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    Education

    BrainWaves: A Neurology Podcast

    BrainWaves is an academic audio podcast whose mission is to educate medical providers through clinical cases and topical reviews in neurology and medicine. Follow us on Twitter @brainwavesaudio, or just tune in every Thursday for the latest shows! **NOT FOR CLINICAL DECISION MAKING**

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    Copyright: © All rights reserved

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    Latest Episodes:
    #151 It's not over yet…part 1: Opening Pandora's black box Nov 14, 2019
    Show notes

    The FDA label for ACTEMRA (tocilizumab)--the first medication approved for use in giant cell arteritis in 2017--is 40 pages long. Of the information provided in this document, which includes important dosing information, dose adjustments based on leukocyte count, clinical trial and epidemiologic data, there is a box of text on the first page of the insert. "WARNING: RISK OF SERIOUS INFECTIONS" it reads.

    What do you make of this warning? And with such a clear and broad-sweeping statement stamped on the medication, how do you mitigate the medico-legal risk for using this drug?

    This week on the program we launch into a 2-part series focused on some of the events which follow major clinical trials. In part 1, we cover the 3 major classifications of FDA alerts for medical treatments using 2 examples from the neurologic pharmacopoeia. In part 2, we emphasize the importance of post-publication peer review. And both are equally instrumental in our medical decision making.

    Produced by James E. Siegler with the support of Michael Rubenstein (University of Pennsylvania) and Zachary Newcomer (University of Florida). Music courtesy of Coldnoise, Cuicuitte, Doctor Turtle, Jahzzar, and Peter Rudenko under a CC license. Sound effects by Mike Koenig and Daniel Simion. BrainWaves' podcasts and online content are intended for medical education only and should not be used for clinical decision making. None of what is discussed here should be misconstrued as medical advice, so don't just go prescribing drugs off-label! (Or willy nilly, as my grandmother might say) Be sure to follow us on Twitter @brainwavesaudio for the latest updates to the podcast.

    REFERENCES

    1. Schneider LS, Dagerman KS and Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA : the journal of the American Medical Association. 2005;294:1934-43.
    2. Ballard C, Hanney ML, Theodoulou M, Douglas S, McShane R, Kossakowski K, Gill R, Juszczak E, Yu LM, Jacoby R and investigators D-A. The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial. The Lancet Neurology. 2009;8:151-7.
    3. Moore TJ, Singh S and Furberg CD. The FDA and new safety warnings. Archives of internal medicine. 2012;172:78-80.
    4. Dorsey ER, Beck CA, Darwin K, Nichols P, Brocht AF, Biglan KM, Shoulson I and Huntington Study Group CI. Natural history of Huntington disease. JAMA Neurol. 2013;70:1520-30.
    5. Hubers AA, van Duijn E, Roos RA, Craufurd D, Rickards H, Bernhard Landwehrmeyer G, van der Mast RC, Giltay EJ and Network RiotEHsD. Suicidal ideation in a European Huntington's disease population. J Affect Disord. 2013;151:248-58.
    6. Shen V, Clarence-Smith K, Hunter C and Jankovic J. Safety and Efficacy of Tetrabenazine and Use of Concomitant Medications During Long-Term, Open-Label Treatment of Chorea Associated with Huntington's and Other Diseases. Tremor Other Hyperkinet Mov (N Y). 2013;3.
    7. Schultz JL, Killoran A, Nopoulos PC, Chabal CC, Moser DJ and Kamholz JA. Evaluating depression and suicidality in tetrabenazine users with Huntington disease. Neurology. 2018;91:e202-e207.
    8. Rose RV and Kass JS. Prescribing Antipsychotic Medications to Patients With Dementia: Boxed Warnings and Mitigation of Legal Liability. Continuum (Minneap Minn). 2019;25:254-259.
    9. US Food and Drug Administration. Guidance for industry: warnings and precautions, contraindications, and boxed warning sections of labeling for human prescription drug and biological products—content and format. www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm075096.pdf. Published October 2011. Accessed 11 July 2019.
    Halloween special 2019: Young Frankenstein Oct 31, 2019
    Show notes

    This year, Halloween falls on a Thursday. So we've put together a special episode to celebrate it! But first...a question: What do Frankenstein's monster, Spock, and Rick Deckard all have in common? Find out in this week's episode of BrainWaves.

    Produced by James E. Siegler. Special guest, Scott Kasner (Hospital of the University of Pennsylvania) with fair use of material from Young Frankenstein (1974), Star Trek: The Original Series (1966-1969), and Blade Runner (1982). Music courtesy of Grossman, Ewell and Grainger, Heftone Banjo Orchestra, Sergey Chereminisov, and Ondrosik under a Creative Commons License. Sound effects by Mike Koenig. BrainWaves' podcasts and online content are intended for medical education only and should not be used for clinical decision making. Be sure to follow us on Twitter @brainwavesaudio for the latest updates to the podcast.

    REFERENCES

    1. Labbe R, Firl A, Jr., Mufson EJ and Stein DG. Fetal brain transplant: reduction of cognitive deficits in rats with frontal cortex lesions. Science. 1983;221:470-2.
    2. Brain transplant for Parkinson's disease. Lancet. 1987;1:1012-3.
    3. Ignacio V, Collins VP, Suard IM and Jacque CM. Survival of astroglial cell lineage from adult brain transplant. Dev Neurosci. 1989;11:175-8.
    4. Landau WM. Clinical neuromythology VII. Artificial intelligence: the brain transplant cure for parkinsonism. Neurology. 1990;40:733-40.
    5. Freed CR, Breeze RE, Rosenberg NL, Schneck SA, Kriek E, Qi JX, Lone T, Zhang YB, Snyder JA, Wells TH and et al. Survival of implanted fetal dopamine cells and neurologic improvement 12 to 46 months after transplantation for Parkinson's disease. The New England journal of medicine. 1992;327:1549-55.
    6. Landau WM. Clinical neuromythology X. Faithful fashion: survival status of the brain transplant cure for parkinsonism. Neurology. 1993;43:644-9.
    7. Grabowski M, Johansson BB and Brundin P. Neocortical grafts placed in the infarcted brain of adult rats: few or no efferent fibers grow from transplant to host. Exp Neurol. 1995;134:273-6.
    8. Schulz MK, McNulty JA, Handa RJ, Hogan TP, Tillotson GL, Shaw PL, Zimmer J and Castro AJ. Fetal neocortical transplants grafted into neocortical lesion cavities made in newborn rats: an analysis of transplant integration with the host brain. Cell Transplant. 1995;4:123-32.
    9. Deacon T, Schumacher J, Dinsmore J, Thomas C, Palmer P, Kott S, Edge A, Penney D, Kassissieh S, Dempsey P and Isacson O. Histological evidence of fetal pig neural cell survival after transplantation into a patient with Parkinson's disease. Nat Med. 1997;3:350-3.
    10. Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R, Dillon S, Winfield H, Culver S, Trojanowski JQ, Eidelberg D and Fahn S. Transplantation of embryonic dopamine neurons for severe Parkinson's disease. The New England journal of medicine. 2001;344:710-9.
    11. Bhattacharya N, Chhetri MK, Mukherjee KL, Ghosh AB, Samanta BK, Mitra R, Bhattacharya M, Bhattacharya S and Bandopadhyaya T. Can human fetal cortical brain tissue transplant (up to 20 weeks) sustain its metabolic and oxygen requirements in a heterotopic site outside the brain? A study of 12 volunteers with Parkinson's disease. Clin Exp Obstet Gynecol. 2002;29:259-66.
    12. Kumar R and Mahapatra AK. Concept of brain transplant in pre-historic era. Childs Nerv Syst. 2009;25:393-4.
    13. Bjorklund A, Dunnett SB, Stenevi U, Lewis ME and Iversen SD. Reinnervation of the denervated striatum by substantia nigra transplants: functional consequences as revealed by pharmacological and sensorimotor testing. Brain Res. 1980;199:307-33.
    #150 Patient narrative part 2: It started with back pain… Oct 17, 2019
    Show notes

    College is a tough time for any kid. But it should also be exciting. Then to experience the freedoms of young adulthood, only later to face the horrifying reality of a progressive neurodegenerative condition...it's not something anyone should experience. In this week's continuation of the patient narrative series, Dr. Paul McIntosh (Duke) shares his life-changing story, and his optimism, about surviving a chronic neurological illness.

    Produced by James E. Siegler with the help of Paul McIntosh. For more information about Pompe Disease, check out the resources provided by the United Pompe Foundation at unitedpompe.com. Music for our program this week was courtesy of Ars Sonor, Franz Danzi, Lee Rosevere, and Scott Holmes. Sound effects by Mike Koenig and Daniel Simion. BrainWaves' podcasts and online content are intended for medical education only and should not be used for clinical decision making. Be sure to follow us on Twitter @brainwavesaudio for the latest updates to the podcast.

    REFERENCES

    1. Kishnani PS and Howell RR. Pompe disease in infants and children. J Pediatr. 2004;144:S35-43.
    2. Van den Hout JM, Kamphoven JH, Winkel LP, Arts WF, De Klerk JB, Loonen MC, Vulto AG, Cromme-Dijkhuis A, Weisglas-Kuperus N, Hop W, Van Hirtum H, Van Diggelen OP, Boer M, Kroos MA, Van Doorn PA, Van der Voort E, Sibbles B, Van Corven EJ, Brakenhoff JP, Van Hove J, Smeitink JA, de Jong G, Reuser AJ and Van der Ploeg AT. Long-term intravenous treatment of Pompe disease with recombinant human alpha-glucosidase from milk. Pediatrics. 2004;113:e448-57.
    3. Klinge L, Straub V, Neudorf U, Schaper J, Bosbach T, Gorlinger K, Wallot M, Richards S and Voit T. Safety and efficacy of recombinant acid alpha-glucosidase (rhGAA) in patients with classical infantile Pompe disease: results of a phase II clinical trial. Neuromuscul Disord. 2005;15:24-31.
    4. Kishnani PS, Corzo D, Nicolino M, Byrne B, Mandel H, Hwu WL, Leslie N, Levine J, Spencer C, McDonald M, Li J, Dumontier J, Halberthal M, Chien YH, Hopkin R, Vijayaraghavan S, Gruskin D, Bartholomew D, van der Ploeg A, Clancy JP, Parini R, Morin G, Beck M, De la Gastine GS, Jokic M, Thurberg B, Richards S, Bali D, Davison M, Worden MA, Chen YT and Wraith JE. Recombinant human acid [alpha]-glucosidase: major clinical benefits in infantile-onset Pompe disease. Neurology. 2007;68:99-109.
    5. Wokke JH, Escolar DM, Pestronk A, Jaffe KM, Carter GT, van den Berg LH, Florence JM, Mayhew J, Skrinar A, Corzo D and Laforet P. Clinical features of late-onset Pompe disease: a prospective cohort study. Muscle Nerve. 2008;38:1236-45.
    6. van der Ploeg AT, Clemens PR, Corzo D, Escolar DM, Florence J, Groeneveld GJ, Herson S, Kishnani PS, Laforet P, Lake SL, Lange DJ, Leshner RT, Mayhew JE, Morgan C, Nozaki K, Park DJ, Pestronk A, Rosenbloom B, Skrinar A, van Capelle CI, van der Beek NA, Wasserstein M and Zivkovic SA. A randomized study of alglucosidase alfa in late-onset Pompe's disease. The New England journal of medicine. 2010;362:1396-406.
    7. Cupler EJ, Berger KI, Leshner RT, Wolfe GI, Han JJ, Barohn RJ, Kissel JT and Disease ACCoL-oP. Consensus treatment recommendations for late-onset Pompe disease. Muscle Nerve. 2012;45:319-33.
    8. Beltran Papsdorf TB, Howard JF, Jr. and Chahin N. Pearls & Oy-sters: clues to the diagnosis of adult-onset acid maltase deficiency. Neurology. 2014;82:e73-5.
    9. Gutierrez-Rivas E, Bautista J, Vilchez JJ, Muelas N, Diaz-Manera J, Illa I, Martinez-Arroyo A, Olive M, Sanz I, Arpa J, Fernandez-Torron R, Lopez de Munain A, Jimenez L, Solera J and Lukacs Z. Targeted screening for the detection of Pompe disease in patients with unclassified limb-girdle muscular dystrophy or asymptomatic hyperCKemia using dried blood: A Spanish cohort. Neuromuscul Disord. 2015;25:548-53.
    10. Lukacs Z, Nieves Cobos P, Wenninger S, Willis TA, Guglieri M, Roberts M, Quinlivan R, Hilton-Jones D, Evangelista T, Zierz S, Schlotter-Weigel B, Walter MC, Reilich P, Klopstock T, Deschauer M, Straub V, Muller-Felber W and Schoser B. Prevalence of Pompe disease in 3,076 patients with hyperCKemia and limb-girdle muscular weakness. Neurology. 2016;87:295-8.
    #149 Patient narrative part 1: The world's disability Oct 03, 2019
    Show notes

    Sara Henya would have you recognize her for her music, not her malady. While she may have Tourette Syndrome, she refuses to let it define her. In this week's episode of BrainWaves, we're launching a two part series featuring people who are living with a chronic neurologic illness--how they were diagnosed, how they cope with it, and of course, the neurobiology that underlies it.

    Produced by James E. Siegler with Dr. Michael Rubenstein and Sara Henya. Music courtesy of Sara Henya (find her music at www.sarahenya.com), Lee Rosevere, Loyalty Freak Music, Marco Trovatello, and Steve Combs. Sound effects by Mike Koenig and Daniel Simion. BrainWaves' podcasts and online content are intended for medical education only and should not be used for clinical decision making. Be sure to follow us on Twitter @brainwavesaudio for the latest updates to the podcast.

    REFERENCES

    1. Pringsheim T, Holler-Managan Y, Okun MS, Jankovic J, Piacentini J, Cavanna AE, Martino D, Muller-Vahl K, Woods DW, Robinson M, Jarvie E, Roessner V and Oskoui M. Comprehensive systematic review summary: Treatment of tics in people with Tourette syndrome and chronic tic disorders. Neurology. 2019;92:907-915.
    2. Pringsheim T, Okun MS, Muller-Vahl K, Martino D, Jankovic J, Cavanna AE, Woods DW, Robinson M, Jarvie E, Roessner V, Oskoui M, Holler-Managan Y and Piacentini J. Practice guideline recommendations summary: Treatment of tics in people with Tourette syndrome and chronic tic disorders. Neurology. 2019;92:896-906.
    3. Swain JE, Scahill L, Lombroso PJ, King RA and Leckman JF. Tourette syndrome and tic disorders: a decade of progress. J Am Acad Child Adolesc Psychiatry. 2007;46:947-68.
    4. Bruun RD. Gilles de la Tourette's syndrome. An overview of clinical experience. J Am Acad Child Psychiatry. 1984;23:126-33.
    5. Robertson MM. Tourette syndrome, associated conditions and the complexities of treatment. Brain. 2000;123 Pt 3:425-62.
    6. Yael D, Vinner E and Bar-Gad I. Pathophysiology of tic disorders. Mov Disord. 2015;30:1171-8.
    7. Pauls DL and Leckman JF. The inheritance of Gilles de la Tourette's syndrome and associated behaviors. Evidence for autosomal dominant transmission. The New England journal of medicine. 1986;315:993-7.
    8. Jankovic J, Jimenez-Shahed J and Brown LW. A randomised, double-blind, placebo-controlled study of topiramate in the treatment of Tourette syndrome. Journal of neurology, neurosurgery, and psychiatry. 2010;81:70-3.
    #34 The ALS multi-disciplinary clinic Sep 26, 2019
    Show notes

    This week on the program, our earlier episode on the multidisciplinary care of ALS patients gets a face lift. Since it originally aired in 2016, there have been several important advances in the treatment of these patients--including the first FDA approved therapy for this condition in more than 2 decades. But many of the core management strategies remain the same. Dr. Lauren Elman, Associate Professor of Neurology, Director of Research Operations and Associate Director of clinical care at the Penn Comprehensive ALS Center, shares her experience in this 2019 update.

    Produced by James E. Siegler. Music courtesy of Chris Zabriskie, Nuno Adelaida, and Meydan. Sound effects by Mike Koenig and Daniel Simion. BrainWaves' podcasts and online content are intended for medical education only and should not be used for clinical decision making. Be sure to follow us on Twitter @brainwavesaudio for the latest updates to the podcast.

    REFERENCES

    1. de Carvalho M, Dengler R, Eisen A, England JD, Kaji R, Kimura J, Mills K, Mitsumoto H, Nodera H, Shefner J and Swash M. Electrodiagnostic criteria for diagnosis of ALS. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology. 2008;119:497-503.
    2. Ludolph A, Drory V, Hardiman O, Nakano I, Ravits J, Robberecht W, Shefner J and ALS/MND WFNRGO. A revision of the El Escorial criteria - 2015. Amyotroph Lateral Scler Frontotemporal Degener. 2015;16:291-2.
    3. Geevasinga N, Loy CT, Menon P, de Carvalho M, Swash M, Schrooten M, Van Damme P, Gawel M, Sonoo M, Higashihara M, Noto Y, Kuwabara S, Kiernan MC, Macaskill P and Vucic S. Awaji criteria improves the diagnostic sensitivity in amyotrophic lateral sclerosis: A systematic review using individual patient data. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology. 2016;127:2684-91.
    4. Geevasinga N, Menon P, Scherman DB, Simon N, Yiannikas C, Henderson RD, Kiernan MC and Vucic S. Diagnostic criteria in amyotrophic lateral sclerosis: A multicenter prospective study. Neurology. 2016;87:684-90.
    5. Weiss MD, Macklin EA, Simmons Z, Knox AS, Greenblatt DJ, Atassi N, Graves M, Parziale N, Salameh JS, Quinn C, Brown RH, Jr., Distad JB, Trivedi J, Shefner JM, Barohn RJ, Pestronk A, Swenson A, Cudkowicz ME and Mexiletine ALSSG. A randomized trial of mexiletine in ALS: Safety and effects on muscle cramps and progression. Neurology. 2016;86:1474-81.
    6. Hardiman O and van den Berg LH. Edaravone: a new treatment for ALS on the horizon? The Lancet Neurology. 2017;16:490-491.
    7. Meininger V, Genge A, van den Berg LH, Robberecht W, Ludolph A, Chio A, Kim SH, Leigh PN, Kiernan MC, Shefner JM, Desnuelle C, Morrison KE, Petri S, Boswell D, Temple J, Mohindra R, Davies M, Bullman J, Rees P, Lavrov A and Group NOGS. Safety and efficacy of ozanezumab in patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet Neurology. 2017;16:208-216.
    8. Radunovic A, Annane D, Rafiq MK, Brassington R and Mustfa N. Mechanical ventilation for amyotrophic lateral sclerosis/motor neuron disease. The Cochrane database of systematic reviews. 2017;10:CD004427.
    9. Writing G and Edaravone ALSSG. Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. The Lancet Neurology. 2017;16:505-512.
    10. Oskarsson B, Moore D, Mozaffar T, Ravits J, Wiedau-Pazos M, Parziale N, Joyce NC, Mandeville R, Goyal N, Cudkowicz ME, Weiss M, Miller RG and McDonald CM. Mexiletine for muscle cramps in amyotrophic lateral sclerosis: A randomized, double-blind crossover trial. Muscle Nerve. 2018.
    11. Luo L, Song Z, Li X, Huiwang, Zeng Y, Qinwang, Meiqi and He J. Efficacy and safety of edaravone in treatment of amyotrophic lateral sclerosis-a systematic review and meta-analysis. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2019;40:235-241.
    12. Statland JM, Moore D, Wang Y, Walsh M, Mozaffar T, Elman L, Nations SP, Mitsumoto H, Fernandes JA, Saperstein D, Hayat G, Herbelin L, Karam C, Katz J, Wilkins HM, Agbas A, Swerdlow RH, Santella RM, Dimachkie MM, Barohn RJ, Rasagiline Investigators of the Muscle Study G and Western ALSC. Rasagiline for amyotrophic lateral sclerosis: A randomized, controlled trial. Muscle Nerve. 2019;59:201-207.
    13. Miller RG, Jackson CE, Kasarskis EJ, England JD, Forshew D, Johnston W, Kalra S, Katz JS, Mitsumoto H, Rosenfeld J, Shoesmith C, Strong MJ, Woolley SC and Quality Standards Subcommittee of the American Academy of N. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: multidisciplinary care, symptom management, and cognitive/behavioral impairment (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2009;73:1227-33.
    14. Miller RG, Jackson CE, Kasarskis EJ, England JD, Forshew D, Johnston W, Kalra S, Katz JS, Mitsumoto H, Rosenfeld J, Shoesmith C, Strong MJ, Woolley SC and Quality Standards Subcommittee of the American Academy of N. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2009;73:1218-26.
    #148 Teaching through clinical cases: A curious case of infectious encephalitis Sep 19, 2019
    Show notes

    In this week's clinical case, Dr. Mike Bradshaw (Chicago Medical School and Billings Clinic) walks us through the case of a young woman with HSV encephalitis.

    With a twist.

    SPOILER ALERT: If you don't want to know the answer, DON'T LOOK AT THE SHOWNOTES!

    Produced by James E. Siegler and Mike Bradshaw. Music courtesy of Yan Terrien, Unheard Music Concepts, Steve Combs, and Montplaisir. Sound effects by Mike Koenig and Daniel Simion. BrainWaves' podcasts and online content are intended for medical education only and should not be used for clinical decision making. Be sure to follow us on Twitter @brainwavesaudio for the latest updates to the podcast.

    REFERENCES

    1. Bacon TH, Boon RJ, Schultz M and Hodges-Savola C. Surveillance for antiviral-agent-resistant herpes simplex virus in the general population with recurrent herpes labialis. Antimicrob Agents Chemother. 2002;46:3042-4.
    2. Granerod J, Ambrose HE, Davies NW, Clewley JP, Walsh AL, Morgan D, Cunningham R, Zuckerman M, Mutton KJ, Solomon T, Ward KN, Lunn MP, Irani SR, Vincent A, Brown DW, Crowcroft NS and Group UKHPAAoES. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis. 2010;10:835-44.
    3. Steiner I, Budka H, Chaudhuri A, Koskiniemi M, Sainio K, Salonen O and Kennedy PG. Viral meningoencephalitis: a review of diagnostic methods and guidelines for management. European journal of neurology : the official journal of the European Federation of Neurological Societies. 2010;17:999-e57.
    4. Gable MS, Sheriff H, Dalmau J, Tilley DH and Glaser CA. The frequency of autoimmune N-methyl-D-aspartate receptor encephalitis surpasses that of individual viral etiologies in young individuals enrolled in the California Encephalitis Project. Clin Infect Dis. 2012;54:899-904.
    5. Pruss H, Finke C, Holtje M, Hofmann J, Klingbeil C, Probst C, Borowski K, Ahnert-Hilger G, Harms L, Schwab JM, Ploner CJ, Komorowski L, Stoecker W, Dalmau J and Wandinger KP. N-methyl-D-aspartate receptor antibodies in herpes simplex encephalitis. Annals of neurology. 2012;72:902-11.
    6. Armangue T, Leypoldt F and Dalmau J. Autoimmune encephalitis as differential diagnosis of infectious encephalitis. Curr Opin Neurol. 2014;27:361-8.
    7. Armangue T, Leypoldt F, Malaga I, Raspall-Chaure M, Marti I, Nichter C, Pugh J, Vicente-Rasoamalala M, Lafuente-Hidalgo M, Macaya A, Ke M, Titulaer MJ, Hoftberger R, Sheriff H, Glaser C and Dalmau J. Herpes simplex virus encephalitis is a trigger of brain autoimmunity. Annals of neurology. 2014;75:317-23.
    8. Venkatesan A and Benavides DR. Autoimmune encephalitis and its relation to infection. Current neurology and neuroscience reports. 2015;15:3.
    9. Linnoila JJ, Binnicker MJ, Majed M, Klein CJ and McKeon A. CSF herpes virus and autoantibody profiles in the evaluation of encephalitis. Neurol Neuroimmunol Neuroinflamm. 2016;3:e245.
    10. Armangue T, Spatola M, Vlagea A, Mattozzi S, Carceles-Cordon M, Martinez-Heras E, Llufriu S, Muchart J, Erro ME, Abraira L, Moris G, Monros-Gimenez L, Corral-Corral I, Montejo C, Toledo M, Bataller L, Secondi G, Arino H, Martinez-Hernandez E, Juan M, Marcos MA, Alsina L, Saiz A, Rosenfeld MR, Graus F, Dalmau J and Spanish Herpes Simplex Encephalitis Study G. Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: a prospective observational study and retrospective analysis. The Lancet Neurology. 2018;17:760-772.
    11. Dubey D, Pittock SJ, Kelly CR, McKeon A, Lopez-Chiriboga AS, Lennon VA, Gadoth A, Smith CY, Bryant SC, Klein CJ, Aksamit AJ, Toledano M, Boeve BF, Tillema JM and Flanagan EP. Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Annals of neurology. 2018;83:166-177.
    Quanta: PREVENTing relapses of Aqp4-Ab NMO Sep 12, 2019
    Show notes

    We just used clinical trial data regarding eculizumab in myasthenia gravis as an example of how to critically appraise the literature, and in this week's program...MORE data on the efficacy of eculizumab in another neurological condition. This week on BrainWaves, the exciting results of the PREVENT trial and the future treatment of NMO spectrum disorder!

    Produced by James E. Siegler. Special thanks to Dr. Olga Rosenveld Thon. Music courtesy of Unheard Music Concepts, TRG Banks, and Aitua. Sound effects by Mike Koenig and baby Sofia Joan Siegler. BrainWaves' podcasts and online content are intended for medical education only and should not be used for clinical decision making. Be sure to follow us on Twitter @brainwavesaudio for the latest updates to the podcast.

    REFERENCES

    1. Pittock SJ, Lennon VA, McKeon A, Mandrekar J, Weinshenker BG, Lucchinetti CF, O'Toole O and Wingerchuk DM. Eculizumab in AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: an open-label pilot study. The Lancet Neurology. 2013;12:554-62.
    2. Pittock SJ, Berthele A, Fujihara K, Kim HJ, Levy M, Palace J, Nakashima I, Terzi M, Totolyan N, Viswanathan S, Wang KC, Pace A, Fujita KP, Armstrong R and Wingerchuk DM. Eculizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. The New England journal of medicine. 2019;381:614-625.
    3. FDA News Release: FDA approved first treatment for neuromyelitis optica spectrum disorder, a rare autoimmune disease of the central nervous system. 27 June 2019. Available online at https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-neuromyelitis-optica-spectrum-disorder-rare-autoimmune-disease-central. Accessed 30 Aug 2019.
    #147 I wonder: p-value Sep 05, 2019
    Show notes

    One study shows that 30 minutes of exercise 5 times a week can reduce your risk of squamous cell carcinoma of the skin, p=0.001. (Let's pretend this is true). What does this mean?

    Well, let's start by asking the question, how IMPORTANT is it that you reduce your risk of SCC of the skin, and how MUCH does exercise reduce that risk? If the effect of exercise is associated with a relative risk reduction of 1% in your lifetime risk of SCC, is that enough to get you to spend 1 week of your life each year on a treadmill?

    In this week's "I wonder" series, Dr. Ali Hamedani joins Jim Siegler to discuss the difference between statistical significance and clinical importance, how to interpret p-values, and exactly what kinds of conclusions you should draw from clinical studies.

    Produced by James E. Siegler and Ali Hamedani. Music courtesy of Jahzzar, Kevin McLeod, Sergey Cheremisinov, and the trio Grossman, Ewell and Grainger. Sound effects by Mike Koenig and Daniel Simion. BrainWaves' podcasts and online content are intended for medical education only and should not be used for clinical decision making. Be sure to follow us on Twitter @brainwavesaudio for the latest updates to the podcast.

    REFERENCES

    1. Gardner MJ and Altman DG. Confidence intervals rather than P values: estimation rather than hypothesis testing. Br Med J (Clin Res Ed). 1986;292:746-50.
    2. Goodman SN. Toward evidence-based medical statistics. 1: The P value fallacy. Annals of internal medicine. 1999;130:995-1004.
    3. Bartolucci AA, Tendera M and Howard G. Meta-analysis of multiple primary prevention trials of cardiovascular events using aspirin. The American journal of cardiology. 2011;107:1796-801.
    4. Pocock SJ and Stone GW. The Primary Outcome Fails - What Next? The New England journal of medicine. 2016;375:861-70.
    5. Howard JF, Jr., Utsugisawa K, Benatar M, Murai H, Barohn RJ, Illa I, Jacob S, Vissing J, Burns TM, Kissel JT, Muppidi S, Nowak RJ, O'Brien F, Wang JJ, Mantegazza R and Group RS. Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study. The Lancet Neurology. 2017;16:976-986.
    6. Muppidi S, Utsugisawa K, Benatar M, Murai H, Barohn RJ, Illa I, Jacob S, Vissing J, Burns TM, Kissel JT, Nowak RJ, Andersen H, Casasnovas C, de Bleecker JL, Vu TH, Mantegazza R, O'Brien FL, Wang JJ, Fujita KP, Howard JF, Jr. and Regain Study G. Long-term safety and efficacy of eculizumab in generalized myasthenia gravis. Muscle Nerve. 2019;60:14-24.
    7. National Institute of Neurological D and Stroke rt PASSG. Tissue plasminogen activator for acute ischemic stroke. The New England journal of medicine. 1995;333:1581-7.
    8. Fritz CO, Morris PE and Richler JJ. Effect size estimates: current use, calculations, and interpretation. J Exp Psychol Gen. 2012;141:2-18.
    #146 Tangled up in squiggles: EEG 101 and the ictal inter-ictal continuum Aug 22, 2019
    Show notes

    This week on the BrainWaves podcast, finally...a REAL show about BRAINWAVES! Dr. Carolina Maciel, of the University of Florida, schools Jim Siegler on how to read EEG and interpret abnormal patterns across the ictal-interictal continuum.

    Produced by James E. Siegler and Carolina Maciel. Music courtesy of Chris Zabriskie, Montplaisir, Rafael Archangel, Steve Combs, Unheard Music Concepts, and Siddhartha. Sound effects by Mike Koenig and Daniel Simion. BrainWaves' podcasts and online content are intended for medical education only and should not be used for clinical decision making. Be sure to follow us on Twitter @brainwavesaudio for the latest updates to the podcast.

    REFERENCES

    1. Chong DJ and Hirsch LJ. Which EEG patterns warrant treatment in the critically ill? Reviewing the evidence for treatment of periodic epileptiform discharges and related patterns. Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society. 2005;22:79-91.
    2. Benbadis SR, LaFrance WC, Jr., Papandonatos GD, Korabathina K, Lin K, Kraemer HC and Workshop NEST. Interrater reliability of EEG-video monitoring. Neurology. 2009;73:843-6.
    3. Hirsch LJ, LaRoche SM, Gaspard N, Gerard E, Svoronos A, Herman ST, Mani R, Arif H, Jette N, Minazad Y, Kerrigan JF, Vespa P, Hantus S, Claassen J, Young GB, So E, Kaplan PW, Nuwer MR, Fountain NB and Drislane FW. American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology: 2012 version. Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society. 2013;30:1-27.
    4. Gaspard N, Hirsch LJ, LaRoche SM, Hahn CD, Westover MB and Critical Care EEGMRC. Interrater agreement for Critical Care EEG Terminology. Epilepsia. 2014;55:1366-73.
    5. Newey CR, Sahota P and Hantus S. Electrographic Features of Lateralized Periodic Discharges Stratify Risk in the Interictal-Ictal Continuum. Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society. 2017;34:365-369.
    6. Rubinos C, Reynolds AS and Claassen J. The Ictal-Interictal Continuum: To Treat or Not to Treat (and How)? Neurocritical care. 2018;29:3-8.
    7. Gerber PA, Chapman KE, Chung SS, Drees C, Maganti RK, Ng YT, Treiman DM, Little AS and Kerrigan JF. Interobserver agreement in the interpretation of EEG patterns in critically ill adults. Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society. 2008;25:241-9.
    8. Beniczky S, Hirsch LJ, Kaplan PW, Pressler R, Bauer G, Aurlien H, Brogger JC and Trinka E. Unified EEG terminology and criteria for nonconvulsive status epilepticus. Epilepsia. 2013;54 Suppl 6:28-9.
    9. Claassen J. How I treat patients with EEG patterns on the ictal-interictal continuum in the neuro ICU. Neurocritical care. 2009;11:437-44.
    #145 Astroglia and Alzheimer's disease Aug 08, 2019
    Show notes

    Clean up on aisle 4!

    Or should it be IL-4? In this week's installment of the BrainWaves Podcast, we submerge ourselves into the microscopic environment of Alzheimer's pathology. It's interesting, it's messy, and whoever made this mess is also responsible for the clean up.

    Produced by James E. Siegler. Music courtesy of Andy Cohen, Brendan Kinsella, Cuicuitte, Damiano Baldoni, Kai Engel, Nctrnm. Sound effects by Mike Koenig, Blastfx.com, Caroline Ford, Robertv, and Daniel Simion. BrainWaves' podcasts and online content are intended for medical education only and should not be used for clinical decision making. Be sure to follow us on Twitter @brainwavesaudio for the latest updates to the podcast.

    REFERENCES

    1. Arranz AM and De Strooper B. The role of astroglia in Alzheimer's disease: pathophysiology and clinical implications. The Lancet Neurology. 2019;18:406-414.
    2. Maragakis NJ and Rothstein JD. Mechanisms of Disease: astrocytes in neurodegenerative disease. Nat Clin Pract Neurol. 2006;2:679-89.
    3. Wisniewski T and Konietzko U. Amyloid-beta immunisation for Alzheimer's disease. The Lancet Neurology. 2008;7:805-11.
    4. Mattsson N, Zetterberg H, Hansson O, Andreasen N, Parnetti L, Jonsson M, Herukka SK, van der Flier WM, Blankenstein MA, Ewers M, Rich K, Kaiser E, Verbeek M, Tsolaki M, Mulugeta E, Rosen E, Aarsland D, Visser PJ, Schroder J, Marcusson J, de Leon M, Hampel H, Scheltens P, Pirttila T, Wallin A, Jonhagen ME, Minthon L, Winblad B and Blennow K. CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA : the journal of the American Medical Association. 2009;302:385-93.
    5. Breitner JC, Baker LD, Montine TJ, Meinert CL, Lyketsos CG, Ashe KH, Brandt J, Craft S, Evans DE, Green RC, Ismail MS, Martin BK, Mullan MJ, Sabbagh M, Tariot PN and Group AR. Extended results of the Alzheimer's disease anti-inflammatory prevention trial. Alzheimers Dement. 2011;7:402-11.
    6. Yan R and Vassar R. Targeting the beta secretase BACE1 for Alzheimer's disease therapy. The Lancet Neurology. 2014;13:319-29.
    7. Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, Jacobs AH, Wyss-Coray T, Vitorica J, Ransohoff RM, Herrup K, Frautschy SA, Finsen B, Brown GC, Verkhratsky A, Yamanaka K, Koistinaho J, Latz E, Halle A, Petzold GC, Town T, Morgan D, Shinohara ML, Perry VH, Holmes C, Bazan NG, Brooks DJ, Hunot S, Joseph B, Deigendesch N, Garaschuk O, Boddeke E, Dinarello CA, Breitner JC, Cole GM, Golenbock DT and Kummer MP. Neuroinflammation in Alzheimer's disease. The Lancet Neurology. 2015;14:388-405.
    8. Kumar A, Singh A and Ekavali. A review on Alzheimer's disease pathophysiology and its management: an update. Pharmacol Rep. 2015;67:195-203.
    9. Rodriguez-Arellano JJ, Parpura V, Zorec R and Verkhratsky A. Astrocytes in physiological aging and Alzheimer's disease. Neuroscience. 2016;323:170-82.
    10. Chun H and Lee CJ. Reactive astrocytes in Alzheimer's disease: A double-edged sword. Neurosci Res. 2018;126:44-52.
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