WHAT’S INSIDE

Offering Hope to Patients with ALS R elaying news of a diagnosis of ALS. Allaying

fears. Providing multi-disciplinary care and support for patients and their families. These are everyday undertakings of neurologists, nurses, and other health professionals – including those at the Kessenich Family MDA ALS Center at the University of Miami Miller School of Medicine – who look after ALS patients. Offering patients a future without ALS, is an essential element to providing comprehensive care.

Michael Benatar, MD, PhD, associate professor of neurology, chief of the Neuromuscular Division, and the Walter Bradley Chair in ALS Research at the Miller School believes that, in the absence of effective treatments for patients with ALS, the opportunity for research participation offers the best hope for patients and their families.

Benatar, who leads an active program of research at the University of Miami, studies patients with sporadic ALS as well as more than 400 families across the U.S. with the familial form of this disease (www.als-research.org). In an effort to identify the genetic cause of ALS in these families, a key step towards development of therapeutic and even preventive strategies, Benatar and his team joined forces with an international consortium led by Bryan Traynor, MD, of the NIH. The collaboration led to the important discovery last year that mutations in the VCP gene, although uncommon in patients with familial ALS, were a shared cause of ALS, FTD, and IBMPFD (Inclusion Body Myopathy, Paget disease, and Frontotemporal Dementia) (Neuron, December 9, 2010).

More recently, the international consortium made the landmark discovery that mutations in the C9ORF72 gene on chromosome 9 are the most common cause identified to date of not only familial ALS, but also a significant minority of patients who appear to have the sporadic form of the disease. The pathogenic mutation is a hexanucleotide repeat expansion believed to exert its effect by interfering with RNA processing, a mechanism increasingly recognized to be central to the pathophysiology of ALS. The C90RF72 discovery was reported in the September 22, 2011 issue of the

journal Neuron, with Benatar and colleague Joanne Wuu, ScM, as the Miller School co-authors on this publication. A team from Mayo Clinic Jacksonville has also independently identified the same repeat expansion as a genetic cause of FTD/ALS; their study is reported in the same issue of Neuron.

In addition to these groundbreaking genetic discoveries, Benatar and his team are at the forefront of many other research efforts, including pioneering the first-ever clinical trial (of a drug called arimoclomol) in patients with familial ALS due to mutations in SOD1, which until recently were the most common known cause of ALS. Benatar also leads the Pre-fALS study, a prospective observational study of unaffected family members of patients with familial ALS; these pre-symptomatic individuals are at risk for developing ALS because they carry mutations in genes known to cause ALS (SOD1, C9ORF72, TARDBP, VCP, etc.). Participants in Pre-fALS and the arimoclomol trial are also systematically evaluated using novel imaging and electrophysiological biomarker techniques. Most recently, Benatar has launched a new study to further elucidate the relationship between ALS and IBMPFD. All three studies are actively recruiting participants (see contact information below) from across the U.S., with the costs of genetic testing and travel to the University of Miami covered by the research program.

These are indeed exciting times in the field of ALS research. New genetic discoveries in the last five years have shed light on new links between familial and sporadic ALS, unmasked important connections between ALS and other degenerative disorders, uncovered important disease mechanisms that had previously been overlooked, and

paved the way for new therapeutic development targeting these newly discovered pathogenic pathways.

Through their participation in research, an often fulfilling and self-empowering experience, ALS patients and their families hold the key to scientific advancement. This-together with the recognition that palpable progress in ALS research is being made, even if the translation into effective therapy is an arduous process-is cause for optimism and hope.

Contact:General inquiry, Pre-fALS study, IBMPFD-ALS study: fals@med.miami.edu, 1-888-413-9315Arimoclomol trial: sod1@med.miami.edu

Pg. 2 - Mohamed Samy Elhammady, M.D. Jackson Memorial Neuro-ICU Clinical Trials Pg. 3 - Unique Heat Shock Protein Vaccine (HSPPC-96)Pg. 4 - In The News What’s Next

Resident Spotlight -New Class Profile

ALS research team (from left) Natasha Garcia, research assistant, Maria Fernandez, clinical research coordinator,

Vanessa Vazquez, senior research coordinator and Michael Benatar, M.D., Ph.D., associate professor of neurology.

NeuroFocusA physician’s newsletter from the Departments of Neurology and Neurological Surgery at the

University of Miami Miller School of Medicine in affiliation with Jackson Memorial Hospital

FALL/WINTER 2011-12

HOSPITALS

2011-12

NATIONALNEUROLOGY &

NEUROSURGERY

Mohamed Samy Elhammady, M.D., now an instructor of clinical neurological surgery

at the University of Miami Miller School of Medicine (UM), completed his residency, a neuroendovascular surgery fellowship and an open cerebrovascular and skull base surgery fellowship at UM/JMH. Dr. Elham-mady earned his medical degree with highest honors from the University of Mansoura in Egypt. He began his neurosurgical training at the University of Mansoura before training in the U.S. at UM.

Dr. Elhammady specializes in the treatment of all aspects of cerebrovascular disease, including coiling and clipping of aneurysms, embolization and resection of arteriovenous malformations (AVMs), and stenting and endarterectomy for carotid stenosis. He is highly trained in brain and skull base tumors, including endovascular tumor embolization, minimally invasive endoscopic skull base approaches for pituitary tumors, resection of benign skull base tumors (such as meningiomas, schwannomas, acoustic neuromas and others) and ma-lignant skull base tumors (such as carcinomas and oth-ers), as well as surgery for gliomas and brain metastases.

Dr. Elhammady runs an endovascular laboratory together with Ali Aziz-Sultan, M.D., where they are involved in researching novel methods for the treatment of aneurysms and AVMs, as well as the embolization and endovascular administration of chemotherapy for tumors. He is in the process of starting a microsurgical

anatomical dissection and vascular laboratory for educa-tion, and a neurosurgeon at Jackson Memorial Hospital training, and research in anatomy of the brain, skull base approaches, and microvascular techniques.

Mohamed Samy Elhammady, M.D., joins the Department of Neurological Surgery as an instructor of clinical neurological surgery.

NEUROLOGY

COMBIRX Mutiple Sclerosis (MS)

CombiRx examines the effects of combining drugs with different modes of action to treat multiple sclerosis (MS). The goal is to see if additive effects can be seen with combination treatment for this disorder.

Human interferon beta 1a administered at 30 micrograms IM (Avonex®) once weekly, and glatiramer acetate (Copaxone®) administered at 20 mg SC daily are established treatments for multiple sclerosis. The effects of combinations, each drug with placebo or each drug with one-another will be examined in this trial. Accordingly, patients will give themselves daily injections of glatiramer acetate and once a week placebo IM, or daily placebo injections and once a week interferon 1a IM, or daily injections of glatiramer and once a week interferon 1a. CombiRx trial is one of the largest clinical trials to be ever undertaken by the NIH in neurology. It is an investigator initiated trial with only minimal influences from Industry and all of the data resides with the investigators.

There is also a biomarker arm to the trial and most of the participants are part of this sub-study, which should provide valuable information regarding biomarkers that influence disease severity and treatment effects in multiple sclerosis.

Clinical Trials

NEUROLOGICAL SURGERY

Traumatic Brain Injury (TBI)Phase II, randomized controlled trial of brain tissue oxygen monitoring

This project is designed to determine whether a device designed to measure brain tissue oxygenation, and thus detect brain ischemia while it is still potentially treatable, shows promise in reducing the duration of brain ischemia, and to obtain information required to conduct a definitive clinical trial of efficacy. This study is the first randomized, controlled clinical trial of pBrO2 monitoring, and is designed to obtain data required for a definitive phase III study, such as efficacy of physiologic maneuvers aimed at treating pBrO2, and feasibility of standardizing a complex intensive care unit management protocol across multiple clinical sites.

Patients with severe TBI will be monitored with Intracranial Pressure Monitoring (ICP) and pBrO2 monitoring, and will be randomized to therapy based on ICP alone (control group) or therapy based on ICP in addition to pBrO2 values (treatment group). 182 participants will be enrolled at four clinical sites. Functional outcome will be assessed at 6-months after injury. Currently enrolling.

PI – M. Ross Bullock, M.D., Ph.D.

For more information on Neurology clinical trials please call 1-877-977-7724.

Mohamed Samy Elhammady, M.D. Joins the Neurosurgery Team

Jackson Memorial Neuro-ICU Serves as an International Patient Care Center

Neuro-critical care team (from left) Mohan Kottapaly, M.D., neurology resident; David Ethan Kahn, D.O., neurocritical care fellow; Kristine O’Phelan, M.D., director neurocritical care, co-director JMH NSICU; Stephen Olvey, M.D., co-director JMH NSICU; Violet Kramer, R.N., nurse manager NSICU; Christopher Morrison, Ph.D., clinical pharmacist NSICU.

Heat Shock Protein Vaccine (HSPPC-96) Introduced at the University of Miami

Coordinating CenterStudy PI UM CenterPI Study Drugs

Mount Sinai Medical Center, New York Fred Lublin, M.D.William Sheremata, M.D.Avonex®, Copaxone® and Placebo24 months

For more information on Neurological Surgery Clinical trials, please call 1-800-996-3783.

Jackson Memorial Hospital (JMH) is home to one of the largest Neuroscience Intensive Care Units

(NSICU) in North America. The NSICU has 24 beds equipped with cutting edge neuromonitoring equipment, including continuous video EEG for constant monitoring of cerebral electrical activity. Staffed by three full time neurointensivists, the unit provides state-of-the-art neurocritical care for patients with acute neurologic and neurosurgical disorders from across the United States and Caribbean Basin. One such patient, Jerry Halabi, was transferred by air ambulance from his native island of Curacao to the NSICU for treatment in the fall of 2010. Mr. Halabi, a 32-year-old, presented with new seizures from epilepsy which could not be brought under control at the local hospital in Curacao. His family then decided to seek out the expertise of the JMH/UM specialists for a more thorough evaluation of his condition and other possible treatment options. Upon arrival, he was placed on continuous video EEG monitoring and received escalating therapies with multiple anticonvulsants, sedatives and pentobarbital to control his seizures. Diagnostic testing, including MRI, was suggestive of encephalitis. Labs were drawn to test for viral encephalitis and serology was strongly positive for IgG for St. Louis encephalitis.

Several attempts to taper off the pentobarbital failed. His medical course was complicated by pneumonia and prolonged mechanical ventilation requiring a tracheostomy tube placement. Finally, after six weeks the barbiturate coma was successfully lifted and Mr. Halabi was able to wake up without continuous seizures. He began to follow commands although he remained extremely weak in his limbs due to a severe peripheral neuropathy.

Ten weeks after his admission to the intensive care unit, he was transferred to Kendall Rehabilitation Center for intensive physical therapy before returning to his home in Curacao. Mr. Halabi is now able to work again full time and can walk independently with only a slight limp due to hip pain. He is still being treated with two anticonvulsants to control his epilepsy, but at a significant lower dosage. Mr. Halabi has made a remarkable recovery in a short period of time. He has been able to return to his previous life, and spend time with his family and friends.

“He has made a fantastic recovery from refractory status epilepticus caused by a rare viral encephalitis. Seeing him do so well after such a difficult illness makes what we do in the Neuro-ICU incredibly rewarding,” said Kristine O’Phelan, M.D., director of neurocritical care and one of

the primary specialists who treated Mr. Halabi.

Like many international patients, Mr. Halabi’s successful recovery was due to the treatment provided by a comprehensive team of specialists including neurologists, neuro-critical care nurses and clinical pharmacists—a highly-trained team that cannot be replicated in their home countries.

Mohamed Samy Elhammady, M.D. Joins the Neurosurgery Team

Jackson Memorial Neuro-ICU Serves as an International Patient Care Center

More than 17,000 new cases of central nervous system cancer are diagnosed annually in the

United States, accounting for more than 13,000 deaths each year. Primary malignant brain tumors are nearly uniformly fatal, and the five-year survival rate for the highest grade of malignant glial neoplasm, glioblastoma multiforme (GBM) remains poor. Improvements in conventional treatment modalities have provided only moderate extension of survival for patients harboring malignant gliomas, at times with undesirable side effects. As a result, experimental techniques such as immunotherapy are being applied to malignant glioma patients with increasing frequency.

To this end, the University of Miami joins a multi-center group to complete phase II of a clinical trial using heat shock protein vaccine (HSPPC-96) for patients with newly diagnosed glioblastoma multiforme (GBM). The trial, which is pioneered by the University of California San Francisco, revolves around cancer immunotherapy, an important new treatment modality, with HSPPC-96 being a novel approach to active specific immunotherapy. Immunotherapy is appealing because it offers the potential for specifically targeting tumor cells, without injury to normal neural and glial structures. The preliminary results using HSPPC-96 have been promising, thereby supporting the concept of active tumor and patient specific immunization with autologous tumor-derived heat-shock protein-peptide complex.

During surgery to remove suspected GBMs, University of Miami neurosurgeons will collect tumor tissue as part of their resection technique. The tissue sample will then be used to develop a vaccine specific to each patient’s tumor type through isolation and purification of the heat shock protein peptide complex. After pathologic confirmation of GBM, patients will receive standard of care radiotherapy and chemotherapy. The vaccine will be administered on a weekly basis along with maintenance temozolamide chemotherapy.

The heat shock protein vaccine has been refined over several years, being used in numerous animal models and clinical trials for the treatment of various systemic malignancies, such as renal cell carcinoma, pancreatic cancer, and lung cancer. Only recently, however, has this adjuvant therapy been employed in glioma patients. The preliminary results are encouraging, with earlier studies documenting increased overall survival and progression free survival in patients receiving the vaccine. Importantly, the vaccine has a favorable side effect profile, with no serious adverse events being reported to date. To be eligible, patients must be at least 18 years of age, functionally independent, and able to tolerate standard radiation

and chemotherapy. They cannot carry the diagnosis of Human Immunodeficiency Virus, other concurrent malignancy, or systemic autoimmune disease and/or any history of immunodeficiency.

By targeting the immune system and activating a patient specific T-cell response, the vaccine offers a new avenue for glioma therapy. At the University of Miami, implementation of this vaccine is facilitated by multidisciplinary care and coordination between neurosurgeons, neurologists, and radiation oncologists. Our team is excited to be one of only 10 medical centers in the country, and the only one in Florida, to offer this treatment.

Neuro-critical care team (from left) Mohan Kottapaly, M.D., neurology resident; David Ethan Kahn, D.O., neurocritical care fellow; Kristine O’Phelan, M.D., director neurocritical care, co-director JMH NSICU; Stephen Olvey, M.D., co-director JMH NSICU; Violet Kramer, R.N., nurse manager NSICU; Christopher Morrison, Ph.D., clinical pharmacist NSICU.

Heat Shock Protein Vaccine (HSPPC-96) Introduced at the University of Miami

Molecular diagram of the Heat Shock Protein Peptide Complex.

MRI demonstrating a Glioblastoma Multiforme.

Want more? Check out these stories online and discover more about the University of Miami Miller School of Medicine and Jackson Memorial Hospital

The Departments of Neurology and Neurological Surgery welcomed a new class of residents in July with an incredible array of backgrounds and experiences. Many new class members are graduates of top 50 medical schools and members of Alpha Omega Alpha Honor Medical Society. They come from a variety of international locations and from across the United States. Their experience and interests include research of hypothermia for traumatic brain injury (TBI), stroke

and neuromuscular and movement disorders. The members of this year’s class are medical alumni of Tulane University School of Medicine, Washington University School of Medicine, University of Miami Miller School of Medicine, Albert Einstein College of Yeshiva University, Medical College of Georgia School of Medicine, Indiana University School of Medicine, Howard University College of Medicine, The University of Texas Medical School at Houston and West Virginia University School of Medicine. The Department of Neurology’s residents are slated to graduate in June 2015 and the Department of Neurological Surgery’s residents will graduate in June 2018.

Neurosurgery Residents (from left): Brian Snelling, M.D., and Nicholas Ferraro, M.D.

New Class ProfileResident Spotlight

The University of MiamiDepartments of Neurosurgery & Neurology1120 NW 14th Street/Suite 1361-2Miami, Florida 33136 Neurology: 305-243-6732 neurology.med.miami.eduNeurological Surgery: 305-243-6946 neurosurgery.med.miami.eduThis newsletter is published by the Departments of Neurology and Neurosurgery at the University of Miami, Miller School of Medicine in affiliation with Jackson Memorial Hospital.

Ralph L. Sacco, MS, MD, FAAN, FAHA, Chairman of Neurology Barth A. Green, MD, FACS, Chairman of Neurological SurgeryRoberto Heros, MD, FACS, Co-Chairman Neurological Surgery M. Ross Bullock, MD, PhD, Medical EditorJessica Busquets, Department of Neurology WriterKasey Hayes, Department of Neurological Surgery WriterRoberto Suazo, Graphics Design and Layout

Non-Profit OrgU.S. PostagePAIDPermit No. 438Miami, FL

NeuroFocus

© 2012 University of Miami, Miller School of Medicine. All Rights Reserved

What’s Next In The News

80th AANS Annual Meeting to be Hosted in MiamiApril 14-18, 2012 | Miami Beach Convention Center | Miami Beach, Florida

This 4-day symposium will be a gathering of experts in neurological surgery who will present on the latest findings in the field. The AANS will also be hosting a special symposium on Saturday, April 14, 2012, for the Latin American Federation of Neurological Societies (FLANC). Roberto C. Heros, M.D. and Jacques J. Morcos, M.D. of the University of Miami Miller School of Medicine and Claudio Yampolsky, M.D., of the University of Buenos Aires are coordinating the event. After the symposium, the University of Miami will be hosting a FLANC Reception for its Members, University of Miami Neurosurgery Alumni and selected guests. Michael Y. Wang, M.D., associate professor of neurological surgery at the University of Miami, is the local host for this esteemed conference.For more information: www.aans.org

Department of Neurology’s 50th AnniversaryFebruary 25, 2012 | Breakers Hotel | Palm Beach, Florida The Department of Neurology at the University of Miami’s Miller School of Medicine is proud to announce that we are celebrating our 50th Anniversary this year by hosting a “Solving the Neurological Puzzle” Gala on Saturday, February 25, 2012 at the Breakers Hotel in Palm Beach, Florida. The event will feature a live auction dinner and dancing and a performance by Jay Leno of the Tonight Show.

Neurology Residents (from left): Brittani L. Conway, M.D., Darian E. Reddick, M.D., M.S., Hilary P. Glazer, M.D., and Christina M. Hupman, M.D.

Amedeo Merenda, M.D., Joins Neurology Faculty

Dr. Merenda joined the faculty at the University of Miami/Jackson Memorial Medical Center in July 2011. He serves as an attending physician in Neurocritical Care and an assistant professor of Neurology and Neurosurgery. He received his medical degree and completed a Neurosurgery Residency at the University of Messina, Italy. He completed a research fellowship in traumatic brain injury (TBI) in the Department of Neurosurgery at the Virginia Commonwealth University Medical Center, under the mentorship of Dr. Ross Bullock, professor of Neurological Surgery at UM/Jackson. Subsequently, he completed a UCNS-accredited clinical fellowship in Neurocritical Care at Case Western Reserve University, under the direction of Michael De Georgia M.D.

Dr. Merenda’s clinical and research interests include traumatic brain injury (TBI), acute cerebrovascular disease and the application of neuromonitoring techniques in patients with acute brain injury.