Breakthrough Technology Advances Diagnosis and Treatment of Epilepsy

Epilepsy treatment

Michael Sather, M.D., surgical director, Penn State Hershey Comprehensive Epilepsy Center, performing open surgery to place subdural electrodes directly on the surface of the brain with the ROSA™ system, which allows for precise placement of the relevant electrodes.

Technological improvements to both testing and treatment have revolutionized the field of epilepsy care in recent years. Clinicians seek to pinpoint the location of seizures to administer more targeted treatment. “There is a growing interest in identifying the seizure focus more precisely and noninvasively,” says Jayant Acharya, M.D., medical director, Penn State Hershey Comprehensive Epilepsy Center of Penn State Hershey Neuroscience Institute.

One example of this breakthrough technology is dense-array EEG, a noninvasive diagnostic technique that records electroencephalography with up to 256 electrodes versus standard techniques that typically employ 19-21 scalp electrodes.1 Past research has shown that information is lost unless EEG sampling provides an intersensor distance of no more than 2 cm, which would require 500 EEG channels distributed evenly over the head.2 This 256-channel sampling technology can approximate adequate spatial sampling and identify the precise area of neurological dysfunction.2 Acharya concludes, “In our setting, the most important feature is that it’s much more sensitive and specific in terms of localizing the seizure focus.” Continue reading

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Researchers Study Biomarkers in Patients with Restless Legs Syndrome

Idiopathic restless legs syndrome (RLS) can severely affect quality of life and disturb sleep, often requiring pharmacological treatment.¹ According to Max Lowden, M.D., clinical director, Penn State Hershey Restless Legs Syndrome Clinic, RLS is also associated with a host of comorbidities considered more clinically severe than RLS alone. In this little-studied field, research into biomarkers is crucial.

Biomarkers in patients with restless leg syndromeAssistant Professor of Neurosurgery Stephanie Patton, Ph.D., received a grant from the Restless Legs Syndrome Foundation in 2012 to conduct a study entitled, “The role that the nitric oxide pathway plays in regulating vasodilation of the legs in restless legs syndrome.”² The study sought to determine whether changes in blood flow occurred in the femoral artery of RLS subjects, and if hypoxia attenuated the increased blood flow response in RLS patients compared to subjects without the condition. The goal was to identify additional mechanistic pathways in RLS, and potentially develop novel diagnostic and treatment strategies.² Continue reading

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Additional RLS Research Examines Iron Deficiency

James R. Connor, Ph.D., vice-chair of neurosurgery at Penn State Hershey Medical Center, has been continuing research that began as a collaboration with scientists at The Johns Hopkins Hospital over a decade ago. These prior autopsy studies indicated the brain is iron-deficient in RLS patients, and proved a biological basis for the condition, as patients had a low ferritin level in common. This iron deficiency has multiple consequences that will provide further insights into therapeutic targets. “One of these consequences is the activation of hypoxic pathways, since there is not enough iron to use the oxygen,” says Connor. “This is clearly related to reduced peripheral blood flow.” In combination with the research being conducted by Dr. Stephanie Patton, this information may deepen the scientific and clinical knowledge of a poorly-understood condition and open multiple doors to future treatment options.


James R. Connor, Ph.D.James R. Connor, Ph.D.
Distinguished Professor of Neurosurgery, Neural and Behavioral Sciences and Pediatrics
Vice-Chair of Neurosurgery
PHONE:
717-531-4541
E-MAIL:
jconnor@hmc.psu.edu
POSTGRADUATE STUDY:
University of California, Berkeley, Calif.
POSTDOCTORAL TRAINING:
Boston University School of Medicine, Boston, Mass.


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Training Future Neurosurgery Leaders

Neurosurgical practice has evolved greatly over the last decade, and has often been at the forefront of technological advancement.¹ Penn State Hershey Neuroscience Institute has increased its focus on fellowships and residencies to meet the growing demands of the field, including an increasing number of tumor resections and a trend towards coiling rather than clipping cerebral aneurysms.¹ Penn State Hershey features the largest number of fellowships in the country approved by CAST (Committee on Advanced Subspecialty Training, a committee of the Society of Neurological Surgeons).² Residents participate in a year of independent study, during which they may apply for one of the six CAST-accredited fellowships offered in peripheral nerve surgery, endovascular neurosurgery, functional neurosurgery, neuro-oncology, neurocritical care and spine surgery.² Continue reading

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Genetic Research leads to Advances in Muscular Dystrophy

While muscular dystrophy (MD) used to define a single type of muscle disorder, it now encompasses more than 150 genetic subtypes of muscular diseases. At least that many genes are associated with progressive muscle disorders, and in the past 20 years, physicians have experienced an explosion in their knowledge of the genetic underpinnings of MD and disorder subtypes. For example, in the case of limb-girdle muscular dystrophy (LGMD), the fourth most common type of genetic muscle disease, scientists used to recognize only a single overarching category; now, there are at least 50 genes identified in causing disorders in a limb-girdle distribution, leading to a more refined classification and specific treatment options.

Penn State Hershey Medical Center conducts a large amount of clinical research in the genetic roots of muscle disease, and is internationally-renowned for its clinical expertise in LGMD, according to Matthew P. Wicklund, M.D., professor of neurology and pediatrics. In fact, after reviewing more than 3,000 articles over four years, Wicklund, along with nine other experts, published a definitive guideline on diagnosis and management of LGMD in October 2014.1 Many acquired and genetic muscle diseases present as weakness in the hip girdle, thighs, shoulder girdle and proximal arms, the classic “limb-girdle” pattern.2 Part of Wicklund’s responsibility is to further subtype those patients. Continue reading

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Ongoing Research Probes Genetic Basis For Amyotrophic Lateral Sclerosis

Genetic Basis for Amyotrophic Lateral Sclerosis

Dr. William Freeman examines the output from an Illumina HiSeq 2500, a Next Generation Sequencing instrument within the Penn State Hershey Institute for Personalized Medicine (IPM) capable of determining the 3 billion base sequence of a patient’s genome in only 24 hours for less than $5000. By comparison, determination of the first genome sequence 15 years ago required 10 years and $3 billion.

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

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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

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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

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MS Medications and Pregnancy: An Evolving Discussion

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

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Clinical Trials Investigate Novel Treatment Methods in Glioblastoma Multiforme Tumors

MRI Scan of Glioblastoma multiforme.

MRI Scan of Glioblastoma multiforme.

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

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