Home Outcomes-based Assessment of a New Reference Standard for Delayed Cerebral Ischemia Related to Vasospasm in Aneurysmal Subarachnoid Hemorrhage
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Outcomes-based Assessment of a New Reference Standard for Delayed Cerebral Ischemia Related to Vasospasm in Aneurysmal Subarachnoid Hemorrhage

Posted Aug 31, 2012 Updated Apr 10, 2023
By Pina C. Sanelli MD MPH , Nikesh Anumula MD , Rachel Gold DO , Elliott Elias MD , Carl Johnson MD , Joseph Comunale MD , Apostolos J. Tsiouris MD , Alan Z. Segal MD
9 min read

Rationale and Objectives

The purpose is to perform outcomes-based assessment of a new reference standard for delayed cerebral ischemia (DCI) related to vasospasm.

Materials and Methods

Retrospective study was performed with consecutive aneurysmal subarachnoid hemorrhage (A-SAH) patients between January 2002 and May 2009. A new reference standard for DCI was applied to the study population incorporating clinical and imaging criteria. Diagnostic accuracy was determined by chart diagnosis. Outcome measures for assessment included: permanent neurologic deficits, infarction, functional disability, treatment, and discharge status. Medical record review was performed by two blinded observers. Chi-square test calculated statistical significance between DCI and no DCI groups.

Results

A total of 137 patients were included; 59% (81/137) classified as DCI and 41% (56/137) as no DCI by the reference standard. Overall accuracy is 96% (95% confidence interval 92–99) with 100% sensitivity, 92% specificity, 94% positive and 100% negative predictive values. Patients classified as DCI had 40% (32/81) permanent neurologic deficits and 57% (46/81) infarction compared to 0% (0/56) classified as no DCI. DCI patients had 33% (27/81) functional disability compared to 13% (7/56) classified as no DCI. Ninety-four percent (76/81) DCI patients received treatment compared to 0% (0/56) classified as no DCI. DCI group had 46% (37/81) discharged to rehabilitation facilities and 11% (9/81) mortality compared to 25% (14/56) and 2% (1/56), respectively, in no DCI group. There are statistically significant differences ( P < .0001) between DCI and no DCI groups for all outcome measures.

Conclusion

This new reference standard has high diagnostic accuracy for DCI related to vasospasm. The outcomes-based assessment further supports its accuracy in correctly classifying A-SAH patients.

Aneurysmal subarachnoid hemorrhage (A-SAH) is a devastating condition resulting in significant morbidity and mortality . Delayed cerebral ischemia (DCI) is a serious complication of A-SAH further contributing to the poor clinical outcomes seen in this patient population with sequelae of permanent neurologic deficits, cerebral infarction, and death. The pathophysiology of DCI is complex often leading to delayed diagnosis and treatment. Early and accurate identification of DCI is necessary to initiate appropriate treatment in order to prevent functional disability and mortality. On the other hand, accurate classification of patients without DCI is also important to prevent unnecessary patient exposure to serious neurologic and systemic complications associated with its treatment. Thereby, critical assessment of the classification scheme and reference standard for DCI is essential in the management and treatment of A-SAH patients.

Recent consensus opinion from an expert panel recommended that clinical trials define DCI using outcome measures of neurologic function and cerebral infarction that are not attributed to other causes . For simplicity, the term vasospasm is reserved for the presence of arterial narrowing on imaging studies . However, DCI and vasospasm may be related with arterial narrowing resulting in reduced cerebral blood flow leading to clinical deterioration and ischemia. In the past, these terms have been considered interchangeable in clinical practice. The caveat is that not all patients with arterial narrowing on angiography develop DCI . Furthermore, not all patients who experience DCI have angiographic vasospasm, which may be partly attributed to circulatory impairment at the microvascular level. Thereby, incorporating both clinical and imaging criteria in the diagnosis of DCI has been reported as most clinically relevant because it has the strongest association with overall poor outcome, cognitive impairment, and reduced quality of life . Thus, efforts have been focused on developing methods to uniformly classify A-SAH patients in clinical trials investigating treatment strategies for DCI.

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Materials and methods

Study Population

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Study Design

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Figure 1, Flow chart for the new reference standard to determine delayed cerebral ischemia (DCI) related to vasospasm. A-SAH, aneurysmal subarachnoid hemorrhage.

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Outcomes-based Assessment

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Statistical Analysis

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Results

Study Population Characteristics

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Table 1

Clinical and Demographic Characteristics of the Study Population

All (n = 137) DCI (n = 81) No DCI (n = 56) Age (y) Median 52 52 52 Range 24–88 28–88 24–83 Gender Female 73% (100/137) 69% (56/81) 79% (44/56) Male 27% (37/137) 31% (25/81) 21% (12/56) Aneurysm location Anterior 93% (127/137) 94% (76/81) 91% (51/56) Posterior 7% (10/137) 6% (5/81) 9% (5/56) Aneurysm treatment Surgical clipping 54% (74/137) 57% (46/81) 50% (28/56) Coil embolization 42% (58/137) 38% (31/81) 48% (27/56) None 4% (5/137) 5% (4/81) 2% (1/56) Hunt and Hess classification Median 2 3 2 Range 1–5 1–5 1–4

DCI, delayed cerebral ischemia.

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Application of the Reference Standard Design

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Outcomes-based Assessment of the New Reference Standard

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Table 2

Clinical and Imaging Outcomes According to the Reference Standard Levels

Reference Standard Levels Neurologic Deficits Cerebral Infarction by Imaging Primary, classified as DCI (n = 57) 44% (25/57) 67% (38/57) Secondary, classified as DCI (n = 11) 64% (7/11) 73% (8/11) Secondary, classified as no DCI (n = 56) 0% (0/56) 0% (0/56) Tertiary, classified as DCI (n = 13) 0% (0/13) 0% (0/13) Total (n = 137) 23% (32/137) 34% (46/137)

DCI, delayed cerebral ischemia.

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Table 3

Functional Status According to the Reference Standard Levels

Reference Standard Levels Functional Status Returned to Baseline Yes No Unknown Primary, classified as DCI (n = 57) 39% (22/57) 37% (21/57) 25% (14/57) Secondary, classified as DCI (n = 11) 55% (6/11) 36% (4/11) 9% (1/11) Secondary, classified as no DCI (n = 56) 77% (43/56) 13% (7/56) 11% (6/56) Tertiary, classified as DCI (n = 13) 85% (11/13) 15% (2/13) 0% (0/13) Total (n = 137) 60% (82/137) 25% (34/137) 15% (21/137)

DCI, delayed cerebral ischemia.

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Table 4

Treatment Received According to the Reference Standard Levels

Reference Standard Levels Treatment HHH IA-therapy None Primary, classified as DCI (n = 57) 18% (10/57) 34% (46/57) 2% (1/57) Secondary, classified as DCI (n = 11) 64% (7/11) 0% (0/11) 36% (4/11) Secondary, classified as no DCI (n = 56) 0% (0/56) 0% (0/56) 100% (56/56) Tertiary, classified as DCI (n = 13) 100% (13/13) 0% (0/13) 0% (0/13) Total (n = 137) 22% (30/137) 34% (46/137) 45% (61/137)

DCI, delayed cerebral ischemia; HHH, hypertension, hypervolemia, and hemodilution; IA-therapy, intra-arterial therapy.

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Table 5

Discharge Status According to the Reference Standard Levels

Reference Standard Levels Discharge Status Home Acute Rehabilitation Long-term Nursing Facility Death Unknown Primary, classified as DCI (n = 57) 30% (17/57) 37% (21/57) 14% (8/57) 14% (8/57) 5% (3/57) Secondary, classified as DCI (n = 11) 36% (4/11) 18% (2/11) 18% (2/11) 9% (1/11) 18% (2/11) Secondary, classified as no DCI (n = 56) 68% (38/56) 18% (10/56) 7% (4/56) 2% (1/56) 5% (3/56) Tertiary, classified as DCI (n = 13) 69% (9/13) 23% (3/13) 8% (1/13) 0% (0/13) 0% (0/13) Total (n = 137) 50% (68/137) 26% (36/137) 11% (15/137) 7% (10/137) 6% (8/137)

DCI, delayed cerebral ischemia.

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Discussion

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Figure 2, A 35-year-old female presents with aneurysmal subarachnoid hemorrhage from a ruptured right middle cerebral artery bifurcation aneurysm. Patient presented as a Hunt and Hess grade 3 and developed symptoms of delayed cerebral ischemia (DCI) on day 7. Digital subtraction angiography was performed with anteroposterior views during injection of the right (a) and left (b) internal carotid arteries. There is severe vasospasm of the internal carotid, anterior, and middle cerebral arteries bilaterally ( arrows ). Patient received treatment with intra-arterial verapamil therapy. Follow-up noncontrast computed tomography (c) performed on day 18 shows no evidence of cerebral infarction.

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Figure 3, A 66-year-old female presents with aneurysmal subarachnoid hemorrhage from a ruptured left posterior communicating artery aneurysm. Patient presented as Hunt and Hess grade 4 and developed symptoms of vasospasm on day 10. Digital subtraction angiography was performed with anteroposterior (a) and lateral (b) views during injection of the left internal carotid artery. There is no evidence of cerebral vasospasm. Follow-up noncontrast computed tomography (c) performed on day 18 demonstrates acute infarction involving the left basal ganglia ( arrows ).

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Academic Radiology, Volume 19, Issue 9
Journals General Radiology
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