33.   Ronald D. Chervin, “Sleepiness, Fatigue, Tiredness, and Lack of Energy in Obstructive Sleep Apnea,” Chest 118 (2000): 372–79.

  34.   Darren Scheer et al., “Prevalence and Incidence of Narcolepsy in a US Health Care Claims Database, 2008–2010,” Sleep 42 (2019): zsz091.

  35.   Maunil K. Desai and Roberta Diaz Brinton, “Autoimmune Disease in Women: Endocrine Transition and Risk Across the Lifespan,” Frontiers in Endocrinology, 2019, https://www.frontiersin.org/articles/10.3389/fendo.2019.00265/full.

  36.   Makoto Kawai et al., “Narcolepsy in African Americans,” Sleep 38 (2015): 1673–81.

  37.   Katherine A. Dudley and Sanjay R. Patel, “Disparities and Genetic Risk Factors in Obstructive Sleep Apnea,” Sleep Medicine 18 (2016): 96–102.

  38.   Hypersomnia Foundation, “A Call to Action,” https://www.hypersomniafoundation.org/a-call-to-action-racial-disparities-in-hypersomnia-disorders/.

  39.   James Stevens, “A Disease of Dignity,” Ars Medica 13 (2018).

  40.   Isabelle Arnulf, “Women and IH,” Hypersomnia Foundation, YouTube video posted April 14, 2019, https://www.youtube.com/watch?v=L7TG5Z5rf3s.

  41.   British Generic Manufacturers Association, “Modafinil: Potential Risk of Congenital Malformations During Pregnancy,” https://assets.publishing.service.gov.uk/media/5e43e03fe5274a6d34ddad60/Modafinil-Jan-2020.pdf.

  42.   Per Damkier and Anna Broe, “First-Trimester Pregnancy Exposure to Modafinil and Risk of Congenital Malformations,” JAMA 323 (2020): 374–76.

  43.   Sigal Kaplan et al., “Pregnancy and Fetal Outcomes Following Exposure to Modafinil and Armodafinil During Pregnancy,” JAMA Internal Medicine 181 (2021): 275–77.

  44.   K. F. Huybrechts et al., “Association Between Methylphenidate and Amphetamine Use in Pregnancy and Risk of Congenital Malformations,” JAMA Psychiatry 75 (2018): 167–75.

  45.   Ilya Kolb et al., “Cleaning Patch-Clamp Pipettes for Immediate Reuse,” Scientific Reports 6 (2016): 35001; Riley E. Perszyk et al., “Automated Intracellular Pharmacological Electrophysiology for Ligand-Gated Ionotropic Receptor and Pharmacology Screening,” Molecular Pharmacology 100 (2021): 73–82.

  46.   Claire Wylds-Wright, “Wake Up Narcolepsy & Dr. Mignot,” Wake Up Narcolepsy, YouTube video posted February 26, 2018, 1h18m–1h22m, https://www.youtube.com/watch?v=iovkibut2vI.

  47.   Peter J. H. Scott et al., “Investigation of Proposed Activity of Clarithromycin at GABAA Receptors Using [11C]Flumazenil PET,” ACS Medicinal Chemistry Letters 7 (2016): 746–50.

  48.   Emmanuel Mignot was quoted as saying: “Marty Scharf is why we have this drug at all.” In Gayle Greene, Insomniac (Piatkus, 2008), 209.

  49.   Low-Dose Naltrexone Trust, “LDN 2021 Conference,” https://www.ldnrtevents.com/pages/ldn-2021.

  50.   Jarred Younger, Luke Parkitny, and David McLain, “The Use of Low-Dose Naltrexone (LDN) as a Novel Anti-inflammatory Treatment for Chronic Pain,” Clinical Rheumatology 33 (2014): 451–59.

  51.   Pamela Weintraub, Cure Unknown: Inside the Lyme Epidemic (St. Martin’s Griffin, 2013).

  52.   Fabian-Xose Fernandez, Julie Flygare, and Michael A. Grandner, “Narcolepsy and COVID-19: Sleeping on an Opportunity?,” Journal of Clinical Sleep Medicine 16 (August 2020): 1415.

  53.   Destin Groff et al., “Short-Term and Long-Term Rates of Postacute Sequelae of SARS-CoV-2 Infection,” JAMA Network Open 4 (2021): e2128568.

  54.   Lucie Barateau et al., “Comorbidity Between Central Disorders of Hypersomnolence and Immune-Based Disorders,” Neurology 88 (2017): 93–100.

  INDEX

  Page numbers refer to the print edition but are hyperlinked to the appropriate location in the e-book.

  Abercrombie, George, 40

  acetylcholine, 30, 50–51, 90, 213

  actigraphy devices, 239–240

  Adderall, 46, 114, 140, 195, 255–256

  adenosine, 89–94, 158, 161, 177

  Adie, William, 55, 169

  alcohol withdrawal, 220

  Alzheimer’s disease, 25, 30, 50, 91, 130, 137

  Ambien, 131

  American Academy of Sleep Medicine (AASM), 60, 98, 196, 247, 250

  American Association of Poison Control Centers, 34

  American Board of Sleep Medicine, 25

  American Journal of Psychiatry, 74

  American Medical Association, 197

  American Mercury, 152

  American Narcolepsy Association, 172, 181, 198, 214

  American Parkinson’s Disease Association, 53

  American Recovery and Reinvestment Act, 80

  American Sleep Apnea Association, 118

  amphetamines, 9, 19, 29, 73, 116, 129, 146, 196, 198–200, 257

  anesthetics, 30–33, 35, 129, 212

  Annals of Neurology, 142–143

  antianxiety drugs, 2

  antidepressants, 29, 36, 59–62, 72, 109, 171, 178, 180, 182, 198, 206, 214, 237, 243, 248, 256

  Archives of General Psychiatry, 76

  armodafinil, 196–198, 203, 206

  Arnulf, Isabelle, 16–17, 118, 165, 208, 211, 253, 256

  Aserinsky, Eugene, 65

  Ashcraft, Betsy, 246

  Aston-Jones, Gary, 177

  ATP (adenosine triphosphate), 90

  attention deficit disorder (ADHD), 17, 48, 201, 203

  autism spectrum disorder, 164, 188, 246, 252

  autoimmune diseases, 185–191

  Avidan, Alon, 195

  Awakenings (Sacks), 152

  baclofen, 227

  Bailey, Percival, 53

  Baker, Bob, 40

  Balance Therapeutics, 145–146, 148, 195, 248

  Baldino, Frank, Jr., 202

  Barré, Jean, 67

  basal forebrain, 90–91, 158

  Bassetti, Claudio, 190

  Bastuji, Helene, 199

  Beard, Jennifer, 106, 118, 145

  Becker, Lorne, 98–99

  Begley, Sharon, 252

  behavioral therapy, 73, 253

  benzodiazepines, 2, 3, 9, 34, 36, 112, 128–129. See also endogenous benzodiazepines

  beta-blockers, 29

  Billiard, Michel, 12, 77, 164

  Bioprojet, 206

  Bliwise, Donald, 25, 55, 58–59, 85

  Borbely, Alexander, 160, 228

  brain fog, 4–5, 15, 113, 147, 156, 209, 253, 260

  brain research: circadian rhythms, 57, 77, 160–163; hypocretin/orexin, 18, 165, 175–181, 178f; hypothalamus, 103, 155–159, 161–162, 175–177, 185–186, 191–194, 200, 226, 236; idiopathic hypersomnia, 149–150, 150f; melatonin measures, 161; suprachiasmatic nucleus, 161–162; VentroLateral PreOptic area, 158–159, 159f

  Broad Institute, 166

  Broughton, Roger, 77, 213

  B12 deficiencies, 13

  Burden of Narcolepsy Disease study, 224

  Butterworth, Roger, 134

  caffeine, 47, 90, 92, 94, 124, 129, 168, 195, 198, 201–202

  candidate gene, 167–168

  canine narcolepsy, 183–185, 184f

  Carey, Eleanore, 152–153, 156

  carnitine O-acetyltransferase (CRAT), 165

  Caronia, Alfred, 218–219

  Carpenter, Daniel, 210

  Carskadon, Mary, 57

  cataplexy: defined, 14; diagnosis difficulty, 174–175; management of, 106; narcolepsy and, 54–56; narcolepsy type 1 and, 169–173; narcolepsy type 2 and, 192; narcolepsy with, 8, 14, 70, 76, 161, 171, 175, 185, 200, 218, 222, 224–225; narcolepsy without, 45, 59, 71, 76, 97, 102, 165, 183, 185, 192, 234; REM sleep and, 178–180

  Cavalla, David, 37

  Centers for Disease Control, 154

  Cephalon, 199–204

  cerebrospinal fluid, 9–10, 18, 21, 33, 45, 79, 93, 104, 116, 126, 177, 185. See also somnogen in cerebrospinal fluid research

  CGRP (calcitonin gene-related peptide), 5

  Chadwick, Michelle, 111, 114

  Chicago Tribune, 76

  chronic fatigue syndrome, 5, 16, 260. See also myalgic encephalomyelitis

  chronic sleep disruption, 94

  chronic sleep insufficiency, 229

  Church, George, 252

  circadian rhythms, 57, 57, 77, 77, 160–163, 160–163

  Circadian Sleep Disorders Network, 247

  clarithromycin, 95–98, 100, 102, 104, 112, 116–117, 141–142, 208, 258–259

  clinical hypersomnia, 76

  clinical trials: DSIP, 89; flumazenil, 96–98; GHB, 210; hypocretin receptor agonists in, 180; IH and, 4, 145, 249–250; modafinil, 199–209; narcolepsy and, 4, 145, 249–250; Orphan Drug Act and, 198; PTZ, 145–148, 195

  Cocaine and Amphetamine-Regulated Transcript (CART), 80

  Cochrane Collaboration, 99

  cognitive behavioral therapy, 253

  Compose21 research, 147

  continuous positive air pressure (CPAP), 62–64, 109, 250

  Copeland, Samantha, 95

  CoRDS registry, 254–255

  Costa, Erminio, 126–127

  COVID-19 pandemic, 5, 189, 260

  Crick, Francis, 50

  cytokines, 87–88, 92, 154

  Czeisler, Charles, 202

  Dang-Vu, Thien Thanh, 234–236, 235f

  Darwin, Charles, 51

  Dauvilliers, Yves, 142–143, 164, 241, 248

  DCSAD (Diagnostic Classification of Sleep and Arousal Disorders), 78

  DeCODE company, 28

  default mode network (DMN), 235–238

  delirium, 15, 96, 151, 153

  DeLong, Mahlon, 52–54, 158

  delta sleep. See DSIP

  Dement, William, 56–57, 215

  depression, 5, 70–72, 230–231

  Desmarais, Amy, 143–144

  dialysis patients, 24–25

  diazepam binding inhibitor (DBI), 126–127, 134–135

  dimmer knob effect, 31

  disease mongering, 27–28

  donepezil (Aricept), 30

  dopamine, 29–31, 54

  Down syndrome, 145–147

  Drews, Jürgen, 130

  drop attacks, 171

  Drosophila fruit fly studies, 92–94

  Drug Enforcement Administration, 97, 215

  DSIP (delta sleep-inducing peptide), 89–90

  DSM-5 (Diagnostic and Statistical Manual of Mental Disorders), 231, 246

  Edgar, Dale, 200

  EDS (excessive daytime sleepiness), 59, 156, 201, 208, 224

  Edwards, Stacy Erickson, 193

  EEG (electroencephalography), 3, 7, 67, 75, 232–233

  Einen, Mali, 215, 221

  Ekbom, Karl-Axel, 26

  Electroencephalography and Clinical Neurophysiology (journal), 75

  electroshock therapy, 71

  Emrich, Michelle, 253

  encephalitis lethargica, 151–156, 151f, 260

  endogenous benzodiazepines (endozepines), 34–35, 79, 124–126, 133–135

  endogenous hypersomnia, 44–45

  endozepine-induced recurrent stupor, 42

  enkephalins, 124

  enteroviruses, 154

  epilepsy, 7, 36, 38, 51, 55, 70, 75, 91, 104, 124, 130–131, 135, 164, 169, 171, 177, 178f

  Epstein-Barr virus infection, 109, 191

  Epworth Sleepiness Scale (ESS), 13, 64, 200, 205, 208–209, 230

  European Congress on Sleep Research, 77

  European Medicines Agency (EMA), 204–205

  Factor S, 86–88

  fake awake, 5

  fibromyalgia, 216–217

  First International Symposium on Narcolepsy (1975), 56, 77

  flumazenil: alternative mechanisms for, 143–144; clinical trials, 96–98; as countermeasure to benzodiazepines, 9, 34, 36, 128–129; grind and bind experiment, 121–123; hepatic encephalopathy and, 131–135; for IH, 9–10, 37–48, 101, 112–117; impact of, 34–36, 112–113, 123–126; inconsistency in effectiveness, 3–4; initial tests, 120–121; lack of success with, 141–142; patch clamping and, 34; Anna Sumner Pieschel and, 7, 34, 37–46, 79–80, 97–98, 112, 131–133, 242; sleeping pill overdose, 7; slowing of research on, 129–131; success with, 139–140, 258–259

  flunitrazepam, 123

  Flygare, Julie, 174, 246

  Foege, William, 154

  Foley, Paul, 154

  Food and Drug Administration (FDA), 40–41, 115, 203–204, 216–217, 250–251

  Foulkes, David, 53

  Franks, Nick, 32

  Frerking, Matt, 174

  functional hypersomnia, 72–74, 77

  GABA (gamma-aminobutyric acid), 30–34, 79–82, 96, 104, 116–117, 142–146, 145f, 212

  GABA-A receptors, 31, 80, 96, 121, 127–131, 128f, 135, 142–146, 225

  GABA-B receptors, 31, 146, 213, 225–227, 258

  Gaillard, Jean-Michel, 124–125

  gamma-hydroxybutyrate (GHB): attempting FDA approval, 216–217; baclofen and, 227; closed distribution system, 216; dangers of, 214–215; fibromyalgia and, 216–217; initial prescriptions, 213–214; initial studies, 212–213, 212f; Jazz Pharmaceuticals and, 206, 210, 216–225; mechanism of action, 225–226; narcolepsy definition and, 224–225; off-label prosecution of, 218–219; price increases, 219–220, 219f; safety issues, 222–224, 223f; Xyrem, 172, 210–212, 216–227

  Garcia, Paul, 33, 37, 44, 81, 96, 137

  Garner, Craig, 146–147

  Gastaut, Henri, 75

  Gelineau, Jean Baptiste Edouard, 18

  genetics and IH, 47–48, 70–72, 163–166, 167–168

  Georgia Mental Health Institute, 53

  Georgia Public Broadcasting, 140

  Georgia Research Alliance, 97, 98

  Gerbsman Partners, 148

  GHB. See gamma-hydroxybutyrate

  GlaxoSmithKline, 187

  Gleason, Peter, 218

  Gordon, Barbara, 36

  Government Accountability Office, 41

  grind and bind experiment, 121–123

  Guidotti, Alessandro, 126

  Guillain, Georges, 66–67

  Guillain-Barré syndrome, 67

  Guilleminault, Christian, 78, 213, 227

  Guillery, Rainer, 50–51

  GWAS (genome-wide association study), 164

  Hacking, Ian, 242

  Haefely, Willy, 121–126, 122f, 131

  Hall, Adam, 32

  hallucinations, 14, 56, 59, 153, 173–175, 178, 214, 234, 244

  Harmony Biosciences, 206

  Harrison, Neil, 35

  Healy, David, 136

  Heller, Craig, 145

  Henner, Kamil, 69

  hepatic encephalopathy, 34–35, 64, 131–135, 150, 260

  high blood pressure, 9, 27, 29, 109

  histamine, 81, 142, 175, 194, 206

  HIV/AIDS medications, 40

  HLA (human leukocyte antigen) genes, 182–183

  H1N1 flu vaccine, 187–189, 260

  Honda, Yutaka, 182

  Hue, Gillian, 54

  Hughes, Virginia, 105, 108, 112

  Hulshizer, Danielle, 114–115

  Human Genome Project, 167

  Hunkeler, Walter, 121–123

  Hyland, M. J., 198–199

  hypersomnia: with automatic behavior, 78; defined, 13; neurochemical basis of, 93–94; pentylenetetrazol for, 145–148; postdormital hypersomnia, 76; primary hypersomnia, 97, 102, 137; REM sleep and, 76; symptomatic hypersomnia, 156; term usage, 16, 74. See also idiopathic hypersomnia

  Hypersomnia Foundation, 4, 105–108, 107f, 117–118, 195–197, 242–243, 249, 252, 255

  Hypersomnolence Australia, 4, 111, 243

  hypnogogic hallucinations, 56, 153, 173, 178, 214, 244

  hypnotherapy, 109, 171

  hypnotoxin, 79, 84–86, 155

  hypocretin/orexin, 18, 165, 175–181, 178f, 192–194

  hypothalamus, 103, 155–159, 161–162, 175–177, 185–186, 191–194, 200, 226, 236

  hypothyroidism, 46, 64, 247

  idiopathic CNS hypersomnolence, 78

  idiopathic hypersomnia (IH): brain research and, 149–150, 150f; classification scheme for, 20–22, 21f; defined, 8, 72, 149–150, 246–247; genetics and, 47–48, 70–72, 163–166, 167–168; hope for successful treatment, 251–253, 254f; initial case research, 151–152; introduction to, 2–6; long sleep IH, 165, 168, 239; as neglected disorder, 11–12, 16–19; relationship to narcolepsy, 12–19, 17f; sex and race disparities in diagnoses, 254–256; sleep medicine research and, 10–12, 65–66; standard test for, 3; symptoms, 15t

  Idiopathic Hypersomnia Awareness Week, 111

  Idiopathic Hypersomnia Facebook group, 110, 111, 112

  Idiopathic Hypersomnia Severity Scale, 248

  idiopathic recurring stupor, 35, 100, 102

  “I Have IH” campaign, 242

  I’m Dancing as Fast as I Can (Gordon), 36

  Imperial Chemical Industries, 129

  incomplete hypocretin loss, 193–194

  IND (Investigational New Drug) application, 41

  infrared goggles, 229

  Institute for Safe Medication Practices, 223–224

  insufficient sleep syndrome, 1

  International Classification of Sleep Disorders, 55, 64, 231–232, 243–244, 244f

  International Pregnancy Safety Study, 257

  International Symposium on Narcolepsy (2018), 190, 244

  inverse agonists, 129

  Jackson, Ronnie, 198

  Jazz Pharmaceuticals, 206, 210, 216–225, 242, 247–249

  Jenkins, Andrew: DBI peptide and, 135; flumazenil studies, 9, 37–39, 42, 44–45; GABA research, 31–34; somnogen in cerebrospinal fluid investigations, 45, 79–84, 83f

  Johnson, Lloyd, 108–117

  Johnson & Johnson, 206

  Jordheim, Dean, 110–111

  Journal of Psychopharmacology, 96

  Jouvet, Michel, 51, 88–89, 199

  Juji, Takeo, 182

  Kawas, Claudia, 203

  K-complex, 233

  Keating, Glenda, 80

  Kellogg, David, 61–63

  Kelty, Erin, 113

  Kemp, John, 131

  Kempner, Joanna, 5