Category Archives: Research

Retinal Vasculopathy – A Potential Early Predictor of Stroke Risk

Impaired retinal vasodilator responses may be an early marker of microvascular disease or endothelial dysfunction and a potential predictor of cerebrovascular risk based on findings from studies in diabetic and prediabetic patients.1,2 Kerstin Bettermann, MD, PhD, associate professor, department of neurology, Penn State Health Milton S. Hershey Medical Center, explains, “Retinal blood flow is controlled by autoregulatory metabolic and pressure mechanisms, which are impaired in diabetes. We also know that impairment of the retinal microvasculature is associated with cerebral ischemia.3 Given these two facts, looking at retinal vasodilator responses may be a low-cost, non-invasive strategy to assess risk for stroke and possibly other cerebrovascular risks in a wide range of individuals in the community.” Dr. Bettermann believes that with further validation, screening for retinal vasculopathy may become part of routine eye exams.

Retinal arterial vasoreactivity over time following flicker light stimulation

Retinal arterial vasoreactivity over time following flicker light stimulation

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Novel Zebrafish Research Contributes to More Effective Diagnosis, Treatment of Neurodegenerative Disorders

Researchers at Penn State Neuroscience Institute not only conduct pre-human scientific studies of various medical conditions, but also see patients daily, giving these physicians a perspective not found in most laboratories. Mark Stahl, M.D., Ph.D., assistant professor of neurology and neural and behavioral sciences, details one such study involving “molecular tweezers” to break up the aggregation of misfolded proteins known as α -synuclein.1 These aggregated proteins are associated with the development of neurodegenerative disorders such as Parkinson’s disease, for which there are currently symptomatic therapies but no treatments that can alter the disease course.1

Zebrafish research

LEFT: Zebrafish overexpressing neuronal human alpha-synuclein (red) have poor morphology, neuronal death and poor survival. RIGHT: “Molecular tweezers” like CLR-01 can rescue this phenotype.

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Pipeline® Embolization Device Features Improved Delivery System

Since the Food and Drug Administration (FDA) approved the Pipeline® Embolization Device (PED) for flow diversion in large or giant wide-necked aneurysms in 2011 after the multicenter Pipeline for Uncoilable or Failed Aneurysms (PUFs) trial proved its safety and efficacy1, the revolutionary device continues to improve treatment of the most complex aneurysms. The latest version, the Pipeline™ Flex, features a vastly improved delivery system. According to Kevin Cockroft, M.D., M.Sc., co-director, Penn State Comprehensive Stroke Center, “We now have the ability to reposition the device, which allows for more precise placement instead of always needing to hit the exact target on the first attempt, and this appears to have shortened the learning curve for clinicians.” Hershey Medical Center was one of the first in the country to offer treatment with the PED, and has performed close to 70 of the procedures to date.

Digital subtraction angiogram

Digital subtraction angiogram in lateral view before and six months after treatment.

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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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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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