Neurology Commons^™

Surgical Outcome In Pet-Positive, Mri-Negative Patients With Temporal Lobe Epilepsy, Carla Lopinto-Khoury, Michael R. Sperling, Christopher Skidmore, Maromi Nei, James Evans, Ashwini Sharan, Scott Mintzer

Department of Neurology Faculty Papers

PURPOSE:

Fluorodeoxyglucose positron emission computed tomography (FDG-PET) hypometabolism is important for surgical planning in patients with temporal lobe epilepsy (TLE), but its significance remains unclear in patients who do not have evidence of mesial temporal sclerosis (MTS) on magnetic resonance imaging (MRI). We examined surgical outcomes in a group of PET-positive, MRI-negative patients and compared them with those of patients with MTS.

METHODS:

We queried the Thomas Jefferson University Surgical Epilepsy Database for patients who underwent anterior temporal lobectomy (ATL) from 1991 to 2009 and who had unilateral temporal PET hypometabolism without an epileptogenic lesion on MRI (PET+/MRI-). We compared …

Conversion From Enzyme-Inducing Antiepileptic Drugs To Topiramate: Effects On Lipids And C-Reactive Protein., Scott Mintzer, Christopher T Skidmore, Sara J Rankin, Inna Chervoneva, Edward Pequinot, David M Capuzzi, Michael R Sperling

Department of Neurology Faculty Papers

PURPOSE: We previously demonstrated that converting patients from the enzyme-inducers phenytoin or carbamazepine to the non-inducers levetiracetam or lamotrigine reduces serum lipids and C-reactive protein (CRP). We sought to determine if the same changes would occur when patients were switched to topiramate, which has shown some evidence of enzyme induction at high doses. We also examined the effects of drug switch on low-density lipoprotein (LDL) particle concentration.

METHODS: We converted 13 patients from phenytoin or carbamazepine monotherapy to topiramate monotherapy (most at doses of 100-150 mg/day). Fasting lipids, including LDL particle concentration, and CRP were obtained before and ≥6 weeks …

The Prevalence Of Cervico-Arterial Dissection In Sub-Arachnoid Hemorrhage In The United States, Ali Seifi, Md, Fred Rincon, Md, Msc, Mitchell Maltenfort, Phd, Pascal Jabbour, Md, Rodney Bell, Md, Michael Moussouttas, Md

Department of Neurology Faculty Papers

Objectives: In this study, we sought to determine the prevalence of cervico-arterial dissection in aubarachnoid hemorrhage (SAH) using a large administrative database.

The Prevalence And Risk Factors Of Acute Myocardial Infarction (Ami) After Acute Ischemic Stroke (Ais) In The United States, Ali Seifi, Md, Fred Rincon, Md, Msc, Michael Moussouttas, Md, Mitchell Maltenfort, Phd, Matthew Vibbert, Md, Rodney Bell, Md, Maria Carissa Pineda, Md, Diana Tzeng, Md, Jacqueline Urtecho, Md, Anish Koka, Md, William Mcbride, Md

Department of Neurology Faculty Papers

Objectives: To determine the prevalence and risk factors for, and the association with in-hospital mortality of, AMI after AIS, and to study the effect of intravenous recombinant tissue plasminogen activator (r-tPA) in this setting. We hypothesized that AMI would be associated with lower survival rate at hospital discharge but that intravenous r-tPA would be associated with lower risk of AMI.

Psychological And Cognitive Determinants Of Vision Function In Age-Related Macular Degeneration., Barry W. Rovner, Robin J Casten, Robert W Massof, Benjamin E Leiby, William S Tasman

Department of Neurology Faculty Papers

OBJECTIVE: To investigate the effect of coping strategies, depression, physical health, and cognition on National Eye Institute Visual Function Questionnaire scores obtained at baseline in a sample of older patients with age-related macular degeneration (AMD) enrolled in the Improving Function in AMD Trial, a randomized controlled clinical trial that compares the efficacy of problem-solving therapy with that of supportive therapy to improve vision function in patients with AMD.

METHODS: Baseline evaluation of 241 older outpatients with advanced AMD who were enrolled in a clinical trial testing the efficacy of a behavioral intervention to improve vision function. Vision function was characterized …

Hormonal Consequences Of Epilepsy And Its Treatment In Men., Kartik Sivaraaman, Scott Mintzer

Department of Neurology Faculty Papers

PURPOSE OF REVIEW: Epilepsy and anticonvulsant medications may substantially alter endocrine homeostasis, including the male reproductive hormonal system.

RECENT FINDINGS: Seizures in medial temporal lobe structures, through their connectivity to the hypothalamus, alter the secretion of gonadotropins. Levels of circulating bioavailable testosterone are affected by changes in the level of binding proteins, which in turn may be affected by seizure medications. The use of older generation medications that induce the cytochrome P450 system is associated with an increase in sex hormone-binding globulin and lower bioactive testosterone. Sexual dysfunction, including decreased libido and decreased potency, and infertility, is seen commonly in …

Depression And Anxiety In Patients With Epilepsy, With Or Without Other Chronic Disorders., A A Asadi-Pooya, M R Sperling

Department of Neurology Faculty Papers

BACKGROUND: Most people with epilepsy lead a normal emotional and cognitive life, however neurobehavioral problems can be found in a large number of patients. This study evaluates the prevalence of depression and anxiety among patients with epilepsy and determines whether having other chronic somatic illnesses increases the prevalence.

METHODS: Adults with epilepsy were recruited in either the inpatient epilepsy monitoring unit or the Outpatient Epilepsy Clinic at Thomas Jefferson University in 2006. Patients anonymously filled out a questionnaire, included data about age, sex, education, having other chronic illnesses, and degree of seizure control. The Hospital Anxiety and Depression scale was …

A Test Of The Role Of The Medial Temporal Lobe In Single-Word Decoding., Karol Osipowicz, Tyler Rickards, Atif Shah, Ashwini Sharan, Michael Sperling, Waseem Kahn, Joseph Tracy

Department of Neurology Faculty Papers

The degree to which the MTL system contributes to effective language skills is not well delineated. We sought to determine if the MTL plays a role in single-word decoding in healthy, normal skilled readers. The experiment follows from the implications of the dual-process model of single-word decoding, which provides distinct predictions about the nature of MTL involvement. The paradigm utilized word (regular and irregularly spelled words) and pseudoword (phonetically regular) stimuli that differed in their demand for non-lexical as opposed lexical decoding. The data clearly showed that the MTL system was not involved in single word decoding in skilled, native …

Acetate Causes Alcohol Hangover Headache In Rats, Christina R. Maxwell, Rebecca Jay Spangenberg, Jan B. Hoek, Stephen D. Silberstein, Michael L. Oshinsky

Department of Neurology Faculty Papers

Background

The mechanism of veisalgia cephalgia or hangover headache is unknown. Despite a lack of mechanistic studies, there are a number of theories positing congeners, dehydration, or the ethanol metabolite acetaldehyde as causes of hangover headache.

Methods

We used a chronic headache model to examine how pure ethanol produces increased sensitivity for nociceptive behaviors in normally hydrated rats.

Results

Ethanol initially decreased sensitivity to mechanical stimuli on the face (analgesia), followed 4 to 6 hours later by inflammatory pain. Inhibiting alcohol dehydrogenase extended the analgesia whereas inhibiting aldehyde dehydrogenase decreased analgesia. Neither treatment had nociceptive effects. Direct administration of acetate …

Acetate Causes Alcohol Hangover Headache In Rats., Christina R Maxwell, Rebecca Jay Spangenberg, Jan B Hoek, Stephen D Silberstein, Michael L Oshinsky

Department of Neurology Faculty Papers

BACKGROUND: The mechanism of veisalgia cephalgia or hangover headache is unknown. Despite a lack of mechanistic studies, there are a number of theories positing congeners, dehydration, or the ethanol metabolite acetaldehyde as causes of hangover headache.

METHODS: We used a chronic headache model to examine how pure ethanol produces increased sensitivity for nociceptive behaviors in normally hydrated rats.

RESULTS: Ethanol initially decreased sensitivity to mechanical stimuli on the face (analgesia), followed 4 to 6 hours later by inflammatory pain. Inhibiting alcohol dehydrogenase extended the analgesia whereas inhibiting aldehyde dehydrogenase decreased analgesia. Neither treatment had nociceptive effects. Direct administration of acetate …

Ms4a4b, A Cd20 Homologue In T Cells, Inhibits T Cell Propagation By Modulation Of Cell Cycle., Hui Xu, Yaping Yan, Mark S Williams, Gregory B Carey, Jingxian Yang, Hongmei Li, Guang-Xian Zhang, Abdolmohamad Rostami

Department of Neurology Faculty Papers

MS4a4B, a CD20 homologue in T cells, is a novel member of the MS4A gene family in mice. The MS4A family includes CD20, FcεRIβ, HTm4 and at least 26 novel members that are characterized by their structural features: with four membrane-spanning domains, two extracellular domains and two cytoplasmic regions. CD20, FcεRIβ and HTm4 have been found to function in B cells, mast cells and hematopoietic cells respectively. However, little is known about the function of MS4a4B in T cell regulation. We demonstrate here that MS4a4B negatively regulates mouse T cell proliferation. MS4a4B is highly expressed in primary T cells, natural …

Clinical And Diagnostic Features Of Patients With Compound Heterozygous A467t/W748s Polg1 Mutations: A Case Report And Review Of Previous Cases, David Roshal, D.O., Andro Zangaladze, Md, Phd

Department of Neurology Faculty Papers

Introduction

Mutations in the POLG1 gene are considered to be the most common gene defect identified in autosomal recessive mitochondrial DNA depletion disorders. POLG1 is a gene encoding the 195kDa catalytic (alpha) subunit of the mitochondrial (gamma) DNA polymerase, located on chromosome 15q25 and is responsible for mtDNA replication. Mutations in POLG1 are associated with chronic progressive external ophthalmoplegia (CPEO). Other genes that have been implicated in causing syndromic and non-syndromic mitochondrial disorders have been found on both mtDNA (3243A>G, 8344A>G, 8993T>G, and 11778A>G) and nDNA (SURF1, POLG1, TWINKLE, and ANT1).

We report a patient with …

Is Phonophobia Associated With Cutaneous Allodynia In Migraine?, Avi Ashkenazi, Irene Yang, Aamir Mushtaq, Michael L. Oshinsky

Department of Neurology Faculty Papers

ABSTRACT

Objective

To determine whether phonophobia and dynamic mechanical (brush) allodynia are associated in episodic migraine (EM).

Methods

Adult patients with EM were prospectively recruited. A structured questionnaire was used to obtain demographic and migraine related data. Phonophobia was tested quantitatively using a real time sound processor and psychoacoustic software. Sound stimuli were pure tones at frequencies of 1000 Hz, 4000 Hz and 8000 Hz, delivered to both ears at increasing intensities, until an aversive level was reached. Allodynia was assessed by brushing the patient’s skin with a gauze pad at different areas. Patients were tested both between and during …

Metabolic Consequences Of Antiepileptic Drugs, Scott Mintzer

Department of Neurology Faculty Papers

Purpose of Review: Chemical properties of the widely used older generation antiepileptic drugs (AEDs) suggest that they might be responsible for a number of medical comorbidities. Recent Findings: AEDs which induce the cytochrome P450 system adversely affect bone, lipid, and gonadal steroid metabolism. Specifically, phenytoin causes loss of bone mass in women, and both phenytoin and carbamazepine produce increases in serum lipids and C-reactive protein, as well as decreases in bioactive testosterone in men. Patients treated with inducing AEDs are at increased risk of fracture. Some contradictory data raise the question of whether bone mass is truly related to enzyme …

Valproate Semisodium Er For Migraine And Cluster Headache Prophylaxis., Brigitte V. Lovell, Michael J. Marmura

Department of Neurology Faculty Papers

IMPORTANCE OF THE FIELD: Migraine and cluster headache (CH) are disabling syndromes that often require prophylactic treatment. Valproate semisodium ER (VPS ER) is FDA-approved for the treatment of epilepsy, acute mania in bipolar disorder and migraine prophylaxis.

AREAS COVERED IN THIS REVIEW: We reviewed literature regarding VPS ER pharmacokinetics and its use in migraine and CH prophylaxis.

WHAT THE READER WILL GAIN: VPS ER is well studied and effective in the preventive treatment of migraine and CH. This article reviews the evidence for its use, describes how to administer and dose this medication, and reviews important safety precautions.

TAKE HOME …

Electronic Medical Records As A Research Tool: Evaluating Topiramate Use At A Headache Center., Michael J. Marmura, Md, Mary Hopkins, Rn, Msn, Jocelyn Andrel, Msph, William B. Young, Md, David M. Biondi, Do, Marcia F.T. Rupnow, Phd, Robert B. Armstrong, Md

Department of Neurology Faculty Papers

Background.—Electronic medical records (EMRs) are used in large healthcare centers to increase efficiency and accuracy of documentation. These databases may be utilized for clinical research or to describe clinical practices such as medication usage.

Methods.—We conducted a retrospective analysis of EMR data from a headache clinic to evaluate clinician prescription use and dosing patterns of topiramate. The study cohort comprised 4833 unique de-identified records, which were used to determine topiramate dose and persistence of treatment.

Results.—Within the cohort, migraine was the most common headache diagnosis (n = 3753, 77.7%), followed by tension-type headache (n = 338, 7.0%) and cluster or …

Fdg Pet-Positive, Mri-Negative Patients With Temporal Lobe Epilepsy: Etiology And Outcomes Compared To Patients With Hippocampal Sclerosis, C. Lopinto Khoury, M. Sperling, C. Skidmore, M. Nei, A. Zangaladze, J. Evans, A. Sharan, S. Mintzer

Department of Neurology Faculty Papers

FDG PET hypometabolism is important for surgical planning in patients with temporal lobe epilepsy (TLE), but its significance remains unclear in patients who do not have evidence of Hippocampal Sclerosis (HS) on MRI.

Improved Inter-Rater Reliability For Sah Ct Grading Scales Through Application Of A Formal Definition Of Clot Thickness, William Mcbride, Md, Valerie Dechant, Md, Michael Moussouttas, Md

Department of Neurology Faculty Papers

Various scales have been devised for the prediction of vasospasm following aneurysmal rupture.

Especially prominent in these scales is their reliance upon a subjective assessment of clot thickness which introduces variability in grading across raters.

The current study seeks to compare the inter-rater reliability of the traditional Fisher and newer "Frontera" scale (Modified Fisher) when a rigid definition of thick clot is employed.

Mechanisms Of Primary Axonal Damage In A Viral Model Of Multiple Sclerosis., Jayasri Das Sarma, Lawrence C. Kenyon, Susan T. Hingley, Kenneth S. Shindler

Department of Neurology Faculty Papers

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. Recent studies have demonstrated that significant axonal injury also occurs in MS patients and correlates with neurological dysfunction, but it is not known whether this neuronal damage is a primary disease process, or occurs only secondary to demyelination. In the current studies, neurotropic strains of mouse hepatitis virus (MHV) that induce meningitis, encephalitis, and demyelination in the CNS, an animal model of MS, were used to evaluate mechanisms of axonal injury. The pathogenic properties of genetically engineered isogenic spike protein recombinant demyelinating and nondemyelinating strains of MHV were compared. …

Functional Interleukin-17 Receptor A Is Expressed In Central Nervous System Glia And Upregulated In Experimental Autoimmune Encephalomyelitis., Jayasri Das Sarma, Bogoljub Ciric, Ryan Marek, Sanjoy Sadhukhan, Michael L. Caruso, Jasmine Shafagh, Denise C. Fitzgerald, Kenneth S. Shindler, Am Rostami

Department of Neurology Faculty Papers

BACKGROUND: Interleukin-17A (IL-17A) is the founding member of a novel family of inflammatory cytokines that plays a critical role in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). IL-17A signals through its receptor, IL-17RA, which is expressed in many peripheral tissues; however, expression of IL-17RA in the central nervous system (CNS) and its role in CNS inflammation are not well understood.

METHODS: EAE was induced in C57Bl/6 mice by immunization with myelin oligodendroglial glycoprotein. IL-17RA expression in the CNS was compared between control and EAE mice using RT-PCR, in situ …

Combined Effects Of Hyperglycemic Conditions And Hiv-1 Nef: A Potential Model For Induced Hiv Neuropathogenesis., Edward A Acheampong, Cassandra Roschel, Muhammad Mukhtar, Alagarsamy Srinivasan, Mohammad Rafi, Roger J Pomerantz, Zahida Parveen

Department of Neurology Faculty Papers

Hyperglycemic conditions associated with diabetes mellitus (DM) or with the use of antiretroviral therapy may increase the risk of central nervous system (CNS) disorders in HIV-1 infected patients. In support of this hypothesis, we investigated the combined effects of hyperglycemic conditions and HIV-1 accessory protein Nef on the CNS using both in vitro and in vivo models. Astrocytes, the most abundant glial cell type required for normal synaptic transmission and other functions were selected for our in vitro study. The results show that in vitro hyperglycemic conditions enhance the expression of proinflammatory cytokines including caspase-3, complement factor 3 (C3), and …

Sensitivity Of The Human Circadian System To Short Wavelength (420 Nm) Light, George C. Brainard, David Silney, John P. Hanifin, Gena Glickman, Brenda Byrne, Jeffrey M. Greeson, Samar Jasser, Edward Gerner, Mark D. Rollag

Department of Neurology Faculty Papers

The circadian and neurobehavioral effects of light are primarily mediated by a retinal ganglion cell photoreceptor in the mammalian eye containing the photopigment, melanopsin. Nine action spectrum studies using rodents, monkeys, and human for these responses indicate peak sensitivities in the blue region of the visible spectrum ranging from 459 nm to 484 nm, with some disagreement in short wavelength sensitivity of the spectrum. The aim of this work was to quantify the sensitivity of human volunteers to monochromatic 420 nm light for plasma melatonin suppression. Adult female (N=14) and male (N=12) subjects participated in two studies, each employing a …

Experimental Optic Neuritis Induced By A Demyelinating Strain Of Mouse Hepatitis Virus., Kenneth S. Shindler, Lawrence C. Kenyon, Mahasweta Dutt, Susan T. Hingley, Jayasri Das Sarma

Department of Neurology Faculty Papers

Optic neuritis (ON), an inflammatory demyelinating optic nerve disease, occurs in multiple sclerosis (MS). Pathological mechanisms and potential treatments for ON have been studied via experimental autoimmune MS models. However, evidence suggests that virus-induced inflammation is a likely etiology triggering MS and ON; experimental virus-induced ON models are therefore required. We demonstrate that MHV-A59, a mouse hepatitis virus (MHV) strain that causes brain and spinal cord inflammation and demyelination, induces ON by promoting mixed inflammatory cell infiltration. In contrast, MHV-2, a nondemyelinating MHV strain, does not induce ON. Results reveal a reproducible virus-induced ON model important for the evaluation of …

Interrelation Of Inflammation And App In Sibm: Il-1 Beta Induces Accumulation Of Beta-Amyloid In Skeletal Muscle., Jens Schmidt, Konstanze Barthel, Arne Wrede, Mohammad Salajegheh, Mathias Bähr, Marinos C Dalakas

Department of Neurology Faculty Papers

Distinct interrelationships between inflammation and beta-amyloid-associated degeneration, the two major hallmarks of the skeletal muscle pathology in sporadic inclusion body myositis (sIBM), have remained elusive. Expression of markers relevant for these pathomechanisms were analysed in biopsies of sIBM, polymyositis (PM), dermatomyositis (DM), dystrophic and non-myopathic muscle as controls, and cultured human myotubes. By quantitative PCR, a higher upregulation was noted for the mRNA-expression of CXCL-9, CCL-3, CCL-4, IFN-gamma, TNF-alpha and IL-1 beta in sIBM muscle compared to PM, DM and controls. All inflammatory myopathies displayed overexpression of degeneration-associated markers, yet only in sIBM, expression of the mRNA of amyloid precursor …

Whiplash: Diagnosis, Treatment, And Associated Injuries., Sanjay Yadla, John K. Ratliff, James Harrop

Department of Neurology Faculty Papers

STUDY DESIGN: Focused review of the current literature.

OBJECTIVE: To identify and synthesize the most current data pertaining to the diagnosis and treatment of whiplash and whiplash-associated disorders (WAD), and to report on whiplash-related injuries.

METHODS: A search of OVID Medline (1996-January 2007) and the Cochrane database of systematic reviews was performed using the keywords whiplash and WAD. Articles under subheadings for pathology, diagnosis, treatment, and epidemiology were chosen for review after identification by the authors.

RESULTS: A total of 485 articles in the English language literature were identified. Thirty-six articles pertained to the diagnosis, treatment, epidemiology of whiplash, and …

Short-Wavelength Light Sensitivity Of Circadian, Pupillary, And Visual Awareness In Humans Lacking An Outer Retina, Farhan H. Zaidi, Joseph T. Hull, Stuart N. Peirson, Katharina Wulff, Daniel Aeschbach, Joshua J. Gooley, George C. Brainard, Kevin Gregory-Evans, Joseph F. Rizzo Iii, Charles A. Czeisler, Russell G. Foster, Merrick J. Moseley, Steven W. Lockley

Department of Neurology Faculty Papers

As the ear has dual functions for audition and balance, the eye has a dual role in detecting light for a wide range of behavioral and physiological functions separate from sight. These responses are driven primarily by stimulation of photosensitive retinal ganglion cells (pRGCs) that are most sensitive to short-wavelength ( approximately 480 nm) blue light and remain functional in the absence of rods and cones. We examined the spectral sensitivity of non-image-forming responses in two profoundly blind subjects lacking functional rods and cones (one male, 56 yr old; one female, 87 yr old). In the male subject, we found …

Teaching Case: Occipital Neuralgia In A Young Patient - Expert Commentary, Avi Ashkenazi

Department of Neurology Faculty Papers

Expert commentary on Carayannopoulos, AG. Teaching case: Occipital neuralgia in a young patient, 47(9):1367-1368, October 2007.

Teaching Case: Headache Stigmata, Michael Marmura, Seymour Solomon

Department of Neurology Faculty Papers

A 38-year-old man with past medical history of hypertension and obesity presented to our clinic for evaluation of severe headaches and multiple episodes of discoloration of the forehead on the same side as the headache.

Meeting Report: The Role Of Environmental Lighting And Circadian Disruption In Cancer And Other Diseases, Richard G. Stevens, David E. Blask, George C. Brainard, Johnni Hansen, Steven W. Lockley, Ignacio Provencio, Mark S. Rea, Leslie Reinlib

Department of Neurology Faculty Papers

Light, including artificial light, has a range of effects on human physiology and behavior and can therefore alter human physiology when inappropriately timed. One example of potential light-induced disruption is the effect of light on circadian organization, including the production of several hormone rhythms. Changes in light-dark exposure (e.g., by nonday occupation or transmeridian travel) shift the timing of the circadian system such that internal rhythms can become desynchronized from both the external environment and internally with each other, impairing our ability to sleep and wake at the appropriate times and compromising physiologic and metabolic processes. Light can also have …

Hemicrania Continua-Like Headache Associated With Carotid Dissection May Respond To Indomethacin, Avi Ashkenazi, Muhammad A. Abbas, Dinesh K. Sharma, Stephen D. Silberstein

Department of Neurology Faculty Papers

Hemicrania continua (HC) is an idiopathic, chronic disorder characterized by a continuous, strictly unilateral headache associated with ipsilateral cranial autonomic symptoms. The symptoms of HC typically respond dramatically to indomethacin therapy. We describe a patient with traumatic internal carotid artery (ICA) dissection, who presented with a clinical picture mimicking HC that initially responded to indomethacin. Patients with a clinical picture similar to HC should be managed with a high index of suspicion for a possible cervical arterial dissection.