BrainWaves: A Neurology Podcast

This week on the program, we have remastered one of our earliest (and most interesting!) episodes on Guillain-Barre syndrome. With an important announcement from Jim Siegler. Produced by James E. Siegler. Music courtesy of Lee Rosevere. The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 Dimachkie MM and Saperstein DS. Acquired immune demyelinating neuropathies. Continuum (Minneap Minn). 2014;20:1241-60. Osler W. The principles and practice of medicine. New York: Appleton; 1892. Gray H. History of lumbar puncture (rachicentesis): The operation and the idea. Arch Neurol Psych. 1921;6:61-69. Asbury AK. Guillain-Barre syndrome: historical aspects. Annals of neurology. 1990;27 Suppl:S2-6. Afifi AK. The landry-guillain-barre strohl syndrome 1859 to 1992 a historical perspective. J Family Community Med. 1994;1:30-4. Bril V and Katzberg HD. Acquired immune axonal neuropathies. Continuum (Minneap Minn). 2014;20:1261-73. Iodice V and Sandroni P. Autonomic neuropathies. Continuum (Minneap Minn). 2014;20:1373-97. Lehmann HC, Hartung HP, Kieseier BC and Hughes RA. Guillain-Barre syndrome after exposure to influenza virus. Lancet Infect Dis. 2010;10:643-51. Sivadon-Tardy V, Orlikowski D, Porcher R, Sharshar T, Durand MC, Enouf V, Rozenberg F, Caudie C, Annane D, van der Werf S, Lebon P, Raphael JC, Gaillard JL and Gault E. Guillain-Barre syndrome and influenza virus infection. Clin Infect Dis. 2009;48:48-56. Stowe J, Andrews N, Wise L and Miller E. Investigation of the temporal association of Guillain-Barre syndrome with influenza vaccine and influenzalike illness using the United Kingdom General Practice Research Database. American journal of epidemiology. 2009;169:382-8. Tam CC, O'Brien SJ, Petersen I, Islam A, Hayward A and Rodrigues LC. Guillain-Barre syndrome and preceding infection with campylobacter, influenza and Epstein-Barr virus in the general practice research database. PloS one. 2007;2:e344. Tam CC, O'Brien SJ and Rodrigues LC. Influenza, Campylobacter and Mycoplasma infections, and hospital admissions for Guillain-Barre syndrome, England. Emerg Infect Dis. 2006;12:1880-7. Dawood FS, Chaves SS, Perez A, Reingold A, Meek J, Farley MM, Ryan P, Lynfield R, Morin C, Baumbach J, Bennett NM, Zansky S, Thomas A, Lindegren ML, Schaffner W, Finelli L and Emerging Infections Program N. Complications and associated bacterial coinfections among children hospitalized with seasonal or pandemic influenza, United States, 2003-2010. The Journal of infectious diseases. 2014;209:686-94. McDermott M, Gelb DJ, Wilson K, Pawloski M, Burke JF, Shelgikar AV and London ZN. Sex Differences in Academic Rank and Publication Rate at Top-Ranked US Neurology Programs. JAMA Neurol. 2018;75:956-961. Keddie S, Pakpoor J, Mousele C, Pipis M, Machado PM, Foster M, Record CJ, Keh RYS, Fehmi J, Paterson RW, Bharambe V, Clayton LM, Allen C, Price O, Wall J, Kiss-Csenki A, Rathnasabapathi DP, Geraldes R, Yermakova T, King-Robson J, Zosmer M, Rajakulendran S, Sumaria S, Farmer SF, Nortley R, Marshall CR, Newman EJ, Nirmalananthan N, Kumar G, Pinto AA, Holt J, Lavin TM, Brennan KM, Zandi MS, Jayaseelan DL, Pritchard J, Hadden RDM, Manji H, Willison HJ, Rinaldi S, Carr AS and Lunn MP. Epidemiological and cohort study finds no association between COVID-19 and Guillain-Barre syndrome. Brain. 2021;144:682-693. Lunn MP, Cornblath DR, Jacobs BC, Querol L, van Doorn PA, Hughes RA and Willison HJ. COVID-19 vaccine and Guillain-Barre syndrome: let's not leap to associations. Brain. 2021;144:357-360.

The field of neurocritical care and traumatic brain injury management is rapidly evolving. We are shifting from older (but not entirely outdated) monitoring techniques to novel diagnostic and therapeutic advances in critical care medicine. Managing intracranial pressure crises involves the careful tiptoeing of a line between maintaining brain circulation and yet reducing intracranial fluid volume. And many of our interventions rely on one simple mathematical construct: CPP = MAP - ICP [Cerebral perfusion pressure = Mean arterial pressure – Intracranial pressure] The importance of this formula cannot be understated. So we are spending 35 minutes today reviewing it, and discussing pearls and pitfalls of ICP monitoring and management. But believe me, it’s worth it. Produced by James E. Siegler and Jon Rosenberg. Music courtesy of Unheard Music Concepts, Rafael Archangel, Milton Arias, and Quincas Moreira. The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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  Rosner MJ and Coley IB. Cerebral perfusion pressure, intracranial pressure, and head elevation. Journal of neurosurgery. 1986;65:636-41. Chesnut RM, Temkin N, Carney N, Dikmen S, Rondina C, Videtta W, Petroni G, Lujan S, Pridgeon J, Barber J, Machamer J, Chaddock K, Celix JM, Cherner M, Hendrix T and Global Neurotrauma Research G. A trial of intracranial-pressure monitoring in traumatic brain injury. The New England journal of medicine. 2012;367:2471-81. Kristiansson H, Nissborg E, Bartek J, Jr., Andresen M, Reinstrup P and Romner B. Measuring elevated intracranial pressure through noninvasive methods: a review of the literature. J Neurosurg Anesthesiol. 2013;25:372-85. Armstead WM. Cerebral Blood Flow Autoregulation and Dysautoregulation. Anesthesiol Clin. 2016;34:465-77. Oddo M, Crippa IA, Mehta S, Menon D, Payen JF, Taccone FS and Citerio G. Optimizing sedation in patients with acute brain injury. Crit Care. 2016;20:128. Carney N, Totten AM, O'Reilly C, Ullman JS, Hawryluk GW, Bell MJ, Bratton SL, Chesnut R, Harris OA, Kissoon N, Rubiano AM, Shutter L, Tasker RC, Vavilala MS, Wilberger J, Wright DW and Ghajar J. Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition. Neurosurgery. 2017;80:6-15. Okonkwo DO, Shutter LA, Moore C, Temkin NR, Puccio AM, Madden CJ, Andaluz N, Chesnut RM, Bullock MR, Grant GA, McGregor J, Weaver M, Jallo J, LeRoux PD, Moberg D, Barber J, Lazaridis C and Diaz-Arrastia RR. Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase-II: A Phase II Randomized Trial. Critical care medicine. 2017;45:1907-1914. Harary M, Dolmans RGF and Gormley WB. Intracranial Pressure Monitoring-Review and Avenues for Development. Sensors (Basel). 2018;18. Koenig MA. Cerebral Edema and Elevated Intracranial Pressure. Continuum (Minneap Minn). 2018;24:1588-1602. Jahns FP, Miroz JP, Messerer M, Daniel RT, Taccone FS, Eckert P and Oddo M. Quantitative pupillometry for the monitoring of intracranial hypertension in patients with severe traumatic brain injury. Crit Care. 2019;23:155. Cook AM, Morgan Jones G, Hawryluk GWJ, Mailloux P, McLaughlin D, Papangelou A, Samuel S, Tokumaru S, Venkatasubramanian C, Zacko C, Zimmermann LL, Hirsch K and Shutter L. Guidelines for the Acute Treatment of Cerebral Edema in Neurocritical Care Patients. Neurocritical care. 2020;32:647-666. Robba C, Pozzebon S, Moro B, Vincent JL, Creteur J and Taccone FS. Multimodal non-invasive assessment of intracranial hypertension: an observational study. Crit Care. 2020;24:379.

What do hip weakness, headache, and neglect have in common? At minimum, they can all be approached with simple neurodiagnostic heuristics. But there's more to neurology and medicine than having an approach to "leg weakness" or an approach to "headache". You have to adapt to new information as it presents itself. You have to know when, and how, to pivot. Produced by James E. Siegler, Minal Patel, and Jesse Thon. Voiceovers by Taryn Hester and Terri Yeager. Music for our program today was courtesy of Lee Rosevere, Rafael Archangel, E’s Jammy Jams, Kai Engel, and Jon Watts under a Creative Commons license. Our theme song was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 Rozen TD. Trigeminal neuralgia and glossopharyngeal neuralgia. Neurol Clin. 2004;22:185-206. Tarulli AW and Raynor EM. Lumbosacral radiculopathy. Neurol Clin. 2007;25:387-405. Cruccu G, Gronseth G, Alksne J, Argoff C, Brainin M, Burchiel K, Nurmikko T, Zakrzewska JM, American Academy of Neurology S and European Federation of Neurological S. AAN-EFNS guidelines on trigeminal neuralgia management. European journal of neurology : the official journal of the European Federation of Neurological Societies. 2008;15:1013-28. Dyck PJ and Thaisetthawatkul P. Lumbosacral plexopathy. Continuum (Minneap Minn). 2014;20:1343-58. Beume LA, Hieber M, Kaller CP, Nitschke K, Bardutzky J, Urbach H, Weiller C and Rijntjes M. Large Vessel Occlusion in Acute Stroke. Stroke; a journal of cerebral circulation. 2018;49:2323-2329. Menon BK. Neuroimaging in Acute Stroke. Continuum (Minneap Minn). 2020;26:287-309.

Who doesn’t enjoy their sleep? For most of us, it can be the most relaxing escape. And for others, a disturbance of sleep may be the first clue to a neurodenerative condition. Produced by James E. Siegler. Dr. Avidan reports that he receives royalties from Elsevier, is a consultant for Merck, and is a speaker for Eisai and Harmony. Music for our program today was by Andy Cohen, Purple Planet Music, Steve Combs, Yan Terrien, and Shane Ivers, whose music can be found at silvermansound.com. Our theme song was composed by Jimothy Dalton. Voiceover was courtesy of Taryn Hester. The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 Boeve BF, Silber MH, Ferman TJ, Lucas JA and Parisi JE. Association of REM sleep behavior disorder and neurodegenerative disease may reflect an underlying synucleinopathy. Mov Disord. 2001;16:622-30. Gilat M, Coeytaux Jackson A, Marshall NS, Hammond D, Mullins AE, Hall JM, Fang BAM, Yee BJ, Wong KKH, Grunstein RR and Lewis SJG. Melatonin for rapid eye movement sleep behavior disorder in Parkinson's disease: A randomised controlled trial. Mov Disord. 2020;35:344-349. Lloyd R, Tippmann-Peikert M, Slocumb N and Kotagal S. Characteristics of REM sleep behavior disorder in childhood. J Clin Sleep Med. 2012;8:127-31. Malhotra R and Avidan AY. Neurodegenerative Disease and REM Behavior Disorder. Current treatment options in neurology. 2012;14:474-92. McGrane IR, Leung JG, St Louis EK and Boeve BF. Melatonin therapy for REM sleep behavior disorder: a critical review of evidence. Sleep Med. 2015;16:19-26. Porter VR and Avidan AY. Clinical Overview of REM Sleep Behavior Disorder. Semin Neurol. 2017;37:461-470. Shin C, Park H, Lee WW, Kim HJ, Kim HJ and Jeon B. Clonazepam for probable REM sleep behavior disorder in Parkinson's disease: A randomized placebo-controlled trial. Journal of the neurological sciences. 2019;401:81-86. St Louis EK, Boeve AR and Boeve BF. REM Sleep Behavior Disorder in Parkinson's Disease and Other Synucleinopathies. Mov Disord. 2017;32:645-658. St Louis EK and Boeve BF. REM Sleep Behavior Disorder: Diagnosis, Clinical Implications, and Future Directions. Mayo Clinic proceedings. 2017;92:1723-1736. Teigen LN, Sharp RR, Hirsch JR, Campbell E, Timm PC, Sandness DJ, Feemster JC, Gossard TR, Faber SM, Steele TA, Rivera S, Junna MR, Lipford MC, Tippmann-Peikert M, Kotagal S, Ju YE, Howell M, Schenck CH, Videnovic A, Jennum P, Hogl B, Stefani A, Arnulf I, Heidbreder A, Lewis S, McCarter SJ, Boeve BF, Silber MH and St Louis EK. Specialist approaches to prognostic counseling in isolated REM sleep behavior disorder. Sleep Med. 2021;79:107-112.

As many as 1% of the world has epilepsy, but far more than will have a seizure in their lifetime. Not everyone needs a seizure medication, some people are even harmed by them. So who warrants treatment, and what do you start with. Consider today’s program an intro to AED decision making. For educational purposes only, of course. Not to guide any healthcare provider’s decision making. Produced by James E. Siegler. Music courtesy of Lee Rosevere, Cellophane Sam, Jon Watts, Josh Woodward, and Rafael Archangel. The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 Hauser WA, Rich SS, Annegers JF and Anderson VE. Seizure recurrence after a 1st unprovoked seizure: an extended follow-up. Neurology. 1990;40:1163-70. Randomized clinical trial on the efficacy of antiepileptic drugs in reducing the risk of relapse after a first unprovoked tonic-clonic seizure. First Seizure Trial Group (FIR.S.T. Group). Neurology. 1993;43:478-83. Hui AC, Tang A, Wong KS, Mok V and Kay R. Recurrence after a first untreated seizure in the Hong Kong Chinese population. Epilepsia. 2001;42:94-7. Koepp MJ and Woermann FG. Imaging structure and function in refractory focal epilepsy. The Lancet Neurology. 2005;4:42-53. Marson A, Jacoby A, Johnson A, Kim L, Gamble C, Chadwick D and Medical Research Council MSG. Immediate versus deferred antiepileptic drug treatment for early epilepsy and single seizures: a randomised controlled trial. Lancet. 2005;365:2007-13. Manjunath R, Davis KL, Candrilli SD and Ettinger AB. Association of antiepileptic drug nonadherence with risk of seizures in adults with epilepsy. Epilepsy Behav. 2009;14:372-8. Fountain NB. Choosing among antiepileptic drugs. Continuum (Minneap Minn). 2010;16:121-35. Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, Engel J, Jr., Forsgren L, French JA, Glynn M, Hesdorffer DC, Lee BI, Mathern GW, Moshe SL, Perucca E, Scheffer IE, Tomson T, Watanabe M and Wiebe S. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014;55:475-82. Krumholz A, Wiebe S, Gronseth GS, Gloss DS, Sanchez AM, Kabir AA, Liferidge AT, Martello JP, Kanner AM, Shinnar S, Hopp JL and French JA. Evidence-based guideline: Management of an unprovoked first seizure in adults: Report of the Guideline Development Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2015;84:1705-13. Bouma HK, Labos C, Gore GC, Wolfson C and Keezer MR. The diagnostic accuracy of routine electroencephalography after a first unprovoked seizure. European journal of neurology : the official journal of the European Federation of Neurological Societies. 2016;23:455-63. Leone MA, Giussani G, Nolan SJ, Marson AG and Beghi E. Immediate antiepileptic drug treatment, versus placebo, deferred, or no treatment for first unprovoked seizure. The Cochrane database of systematic reviews. 2016:CD007144.

To quote Donald Rumsfeld, “there are things we know we know…. we know there are some things we do not know... But there are also unknown unknowns—the ones we don't know we don't know…it is the latter category that tends to be the difficult ones.” In neurology, the agnosias are not that dissimilar from Rumsfeld’s 'unknown unknowns.' In this week’s program, we discuss the nosology and nomenclature for the agnosias, the localization, and the importance of recognizing one. Produced by James E. Siegler. Music courtesy of Dr. Turtle, Grossman, Ewell and Grainger, Marco Trovatelli, and Purple Planet Music. The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 Milner AD, Perrett DI, Johnston RS, Benson PJ, Jordan TR, Heeley DW, Bettucci D, Mortara F, Mutani R, Terazzi E and et al. Perception and action in 'visual form agnosia'. Brain. 1991;114 ( Pt 1B):405-28. Zeki S and Ffytche DH. The Riddoch syndrome: insights into the neurobiology of conscious vision. Brain. 1998;121 ( Pt 1):25-45. Biran I and Coslett HB. Visual agnosia. Current neurology and neuroscience reports. 2003;3:508-12. Coslett HB. Apraxia, Neglect, and Agnosia. Continuum (Minneap Minn). 2018;24:768-782. Dhont S, Derom E, Van Braeckel E, Depuydt P and Lambrecht BN. The pathophysiology of 'happy' hypoxemia in COVID-19. Respir Res. 2020;21:198. Li YC, Bai WZ and Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol. 2020;92:552-555. Matschke J, Lutgehetmann M, Hagel C, Sperhake JP, Schroder AS, Edler C, Mushumba H, Fitzek A, Allweiss L, Dandri M, Dottermusch M, Heinemann A, Pfefferle S, Schwabenland M, Sumner Magruder D, Bonn S, Prinz M, Gerloff C, Puschel K, Krasemann S, Aepfelbacher M and Glatzel M. Neuropathology of patients with COVID-19 in Germany: a post-mortem case series. The Lancet Neurology. 2020;19:919-929.

Almost 5 years ago, we published a show on chronic traumatic encephalopathy and its relationship to American football. But a lot has happened since 2016. New rules in the NFL. Emerging data on how the developing human brain of a child or adolescent is even more vulnerable to pathologic changes following mild head injury. And a heightened awareness of the disingenuous campaign against contact sports among one of the most outspoken whistleblowers in the medical field. This week on the program, we have remastered and updated the 2016 program. With some additional commentary on how parenthood may yield a new perspective on contact sports. Produced by James E. Siegler. Music courtesy of Chris Haugen, Kevin McLeod, and Meydan. The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 Montenigro PH, Corp DT, Stein TD, Cantu RC and Stern RA. Chronic traumatic encephalopathy: historical origins and current perspective. Annu Rev Clin Psychol. 2015;11:309-30. Giza CC, Kutcher JS, Ashwal S, Barth J, Getchius TS, Gioia GA, Gronseth GS, Guskiewicz K, Mandel S, Manley G, McKeag DB, Thurman DJ and Zafonte R. Summary of evidence-based guideline update: evaluation and management of concussion in sports: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2013;80:2250-7. Guskiewicz KM, Marshall SW, Bailes J, McCrea M, Cantu RC, Randolph C and Jordan BD. Association between recurrent concussion and late-life cognitive impairment in retired professional football players. Neurosurgery. 2005;57:719-26; discussion 719-26. Stamm JM, Bourlas AP, Baugh CM, Fritts NG, Daneshvar DH, Martin BM, McClean MD, Tripodis Y and Stern RA. Age of first exposure to football and later-life cognitive impairment in former NFL players. Neurology. 2015;84:1114-20. Ling H, Morris HR, Neal JW, Lees AJ, Hardy J, Holton JL, Revesz T and Williams DD. Mixed pathologies including chronic traumatic encephalopathy account for dementia in retired association football (soccer) players. Acta Neuropathol. 2017;133:337-352. Alosco ML, Mez J, Tripodis Y, Kiernan PT, Abdolmohammadi B, Murphy L, Kowall NW, Stein TD, Huber BR, Goldstein LE, Cantu RC, Katz DI, Chaisson CE, Martin B, Solomon TM, McClean MD, Daneshvar DH, Nowinski CJ, Stern RA and McKee AC. Age of first exposure to tackle football and chronic traumatic encephalopathy. Annals of neurology. 2018;83:886-901. Hobson W. "From Scientist to Salesman". Available online at https://www.washingtonpost.com/graphics/2020/sports/cte-bennet-omalu/. Accessed 31 December 2020.

Happy New Year, and good riddance 2020! Hopefully there is more that you will take away from the past 12 months other than your personal experience with the coronavirus pandemic. Whether you lost a job, a loved one, or an invaluable life experience, I think we can all say BRING ON 2021! So let's welcome the new year with positive mental attitude, a bit more luck, and an unquenchable thirst for knowledge. Produced by James E. Siegler. Music courtesy of Jahzzar, Kevin McLeod, Patches, Montplaisir, Steve Combs, Lee Roosevere, Siddhartha, Soft and Furious, Magic in the Other, and Loyalty Freak Music. The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 EEG Wiebe S, Blume WT, Girvin JP, Eliasziw M, Effectiveness and Efficiency of Surgery for Temporal Lobe Epilepsy Study G. A randomized, controlled trial of surgery for temporal-lobe epilepsy. The New England journal of medicine. 2001;345:311-8. Cascino GD. Clinical indications and diagnostic yield of video-electroencephalographic monitoring in patients with seizures and spells. Mayo Clinic proceedings. 2002;77:1111-20. Pillai J and Sperling MR. Interictal EEG and the diagnosis of epilepsy. Epilepsia. 2006;47 Suppl 1:14-22. Bouma HK, Labos C, Gore GC, Wolfson C and Keezer MR. The diagnostic accuracy of routine electroencephalography after a first unprovoked seizure. European journal of neurology : the official journal of the European Federation of Neurological Societies. 2016;23:455-63. Debicki DB. Electroencephalography after a single unprovoked seizure. Seizure. 2017;49:69-73. DYSFERLINOPATHY Suresh E and Wimalaratna S. Proximal myopathy: diagnostic approach and initial management. Postgraduate medical journal. 2013;89:470-7. Walter MC, Reilich P, Thiele S, Schessl J, Schreiber H, Reiners K, Kress W, Muller-Reible C, Vorgerd M, Urban P, Schrank B, Deschauer M, Schlotter-Weigel B, Kohnen R and Lochmuller H. Treatment of dysferlinopathy with deflazacort: a double-blind, placebo-controlled clinical trial. Orphanet J Rare Dis. 2013;8:26. Fayssoil A, Ogna A, Chaffaut C, Chevret S, Guimaraes-Costa R, Leturcq F, Wahbi K, Prigent H, Lofaso F, Nardi O, Clair B, Behin A, Stojkovic T, Laforet P, Orlikowski D and Annane D. Natural History of Cardiac and Respiratory Involvement, Prognosis and Predictive Factors for Long-Term Survival in Adult Patients with Limb Girdle Muscular Dystrophies Type 2C and 2D. PloS one. 2016;11:e0153095. Harris E, Bladen CL, Mayhew A, James M, Bettinson K, Moore U, Smith FE, Rufibach L, Cnaan A, Bharucha-Goebel DX, Blamire AM, Bravver E, Carlier PG, Day JW, Diaz-Manera J, Eagle M, Grieben U, Harms M, Jones KJ, Lochmuller H, Mendell JR, Mori-Yoshimura M, Paradas C, Pegoraro E, Pestronk A, Salort-Campana E, Schreiber-Katz O, Semplicini C, Spuler S, Stojkovic T, Straub V, Takeda S, Rocha CT, Walter MC, Bushby K and Jain COSC. The Clinical Outcome Study for dysferlinopathy: An international multicenter study. Neurol Genet. 2016;2:e89. Clark KEN and Isenberg DA. A review of inflammatory idiopathic myopathy focusing on polymyositis. European journal of neurology : the official journal of the European Federation of Neurological Societies. 2018;25:13-23. Wicklund MP. The Limb-Girdle Muscular Dystrophies. Continuum (Minneap Minn). 2019;25:1599-1618. Preston DC and Shapiro BE. Electromyography and neuromuscular disorders: clinical-electrophysiologic correlations. 3rd ed. London; New York: Elsevier Saunders; 2013. “rAAVrh74.MHCK7.DYSF.DV for Treatment of Dysferlinopathies.” Clinicaltrials.gov. Retrieved from https://clinicaltrials.gov/ct2/show/NCT02710500?cond=dysferlinopathy&draw=2&rank=1 on 22 December 2019. SPINAL DURAL AV FISTULA Jellema K, Tijssen CC, van Rooij WJ, Sluzewski M, Koudstaal PJ, Algra A and van Gijn J. Spinal dural arteriovenous fistulas: long-term follow-up of 44 treated patients. Neurology. 2004;62:1839-41. Mull M, Nijenhuis RJ, Backes WH, Krings T, Wilmink JT and Thron A. Value and limitations of contrast-enhanced MR angiography in spinal arteriovenous malformations and dural arteriovenous fistulas. AJNR American journal of neuroradiology. 2007;28:1249-58. Krings T and Geibprasert S. Spinal dural arteriovenous fistulas. AJNR American journal of neuroradiology. 2009;30:639-48. Alexander MD, Oliff MC, Olorunsola OG, Brus-Ramer M, Nickoloff EL and Meyers PM. Patient radiation exposure during diagnostic and therapeutic interventional neuroradiology procedures. J Neurointerv Surg. 2010;2:6-10. Cifarelli CP, Kaptain G, Yen CP, Schlesinger D and Sheehan JP. Gamma knife radiosurgery for dural arteriovenous fistulas. Neurosurgery. 2010;67:1230-5; discussion 1235. Kim DJ, Willinsky R, Geibprasert S, Krings T, Wallace C, Gentili F and Terbrugge K. Angiographic characteristics and treatment of cervical spinal dural arteriovenous shunts. AJNR American journal of neuroradiology. 2010;31:1512-5. Chen J and Gailloud P. Safety of spinal angiography: complication rate analysis in 302 diagnostic angiograms. Neurology. 2011;77:1235-40. Manninen AL, Isokangas JM, Karttunen A, Siniluoto T and Nieminen MT. A comparison of radiation exposure between diagnostic CTA and DSA examinations of cerebral and cervicocerebral vessels. AJNR American journal of neuroradiology. 2012;33:2038-42.

I shouldn’t have to tell you that traumatic brain injury is a major cause of morbidity and mortality. I shouldn’t have to. But I will. And it is. In severe cases of head injury, there can be delayed and irreversible deterioration in the nervous system for which there is no treatment and the prognosis is grim. This week on the program, Dr. Monisha Kumar (University of Pennsylvania) discusses the worst of the worst of these scenarios, what to look out for, and expert recommendations on what to do when it happens. Produced by James E. Siegler and Monisha Kumar. Music courtesy of Rui, Swelling, Unheard Music Concepts, Jahzzar, Ian Southerland, and TRG Banks. The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 Strich SJ. Diffuse degeneration of the cerebral white matter in severe dementia following head injury. Journal of neurology, neurosurgery, and psychiatry. 1956;19:163-85. Adams JH, Graham DI, Murray LS and Scott G. Diffuse axonal injury due to nonmissile head injury in humans: an analysis of 45 cases. Annals of neurology. 1982;12:557-63. Povlishock JT, Becker DP, Cheng CL and Vaughan GW. Axonal change in minor head injury. J Neuropathol Exp Neurol. 1983;42:225-42. Gentry LR. Imaging of closed head injury. Radiology. 1994;191:1-17. Meythaler JM, Peduzzi JD, Eleftheriou E and Novack TA. Current concepts: diffuse axonal injury-associated traumatic brain injury. Arch Phys Med Rehabil. 2001;82:1461-71. Arfanakis K, Haughton VM, Carew JD, Rogers BP, Dempsey RJ and Meyerand ME. Diffusion tensor MR imaging in diffuse axonal injury. AJNR American journal of neuroradiology. 2002;23:794-802. Scheid R, Preul C, Gruber O, Wiggins C and von Cramon DY. Diffuse axonal injury associated with chronic traumatic brain injury: evidence from T2*-weighted gradient-echo imaging at 3 T. AJNR American journal of neuroradiology. 2003;24:1049-56. DeKosky ST, Ikonomovic MD and Gandy S. Traumatic brain injury--football, warfare, and long-term effects. The New England journal of medicine. 2010;363:1293-6. Johnson VE, Stewart W and Smith DH. Widespread tau and amyloid-beta pathology many years after a single traumatic brain injury in humans. Brain Pathol. 2012;22:142-9. Schrag M and Greer DM. Clinical associations of cerebral microbleeds on magnetic resonance neuroimaging. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association. 2014;23:2489-2497. Haghbayan H, Boutin A, Laflamme M, Lauzier F, Shemilt M, Moore L, Zarychanski R, Douville V, Fergusson D and Turgeon AF. The Prognostic Value of MRI in Moderate and Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis. Critical care medicine. 2017;45:e1280-e1288. Izzy S, Mazwi NL, Martinez S, Spencer CA, Klein JP, Parikh G, Glenn MB, Greenberg SM, Greer DM, Wu O and Edlow BL. Revisiting Grade 3 Diffuse Axonal Injury: Not All Brainstem Microbleeds are Prognostically Equal. Neurocritical care. 2017;27:199-207. van Eijck MM, Schoonman GG, van der Naalt J, de Vries J and Roks G. Diffuse axonal injury after traumatic brain injury is a prognostic factor for functional outcome: a systematic review and meta-analysis. Brain Inj. 2018;32:395-402.

COVID-19 is more than just a threat to your physical health. Even if you are never infected, you may not be free of it. In today's program, we take lessons from prior pandemics and consider the sociocultural effects of a global infectious disease. Be advised, this one is of the "sentimental" variety. Produced by James E. Siegler. Music courtesy of Purple Planet Music, Meydn, Kevin MacLeod and Shane Ivers, which you can find at Silvermansound.com. The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2095-128. Fineberg HV. Pandemic preparedness and response--lessons from the H1N1 influenza of 2009. The New England journal of medicine. 2014;370:1335-42. Shanks GD. Insights from unusual aspects of the 1918 influenza pandemic. Travel Med Infect Dis. 2015;13:217-22. Armitage R and Nellums LB. COVID-19 and the consequences of isolating the elderly. Lancet Public Health. 2020;5:e256. Bonaccorsi G, Pierri F, Cinelli M, Flori A, Galeazzi A, Porcelli F, Schmidt AL, Valensise CM, Scala A, Quattrociocchi W and Pammolli F. Economic and social consequences of human mobility restrictions under COVID-19. Proc Natl Acad Sci U S A. 2020;117:15530-15535. Dinmohamed AG, Visser O, Verhoeven RHA, Louwman MWJ, van Nederveen FH, Willems SM, Merkx MAW, Lemmens V, Nagtegaal ID and Siesling S. Fewer cancer diagnoses during the COVID-19 epidemic in the Netherlands. Lancet Oncol. 2020;21:750-751. Jeffery MM, D'Onofrio G, Paek H, Platts-Mills TF, Soares WE, 3rd, Hoppe JA, Genes N, Nath B and Melnick ER. Trends in Emergency Department Visits and Hospital Admissions in Health Care Systems in 5 States in the First Months of the COVID-19 Pandemic in the US. JAMA internal medicine. 2020;180:1328-1333. Rabinovitz B, Jaywant A and Fridman CB. Neuropsychological functioning in severe acute respiratory disorders caused by the coronavirus: implications for the current COVID-19 pandemic. Clin Neuropsychol. 2020:1-27. Santini ZI, Jose PE, York Cornwell E, Koyanagi A, Nielsen L, Hinrichsen C, Meilstrup C, Madsen KR and Koushede V. Social disconnectedness, perceived isolation, and symptoms of depression and anxiety among older Americans (NSHAP): a longitudinal mediation analysis. Lancet Public Health. 2020;5:e62-e70. Wong LE, et al. Where are all the patients? New Eng J Med (2020): Published online 14 May 2020. Available at https://catalyst.nejm.org/doi/full/10.1056/CAT.20.0193.

The mental status exam is a keystone of the neurologic assessment. Dr. Andrea Casher (Cooper University Hospital) builds upon this metaphor in our program this week. Making a special appearance is US President Donald Trump, who underwent a mental status exam and recounts his experience. Produced by James E. Siegler and Andrea Casher. Music courtesy of Unheard Music Concepts, Purple Planet Music, Lee Rosevere, and Scott Holmes. The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 Tombaugh TN and McIntyre NJ. The mini-mental state examination: a comprehensive review. J Am Geriatr Soc. 1992;40:922-35. Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL and Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53:695-9. Dong Y, Sharma VK, Chan BP, Venketasubramanian N, Teoh HL, Seet RC, Tanicala S, Chan YH and Chen C. The Montreal Cognitive Assessment (MoCA) is superior to the Mini-Mental State Examination (MMSE) for the detection of vascular cognitive impairment after acute stroke. Journal of the neurological sciences. 2010;299:15-8. Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, Ogar JM, Rohrer JD, Black S, Boeve BF, Manes F, Dronkers NF, Vandenberghe R, Rascovsky K, Patterson K, Miller BL, Knopman DS, Hodges JR, Mesulam MM and Grossman M. Classification of primary progressive aphasia and its variants. Neurology. 2011;76:1006-14. Ng KP, Chiew HJ, Lim L, Rosa-Neto P, Kandiah N and Gauthier S. The influence of language and culture on cognitive assessment tools in the diagnosis of early cognitive impairment and dementia. Expert review of neurotherapeutics. 2018;18:859-869. Rabinovitz B, Jaywant A and Fridman CB. Neuropsychological functioning in severe acute respiratory disorders caused by the coronavirus: implications for the current COVID-19 pandemic. Clin Neuropsychol. 2020:1-27.

October 29 is World Stroke Day! Might as well know how it is best treated. This week, Jim Siegler revisits a 2017 episode on the differences between two of the most commonly prescribed post-stroke treatments, with some key updates, recent trial results, and practice-changing paradigms. Produced by James E. Siegler. Music courtesy of William Ross Chernoff’s Nomads, Steve Combs, Rui, Little Glass Men, and Peter Rudenko. The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 Jauch EC, Saver JL, Adams HP, Jr., Bruno A, Connors JJ, Demaerschalk BM, Khatri P, McMullan PW, Jr., Qureshi AI, Rosenfield K, Scott PA, Summers DR, Wang DZ, Wintermark M, Yonas H, American Heart Association Stroke C, Council on Cardiovascular N, Council on Peripheral Vascular D and Council on Clinical C. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke; a journal of cerebral circulation. 2013;44:870-947. The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. Lancet. 1997;349:1569-81. CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group. Lancet. 1997;349:1641-9. Kennedy J, Hill MD, Ryckborst KJ, Eliasziw M, Demchuk AM, Buchan AM and Investigators F. Fast assessment of stroke and transient ischaemic attack to prevent early recurrence (FASTER): a randomised controlled pilot trial. The Lancet Neurology. 2007;6:961-9. Wang Y, Wang Y, Zhao X, Liu L, Wang D, Wang C, Wang C, Li H, Meng X, Cui L, Jia J, Dong Q, Xu A, Zeng J, Li Y, Wang Z, Xia H, Johnston SC and Investigators C. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. The New England journal of medicine. 2013;369:11-9. Hong KS, Lee SH, Kim EG, Cho KH, Chang DI, Rha JH, Bae HJ, Lee KB, Kim DE, Park JM, Kim HY, Cha JK, Yu KH, Lee YS, Lee SJ, Choi JC, Cho YJ, Kwon SU, Kim GM, Sohn SI, Park KY, Kang DW, Sohn CH, Lee J, Yoon BW and Investigators C. Recurrent Ischemic Lesions After Acute Atherothrombotic Stroke: Clopidogrel Plus Aspirin Versus Aspirin Alone. Stroke; a journal of cerebral circulation. 2016;47:2323-30. Liu L, Wong KS, Leng X, Pu Y, Wang Y, Jing J, Zou X, Pan Y, Wang A, Meng X, Wang C, Zhao X, Soo Y, Johnston SC, Wang Y and Investigators C. Dual antiplatelet therapy in stroke and ICAS: Subgroup analysis of CHANCE. Neurology. 2015;85:1154-62. Collaborative overview of randomised trials of antiplatelet therapy--I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists' Collaboration. Bmj. 1994;308:81-106. Antithrombotic Trialists C. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Bmj. 2002;324:71-86. Committee CS. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996;348:1329-39. Ringleb PA, Bhatt DL, Hirsch AT, Topol EJ, Hacke W and Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events I. Benefit of clopidogrel over aspirin is amplified in patients with a history of ischemic events. Stroke; a journal of cerebral circulation. 2004;35:528-32. Diener HC, Bogousslavsky J, Brass LM, Cimminiello C, Csiba L, Kaste M, Leys D, Matias-Guiu J, Rupprecht HJ and investigators M. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet. 2004;364:331-7. Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, Cacoub P, Cohen EA, Creager MA, Easton JD, Flather MD, Haffner SM, Hamm CW, Hankey GJ, Johnston SC, Mak KH, Mas JL, Montalescot G, Pearson TA, Steg PG, Steinhubl SR, Weber MA, Brennan DM, Fabry-Ribaudo L, Booth J, Topol EJ and Investigators C. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. The New England journal of medicine. 2006;354:1706-17. Rothwell PM, Price JF, Fowkes FG, Zanchetti A, Roncaglioni MC, Tognoni G, Lee R, Belch JF, Wilson M, Mehta Z and Meade TW. Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet. 2012;379:1602-12. Sahlen A, Varenhorst C, Lagerqvist B, Renlund H, Omerovic E, Erlinge D, Wallentin L, James SK and Jernberg T. Outcomes in patients treated with ticagrelor or clopidogrel after acute myocardial infarction: experiences from SWEDEHEART registry. European heart journal. 2016;37:3335-3342. Bath PM, Woodhouse LJ, Appleton JP, Beridze M, Christensen H, Dineen RA, Duley L, England TJ, Flaherty K, Havard D, Heptinstall S, James M, Krishnan K, Markus HS, Montgomery AA, Pocock SJ, Randall M, Ranta A, Robinson TG, Scutt P, Venables GS, Sprigg N and Investigators T. Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial. Lancet. 2018;391:850-859. Lopes RD, Heizer G, Aronson R, Vora AN, Massaro T, Mehran R, Goodman SG, Windecker S, Darius H, Li J, Averkov O, Bahit MC, Berwanger O, Budaj A, Hijazi Z, Parkhomenko A, Sinnaeve P, Storey RF, Thiele H, Vinereanu D, Granger CB, Alexander JH and Investigators A. Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation. The New England journal of medicine. 2019;380:1509-1524. Wang Y, Chen W, Lin Y, Meng X, Chen G, Wang Z, Wu J, Wang D, Li J, Cao Y, Xu Y, Zhang G, Li X, Pan Y, Li H, Zhao X, Liu L, Lin J, Dong K, Jing J, Johnston SC, Wang D, Wang Y and Group PPS. Ticagrelor plus aspirin versus clopidogrel plus aspirin for platelet reactivity in patients with minor stroke or transient ischaemic attack: open label, blinded endpoint, randomised controlled phase II trial. Bmj. 2019;365:l2211.

This week on the program, we bring to you a special episode on the impact of the COVID-19 pandemic on the neurology 2021 match--and potentially MANY subsequent matches. Jim Siegler is joined by the Assistant Program Director of the Cooper Neurology Residency Program, Olga Thon, and the creators of the @NMatch2021 Twitter account (who you should DEFINITELY follow after listening to our episode). If you are an applicant for the 2021 cycle, this show is MANDATORY. (only kidding, this is just a podcast) Produced by James E. Siegler, with assistance by Olga Thon, Adriana Romirez, Dylan Del Papa, Justine Ker, and Alvin Singh. Music courtesy of Akash Gandi, Little Glass Men, Kevin MacLeod, Josh Woodward, Julie Maxwell, and Kai Engel. The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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.

Halloween is one of the most exciting and festive holidays, but this year I imagine many of us are going to spend it indoors. To help pass the time, enjoy this seasonal special about the neurologic manifestations of zombie-ism. Today's program is a re-run from 2017, featuring Dr. Brian Hanrahan, and has been remastered and updated with some recent additions in light of the coronavirus pandemic. Produced by James E. Siegler. Music courtesy of Andrew Sacco, Ars Sonor, Yan Terrien, and Unheard Music Concepts. The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig, with some original recordings out of Studio 3. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 Smith TC. Zombie infections: Epidemiology, treatment, and prevention. Bmj. 2015;351:h6423 Adams AJ, Banister SD, Irizarry L, Trecki J, Schwartz M, Gerona R. "Zombie" outbreak caused by the synthetic cannabinoid amb-fubinaca in new york. The New England journal of medicine. 2017;376:235-242 Rabinovitz B, Jaywant A, Fridman CB. Neuropsychological functioning in severe acute respiratory disorders caused by the coronavirus: Implications for the current covid-19 pandemic. Clin Neuropsychol. 2020:1-27 Gilmour SJ, Saito E, Yoneoka D. Importance of survival strategies after a zombie pandemic. Bmj. 2016;532:i259 Hughes DP, Andersen SB, Hywel-Jones NL, Himaman W, Billen J, Boomsma JJ. Behavioral mechanisms and morphological symptoms of zombie ants dying from fungal infection. BMC Ecol. 2011;11:13

As the second most common vascular malformation in the central nervous system, cerebral cavernomas are often incidental radiographic findings. Also incidental is Jim’s interest in mediocre sci-fi television shows, such as Netflix’s recent series, Away—which incidentally includes one character with a symptomatic cerebral cavernoma. This week on the podcast, Dr. Siegler discusses with Dr. Dena Little (Cooper University Hospital) the epidemiology, clinical course, and management (including counseling) of patients with this vascular malformation. Plus, a critical appraisal of Away’s medical consultant. 0_o Produced by James E. Siegler and Dena Little. Music courtesy of Ars Sonor, Andrew Sacco, Chris Zabriskie, and Purple Planet Music. The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 Pozzati E, Acciarri N, Tognetti F, Marliani F and Giangaspero F. Growth, subsequent bleeding, and de novo appearance of cerebral cavernous angiomas. Neurosurgery. 1996;38:662-9; discussion 669-70. Batra S, Lin D, Recinos PF, Zhang J and Rigamonti D. Cavernous malformations: natural history, diagnosis and treatment. Nature reviews Neurology. 2009;5:659-70. Gross BA, Lin N, Du R and Day AL. The natural history of intracranial cavernous malformations. Neurosurgical focus. 2011;30:E24. Horne MA, Flemming KD, Su IC, Stapf C, Jeon JP, Li D, Maxwell SS, White P, Christianson TJ, Agid R, Cho WS, Oh CW, Wu Z, Zhang JT, Kim JE, Ter Brugge K, Willinsky R, Brown RD, Jr., Murray GD, Al-Shahi Salman R and Cerebral Cavernous Malformations Individual Patient Data Meta-analysis C. Clinical course of untreated cerebral cavernous malformations: a meta-analysis of individual patient data. The Lancet Neurology. 2016;15:166-173. Zafar A, Quadri SA, Farooqui M, Ikram A, Robinson M, Hart BL, Mabray MC, Vigil C, Tang AT, Kahn ML, Yonas H, Lawton MT, Kim H and Morrison L. Familial Cerebral Cavernous Malformations. Stroke; a journal of cerebral circulation. 2019;50:1294-1301. Zuurbier SM, Hickman CR, Tolias CS, Rinkel LA, Leyrer R, Flemming KD, Bervini D, Lanzino G, Wityk RJ, Schneble HM, Sure U, Al-Shahi Salman R and Scottish Audit of Intracranial Vascular Malformations Steering C. Long-term antithrombotic therapy and risk of intracranial haemorrhage from cerebral cavernous malformations: a population-based cohort study, systematic review, and meta-analysis. The Lancet Neurology. 2019;18:935-941.

You know the triad for normal pressure hydrocephalus (NPH). Wet, wobbly, and wacky. And you have probably heard of the Evan’s index—the relative proportion of the lateral ventricles in reference to the inner table of the skull. But you might not have heard of high-convexity tight sulci. Now you have. Produced by James E. Siegler. Music courtesy of Jason Shaw, Javolenus, and Lee Rosevere, under a Creative Commons License. The opening theme was composed by Jimothy Dalton. 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 Kitagaki H, Mori E, Ishii K, Yamaji S, Hirono N and Imamura T. CSF spaces in idiopathic normal pressure hydrocephalus: morphology and volumetry. AJNR American journal of neuroradiology. 1998;19:1277-84. Sasaki M, Honda S, Yuasa T, Iwamura A, Shibata E and Ohba H. Narrow CSF space at high convexity and high midline areas in idiopathic normal pressure hydrocephalus detected by axial and coronal MRI. Neuroradiology. 2008;50:117-22. Allali G, Laidet M, Armand S, Momjian S, Marques B, Saj A and Assal F. A combined cognitive and gait quantification to identify normal pressure hydrocephalus from its mimics: The Geneva's protocol. Clinical neurology and neurosurgery. 2017;160:5-11. Graff-Radford J, Gunter JL, Jones DT, Przybelski SA, Schwarz CG, Huston J, 3rd, Lowe V, Elder BD, Machulda MM, Gunter NB, Petersen RC, Kantarci K, Vemuri P, Mielke MM, Knopman DS, Graff-Radford NR and Jack CR, Jr. Cerebrospinal fluid dynamics disorders: Relationship to Alzheimer biomarkers and cognition. Neurology. 2019;93:e2237-e2246.

Myoclonus is the most etiologically non-specific motor manifestation of neurologic and systemic disease. It’s like slurred speech or altered mental status. But in the appropriate context, it can become a useful clue in your differential diagnosis. Dr. John Caviness of the Mayo Clinic joins Jim Siegler this week for a discussion on this abnormal movement and what it may indicate. Produced by James E. Siegler and John Caviness. Music courtesy of Kevin McLeod and E’s Jammy Jams. “Endings” and  “What’s the Angle” were produced by Shane Ivers (https://www.silvermansound.com). The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 Caviness JN. Myoclonus and neurodegenerative disease--what's in a name? Parkinsonism Relat Disord. 2003;9:185-92. Caviness JN. Parkinsonism & related disorders. Myoclonus. Parkinsonism Relat Disord. 2007;13 Suppl 3:S375-84. Caviness JN. Pathophysiology and treatment of myoclonus. Neurol Clin. 2009;27:757-77, vii. Zutt R, van Egmond ME, Elting JW, van Laar PJ, Brouwer OF, Sival DA, Kremer HP, de Koning TJ and Tijssen MA. A novel diagnostic approach to patients with myoclonus. Nature reviews Neurology. 2015;11:687-97. Levy A and Chen R. Myoclonus: Pathophysiology and Treatment Options. Current treatment options in neurology. 2016;18:21. Caviness JN. Myoclonus. Continuum (Minneap Minn). 2019;25:1055-1080.

A lot can happen in two years. You might have matched into residency, graduated from fellowship, had a kid... Or several phase II trials in low grade glioma research could have been published. Since the original airing of this episode in May 2018, there have been a few updates in neuro-oncology. We'll cover some of the major ones this week in the BrainWaves podcast. Produced by James E. Siegler, Brian Nahed and Jorg Dietrich. Music courtesy of Ian Sutherland, Lovira, and Lee Roosevere. The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 McGirt MJ, Chaichana KL, Attenello FJ, Weingart JD, Than K, Burger PC, Olivi A, Brem H and Quinones-Hinojosa A. Extent of surgical resection is independently associated with survival in patients with hemispheric infiltrating low-grade gliomas. Neurosurgery. 2008;63:700-7; author reply 707-8. Shaw EG, Wang M, Coons SW, Brachman DG, Buckner JC, Stelzer KJ, Barger GR, Brown PD, Gilbert MR and Mehta MP. Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult low-grade glioma: initial results of RTOG 9802. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2012;30:3065-70. Schiff D. Low-grade Gliomas. Continuum (Minneap Minn). 2017;23:1564-1579. Wen PY and Huse JT. 2016 World Health Organization Classification of Central Nervous System Tumors. Continuum (Minneap Minn). 2017;23:1531-1547. Bell EH, Zhang P, Fisher BJ, Macdonald DR, McElroy JP, Lesser GJ, Fleming J, Chakraborty AR, Liu Z, Becker AP, Fabian D, Aldape KD, Ashby LS, Werner-Wasik M, Walker EM, Bahary JP, Kwok Y, Yu HM, Laack NN, Schultz CJ, Gray HJ, Robins HI, Mehta MP and Chakravarti A. Association of MGMT Promoter Methylation Status With Survival Outcomes in Patients With High-Risk Glioma Treated With Radiotherapy and Temozolomide: An Analysis From the NRG Oncology/RTOG 0424 Trial. JAMA Oncol. 2018;4:1405-1409. van den Bent MJ, Klein M, Smits M, Reijneveld JC, French PJ, Clement P, de Vos FYF, Wick A, Mulholland PJ, Taphoorn MJB, Lewis J, Weller M, Chinot OL, Kros JM, de Heer I, Verschuere T, Coens C, Golfinopoulos V, Gorlia T and Idbaih A. Bevacizumab and temozolomide in patients with first recurrence of WHO grade II and III glioma, without 1p/19q co-deletion (TAVAREC): a randomised controlled phase 2 EORTC trial. Lancet Oncol. 2018;19:1170-1179. Fangusaro J, Onar-Thomas A, Young Poussaint T, Wu S, Ligon AH, Lindeman N, Banerjee A, Packer RJ, Kilburn LB, Goldman S, Pollack IF, Qaddoumi I, Jakacki RI, Fisher PG, Dhall G, Baxter P, Kreissman SG, Stewart CF, Jones DTW, Pfister SM, Vezina G, Stern JS, Panigrahy A, Patay Z, Tamrazi B, Jones JY, Haque SS, Enterline DS, Cha S, Fisher MJ, Doyle LA, Smith M, Dunkel IJ and Fouladi M. Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial. Lancet Oncol. 2019;20:1011-1022. Bell EH, Zhang P, Shaw EG, Buckner JC, Barger GR, Bullard DE, Mehta MP, Gilbert MR, Brown PD, Stelzer KJ, McElroy JP, Fleming JL, Timmers CD, Becker AP, Salavaggione AL, Liu Z, Aldape K, Brachman DG, Gertler SZ, Murtha AD, Schultz CJ, Johnson D, Laack NN, Hunter GK, Crocker IR, Won M and Chakravarti A. Comprehensive Genomic Analysis in NRG Oncology/RTOG 9802: A Phase III Trial of Radiation Versus Radiation Plus Procarbazine, Lomustine (CCNU), and Vincristine in High-Risk Low-Grade Glioma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2020:JCO1902983. Breen WG, Anderson SK, Carrero XW, Brown PD, Ballman KV, O'Neill BP, Curran WJ, Abrams RA, Laack NN, Levitt R, Galanis E, Buckner JC and Shaw EG. Final report from Intergroup NCCTG 86-72-51 (Alliance): a phase III randomized clinical trial of high-dose versus low-dose radiation for adult low-grade glioma. Neuro Oncol. 2020;22:830-837. Ullrich NJ, Prabhu SP, Reddy AT, Fisher MJ, Packer R, Goldman S, Robison NJ, Gutmann DH, Viskochil DH, Allen JC, Korf B, Cantor A, Cutter G, Thomas C, Perentesis JP, Mizuno T, Vinks AA, Manley PE, Chi SN, Kieran MW and Consortium NFCT. A Phase II Study of Continuous Oral mTOR Inhibitor Everolimus for Recurrent, Radiographic-Progressive Neurofibromatosis Type 1-Associated Pediatric Low-Grade Glioma: A Neurofibromatosis Clinical Trials Consortium Study. Neuro Oncol. 2020.

The electroencephalogram is a nearly 100-year old neurodiagnostic instrument. And yet, we learn new things from it every day. This week on the BrainWaves podcast, Dr. Tracey Milligan (Mass General Brigham) reviews the indications and utilization of a routine scalp EEG. Also discussed: Limitations of scalp EEG Brain surgery Non-epileptic events Why YOU should consider becoming an epileptologist Produced by James E. Siegler and Tracey Milligan. Music courtesy of Steve Combs, Lee Roosevere, Siddhartha, Soft and Furious, Patches, and Magic in the Other. The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. James Siegler reports having received consulting fees from Ceribell, which produces a bedside scalp EEG with automated seizure detection. However, there is no specific reference to this device or company, nor was this episode sponsored by Ceribell. 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        Wiebe S, Blume WT, Girvin JP, Eliasziw M, Effectiveness and Efficiency of Surgery for Temporal Lobe Epilepsy Study G. A randomized, controlled trial of surgery for temporal-lobe epilepsy. The New England journal of medicine. 2001;345:311-8. Cascino GD. Clinical indications and diagnostic yield of video-electroencephalographic monitoring in patients with seizures and spells. Mayo Clinic proceedings. 2002;77:1111-20. Pillai J and Sperling MR. Interictal EEG and the diagnosis of epilepsy. Epilepsia. 2006;47 Suppl 1:14-22. Bouma HK, Labos C, Gore GC, Wolfson C and Keezer MR. The diagnostic accuracy of routine electroencephalography after a first unprovoked seizure. European journal of neurology : the official journal of the European Federation of Neurological Societies. 2016;23:455-63. Debicki DB. Electroencephalography after a single unprovoked seizure. Seizure. 2017;49:69-73.

The locked-in syndrome is a rare clinical consequence following many types of neurologic injury. In general, the locked-in patient is fully paralyzed, with perhaps minimal function of the fingers, the eyes, or the mouth. What's more, the gross motor dysfunction is enormously disproportional to the cognitive function of the individual. The locked-in patient is conscious and completely aware of their surroundings. They can often hear, see, smell, and feel just as any other person would. But because of their profound physical disability, they have a very limited means of communicating even the simplest thoughts. "I feel hot." "My head hurts." "My cheek itches." It may surprise you that the patient's perspective of their condition is wholly different from how the healthcare provider or caregiver imagines it to be. This week on the program, Dr. Lauren Elman (Pennsylvania Medical Center ALS Multi-disiplinary Clinic) reviews this discrepancy. Dr. Elman also shares her experience  managing this inevitable consequence of ALS when all life-sustaining measures are desired. REFERENCES Patterson JR and Grabois M. Locked-in syndrome: a review of 139 cases. Stroke; a journal of cerebral circulation. 1986;17:758-64. Trail M, Nelson ND, Van JN, Appel SH and Lai EC. A study comparing patients with amyotrophic lateral sclerosis and their caregivers on measures of quality of life, depression, and their attitudes toward treatment options. Journal of the neurological sciences. 2003;209:79-85. Rousseau MC, Baumstarck K, Alessandrini M, Blandin V, Billette de Villemeur T and Auquier P. Quality of life in patients with locked-in syndrome: Evolution over a 6-year period. Orphanet J Rare Dis. 2015;10:88. Kuzma-Kozakiewicz M, Andersen PM, Ciecwierska K, Vazquez C, Helczyk O, Loose M, Uttner I, Ludolph AC and Lule D. An observational study on quality of life and preferences to sustain life in locked-in state. Neurology. 2019;93:e938-e945. Niedermeyer S, Murn M and Choi PJ. Respiratory Failure in Amyotrophic Lateral Sclerosis. Chest. 2019;155:401-408.

Webster defines ‘idiopathic’ as “arising spontaneously or from an obscure or unknown cause”. By definition, this means idiopathic intracranial hypertension (IIH) has no proximate cause. But that’s not exactly true. This week on the podcast, we explore the recent evidence behind the theory that transverse sinus stenosis may contribute to this condition. Disclaimer: No chicken or eggs were harmed in the making of this episode. Produced by James E. Siegler. Music courtesy of Squire Tuck, Swelling, Three Chain Links, and Unheard Music Concepts. The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 Martins AN. Resistance to drainage of cerebrospinal fluid: clinical measurement and significance. Journal of neurology, neurosurgery, and psychiatry. 1973;36:313-8. Gjerris F, Soelberg Sorensen P, Vorstrup S and Paulson OB. Intracranial pressure, conductance to cerebrospinal fluid outflow, and cerebral blood flow in patients with benign intracranial hypertension (pseudotumor cerebri). Annals of neurology. 1985;17:158-62. Orefice G, Celentano L, Scaglione M, Davoli M and Striano S. Radioisotopic cisternography in benign intracranial hypertension of young obese women. A seven-case study and pathogenetic suggestions. Acta Neurol (Napoli). 1992;14:39-50. Karahalios DG, Rekate HL, Khayata MH and Apostolides PJ. Elevated intracranial venous pressure as a universal mechanism in pseudotumor cerebri of varying etiologies. Neurology. 1996;46:198-202. King JO, Mitchell PJ, Thomson KR and Tress BM. Manometry combined with cervical puncture in idiopathic intracranial hypertension. Neurology. 2002;58:26-30. Farb RI, Vanek I, Scott JN, Mikulis DJ, Willinsky RA, Tomlinson G and terBrugge KG. Idiopathic intracranial hypertension: the prevalence and morphology of sinovenous stenosis. Neurology. 2003;60:1418-24. Rohr A, Dorner L, Stingele R, Buhl R, Alfke K and Jansen O. Reversibility of venous sinus obstruction in idiopathic intracranial hypertension. AJNR American journal of neuroradiology. 2007;28:656-9. Sinclair AJ, Kuruvath S, Sen D, Nightingale PG, Burdon MA and Flint G. Is cerebrospinal fluid shunting in idiopathic intracranial hypertension worthwhile? A 10-year review. Cephalalgia. 2011;31:1627-33. Riggeal BD, Bruce BB, Saindane AM, Ridha MA, Kelly LP, Newman NJ and Biousse V. Clinical course of idiopathic intracranial hypertension with transverse sinus stenosis. Neurology. 2013;80:289-95. Satti SR, Leishangthem L and Chaudry MI. Meta-Analysis of CSF Diversion Procedures and Dural Venous Sinus Stenting in the Setting of Medically Refractory Idiopathic Intracranial Hypertension. AJNR American journal of neuroradiology. 2015;36:1899-904. Dinkin MJ and Patsalides A. Venous Sinus Stenting in Idiopathic Intracranial Hypertension: Results of a Prospective Trial. J Neuroophthalmol. 2017;37:113-121. Mohammaden MH, Husain MR, Brunozzi D, Hussein AE, Atwal G, Charbel FT and Alaraj A. Role of Resistivity Index Analysis in the Prediction of Hemodynamically Significant Venous Sinus Stenosis in Patient With Idiopathic Intracranial Hypertension. Neurosurgery. 2020;86:631-636.

It’s more than just a headache. Migraine is a disturbance of normal neurological function, and as you are aware, it causes more than just severe head pain. This week on BrainWaves, Dr. Deborah Friedman (UT Southwestern) shares her experience evaluating and managing the unusual neurologic manifestations of migraine that aren’t just the misery from recurrent attacks. Produced by James E. Siegler & Deborah Friedman. Music courtesy of Josh Woodward, Kevin McLeod and Lee Rosevere. The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 Bianchin MM, Londero RG, Lima JE and Bigal ME. Migraine and epilepsy: a focus on overlapping clinical, pathophysiological, molecular, and therapeutic aspects. Curr Pain Headache Rep. 2010;14:276-83. Dreier JP, Reiffurth C, Woitzik J, Hartings JA, Drenckhahn C, Windler C, Friedman A, MacVicar B, Herreras O and group Cs. How spreading depolarization can be the pathophysiological correlate of both migraine aura and stroke. Acta neurochirurgica Supplement. 2015;120:137-40. Goadsby PJ. Unique Migraine Subtypes, Rare Headache Disorders, and Other Disturbances. Continuum (Minneap Minn). 2015;21:1032-40. Orr SL, Friedman BW, Christie S, Minen MT, Bamford C, Kelley NE and Tepper D. Management of Adults With Acute Migraine in the Emergency Department: The American Headache Society Evidence Assessment of Parenteral Pharmacotherapies. Headache. 2016;56:911-40. Rozen TD, Niknam RM, Shechter AL, Young WB and Silberstein SD. Cluster headache in women: clinical characteristics and comparison with cluster headache in men. Journal of neurology, neurosurgery, and psychiatry. 2001;70:613-7. Shah DR, Dilwali S and Friedman DI. Migraine Aura Without Headache [corrected]. Curr Pain Headache Rep. 2018;22:77. Solomon S, Grosberg BM, Friedman DI and Lipton RB. Retinal migraine. J Neuroophthalmol. 2007;27:243-4; author reply 244-5. Tippin J, Corbett JJ, Kerber RE, Schroeder E and Thompson HS. Amaurosis fugax and ocular infarction in adolescents and young adults. Annals of neurology. 1989;26:69-77. Viana M, Tronvik EA, Do TP, Zecca C and Hougaard A. Clinical features of visual migraine aura: a systematic review. J Headache Pain. 2019;20:64.

On rounds, I sometimes joke that the two most important organs in the body are the right and left hemisphere. Only one of many, terrible, dad jokes my poor residents and students have to endure. But what happens when one organ fails, or you have to remove it? This week on BrainWaves, we’ll review a unique neurologic condition where such incredible hemispheric dysfunction can only be treated by surgically removing half of the brain. And OMG, a show about pediatrics! ** IF YOU’RE TAKING YOUR NEUROLOGY BOARDS THIS SUMMER, CHECK OUT THE PENN NEUROLOGY BOARD REVIEW COURSE AT https://upenn.cloud-cme.com/default.aspx?P=5&EID=65373. AND FOR A DISCOUNTED RATE ON THE ONLINE OR STREAMING RESOURCES, USE PROMO CODE ‘WAVES2020’. ** Produced by James E. Siegler. Music courtesy of Ars Sonor, Daniel Birch, Jon Watts, and Lish Grooves. The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 Rasmussen T, Olszewski J and Lloydsmith D. Focal seizures due to chronic localized encephalitis. Neurology. 1958;8:435-45. Hart YM, Cortez M, Andermann F, Hwang P, Fish DR, Dulac O, Silver K, Fejerman N, Cross H, Sherwin A and et al. Medical treatment of Rasmussen's syndrome (chronic encephalitis and epilepsy): effect of high-dose steroids or immunoglobulins in 19 patients. Neurology. 1994;44:1030-6. Andrews PI, Dichter MA, Berkovic SF, Newton MR and McNamara JO. Plasmapheresis in Rasmussen's encephalitis. Neurology. 1996;46:242-6. Leach JP, Chadwick DW, Miles JB and Hart IK. Improvement in adult-onset Rasmussen's encephalitis with long-term immunomodulatory therapy. Neurology. 1999;52:738-42. Bien CG, Granata T, Antozzi C, Cross JH, Dulac O, Kurthen M, Lassmann H, Mantegazza R, Villemure JG, Spreafico R and Elger CE. Pathogenesis, diagnosis and treatment of Rasmussen encephalitis: a European consensus statement. Brain. 2005;128:454-71. Varadkar S, Bien CG, Kruse CA, Jensen FE, Bauer J, Pardo CA, Vincent A, Mathern GW and Cross JH. Rasmussen's encephalitis: clinical features, pathobiology, and treatment advances. The Lancet Neurology. 2014;13:195-205. Tan AP, Wong YLJ, Lin BJ, Yong HRC and Mankad K. Clinico-radiological approach to cerebral hemiatrophy. Childs Nerv Syst. 2018;34:2377-2390.

Lewy Body Dementia may be the second most common neuropathologic cause of dementia behind Alzheimer disease, but it remains largely a clinical diagnosis with limited treatment options. This week on BrainWaves, Dr. Amy Colcher (Cooper University Hospital) reviews the diagnostic criteria and management strategies for patients and their caregivers who suffer from this condition. Plus, a sort of tribute to Robin Williams. ** IF YOU’RE TAKING YOUR NEUROLOGY BOARDS THIS SUMMER, CHECK OUT THE PENN NEUROLOGY BOARD REVIEW COURSE AT https://upenn.cloud-cme.com/default.aspx?P=5&EID=65373. AND FOR A DISCOUNTED RATE ON THE ONLINE OR STREAMING RESOURCES, USE PROMO CODE ‘WAVES2020’. ** Produced by James E. Siegler and Amy Colcher. Music courtesy of Andrew Sacco, Axletree, Damiano Baldoni, Josh Woodward, and Julie Maxwell. The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 McKeith IG. Spectrum of Parkinson's disease, Parkinson's dementia, and Lewy body dementia. Neurol Clin. 2000;18:865-902. Frieling H, Hillemacher T, Ziegenbein M, Neundorfer B and Bleich S. Treating dopamimetic psychosis in Parkinson's disease: structured review and meta-analysis. Eur Neuropsychopharmacol. 2007;17:165-71. Galvin JE, Duda JE, Kaufer DI, Lippa CF, Taylor A and Zarit SH. Lewy body dementia: the caregiver experience of clinical care. Parkinsonism Relat Disord. 2010;16:388-92. Koga S, Aoki N, Uitti RJ, van Gerpen JA, Cheshire WP, Josephs KA, Wszolek ZK, Langston JW and Dickson DW. When DLB, PD, and PSP masquerade as MSA: an autopsy study of 134 patients. Neurology. 2015;85:404-12. Stinton C, McKeith I, Taylor JP, Lafortune L, Mioshi E, Mak E, Cambridge V, Mason J, Thomas A and O'Brien JT. Pharmacological Management of Lewy Body Dementia: A Systematic Review and Meta-Analysis. Am J Psychiatry. 2015;172:731-42. Desmarais P, Massoud F, Filion J, Nguyen QD and Bajsarowicz P. Quetiapine for Psychosis in Parkinson Disease and Neurodegenerative Parkinsonian Disorders: A Systematic Review. J Geriatr Psychiatry Neurol. 2016;29:227-36. McKeith IG, Boeve BF, Dickson DW, Halliday G, Taylor JP, Weintraub D, Aarsland D, Galvin J, Attems J, Ballard CG, Bayston A, Beach TG, Blanc F, Bohnen N, Bonanni L, Bras J, Brundin P, Burn D, Chen-Plotkin A, Duda JE, El-Agnaf O, Feldman H, Ferman TJ, Ffytche D, Fujishiro H, Galasko D, Goldman JG, Gomperts SN, Graff-Radford NR, Honig LS, Iranzo A, Kantarci K, Kaufer D, Kukull W, Lee VMY, Leverenz JB, Lewis S, Lippa C, Lunde A, Masellis M, Masliah E, McLean P, Mollenhauer B, Montine TJ, Moreno E, Mori E, Murray M, O'Brien JT, Orimo S, Postuma RB, Ramaswamy S, Ross OA, Salmon DP, Singleton A, Taylor A, Thomas A, Tiraboschi P, Toledo JB, Trojanowski JQ, Tsuang D, Walker Z, Yamada M and Kosaka K. Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology. 2017;89:88-100. Armstrong MJ. Lewy Body Dementias. Continuum (Minneap Minn). 2019;25:128-146. Taylor JP, McKeith IG, Burn DJ, Boeve BF, Weintraub D, Bamford C, Allan LM, Thomas AJ and O'Brien JT. New evidence on the management of Lewy body dementia. The Lancet Neurology. 2020;19:157-169.

Can you hear that too? You can’t? Well, that doesn’t mean I’m having auditory hallucinations. It could just be tinnitus, which describes the irritating sound of ringing, buzzing, clicking, or hissing that affect 10-20% of the world's population. But is this a ringing in the ears, or a ringing in the brain? ** IF YOU’RE TAKING YOUR NEUROLOGY BOARDS THIS SUMMER, CHECK OUT THE PENN NEUROLOGY BOARD REVIEW COURSE AT https://upenn.cloud-cme.com/default.aspx?P=5&EID=65373. AND FOR A DISCOUNTED RATE ON THE ONLINE OR STREAMING RESOURCES, USE PROMO CODE ‘WAVES2020’. ** Produced by James E. Siegler. Music courtesy of Andrew Sacco, Jon Watts, Kai Engel, Lovira, Patches, and Kevin McLeod. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 Arenberg IK, Countryman LF, Bernstein LH and Shambaugh GE, Jr. Van Gogh had Meniere's disease and not epilepsy. JAMA : the journal of the American Medical Association. 1990;264:491-3. Sullivan M, Katon W, Russo J, Dobie R and Sakai C. A randomized trial of nortriptyline for severe chronic tinnitus. Effects on depression, disability, and tinnitus symptoms. Archives of internal medicine. 1993;153:2251-9. Dobie RA. A review of randomized clinical trials in tinnitus. Laryngoscope. 1999;109:1202-11. Lockwood AH, Salvi RJ, Burkard RF, Galantowicz PJ, Coad ML and Wack DS. Neuroanatomy of tinnitus. Scand Audiol Suppl. 1999;51:47-52. Palomar Garcia V, Abdulghani Martinez F, Bodet Agusti E, Andreu Mencia L and Palomar Asenjo V. Drug-induced otoxicity: current status. Acta Otolaryngol. 2001;121:569-72. Crummer RW and Hassan GA. Diagnostic approach to tinnitus. Am Fam Physician. 2004;69:120-6. Lockwood AH. Tinnitus. Neurol Clin. 2005;23:893-900, viii. Mattox DE and Hudgins P. Algorithm for evaluation of pulsatile tinnitus. Acta Otolaryngol. 2008;128:427-31. Han BI, Lee HW, Kim TY, Lim JS and Shin KS. Tinnitus: characteristics, causes, mechanisms, and treatments. J Clin Neurol. 2009;5:11-9. Langguth B, Kreuzer PM, Kleinjung T and De Ridder D. Tinnitus: causes and clinical management. The Lancet Neurology. 2013;12:920-930.

It’s 2020, and for the first time in its 72-year history, the American Academy of Neurology has cancelled its annual meeting because of the COVID-19 pandemic. But that does not mean we (BrainWaves producers, not the AAN) can’t provide a few major updates to advances in neurology and neurotherapeutics! This week on the program, Jim Siegler is joined by Dr. Sammita Satyanarayan (Stanford) on a whirlwind tour of some of the latest advances in neurology from this past year. Enjoy! ** IF YOU’RE TAKING YOUR NEUROLOGY BOARDS THIS SUMMER, CHECK OUT THE PENN NEUROLOGY BOARD REVIEW COURSE AT https://upenn.cloud-cme.com/default.aspx?P=5&EID=65373. AND FOR A DISCOUNTED RATE ON THE ONLINE OR STREAMING RESOURCES, USE PROMO CODE ‘WAVES2020’. ** DISCLAIMER: BrainWaves: A Neurology Podcast is not a product of the American Academy of Neurology (AAN) or its affiliates. Any content discussed on the program does not reflect the opinions of the AAN or its leadership nor does it contain any copyrighted material by the AAN or its affiliates. This program is neither published in collaboration with the AAN nor is it intended to plagiarize any content or programming of the AAN or its affiliates. The opinions discussed in this program are those of the producers and are not reflective of their employers or affiliates. This episode was produced by Sammita Satyanarayan and James E. Siegler. Music courtesy of E’s Jammy Jams, Lee Roosevere, Rui, and Steve Combs. The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 Dodick D, Lipton RB, Martin V, Papademetriou V, Rosamond W, MaassenVanDenBrink A, et al. Consensus statement: Cardiovascular safety profile of triptans (5-ht agonists) in the acute treatment of migraine. Headache. 2004;44:414-425 Hall GC, Brown MM, Mo J, MacRae KD. Triptans in migraine: The risks of stroke, cardiovascular disease, and death in practice. Neurology. 2004;62:563-568 Campbell BCV, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, et al. Tenecteplase versus alteplase before thrombectomy for ischemic stroke. The New England journal of medicine. 2018;378:1573-1582 Kuca B, Silberstein SD, Wietecha L, Berg PH, Dozier G, Lipton RB, et al. Lasmiditan is an effective acute treatment for migraine: A phase 3 randomized study. Neurology. 2018;91:e2222-e2232 Cortese I, Muranski P, Enose-Akahata Y, Ha SK, Smith B, Monaco M, et al. Pembrolizumab treatment for progressive multifocal leukoencephalopathy. The New England journal of medicine. 2019;380:1597-1605 Goadsby PJ, Wietecha LA, Dennehy EB, Kuca B, Case MG, Aurora SK, et al. Phase 3 randomized, placebo-controlled, double-blind study of lasmiditan for acute treatment of migraine. Brain. 2019;142:1894-1904 Tabrizi SJ, Leavitt BR, Landwehrmeyer GB, Wild EJ, Saft C, Barker RA, et al. Targeting huntingtin expression in patients with huntington's disease. The New England journal of medicine. 2019;380:2307-2316 Campbell BCV, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, et al. Effect of intravenous tenecteplase dose on cerebral reperfusion before thrombectomy in patients with large vessel occlusion ischemic stroke: The extend-ia tnk part 2 randomized clinical trial. JAMA : the journal of the American Medical Association. 2020. Epub ahead of print.

As my wife and I are raising our 9-month old daughter, and she is eating more solid food, I can’t help but think about how important it is she keep an open mind to new food groups. But being open minded is not just a lesson for toddlers. I emphasize it every day on rounds when seeing patients for a “stroke consult”, or a consult for “ICU delirium”. If you reduce yourself to the same anchoring biases that you've grown accustomed to, you’ll never entertain the possibility of other important, and treatable conditions. Or tasty foods. This week on the BrainWaves Podcast, Dr. Brian Jankowitz (Cooper University Hospital Vascular Neurosurgeon) joins Jim in a discussion about a rare, but treatable cause of myelopathy. A condition you won’t want to miss. ** IF YOU’RE TAKING YOUR NEUROLOGY BOARDS THIS SUMMER, CHECK OUT THE PENN NEUROLOGY BOARD REVIEW COURSE AT https://upenn.cloud-cme.com/default.aspx?P=5&EID=65373. AND FOR A DISCOUNTED RATE ON THE ONLINE OR STREAMING RESOURCES, USE PROMO CODE ‘WAVES2020’. ** Produced by Brian Jankowitz and James E. Siegler. Music courtesy of Kevin McLeod, Lee Rosevere, and Loyalty Freak Music. The opening theme was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 Jellema K, Tijssen CC, van Rooij WJ, Sluzewski M, Koudstaal PJ, Algra A and van Gijn J. Spinal dural arteriovenous fistulas: long-term follow-up of 44 treated patients. Neurology. 2004;62:1839-41. Mull M, Nijenhuis RJ, Backes WH, Krings T, Wilmink JT and Thron A. Value and limitations of contrast-enhanced MR angiography in spinal arteriovenous malformations and dural arteriovenous fistulas. AJNR American journal of neuroradiology. 2007;28:1249-58. Krings T and Geibprasert S. Spinal dural arteriovenous fistulas. AJNR American journal of neuroradiology. 2009;30:639-48. Alexander MD, Oliff MC, Olorunsola OG, Brus-Ramer M, Nickoloff EL and Meyers PM. Patient radiation exposure during diagnostic and therapeutic interventional neuroradiology procedures. J Neurointerv Surg. 2010;2:6-10. Cifarelli CP, Kaptain G, Yen CP, Schlesinger D and Sheehan JP. Gamma knife radiosurgery for dural arteriovenous fistulas. Neurosurgery. 2010;67:1230-5; discussion 1235. Kim DJ, Willinsky R, Geibprasert S, Krings T, Wallace C, Gentili F and Terbrugge K. Angiographic characteristics and treatment of cervical spinal dural arteriovenous shunts. AJNR American journal of neuroradiology. 2010;31:1512-5. Chen J and Gailloud P. Safety of spinal angiography: complication rate analysis in 302 diagnostic angiograms. Neurology. 2011;77:1235-40. Manninen AL, Isokangas JM, Karttunen A, Siniluoto T and Nieminen MT. A comparison of radiation exposure between diagnostic CTA and DSA examinations of cerebral and cervicocerebral vessels. AJNR American journal of neuroradiology. 2012;33:2038-42.

Perfusion imaging employs concepts that date back to the early 1830s, and it leverages hardware and software that emerged around the same time at multidetector helical CT scans. But it has only become popular in recent years for thrombectomy decision-making. If I'm being honest, I often never use it for this purpose. So what other purposes might it serve? And how does it work? This week, we review the fundamental concepts of perfusion CT, its utility in stroke care, and how it might prove useful for other neurologic conditions as well. ** IF YOU’RE TAKING YOUR NEUROLOGY BOARDS THIS SUMMER, CHECK OUT THE PENN NEUROLOGY BOARD REVIEW COURSE. FOR A DISCOUNTED RATE ON THE ONLINE OR STREAMING RESOURCES, USE PROMO CODE ‘WAVES2020’. ** Produced by James E. Siegler. Music courtesy of Julie Maxwell, John Bartmann, Kai Engel, and Pachyderm. Our theme song was composed by Jimothy Dalton. Sound effects by Mike Koenig and Daniel Simion. Some of the voices you heard throughout the program were those of Dr. Mathias Prokop, Radbound Medical Center, Netherlands; Terri Yeager, Comprehensive Stroke Program Coordinator at Cooper University Hospital; and a recording that was produced by GE Healthcare, which are freely available on YouTube. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 Campbell BC, Christensen S, Levi CR, Desmond PM, Donnan GA, Davis SM and Parsons MW. Comparison of computed tomography perfusion and magnetic resonance imaging perfusion-diffusion mismatch in ischemic stroke. Stroke; a journal of cerebral circulation. 2012;43:2648-53. Boned S, Padroni M, Rubiera M, Tomasello A, Coscojuela P, Romero N, Muchada M, Rodriguez-Luna D, Flores A, Rodriguez N, Juega J, Pagola J, Alvarez-Sabin J, Molina CA and Ribo M. Admission CT perfusion may overestimate initial infarct core: the ghost infarct core concept. J Neurointerv Surg. 2017;9:66-69. Martins N, Aires A, Mendez B, Boned S, Rubiera M, Tomasello A, Coscojuela P, Hernandez D, Muchada M, Rodriguez-Luna D, Rodriguez N, Juega JM, Pagola J, Molina CA and Ribo M. Ghost Infarct Core and Admission Computed Tomography Perfusion: Redefining the Role of Neuroimaging in Acute Ischemic Stroke. Interv Neurol. 2018;7:513-521. Campbell BCV, Ma H, Ringleb PA, Parsons MW, Churilov L, Bendszus M, Levi CR, Hsu C, Kleinig TJ, Fatar M, Leys D, Molina C, Wijeratne T, Curtze S, Dewey HM, Barber PA, Butcher KS, De Silva DA, Bladin CF, Yassi N, Pfaff JAR, Sharma G, Bivard A, Desmond PM, Schwab S, Schellinger PD, Yan B, Mitchell PJ, Serena J, Toni D, Thijs V, Hacke W, Davis SM, Donnan GA, Extend E and Investigators E. Extending thrombolysis to 4.5-9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data. Lancet. 2019;394:139-147. Siegler JE, Messe SR, Sucharew H, Kasner SE, Mehta T, Arora N, Starosciak AK, De Los Rios La Rosa F, Barnhill NR, Mistry AM, Patel K, Assad S, Tarboosh A, Dakay K, Wagner J, Bennett A, Jagadeesan B, Streib C, Weber SA, Chitale R, Volpi JJ, Mayer SA, Yaghi S, Jayaraman MV, Khatri P and Mistry EA. Noncontrast CT versus Perfusion-Based Core Estimation in Large Vessel Occlusion: The Blood Pressure after Endovascular Stroke Therapy Study. J Neuroimaging. 2019. Epub ahead of print. Barber PA, Demchuk AM, Zhang J and Buchan AM. Validity and reliability of a quantitative computed tomography score in predicting outcome of hyperacute stroke before thrombolytic therapy. ASPECTS Study Group. Alberta Stroke Programme Early CT Score. Lancet. 2000;355:1670-4. Wintermark M, Reichhart M, Thiran JP, Maeder P, Chalaron M, Schnyder P, Bogousslavsky J and Meuli R. Prognostic accuracy of cerebral blood flow measurement by perfusion computed tomography, at the time of emergency room admission, in acute stroke patients. Annals of neurology. 2002;51:417-32. Parsons MW, Pepper EM, Chan V, Siddique S, Rajaratnam S, Bateman GA and Levi CR. Perfusion computed tomography: prediction of final infarct extent and stroke outcome. Annals of neurology. 2005;58:672-9. Campbell BC, Weir L, Desmond PM, Tu HT, Hand PJ, Yan B, Donnan GA, Parsons MW and Davis SM. CT perfusion improves diagnostic accuracy and confidence in acute ischaemic stroke. Journal of neurology, neurosurgery, and psychiatry. 2013;84:613-8. Mangla R, Ekhom S, Jahromi BS, Almast J, Mangla M and Westesson PL. CT perfusion in acute stroke: know the mimics, potential pitfalls, artifacts, and technical errors. Emerg Radiol. 2014;21:49-65. Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, McTaggart RA, Torbey MT, Kim-Tenser M, Leslie-Mazwi T, Sarraj A, Kasner SE, Ansari SA, Yeatts SD, Hamilton S, Mlynash M, Heit JJ, Zaharchuk G, Kim S, Carrozzella J, Palesch YY, Demchuk AM, Bammer R, Lavori PW, Broderick JP, Lansberg MG and Investigators D. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. The New England journal of medicine. 2018;378:708-718. Van Cauwenberge MGA, Dekeyzer S, Nikoubashman O, Dafotakis M and Wiesmann M. Can perfusion CT unmask postictal stroke mimics? A case-control study of 133 patients. Neurology. 2018;91:e1918-e1927. Siegler JE, Olsen A, Pulst-Korenberg J, Cristancho D, Rosenberg J, Raab L, Cucchiara B and Messe SR. Multicenter Volumetric Assessment of Artifactual Hypoperfusion Patterns using Automated CT Perfusion Imaging. J Neuroimaging. 2019;29:573-579.

Imagine what it would have been like, to have lived in 1918. Spanish influenza killed approximately 3% of the world’s population. Other than the world war, international travel was fairly limited. There was no social media. No flu vaccine. No mechanical ventilators. No World Health Organization. A century later, we’re facing the next great pandemic. And what have we learned? What do we know? From the neurologic complications of SARS-CoV-2, to non-infectious consequences, the environmental impact of a pandemic, and lessons learned polio, we hope to leave you with a few important take-home messages, a silver lining—and some food for thought—about the ongoing COVID pandemic. ** IF YOU’RE TAKING YOUR NEUROLOGY BOARDS THIS SUMMER, CHECK OUT THE PENN NEUROLOGY BOARD REVIEW COURSE AT https://upenn.cloud-cme.com/default.aspx?P=5&EID=65373. AND FOR A DISCOUNTED RATE ON THE ONLINE OR STREAMING RESOURCES, USE PROMO CODE ‘WAVES2020’. ** REFERENCES Murata K, Inoue O, Akutsu M and Iwata T. Neuromotor effects of short-term and long-term exposures to trichloroethylene in workers. Am J Ind Med. 2010;53:915-21. Umapathi T, Kor AC, Venketasubramanian N, Lim CC, Pang BC, Yeo TT, Lee CC, Lim PL, Ponnudurai K, Chuah KL, Tan PH, Tai DY and Ang SP. Large artery ischaemic stroke in severe acute respiratory syndrome (SARS). Journal of neurology. 2004;251:1227-31. Li Y, Wang M, Zhou Y, Chang J, Xian Y, Mao L, Hong C, Chen S, Wang Y, Wang H, Li M, Jin H and Hu B. Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study. Lancet. 2020;Epub ahead of print. Mao L, Wang M, Chen S, He Q, Chang J, Hong C, Zhou Y, Wang D, Miao X, Hu Y, Li Y, Jin H and Hu B. Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: A Retrospective Case Series Study. Lancet. 2020;Epub ahead of print. Perbellini L, Olivato D, Zedde A and Miglioranzi R. Acute trichloroethylene poisoning by ingestion: clinical and pharmacokinetic aspects. Intensive care medicine. 1991;17:234-5. Guehl D, Bezard E, Dovero S, Boraud T, Bioulac B and Gross C. Trichloroethylene and parkinsonism: a human and experimental observation. European journal of neurology : the official journal of the European Federation of Neurological Societies. 1999;6:609-11. Gash DM, Rutland K, Hudson NL, Sullivan PG, Bing G, Cass WA, Pandya JD, Liu M, Choi DY, Hunter RL, Gerhardt GA, Smith CD, Slevin JT and Prince TS. Trichloroethylene: Parkinsonism and complex 1 mitochondrial neurotoxicity. Annals of neurology. 2008;63:184-92. Wang G, Zhang Z, Ayala C, Dunet DO, Fang J and George MG. Costs of hospitalization for stroke patients aged 18-64 years in the United States. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association. 2014;23:861-8. West JB. The physiological challenges of the 1952 Copenhagen poliomyelitis epidemic and a renaissance in clinical respiratory physiology. J Appl Physiol (1985). 2005;99:424-32.

They say the eyes are the window to the soul. Well, maybe. They also happen to be the first organ we (perhaps, unknowingly) examine whenever we encounter a patient. This week on the program, we build on the prior episode about anisocoria (featuring Dr. Ali Hamedani, episode 74) and discuss the examination of the pupil, and all that these 3-5 millimeters of tissue can teach us. Plus, some Dad jokes at the end... Produced by James E. Siegler. Music courtesy of Chris Haugen, Daniel Birch, and Lee Roosevere. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 Bouffard MA. The Pupil. Continuum (Minneap Minn). 2019;25:1194-1214. Liu G, Volpe NJ and Galetta S. Neuro-Ophthalmology: Diagnosis and Management: Elsevier; 2018. https://www.amazon.com/Liu-Volpe-Galettas-Neuro-Ophthalmology-Management/dp/032334044X  

Generalized weakness is a common complaint. Much of the time, we as neurologists don’t even see these patients in the hospital or the clinic. But more often than not, “generalized” weakness may be the only way a patient describes difficulty brushing their hair or climbing stairs. In these situations, it’s not exactly generalized weakness. It’s something else. This week on BrainWaves, we review the major patterns of weakness that characterize the most common muscle disorders. With a quick review of EMG findings. Enjoy! Produced by James E. Siegler. Music courtesy of Jahzzar, Kevin McLeod, Patches, and Montplaisir. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 Suresh E and Wimalaratna S. Proximal myopathy: diagnostic approach and initial management. Postgraduate medical journal. 2013;89:470-7. Walter MC, Reilich P, Thiele S, Schessl J, Schreiber H, Reiners K, Kress W, Muller-Reible C, Vorgerd M, Urban P, Schrank B, Deschauer M, Schlotter-Weigel B, Kohnen R and Lochmuller H. Treatment of dysferlinopathy with deflazacort: a double-blind, placebo-controlled clinical trial. Orphanet J Rare Dis. 2013;8:26. Fayssoil A, Ogna A, Chaffaut C, Chevret S, Guimaraes-Costa R, Leturcq F, Wahbi K, Prigent H, Lofaso F, Nardi O, Clair B, Behin A, Stojkovic T, Laforet P, Orlikowski D and Annane D. Natural History of Cardiac and Respiratory Involvement, Prognosis and Predictive Factors for Long-Term Survival in Adult Patients with Limb Girdle Muscular Dystrophies Type 2C and 2D. PloS one. 2016;11:e0153095. Harris E, Bladen CL, Mayhew A, James M, Bettinson K, Moore U, Smith FE, Rufibach L, Cnaan A, Bharucha-Goebel DX, Blamire AM, Bravver E, Carlier PG, Day JW, Diaz-Manera J, Eagle M, Grieben U, Harms M, Jones KJ, Lochmuller H, Mendell JR, Mori-Yoshimura M, Paradas C, Pegoraro E, Pestronk A, Salort-Campana E, Schreiber-Katz O, Semplicini C, Spuler S, Stojkovic T, Straub V, Takeda S, Rocha CT, Walter MC, Bushby K and Jain COSC. The Clinical Outcome Study for dysferlinopathy: An international multicenter study. Neurol Genet. 2016;2:e89. Clark KEN and Isenberg DA. A review of inflammatory idiopathic myopathy focusing on polymyositis. European journal of neurology : the official journal of the European Federation of Neurological Societies. 2018;25:13-23. Wicklund MP. The Limb-Girdle Muscular Dystrophies. Continuum (Minneap Minn). 2019;25:1599-1618. Preston DC and Shapiro BE. Electromyography and neuromuscular disorders: clinical-electrophysiologic correlations. 3rd ed. London; New York: Elsevier Saunders; 2013. “rAAVrh74.MHCK7.DYSF.DV for Treatment of Dysferlinopathies.” Clinicaltrials.gov. Retrieved from https://clinicaltrials.gov/ct2/show/NCT02710500?cond=dysferlinopathy&draw=2&rank=1 on 22 December 2019. For great video examples of EMG findings in nerve and muscle disease, check out KImura & Kohara's YouTube recordings: https://www.youtube.com/watch?v=6-3PP_S-Q8I&list=PLCC_NQWOABCY18PEzlGELGOR_-IDNaDQ_

This week on BrainWaves, we're revisiting the 2017 episode on recurrent meningitis featuring Dr. Jon Rosenberg (New York Presbyterian-Columbia). While we may not have made much headway in the treatment of these patients since the original show came out, we have made some progress in the neurodiagnostics. Produced by James E. Siegler and Jon Rosenberg. Music courtesy of Coldnoise, Three Chain Links, and Uncanny. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 Zunt JR and Baldwin KJ. Chronic and subacute meningitis. Continuum (Minneap Minn). 2012;18:1290-318. Ginsberg L and Kidd D. Chronic and recurrent meningitis. Pract Neurol. 2008;8:348-61. Rosenberg J and Galen BT. Recurrent Meningitis. Curr Pain Headache Rep. 2017;21:33. Baldwin KJ and Avila JD. Diagnostic Approach to Chronic Meningitis. Neurol Clin. 2018;36:831-849. Wilson MR, O'Donovan BD, Gelfand JM, Sample HA, Chow FC, Betjemann JP, Shah MP, Richie MB, Gorman MP, Hajj-Ali RA, Calabrese LH, Zorn KC, Chow ED, Greenlee JE, Blum JH, Green G, Khan LM, Banerji D, Langelier C, Bryson-Cahn C, Harrington W, Lingappa JR, Shanbhag NM, Green AJ, Brew BJ, Soldatos A, Strnad L, Doernberg SB, Jay CA, Douglas V, Josephson SA and DeRisi JL. Chronic Meningitis Investigated via Metagenomic Next-Generation Sequencing. JAMA Neurol. 2018;75:947-955. Wilson MR, Sample HA, Zorn KC, Arevalo S, Yu G, Neuhaus J, Federman S, Stryke D, Briggs B, Langelier C, Berger A, Douglas V, Josephson SA, Chow FC, Fulton BD, DeRisi JL, Gelfand JM, Naccache SN, Bender J, Dien Bard J, Murkey J, Carlson M, Vespa PM, Vijayan T, Allyn PR, Campeau S, Humphries RM, Klausner JD, Ganzon CD, Memar F, Ocampo NA, Zimmermann LL, Cohen SH, Polage CR, DeBiasi RL, Haller B, Dallas R, Maron G, Hayden R, Messacar K, Dominguez SR, Miller S and Chiu CY. Clinical Metagenomic Sequencing for Diagnosis of Meningitis and Encephalitis. The New England journal of medicine. 2019;380:2327-2340.

Immune checkpoint inhibitors have revolutionized cancer treatment. Unlike chemotherapy, which essentially includes cellular toxins that can cause widespread and unnecessary tissue damage, checkpoint inhibitors are used to train the body’s natural immune system to fight off the cancer. And while they are extraordinarily effective options for patients with malignant disease, they are not without risk. Every day, we are learning more and more about the autoimmune side effects of these novel therapies. This week on the BrainWaves Podcast, Dr. Justine Cohen (University of Pennsylvania) shares her experience managing patients with checkpoint inhibitor neurotoxicity. Produced by James E. Siegler and Justine Cohen. Music courtesy of Jon Watts, Kai Engel, and Kevin McLeod--as well as a cameo appearance by the Checkpoints. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. 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 Bhatia S, Tykodi SS and Thompson JA. Treatment of metastatic melanoma: an overview. Oncology (Williston Park). 2009;23:488-96. Hottinger AF. Neurologic complications of immune checkpoint inhibitors. Curr Opin Neurol. 2016;29:806-812. Wick W, Hertenstein A and Platten M. Neurological sequelae of cancer immunotherapies and targeted therapies. Lancet Oncol. 2016;17:e529-e541. Cohen JV and Buchbinder EI. The Evolution of Adjuvant Therapy for Melanoma. Curr Oncol Rep. 2019;21:106. Cohen JV, Wang N, Venur VA, Hadfield MJ, Cahill DP, Oh K and Brastianos PK. Neurologic complications of melanoma. Cancer. 2019. Epub ahead of print. Graus F and Dalmau J. Paraneoplastic neurological syndromes in the era of immune-checkpoint inhibitors. Nat Rev Clin Oncol. 2019;16:535-548. Zekeridou A and Lennon VA. Neurologic Autoimmunity in the Era of Checkpoint Inhibitor Cancer Immunotherapy. Mayo Clinic proceedings. 2019;94:1865-1878. Zubiri L, Allen IM, Taylor MS, Guidon AC, Chen ST, Schoenfeld SR, Neilan TG, Sise ME, Mooradian MJ, Rubin KM, Leaf RK, Parikh AR, Faje A, Gainor JF, Cohen JV, Fintelmann FJ, Kohler MJ, Dougan M and Reynolds KL. Immune-Related Adverse Events in the Setting of PD-1/L1 Inhibitor Combination Therapy. Oncologist. 2019. Epub ahead of print.

The sole FDA approved indication for clobazam is as a therapeutic adjunct in Lennox Gastaut Syndrome. But as more and more clinicians publish their experience with the off-label success of certain therapies, we may see new indications for this and other pharmacologic agents in the treatment of neurologic disease. Produced by James E. Siegler. Unless otherwise mentioned in the podcast, no competing financial interests exist in the content of this episode. Music courtesy of Chris Zabriskie, Milton Arias, and John Bartmann. 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 Schmidt D, Rohde M, Wolf P and Roeder-Wanner U. Clobazam for refractory focal epilepsy. A controlled trial. Archives of neurology. 1986;43:824-6. Keene DL, Whiting S and Humphreys P. Clobazam as an add-on drug in the treatment of refractory epilepsy of childhood. Can J Neurol Sci. 1990;17:317-9. Remy C. Clobazam in the treatment of epilepsy: a review of the literature. Epilepsia. 1994;35 Suppl 5:S88-91. Montenegro MA, Cendes F, Noronha AL, Mory SB, Carvalho MI, Marques LH and Guerreiro CA. Efficacy of clobazam as add-on therapy in patients with refractory partial epilepsy. Epilepsia. 2001;42:539-42. Ng YT and Collins SD. Clobazam. Neurotherapeutics. 2007;4:138-44. Montenegro MA, Arif H, Nahm EA, Resor SR, Jr. and Hirsch LJ. Efficacy of clobazam as add-on therapy for refractory epilepsy: experience at a US epilepsy center. Clin Neuropharmacol. 2008;31:333-8. Mahmoud SH and Rans C. Systematic review of clobazam use in patients with status epilepticus. Epilepsia Open. 2018;3:323-330. Bresnahan R, Martin-McGill KJ, Williamson J, Michael BD and Marson AG. Clobazam add-on therapy for drug-resistant epilepsy. The Cochrane database of systematic reviews. 2019;10:CD004154. YOUTUBE EXCERPTS (shared via fair use) Kathryn Davis, MD (Hospital of the University of Pennsylvania): https://www.youtube.com/watch?v=XInZ7Y0lgKg Patty McGoldrick, NP, MPA (Beth Israel Deaconness Medical Center/Roosevelt Hospital): https://www.youtube.com/watch?v=sE2BkYXqxJs&t=14s

In a patient with isolated, progressive hand numbness and weakness, there is a much to be learned about the clinical exam. Often, its all you need. This week, Dr. Aakriti Kothiwal (Cooper University Hospital) presents this week's clinical case and helps localize the lesion. Produced by James E. Siegler and Aakriti Kothiwal. Music courtesy of Jazzar, Lee Rosevere, and Loyalty Freak Music. 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 Gross PT and Jones HR, Jr. Proximal median neuropathies: electromyographic and clinical correlation. Muscle Nerve. 1992;15:390-5. Gross PT and Tolomeo EA. Proximal median neuropathies. Neurol Clin. 1999;17:425-45, v. Peters N, Muller-Schunk S, Freilinger T, During M, Pfefferkorn T and Dichgans M. Ischemic stroke of the cortical "hand knob" area: stroke mechanisms and prognosis. Journal of neurology. 2009;256:1146-51. Bouche P. Compression and entrapment neuropathies. Handbook of clinical neurology. 2013;115:311-66. Padua L, Coraci D, Erra C, Pazzaglia C, Paolasso I, Loreti C, Caliandro P and Hobson-Webb LD. Carpal tunnel syndrome: clinical features, diagnosis, and management. The Lancet Neurology. 2016;15:1273-1284. Aamodt WW, Siegler JE and Elman L. Teaching NeuroImages: Acute infarction of the left medial lemniscus masquerading as a peripheral neuropathy. Neurology. 2017;88:e178. Hobson-Webb LD and Juel VC. Common Entrapment Neuropathies. Continuum (Minneap Minn). 2017;23:487-511.

The common teaching is that restricted diffusion on MRI indicates stroke—acute cerebral infarction. When, more specifically, the changes on DWI and ADC indicate impairment in the random movement of water molecules in a given tissue. With slower movement, as in energy-depleted tissues with failing ATP-dependent sodium/potassium channels, high cellularity, or a highly viscous extra-cellular space, there is restricted diffusion (of water) and a corresponding bright signal on DWI. These and other considerations are the focus of this week's episode of BrainWaves. Produced by James E. Siegler. Music courtesy of Uncanny and Kevin McLeod. 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 Filippi M, Iannucci G, Cercignani M, Assunta Rocca M, Pratesi A and Comi G. A quantitative study of water diffusion in multiple sclerosis lesions and normal-appearing white matter using echo-planar imaging. Archives of neurology. 2000;57:1017-21. Meyer JR, Gutierrez A, Mock B, Hebron D, Prager JM, Gorey MT and Homer D. High-b-value diffusion-weighted MR imaging of suspected brain infarction. AJNR American journal of neuroradiology. 2000;21:1821-9. Roberts TP and Rowley HA. Diffusion weighted magnetic resonance imaging in stroke. Eur J Radiol. 2003;45:185-94. McKinney AM, Short J, Truwit CL, McKinney ZJ, Kozak OS, SantaCruz KS and Teksam M. Posterior reversible encephalopathy syndrome: incidence of atypical regions of involvement and imaging findings. AJR Am J Roentgenol. 2007;189:904-12. Maier SE, Sun Y and Mulkern RV. Diffusion imaging of brain tumors. NMR Biomed. 2010;23:849-64. 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. Hegde AN, Mohan S, Lath N and Lim CC. Differential diagnosis for bilateral abnormalities of the basal ganglia and thalamus. Radiographics. 2011;31:5-30. Aliaga ES and Barkhof F. MRI mimics of multiple sclerosis. Handbook of clinical neurology. 2014;122:291-316. Starkey J, Kobayashi N, Numaguchi Y and Moritani T. Cytotoxic Lesions of the Corpus Callosum That Show Restricted Diffusion: Mechanisms, Causes, and Manifestations. Radiographics. 2017;37:562-576.

2019 was a big year. The year of the Mueller report. The American college admissions scandals. Brexit. But it was also the year the US Women's team won the World Cup, and lobbied for the equal pay of women and men in sports. It was the year of NMO, in which several pivotal trials showed benefit of disease modulating therapy in this condition. The year Will Smith played Genie in Aladdin. 2019 was a great year. And as we wrap up 2019, this week's episode includes some of the highlights. Enjoy! Produced by James E. Siegler with support from Erika Mejia, Rajat Dhar, and the entire Siegler family. Music courtesy of Axletree, Chris Zabriskie, John Paston, Kevin Mcleod, Josh Woodward, Steve Combs, Lee Rosevere, Scott Holmes, Advent Chamber Orchestra, Coldnoise, and Pachyderm. 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 [BRAIN FOOD] Kennedy DO, Wightman EL, Reay JL, Lietz G, Okello EJ, Wilde A and Haskell CF. Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation. Am J Clin Nutr. 2010;91:1590-7. Devore EE, Kang JH, Breteler MM and Grodstein F. Dietary intakes of berries and flavonoids in relation to cognitive decline. Annals of neurology. 2012;72:135-43. Norton S, Matthews FE, Barnes DE, Yaffe K and Brayne C. Potential for primary prevention of Alzheimer's disease: an analysis of population-based data. The Lancet Neurology. 2014;13:788-94. Morris MC, Tangney CC, Wang Y, Sacks FM, Barnes LL, Bennett DA and Aggarwal NT. MIND diet slows cognitive decline with aging. Alzheimers Dement. 2015;11:1015-22. Valls-Pedret C, Sala-Vila A, Serra-Mir M, Corella D, de la Torre R, Martinez-Gonzalez MA, Martinez-Lapiscina EH, Fito M, Perez-Heras A, Salas-Salvado J, Estruch R and Ros E. Mediterranean Diet and Age-Related Cognitive Decline: A Randomized Clinical Trial. JAMA internal medicine. 2015;175:1094-1103. Newman JC, Covarrubias AJ, Zhao M, Yu X, Gut P, Ng CP, Huang Y, Haldar S and Verdin E. Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice. Cell Metab. 2017;26:547-557 e8. Miller MG, Hamilton DA, Joseph JA and Shukitt-Hale B. Dietary blueberry improves cognition among older adults in a randomized, double-blind, placebo-controlled trial. Eur J Nutr. 2018;57:1169-1180. Okkersen K, Jimenez-Moreno C, Wenninger S, Daidj F, Glennon J, Cumming S, Littleford R, Monckton DG, Lochmuller H, Catt M, Faber CG, Hapca A, Donnan PT, Gorman G, Bassez G, Schoser B, Knoop H, Treweek S, van Engelen BGM and consortium O. Cognitive behavioural therapy with optional graded exercise therapy in patients with severe fatigue with myotonic dystrophy type 1: a multicentre, single-blind, randomised trial. The Lancet Neurology. 2018;17:671-680. Radd-Vagenas S, Duffy SL, Naismith SL, Brew BJ, Flood VM and Fiatarone Singh MA. Effect of the Mediterranean diet on cognition and brain morphology and function: a systematic review of randomized controlled trials. Am J Clin Nutr. 2018;107:389-404. Xu W, Wang H, Wan Y, Tan C, Li J, Tan L and Yu JT. Alcohol consumption and dementia risk: a dose-response meta-analysis of prospective studies. Eur J Epidemiol. 2017;32:31-42. Lefevre-Arbogast S, Gaudout D, Bensalem J, Letenneur L, Dartigues JF, Hejblum BP, Feart C, Delcourt C and Samieri C. Pattern of polyphenol intake and the long-term risk of dementia in older persons. Neurology. 2018;90:e1979-e1988. Liu QP, Wu YF, Cheng HY, Xia T, Ding H, Wang H, Wang ZM and Xu Y. Habitual coffee consumption and risk of cognitive decline/dementia: A systematic review and meta-analysis of prospective cohort studies. Nutrition. 2016;32:628-36. [OF MEASLES AND MEN] Murch SH, Anthony A, Casson DH, Malik M, Berelowitz M, Dhillon AP, Thomson MA, Valentine A, Davies SE and Walker-Smith JA. Retraction of an interpretation. Lancet. 2004;363:750. Perry RT and Halsey NA. The clinical significance of measles: a review. The Journal of infectious diseases. 2004;189 Suppl 1:S4-16. Campbell H, Andrews N, Brown KE and Miller E. Review of the effect of measles vaccination on the epidemiology of SSPE. Int J Epidemiol. 2007;36:1334-48. Poland GA and Jacobson RM. The age-old struggle against the antivaccinationists. The New England journal of medicine. 2011;364:97-9. Maglione MA, Das L, Raaen L, Smith A, Chari R, Newberry S, Shanman R, Perry T, Goetz MB and Gidengil C. Safety of vaccines used for routine immunization of U.S. children: a systematic review. Pediatrics. 2014;134:325-37. Bester JC. Measles and Measles Vaccination: A Review. JAMA Pediatr. 2016;170:1209-1215. Bester JC. Not a matter of parental choice but of social justice obligation: Children are owed measles vaccination. Bioethics. 2018;32:611-619. Fournet N, Mollema L, Ruijs WL, Harmsen IA, Keck F, Durand JY, Cunha MP, Wamsiedel M, Reis R, French J, Smit EG, Kitching A and van Steenbergen JE. Under-vaccinated groups in Europe and their beliefs, attitudes and reasons for non-vaccination; two systematic reviews. BMC Public Health. 2018;18:196.  Trump’s tweet: https://twitter.com/realdonaldtrump/status/449525268529815552?lang=en [NON-INFECTIOUS NEUROLOGIC COMPLICATIONS OF ORGAN TRANSPLANT] Senzolo M, Ferronato C and Burra P. Neurologic complications after solid organ transplantation. Transpl Int. 2009;22:269-78. Dhar R. Neurologic complications of transplantation. Handbook of clinical neurology. 2017;141:545-572. Mateen FJ, Dierkhising RA, Rabinstein AA, van de Beek D and Wijdicks EF. Neurological complications following adult lung transplantation. Am J Transplant. 2010;10:908-14. Munoz P, Valerio M, Palomo J, Fernandez-Yanez J, Fernandez-Cruz A, Guinea J and Bouza E. Infectious and non-infectious neurologic complications in heart transplant recipients. Medicine (Baltimore). 2010;89:166-75. Wu Q, Marescaux C, Wolff V, Jeung MY, Kessler R, Lauer V and Chen Y. Tacrolimus-associated posterior reversible encephalopathy syndrome after solid organ transplantation. Eur Neurol. 2010;64:169-77. Dhar R, Young GB and Marotta P. Perioperative neurological complications after liver transplantation are best predicted by pre-transplant hepatic encephalopathy. Neurocritical care. 2008;8:253-8.

In the TV show, HOUSE, it's either lupus or its sarcoidosis. Only, it's never sarcoidosis. That's because sarcoidosis is such a heterogeneous condition and can affect practically any age group. In some patients, this idiopathic inflammatory disorder can also involve the nervous system. Also causing a variety of signs and symptoms ranging from mild headache to a proximal myopathy or even a CNS vasculitis. This week on the BrainWaves podcast, Dr. Jesse Thon reflects on the literature and shares his experience managing patients with this troubling condition. Produced by Jesse Thon and James E. Siegler. Music courtesy of Steve Combs, Lovira, and Yakov Goldman. 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 Petereit HF, Reske D, Tumani H, Jarius S, Markus Leweke F, Woitalla D, Pfister HW and Rubbert A. Soluble CSF interleukin 2 receptor as indicator of neurosarcoidosis. Journal of neurology. 2010;257:1855-63. Agnihotri SP, Singhal T, Stern BJ and Cho TA. Neurosarcoidosis. Semin Neurol. 2014;34:386-94. Bitoun S, Bouvry D, Borie R, Mahevas M, Sacre K, Haroche J, Psimaras D, Pottier C, Mathian A, Hie M, Boutin DL, Papo T, Godeau B, Valeyre D, Nunes H, Amoura Z and Cohen Aubart F. Treatment of neurosarcoidosis: A comparative study of methotrexate and mycophenolate mofetil. Neurology. 2016;87:2517-2521. Gelfand JM, Bradshaw MJ, Stern BJ, Clifford DB, Wang Y, Cho TA, Koth LL, Hauser SL, Dierkhising J, Vu N, Sriram S, Moses H, Bagnato F, Kaufmann JA, Ammah DJ, Yohannes TH, Hamblin MJ, Venna N, Green AJ and Pawate S. Infliximab for the treatment of CNS sarcoidosis: A multi-institutional series. Neurology. 2017;89:2092-2100. Jolliffe EA, Keegan BM and Flanagan EP. Trident sign trumps Aquaporin-4-IgG ELISA in diagnostic value in a case of longitudinally extensive transverse myelitis. Mult Scler Relat Disord. 2018;23:7-8. Wallaert B, Ramon P, Fournier EC, Hatron PY, Muir JF, Tonnel AB and Voisin C. High-dose methylprednisolone pulse therapy in sarcoidosis. Eur J Respir Dis. 1986;68:256-62. Agbogu BN, Stern BJ, Sewell C and Yang G. Therapeutic considerations in patients with refractory neurosarcoidosis. Archives of neurology. 1995;52:875-9. Baughman RP and Lower EE. Infliximab for refractory sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2001;18:70-4. Baughman RP, Drent M, Kavuru M, Judson MA, Costabel U, du Bois R, Albera C, Brutsche M, Davis G, Donohue JF, Muller-Quernheim J, Schlenker-Herceg R, Flavin S, Lo KH, Oemar B, Barnathan ES and Sarcoidosis I. Infliximab therapy in patients with chronic sarcoidosis and pulmonary involvement. Am J Respir Crit Care Med. 2006;174:795-802. Rossman MD, Newman LS, Baughman RP, Teirstein A, Weinberger SE, Miller W, Jr. and Sands BE. A double-blinded, randomized, placebo-controlled trial of infliximab in subjects with active pulmonary sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2006;23:201-8.

In 2016, when we first launched the BrainWaves podcast, cryptogenic stroke was a poorly understood concept. 3 years later, it remains poorly understood. But we are making progress. In this week's update of episode 10, we review the progress that has been made in the pathogenesis, diagnosis, and management of these patients. Produced by James E. Siegler. The original 2016 version of this show was also produced by Dr. Noah Levinson. Music courtesy of Josh Woodward, Julie Maxwell, Dan Lebowitz, and this group called E’s Jammy Jams. 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 Siegler JE, Swaminathan B, Giruparajah M, Bosch J, Perera KS, Hart RG, Kasner SE and Investigators EGR. Age disparity in diagnostic evaluation of stroke patients: Embolic Stroke of Undetermined Source Global Registry Project. Eur Stroke J. 2016;1:130-138. Jacobs BS, Boden-Albala B, Lin IF and Sacco RL. Stroke in the young in the northern Manhattan stroke study. Stroke; a journal of cerebral circulation. 2002;33:2789-93. Hart RG, Sharma M, Mundl H, Kasner SE, Bangdiwala SI, Berkowitz SD, Swaminathan B, Lavados P, Wang Y, Wang Y, Davalos A, Shamalov N, Mikulik R, Cunha L, Lindgren A, Arauz A, Lang W, Czlonkowska A, Eckstein J, Gagliardi RJ, Amarenco P, Ameriso SF, Tatlisumak T, Veltkamp R, Hankey GJ, Toni D, Bereczki D, Uchiyama S, Ntaios G, Yoon BW, Brouns R, Endres M, Muir KW, Bornstein N, Ozturk S, O'Donnell MJ, De Vries Basson MM, Pare G, Pater C, Kirsch B, Sheridan P, Peters G, Weitz JI, Peacock WF, Shoamanesh A, Benavente OR, Joyner C, Themeles E, Connolly SJ and Investigators NE. Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source. The New England journal of medicine. 2018;378:2191-2201. Diener HC, Sacco RL, Easton JD, Granger CB, Bernstein RA, Uchiyama S, Kreuzer J, Cronin L, Cotton D, Grauer C, Brueckmann M, Chernyatina M, Donnan G, Ferro JM, Grond M, Kallmunzer B, Krupinski J, Lee BC, Lemmens R, Masjuan J, Odinak M, Saver JL, Schellinger PD, Toni D, Toyoda K, Committee R-SES and Investigators. Dabigatran for Prevention of Stroke after Embolic Stroke of Undetermined Source. The New England journal of medicine. 2019;380:1906-1917. Di Tullio M, Sacco RL, Gopal A, Mohr JP and Homma S. Patent foramen ovale as a risk factor for cryptogenic stroke. Annals of internal medicine. 1992;117:461-5. Overell JR, Bone I and Lees KR. Interatrial septal abnormalities and stroke: a meta-analysis of case-control studies. Neurology. 2000;55:1172-9. Li J, Liu J, Liu M, Zhang S, Hao Z, Zhang J and Zhang C. Closure versus medical therapy for preventing recurrent stroke in patients with patent foramen ovale and a history of cryptogenic stroke or transient ischemic attack. The Cochrane database of systematic reviews. 2015;9:CD009938. Mas JL, Derumeaux G, Guillon B, Massardier E, Hosseini H, Mechtouff L, Arquizan C, Bejot Y, Vuillier F, Detante O, Guidoux C, Canaple S, Vaduva C, Dequatre-Ponchelle N, Sibon I, Garnier P, Ferrier A, Timsit S, Robinet-Borgomano E, Sablot D, Lacour JC, Zuber M, Favrole P, Pinel JF, Apoil M, Reiner P, Lefebvre C, Guerin P, Piot C, Rossi R, Dubois-Rande JL, Eicher JC, Meneveau N, Lusson JR, Bertrand B, Schleich JM, Godart F, Thambo JB, Leborgne L, Michel P, Pierard L, Turc G, Barthelet M, Charles-Nelson A, Weimar C, Moulin T, Juliard JM, Chatellier G and Investigators C. Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke. The New England journal of medicine. 2017;377:1011-1021. Saver JL, Carroll JD, Thaler DE, Smalling RW, MacDonald LA, Marks DS, Tirschwell DL and Investigators R. Long-Term Outcomes of Patent Foramen Ovale Closure or Medical Therapy after Stroke. The New England journal of medicine. 2017;377:1022-1032. Sondergaard L, Kasner SE, Rhodes JF, Andersen G, Iversen HK, Nielsen-Kudsk JE, Settergren M, Sjostrand C, Roine RO, Hildick-Smith D, Spence JD, Thomassen L and Gore RCSI. Patent Foramen Ovale Closure or Antiplatelet Therapy for Cryptogenic Stroke. The New England journal of medicine. 2017;377:1033-1042. Juul K, Tybjaerg-Hansen A, Steffensen R, Kofoed S, Jensen G and Nordestgaard BG. Factor V Leiden: The Copenhagen City Heart Study and 2 meta-analyses. Blood. 2002;100:3-10. Kaku DA and Lowenstein DH. Emergence of recreational drug abuse as a major risk factor for stroke in young adults. Annals of internal medicine. 1990;113:821-7. Fonseca AC and Ferro JM. Drug abuse and stroke. Current neurology and neuroscience reports. 2013;13:325. Susac JO, Egan RA, Rennebohm RM and Lubow M. Susac's syndrome: 1975-2005 microangiopathy/autoimmune endotheliopathy. Journal of the neurological sciences. 2007;257:270-2. Perera KS, Ng KKH, Nayar S, Catanese L, Dyal L, Sharma M, Connolly SJ, Yusuf S, Bosch J, Eikelboom JW and Hart RG. Association Between Low-Dose Rivaroxaban With or Without Aspirin and Ischemic Stroke Subtypes: A Secondary Analysis of the COMPASS Trial. JAMA Neurol. 2019. Epub ahead of print.

Peer review prior to publication of medical data dates back to the 9th century CE, but has only really gained steam in the past 70 or 80 years. Ideally, peer review would serve as an initial filter for data that enters a permanent public scientific record. But peer review is not without flaws. In the second installment of the BrainWaves segment, “It’s not over yet…”, we discuss publication as a potential source of bias, and highlight the reasons why it should not be the final step of the peer review process. Produced by James E. Siegler. Music courtesy of Cullah, Lee Rosevere, John Bartmann, Kevin McLeod, and Jon Watts. 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 Bingham C. Peer review on the Internet: A better class of conversation. Lancet. 1998;351:S10-14. Godlee F, Gale CR and Martyn CN. Effect on the quality of peer review of blinding reviewers and asking them to sign their reports: a randomized controlled trial. JAMA : the journal of the American Medical Association. 1998;280:237-40. Jefferson T, Alderson P, Wager E and Davidoff F. Effects of editorial peer review: a systematic review. JAMA : the journal of the American Medical Association. 2002;287:2784-6. Jefferson T, Rudin M, Brodney Folse S and Davidoff F. Editorial peer review for improving the quality of reports of biomedical studies. The Cochrane database of systematic reviews. 2007:MR000016. Ware M. Peer review: Benefits, perspectives, and alternatives: Publishing Research Consortium; 2008. Mandavilli A. Peer review: Trial by Twitter. Nature. 2011;469:286-7. Haffar S, Bazerbachi F and Murad MH. Peer Review Bias: A Critical Review. Mayo Clinic proceedings. 2019;94:670-676.

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 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. 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. Moore TJ, Singh S and Furberg CD. The FDA and new safety warnings. Archives of internal medicine. 2012;172:78-80. 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. 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. 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. 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. 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. 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.

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 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. Brain transplant for Parkinson's disease. Lancet. 1987;1:1012-3. Ignacio V, Collins VP, Suard IM and Jacque CM. Survival of astroglial cell lineage from adult brain transplant. Dev Neurosci. 1989;11:175-8. Landau WM. Clinical neuromythology VII. Artificial intelligence: the brain transplant cure for parkinsonism. Neurology. 1990;40:733-40. 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. Landau WM. Clinical neuromythology X. Faithful fashion: survival status of the brain transplant cure for parkinsonism. Neurology. 1993;43:644-9. 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. 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. 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. 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. 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. Kumar R and Mahapatra AK. Concept of brain transplant in pre-historic era. Childs Nerv Syst. 2009;25:393-4. 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.

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 Kishnani PS and Howell RR. Pompe disease in infants and children. J Pediatr. 2004;144:S35-43. 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. 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. 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. 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. 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. 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. 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. 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. 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.

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 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. 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. 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. Bruun RD. Gilles de la Tourette's syndrome. An overview of clinical experience. J Am Acad Child Psychiatry. 1984;23:126-33. Robertson MM. Tourette syndrome, associated conditions and the complexities of treatment. Brain. 2000;123 Pt 3:425-62. Yael D, Vinner E and Bar-Gad I. Pathophysiology of tic disorders. Mov Disord. 2015;30:1171-8. 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. 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.

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 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. 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. 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. 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. 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. Hardiman O and van den Berg LH. Edaravone: a new treatment for ALS on the horizon? The Lancet Neurology. 2017;16:490-491. 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. 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. 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. 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. 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. 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. 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. 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.

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 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. 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. 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. 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. 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. Armangue T, Leypoldt F and Dalmau J. Autoimmune encephalitis as differential diagnosis of infectious encephalitis. Curr Opin Neurol. 2014;27:361-8. 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. Venkatesan A and Benavides DR. Autoimmune encephalitis and its relation to infection. Current neurology and neuroscience reports. 2015;15:3. 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. 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. 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.

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  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. 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. 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.

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 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. Goodman SN. Toward evidence-based medical statistics. 1: The P value fallacy. Annals of internal medicine. 1999;130:995-1004. 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. Pocock SJ and Stone GW. The Primary Outcome Fails - What Next? The New England journal of medicine. 2016;375:861-70. 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. 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. 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. Fritz CO, Morris PE and Richler JJ. Effect size estimates: current use, calculations, and interpretation. J Exp Psychol Gen. 2012;141:2-18.

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 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. 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. 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. 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. 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. 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. 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. 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. Claassen J. How I treat patients with EEG patterns on the ictal-interictal continuum in the neuro ICU. Neurocritical care. 2009;11:437-44.

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 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. Maragakis NJ and Rothstein JD. Mechanisms of Disease: astrocytes in neurodegenerative disease. Nat Clin Pract Neurol. 2006;2:679-89. Wisniewski T and Konietzko U. Amyloid-beta immunisation for Alzheimer's disease. The Lancet Neurology. 2008;7:805-11. 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. 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. Yan R and Vassar R. Targeting the beta secretase BACE1 for Alzheimer's disease therapy. The Lancet Neurology. 2014;13:319-29. 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. Kumar A, Singh A and Ekavali. A review on Alzheimer's disease pathophysiology and its management: an update. Pharmacol Rep. 2015;67:195-203. Rodriguez-Arellano JJ, Parpura V, Zorec R and Verkhratsky A. Astrocytes in physiological aging and Alzheimer's disease. Neuroscience. 2016;323:170-82. Chun H and Lee CJ. Reactive astrocytes in Alzheimer's disease: A double-edged sword. Neurosci Res. 2018;126:44-52.

In one of our previous Teaching through Clinical Cases, Dr. Sneha Mantri (formerly a movement disorders fellow at the Philadelphia VA, now an Assistant Professor of Neurology at Duke) took us through the case of a gentleman with gait instability and falls. We are re-releasing this show with an update on the 2017 revised diagnostic criteria for the neurologic condition experienced by this patient. Produced by James E. Siegler. Music courtesy of Julie Maxwell, Yan Terrien, Josh Woodward, Quantum Jazz, and Pachyderm. 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 Hess CW and Okun MS. Diagnosing Parkinson Disease. Continuum (Minneap Minn). 2016;22:1047-63. Garbutt S, Riley DE, Kumar AN, Han Y, Harwood MR and Leigh RJ. Abnormalities of optokinetic nystagmus in progressive supranuclear palsy. Journal of neurology, neurosurgery, and psychiatry. 2004;75:1386-94. McFarland NR. Diagnostic Approach to Atypical Parkinsonian Syndromes. Continuum (Minneap Minn). 2016;22:1117-42. Boxer AL, Yu JT, Golbe LI, Litvan I, Lang AE and Hoglinger GU. Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches. The Lancet Neurology. 2017;16:552-563. Hoglinger GU, Respondek G, Stamelou M, Kurz C, Josephs KA, Lang AE, Mollenhauer B, Muller U, Nilsson C, Whitwell JL, Arzberger T, Englund E, Gelpi E, Giese A, Irwin DJ, Meissner WG, Pantelyat A, Rajput A, van Swieten JC, Troakes C, Antonini A, Bhatia KP, Bordelon Y, Compta Y, Corvol JC, Colosimo C, Dickson DW, Dodel R, Ferguson L, Grossman M, Kassubek J, Krismer F, Levin J, Lorenzl S, Morris HR, Nestor P, Oertel WH, Poewe W, Rabinovici G, Rowe JB, Schellenberg GD, Seppi K, van Eimeren T, Wenning GK, Boxer AL, Golbe LI, Litvan I and Movement Disorder Society-endorsed PSPSG. Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria. Mov Disord. 2017;32:853-864. PW Brazis, Masdeu JC, Biller J. Localization in Clinical Neurology, 6th 2011 Lippincott Williams and Wilkins.