Time Course of Symptoms in Extracranial Carotid Artery Dissections
A Series of 80 Patients
Background and Purpose Cerebral infarction is the most frequent and severe manifestation of extracranial internal carotid artery dissection. However, few data exist on the precise time course of symptoms preceding the onset of stroke.
Methods We studied 80 consecutive patients (29 retrospectively, 51 prospectively) with angiographically diagnosed extracranial internal carotid artery dissection and, during a 6-month follow-up, recorded the time elapsed between the onset of the first symptoms and the onset of any ischemic event (transient ischemic attack or stroke). We compared patients with and without ischemic events, with and without completed stroke, and, among patients who had local signs at onset, those with and without subsequent ischemic events.
Results Cerebral or retinal infarction occurred in 42 patients. It was inaugural in 9 patients. In the 33 others, the time interval between the first symptoms (local signs and/or transient ischemic attacks) and the onset of stroke ranged from a few minutes to 31 days; it was ≤7 days in 82% of the patients. No significant difference in the baseline characteristics of the patients or in the angiographic pattern of dissection was found based on the presence or absence of ischemic signs or of completed stroke.
Conclusions In carotid artery dissections, completed stroke usually occurs in the first few days after the onset of the first symptoms, whether local or ischemic, but it can occur as much as 1 month later. This suggests that any potential preventive treatment should be initiated as early as possible after the onset of the first symptoms but might also be worth initiating even 1 month later.
Cerebral infarction is the most frequent and severe manifestation of extracranial internal carotid artery (ICA) dissection.1 2 3 4 5 6 7 8 9 10 11 Although sometimes inaugural, it is most often preceded by local symptoms such as head or neck pain, Horner’s syndrome, and tinnitus, which are the initial symptoms in up to 96% of cases3 ; this potentially allows early diagnosis and initiation of treatment before the occurrence of stroke. There is so far no treatment of proven efficacy: heparin is most widely used, but aspirin is sometimes favored, particularly in the absence of ischemic signs.1 4 Whatever treatment regimen is chosen, it is important to determine the temporal profile of the condition and, in particular, to estimate for how long after the first symptoms the patient is at risk of suffering an ischemic stroke. We therefore studied the time course of local and ischemic symptoms in a consecutive series of 80 patients with extracranial ICA dissection.
Subjects and Methods
Patients with extracranial ICA dissection examined from 1972 through 1984 (retrospectively from 1972 through 1984 and prospectively after 1984) were included in the study if they satisfied the following criteria: (1) angiographic diagnosis based on the classic signs of irregular stenosis (string sign), tapered occlusion beginning distal to the cervical bifurcation, and aneurysm1 2 4 (established by systematic review by two investigators who had to agree on angiogram interpretation); and (2) follow-up of at least 6 months.
Traumatic and spontaneous dissections were grouped together because of the well-known difficulty in determining whether a dissection is spontaneous or secondary to a minor or trivial trauma and because their clinical presentation does not significantly differ.1 5 7 In the present study, dissections were classified as traumatic when occurring after an obvious head or neck trauma, during sport activities involving the neck, or after unusual neck movements. Dissections were otherwise classified as spontaneous.
No uniform treatment was applied in the first (retrospective) part of the study, but heparin was systematically used as soon as the diagnosis was established in the prospective part of the study whether or not ischemic signs were present.
We recorded the baseline characteristics of the patients, including age, sex, history of hypertension, present or past use of oral contraceptives, history of migraine, and the angiographic pattern of the dissection. We recorded all ischemic events that occurred in the 6 months after the dissection.
We first compared patients with and without ischemic events (transient or permanent); second, those with and without completed stroke (cerebral or retinal infarction); and third, patients with local signs at onset with or without subsequent ischemic events. These groups were compared using the χ2 test for proportion.
Eighty patients were included in the study (35 women, 45 men; age range, 14 to 67 years), 29 in the retrospective part and 51 in the prospective. Six patients had bilateral extracranial ICA dissection, and 4 had associated extracranial vertebral artery dissection, which was unilateral in 3 and bilateral in 1. Early treatment consisted of heparin in 58 patients (53 with ischemic signs), aspirin in 15, and surgery in 1. Six patients with purely local signs who were examined in the early years of the study received no treatment.
Ischemic events occurred in 66 patients (82.5%). These events were more frequently observed in the early (27/29) than in the late (42/53) part of the study. They were purely transient in 24 subjects (36.5%), but a completed stroke occurred in 42 subjects (63.5%). Baseline characteristics of the patients and angiographic patterns of dissections according to the presence or absence of ischemic events, or of completed stroke, are shown in Tables 1⇓ and 2⇓. There were no significant differences between these groups.
Inaugural symptoms were local in 53 patients (isolated head or neck pain in 31, painful Horner’s syndrome in 15, tinnitus in 7 [with pain in 3]) and ischemic in 27 (completed stroke in 9, transient ischemic attack [TIA] in 18) (Fig 1⇓). Among the 53 patients with local symptoms, 39 (73.5%) later had ischemic events (TIAs in 23, completed stroke in 16). Characteristics of the patients and the dissection according to the presence or absence of ischemic events are shown in Table 3⇓. There was no difference between these two groups.
Time Course of Symptoms
No apparent difference was found in the time course of symptoms between the retrospective and the prospective part of the study. Results concerning the two parts of the study were therefore grouped (Fig 1⇑).
Nine patients had a completed stroke at onset; 1 patient with a bilateral extracranial ICA dissection and suffering from Ehlers-Danlos syndrome experienced recurrent strokes that occurred 52, 68, and 81 days, respectively, after the first completed stroke.
Eighteen patients had TIAs as presenting symptoms (10 amaurosis fugax, 8 cerebral TIAs). Eight of them experienced a single TIA, 6 had two TIAs, and 4 had three TIAs. The time interval between the first and last TIA ranged from 2 hours to 27 days (6±9 days). Ten patients with TIA as an inaugural symptom later had a completed stroke that occurred from 6 hours to 31 days after the first TIA (mean, 5.7±9 days). Among the 53 patients with local symptoms at onset of ICA dissection, 23 later had TIAs, which occurred from a few minutes to 66 days (10.5±13.5 days) after onset, and 16 had a completed stroke occurring from 2 hours to 16 days after the onset of local symptoms. Among the 23 TIA patients, 11 had recurrent TIAs, with the time interval between the first and last TIA being 2 hours to 45 days (8±13.1 days) and the number of TIAs ranging from one to six. Seven of the 23 patients who presented with local signs followed by TIAs had a completed stroke that occurred from a few minutes to 10 days (mean, 3.8±3.8 days) after the first TIA and from 1 hour to 31 days (9.2±10 days) after the onset of local symptoms. In this group of 53 patients with local symptoms at onset, 14 had no ischemic sign (2 in the retrospective part of the study, 12 in the prospective): 11 had isolated painful Horner’s syndrome, 1 had Horner’s syndrome with tinnitus, and 2 had isolated head and cervical pain.12
Among the 42 patients who had a completed stroke (Fig 1⇑), this was preceded by other symptoms in 33: purely local signs in 16 and TIAs in 7. The time interval between the inaugural symptom and the onset of stroke is represented in Fig 2⇓: it ranged from a few minutes to 31 days, with the majority of strokes (82%) occurring in the first 7 days.
The time course of symptoms in the 16 patients with traumatic ICA dissection was as follows: the time elapsed between the trauma and the first symptom ranged from 0 to 15 days (2.3±4 days), and the time between the trauma and TIA and/or completed stroke (n=14) ranged from 0 to 31 days (4.8±8.4 days).
In the present study of 80 extracranial ICA dissections, completed stroke occurred in 42 patients, most often (88%) during the first 7 days after onset of symptoms. No difference was found in the characteristics of the patients or the dissection between those with an ischemic stroke and those without.
The overall frequency of ischemic events (TIAs and completed strokes) was 82.5%, which is in accordance with the 50% to 95% rates seen in other series (Table 4⇓). However, the frequency in our series is possibly overestimated because, in the early years, the diagnosis was suspected mainly in the presence of ischemic events, and noninvasive screening was not available. Ischemic signs were thus more frequent in the early part (93%) of the study than in the late part (77%). This difference in the frequency of ischemic events will be important to consider when planning future therapeutic trials, but it should not interfere with the time course of ischemic signs.
All but 7 of our patients received some form of antithrombotic treatment (heparin in 58 and aspirin in 15), which might have altered the course of the disease. The present study is thus not a study of the natural history of extracranial ICA dissection, which would have been ethically difficult to justify given the frequency of ischemic signs and the documented importance of thromboembolism in their pathogenesis.1 7 9 The present study is not a therapeutic trial either, and no firm conclusion can be drawn about the efficacy of treatments. It can only be said that heparin did not prevent all infarcts since, among the 5 patients who experienced stroke more than 2 weeks after the onset of the first symptoms, 4 were treated with heparin when these strokes occurred. The time course of symptoms as recorded in this study is thus mostly that of patients receiving antithrombotic treatment in the form of heparin or aspirin.
Forty-two patients experienced a completed stroke. Of these patients, 33 had previous symptoms, local and/or TIAs, that preceded the onset of stroke by a few minutes to 31 days (Figs 1⇑ and 2⇑). Most strokes (82%) occurred in the first week after the first symptoms appeared, which is in agreement with previous reports1 2 3 4 5 6 7 8 9 10 and implies that any potential preventive treatment should be started as early as possible. It is, however, important to note that five strokes occurred as late as 3 or 4 weeks after onset of the first symptoms. The longest interval was 31 days, regardless of the pattern of inaugural symptoms, local signs, or TIAs and whether the dissection was considered traumatic or spontaneous. This late occurrence suggests that it might be worth initiating treatment even as much as 1 month after the onset of symptoms. Stroke recurrence was observed in only one case, a patient with Ehlers-Danlos syndrome who had bilateral ICA dissections and experienced three recurrent strokes from 52 to 81 days after the initial stroke. Such recurrences would support prolonged treatment, at least in patients with underlying arterial disease.13 Ischemic events have been reported years after traumatic dissections in retrospective series5 and weeks after spontaneous vertebral artery dissections,14 but such late strokes are extremely rare. This issue was not addressed in the present study, in which follow-up was limited to the first 6 months.
TIAs occurred in 41 patients: as inaugural symptoms in 18 and following local signs in 23. Most occurred in the first few days, but in contrast to completed strokes, they were often recurrent (50%), and in 2 patients they recurred after the first month (45 and 66 days). The mechanism of these late TIAs might be hemodynamic, since both patients had a persisting carotid occlusion. Such patients with TIAs occurring up to 5 months later were also reported by Fisher3 in his series of 26 patients. Despite these late TIAs, no completed strokes occurred in Fisher’s patients or in our 2 patients.
Given the prognostic importance of ischemic strokes in ICA dissections, we compared some of the characteristics of the patients and of the dissections in patients with or without ischemic events. No difference could be found as far as age, sex, presence of hypertension, use of oral contraceptives, history of migraine, or angiographic pattern of the dissection (stenosis, aneurysm, or occlusion) were concerned. We were thus unable to identify clinical or angiographic features predictive of stroke associated with ICA dissection. These negative results, however, should be interpreted cautiously because of the small numbers of patients in each group and the absence of other similar studies. Large prospective studies are needed to clarify this important issue.
In conclusion, the risk of ischemic stroke in ICA dissection remains unpredictable. Stroke usually occurs in the first few days but can occur up to 1 month later. This suggests that any potential preventive treatment should be initiated as early as possible after the onset of the first symptoms and might be worth initiating even as much as 1 month later.
Review of this manuscript was directed by Editor-in-Chief Mark L. Dyken.
- Received June 27, 1994.
- Revision received November 18, 1994.
- Accepted November 19, 1994.
- Copyright © 1995 by American Heart Association
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