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Delayed Diagnosis of Intracranial Aneurysms: Confounding Factors in Clinical Presentation and the Influence of Misdiagnosis on Outcome.

ABSTRACT: The initial presentation of intracranial aneurysm can be missed in routine clinical practice. An underlying aneurysm may have a subtle presentation that warrants definitive diagnostic procedures. A retrospective review of 270 patients with aneurysms at our institution revealed 40 patients (14.8%) with a significant delay in diagnosis before definitive treatment. The delay due to missed diagnosis varied from 2 days to a few months. In retrospect, 58% had a Hunt and Hess grade I clinical presentation at readmission. Clinical status was rated as grade 0-I in the majority of patients (65%), grade II in 20%, and grade Ill in 12.5%. One patient had grade IV status. These grades are significantly different from the initial grade at which each of the patients first sought medical attention. The second admission significantly affected the outcome. A delay in diagnosis of aneurysmal subarachnoid hemorrhage resulting in poor clinical grade influenced neurologic outcome significantly.

ANEURYSMAL subarachnoid hemorrhage affects 28,000 people per year and is associated with death or permanent disability in nearly two thirds of patients. (1) Many patients with intracranial aneurysms have symptoms preceding the major rupture, (2,3) but the significance of these symptoms is often not recognized by medical personnel. (4) Recent neurosurgical improvements have reduced the mortality and morbidity of ruptured aneurysms. (5,6) The association between clinical status and outcome warrants vigilance on the part of the physician in the early diagnosis of aneurysms when only premonitory symptoms are present. A warning leak, if interpreted correctly to diagnose. aneurysmal subarachnoid hemorrhage, has significant potential to improve overall outcome. (7,8)

METHODS

A detailed chart review of 270 consecutive patients with intracranial aneurysms revealed that 44 patients self-treated, visited a medical practitioner, or sought emergency medical care for symptoms related to an aneurysm, without the discovery of the aneurysm. Four patients who had symptoms a year or more before the first diagnosis were not included. Among the 40 patients (14.8%) who had a delay in diagnosis, the following factors were analyzed: age, sex, clinical status according to the grading system of Hunt and Hess (9) at initial visit and at the time of definitive admission, size and location of aneurysm, delay in diagnosis, and score on the Glasgow Outcome Scale. (10)

The data are expressed as the mean +/- standard deviation. For comparison, the chi-square test was used, and P values less than .05 were considered to be statistically significant.

RESULTS

The majority of patients initiated their first visit and recalled the incident clearly. The symptoms they reported were strikingly similar in both the first and second episodes. There were 13 men and 27 women, with a mean age of 46 years (range, 11 to 66 years).

Initial Presentation

Initial clinical status was grade I in 17 patients and grade 0 in 23. Nearly 80% initially had severe headache associated with features of meningeal irritation as a predominant symptom (Table 1). The headache was most often characterized as unusual, severe, or sudden, and always featured additional symptoms such as nausea, vomiting, giddiness, diplopia, syncope, or neck stiffness. Each patient received symptomatic treatment and was sent home. In 50% of the cases, a working diagnosis of nonspecific headache was made (Table 2). In 5 cases (12.5%), computed tomography (CT) of the brain revealed no abnormalities.

Posterior Communicating Artery Aneurysm (n = 13)

Headache was the most common complaint in 11 (85%). Four patients self-treated their headache until the symptoms worsened. Nine patients were seen for aneurysm-related symptoms in a hospital or by a family physician. Two patients went to the emergency room but were sent home after symptomatic treatment; both patients returned with third nerve palsy and increased headache. The working diagnoses in seven patients included syncopal attack, meningitis, hypertension, nonspecific neck pain, stroke, and head injury. In two cases, a CT scan was negative at the time of initial presentation.

Anterior Communicating Artery Aneurysm (n = 11)

The leading complaint in nearly two thirds of these patients was headache. Two patients had blurring of vision associated with severe headaches. Severe neck pain in two patients was treated with cervical nerve blocks or muscle relaxants. One patient had adult-onset seizures, and another patient had had a head injury. Three patients self-treated their symptoms. In two patients, an initial CT scan showed no abnormalities.

Middle Cerebral Artery Aneurysm (n = 7)

Six of these patients had severe headache that was refractory and recurrent. Sinusitis and migraine-like headache were the diagnoses. One patient presented with seizures, and one patient presented with stroke. One of these seven patients had a CT scan that showed no abnormalities.

Basilar Artery Aneurysm (n = 3)

Two patients had severe neck pain. One patient was treated for cervical spondylosis by a chiropractor for 2 weeks and was then referred. A second patient had neck stiffness, diplopia, and headache; she was treated for meningitis. When a giant basilar aneurysm was diagnosed 10 months later, her clinical status was grade III. The third patient was sent home after symptomatic treatment for a severe headache and was readmitted 10 days later with a ruptured 8 mm aneurysm and grade III clinical status.

Ophthalmic Artery Aneurysm (n = 3)

Two of these patients were seen for refractory error. Both had significant impairment of vision at the time of diagnosis (aneurysms were 8 mm and 15 mm). The third patient had a 3-month history of seizures, and the diagnosis was established during workup for adult-onset seizures.

One patient with superior hypophyseal artery aneurysm self-treated her severe headache for 5 days. At presentation after rupture of the aneurysm, her clinical status was grade II.

Clinical Grade at Second Presentation

Hunt and Hess grade was worse at the time of second presentation (P < .0001). Sixty-five percent of patients returned in grade I, 20% in grade II, and 12.5% in grade III. One patient was in grade IV, which significantly influenced the outcome.

Delay in Presentation

Within the first week, 37.5% of the patients came back with recurrent symptoms; another 17% returned within 2 weeks (median 7 days). In 1 month, 77% returned with recurrent symptoms that provided a more overt picture of subarachnoid hemorrhage.

Location and Size of Aneurysm

The internal carotid artery was the most common location, accounting for 42.5% of aneurysms (3 on the ophthalmic, 13 on the posterior communicating, and 1 on the superior hypophyseal artery). The anterior communicating artery was the site of 27% of the aneurysms, the middle cerebral artery 17.5%, and the basilar artery 7.5%. The mean size of these aneurysms was 11.8 [+ or -] 6.9 mm (range, 3 to 30 mm). Fifty-seven percent were less than 10 mm, and 15% had reached a size of 25 mm. Ten of the 40 patients (25%) had multiple aneurysms.

Outcome

After surgical treatment, 77.5% of the patients had a good outcome, 17.5% had moderate disability, and 5% were severely disabled (score of 3 on the Glasgow Outcome Scale). Multivariate analysis showed that the Hunt and Hess grade at the second admission significantly influenced the Glasgow Outcome Scale) (P < .006). Poor neurologic status and disability were directly proportional.

DISCUSSION

Unrecognized warning signs of a major aneurysm rupture have been reported to vary between 13.5% and 60%. (2,11-13) In the Danish Aneurysmal Study, 15% of patients had a history of warning leak. (5) Okawara (14) and Waga et al (15) reported an incidence of 48.2% and 58.8%, respectively. The incidence varies with awareness and availability of history in patients with a poor clinical grade and is difficult to establish; 17% of all patients with subarachnoid hemorrhage die before reaching the hospital. (16) The usual misdiagnoses include migraine, tension headaches, sinusitis, meningitis, and cervical spine disorder. (8,17,18) Hypertensive crisis and syncope were also recorded as working diagnoses in our patients.

Okawara (14) attributed 50% of warning signs to a minor leak. In all these cases, a lumbar puncture was positive, but a CT scan was not informative. Bassi et al (2) stated that every CT and lumbar puncture done in their study within 3 days and 1 week, respectively, was positive in the suspected cases. Seventy-five percent of this group presented with unusual or severe manifestations, but a diagnosis of impending aneurysmal subarachnoid hemorrhage was overlooked. (2) Drake (4) estimated a 70% occurrence of warning leak in his patients. A warning leak may be difficult to diagnose because headache is a common symptom; however, localized headache in association with symptoms such as nausea, vomiting, visual impairment, syncope, transient neurologic deficits, and transient loss of consciousness is observed in more than half of the patients. (2) A combination of neck pain and headache is highly significant and should be strongly considered a warning sign of an active aneurysm. (17) Five of our patients had neck sti ffness and received treatment for sprained neck, meningitis, and nonspecific pain. Two of them had basilar artery aneurysms, and one had poor outcome after treatment. Meningism of subarachnoid hemorrhage closely mimics meningitis, making the need for an accurate diagnosis crucial. (17) Sometimes the classical Kernig's sign is absent. Both decreasing vision and blurred vision with unilateral headaches represent warning signs of an underlying aneurysm of the ophthalmic or posterior communicating artery. Similar clinical features and misdiagnosis are reported by Bassi et al. (2) Okawara (14) described the signs of an expanding aneurysm indicating the growth and active nature of an aneurysm. The case reported by Day and Raskin, (19) in which both CT and lumbar puncture were negative but angiography showed an aneurysm, emphasizes the significance of clinical suspicion; this is similar to four of our cases. The relevance of pathogenesis of the warning signs cannot be overemphasized. If lumbar puncture shows no bloo d, the symptoms may be due to nonhemorrhagic causes. When a high index of clinical suspicion exists, noninvasive diagnostic methods such as magnetic resonance imaging and/or angiography, CT angiography, or real time Doppler duplex scan are possible options. The improving sensitivity of magnetic resonance imaging in this regard is encouraging, and routine practice of magnetic resonance angiography with clinical application may be recommended. (7)

The importance of early diagnosis and prompt treatment of aneurysms cannot be overemphasized in light of the differences in the outcome with worsening clinical grades. In a series by Yasui et al, (20) 44% of the 25 patients with known unruptured aneurysm and a later subarachnoid hemorrhage died. Many studies have confirmed a significant association between clinical grade and outcome. (6,21,22) The delayed diagnosis and its concomitant influence on the outcome is illustrated by our study (P < .01) and others. (2,7,8) Leblanc (8) reported a high mortality of 53%, compared with 0% mortality in the group that was treated promptly. Accurate diagnosis of a warning leak was estimated to have yielded a 2.8% increase in good outcome in the group of 34 patients analyzed by Jakobbson et al. (7) These authors applied the outcome figures of patients with good clinical grade and those with delayed diagnosis. However, even at the time of second presentation, there were patients with good clinical grades. By considering only the patients with grade II, III, and IV clinical status, reflecting the deterioration resulting from a missed diagnosis, the figures of good outcome could be achieved in 12 of 14 (85.7%). This means a reduction in poor outcome of 8.5% in the study population. Of the 6 patients with grade III and IV status, 5 could have had a good outcome, but 33% ended up with poor outcome. With these figures, extrapolated, the improved annual mortality and morbidity rate of subarachnoid hemorrhage in the United States would be significantiy different. Jakobsson et al(7) reported that 785 patients would be saved from death or disability by recognizing the importance of the premonitory signs of subarachnoid hemorrhage. With a 90% favorable outcome in our control group, an improved result of 12.5% can be estimated in the present study. This implies that with prompt diagnosis, about 600 people could be saved every year from the disabling outcome of aneurysmal subarachnoid hemorrhage.

The exact incidence of missed diagnosis of aneurysmal subarachnoid hemorrhage could be higher than reported.(7) Autopsy studies of sudden but explainable deaths or medical histories of patients with poor clinical grade are not usually available. Improved diagnostic ability reportedly improved hospital admissions for aneurysmal subarachnoid hemorrhage by 27% in the Danish population.(5) When there is a high index of clinical suspicion, judicious use of CT and lumbar puncture can improve the diagnostic yield,(23) and other noninvasive neuroimaging methods are certainly indicated in establishing the diagnosis. All investigations and neuro surical procedures that can potentially avert a disabling result from subarachnoid hemorrhage have a highly favorable cost-benefit ratio.(24) In this regard, improving the awareness of general physicians remains the best option.

References

(1.) Kassel NF, Drake CG: Timing of aneurysm surgery. Neurosurgery 1982; 10:514-519

(2.) Bassi P, Bandera R, Loiero M, et al: Warning signs in subarachnoid hemorrhage: a cooperative study. Acta Neurol Scand 1991; 84:277-281

(3.) Edner G, Kagstrom E, Wallstedt L: Total overall management and surgical outcome after aneurysmal subarachnoid hemorrhage in a defined population. Br J Neurosurg 1992;6:409-420

(4.) Drake CG: Management of cerebral aneurysms. Stroke 1981; 12:273-283

(5.) Rosenorn J, Eskesen V, Schimidt K, et al: Clinical features and outcome in 1076 patients with ruptured intracranial saccular aneurysms. a prospective consecutive study. Br J Neurosurg 1987; 1:33-46

(6.) Saveland H, Hillman J, Brandt L, et al: Overall outcome in aneurysmal subarachnoid hemorrhage. a prospective study from neurosurgical units in Sweden during a 1-year period. J Neurosurg 1992; 76:729-734

(7.) Jakobsson KE, Saveland H, Hillman J, et al: Warning leak and management outcome in aneurysmal subarachnoid hemorrhage. J Neurosurg 1996; 85:995-999

(8.) Leblanc R: The minor leak preceding subarachnoid hemorrhage. J Neurosurg 1987; 66:35-39

(9.) Hunt WE, Hess RM: Surgical risk related to time of intervention in the repair of intracranial aneurysms. J Neurosurg 1968; 28:14-20

(10.) Jennett B, Bond M: Assessment of outcome after severe brain damage. a practical scale. Lancet 1975; 1:480-484

(11.) Duffy GP: The warning leak in spontaneous subarachnoid hemorrhage. J Neurosurg 1987; 66:35-39

(12.) Juvela S: Minor leak before rupture of an intracranial aneurysm and subarachnoid hemorrhage of unknown etiology. Neurosurgery 1992; 30:7-11

(13.) Verweij RD, Wijdicks EF, Van Gijn J: Warning headache in aneurysmal subarachnoid hemorrhage. a case-control study. Arch Neurol 1988; 45:1019-1020

(14.) Okawara JH: Warning signs prior to rupture of an intracranial aneurysm. J Neurosurg 1973; 38:575-580

(15.) Waga S, Ohtsubo K, Handa H: Warning signs in intracranial aneurysms. Surg Neurol 1973; 3:15-20

(16.) Ljunggren B, Saveland H, Brandt L, et al: Early operation and overall outcome in aneurysmal subarachnoid hemorrhage. J Neurosurg 1985; 62:547-551

(17.) Dorsch NWC: Cerebral aneurysms and the "missed" hemorrhage. Aust NZ J Med 1986; 16:486-490

(18.) Shields CB: Current trends in management of cerebral aneurysms. J Ky Med Assoc 1977; 75:529-535

(19.) Day JW, Raskin NH: Thunderclap headache: symptoms of unruptured cerebral aneurysm. Lancet 1986; 2:1247-1248

(20.) Yasui N, Magarisawa S, Suzuki A, et al: Subarachnoid hemorrhage caused by previously diagnosed, previously unruptured intracranial aneurysms: a retrospective analysis of 25 cases. Neurosurgery 1996; 39:1096-1100

(21.) Kassel NF, Torner JC, Haley EC Jr, et al: The international cooperative study on the timing of aneurysm surgery. Part I. Overall management results. J Neurosurg 1990; 73:18-31

(22.) Gotoh O, Tamura A, Yasui N, et al: Glasgow coma scale in the prediction of outcome after early aneurysm surgery. Neurosurgery 1996; 39:19-24

(23.) Kopitnik TA, Samson DS: Management of subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry 1993; 56:947-959

(24.) PickardJD, Bailey S, Sanderson H, et al: Steps towards cost-benefit analysis of regional neurosurgical care. BMJ 1990; 301:629-635
TABLE 1. Symptoms at Initial Presentation

 No. (%)

Headache 31 (77.5)
Neck stiffness 6 (15.0)
Ocular complaints 5 (12.5)
Seizures 3 (7.5)
Decreased vision 2 (5.0)
Stroke 2 (5.0)
Syncope 1 (2.5)
Hypertension 1 (2.5)
TABLE 2. Working Diagnosis at First Presentation

 No. (%)

Nonspecific headache 20 (50.0)
Sinusitis 3 (7.5)
Neck pain 3 (7.5)
Seizures 3 (7.5)
Meningitis 2 (5.0)
Refractory error 2 (5.0)
Spondylosis 1 (2.5)
Hypertension 1 (2.5)
Syncope 1 (2.5)
Self treatment 4 (10.0)

Computed tomography of brain was negative in 5 patients (12.5%).


KEY POINTS

* Recognizing initial symptoms of aneurysmal subarachnoid hemorrhage is important.

* A delayed or missed diagnosis of aneurysmal subarachnoid hemorrhage is common.

* Findings on computed tomography are frequently ambiguous.
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Article Details
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Author:Baskaya, Mustafa K.
Publication:Southern Medical Journal
Article Type:Statistical Data Included
Geographic Code:1USA
Date:Nov 1, 2001
Words:2773
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