Tag Archives: Neurology

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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TeleStroke Program Overcomes Geographical Barriers to Provide Cutting-Edge Neurological Care


Map of Pennsylvania depicting Telestroke Program Regional Partners with a barchart display of the number partnerships from years 2013 to 2016.LionNet
, Penn State Health Milton S. Hershey Medical Center’s virtual telestroke program, partners with 16 regional hospitals. The telestroke network provides stroke patients rapid access to expert stroke neurologists and neurosurgeons, no matter how remote or rural the community hospital. Stroke patients at a partner site emergency department (ED) are assessed in real-time via audio/ video feed by a stroke neurologist or neurosurgeon at Hershey Medical Center; physicians at both sites can share patient imaging, charts, and test results. Since its July 2012 inception, the program has grown exponentially and more than 5,000 patient consults (approximately 2,000 of which were ischemic stroke patients) have now been performed using LionNet. Continue reading

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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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Early Testing Aids in Correctly Diagnosing, Potentially Treating Patients with Autonomic Dysfunction

Autonomic Dysfunction TestingOver one million Americans are impacted with a primary autonomic system disorder, and the more common forms of these conditions include Postural Orthostatic Tachycardia Syndrome (POTS), Neurocardiogenic Syncope (NCS), Pure Autonomic Failure (PAF) and Multiple Systems Atrophy (MSA).1 In addition, seemingly vague symptoms such as unexplained palpitations, gastroparesis, orthostatic hypotension, syncope, flushing, unexplained sweating, abnormal nasal secretions or lachrymation, or sexual dysfunction can signal autonomic dysfunction (AD), especially in patients with diabetes. Other conditions commonly associated with AD are Parkinson’s disease and migraine. AD is often underdiagnosed or even dismissed, since patients may not recognize or report their symptoms, but early diagnosis of AD can be crucial. In diabetes patients in particular, AD has been shown to correlate with poor cardiovascular outcomes.2 Patients with any of these conditions who display symptoms of AD should receive testing, as this can show the severity of the dysfunction, indicate which body systems are involved, and direct a treatment plan.

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Newer Treatment Options Show Promise for Improved and Individualized Migraine Prevention and Treatment

Migraine prevention and treatment

Single-pulse transcranial magnetic stimulation, marketed as SpringTMS™, is indicated for PRN acute management of migraine pain. Image courtesy of ENeura®.

Migraine headaches are among the most common neurological disorders, with an estimated 12 to 23 percent of U.S. adults having had a migraine in the past three months.1 Despite their frequency, migraines are often treated incorrectly, with prevention strategies underutilized and acute therapies used inappropriately.1 Several steps are needed to advance the quality of migraine treatment, says Stephen Ross, M.D., vice chair, Penn State Department of Neurology. “It’s important that both clinicians and patients are more aware of what is available, and clinicians understand that other effective treatment options are available to replace medications such as opioids, which have been shown to be problematic.” Continue reading

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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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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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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.

Targeted and Untargeted DXR/LIPThe 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

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The Parkinson’s/Statin Paradox: New Analysis Raises Questions About Previous Findings

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

Changes in statin use

The changes of statin usage (A) and plasma total cholesterol levels in Atherosclerosis Risk in Community Study (ARIC) stratified by statin usage (B) and Parkinson’s disease (C) status.2

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