens Medical School. It is also exploring the mechanism of painful conditions such as fibromyalgia, with ongoing evidence that a number of patients have small fiber sensory neuropathy.

Various studies are also performed on muscle, nerve and skin biopsies using molecular approaches. Findings have been published in leading journals.

A better understanding of the underlying autoimmune mechanisms of these diseases is expected to lead to the development of specific therapies. The neuromuscular program is planning clinical trials for chronic inflammatory neuropathy, dermatomyositis, and stiff-person syndrome.

Jefferson’s Neuromuscular Disease Program routinely sees difficult cases that have defied easy

explanation elsewhere, including rare disorders such as stiff-person syndrome.

Marinos Dalakas, MD

DisordersMovement

The Jefferson Parkinson’s Disease and Movement Disorders Program is a major referral program for Parkinson’s disease (PD) and related disorders, tremors, dystonia, Huntington’s chorea, Tourette’s syndrome, gait disorders and other conditions. A patient-centered approach allows for the development of individualized treatment plans to make the best use of medical, surgical, psychological and rehabilitative treatments. The clinicians evaluate over 500 new patients a year and currently have more than 2,000 active patients in the clinic.

At Jefferson, patients have access to the latest diagnostic tools and technology. The program offers DaTscanTM, an innovative brain imaging technology that allows clinicians to detect abnormalities of dopamine structures in patients with possible or early PD. The imaging can help to confirm or exclude a diagnosis when clinical symptoms paint an inconclusive picture.

Jefferson is experienced in the use of deep brain stimulation (DBS) for medically refractory PD, tremor and dystonia. DBS has long been recognized to improve symptoms of movement disorders when

medications fail, and several randomized clinical trials have highlighted its benefits for quality of life in both advanced and early PD.

Clinicians are also actively seeking innovative methods to enhance and refine the use of botulinum toxin treatment for cervical dystonia, blepharospasm and other forms of dystonia.

The program’s clinicians are researchers as well, helping to develop novel therapies and understand the mechanisms of disease. Patients have access to NIH-sponsored clinical trials and industry-sponsored investigations of new pharmacologic therapeutics. Therapies under investigation for possible neuro-protective effects in PD include creatine and pioglitazone, a drug traditionally used in diabetes therapy.

Jefferson researchers collaborate with experts throughout the region to uncover the genetics of disease. Recently, Tsao-Wei Liang, MD, Assistant Professor of Neurology, Jefferson Medical College of Thomas Jefferson University, was part of a multicenter team that identified a new gene for primary torsion dystonia.


The program’s clinicians are researchers as well, helping to develop novel therapies and unravel the

mechanisms of disease.

The patient experienced gradual improvement in gait, balance, and vertigo over the course of a year, and reported complete resolution of symptoms four years after removal of the ovarian lesions. Follow-up body and brain PET scans did not show any signs of active malignancy. The case suggests that acute cerebellar ataxia may be associated with an underlying ovarian teratoma. The patient’s marked clinical improvement after the removal of the teratoma, as well as the inflammatory infiltrates in the neural tissue found in the teratoma, suggest that the tumor played a role in triggering an immune response, leading to paraneoplastic cerebellar ataxia. The case represents a new category of immune-medicated cerebellar ataxia that is reversible with removal of an underlying tumor.


Jefferson clinicians often evaluate cases that have challenged experts elsewhere. Here is a summary of a case study recently presented at the annual meeting of the American Academy of Neurology in San Diego, CA:

reVersiBLe cereBeLLAr ATAxiA Due To oVAriAN TerATomACerebellar dysfunction is a classic paraneoplastic syndrome associated with various types of cancer, including gynecological and breast tumors, small-cell lung cancer, thymoma and Hodgkin’s lymphoma. Jung E. Park, MD, Neurology Resident, and Dr. Liang reported on the case of a 22-year-old woman with acute cerebellar ataxia that subsided upon removal of an ovarian teratoma.

The woman presented with acute ataxia associated with vertigo, vomiting, oscillopsia and dysarthria. She was initially admitted to a local hospital, where she underwent a workup including brain MRI, MR venography and angiography of the head and neck, which were unrevealing, and a lumbar puncture that showed a lymphocytic pleocytosis. She was treated for presumed post-infectious cerebellitis with intravenous corticosteroids, five treatments of plasma exchange and three doses of IV immunoglobulin without benefit, and was transferred to a local rehabilitation center. Her family then requested transfer to Jefferson for further evaluation.

Neurologic examination was notable for nystagmus, dysarthria, and severe limb and gait ataxia. She underwent a repeat lumbar puncture, which revealed a lymphocytic pleocytosis and an increase in immunoglobulin G. Brain MRI/MRA were repeated and unremarkable. There was minimal benefit with IV methylprednisolone, IV immunoglobulin and plasma exchange.

Cerebrospinal fluid and serum paraneoplastic and autoimmune testing (anti-Ri, CRMP5, Tr, NMDAR, AMPAR, mGluR1, GluR5, amphiphysin and GAD65 antibodies) were negative. A computed tomography scan revealed bilateral ovarian dermoid masses, which were ultimately removed and identified as a mature left ovarian teratoma and a right ovarian simple cyst. Further staining of the ovarian teratoma was performed, including an H&E stain that revealed lymphoid infiltrates in neural tissue and immunohisto-chemical staining that was significant for perivascular T-cell infiltration.

Movement Disorders

32

DaTScanTM brain imaging technology allows clinicians to detect abnormalities of dopamine structures in patients with possible or early Parkinson’s disease and confirm or exclude a diagnosis.

Normal

Abnormal


Tsao-Wei Liang, MD, and Daniel E. Kremens, MD

Headache

Recurrent headache is an extremely prevalent neurologic disorder, and migraine is a particularly disabling condition. It causes debilitating pain, absenteeism from work and school, disruptions in everyday activities and sometimes even significant damage to personal relationships. Given the tremendous burden of migraine and other forms of headache on both the patient and society as a whole, it is critical to find new treatments. In addition, identifying effective preventive therapies could result in tremendous health-related savings.

The clinicians at the Jefferson Headache Center are recognized international leaders in headache treatment, prevention and research. As one of only a few university-based headache treatment centers in the U.S., Jefferson Headache Center’s mission is to turn basic research findings and the latest in clinical evidence into therapies that will improve the lives of headache sufferers. Its clinicians routinely set the standards for the care of headache patients.

The Center is actively involved in education and is a resource for other physicians. With a United Council for Neuologic Subspecialties-accredited Headache

Fellowship Program, the center is important training ground for future headache specialists.

In the laboratory, Jefferson scientists are probing the causes of the chronification of headaches at the molecular level. They are also developing new animal models that are crucial for understanding how headaches are triggered and to develop novel therapies. With a constant flow of information from the laboratory to the clinic, patients benefit from the latest knowledge in the field of headache care.

Here are some examples of research that are furthering the understanding, treatment and prevention of headaches:

The sTigmA of migrAiNeA number of diseases, such as HIV, depression and epilepsy, are known to be stigmatizing, and that stigma can result in harm to patients’ relationships, a decreased quality of life and loss of employment. While being stigmatized is in itself a negative consequence of disease, it also has health implications because it can affect whether or not patients seek out and embrace care. Feeling


The clinicians at the Jefferson Headache Center are recognized international leaders in headache

treatment, prevention and research.


stigmatized can also cause patients to feel socially isolated, which can lead to stress, anxiety and depression. Research has shown that feeling stigmatized can cause damage to a person’s sense of self-worth and well-being.

While it’s been suggested that migraine patients are sometimes stigmatized, scant research has been done on the subject. A research team headed by William B. Young, MD, Assistant Professor of Neurology, Jefferson Medical College of Thomas Jefferson University, conducted a study to quantify to what extent stigma is attached to migraine, using epilepsy as a comparison. The researchers recruited 123 episodic migraine patients, 123 chronic migraine patients and 62 epilepsy patients from the Jefferson Headache Center and the Jefferson Comprehensive Epilepsy Center. The patients, between the ages of 18 and 65, responded to a series of questionnaires, including the stigma scale for chronic illness (SSCI) and the short form of the medical outcomes health survey (SF-12). Both the migraine and epilepsy patients also completed questionnaires specific to their illnesses to gauge their degree of impairment.

Patients with chronic migraine had higher scores on the stigma scale (54 out of a possible 120) than either episodic migraine (41.7) or epilepsy (44.6). Stigma correlated most strongly with inability to work, and migraine patients reported greater inability to work than episodic migraine patients or patients with epilepsy. After statistically adjusting for inability to work, migraine sufferers experienced about the same degree of stigmatization as epilepsy patients.

The findings, published in PLOS ONE, point to the need to better educate the public about migraine. Education efforts targeted at epilepsy may have already caused a favorable shift in public perceptions of the disease. Similar anti-stigma efforts aimed at migraine should take place at multiple levels, through education, advocacy and legal and policy interventions. Migraine patients also need help with the mental aspects of feeling stigmatized, through better availability of counseling, support groups and empowerment programs.

The impact of such efforts could be huge, given that an estimated 38 million people in the U.S. alone have migraines. Reducing the stigma around migraine should help many of those patients get the medical treatment and emotional support they need to stay well and thrive.

headache

36


Stephen D. Silberstein, MD


headache

38

20.00 40.00 60.00 80.00 100.00 120.00

25

20

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20.00 40.00 60.00 80.00 100.00 120.00

25

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20.00 40.00 60.00 80.00 100.00 120.00

25

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Histogram of Stigma ScoresP

erc

en

tP

erc

en

tP

erc

en

t

Total SSCI Score

Epilepsy44.6+/-16.3 (median 42.5)

Chronic Migraine54.0+/-20.2 (median 53.0)

Episodic Migraine41.7+/-14.8 (median 36.0)

Distribution of stigma scores for EM, CM and Ep. Scores for CM are significantly higher than for EM or Ep. CM scores were higher than SSCI scores of 42.7+/-19.7 for an internet panel of diverse neurological patients used to validate the SSCI (p<0.001, z-test), while EM and Ep were not.

Source: PLOS ONE, January 2013, Volume 8, Issue 1


PhArmAcoLogic TreATmeNT for ePisoDic migrAiNe PreVeNTioNEpidemiologic studies suggest that nearly 40 percent of migraine patients could benefit from preventive therapy, but only a small fraction of them use it. An updated guideline for migraine prevention, coauthored by Stephen D. Silberstein, MD, Professor of Neurology, Jefferson Medical College of Thomas Jefferson University, will help clinicians identify effective preventive treatments for their patients and provide a rationale for why patients should consider taking daily medication to reduce the likelihood and severity of attacks.

The guideline, released in 2012 by the American Academy of Neurology and the American Headache Society, analyzed published studies from June 1999 to May 2009 that met the criteria for Class I or Class II evidence. The resulting recommendations, published in Neurology, list as “effective” preventive therapies the antiepileptic drugs divalproex sodium, sodium valproate and topiramate; the beta-blockers metoprolol, propanolol and timolol; and frovatriptan for short-term menstrual-related migraine prevention. Included in the “ineffective” or “probably not effective” categories are lamotrigine and clomipramine.

The guideline noted that there is insufficient evidence to say whether one of the recommended drugs works better than another. It stressed that clinicians should select medications on a case-by-case basis, taking into consideration the patient’s migraine history, coexisting conditions, patient preferences and the cost of the medication. Settling on the right medication for any given patient might take some time while different therapies are tried.

DeVeLoPiNg AN ANimAL moDeL for PrimAry heADAche reseArchAnimal models are essential for the study of basic headache mechanisms and lead to improved treatments. Most headache models involve modifying an animal to mimic migraine symptoms. While such models provide a good representation of secondary headache, they are limited in their usefulness because they fail to capture the fact that migraine is more

than a pain disorder. Patients have interictal hypersensitivity and changes in sensory processing, as well as increased sound sensitivity between migraine attacks.

In a report published in the journal Headache, a Jefferson team led by Michael L. Oshinsky, PhD, Assistant Professor of Neurology, Jefferson Medical College of Thomas Jefferson University, reported on the development of a new rat model that closely mimics the symptoms found in human migraine. This rodent model of spontaneous headache will help advance the understanding of the pathophysiology of human migraine and lead to new therapeutic targets. This model can also contribute to the discovery of new genes and biomarkers for migraine in humans.

ALcohoL hANgoVer heADAcheAlcohol hangover, technically known as veisalgia cephalgia, is one of the most common types of headaches. Even people who have never had a migraine or recurring headaches sometimes experience an alcohol hangover. The throbbing pain typically begins four to 24 hours after drinking ends and can be temporarily debilitating. People with a history of migraine tend to experience alcohol hangover more severely with less alcohol consumption than drinkers who don’t get migraines.

The mechanism of headache hangover is unknown, though varying theories point to chemical compounds used to increase the taste or smell of alcoholic beverages, dehydration or the ethanol metabolite acetaldehyde as potential causes.

Jefferson Headache Center researchers working with a rat model of recurrent headache found that another ethanol metabolite, acetate, contributes to the headache component of alcohol hangover. The findings were published in PLOS ONE.

Understanding the mechanism by which acetate triggers headache could lead to a new treatment for hangover headaches and other headache disorders such as migraine.

Cognitive Impairment

More than five million Americans have Alzheimer’s disease (AD) and that number will grow rapidly as the population continues to age. By 2025, an estimated 7.1 million Americans will have Alzheimer’s, placing an even greater demand on healthcare services and caregivers. This year alone, the medical cost of caring for patients with Alzheimer’s in the U.S. will reach $203 billion. That number does not begin to reflect the tremendous strain, both financial and emotional, faced by patients and family members.

Those demographic and cost imperatives are driving clinicians and researchers at the Jefferson Alzheimer’s Disease and Dementia Center to investigate new treatments for AD and other dementias, find better diagnostic methods and target risk factors that may slow down or even prevent the loss of memory and other cognitive functions. The Center is a major referral site for the region and sees patients at all stages of disease, from those experiencing the often subtle early signs of cognitive impairment, to others whose disease is disrupting everyday living. The goal is to conduct a thorough evaluation to pinpoint the precise cause of the patient’s problems – whether Alzheimer’s, stroke, Parkinson’s or some other condition – and then develop an individualized

therapeutic plan aimed at maximizing the patient’s cognitive, functional and social capacities. The Center works closely with family members to help them develop caregiver skills and connect them with resources in the community.

Strong research provides the rationale for every dimension of care provided to patients. Jefferson is an active participant in clinical trials that are investigating new treatments for Alzheimer’s. Patients can benefit directly from taking part in a study if they choose. Basic science research at Jefferson is simultaneously zeroing in on the molecular basis of AD and other dementia disorders, and those laboratory findings may someday lead to the discovery of new ways to treat and perhaps prevent the disease.

One area of special interest to Jefferson researchers is identifying the cultural factors that influence the diagnosis and treatment of Alzheimer’s. Just as no two people necessarily respond to the same treatment in precisely the same way, persons from different ethnic, cultural and socioeconomic backgrounds may hold varying views on sickness and health care that influence whether, when and how they seek treatment.


Basic science research at Jefferson is zeroing in on the molecular basis of Alzheimer’s disease and

other dementia disorders.


Two community-based projects led by Barry W. Rovner, MD, Professor of Neurology, Jefferson Medical College of Thomas Jefferson University, focus on older African Americans, who as a group are at higher risk for developing AD and tend to have worse health outcomes compared to Caucasians. One of those studies is evaluating whether mild cognitive impairment can be slowed using an in-home intervention aimed at increasing a person’s level of activity. The other project focused on cultural and personal beliefs that could influence an individual’s knowledge of personal risk for Alzheimer’s.

Here are some details on those research projects:

PreVeNTiNg cogNiTiVe DecLiNe iN oLDer AfricAN AmericANs WiTh mciMild cognitive impairment (MCI) affects 25 percent of older African Americans, and the condition increases the risk of progression to AD. An extensive body of literature suggests that cognitive, physical and/or social activities may prevent or slow cognitive decline. Jefferson researchers are conducting a community-based randomized clinical trial to test that hypothesis.

The ongoing study will evaluate 200 older African Americans with MCI. Participants are volunteers from senior centers, churches, apartment houses and homecare and community medical practices in Philadelphia. Half receive a form of intervention called behavioral activation and the others received support therapy, with each approach delivered by way of six in-home sessions over three months, followed by six booster sessions.

In the case of behavioral activation, a community-health worker helps the participant set specific goals and strategies for staying active and engaged with life and then monitors follow-through. The goals are designed to be very focused and based on activities

the individual values, such as knitting half an hour each day or going to church.

The participants who receive support therapy are visited by a health worker who talks with them about the impact of aging and memory loss. The worker does not discuss the importance of staying active.

The primary outcome is episodic memory, as measured by the Hopkins Verbal Learning Test at baseline and again at 3, 12, 18 and 24 months. The hypothesis is that those participants who receive behavioral activation will experience less cognitive decline than those who receive support therapy.

The study, funded by the National Institute on Aging, is believed to be the first rigorously designed randomized clinical trial to determine whether participation in ordinary cognitive, physical and/or social activities can prevent cognitive decline in older African Americans. Other research projects have focused on a prescribed activity, but this study takes a different approach by encouraging seniors to stay involved in activities that they value.

MCI is a serious public health problem for which there is no effective pharmaceutical treatment. As a possible precursor to Alzheimer’s, MCI portends increasing caregiver burden, costly and complicated medical care, and, perhaps, nursing home placement. Behavioral interventions may hold the best hope for preserving cognitive function in an aging society. Identifying a practical, non-pharmaceutical prevention strategy against MCI would benefit not only African Americans, but could be life-altering for older persons from all communities.

cuLTurAL DiVersiTy AND VieWs oN ALzheimer’s AmoNg oLDer AfricAN AmericANsCultural views prevalent in the African-American community may influence people’s perceptions about their risk for AD, as well as their knowledge of the disease. Such views may influence whether a person seeks treatment for early signs of AD and accesses available treatment and services in the community. In fact, research has shown that African Americans tend to seek care at a later stage of disease than Caucasians. A better understanding of cultural diversity could help healthcare providers tailor AD prevention efforts and reduce disparities in care among different ethnic and cultural groups.

This study involved 271 older African Americans enlisted from a community senior center and local churches in Philadelphia. The participants were

Cognitive impairment

42

Brain MRI of a patient with Alzheimer’s disease.


administered two scales to measure cultural constructs that can influence health decisions and practices. The first focused on whether the person is present oriented or future-time oriented and the other measured the person’s religiosity. Participants were also given the Alzheimer’s Disease Knowledge Scale and another questionnaire to gauge their perceptions about having control over their health as well as their particular concerns about Alzheimer’s.

Overall, 70.5 percent of participants believed they could control risks to their health, 68 percent believed that they could take steps to prevent AD and nearly 60 percent were concerned about developing Alzheimer’s. Ninety-four percent said they would ask their primary-care physician about AD and nearly 50 percent said it was “God’s Will” if they developed the disease. More than half of the participants, 57.6 percent, were unaware that African Americans were more likely to develop AD.

The data also showed that African Americans’ perceptions of AD depended on two culturally influenced characteristics – present oriented or future-time oriented; and whether they considered themselves highly religious.

People who scored high on present-time orientation – those who tended to live in the moment – were less likely than future-oriented people to believe they could control their health. People who were present-oriented also had less knowledge of AD.

On the other hand, participants who reported being highly religious tended to have a greater sense of control over their health than those who were not so religious. One explanation might be that greater faith and religious practices reinforce a sense of empowerment or self-efficacy.

These data highlight the potential impact of culturally influenced views on health behaviors, particularly when it comes to attitudes around memory loss and AD. Previous reports have suggested that disparities in AD risk and outcomes between African Americans and Caucasians could be due to predisposing medical, genetic and environmental factors such as fewer years of education, lower quality of education and early life nutritional deficiencies. These findings suggest that culturally influenced views might also play a role. By understanding cultural factors related to attitudes about aging and health, healthcare providers can more effectively care for their patients.

Barry W. Rovner, MD

Multiple Sclerosis

Finding new and better ways to treat multiple sclerosis (MS) is critical, given the prevalence and gravity of the disease, which affects more than 400,000 individuals in the United States and more than two million worldwide.

Jefferson’s MS program has a dual focus: to provide state-of-the-art patient care and to conduct research that will advance the understanding of MS, which, hopefully will lead to the development of better therapies.

jeffersoN comPreheNsiVe muLTiPLe scLerosis ceNTer

Jefferson’s Comprehensive Multiple Sclerosis Center is a recognized leader in diagnosing and treating MS. The diagnosis of MS can be difficult, mainly because the first clinical symptoms, such as weakness, vision loss or numbness, may be of short duration or mimic another disorder. It is important for patients to get a timely evaluation and to begin treatment in order to minimize the potential for neurodegeneration. Patients are assessed using the latest brain imaging and other technologies, combined with a thorough clinical evaluation. Neurologists at the Center – which is directed by Thomas P. Leist, MD, PhD, Associate

Professor of Neurology, Jefferson Medical College of Thomas Jefferson University – work closely with other specialists, including physiatrists, neuro-ophthalmologists, urologists, psychiatrists and the patient’s own primary care physician, to ensure a comprehensive treatment plan designed to evolve with the changing needs of the patient. Patients have access to the latest therapies and can participate in clinical trials to evaluate new drug therapies.

jeffersoN NeuroimmuNoLogy AND muLTiPLe scLerosis reseArch LABorAToryThere is still much to be learned about MS. The Jefferson Neuroimmunology and Multiple Sclerosis Research Laboratory is dedicated to scientific investigations, and those findings have the potential of being translated into new therapies that will slow or even halt disease progression. The laboratory, which is funded by the National Institutes of Health (NIH) and the National Multiple Sclerosis Society, is directed by A.M. Rostami, MD, PhD, Professor, Department of Neurology, Jefferson Medical College of Thomas Jefferson University and an internationally recognized expert in neuroimmunology and MS.


Jefferson’s Comprehensive Multiple Sclerosis Center is a recognized leader

in diagnosing and treating MS.


The laboratory also includes the NIH-funded Jefferson Autoimmunity Center of Excellence, whose primary goal is to better understand autoimmune diseases, including MS. Researchers are studying the involvement of immune-related cells in the peripheral immune system and the central nervous system (CNS) and identifying potential new targets for MS therapy. Their findings have been published in mulitple journals, including Nature Immunology, The Journal of Immunology and the Journal of Neurological Sciences.

Some key areas of research are:

• The role of cytokines – specifically the IL-12, IL-17 and IL-23 axis – in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), which is the animal model of MS, and human MS. The goal of this study is to shed light on the process of inflammatory demyelination in MS.

• The effect of the Bowman-Birk protease inhibitor on the course of EAE. This research could lead to the development of a novel oral therapy for MS.

• Understanding the role of Th17 cells in CNS inflammatory demyelination. This newly discovered T-cell subset has been shown by the Jefferson laboratory and others to play an important role in the immunopathogenesis of MS and its experimental models.

• The role of immunological tolerance in the suppression of inflammation in the CNS. The laboratory uses myelin antigens to suppress disease in experimental models of MS. Researchers are striving to understand the mechanisms of immunological tolerance, in hopes of applying this approach to the treatment of MS and other autoimmune diseases.

Multiple Sclerosis

46

Patient A: FLAIR images or patient with MS (left sagittal image, right axial image). Patient B: Gadolinium enhanced T1 weighted image of patient with disease activity.

A A

B B


A.M. Rostami, MD, PhD

NeurocriticalCare

Jefferson is a leader in both clinical care and research involving patients with life-threatening conditions of the nervous system, including stroke, brain and spinal cord injuries and ruptured aneurysm.

Patients admitted to JHN’s dedicated 40-bed Neurointensive Care Unit benefit from the combined expertise of neurointensivists, neurologists, neurosurgeons, radiologists and others trained to focus both on the acute neurological issue and other coexisting medical conditions that can impact a patient’s recovery. The unit utilizes the latest technology for diagnosing and managing patients, including invasive and semi-invasive cardiac output measurements, conventional and transesophageal echocardiography for hemodynamic assessment, multimodality neuromonitoring with continuous EEG, brain tissue oxygenation, cerebral blood flow (near-infrared spectroscopy) and transcranial Doppler and advanced temperature modulation with both surface and endovascular cooling.

Jefferson researchers are active contributors to research on the most pressing issues in neurocritical care, including pulmonary complications, sepsis and gyclemic control to reduce the risk of infection.

Here are summaries of some of that research:

effecT of hyPeroxiA oN iN-hosPiTAL morTALiTy AfTer BrAiN iNjuryThe classic paradox with oxygen supplementation is that while oxygen is necessary to maintain energy metabolism, excessive oxygen may potentiate primary or secondary brain injury by triggering free radical production, activation of apoptotic cascades, and facilitating organ-specific hypoperfusion.

Because tissue hypoxia plays a critical role in primary and secondary neuronal damage, normobaric hyperoxia is generally thought to be a logical stroke or traumatic brain injury (TBI) therapy despite controversial results of animal models of ischemic and hemorrhagic stroke and TBI, and other clinical studies. Animal data from stroke models demonstrate that hyperoxia is associated with increased oxidative stress and overall mortality. But clinical and observational data in critically ill stroke and TBI populations are lacking.

Based on that paucity of data, researchers at Jefferson, led by Fred Rincon, MD, Assistant


Jefferson researchers are active contributors to research on the most pressing issues in

neurocritical care.Care


Professor of Neurology and Neurological Surgery, and Jack Jallo, MD, PhD, Professor and Vice Chair for Academic Services, Jefferson Medical College of Thomas Jefferson University, reviewed multicentered hospital data. Two studies – which included more than 4,000 patients with TBI, acute ischemic stroke (AIS), subarachnoid hemorrhage (SAH), and intracerebral hemorrhage (ICH) who had arterial blood gases (ABG) within 24 hours of admission to the ICU at 84 U.S. ICUs between 2003-2008 – were accepted for publication in Critical Care Medicine and the Journal of Neurosurgery, Neurology and Psychiatry. The studies found that in ventilated stroke and TBI patients admitted to the ICU, arterial hyperoxia was independently associated with in-hospital death as compared to either normoxia or hypoxia. These data underscore the need for studies of controlled reoxygenation in ventilated critically ill stroke populations. Additionally, the authors concluded that in the absence of results from clinical trials, unnecessary oxygen delivery should be avoided in ventilated stroke or TBI patients.

imPAcT of LuNg comPLicATioNs AfTer TrAumATic BrAiN iNjuryAcute Respiratory Distress Syndrome (ARDS) and the less-severe Acute Lung Injury (ALI) are common in-hospital complications after admission for TBI. The burden of ARDS/ALI on overall patient morbidity and mortality is significant, causing an estimated in-patient mortality of 39 percent and an economic toll for society of three million hospital days per year. But the extent to which ARDS/ALI specifically impacts TBI patients has been less clear. Gaining a better understanding of the reach of ARD/ALI could lead to improvements in treatment for TBI patients.

Drs. Rincon and Jallo reviewed nationwide hospital data (Nationwide Inpatient Sample) for TBI patients from 1988 to 2008 to determine the epidemiology of ARDS/ALI, the prevalence of risk factors and the impact on in-hospital mortality. There were 987,305 admissions for TBI during the two decades.

The analysis found that:

• Just over 21 percent of TBI patients developed ARDS/ALI.

• The prevalence of ARDS/ALI after TBI increased from 2 percent in 1988 to 22 percent in 2008 – an increase that could be explained at least in part by better diagnosing and economic incentives related to coding and billing.

• ARDS/ALI was more prevalent in younger patients, males, Caucasians and patients with comorbidities such as congestive heart failure, hypertension, chronic pulmonary disease and sepsis.

• Overall mortality after TBI decreased from 13 percent in 1988 to nine percent in 2008.

• The complication of ARDS/ALI increased mortality three-fold, though ARDS/ALI-related mortality after TBI decreased from 33 percent to 28 percent over the 20-year period.

• The risk for mortality after TBI was also higher in older patients, males, Caucasians and patients with comorbidities such as cancer, kidney disease and sepsis.

The findings, published in Neurosurgery, should help inform patient-care initiatives and research. While mortality from TBI is decreasing, the increasing prevalence of ARDS/ALI among TBI patients suggests that caring for survivors of ARDS/ALI will be an important public health challenge in the years ahead.

hosPiTAL morTALiTy for sePTic PATieNTs WiTh sTATus ePiLePTicusSepsis is an important cause of morbidity and mortality in patients admitted to hospitals and ICUs nationwide. One potential result of sepsis is nonconvulsive status epilepticus (SE), which can be deadly or associated with long-term morbidity due to secondary brain damage. Although continuous electrophysiological monitoring with EEG can detect cortical dysfunction, limitations in technology and available clinical expertise in interpreting results may limit the recognition of SE.

To determine the scope of SE among septic patients, a Jefferson team headed by Jacqueline Urtecho, MD, Assistant Professor of Neurology, and Dr. Rincon analyzed data for 1988 to 2008 from the Nationwide Inpatient Sample. There were 7,669,125 admissions of patients 18 or older with a primary diagnosis of sepsis.

Among the findings:

• A total of 7,688 septic patients, (0.1 percent), had a concomitant diagnosis of SE.

• The prevalence of SE among septic patients increased from 0.1 percent in 1988 to 0.2 percent in 2008.

• SE was more common among younger patients, females, African Americans, rural hospital admissions and in patients with organ dysfunction.

Neurocritical Care

50


• The impact of SE on mortality among septic patients is large, even though mortality in SE during sepsis decreased from 43 percent to 28 percent during the two decades.

• Overall mortality among patients with a primary sepsis admission decreased from 20 percent to 18 percent from 1998 to 2008.

• Mortality was associated with SE, older age, African American or Native American/Eskimo race, organ dysfunction and admission to a rural hospital.

This study, accepted for publication by Critical Care Medicine, underscores the fact that SE plays a large role in sepsis-related mortality. The 0.1 percent rate of SE among septic patients identified in this study is significantly lower than rates reported in single academic-center studies. It’s likely that there is an under-recognition of SE in sepsis.

More aggressive electrophysiological monitoring and a high level of suspicion for the diagnosis of sepsis may be indicated in patients with CNS organ dysfunction during sepsis. Stepped-up recognition and treatment of SE will save lives and reduce morbidity.

NATioNAL TreNDs iN morTALiTy iN NoN-TrAumATic suBArAchNoiD hemorrhAgeSubarachnoid hemorrhage (SAH) causes five to 10 percent of strokes annually in the U.S. Population-based studies indicate that the incidence varies according to the geographic region. The outcome depends on several factors, including age, severity,

timing of treatment, intensive-care unit management and the incidence of medical complication. Updated long-term nationwide studies regarding the epidemiology and trends in overall in-hospital mortality after SAH in the U.S. are lacking.

Epidemiological studies using large databases are key to the delineation of trends, impact of treatments and allocation of healthcare resources and research budgets. Jefferson researchers led by Dr. Rincon reviewed data from the National Hospital Discharge Survey on more than one billion hospitalizations in the U.S. over a 30-year period. The study investigated the temporal trends in admissions of SAH using a representative sample of all non-federal hospitals with specific attention to admission rates, dispositions and in-hospital mortality.

The study, published in Neurosurgery, found that the rate of hospital admission for aneurysmal SAH remained stable from 1979 to 2008. During that same period, in-hospital mortality fell from 30 percent to 20 percent. In-hospital mortality rates were lower in large referral hospitals (26 percent) as compared to small (39 percent) and medium-sized hospitals (36 percent). Dr. Rincon also found an increase in discharge to long-term care facilities (nine percent to 16.3 percent) and a decrease in hospital length of stay (from 17 days to 11 days) over this period.

A better understanding of trends related to SAH should help inform decisions about how best to organize and deliver care for stroke. The hope is that advances in neurosurgical and neurocritical care will continue to make SAH less of a lethal condition.

Jack Jallo, MD, PhD


ResearchActive

Grant Title Primary Investigator(s)

ACE: Philadelphia Center of Excellence, Project 3

ACE: Philadelphia Center of Excellence (Core A: Admin Core)

The Role of IL-27 in I.V. Tolerance in EAE

The Role of the TH17 Cells in the Pathogenesis of EAE

The Role of Dendritic Cells in Intravenous Tolerance

Anti-Inflammatory Mechanisms of Soybean-Derived Bowman-Birk Protease Inhibitor

Mechanisms of B Cell Responses in Autoimmune Disease: A09-TJU

Confronting Unequal Eye Care in Pennsylvania

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy and Safety Trial of Bapineuzumab (AAB-001, ELN115727) in Subjects with Mild to Moderate Alzheimer’s Disease Who Are Apolipoprotein E 4 Carriers

A Phase 3 Extension, Multicenter, Double-Blind, Long-Term Safety and Tolerability Treatment Trial of Bapineuzumab (AAB-001, ELN115727) in Subjects with Alzheimer’s Disease Who Participated in Study ELN115727-301 or in Study ELN115727-302

A Phase 3 Extension, Multicenter, Long-Term, Safety and Tolerability Trial of Bapineuzumab (AAB-001, ELN115727) in Subjects with Alzheimer’s Disease Who Are Apolipoprotein E4 Carriers and Participated in Study 3133K1-3001-WW

Low Vision Depression Prevention Trial for Age-Related Macular Degeneration

Preventing Cognitive Decline in African Americans with Mild Cognitive Impairment

The Role of GM-CSF in the Encephalitiogenicity of Th17 Cells

Abdolmohamad Rostami, MD, PhD







Barry W. Rovner, MD

Barry W. Rovner, MD

Barry W. Rovner, MD

Barry W. Rovner, MD

Barry W. Rovner, MD

Barry W. Rovner, MD

Bogoljub Ciric, MD

Projects



Tc17 Cells in Autoimmune Inflammation of the CNS

GM-CSF in CD8+ T Cell-Mediated EAE

ACE: Philadelphia Center of Excellence (Core B: Flow Cytometry/Cell Sorting)

RNS System Long-Term Treatment Clinical Investigation

A Phase 3, 12-Week, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Preladenant in Subjects with Moderate to Severe Parkinson’s Disease

Intracerebroventricular and Intravenous Injections of AAVrh10-cGALC into the Dog Model of Krabbe Disease

From Photons to Human Health: Exploring the Power of Light

Team Leader: Human Factors and Performance Team

Optimizing Light Spectrum for Long Duration Space Flight

Subject Matter Expertise for Lighting in Space and Analog Environments

Role of IL-12/IL-23 in the Differentiation of Microglia into Dendritic Cells

Remyelination by LINGO-1-Fc Producing Neural Stem Cells

Enhanced Neural Stem Cell Chemoxis Toward CNS Inflammatory Foci in EAE

NSCs Produce a Triply Effective Cocktail in the CNS for MS/EAE Therapy

Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial

A Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Intranasal Midazolam in the Outpatient Treatment of Subjects with Seizure Clusters

An Open-Label Safety Study of USL261 in the Outpatient Treatment of Subjects with Seizure Clusters

Mechanism of Action of Occipital Nerve Stimulation on Trigeminal Sensitization

A Blinded Study of the Effects of a CGRP Antagonist and TRPA1 Antagonist in 2 Models of Migraine in Rat

Occipital Nerve Stimulation in a Rat Model of Spontaneous Chronic Allodynia and Headache

Progression of Headache Associated with Recurrent Dural Inflammation (CFDA# 93.853)

Nervous System Mechanisms of Dry Eye

Bogoljub Ciric, MD

Bogoljub Ciric, MD

Bogoljub Ciric, MD

Christopher T. Skidmore, MD

Daniel E. Kremens, MD David A. Wenger, MD

George Brainard, MD

George Brainard, MD

George Brainard, MD

George Brainard, MD

Guang-Xian Zhang, MD




Maria Carissa Pineda, MD

Maromi Nei, MD

Maromi Nei, MD

Michael Oshinsky, MD







An Open-Label, Multicenter, Follow-Up Trial to Evaluate the Long-Term Safety and Efficacy of Brivaracetam Used as Adjunctive Treatment at a Flexible Dose up to a Maximum of 100mg/day in Subjects Aged 16 Years or Older Suffering from Partial Onset Seizures

SANTE: Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy

A Historical-Controlled, Multicenter, Double-Blind, Randomized Trial to Assess the Efficacy and Safety of Conversion to Lacosamide 400mg/day Monotherapy in Subjects with Partial-Onset Seizures

A Multicenter, Open-Label Extension Trial to Assess the Long-Term Use of Lacosamide (LCM) Monotherapy and Adjunctive Therapy in Subjects with Partial-Onset Seizures (with and without Secondary Generalization) Who Were Enrolled in the Conversion to Monotherapy Trial. Schwarz 904

A 14-Month, Open-Label, Extension, Phase of the Double-Blind, Placebo-Controlled, Dose-Escalation, Parallel-Group Studies to Evaluate the Efficacy and Safety of E2007 (perampanel) Given as Adjunctive Therapy in Subjects with Refractory Partial Seizures

Double-Blind, Randomized, Historical Control Study of the Safety and Efficacy of Eslicarbazepine Acetate Monotherapy in Subjects with Partial Epilepsy Unresponsive to Current Antiepoleptic Drugs

Long-Term Eslicarbazepine Acetate Extension Study

Efficacy and Safety of Eslicarbazepine Acetate (Bia 2-093) as Adjunctive Therapy for Refractory Partial Seizures in a Double- Blind, Radomized, Placebo-Controlled, Parallel-Group, Multicenter Clinical Trial

An Open-Label, Mutlicenter, Follow-Up Study to Evaluate the Long-Term Safety and Efficacy of Brivaracetam Used as Adjunctive Treatment in Subjects Aged 16 Years or Older with Partial Onset Seizures

A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Parallel-Group Study to Evaluate the Efficacy and Safety of Brivarecetam in Subjects (>16 to 80 years old) with Partial Onset Seizures

A Pilot Study to Evaluate MR-Guided Laser Ablation of Focal Lesions in Patients with Medically Refractory Epilepsy

An Open-Label Study to Determine the Pharmacokinetics of a Single Dose of DZNS in Adult Epileptic Patients Experiencing a Seizure Episode for which Acute Treatment with a Benzodiazepine is Clinically Indicated

A Phase 2, Multicenter, Double-Blind, Andomized, Adjunctive Placebo-Controlled Trial to Evaluate the Efficacy and Safety of YKP3089 in Subjects with Treatment-Resistant Partial Onset Seizures
















A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Parallel-Group with an Open Label Extension Phase to Evaluate the Efficacy and Safety of Adjunctive Perampanel in Primary Generalized Tonic-Clonic Seizures

A Prospective, Open-Label Study of the Structure and Function of the Retina in Adult Patients with Refractory Complex Partial Seizures Treated with Vigabatrin (Sabril)

A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Study to Evaluate the Efficacy and Safety of VX-765 in Subjects with Treatment-Resistant Partial Epilespy

Associative Processes in Episodic Memory

A Multicenter Observational Study to Evaluate the Simplified-Stroke Rehabilitation Assessment of Movement Scale (S-STREAM) in Subjects within 24 Hours of Non-Hemorrhagic Stroke

The Effects of Antiepileptic Drugs on Serologic Indices of Vascular Risk

Diagnosing and Managing the Headache Patient – Staying Ahead of Headache Pain Management Challenges

Prospective Randomized Investigation to Evaluate Incidence of Headache Reduction in Subjects with Migraine and PFO Using the AMOLATZER PFO Occuluder Compared to Medical Management (PREMIUM Trial)

A Long-Term Follow-Up Study of the Management of Chronic Migraine Headaches with Peripheral Nerve Stimulation

A Double-Blind, Placebo-Controlled Pilot Study to Collect and Evaluate Data on the Use of Intravenous Ibuprofen in the Treatment of an Acute Migraine Attack

A Study to Evaluate the Safety and Efficacy of STOPAIN in the Treatment of a Single Migraine Attack

A Randomized, Double-Blind, Double-Dummy, Active-Controlled, Cross-Over Study Evaluating the Efficacy and Safety of 20 mg. Sumatriptan Powder Delivered Intranasally with the Bidirectional Device Compared with 100 mg. Sumatriptan Tablets in Adults with Acute Migraine with or without Aura (COMPASS Trial)

Noninvasive Neurostimulation of the Vagus Nerve with the GammaCore Device for the Prevention of Chronic Migraine

Noninvasive Neurostimulation of the Vagus Nerve with the GammaCore Device for the Treatment of Chronic Cluster Headache

Multicenter, Double-Blind, Placebo-Controlled Study of Ethosuximide in the Prevention of Episodic Migraine Comparing Number of Migraine Headache Days per 4 Weeks at End of Study with Baseline

Examining the Relationship between MS Progression and Driving




Michael R. Sperling, MD Rodney D. Bell, MD

Scott Mintzer, MD

Stephanie Nahas-Geiger, MD









Thomas P. Leist, MD, PhD



An International, Multicenter, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Teriflunomide 7 mg Once Daily and 14 mg Once Daily Versus Placebo in Patients with Relapsing Multiple Sclerosis Using Interferon-Beta 1a (Rebif) as an Open-Label Rater-Blind Calibrator

JCV Antibody Program in Patients with Relapsing Multiple Sclerosis Receiving or Considering Treatment with Tysabri: STRATIFY-2

A Placebo-Controlled Randomized Withdrawal Evaluation of the Efficacy and Safety of Baclofen ER Capsules (GRS) in Subjects with Spasticity Due to Multiple Sclerosis

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Study to Investigate the MRI Efficacy and Safety of Six Months Administration of Ofatumumab in Subjects with Relapsing-Remitting Multiple Sclerosis (RRMS). OMS112831

Validation of the Fatigue Symptoms and Impacts Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS)

Prospective, Observational Trial Examining Xeomin for Cervical Dystonia of Blepharospasm in the United States

CD Probe-Cervical Dystonia-Patient Registry for Observation of BOTOX Efficacy

Parkinson Council Service Grant 2013

Neural Basis of Generalized Quantifiers

A Single-Center, Open-Label, Pilot Study Examining the Use of Duloxetine in the Prevention of Episodic Migraine (Protocol #F1J-MC-1011)

An Open-Label, Multicenter Study of the Long-Term Efficacy, Safety and Tolerability of BOTOX® (OnabotulinumtoxinA) for the Prophylaxis of Headaches in Adult Patients with Chronic Migraine (the COMPEL Study)

A Retrospective Review of Patients with Type III Odontoid Fracture and Treatment with Posterior Fusion

A Retrospecitve Review of Patients with Carotid Blowout Syndrome Treated with Endovascular Therapy with Focus on Clinical Outcome

Geometric Study of the Ophthalmic Artery

Decision-Making in the Treatment of Small Aneurysms

Use of Temporary Balloon Occlusion Prior to Permanent Balloon Occlusion as Predictor for Stroke, Institutional Experience and Review of the Literature

Thrombolysis of the Posterior Circulation: Institutional Experience and Review of the Literature

Vertebral Artery Occlusion Sequelae






Tsao-Wei Liang, MD

Tsao-Wei Liang, MD

Tsao-Wei Liang, MD

Tsao-Wei Liang, MD

William B. Young, MD

William B. Young, MD

James S. Harrop, MD

Pascal Jabbour, MD

Pascal Jabbour, MD

Aaron S. Dumont, MD



James S. Harrop, MD



Retrospective Review of Acute Ischemic Stroke Management

A Retrospective Review of Packing Density in Endovascular Treatment of Aneurysms

Retrospective Study of Epidemiological, Morphological and Laboratory Factors Associated with Intracranial Aneurysms and Subsequently Leading to Their Rupture and SAH

Clinical Validation of the ARDS Diagnostic Criteria from Reynolds and Thomsen by Retrospective Case-Control Study

Retrospective Review of Impedance Data and Seizure Frequency on Patients Who Were Enrolled in the Neuropace Study

Endovascular Management of Basilar Artery Aneurysms

Efficacy Evaluation of Intraoperative Cerebral Angiography

Posteroinferior Cerebellar Artery (PICA) Aneurysms: Comparison of Surgical and Endovascular Treatment

A Retrospective Review on Patients with Occipital Cervical Injury with Focus on Clinical Outcome of Radiographic Measurements

Safety and Pharmacokinetics of Riluzole in Patients with Traumatic Acute Spinal Cord Injury

A Radiographic and Clinical Study Evaluating a Novel Allogenic Cancellous, Bone Matrix Containing Viable Stem Cells (Trinity Evolution™ Viable Cryopreserved Cellular Bone Matrix) in Patients Undergoing Anterior Cervical Discectomy and Fusion

A Double-Blind, Randomized, Placebo-Controlled, Parallel Group, Multicenter Phase 3 Pivotal Study to Assess the Safety and Efficacy of 1mg/kg/day Intravenous DP-b99 Over 4 Consecutive Days Versus Placebo when Initiated within Nine Hours of Acute Ischemic Stroke Onset

EXO-SPINE A Prospective, Multicenter, Double-Blind, Randomized, Placebo Controlled Pivotal Study of Ultrasound Therapy as Adjunctive Therapy for Increasing Posterolateral Fusion Success Following Single Level Posterior Instrumented Lumbar Surgery

Spinal Cord Stimulation with Precision® SCS System Versus Reoperation for Failed Back Surgery Syndrome

A Phase 2 Study of Verubulin (MPC-6827) with Radiation Therapy and Temozolomide in Subjects Newly Diagnosed with Glioblastoma Multiforme

Thromectomy Revascularization of Large Vessel Occulsions in Acute Ischemic Stroke

A Phase IV, Multicenter, Observational Study Evaluating Hemodynamic Outcomes with BREVIBLOC Premixed Injection (Esmolol Hydrochloride) in Patients with Supraventricular Tachycardia/Atrial Fibrillation in Medial and Neurological Intensive Care Units in the United States

Pascal Jabbour, MD

Pascal Jabbour, MD

Jack Jallo, MD, PhD

Fred Rincon, MD




Aaron S. Dumont, MD


James S. Harrop, MD



James S. Harrop, MD


Lyndon Kim, MD

Robert H. Rosenwasser, MD

Fred Rincon, MD



Multicenter, Prospective, Randomized, Controlled Clinical Trial to Demonstrate Non-Inferiority of the Senza™ Spinal Cord Stimulation (SCS) System in the Treatment of Chronic Pain as Compared to Commercially Available SCS Devices

Surgical Treatment of Pituitary Tumor-Transition from Open to Endoscopic Approach

Overall Experience of Pituitary Tumor Patients at Thomas Jefferson University

Growth of the Cranial Base Program-Otolaryngology/ Neurosurgery Experience

The Use of Fractionated Stereotactic Radiotherapy for the Treatment of Optic Nerve Sheath Meningiomas: A Retrospective Medical Record Review

Incidence and Outcome of Patients with Spinal Fracture and Ankylosing Spondylitis

Magnetic Resonance Analysis of Postsurgical Temporal Lobectomy and Correlation to Seizure Outcome

Endoscopic Resection of Clival Chordoma: A Case Series

A Retrospective Chart Review of Cases Done at Thomas Jefferson University: The Failure Rate in Surgical Treatment with Fixation of C1-C2 Fracture

A Retrospective Chart Review of TJUH Patients who Obtained Epidural Injections: Looking at the Post Procedural Complications

Prospective Database of Primary Spinal Neoplasms

A Comprehensive Retrospective Review of Anterior Corpus Callosotomy Outcomes at Thomas Jefferson University Hospitals

A Study of Seizure Outcomes in Patients Status Post Temporal Lobectomy with Secondarily Generalized Seizures Comparing Patients With and Without Intracranial Implants

A Retrospective Review of Regional Incidence of Spinal Infection and Timing of Post-OP IV Antibiotics

Analysis of AVM Treatment and Complications

A Retrospective Chart Review of Stent Assisted Coiling and Coil Embolization on Patients Who Have Had Any Type of Aneurysm

A Retrospective Chart Review Studying Complications in Patients Who Have Had a Decompressive Craniectomy

Retrospective and Prospective Molecular Analyses of Frozen Giloma Tissues from Established Brain Tumor Bank

Retrospective Review on Patients Who Had Occipital and Supraorbital Nerve Stimulator for a Variety of Headache Disorders


James J. Evans, MD

James J. Evans, MD

James J. Evans, MD




James J. Evans, MD

James S. Harrop, MD

James S. Harrop, MD

James S. Harrop, MD



James S. Harrop, MD

Pascal Jabbour, MD

Pascal Jabbour, MD

Jack Jallo, MD, PhD





Long-Term Angiographic Follow-Up of Cerebral Aneurysms Treated by Surgical Clipping Versus Endovascular Coiling

A Database of Patients Undergoing Endoscopic Skullbase Surgery at Thomas Jefferson University Hospital

Retrospective Review of Patients Receiving Pipeline Embolization Device – Cost Analysis of Pipeline Embolization Device Versus Coils

Pan Spinal Abscesses, Diagnosis, Management and Operative Experience at Thomas Jefferson University Hospital

Impact of Status Epileptics on Mortality after Cardiac Arrest in the United States

The Yield of Repeat Cerebral Angiograms in Angiogram-Negative Subarachnoid Hemorrhages

Arteriovenous Malformation, Treatment and Demographics

Endovascular Intervention of Stroke in the Elderly

Early Predictors for Tracheostomy in Subarachnoid Hemorrhage


James J. Evans, MD


James S. Harrop, MD

Fred Rincon, MD




Matthew Vibbert, MD



A Clinical Registry of Patients Screened for Neurological Surgery Clinical Trials

A Clinical Registry of Patients Receiving Thermic and Hypothermic Management

Database of Neurovascular Diseases, Treatments, and Outcomes

Endovascular Deconstruction of Carotid or Vertebral Artery with a Combination of Onyx and Coils

Cost Analysis of Variable Dural Repair Techniques Used in Endoscopic Transphenoidal Adenohypophysectomy

Incidence of VP Shunt Infection Following Treated Ventriculitis

Balloon-Assisted and Stent-Assisted Coiling: Comparison of Angiographic Outcomes

Retrospective Review of Patients with Ventriculus Terminalis Lesions

Outcome Evaluation of Intradural Spinal Cord Tumors

Deep Vein Thrombosis and Pulmonary Embolism in the Neurosurgical Population

Long-Term Follow-up of Wingspan Stents in Preventing Acute Stroke

Retrospective Review of Spine Tumor Embolization

Endovascular Intervention for Acute Stroke Patients Less than 45 Years Old

Retrospective Review of Outcomes and Complications of Spinal Cord Stimulator Patients – A Clinical Chart Review

Analysis of Long-Axis Cannulation of the Hippocampus Using an Occipital Burr Hole in Patients with Epilepsy

Surgical Clipping Versus Endovascular Therapy for Posterior Communicating Aneurysms Presenting with a Third Nerve Palsy

Incidence of Aneurysms in Patients Presenting with CT Negative for SAH and LP Positive for SAH

Comparative Analysis of Morbidity and Mortality in Subarachnoid Hemorrhage of Endovascular Embolization vs. Microsurgical Clipping

Results from Intravenous t-PA Administration in Community Hospitals via Robotic Medicine

The Safety and Efficacy of Radiosurgery for Cerebral Arteriovenous Malformations

The Safety and Efficacy of Radiosurgery for Cerebral Arteriovenous Malformations

Clinical Practice Survey: Are You Using Pharmacological Agents to Improve Wakefulness in Patients who Suffer from Severe Brain Injury



Aaron S. Dumont, MD

Aaron S. Dumont, MD

James J. Evans, MD

Christopher Farrell, MD


James S. Harrop, MD

James S. Harrop, MD

James S. Harrop, MD

Pascal Jabbour, MD

Pascal Jabbour, MD

Pascal Jabbour, MD








Matthew Vibbert, MD

Muhammad Kamran Athar, MD



Diagnostic Accuracy of Procalcitonin in Differentiating Sepsis from Noninfectious SIRS in Adult Patients with Brain Injury

Database of Neurological Diseases, Treatments, and Outcomes

Retrospective and Prospective Review of the Departmental Vascular Database to Determine the State of Platelet Inhibition on Patients Who Are Admitted with Hemorrhagic Complications in Presence of Clopidrogel Prior and After They Receive Platelet Transfusion

Validation of Bedside Critical Care Ultrasound Performed by Neurointensivists

Hemodynamic Assessment and Management of Neurologically Injured Critically III Patients Using Transesophageal Echocardiography

Endonasal Surgery of the Upper Cervical Spine: A Morphometric Analysis

Prospective Study of Glioma Patients

Neurophysiological Monitoring During Craniotomy for Aneurysm Clipping

Suboccipital Craniotomy Versus Craniectomy: Comparison of Outcomes for Posterior Fossa Surgery

Epidemiological Trends of Adult Respiratory Distress Syndrome (ARDS) after Traumatic Brain Injury from National Inpatient Sample

Evaluation of Temperature Distribution after Acute Brain Injury: The Relationship between Hyperthermia and Clinical Outcomes

Association between Hyperthermia, Functional Outcome, and Hematoma Growth after Intracerebral Hemorrhage (ICH)

Neuroform and Enterprise In-Stent Stenosis: Incidence and Management

Contribution of Diffusion-Weighted Imaging in Determination of Post-Stroke Intra-Arterial Thrombolysis

Humanitarian Use Device: Neuroform Microdelievery Stent

The Wingspan Stent System and Gateway PTA Balloon Catheter: A Humanitarian Use Device

Cordis Enterprise Vascular Reconstruction Device (VRD) and Delivery System (DS): A Humanitarian Device (HUD)

Onyx Liquid Embolic Systems for Intracranial Aneurysms: Humanitarian Use Device

Carotid Revascularization Endarterectomy Versus Stent Trial

A Prospective National Study to Molecularly and Genetically Characterize Human Gliomas: The Glioma Molecular Diagnostic Initiative

Muhammad Kamran Athar, MD



Fred Rincon, MD

Jacqueline S. Urtecho, MD

James J. Evans, MD



Yaron Moshel, MD, PhD

Fred Rincon, MD

Fred Rincon, MD

Fred Rincon, MD











An Assessment of P-15 Bone Putty in Anterior Cervical Fusion with Instrumentation Investigational Plan

Assessment of Intracranial Aneurysm Shape as an Indicator of Rupture Risk

Minimally Invasive Surgery Plus rt-PA for ICH (Intracerebral Hemorrhage) Evacuation: Intraoperative Stereotactic CT Guided Endoscopic Surgery

North American Clinical Trials Network for Treatment of Spinal Cord Injury

Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis

Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III

Gaining Efficacy Long Term: HydroSoft and Emerging, New, Embolic Coil

Prospective Study of Outcome after Surgery for Spinal Metastases – GSTSG Database

Intra-Arterial (Ophthalmic Artery) Chemotherapy for Retinoblastoma

Progesterone for the Treatment of Traumatic Brain Injury

Stenting and Angioplasty with Protection in Patients at High Risk for Endaterectomy

Axium™ MicroFX™ for Endovascular Repair of IntraCranial Aneurysm: A MultiCenter, Prospective Observational Registry

A Randomized, Controlled, Open-Label, Parallel-Group, Multicenter Study to Compare the Effect of Intrathecal Baclofen Therapy (TB Therapy) Versus Best Medical Treatment (BMT) on Severe Spasticity in Post Stroke Patients after 6 Months Active Treatment

A Feasibility Study of the MicroVention, Inc. Neurovascular Self-Expanding Retrievable Stent System in the Treatment of Wide-Necked Intracranial Artery Aneurysms

Phase I Study in Humans Evaluating the Safety of Rectus Sheath Implantation of Diffusion Chambers Encapsulating Autologous Malignant Glioma Cells Treated with Insulin Like Growth Factor Receptor-1 Antisense Oligodeoxynucleotide (IGF-1R/AS ODN, Antisense) in 12 Patients with Recurrent Malignant Glioma

Aneurysm Study of the Pipeline Embolization Device in an Observational Registry – PED002

Randomized Clinical Trial of the Safety and Efficacy of Brain Tissue Oxygen (pBtO2) Monitoring in the Management of Severe Traumatic Brain Injury

James Harrop, MD


Jack Jallo, MD

James S. Harrop, MD


Jack Jallo, MD, PhD

Pascal Jabbour, MD

James S. Harrop, MD

Wills Eye, Robert H. Rosenwasser, MD, and Pascal Jabbour, MD

Jack Jallo, MD, PhD


Aaron S. Dumont, MD


Pascal Jabbour, MD


Pascal Jabbour, MD

Jack Jallo, MD, PhD



Brain Compliance Determination of Clinical Relevance of Phase Differences between Intracranial Pressure and Arterial Pressure Waveforms as a Measure of Cerebral Compliance

Brain Injury Patients and Enteral Nutrition: How Much Are They Receiving and How Does This Impact Outcome?

New Generation Hydrogel Endovascular Aneurysm Treatment Trial

International Retrospective Study of Pipeline Embolization Device

Evaluation of Presidio and Cerecyte Coils in Large and Giant Aneurysms

Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial

PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma without MGMT Methylation: A Randomized Phase II Study: BrUOG 244

Occipital Nerve Stimulation (ONS) for Migraine

Packing Density in Smaller Aneurysms: How Significant?

Safety and Tolerability of a Protocol of Targeted Temperature Management after Intracerebral Hemorrhage

A Multicenter Observational Study to Evaluate the Simplified-Stroke Rehabilitation Assessment of Movement (S-STREAM) Scale in Subjects within 24 Hours of a Nonhemorrhagic Ischemic Stroke

Stoke Hyperglycemia Insulin Network Effort Trial

A Randomized, Double-Blind, Controlled Phase IIB Study of the Safety and Efficacy of ICT-107 in Newly Diagnosed Patients with Glioblastoma Multiforme Following Resection and Chemoradiation

A Randomized, Concurrent Controlled Trial to Assess the Safety and Effectiveness of the Separator 3D as a Component of the Penumbra System in the Revascularization of Large Vessel Occlusion in Acute Ischemic Stroke

A Phase III Clinical Trial Evaluating DCVax®-L, Autologous Dendritic Cells Pulsed with Tumor Lysate Antigen for the Treatment of Glioblastoma Multiforme

Neurocognitive and fMRI Activation Changes Observed after Whole Brain Radiation Versus Radiosurgery for Cerebral Metastases

The Penumbra Liberty Trial: Safety and Effectiveness in the Treatment of Wide-Neck Intracranial Aneurysms

The Surpass Intracranial Aneurysm Embolization System Pivotal Trial to Treat Large or Giant Wide Neck Aneurysms

Ashwini D. Sharan, MD (Chenyuan Wu)

Fred Rincon, MD (Stephanie Dobak)

Pascal Jabbour, MD

Pascal Jabbour, MD



Lyndon Kim, MD



Fred Rincon, MD

Rodney D. Bell, MD


Lyndon Kim, MD

Aaron S. Dumont, MD

Lyndon Kim, MD

Yaron Moshel, MD , PhD

Aaron S. Dumont, MD

Pascal Jabbour, MD


New research projects are continually conceived and added to this list.


Pivotal Study: A Prospective, Randomized, Controlled Study to Evaluate the Safety and Efficacy of Subcutaneous Nerve Stimulation

Prospective Phase II Trial Assessing the Efficacy of Low-Dose Fractionated Stereotactic Radiotherapy for the Treatment of Patients with Acoustic Neuromas and Serviceable Hearing

A Double-Blind, Placebo-Controlled Study of AC105 in Patients with Acute Traumatic Spinal Cord Injury

A Multicenter, Randomized, Placebo-Controlled, Double-Blinded, Trial of Efficacy and Safety of Riluzole in Acute Spinal Cord Injury

Large Aneurysm Randomized Trial: Flow Diversion versus Traditional GDC Based Endovascular Therapy

Pivotal Study of the MicroVention, Inc. Neurovascular Self-Expanding Retrievable Stent System LVISTM in the Treatment of Wide-Necked Intracranial Artery Aneurysms

Is a Lot of Oxygen Good for the Injured Brain?

A Phase III Randomized Multicenter Clinical Trial of High-Dose Human Albumin Therapy for Neuroprotection in Acute Ischemic Stroke

A Pilot Study of the Use of Hypertonic Saline in Patients with Subarachnoid Hemorrhage

High Dose Deferoxamine in Intracerebral Hemorrhage (Hi-Def in ICH) Trial



James S. Harrop, MD

James S. Harrop, MD

Pascal Jabbour, MD

Pascal Jabbour, MD

Fred Rincon, MD

Matthew Vibbert, MD

Matthew Vibbert, MD

Matthew Vibbert, MD

JG 13-0883 MC 12-05588

Department of Neurology

A.M. Rostami, MD, PhD, Chair

Division Directors

Cerebrovascular Neurocritical Care .......................... Rodney D. Bell, MD

Clinical Neuroimmunology/Multiple Sclerosis ........... Thomas P. Leist, MD, PhD

Epilepsy and Clinical Neurophysiology ..................... Michael R. Sperling, MD

Jefferson Headache Center ..................................... Stephen D. Silberstein, MD

Movement Disorders ............................................... Tsao-Wei Liang, MD

Neuromuscular Disorders ........................................ Marinos Dalakas, MD

Neuro-Oncology ...................................................... Jon Glass, MD

Cognitive Neurology ................................................ Mijail Serruya, MD, PhD

General Neurology ................................................... Lori Sheehan, MD

department of Neurological surgery

Robert H. Rossenwasser, MD, Chair

Division Directors

Vascular ................................................................... Pascal Jabbour, MD

Tumor ...................................................................... David W. Andrews, MD

Spine ....................................................................... James S. Harrop, MD

Functional ................................................................ Ashwini D. Sharan, MD

Research and Critical Care ...................................... Jack Jallo, MD, PhD

Thomas Jefferson University hospitals

Departments of Neurology and Neurological Surgery

Philadelphia, PA 19107

Patient Appointments: 1-800-JEFF-NOW

Patient transfers: 1-800-JEFF-121

Physician Referrals: 215-503-8888

neurology and neurosurgery · neurology and neurosurgery outcomes and research. our...

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