Delirium is an acute, fluctuating change in mental status, with inattention, disorganized thinking, and altered levels of consciousness.[1] It is a potentially life-threatening disorder characterized by high morbidity and mortality. Guidelines address recognition, risk factors, and treatment for delirium.[2] [3]
Summary
Introduction
Adverse sequelae
Mortality for those diagnosed with delirium in the hospital is twice that of patients with similar medical conditions without delirium and rises as high as 14% within 1 month of diagnosis.[4] Delirium occurs in >20% of hospitalizations annually and is the most common hospital-related complication in the US.[5] [6] Delirium is common in the intensive care unit especially among mechanically ventilated patients. In critically ill patients, it is associated with an increased length of stay and increased mortality.[7] Studies have demonstrated a 12% prevalence of delirium in older emergency department patients.[8] Despite its frequency, delirium is frequently under-recognized given the fluctuating nature of symptoms and an overall underappreciation of its significance by healthcare providers. Moreover, delirium has also been associated with elevated risks for functional and cognitive decline, poor rehabilitation potential, institutionalization, and rehospitalization.[1] [9] [10] [11] [12] While delirium is generally considered reversible, studies suggest that delirium symptoms can last for weeks to months following onset.[13] Persistent delirium has been found to be frequent in older hospitalized patients, and associated with adverse outcomes.[14]
Classification
The Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) notes that in order to be diagnosed with delirium, a patient must show all 4 of the following features.[15]
- A disturbance in attention (i.e., reduced clarity of awareness of the environment) is evident, with reduced ability to focus, sustain, or shift attention. This disturbance in consciousness might be subtle, initially presenting solely as lethargy or distractibility, and might be frequently dismissed by clinicians and/or family members as being related to the primary illness.
- A change in cognition (such as memory deficit, disorientation, language disturbance) or the development of a perceptual disturbance not better accounted for by a pre-existing or evolving dementia.
- The disturbance develops over a short period of time (usually hours to days), represents an acute change from baseline, and tends to fluctuate during the course of the day.
- There is evidence from the history, physical examination, or laboratory findings that the disturbance is caused by the direct physiologic consequences of a general medical condition, substance intoxication, or substance withdrawal. The changes in attention and cognition must not occur in the context of a severely reduced level of arousal, such as coma.
- Hyperactive delirium - a condition where a patient might have heightened arousal, with restlessness, agitation, hallucinations, and inappropriate behavior
- Hypoactive delirium - a condition where a patient might display lethargy, reduced motor activity, incoherent speech, and lack of interest
- Mixed delirium - a combination of hyperactive and hypoactive signs and symptoms.
The term subsyndromal delirium has also been used to define partially resolved or incomplete forms of delirium.
Epidemiology
Pathophysiology
- The pathophysiology of delirium remains relatively unclear. In general, neuroimaging studies reveal disruptions in higher cortical functioning in multiple disparate areas of the brain, including the prefrontal cortex, subcortical structures, thalamus, basal ganglia, lingual gyri, and frontal, fusiform and temporoparietal cortex.[22] [23]
- Electroencephalographic (EEG) studies also show diffuse slowing of cortical activity.
- Theories on the pathogenesis of delirium point to the role of neurotransmitters, inflammation, and chronic stress on the brain. For example, the role of cholinergic deficiency in inducing delirium is strengthened by the clear association of anticholinergic drug use with increased incidence.[24] Studies in surgical patients have demonstrated a dysfunctional interaction between the cholinergic and immune systems in patients who developed postoperative delirium.[25]
- Other neurotransmitters implicated in the pathophysiology of delirium include norepinephrine, serotonin, gamma-aminobutyric acid, glutamate, and melatonin.
- Evidence also points to the role of cytokines such as interleukins 1 and 2 and TNF-alpha and interferon in contributing to delirium.[34]
- Finally, chronic hypercortisolism, as induced by chronic stress secondary to illness or trauma, may also contribute to delirium initiation.[35]
Last updated
Citations
Devlin JW, Skrobik Y, Gélinas C, et al; American College of Critical Care Medicine. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018 Sep;46(9):e825-e73.[Abstract][Full Text]
National Institute for Health and Care Excellence. Delirium: prevention, diagnosis and management in hospital and long-term care. Jan 2023 [internet publication].[Full Text]
American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 5th ed., text revision (DSM-5-TR). Washington, DC: American Psychiatric Publishing; 2022
1. Inouye SK, Schlesinger MJ, Lydon TJ. Delirium: a symptom of how hospital care is failing older persons and a window to improve quality of hospital care. Am J Med. 1999 May;106(5):565-73.[Abstract]
2. Devlin JW, Skrobik Y, Gélinas C, et al; American College of Critical Care Medicine. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018 Sep;46(9):e825-e73.[Abstract][Full Text]
3. National Institute for Health and Care Excellence. Delirium: prevention, diagnosis and management in hospital and long-term care. Jan 2023 [internet publication].[Full Text]
4. Cole MG, Primeau FJ. Prognosis of delirium in elderly hospital patients. CMAJ. 1993 Jul 1;149(1):41-6.[Abstract]
5. Brown TM, Boyle MF. Delirium. BMJ. 2002 Sep 21;325(7365):644-7.[Abstract][Full Text]
6. US Department of Health and Human Services. 2004 CMS Statistics. Washington, DC: Centers for Medicare and Medicaid Services, 2004:34. (CMS Publication No 03445)
7. Cavallazzi R, Saad M, Marik PE. Delirium in the ICU: an overview. Ann Intensive Care. 2012 Dec 27;2(1):49.[Abstract][Full Text]
8. Han JH, Wilson A, Vasilevskis EE, et al. Diagnosing delirium in older emergency department patients: validity and reliability of the delirium triage screen and the brief confusion assessment method. Ann Emerg Med. 2013 Nov;62(5):457-65.[Abstract]
9. Kiely DK, Bergmann MA, Murphy KM, et al. Delirium among newly admitted postacute facility patients: prevalence, symptoms, and severity. J Gerontol A Biol Sci Med Sci. 2003 May;58(5):441-5.[Abstract]
10. Murray AM, Levkoff SE, Wetle T, et al. Acute delirium and functional decline in the hospitalized elderly patient. J Gerontol. 1993 Sep;48(5):M181-6.[Abstract]
11. Marcantonio ER, Simon SE, Bergmann MA, et al. Delirium symptoms in post-acute care: prevalent, persistent, and associated with poor functional recovery. J Am Geriatr Soc. 2003 Jan;51(1):4-9.[Abstract]
12. van den Boogaard M, Schoonhoven L, Evers AW, et al. Delirium in critically ill patients: impact on long-term health-related quality of life and cognitive functioning. Crit Care Med. 2012 Jan;40(1):112-8.[Abstract]
13. Roche V. Southwestern Internal Medicine Conference. Etiology and management of delirium. Am J Med Sci. 2003 Jan;325(1):20-30.[Abstract]
14. Cole MG, Ciampi A, Belzile E, et al. Persistent delirium in older hospital patients: a systematic review of frequency and prognosis. Age Ageing. 2009 Jan;38(1):19-26.[Abstract][Full Text]
15. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 5th ed., text revision (DSM-5-TR). Washington, DC: American Psychiatric Publishing; 2022
16. Potter J, George J; Guideline Development Group. The prevention, diagnosis and management of delirium in older people: concise guidelines. Clin Med. 2006 May-June;6(3):303-8.[Abstract]
17. Gupta N, de Jonghe J, Schieveld J, et al. Delirium phenomenology: what can we learn from the symptoms of delirium? J Psychosom Res. 2008 Sep;65(3):215-22.[Abstract]
18. Meagher DJ, Leonard M, Donnelly S, et al. A longitudinal study of motor subtypes in delirium: frequency and stability during episodes. J Psychosom Res. 2012 Mar;72(3):236-41.[Abstract]
19. Inouye SK. Delirium in hospitalized older patients. Clin Geriatr Med. 1998 Nov;14(4):745-64.[Abstract]
20. Pisani MA, McNicoll L, Inouye SK. Cognitive impairment in the intensive care unit. Clin Chest Med. 2003 Dec;24(2):727-37.[Abstract]
21. Neufeld KJ, Thomas C. Delirium: definition, epidemiology, and diagnosis. J Clin Neurophysiol. 2013 Oct;30(5):438-42.[Abstract]
22. Singer GG, Brenner BM. Fluid and electrolyte disturbances. In: Kasper DL, Fauci AS, Longo DL, et al. eds. Harrison's Principles of Internal Medicine, 16th ed. New York, NY: McGraw Hill; 2005:252-63.
23. Choi SH, Lee H, Chung TS, et al. Neural network functional connectivity during and after an episode of delirium. Am J Psychiatry. 2012 May;169(5):498-507.[Abstract]
24. Trzepacz P, van der Mast R. The neuropathophysiology of delirium. In: Lindesay J, Rockwood K, Macdonald A, eds. Delirium in old age. Oxford, UK: Oxford University Press; 2002:51-90.
25. Cerejeira J, Nogueira V, Luís P, et al. The cholinergic system and inflammation: common pathways in delirium pathophysiology. J Am Geriatr Soc. 2012 Apr;60(4):669-75.[Abstract]
26. Oh ES, Needham DM, Nikooie R, et al. Antipsychotics for preventing delirium in hospitalized adults: a systematic review. Ann Intern Med. 2019 Oct 1;171(7):474-84.[Abstract][Full Text]
27. Janssen TL, Alberts AR, Hooft L, et al. Prevention of postoperative delirium in elderly patients planned for elective surgery: systematic review and meta-analysis. Clin Interv Aging. 2019;14:1095-117.[Abstract][Full Text]
28. Siddiqi N, Harrison JK, Clegg A, et al. Interventions for preventing delirium in hospitalised non-ICU patients. Cochrane Database Syst Rev. 2016 Mar 11;3:CD005563.[Abstract][Full Text]
29. Nikooie R, Neufeld KJ, Oh ES, et al. Antipsychotics for treating delirium in hospitalized adults: a systematic review. Ann Intern Med. 2019 Oct 1;171(7):485-95.[Abstract][Full Text]
30. Zayed Y, Barbarawi M, Kheiri B, et al. Haloperidol for the management of delirium in adult intensive care unit patients: a systematic review and meta-analysis of randomized controlled trials. J Crit Care. 2019 Apr;50:280-6.[Abstract][Full Text]
31. Burry L, Hutton B, Williamson DR, et al. Pharmacological interventions for the treatment of delirium in critically ill adults. Cochrane Database Syst Rev. 2019 Sep 3;9:CD011749.[Abstract][Full Text]
32. Kishi T, Hirota T, Matsunaga S, et al. Antipsychotic medications for the treatment of delirium: a systematic review and meta-analysis of randomised controlled trials. J Neurol Neurosurg Psychiatry. 2016 Jul;87(7):767-74.[Abstract][Full Text]
33. Finucane AM, Jones L, Leurent B, et al. Drug therapy for delirium in terminally ill adults. Cochrane Database Syst Rev. 2020 Jan 21;1(1):CD004770.[Abstract][Full Text]
34. Cerejeira J, Lagarto L, Mukaetova-Ladinska EB. The immunology of delirium. Neuroimmunomodulation. 2014;21(2-3):72-8.[Abstract]
35. Inouye SK. Delirium in older persons. N Engl J Med. 2006 Mar 16;354(11):1157-65.[Abstract]
36. Khan BA, Zawahiri M, Campbell NL, et al. Delirium in hospitalized patients: implications of current evidence on clinical practice and future avenues for research - a systematic evidence review. J Hosp Med. 2012 Sep;7(7):580-9.[Abstract][Full Text]
37. Tow A, Holtzer R, Wang C, et al. Cognitive reserve and postoperative delirium in older adults. J Am Geriatr Soc. 2016 Jun;64(6):1341-6.[Abstract]
38. Rothberg MB, Herzig SJ, Pekow PS, et al. Association between sedating medications and delirium in older inpatients. J Am Geriatr Soc. 2013 Jun;61(6):923-30.[Abstract]
39. McPherson JA, Wagner CE, Boehm LM, et al. Delirium in the cardiovascular ICU: exploring modifiable risk factors. Crit Care Med. 2013 Feb;41(2):405-13.[Abstract]
40. Fox C, Smith T, Maidment I, et al. Effect of medications with anti-cholinergic properties on cognitive function, delirium, physical function and mortality: a systematic review. Age Ageing. 2014 Sep;43(5):604-15.[Abstract][Full Text]
41. Guenther U, Theuerkauf N, Frommann I, et al. Predisposing and precipitating factors of delirium after cardiac surgery: a prospective observational cohort study. Ann Surg. 2013 Jun;257(6):1160-7.[Abstract]
42. Slatore CG, Goy ER, OʼHearn DJ, et al. Sleep quality and its association with delirium among veterans enrolled in hospice. Am J Geriatr Psychiatry. 2012 Apr;20(4):317-26.[Abstract][Full Text]
43. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10.[Abstract][Full Text]
44. National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. Sept 2017 [internet publication].[Full Text]
45. Royal College of Physicians. National Early Warning Score (NEWS) 2. December 2017 [internet publication].[Full Text]
46. American College of Emergency Physicians (ACEP) Expert Panel on Sepsis. DART: an evidence-driven tool to guide the early recognition and treatment of sepsis and septic shock. 2023 [internet publication].[Full Text]
47. Academy of Medical Royal Colleges. Statement on the initial antimicrobial treatment of sepsis. May 2022 [internet publication].[Full Text]
48. Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Crit Care Med. 2021 Nov 1;49(11):e1063-143.[Abstract][Full Text]
49. Society of Critical Care Medicine. Surviving sepsis campaign: hour-1 bundle. 2019 [internet publication].[Full Text]
50. van Meenen LC, van Meenen DM, de Rooij SE, et al. Risk prediction models for postoperative delirium: a systematic review and meta-analysis. J Am Geriatr Soc. 2014 Dec;62(12):2383-90.[Abstract]
51. Oh ES, Li M, Fafowora TM, et al. Preoperative risk factors for postoperative delirium following hip fracture repair: a systematic review. Int J Geriatr Psychiatry. 2015 Sep;30(9):900-10.[Abstract][Full Text]
52. Fortes-Filho SQ, Apolinario D, Melo JA, et al. Predicting delirium after hip fracture with a 2-min cognitive screen: prospective cohort study. Age Ageing. 2016 Sep;45(5):713-7.[Abstract]
53. Young J, Inouye SK. Delirium in older people. BMJ. 2007 Apr 21;334(7598):842-6.[Abstract]
54. Doriath V, Paesmans M, Catteau G et al. Acute confusion in patients with systemic cancer. J Neurooncol. 2007 Jul;83(3):285-9.[Abstract]
55. Leonard MM, Nekolaichuk C, Meagher DJ, et al. Practical assessment of delirium in palliative care. J Pain Symptom Manage. 2014 Aug;48(2):176-90.[Abstract]
56. Inouye SK, Foreman MD, Mion LC, et al. Nurses' recognition of delirium and its symptoms: comparison of nurse and researcher ratings. Arch Intern Med. 2001 Nov 12;161(20):2467-73.[Abstract]
57. Registered Nurses Association of Ontario. Delirium, dementia, and depression in older adults: assessment and care, 2nd edition. 2016 [internet publication].[Full Text]
58. Quispel-Aggenbach DWP, Holtman GA, Zwartjes HAHT, et al. Attention, arousal and other rapid bedside screening instruments for delirium in older patients: a systematic review of test accuracy studies. Age Ageing. 2018 Sep 1;47(5):644-653.[Abstract][Full Text]
59. National Institute for Health and Care Excellence. Dementia: assessment, management and support for people living with dementia and their carers. June 2018 [internet publication].[Full Text]
60. Inouye SK, van Dyck CH, Alessi CA, et al. Clarifying confusion: the Confusion Assessment Method. A new method for detection of delirium. Ann Intern Med. 1990 Dec 15;113(12):941-8.[Abstract]
61. Vreeswijk R, Timmers JF, de Jonghe JFM, et al. Assessment scales for delirium. Aging Health. 2009 Jun 8;5(3):409-25.
62. Wei LA, Fearing MA, Sternberg EJ, et al. The Confusion Assessment Method: a systematic review of current usage. J Am Geriatr Soc. 2008 May;56(5):823-30.[Abstract][Full Text]
63. Gusmao-Flores D, Salluh JI, Chalhub RA, et al. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and Intensive Care Delirium Screening Checklist (ICDSC) for the diagnosis of delirium: a systematic review and meta-analysis of clinical studies. Crit Care. 2012 Jul 3;16(4):R115.[Abstract][Full Text]
64. Marcantonio ER, Ngo LH, O'Connor M, et al. 3D-CAM: derivation and validation of a 3-minute diagnostic interview for CAM-defined delirium: a cross-sectional diagnostic test study. Ann Intern Med. 2014 Oct 21;161(8):554-61.[Abstract][Full Text]
65. Vasunilashorn SM, Guess J, Ngo L, et al. Derivation and validation of a severity scoring method for the 3-minute diagnostic interview for confusion assessment method - defined delirium. J Am Geriatr Soc. 2016 Aug;64(8):1684-9.[Abstract]
66. Inouye SK, Kosar CM, Tommet D, et al. The CAM-S: development and validation of a new scoring system for delirium severity in 2 cohorts. Ann Intern Med. 2014 Apr 15;160(8):526-33.[Abstract]
67. LaMantia MA, Messina FC, Hobgood CD, et al. Screening for delirium in the emergency department: a systematic review. Ann Emerg Med. 2014 May;63(5):551-60.[Abstract][Full Text]
68. Han JH, Wilson A, Graves AJ, et al. Validation of the Confusion Assessment Method for the Intensive Care Unit in older emergency department patients. Acad Emerg Med. 2014 Feb;21(2):180-7.[Abstract]
69. Han JH, Vasilevskis EE, Schnelle JF, et al. The diagnostic performance of the Richmond Agitation Sedation Scale for detecting delirium in older emergency department patients. Acad Emerg Med. 2015 Jul;22(7):878-82.[Abstract]
70. Traube C, Silver G, Kearney J, et al. Cornell Assessment of Pediatric Delirium: a valid, rapid, observational tool for screening delirium in the PICU. Crit Care Med. 2014 Mar;42(3):656-63.[Abstract]
71. Morandi A, McCurley J, Vasilevskis EE, et al. Tools to detect delirium superimposed on dementia: a systematic review. J Am Geriatr Soc. 2012 Nov;60(11):2005-13.[Abstract]
72. Alagiakrishnan K, Wiens CA. An approach to drug induced delirium in the elderly. Postgrad Med J. 2004 Jul;80(945):388-93.[Abstract][Full Text]
73. Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet. 2014 Mar 8;383(9920):911-22.[Abstract][Full Text]
74. Carrasco MP, Villarroel L, Andrade M, et al. Development and validation of a delirium predictive score in older people. Age Ageing. 2014 May;43(3):346-51.[Abstract][Full Text]
75. Neto AS, Nassar AP Jr, Cardoso SO, et al. Delirium screening in critically ill patients: a systematic review and meta-analysis. Crit Care Med. 2012 Jun;40(6):1946-51.[Abstract]
76. Devlin JW, Fong JJ, Fraser GL, et al. Delirium assessment in the critically ill. Intensive Care Med. 2007 Jun;33(6):929-40.[Abstract]
77. Van Rompaey B, Schuurmans MJ, Shortridge-Baggett LM, et al. Risk factors for intensive care delirium: a systematic review. Intensive Crit Care Nurs. 2008 Apr;24(2):98-107.[Abstract]
78. Van Den Boogaard MP. Assessment of delirium in ICU patients: a literature review. Neth J Crit Care. 2010 May;14(3):10-5.
79. Soiza RL, Sharma V, Ferguson K, et al. Neuroimaging studies of delirium: a systematic review. J Psychosom Res. 2008 Sep;65(3):239-48.[Abstract]
80. Sidhu KS, Balon R, Ajluni V, et al. Standard EEG and the difficult-to-assess mental status. Ann Clin Psychiatry. 2009 Apr-Jun;21(2):103-8.[Abstract]
81. Lavi R, Yarnitsky D, Rowe JM, et al. Standard vs atraumatic Whitacre needle for diagnostic lumbar puncture: a randomized trial. Neurology. 2006 Oct 24;67(8):1492-4.[Abstract]
82. Arendt K, Demaerschalk BM, Wingerchuk DM, et al. Atraumatic lumbar puncture needles: after all these years, are we still missing the point? Neurologist. 2009 Jan;15(1):17-20.[Abstract]
83. Nath S, Koziarz A, Badhiwala JH, et al. Atraumatic versus conventional lumbar puncture needles: a systematic review and meta-analysis. Lancet. 2018 Mar 24;391(10126):1197-204.[Abstract]
84. Rochwerg B, Almenawer SA, Siemieniuk RAC, et al. Atraumatic (pencil-point) versus conventional needles for lumbar puncture: a clinical practice guideline. BMJ. 2018 May 22;361:k1920.[Abstract][Full Text]
85. Ahmed SV, Jayawarna C, Jude E. Post lumbar puncture headache: diagnosis and management. Postgrad Med J. 2006 Nov;82(973):713-6.[Abstract][Full Text]
86. Arevalo-Rodriguez I, Ciapponi A, Roqué i Figuls M, et al. Posture and fluids for preventing post-dural puncture headache. Cochrane Database Syst Rev. 2016 Mar 7;(3):CD009199.[Abstract][Full Text]
87. Simundic AM, Bölenius K, Cadamuro J, et al. Joint EFLM-COLABIOCLI recommendation for venous blood sampling. Clin Chem Lab Med. 2018;56(12):2015-38.[Abstract]
88. Kalapatapu RK, Neugroschl JA. Update on neuropsychiatric symptoms of dementia: evaluation and management. Geriatrics. 2009 Apr;64(4):20-6.[Abstract]
89. van der Worp HB, van Gijn J. Clinical practice: acute ischemic stroke. N Engl J Med. 2007 Aug 9;357(6):572-9.[Abstract]
90. von Kummer R, Allen K, Holle R, et al. Acute stroke: usefulness of early CT findings before thrombolytic therapy. Radiology. 1997 Nov;205(2):327-33.[Abstract]
91. Johnson JC, Jayadevappa R, Baccash PD et al. Nonspecific presentation of pneumonia in hospitalized older people: age effect of dementia? J Am Geriatr Soc. 2000 Oct;48(10):1316-20.[Abstract]
92. Warshaw G, Tanzer F. The effectiveness of lumbar puncture in the evaluation of delirium and fever in the hospitalized elderly. Arch Fam Med. 1993 Mar;2(3):293-7.[Abstract]
93. Manepalli J, Grossberg GT, Mueller C. Prevalence of delirium and urinary tract infection in a psychogeriatric unit. J Geriatr Psychiatry Neurol. 1990 Oct-Dec;3(4):198-202.[Abstract]
94. Siami S, Annane D, Sharshar T. The encephalopathy in sepsis. Crit Care Clin. 2008 Jan;24(1):67-82, viii.[Abstract]
95. Seaman JS, Schillerstrom J, Carroll D, et al. Impaired oxidative metabolism precipitates delirium: a study of 101 ICU patients. Psychosomatics. 2006 Jan-Feb;47(1):56-61.[Abstract]
96. Workgroup on Hypoglycemia, American Diabetes Association. Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care. 2005 May;28(5):1245-9.[Abstract][Full Text]
97. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatic encephalopathy. J Hepatol. 2022 Sep;77(3):807-24.[Abstract][Full Text]
98. Potts JT Jr. Diseases of the Parathyroid gland and other hyper- and hypocalcemic disorders. In: Kasper DL, Fauci AS, Longo DL, et al. eds. Harrison's Principles of Internal Medicine, 16th ed. New York, NY: McGraw Hill; 2005:2252.
99. van de Beek D, de Gans J, Spanjaard L, et al. Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med. 2004 Oct 28;351(18):1849-59.[Abstract][Full Text]
100. Rushworth RL, Torpy DJ, Falhammar H. Adrenal Crisis. N Engl J Med. 2019 Aug 29;381(9):852-61.[Abstract][Full Text]
101. Hsieh MJ, Chang WN, Lui CC, et al. Clinical characteristics of fusobacterial brain abscess. Jpn J Infect Dis. 2007 Feb;60(1):40-4.[Abstract][Full Text]
102. Timmermans M, Carr J. Neurosyphilis in the modern era. J Neurol Neurosurg Psychiatry. 2004 Dec;75(12):1727-30.[Abstract][Full Text]
