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Brief Report |

Initial Misdiagnosis and Outcome After Subarachnoid Hemorrhage FREE

Robert G. Kowalski, BS; Jan Claassen, MD; Kurt T. Kreiter, PhD; Joseph E. Bates, MA; Noeleen D. Ostapkovich, MS; E. Sander Connolly, MD; Stephan A. Mayer, MD
[+] Author Affiliations

Author Affiliations: Division of Stroke and Critical Care Neurology, Department of Neurology (Mssrs Kowalski and Bates, Ms Ostapkovich, and Drs Claassen, Kreiter, and Mayer), and Department of Neurosurgery (Drs Connolly and Mayer), Columbia University College of Physicians and Surgeons, New York, NY.


JAMA. 2004;291(7):866-869. doi:10.1001/jama.291.7.866.
Text Size: A A A
Published online

Context Mortality and morbidity can be reduced if aneurysmal subarachnoid hemorrhage (SAH) is treated urgently.

Objective To determine the association of initial misdiagnosis and outcome after SAH.

Design, Setting, and Participants Inception cohort of 482 SAH patients admitted to a tertiary care urban hospital between August 1996 and August 2001.

Main Outcome Measures Misdiagnosis was defined as failure to correctly diagnose SAH at a patient's initial contact with a medical professional. Functional outcome was assessed at 3 and 12 months with the modified Rankin Scale; quality of life (QOL), with the Sickness Impact Profile.

Results Fifty-six patients (12%) were initially misdiagnosed, including 42 of 221 (19%) of those with normal mental status at first contact. Migraine or tension headache (36%) was the most common incorrect diagnosis, and failure to obtain a computed tomography (CT) scan was the most common diagnostic error (73%). Neurologic complications occurred in 22 patients (39%) before they were correctly diagnosed, including 12 patients (21%) who experienced rebleeding. Normal mental status, small SAH volume, and right-sided aneurysm location were independently associated with misdiagnosis. Among patients with normal mental status at first contact, misdiagnosis was associated with worse QOL at 3 months and an increased risk of death or severe disability at 12 months.

Conclusions In this study, misdiagnosis of SAH occurred in 12% of patients and was associated with a smaller hemorrhage and normal mental status. Among individuals who initially present in good condition, misdiagnosis is associated with increased mortality and morbidity. A low threshold for CT scanning of patients with mild symptoms that are suggestive of SAH may reduce the frequency of misdiagnosis.

Subarachnoid hemorrhage (SAH) affects nearly 30 000 individuals annually in North America and results in serious impairment or death in 40% to 60% of cases.1 Outcome is highly dependent on early diagnosis and aggressive intervention.1,2 Immediate aneurysm repair is particularly crucial because rebleeding occurs in 26% to 73% of patients within days or weeks after the initial rupture if the aneurysm is untreated.1,2

The reported frequency of misdiagnosis of SAH ranges from 12% to 51%.311 Correct diagnosis can be confounded because a key symptom of SAH, headache, is among the most common symptoms reported to emergency physicians.12 Accordingly, misdiagnosed SAH represents one of the largest sources of emergency department litigation claims and malpractice settlement payments in the United States.13 We sought to identify the frequency, risk factors, and impact on outcome of initial misdiagnosis in patients hospitalized with SAH.

All patients who were diagnosed with SAH and were admitted to the Neurological Intensive Care Unit at Columbia-Presbyterian Medical Center in New York between August 1996 and August 2001 were invited to enroll in the Columbia University SAH Outcomes Project. The study was approved by the hospital's institutional review board, and written informed consent was obtained from the patient or a surrogate. SAH was diagnosed according to computed tomography (CT) or by xanthochromia of cerebrospinal fluid (CSF). Patients with spontaneous aneurysmal and nonaneurysmal SAH were included. Individuals with SAH caused by trauma, arteriovenous malformations, or other secondary causes were excluded, as were patients younger than 18 years and those admitted more than 14 days after their most recent hemorrhage.

Demographic data, medical and social history, and clinical features at admission were obtained through patient and surrogate interviews and medical record review by a study neurointensivist. Details about symptoms at the onset of hemorrhage, admission Hunt-Hess grade, and CT and angiographic findings were recorded, as described previously.1417 Sentinel headaches were defined as discrete episodes of severe headache that preceded the headache that initially led the patient to seek medical attention. Aneurysms were designated right-sided if located on the right middle cerebral artery (MCA) or internal carotid artery (ICA) and left-sided if located on the left MCA or ICA.

Misdiagnosis was defined as failure to correctly identify a subsequently documented SAH on previous presentation to a health care professional. Types of encounters included ambulance calls, emergency department visits, clinician office visits, telephone calls to a health care professional (physician, nurse, or physician assistant), or hospitalization. For patients whose SAH was initially misdiagnosed, the date and type of medical contact, preliminary diagnosis, and initial Hunt-Hess grade according to descriptions of the patients' condition were recorded. The presumed error in diagnosis and complications that occurred between the initial misdiagnosis and eventual correct diagnosis (neurologic deterioration, aneurysm rebleeding, and symptomatic vasospasm or hydrocephalus) were determined by the admitting study neurointensivist and adjudicated by consensus of other members of the study team.

Patients and surrogate informants were interviewed at 3 and 12 months either by telephone or in person. Global outcome and functional status were assessed with the modified Rankin Scale18 (mRS; 0, no symptoms or disability; 6, dead), and quality of life (QOL) was evaluated with the Sickness Impact Profile (SIP; 0, best; 100, worst).19 Proxy responses from an informant were used for patients who were too severely impaired to complete the mRS or SIP.20 All assessment instruments were administered in the native language (English or Spanish) of the patient or surrogate informant.

We analyzed all patients and those initially presenting with normal mental status (Hunt-Hess grade I or II) to control for the confounding effects of baseline clinical grade on outcome. Differences in proportions were compared with the χ2 test or Fisher exact test. The independent samples t test (2-tailed) was used to analyze normally distributed continuous variables, with correction for unequal variances as appropriate. Independent predictors of misdiagnosis were identified with forward stepwise logistic regression. Modified Rankin Scale scores were dichotomized to identify patients who died (mRS 6), those who died or had severe disability (mRS 4-6), and those who died or had any disability (mRS 2-6); when 12-month data were missing, the 3-month score was substituted (last observation carried forward). Level of significance was set at P<.05. Data were analyzed with SPSS version 9.0 (SPSS Inc, Chicago, Ill).

Of 482 patients with SAH, 56 (12%) were misdiagnosed on first medical contact. In 75% of cases, the misdiagnosis occurred in a hospital emergency department or in a physician's office (Table 1). The interval between initial SAH onset and correct diagnosis was greater for initially misdiagnosed than correctly diagnosed patients (median, 4.0 [range, 0-35] vs 0.0 [range, 0-14] days, P<.001). The most common diagnostic error was failure to obtain a CT, and migraine or tension headache was the most common incorrect diagnosis (Table 1). Twenty-two of the 56 (39%) misdiagnosed patients experienced at least 1 complication before hospital admission: the most common were a decreased level of consciousness and rebleeding (Table 1). There were no trends in the rate of misdiagnosis throughout the 5-year study period.

Table Graphic Jump LocationTable 1. Clinical Features of 56 Misdiagnosed Patients

Compared with patients with an initially correct SAH diagnosis, misdiagnosed patients had smaller hemorrhages, were less likely to have lost consciousness at ictus, and were more likely to have experienced sentinel headaches or to have a right-sided aneurysm (Table 2). Independent predictors of misdiagnosis in the final multivariate model included Hunt-Hess grade I or II condition (indicating normal mental status) at first medical contact (adjusted odds ratio [AOR], 10.8; 95% confidence interval [CI], 3.2-37.1; P<.001), smaller SAH volume (SAH score <15) (AOR, 5.1; 95% CI, 1.8-13.9; P = .002), and right-sided aneurysm location (AOR, 3.3; 95% CI, 1.5-7.0; P = .003).

Table Graphic Jump LocationTable 2. Risk Factors for Misdiagnosis*

Among patients who were Hunt-Hess grade I or II at first medical contact, misdiagnosed patients were also less likely to be fluent in English, to be married, and to have 12 or more years of education (Table 2). Independent predictors of misdiagnosis in this subset of patients included less than 12 years of education (AOR, 4.5; 95% CI, 1.9-10.5; P<.001) and smaller SAH volume (AOR, 13.5; 95% CI, 3.0-60.8; P<.001).

Overall, 18% of patients died during hospitalization, and 24% were dead at 12 months. Mortality and functional disability (Table 3) and SIP total scores at 3 and 12 months were not significantly different between misdiagnosed and correctly diagnosed patients. Among the 221 patients who were Hunt-Hess grade I or II at first medical contact, misdiagnosed patients were more likely to have died or to have died or be severely disabled at 3 and 12 months (Table 3). Among survivors, misdiagnosed patients also had significantly poorer QOL, as assessed by the SIP total score at 3 months (21 [17] vs 12 [12]; P = .03) but not at 12 months (19 [19] vs 13 [13]; P = .10).

Table Graphic Jump LocationTable 3. Three-Month and 12-Month Outcomes*

Of 482 patients diagnosed with SAH and admitted to our institution over 5 years, 12% were initially misdiagnosed. Previous studies have generally reported higher frequencies of initial misdiagnosis, ranging from 12% to 51%.39 These differences may be explained by variations in patient behavior, clinical practice, access to emergency medical care, or methods of case ascertainment. Increased awareness among clinicians about the importance of ruling out SAH in patients with sudden, severe headache may also explain the lower rate in our study.

Our results confirm that patients with good neurologic grade (ie, those most likely to benefit from urgent aneurysm repair) have the highest risk of being misdiagnosed.3,4 Unlike previous studies that found that the most common diagnostic errors were failure to interpret subtle CT or CSF findings properly,3,11 we found that failure to obtain a CT at initial contact was the most frequent diagnostic error. The spectrum of incorrect working diagnoses (Table 1) and the median delay of 4 days to establish the correct diagnosis in our study are similar to previous findings.39

To our knowledge, our study is the largest to analyze the association between initial misdiagnosis and outcome after SAH and the first to identify risk factors in a multivariate analysis. In addition to good clinical grade, smaller hemorrhages (perhaps relating to less severe headache) and right-sided aneurysm location were independently associated with initial misdiagnosis. Reduced SAH volume might also be explained by the gradual disappearance of blood on CT before the correct diagnosis was made.21 The importance of the association with right-sided aneurysm location is unclear; perhaps right hemisphere dysfunction may lead to neglect or lack of concern on the part of the patient when he or she describes symptoms to a medical practitioner. Misdiagnosed patients also were more likely to report antecedent sentinel headaches than those who were correctly diagnosed, which might be explained by a tendency for clinicians to incorrectly assume that recent recurrent headaches make a benign condition such as migraine or tension headache more likely.

Among patients who were Hunt-Hess grade I or II at first medical contact, lower education (≤12 years), smaller hemorrhages, nonfluency in English, and being unmarried were also associated with misdiagnosis. These findings implicate sociocultural barriers and lack of social support in explaining some SAH misdiagnoses.

Although initial misdiagnosis was not related to outcome in our study population as a whole, this comparison is confounded by the fact that misdiagnosed patients were generally in better neurologic condition. When we restricted our analysis to the 45% of patients who initially presented with a normal neurologic examination (Hunt-Hess grade I or II), nearly 20% were misdiagnosed, and the impact was devastating: misdiagnosis was associated with a nearly 4-fold increase in the likelihood of death at 12 months and with worse functional recovery and QOL among survivors.

Our study has several limitations. First, our hospital-based series may not accurately reflect the true frequency and impact of SAH misdiagnosis, because 12% to 50% of patients with SAH who have rebleeding may die without being hospitalized.22,23 In addition, we have no data on misdiagnosed patients with a good outcome who were not subsequently hospitalized. Second, our assessments of initial level of consciousness, diagnostic error, and complications of delayed diagnosis were based on subjective assessments of historical data. To address these limitations, these variables were adjudicated by multiple study team members who obtained their own history. Finally, our study is a single-center study and may have referral bias.

Important clues to the diagnosis of SAH, in addition to the complaint of a sudden "thunderclap" headache, include loss of consciousness or vomiting at onset, meningismus, prominent neck or back pain, retinal subhyaloid hemorrhages, and recent headaches that have lasted for days at a time.2,11,24 In addition to careful attention to these symptoms and signs, CT imaging (and CSF examination when necessary) should be used to exclude SAH for any patient with mild symptoms and for whom the diagnosis is a consideration.25

Mayberg MR, Batjer HH, Dacey R.  et al.  Guidelines for the management of aneurysmal subarachnoid hemorrhage.  Stroke.1994;25:2315-2328.
PubMed
van Gijn J, Rinkel GJ. Subarachnoid haemorrhage: diagnosis, causes and management.  Brain.2001;124:249-278.
PubMed
Adams HP, Jergenson DD, Kassell NF, Sahs AL. Pitfalls in the recognition of subarachnoid hemorrhage.  JAMA.1980;244:794-796.
PubMed
Mayer PL, Awad IA, Todor R.  et al.  Misdiagnosis of symptomatic cerebral aneurysm: prevalence and correlation with outcome at four institutions.  Stroke.1996;27:1558-1563.
PubMed
Vannemreddy P, Nanda A, Kelley R, Baskaya MK. Delayed diagnosis of intracranial aneurysms: confounding factors in clinical presentation and the influence of misdiagnosis on outcome.  South Med J.2001;94:1108-1111.
PubMed
Chan BS, Dorsch NW. Delayed diagnosis in subarachnoid haemorrhage.  Med J Aust.1991;154:509-511.
PubMed
Kassell NF, Kongable GL, Torner JC.  et al.  Delay in referral of patients with ruptured aneurysms to neurosurgical attention.  Stroke.1985;16:587-590.
PubMed
Schievink WI, van der Werf DJ, Hageman LM, Dreissen JJ. Referral pattern of patients with aneurysmal subarachnoid hemorrhage.  Surg Neurol.1988;29:367-371.
PubMed
Neil-Dwyer G, Lang D. "Brain attack" aneurysmal subarachnoid hemorrhage: death due to delayed diagnosis.  J R Coll Phys Lond.1997;31:49-52.
Fridriksson S, Hillman J, Landtblom AM, Boive J. Education of referring doctors about sudden onset headache in subarachnoid hemorrhage: a prospective study.  Acta Neurol Scand.2001;103:238-242.
PubMed
Edlow JA, Caplan LR. Avoiding pitfalls in the diagnosis of subarachnoid hemorrhage.  N Engl J Med.2000;342:29-36.
PubMed
Barton CW. Evaluation and treatment of headache patients in the emergency department: a survey.  Headache.1994;34:91-94.
PubMed
Karcz A, Holbrook J, Burke MC.  et al.  Massachusetts emergency medicine closed malpractice claims: 1988-1990.  Ann Emerg Med.1993;22:553-559.
PubMed
Hunt WE, Hess RM. Surgical risk as related to time of intervention in the repair of intracranial aneurysms.  J Neurosurg.1968;28:14-20.
PubMed
Hijdra A, van Gijn J, Nagelkerke NJ, Vermeulen M, van Crevel H. Prediction of delayed cerebral ischemia, rebleeding, and outcome after aneurysmal subarachnoid hemorrhage.  Stroke.1988;19:1250-1256.
PubMed
van Gijn J, Hijdra A, Wijdicks EF.  et al.  Acute hydrocephalus after aneurysmal subarachnoid hemorrhage.  J Neurosurg.1985;63:355-362.
PubMed
Claassen J, Carhuapoma JR, Kreiter KT, Du EY, Connolly ES, Mayer SA. Global cerebral edema after subarachnoid hemorrhage: frequency, predictors, and impact on outcome.  Stroke.2002;33:1225-1232.
PubMed
Van Swieten JC, Koudstaal PJ, Visser MC.  et al.  Interobserver agreement for the assessment of handicap in stroke patients.  Stroke.1988;19:604-607.
PubMed
Damiano AM. Sickness Impact Profile: User's Manual and Interpretation GuideBaltimore, Md: The Johns Hopkins University; 1996.
Ostapkovich N, Kreiter K, Peery S.  et al.  Are proxy ratings valid for assessing quality of life after subarachnoid hemorrhage?  Ann Neurol.2001;50:S78-S79.
Vermeulen M, van Gijn J. The diagnosis of subarachnoid haemorrhage.  J Neurol Neurosurg Psychiatry.1990;53:365-372.
PubMed
Schievink WI, Wijdicks EF, Parisi JE.  et al.  Sudden death from aneurysmal subarachnoid hemorrhage.  Neurology.1995;45:871-874.
PubMed
Broderick JP, Brott TG, Duldner JE, Tomsick T, Leach A. Initial and recurrent bleeding are the major causes of death following subarachnoid hemorrhage.  Stroke.1994;25:1342-1347.
PubMed
Mayer SA, Bernardini GL, Brust JCM, Solomon RA. Subarachnoid hemorrhage. In: Rowland LP, ed. Merritt's Textbook of Neurology. 10th ed. Baltimore, Md: Williams & Wilkins; 2000:260-267.
Morgenstern LB, Luna-Gonzales H, Huber Jr JC.  et al.  Worst headache and subarachnoid hemorrhage: prospective, modern computed tomography and spinal fluid analysis.  Ann Emerg Med.1998;32:297-304.
PubMed

Figures

Tables

Table Graphic Jump LocationTable 1. Clinical Features of 56 Misdiagnosed Patients
Table Graphic Jump LocationTable 2. Risk Factors for Misdiagnosis*
Table Graphic Jump LocationTable 3. Three-Month and 12-Month Outcomes*

References

Mayberg MR, Batjer HH, Dacey R.  et al.  Guidelines for the management of aneurysmal subarachnoid hemorrhage.  Stroke.1994;25:2315-2328.
PubMed
van Gijn J, Rinkel GJ. Subarachnoid haemorrhage: diagnosis, causes and management.  Brain.2001;124:249-278.
PubMed
Adams HP, Jergenson DD, Kassell NF, Sahs AL. Pitfalls in the recognition of subarachnoid hemorrhage.  JAMA.1980;244:794-796.
PubMed
Mayer PL, Awad IA, Todor R.  et al.  Misdiagnosis of symptomatic cerebral aneurysm: prevalence and correlation with outcome at four institutions.  Stroke.1996;27:1558-1563.
PubMed
Vannemreddy P, Nanda A, Kelley R, Baskaya MK. Delayed diagnosis of intracranial aneurysms: confounding factors in clinical presentation and the influence of misdiagnosis on outcome.  South Med J.2001;94:1108-1111.
PubMed
Chan BS, Dorsch NW. Delayed diagnosis in subarachnoid haemorrhage.  Med J Aust.1991;154:509-511.
PubMed
Kassell NF, Kongable GL, Torner JC.  et al.  Delay in referral of patients with ruptured aneurysms to neurosurgical attention.  Stroke.1985;16:587-590.
PubMed
Schievink WI, van der Werf DJ, Hageman LM, Dreissen JJ. Referral pattern of patients with aneurysmal subarachnoid hemorrhage.  Surg Neurol.1988;29:367-371.
PubMed
Neil-Dwyer G, Lang D. "Brain attack" aneurysmal subarachnoid hemorrhage: death due to delayed diagnosis.  J R Coll Phys Lond.1997;31:49-52.
Fridriksson S, Hillman J, Landtblom AM, Boive J. Education of referring doctors about sudden onset headache in subarachnoid hemorrhage: a prospective study.  Acta Neurol Scand.2001;103:238-242.
PubMed
Edlow JA, Caplan LR. Avoiding pitfalls in the diagnosis of subarachnoid hemorrhage.  N Engl J Med.2000;342:29-36.
PubMed
Barton CW. Evaluation and treatment of headache patients in the emergency department: a survey.  Headache.1994;34:91-94.
PubMed
Karcz A, Holbrook J, Burke MC.  et al.  Massachusetts emergency medicine closed malpractice claims: 1988-1990.  Ann Emerg Med.1993;22:553-559.
PubMed
Hunt WE, Hess RM. Surgical risk as related to time of intervention in the repair of intracranial aneurysms.  J Neurosurg.1968;28:14-20.
PubMed
Hijdra A, van Gijn J, Nagelkerke NJ, Vermeulen M, van Crevel H. Prediction of delayed cerebral ischemia, rebleeding, and outcome after aneurysmal subarachnoid hemorrhage.  Stroke.1988;19:1250-1256.
PubMed
van Gijn J, Hijdra A, Wijdicks EF.  et al.  Acute hydrocephalus after aneurysmal subarachnoid hemorrhage.  J Neurosurg.1985;63:355-362.
PubMed
Claassen J, Carhuapoma JR, Kreiter KT, Du EY, Connolly ES, Mayer SA. Global cerebral edema after subarachnoid hemorrhage: frequency, predictors, and impact on outcome.  Stroke.2002;33:1225-1232.
PubMed
Van Swieten JC, Koudstaal PJ, Visser MC.  et al.  Interobserver agreement for the assessment of handicap in stroke patients.  Stroke.1988;19:604-607.
PubMed
Damiano AM. Sickness Impact Profile: User's Manual and Interpretation GuideBaltimore, Md: The Johns Hopkins University; 1996.
Ostapkovich N, Kreiter K, Peery S.  et al.  Are proxy ratings valid for assessing quality of life after subarachnoid hemorrhage?  Ann Neurol.2001;50:S78-S79.
Vermeulen M, van Gijn J. The diagnosis of subarachnoid haemorrhage.  J Neurol Neurosurg Psychiatry.1990;53:365-372.
PubMed
Schievink WI, Wijdicks EF, Parisi JE.  et al.  Sudden death from aneurysmal subarachnoid hemorrhage.  Neurology.1995;45:871-874.
PubMed
Broderick JP, Brott TG, Duldner JE, Tomsick T, Leach A. Initial and recurrent bleeding are the major causes of death following subarachnoid hemorrhage.  Stroke.1994;25:1342-1347.
PubMed
Mayer SA, Bernardini GL, Brust JCM, Solomon RA. Subarachnoid hemorrhage. In: Rowland LP, ed. Merritt's Textbook of Neurology. 10th ed. Baltimore, Md: Williams & Wilkins; 2000:260-267.
Morgenstern LB, Luna-Gonzales H, Huber Jr JC.  et al.  Worst headache and subarachnoid hemorrhage: prospective, modern computed tomography and spinal fluid analysis.  Ann Emerg Med.1998;32:297-304.
PubMed
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