Office Evaluation of the “Tired” or “Sleepy” Patient

ABSTRACT

In an outpatient neurologic practice, the patient complaint of being “tired” is frequently encountered yet often not specifically addressed. Clarifying the symptoms and determining whether the tiredness is the result of excessive daytime sleepiness versus fatigue or weakness is the first step in diagnosing and treating the patient. A detailed neurologic and sleep history and exam can often distinguish among these different symptoms, establish the potential causes of excessive sleepiness, and decide on the additional ancillary tests that may be helpful to determine the underlying etiology. Understanding the etiology of patient's symptoms is necessary to initiate appropriate treatment.

KEYWORDS

Excessive daytime sleepiness - hypersomnia - fatigue

REFERENCES

• 1 The International Classification of Sleep Disorders .Diagnostic and Coding Manual. 2nd ed. Westchester, IL: American Academy of Sleep Medicine; 2005
• 2 Mills R J, Young C A. A medical definition of fatigue in multiple sclerosis.  QJM. 2008;  101 (1) 49-60
• 3 Radbruch L, Strasser F, Elsner F Research Steering Committee of the European Association for Palliative Care (EAPC) et al. Fatigue in palliative care patients — an EAPC approach.  Palliat Med. 2008;  22 (1) 13-32
• 4 Dobkin B H. Fatigue versus activity-dependent fatigability in patients with central or peripheral motor impairments.  Neurorehabil Neural Repair. 2008;  22 (2) 105-110
• 5 Lerdal A, Bakken L N, Kouwenhoven S E et al.. Poststroke fatigue—a review.  J Pain Symptom Manage. 2009;  38 (6) 928-949
• 6 Multiple Sclerosis Council for Clinical Practice Guidelines .Fatigue and Multiple Sclerosis: Evidence-Based Management Strategies for Fatigue in Multiple Sclerosis. Washington, DC: Paralyzed Veterans of America; 1998
• 7 Hoddes E, Zarcone V, Smythe H, Phillips R, Dement W C. Quantification of sleepiness: a new approach.  Psychophysiology. 1973;  10 (4) 431-436
• 8 Johns M W. A new method for measuring daytime sleepiness: the Epworth sleepiness scale.  Sleep. 1991;  14 (6) 540-545
• 9 Chervin R D, Aldrich M S, Pickett R, Guilleminault C. Comparison of the results of the Epworth Sleepiness Scale and the Multiple Sleep Latency Test.  J Psychosom Res. 1997;  42 (2) 145-155
• 10 Furuta H, Kaneda R, Kosaka K, Arai H, Sano J, Koshino Y. Epworth Sleepiness Scale and sleep studies in patients with obstructive sleep apnea syndrome.  Psychiatry Clin Neurosci. 1999;  53 (2) 301-302
• 11 Benbadis S R, Mascha E, Perry M C, Wolgamuth B R, Smolley L A, Dinner D S. Association between the Epworth sleepiness scale and the multiple sleep latency test in a clinical population.  Ann Intern Med. 1999;  130 (4 Pt 1) 289-292
• 12 Chervin R D, Aldrich M S. The Epworth Sleepiness Scale may not reflect objective measures of sleepiness or sleep apnea.  Neurology. 1999;  52 (1) 125-131
• 13 Krupp L B, LaRocca N G, Muir-Nash J, Steinberg A D. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus.  Arch Neurol. 1989;  46 (10) 1121-1123
• 14 Michielsen H J, De Vries J, Van Heck G L. Psychometric qualities of a brief self-rated fatigue measure: The Fatigue Assessment Scale.  J Psychosom Res. 2003;  54 (4) 345-352
• 15 Fisk J D, Pontefract A, Ritvo P G, Archibald C J, Murray T J. The impact of fatigue on patients with multiple sclerosis.  Can J Neurol Sci. 1994;  21 (1) 9-14
• 16 Mendoza T R, Wang X S, Cleeland C S et al.. The rapid assessment of fatigue severity in cancer patients: use of the Brief Fatigue Inventory.  Cancer. 1999;  85 (5) 1186-1196
• 17 Fisk J D, Ritvo P G, Ross L, Haase D A, Marrie T J, Schlech W F. Measuring the functional impact of fatigue: initial validation of the fatigue impact scale.  Clin Infect Dis. 1994;  18 (Suppl 1) S79-S83
• 18 Belza B L. Comparison of self-reported fatigue in rheumatoid arthritis and controls.  J Rheumatol. 1995;  22 (4) 639-643
• 19 Smets E M, Garssen B, Bonke B, De Haes J C. The Multidimensional Fatigue Inventory (MFI) psychometric qualities of an instrument to assess fatigue.  J Psychosom Res. 1995;  39 (3) 315-325
• 20 Stein K D, Martin S C, Hann D M, Jacobsen P B. A multidimensional measure of fatigue for use with cancer patients.  Cancer Pract. 1998;  6 (3) 143-152
• 21 Whitehead L. The measurement of fatigue in chronic illness: a systematic review of unidimensional and multidimensional fatigue measures.  J Pain Symptom Manage. 2009;  37 (1) 107-128
• 22 Carskadon M A, Dement W C, Mitler M M, Roth T, Westbrook P R, Keenan S. Guidelines for the multiple sleep latency test (MSLT): a standard measure of sleepiness.  Sleep. 1986;  9 (4) 519-524
• 23 Arand D, Bonnet M, Hurwitz T, Mitler M, Rosa R, Sangal R B. The clinical use of the MSLT and MWT.  Sleep. 2005;  28 (1) 123-144
• 24 Randomized trial of modafinil as a treatment for the excessive daytime somnolence of narcolepsy: US Modafinil in Narcolepsy Multicenter Study Group.  Neurology. 2000;  54 (5) 1166-1175
• 25 Singh M, Drake C L, Roth T. The prevalence of multiple sleep-onset REM periods in a population-based sample.  Sleep. 2006;  29 (7) 890-895
• 26 Bishop C, Rosenthal L, Helmus T, Roehrs T, Roth T. The frequency of multiple sleep onset REM periods among subjects with no excessive daytime sleepiness.  Sleep. 1996;  19 (9) 727-730
• 27 Laberge L, Bégin P, Dauvilliers Y et al.. A polysomnographic study of daytime sleepiness in myotonic dystrophy type 1.  J Neurol Neurosurg Psychiatry. 2009;  80 (6) 642-646
• 28 Arii J, Kanbayashi T, Tanabe Y, Ono J, Nishino S, Kohno Y. A hypersomnolent girl with decreased CSF hypocretin level after removal of a hypothalamic tumor.  Neurology. 2001;  56 (12) 1775-1776
• 29 Scammell T E, Nishino S, Mignot E, Saper C B. Narcolepsy and low CSF orexin (hypocretin) concentration after a diencephalic stroke.  Neurology. 2001;  56 (12) 1751-1753
• 30 Kato T, Kanbayashi T, Yamamoto K et al.. Hypersomnia and low CSF hypocretin-1 (orexin-A) concentration in a patient with multiple sclerosis showing bilateral hypothalamic lesions.  Intern Med. 2003;  42 (8) 743-745
• 31 Oka Y, Kanbayashi T, Mezaki T et al.. Low CSF hypocretin-1/orexin-A associated with hypersomnia secondary to hypothalamic lesion in a case of multiple sclerosis.  J Neurol. 2004;  251 (7) 885-886
• 32 Rubinstein I, Gray T A, Moldofsky H, Hoffstein V. Neurosarcoidosis associated with hypersomnolence treated with corticosteroids and brain irradiation.  Chest. 1988;  94 (1) 205-206
• 33 Morgenthaler T, Alessi C, Friedman L Standards of Practice Committee et al. Practice parameters for the use of actigraphy in the assessment of sleep and sleep disorders: an update for 2007.  Sleep. 2007;  30 (4) 519-529
• 34 Nishino S, Ripley B, Overeem S, Lammers G J, Mignot E. Hypocretin (orexin) deficiency in human narcolepsy.  Lancet. 2000;  355 (9197) 39-40
• 35 Mignot E, Lin X, Arrigoni J et al.. DQB1*0602 and DQA1*0102 (DQ1) are better markers than DR2 for narcolepsy in Caucasian and black Americans.  Sleep. 1994;  17 (8, Suppl) S60-S67
• 36 Mignot E. Genetic and familial aspects of narcolepsy.  Neurology. 1998;  50 (2, Suppl 1) S16-S22
• 37 Avidan A Y. Parasomnias and movement disorders of sleep.  Semin Neurol. 2009;  29 (4) 372-392
• 38 Avidan A Y. Clinical sleep neurology.  Semin Neurol. 2009;  29 (4) 275-276
• 39 Bae C J, Lee J K, Foldvary-Schaefer N. The use of sleep studies in neurologic practice.  Semin Neurol. 2009;  29 (4) 305-319
• 40 Baran A S, Chervin R D. Approach to the patient with sleep complaints.  Semin Neurol. 2009;  29 (4) 297-304
• 41 Brennan K C, Charles A. Sleep and headache.  Semin Neurol. 2009;  29 (4) 406-418
• 42 Chokroverty S. Sleep and neurodegenerative diseases.  Semin Neurol. 2009;  29 (4) 446-467
• 43 Culebras A. Sleep and stroke.  Semin Neurol. 2009;  29 (4) 438-445
• 44 Foldvary-Schaefer N, Grigg-Damberger M. Sleep and epilepsy.  Semin Neurol. 2009;  29 (4) 419-428
• 45 Frenette E, Kushida C A. Primary hypersomnias of central origin.  Semin Neurol. 2009;  29 (4) 354-367
• 46 Goel N, Rao H, Durmer J S, Dinges D F. Neurocognitive consequences of sleep deprivation.  Semin Neurol. 2009;  29 (4) 320-339
• 47 Guilleminault C, Ramar K. Neurologic aspects of sleep apnea: is obstructive sleep apnea a neurologic disorder?.  Semin Neurol. 2009;  29 (4) 368-371
• 48 Neubauer D N, Flaherty K N. Chronic insomnia.  Semin Neurol. 2009;  29 (4) 340-353
• 49 Nicolle M W. Sleep and neuromuscular disease.  Semin Neurol. 2009;  29 (4) 429-437
• 50 Reid K J, Zee P C. Circadian rhythm disorders.  Semin Neurol. 2009;  29 (4) 393-405
• 51 Siegel J M. The neurobiology of sleep.  Semin Neurol. 2009;  29 (4) 277-296
• 52 Ohayon M M, Reynolds III C F. Epidemiological and clinical relevance of insomnia diagnosis algorithms according to the DSM-IV and the International Classification of Sleep Disorders (ICSD).  Sleep Med. 2009;  10 (9) 952-960
• 53 Dinges D F, Pack F, Williams K et al.. Cumulative sleepiness, mood disturbance, and psychomotor vigilance performance decrements during a week of sleep restricted to 4-5 hours per night.  Sleep. 1997;  20 (4) 267-277
• 54 Janjua T, Samp T, Cramer-Bornemann M, Hannon H, Mahowald M W. Clinical caveat: prior sleep deprivation can affect the MSLT for days.  Sleep Med. 2003;  4 (1) 69-72
• 55 Marti I, Valko P O, Khatami R, Bassetti C L, Baumann C R. Multiple sleep latency measures in narcolepsy and behaviourally induced insufficient sleep syndrome.  Sleep Med. 2009;  10 (10) 1146-1150
• 56 Aeschbach D, Cajochen C, Landolt H, Borbély A A. Homeostatic sleep regulation in habitual short sleepers and long sleepers.  Am J Physiol. 1996;  270 (1 Pt 2) R41-R53
• 57 Hartmann E, Baekeland F, Zwilling G R. Psychological differences between long and short sleepers.  Arch Gen Psychiatry. 1972;  26 (5) 463-468
• 58 Young T, Peppard P E, Gottlieb D J. Epidemiology of obstructive sleep apnea: a population health perspective.  Am J Respir Crit Care Med. 2002;  165 (9) 1217-1239
• 59 Epstein L J, Kristo D, Strollo Jr P J Adult Obstructive Sleep Apnea Task Force of the American Academy of Sleep Medicine et al. Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults.  J Clin Sleep Med. 2009;  5 (3) 263-276
• 60 Montplaisir J, Boucher S, Poirier G, Lavigne G, Lapierre O, Lespérance P. Clinical, polysomnographic, and genetic characteristics of restless legs syndrome: a study of 133 patients diagnosed with new standard criteria.  Mov Disord. 1997;  12 (1) 61-65
• 61 Anderson K N, Pilsworth S, Sharples L D, Smith I E, Shneerson J M. Idiopathic hypersomnia: a study of 77 cases.  Sleep. 2007;  30 (10) 1274-1281
• 62 Dauvilliers Y, Billiard M, Montplaisir J. Clinical aspects and pathophysiology of narcolepsy.  Clin Neurophysiol. 2003;  114 (11) 2000-2017
• 63 Overeem S, Mignot E, van Dijk J G, Lammers G J. Narcolepsy: clinical features, new pathophysiologic insights, and future perspectives.  J Clin Neurophysiol. 2001;  18 (2) 78-105
• 64 Kanbayashi T, Inoue Y, Chiba S et al.. CSF hypocretin-1 (orexin-A) concentrations in narcolepsy with and without cataplexy and idiopathic hypersomnia.  J Sleep Res. 2002;  11 (1) 91-93
• 65 Mignot E, Lammers G J, Ripley B et al.. The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias.  Arch Neurol. 2002;  59 (10) 1553-1562
• 66 Mayer G, Leonhard E, Krieg J, Meier-Ewert K. Endocrinological and polysomnographic findings in Kleine-Levin syndrome: no evidence for hypothalamic and circadian dysfunction.  Sleep. 1998;  21 (3) 278-284
• 67 Morgenthaler T I, Kapur V K, Brown T Standards of Practice Committee of the American Academy of Sleep Medicine et al. Practice parameters for the treatment of narcolepsy and other hypersomnias of central origin.  Sleep. 2007;  30 (12) 1705-1711
• 68 Huck N O, McBride S A, Kendall A P, Grugle N L, Killgore W D. The effects of modafinil, caffeine, and dextroamphetamine on judgments of simple versus complex emotional expressions following sleep deprivation.  Int J Neurosci. 2008;  118 (4) 487-502
• 69 Killgore W D, Grugle N L, Killgore D B et al.. Restoration of risk-propensity during sleep deprivation: caffeine, dextroamphetamine, and modafinil.  Aviat Space Environ Med. 2008;  79 (9) 867-874
• 70 Killgore W D, Kahn-Greene E T, Grugle N L, Killgore D B, Balkin T J. Sustaining executive functions during sleep deprivation: A comparison of caffeine, dextroamphetamine, and modafinil.  Sleep. 2009;  32 (2) 205-216
• 71 Killgore W D, Rupp T L, Grugle N L, Reichardt R M, Lipizzi E L, Balkin T J. Effects of dextroamphetamine, caffeine and modafinil on psychomotor vigilance test performance after 44 h of continuous wakefulness.  J Sleep Res. 2008;  17 (3) 309-321
• 72 Wesensten N J, Killgore W D, Balkin T J. Performance and alertness effects of caffeine, dextroamphetamine, and modafinil during sleep deprivation.  J Sleep Res. 2005;  14 (3) 255-266
• 73 Roth T, Schwartz J R, Hirshkowitz M, Erman M K, Dayno J M, Arora S. Evaluation of the safety of modafinil for treatment of excessive sleepiness.  J Clin Sleep Med. 2007;  3 (6) 595-602
• 74 Orlikowski D, Chevret S, Quera-Salva M A et al.. Modafinil for the treatment of hypersomnia associated with myotonic muscular dystrophy in adults: a multicenter, prospective, randomized, double-blind, placebo-controlled, 4-week trial.  Clin Ther. 2009;  31 (8) 1765-1773
• 75 Damian M S, Gerlach A, Schmidt F, Lehmann E, Reichmann H. Modafinil for excessive daytime sleepiness in myotonic dystrophy.  Neurology. 2001;  56 (6) 794-796
• 76 MacDonald J R, Hill J D, Tarnopolsky M A. Modafinil reduces excessive somnolence and enhances mood in patients with myotonic dystrophy.  Neurology. 2002;  59 (12) 1876-1880
• 77 Talbot K, Stradling J, Crosby J, Hilton-Jones D. Reduction in excess daytime sleepiness by modafinil in patients with myotonic dystrophy.  Neuromuscul Disord. 2003;  13 (5) 357-364
• 78 Wintzen A R, Lammers G J, van Dijk J G. Does modafinil enhance activity of patients with myotonic dystrophy?: a double-blind placebo-controlled crossover study.  J Neurol. 2007;  254 (1) 26-28
• 79 Adler C H, Caviness J N, Hentz J G, Lind M, Tiede J. Randomized trial of modafinil for treating subjective daytime sleepiness in patients with Parkinson's disease.  Mov Disord. 2003;  18 (3) 287-293
• 80 Ondo W G, Fayle R, Atassi F, Jankovic J. Modafinil for daytime somnolence in Parkinson's disease: double blind, placebo controlled parallel trial.  J Neurol Neurosurg Psychiatry. 2005;  76 (12) 1636-1639
• 81 Darwish M, Kirby M, Hellriegel E T, Robertson Jr P. Armodafinil and modafinil have substantially different pharmacokinetic profiles despite having the same terminal half-lives: analysis of data from three randomized, single-dose, pharmacokinetic studies.  Clin Drug Investig. 2009;  29 (9) 613-623
• 82 Darwish M, Kirby M, Hellriegel E T. Comparison of steady-state plasma concentrations of armodafinil and modafinil late in the day following morning administration: post hoc analysis of two randomized, double-blind, placebo-controlled, multiple-dose studies in healthy male subjects.  Clin Drug Investig. 2009;  29 (9) 601-612
• 83 Jha A, Weintraub A, Allshouse A et al.. A randomized trial of modafinil for the treatment of fatigue and excessive daytime sleepiness in individuals with chronic traumatic brain injury.  J Head Trauma Rehabil. 2008;  23 (1) 52-63
• 84 Brioschi A, Gramigna S, Werth E et al.. Effect of modafinil on subjective fatigue in multiple sclerosis and stroke patients.  Eur Neurol. 2009;  62 (4) 243-249
• 85 Rammohan K W, Rosenberg J H, Lynn D J, Blumenfeld A M, Pollak C P, Nagaraja H N. Efficacy and safety of modafinil (Provigil) for the treatment of fatigue in multiple sclerosis: a two centre phase 2 study.  J Neurol Neurosurg Psychiatry. 2002;  72 (2) 179-183
• 86 Stankoff B, Waubant E, Confavreux C French Modafinil Study Group et al. Modafinil for fatigue in MS: a randomized placebo-controlled double-blind study.  Neurology. 2005;  64 (7) 1139-1143
• 87 Vasconcelos O M, Prokhorenko O A, Salajegheh M K et al.. Modafinil for treatment of fatigue in post-polio syndrome: a randomized controlled trial.  Neurology. 2007;  68 (20) 1680-1686
• 88 Chan K M, Strohschein F J, Rydz D, Allidina A, Shuaib A, Westbury C F. Randomized controlled trial of modafinil for the treatment of fatigue in postpolio patients.  Muscle Nerve. 2006;  33 (1) 138-141
• 89 Rabkin J G, Gordon P H, McElhiney M, Rabkin R, Chew S, Mitsumoto H. Modafinil treatment of fatigue in patients with ALS: a placebo-controlled study.  Muscle Nerve. 2009;  39 (3) 297-303
• 90 Kumar R. Approved and investigational uses of modafinil: an evidence-based review.  Drugs. 2008;  68 (13) 1803-1839
• 91 The Canadian MS Research Group . A randomized controlled trial of amantadine in fatigue associated with multiple sclerosis.  Can J Neurol Sci. 1987;  14 (3) 273-278
• 92 Lange R, Volkmer M, Heesen C, Liepert J. Modafinil effects in multiple sclerosis patients with fatigue.  J Neurol. 2009;  256 (4) 645-650
• 93 Pucci E, Branãs P, D'Amico R, Giuliani G, Solari A, Taus C. Amantadine for fatigue in multiple sclerosis.  Cochrane Database Syst Rev. 2007;  (1) CD002818
• 94 McGeough E, Pollock A, Smith L N et al.. Interventions for post-stroke fatigue.  Cochrane Database Syst Rev. 2009;  (3) CD007030
• 95 Malouff J M, Thorsteinsson E B, Rooke S E, Bhullar N, Schutte N S. Efficacy of cognitive behavioral therapy for chronic fatigue syndrome: a meta-analysis.  Clin Psychol Rev. 2008;  28 (5) 736-745
• 96 Edmonds M, McGuire H, Price J. Exercise therapy for chronic fatigue syndrome.  Cochrane Database Syst Rev. 2004;  (3) CD003200