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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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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