It has been long assumed that the majority of amyotrophic lateral sclerosis (ALS) cases occur sporadically, while only 5 to 10 percent are defined as genetic, in which ALS is inherited via a straightforward autosomal-dominant mechanism. However, researchers at the Penn State Hershey ALS Clinic and Research Center, working in collaboration with the Institute for Personalized Medicine at Penn State Hershey Medical Center, have now found that more cases occur as the result of extremely complex genetic factors than previously thought. Researchers have helped determine that many cases appear to be recessively inherited, which would account for the fact that there is no identifiable history elsewhere in close relatives. Continue reading
Research Examines Customization of Brain-Computer Interface (BCI) Technology in Patients with ALS and Cognitive Decline
The novel technology of brain-computer interface (BCI) uses brain activity, as measured by electroencephalogram (EEG) to control external devices, facilitating paralyzed patients’ ability to communicate. This technology¹ can allow patients with amyotrophic lateral sclerosis (ALS) to communicate even after they have lost the gaze control necessary for eye-tracking communication programs.¹ For maximum efficacy, BCI programs must account for aspects of disease heterogeneity, such as cognitive impairment, according to Andrew Geronimo, Ph.D., instructor, Penn State Hershey Neurosurgery.
“Our primary contribution to the ongoing ALS patient research is to account for cognitive impairment as we customize BCI programs for each patient,” says Geronimo, who is conducting ongoing studies in the area. “It represents the future direction of this field.” Cognitive decline is present in 50 percent of patients with ALS, once thought to be a purely motor neuron disease, with 15 percent of patients meeting the clinical criteria for dementia. While most clinicians are aware of this fact, the majority of BCI designers are not, a knowledge gap that Geronimo hopes to bridge with his work. Continue reading
Clinician/Patient Dialogue Crucial In Assessing Potential Impact Of Multiple Sclerosis (MS) On Pregnancy, Breastfeeding
Questions have long surrounded the influence of multiple sclerosis (MS) on pregnancy and breastfeeding, and vice versa, especially given the majority of patients are taking disease modifying therapy (DMT) medications.1 Although female MS patients of childbearing age were discouraged from considering pregnancy or breastfeeding, more research suggests that, with proper oversight, the majority of MS patients experience no side-effects. Depending on the severity of the disease, breastfeeding can be an option for some patients, if they do not require DMT medications during that period.2
The PRegnancy In Multiple Sclerosis (PRIMS) study was the first large prospective study to assess the possible influence of pregnancy, delivery, and breastfeeding on the clinical course of MS.2 In that trial, 254 women with MS were followed during pregnancy and through their second year post-partum.2 Researchers found a reduced rate of relapse during pregnancy as compared with the 12 months prior, which was especially marked in the third trimester.2 A significant increase in the relapse rate in the first trimester post-partum was noted, but the relapse rate did not significantly differ from the pre-pregnancy rate at the beginning of the second trimester post-partum.2 In addition, the study found that women who chose to breastfeed experienced fewer relapses and had milder disability scores in the year before and during pregnancy compared with women who chose not to breastfeed.2 Continue reading
Many disease modifying treatments for patients with relapsing form of multiple sclerosis are currently Category C, with one being Category X, which has contributed to the prevailing sentiment that MS patients should avoid becoming pregnant while taking these medications. While pregnancy avoidance is not always required, caution should be used when patients are taking the newer MS medications. For some medications, pregnancy should be avoided, and otherwise a clear plan for an appropriate wash-out period should be in place. Reproductive plans should also be discussed with male patients in some circumstances, as one of the oral medications (Aubagio) is known to pass through semen. The chart below summarizes what studies have shown regarding the safety of commonly used DMTs on perinatal and developmental outcomes in offspring of mothers with MS. Continue reading
Glioblastoma multiforme (GBM) is one of the most medically challenging brain tumors, and can be fatal within one year.¹ Approximately 18,000 patients are diagnosed with GBM in the U.S., annually.² The current standard of treatment—maximal resection, followed by radiation with concurrent and adjuvant temozolomide chemotherapy has shown only modest improvement, with a median survival of 14.6 months, and a two-year survival rate of 26.5 percent.¹ “We need new avenues to improve survival rates,” says Assistant Professor of Neuro-Oncology Dawit Aregawi, M.D. He explains that Penn State Hershey Medical Center is conducting trials in immunologically-mediated therapy among the 90 percent of patients who experience tumor recurrences.³
While past GBM research has focused on chemotherapy, scientists have switched their focus to therapy utilizing the body’s own immune system to create tumor-fighting vaccines. Two upcoming phase 1 trials at Penn State Hershey, ICT-121 and WT2725, target cancer stem cells traditionally resistant to any form of treatment. Continue reading
New Targeted Therapy: Nanotechnology Breakthrough Allows Chemotherapeutic Agents To Cross Blood-Brain Barrier, Target Astrocytoma Cells
Two major challenges of treating glioblastoma multiforme have been the type and location of these aggressive brain tumors.¹ Surgical tumor resection is difficult due to the widespread nature of gliomas. Chemotherapeutic treatments are often unable to cross the blood-brain barrier or cannot be confined to cancerous cells only, thus causing toxicity in normal tissue.¹ One viable option is targeted therapy, which can result in both improved chemotherapeutic and surgical results.
Research initiated by Achuthamangalam Madhankumar, Ph.D., assistant professor of neurosurgery at Penn State Hershey, has shown it is possible to use targeted nanovesicles to carry anti-cancer drugs or contrast agents selectively to tumor cells. The latter approach enhances tumor visibility, enabling the surgeon to more accurately assess the extent of the tumor. In addition, because of the unique expression of the interleukin-13 (IL-13) receptor on certain types of brain tumors, this targeted delivery system may be useful in the diagnosis of tumors.
The research used a murine model to test parameters including the efficacy of targeted versus untargeted liposomal doxorubicin, a chemotherapeutic agent.¹ Mice with intracranial tumors measuring five millimeters received fifteen milligrams of doxorubicin for each kilogram of body weight once a week.¹ Over six weeks, the size of the tumor decreased to less than one millimeter in the group receiving targeted liposomes, but did not decrease in the two of eight surviving mice receiving untargeted liposomes with doxorubicin.¹ There was a significant decrease in the tumor volume on contrast MRI images in the targeted liposome group, as seen in the figure.¹ Continue reading
In 2013, a paper published in Neurology advocated a clinical opinion that statin use was protective against Parkinson’s disease (PD).¹ However, Xuemei Huang, M.D., Ph.D., professor and vice chair for research, Penn State Hershey Neurology, led a team in a prospective analysis of the connection between statins and PD in the Atherosclerosis Risk in Communities (ARIC) study, which strongly suggests the opposite finding.²
While the analysis was based on just 106 cases of the more than 15,000 patients enrolled in ARIC, Huang says, “The length of the study, measurement of cholesterol, and recording of patients’ statin history all combine to make top-notch data collection.” One especially interesting feature of the ARIC patient cohort is that the study began before statins were widely used, but continued for twenty years, marking a unique opportunity to analyze pre- and post-statin disease correlates. In addition, not only did Huang’s study find that statins may not confer a protective effect against the development of PD, but they may actually increase the risk of developing PD with long-term use.²
Multi-Disciplinary Approach and Collaborative Research Spawn Innovations, New Fellowship in Peripheral Nerve Program
The peripheral nerve program at Penn State Hershey Neuroscience Institute uses nerve transfer procedures to treat complex cases. Division Chief of Peripheral Nerve Surgery, Kimberly S. Harbaugh, M.D., explains one option, “Oberlin transfer is a procedure in which the clinician harvests part of one of the nerves from the hand and transfers it to the nerve in the patient’s bicep muscle. In this way, we have been able to restore significant levels of elbow flexion.” This has multiple potential applications, even in patients with spinal cord injuries. A portion of the nerves that are still intact above the level of the injury can be transferred to areas below the injury. In this way, spinal cord injury patients may be able to reclaim some finger and hand function, leading to improved self-care options.¹
Assistant Professor of Neurosurgery, Elias B. Rizk, M.D., M.Sc., details a recent case: “I had a male patient in his mid- 20s with a direct injury to his brachial plexus. He had been in a car accident, and in a state of semi-consciousness, he tried to release himself by using a pocket knife. He stuck it into his chest wall, severing one of the nerves to the arm. As a result, he lost his functional elbow movement. After six months, we elected to do an Oberlin nerve transfer to his bicep muscle. He had a very good recovery, with restoration of elbow flexion, and is now back to work.” Continue reading
Penn State Hershey Neuroscience Institute, has a global perspective when it comes to providing quality, multi-disciplinary care. This is best represented by the Institute’s expansive global exchange program among neuroscience clinicians and researchers, spanning four continents. Every neurosurgical resident is given the opportunity to hone his or her skills abroad, and almost half choose to do so. The primary exchange program is with the Bureau of Public Health in Tianjin, China, a formal relationship that began in 2006. Through a grant funded by Integra Foundation, eight Penn State Hershey Medical Center faculty members have studied there, while thirty-four exchange students have learned alongside Penn State College of Medicine faculty.
The exchange program functions as part of a developing program to encourage collaboration between clinicians and researchers at Penn State Hershey Medical Center and Tianjin’s largest hospitals. These reciprocal relationships enable providers to share best practices and advanced technology to improve patient outcomes. From a clinical standpoint, foreign physicians can gain experience with virtually every neurosurgical procedure that is currently performed at Penn State Hershey Medical Center. In the research arena, groundbreaking studies are being conducted through the Center for Neural Engineering and Penn State Hershey Neurosurgery laboratory. Research is ongoing in neurodegenerative disease, brain iron deficiency, brain tumors, epilepsy, and brain-machine interfaces. Physicians from the US and China also collaborate on clinical trials, mutually benefiting with shared data from their genetically disparate populations. Continue reading
Robert Harbaugh, M.D., professor and chair of Penn State Department of Neurosurgery and director of Penn State Hershey Neuroscience Institute, encourages all members of his department to take an active role in the field. “One thing we encourage in our residency training, aside from the usual missions of education, patient care, and research, is involvement in organized neurosurgery.” As they train new residents, Penn State Hershey Neurosurgery faculty members also encourage younger physicians to pass on their knowledge and adopt a citizenship role in the field.
Harbaugh himself holds multiple leadership positions, including president of the Society of Neurological Surgeons. He previously served as immediate past president of the American Association of Neurological Surgeons and director and member of the Advisory Council of the American Board of Neurological Surgery. Harbaugh has traveled extensively to lecture on various topics, including his clinical specialty of cerebrovascular neurosurgery and his research work on computer modeling of intracranial aneurysms.
Robert E. Harbaugh, M.D., FAANS, FACS, FAHA
Director, Penn State Hershey Neuroscience Institute
Distinguished Professor and Chair, Department of Penn State Hershey Neurosurgery
Professor, Department of Engineering Science and Mechanics
RESIDENCY: Neurological Surgery, Dartmouth Hitchcock Medical Center
MEDICAL SCHOOL: Penn State College of Medicine