European Journal of Vascular & Endovascular Surgery
Volume 25, Issue 1 , Pages 60-67, January 2003

Carotid surgery in acute symptomatic patients

This paper was presented at EJVS 2000 in London.

Departments of 1Vascular Surgery and Kidney Transplantation, 2Neurology and 3Institute of Diagnostic Radiology, Heinrich Heine University, Düsseldorf

Accepted 28 August 2002.

*Please address all correspondence to: R. Huber, Klinik für Gefäβchirurgie und Nierentransplantation, Heinrich Heine Universität, D-40225 Düsseldorf.

Article Outline

Abstract 

Objectives: evaluation of urgent carotid artery surgery with new diagnostic techniques and changing surgical considerations at a university hospital. Design, material and methods: prospective monitoring and assessment of outcome in 67 patients who underwent urgent carotid surgery because of symptomatic extracranial carotid artery involvement. Patients were examined via the stroke unit: duplex sonography was mandatory for diagnosis of extracranial carotid artery disease, as was proof of an open middle cerebral artery (MCA). Assessment of intracerebral damage followed CT or MR imaging procedures. Perioperative and surgical management was standardized. Neurological impairment was assessed pre-, postoperatively and at follow-up using the Rankin scale. “Urgent” was defined as “immediate” after the final diagnostic step had been performed. Results: within a period of 26 months 67 symptomatic patients (58% stroke, 42% TIA) underwent urgent carotid surgery. Median time from admission to surgery was 2 days. In all but five cases flow through the ICA could technically be restored (93%). Thirty-day mortality was 3% and disease-related morbidity 13%. The one and two year survival rates were 92 and 90%, respectively. No ipsilateral recurrent stroke occurred during follow-up. Conclusions: clinical decision-making based on stratified diagnostic workup by means of extra- and intracranial as well as intracerebral hemodynamics using new imaging techniques may select patients who will benefit more from urgent surgery than from conservative management.

Eur J Vasc Endovasc Surg 25, 60–67 (2003)

Keywords:  Cerebral ischemia, Stroke, Stroke unit, Diagnostic criteria, Internal carotid artery reconstruction, Urgent carotid surgery

 

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Introduction 

In the past vascular surgeons have been taught to avoid carotid artery surgery in acute stroke because of the high probability of intracranial bleeding leading to high perioperative mortality and morbidity.1, 2, 3, 4 Only recently have neurologists accepted indications for urgent carotid surgery.5, 6, 7, 8 based on new diagnostic techniques9, 10, 11, 12 and close clinical observation during care in the stroke unit.13, 14 The new and old aims are to prevent disabling or recurrent stroke. However, so far the indications for urgent reconstruction of the internal carotid artery (ICA) have not yet been defined precisely. Surgical safety measures and the diagnostic armentarium have changed substantially during recent years. By combining Doppler/duplex sonography, i.a. DSA and magnetic resonance imaging (MRI) techniques, patients with dangerous ICA occlusive disease but substantial tissue to rescue (i.e., the penumbra) can be identified. The results and assessment of this concept are presented in 67 prospectively followed cases.

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Material and methods 

Patients 

From the start of the neurological stroke unit (SU) at the University of Düsseldorf on 1 November, 1997 until 31 December, 1999, we prospectively monitored all patients who were diagnosed via the SU and transferred to our operating theatre for urgent carotid surgery. In close collaboration with neurologists, neuroradiologists, and vascular surgeons, consensus was arrived at on the basis of the following criteria for patient selection: (1) presence of symptomatic extracranial carotid disease; (2) patent ipsilateral middle cerebral artery (MCA); (3) acute stroke, recurrent stroke or recent TIA with crescendo symptoms or aggravation within the last 7 days but (4) remaining consciousness.

Patients who met the criteria retrospectively, but were not selected for carotid artery surgery by the neurologist and/or vascular surgeon on duty, were treated simply with body-weight-adapted heparin. They were followed up independently for the purpose of matched-pair controls.

A total of 67 patients underwent urgent carotid surgery after diagnostic work-up. These patients constituted 11% of all carotid artery operations (n = 584) performed at our department during this time period. The overall number of reconstructions performed was 70 because three patients had bilateral surgery during the same anesthesia. General characteristics of patients, demographic data, possible risk factors and co-morbidities as well as diagnostic data and reconstructive techniques applied15 are shown in Table 1.

Table 1. General patient characteristics.
Demographic data
Patients (n)67
Men (n)47 (70%)
Women (n)20 (30%)
Age–median (range) (y)65 (36–84)
Risk factors/co-morbidity
Hypertension (systolic pressure on admissions ≥160 and/or diastolic pressure ≥100mmHg)57 (92%)
Smoking (more than 1 cigarette/day and longer than 1 year)48 (77%)
Coronary heart disease (myocardial infarction, angina, congestive heart failure, valvular heart disease, atrial fibrillation)41 (66%)
Diabetes70 (27%)
Diagnostic procedures
Doppler/duplex67 (100%)
i.a. DSA28 (42%)
MRA/MRI48 (72%)
Old lesions5 (10%)
PWI/DWI mismatch33 (69%)
No DWI lesions10 (21%)
Vascular characteristics
Ipsilateral ICA
Occlusion22 (33%)
Stenosis ≥70%40 (60%)
Pseudo-occlusion5 (7%)
ICA contralateral
Normal42 (63%)
Occlusion13 (19%)
Stenosis ≥70%12 (18%)
Clinical presentation
Stroke:39 (58%)
Stable11 (16%)
Stuttering11 (16%)
Progressive10 (15%)
Stroke following TIA7 (10%)
TIA:28 (42%)
Crescendo TIA24 (36%)
TIA (critical findings)4 (6%)
Operationsin total 70 (100%)
CEA, vein patch closure55 (82%)
Eversion CEA155 (7%)
Vein graft interposition2 (3%)
No reconstruction5 (7%)
Additional thrombectomy14 (21%)
Bilateral reconstruction3 (4%)

Preoperative clinical findings were stroke in 39 patients (58%) and TIA in 28 patients (42%) (Table 1). Stroke with a stable neurological deficit occurred in 11 patients (16%), stroke with stuttering symptoms in 11 patients (16%) and progressive stroke in 10 patients (15%), and seven patients (10%) had developed stroke subsequent to TIA. Crescendo TIA was present in 24 patients (36%). In three patients with TIA, angiographic findings were critical: a small, mobile thrombus in one patient, subtotal carotid artery stenosis in the second and high-grade carotid artery stenosis on both sides in the third. In one case progression from stenosis to carotid occlusion was found accidentally by duplex sonography within 12 h after the acute symptomatology, but without new clinical symptoms.

Median time between admittance to our university and operation was 2 days and ranged from 0 to 18 days, depending on the stability of the patient or progression of clinical symptoms and embolisation from or progression of the occlusive lesion.

Diagnostic procedures 

Diagnosis of high-grade (≥70%) stenosis or acute occlusion was established by means of Doppler and duplex sonography. Magnetic resonance arteriography (MRA) and/or i.a. DSA was additionally performed in cases of multivessel involvement, suspicion of pseudo-occlusion, contralateral occlusive disease of the distal ICA and in cases with inconclusive non-invasive findings. A patent MCA had to be documented by transcranial Doppler (TCD), MR arteriography (Fig. 1a), or i.a. DSA (Table 1).

  • View full-size image.
  • Fig. 1. 

    Acute MCA infarction: (a) MRA: preoperative missing perfusion in ICA and severely reduced perfusion in left MCA (left) and postoperative normal MRA (right). (b) MRI: severe PWI/DWI mismatch in acute left carotid artery occlusion 5 h after stroke onset: small DWI lesion in left insular cortex, surrounded of a large area of severely delayed perfusion in the entire MCA territory, normal perfusion in basal ganglia and thalamus.

MRI procedures were used to quantify acute reversible and irreversible ischemic brain damage.9, 10, 11, 12 For assessment of actual brain tissue damage, CT or, whenever possible, MRI with diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) was performed (Fig. 1b). By means of color-coded PWI the cerebral area of critical ischemia was visualized. As shown earlier, a time-to-peak delay in perfusion imaging of greater than 4 s compared to the contralateral hemisphere had to be considered “tissue at risk”.9, 12 Because quantitative lesion volumetry as detailed by WITTSACK16 is time consuming and not always available outside normal working hours, it was only performed in selected cases: volumetric analysis was performed only on DWI and time-topeak (TTP) PWI maps. A semiautomatic segmentation technique was used for tracing manually defined regions in the contralesional hemisphere. The average value of these reference region-of-interest signal intensities served as the control. Lesion volumes in DWI were determined by using a threshold of 20% of the signal intensity above the control. The resulting 20 lesion volumes were then compared with the volume of the infarction at day 8. This latter volume was determined manually by tracing the edge of the hyperintense area on T2-weighted MR images.

Impairment was assessed clinically following the RANKIN impairment scale,17 the BARTHEL index18 and the European Stroke Scale (ESS)19 before transfer to the operating theatre, 8 days after surgery, and during follow-up.

Perioperative management 

Surgery was performed under general anesthesia and was standardized with early clamping of the common carotid artery before dissection of the bifurcation and the distal ICA. On the basis of earlier studies, shunting was applied routinely because patients who had experienced a previous stroke or showed CT findings positive for stroke (regardless the hemisphere involved) tended to have a better outcome with shunting.20 Patients were placed on heparin in the SU, and heparin therapy was maintained during surgery and continued with a low dosage afterwards, followed by aspirin 100 mg daily.

Statistics 

Quantitative lesion volumetry16 was compared in eight patients who were matched for gender, age and neurological scale (ESS)19 with patients who were managed by anticoagulation with heparin alone. Survival rates were calculated using the Kaplan–Meier method. Survival times were treated as censored observations if the respective patient was alive at the last follow-up (15 August, 2000). All statistics and graphics used below are descriptive and were prepared using the SPSS® statistical package.

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Results 

Flow through the ICA could technically be restored in 62 patients (93%). In five (7%) patients the carotid artery could not be reconstructed. Backflow after thrombectomy could not be achieved because thrombosis extended into the siphon.

The 30-day mortality was 3% (2/67). Death occurred in two patients with contralateral ICA occlusion; one of them died 2 days postoperatively, the other developed a secondary infarction with brain edema 5 days postoperatively and died 24 days later. Postoperative procedure-related morbidity concerning peripheral nerve lesions (n = 2) delayed wound healing (n = 2), and reoperation because of hematoma (n = 1) was 7%.

Postoperative neurological morbidity was 13% (9/67). Twenty-six (39%) patients remained free of symptoms. According to evaluation by the Rankin scale17 done on day 8 postoperatively, clinical disability improved or remained stable (Rankin ≤3) in 25 (37%) stroke patients. Sixteen (24%) patients remained severely disabled (Rankin 4,5) or deteriorated (Table 2).

Table 2. Outcome of carotid surgery in acute symptomatic patients.
Rankin postoperativeTotal
0123456
Rankin preoperative
026 2 28
11 1
2 71 8
3134311114
4 2 253 12
5 1 214
Total28126766267

Bold: Unchanged and postoperative RANKIN 0–3 (n = 51, 76%).

Italic: Deteriorated and RANKIN >3 (n = 16; 24%).

Three patients, in whom flow through the ICA could not be restored developed brain edema, which resolved spontaneously in two patients. In the third patient craniotomy was necessary for shifting of the midline. Of the total 67 patients only one patient had secondary intracerebral bleeding detected by CT scanning performed routinely, but without new clinical symptomatology.

The volume of the ischemic brain lesions had decreased in eight patients until day 8, as assessed by quantitative lesion volumetry16 compared to a different group of patients matched for gender, age and ESS19 who were managed by anticoagulation with heparin alone. Barthel index18 improved too, but similarly in the two groups (Table 3).

Table 3. Matched-pair selection for MRI lesion volumetry (gender, age, ESS).
GenderAgePreoperativePostoperative
ESS ScoreBarthel IndexMRI PWI 4s (ml)ESS ScoreBarthel IndexMRI T2 (ml)
Endarterectomy patients
Female476140978910027
Male658490152981004
Male71883075886017
Female68423042423026
Male74663539663575
Male534820659210010
Female6090100939010025
Female55574537775510
Median (range)63 (47–74)64 (42–90)38 (20–100)72 (37–152)89 (42–98)78 (30–100)21* (4–75)
Before heparinAfter heparin
Matched heparin treated patients
Female64828055909033
Male5868100299610031
Male75724543563541
Female5536101167125104
Male674710196917593
Male5030251529175165
Female6092854010010010
Female61391092866559
Median (range)61 (50–75)58 (30–92)35 (10–100)74 (29–196)88 (49–100)70 (25–100)50 (10–165)
*p < 0.05 compared with preoperative volume, Wilcoxon Rank test.

Median follow-up was 1.5 years; until 15 August, 2000 and was complete for all patients. During this time period all patients were on aspirin 100 mg/day. Five patients died after 39, 300, 314, 471, and 927 days, respectively. The causes of death were intracerebral bleeding on the contralateral side with ventricular rupture in one case, myocardial infarction in two cases, postoperative peritonitis after surgery for cancer in two patients. Survival after 1 or 2 years was 92 and 90%, respectively (Fig. 2).

All surviving patients live at their home. Five patients are dependent on help from their families. No further strokes or TIAs have occurred. Two patients developed grand mal seizures after stroke and are under anticonvulsive medication. One patient was reoperated on later for asymptomatic recurrent stenosis and has subsequently remained asymptomatic.

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Discussion 

The results of ECST21, 22 and NASCET6, 23 and the therapeutic demands of stroke units13, 14, 24 based on new imaging techniques have continually changed the general view of carotid surgery in acute symptomatic patients. Although some surgeons have always insisted that there is a place for this particular indication, there have been no guidelines and clear criteria defining the objectives under which a patient with acute stroke from occlusive carotid artery disease should, might, or should not undergo urgent reconstruction.

Morphological abnormalities of the ICA require technical skills in dealing with specific problems of carotid artery surgery, such as occlusive disease near the skull base, siphon involvement, loose thrombi not adherent to the vessel wall, continuous embolization, and even dissection. In our series flow through the ICA could technically be restored in 93%, in five patients surgery was unsuccessful because the ICA was found to be occluded at surgery even though preoperative arteriography indicated it was not. Three patients probably got worse as a result of the intraoperative thrombectomy maneuvers. None-theless outcome studies have shown better long-term results with the ICA remaining patent, resulting in a lower risk of stroke recurrence.25, 26, 27, 28 In our opinion, today acute occlusion of the ICA should always be removed if the probability of infarction or reinfarction during the spontaneous course of the disease is estimated to be extremely high.28, 29

A 30-day mortality of 3% and a morbidity of 13% (= aggravation of stroke symptoms) still remain higher than in 2262 patients that underwent elective carotid surgery at our hospital from 1990 to 199930 (30-day mortality 0.9%, morbidity 4.8%). These figures do not represent an argument against urgent carotid surgery, because during the spontaneous course of the disease early reinfarction rates (= onset of new stroke) of 1.2–9% have been reported.31 The major concern about urgent surgery was the possibility of intracranial hemorrhage, as long as the blood-brain barrier is not closed. Despite former reports1, 2, 3, 4 we have evidence that early carotid surgery is not associated with high intracerebral bleeding rates (1%) even during the first days after the stroke.

With the availability of MRI-derived assessment of structural and perfusion deficit, the decision for surgery is made on the basis of how much tissue is at risk and how much the patient might improve after removal of the perfusion deficit.

We assumed that cases in which the perfusion-deficit area (PWI) was significantly more extensive than the DWI lesion, reflecting the PWI/DWI mismatch area, would be ideal candidates for urgent carotid artery reconstruction, because the volume mismatch indicates critically hypoperfused tissue at risk for ischemic damage16, 32, 33 (Fig. 1b). Other reasons for aggressive treatment are the individual limitations of collateral circulation in acute infarction, both resulting in hemodynamic impairment within the territory of the ICA exposed, as well as the contralateral hemisphere in the case of bilateral ICA occlusion (Fig. 3).

  • View full-size image.
  • Fig. 3. 

    Effect of acute CEA in bilateral ICA occlusion as assessed in time-to-peak perfusion maps: (a) Preoperative severe deprivation of perfusion in ICA and MCA territory of both hemispheres (yellow) and total lack of perfusion in the right prefrontal cortex (red), normal perfusion in cerebellum and brainstem including both thalami (blue). (b) Virtually complete restoration of perfusion after CEA right side. Note persistent lack of perfusion in the infarcted right prefrontal cortex.

The new and sensitive MRI techniques show even more clearly than computed tomography that the distinct differentiation between TIA and stroke is only clinical: following MRI criteria, a TIA patient can easily have a brain infarction (Fig. 4); this renders carotid surgery even more urgent in patients with crescendo TIA and DWI lesions.
  • View full-size image.
  • Fig. 4. 

    (Clinical) TIA can be associated with (brain tissue) infarct. Lesion evolution in TIA patient 24 h after TIA: MRI correlates of TIA. Severe focal perfusion deficit (red arrows) 2 h after TIA onset. Restoration of perfusion after 24 h and manifestation of DWI lesion (red arrows).

From the patient's point of view, the result of surgery will always be classified clinically, but the perspective that restoration of blood flow in the carotid artery also restores cerebral perfusion, thereby salvaging brain tissue at risk, might be equally important and remains a challenging question. In eight patients in whom we were able to obtain pre- and postoperative MRI, a decrease in lesion volume and neurological improvement were evident, as assessed with the Barthel score of daily activities.18 When we compared these findings to a group of stroke patients matched for gender, age and neurologic status (ESS19) that were treated with heparin alone, we observed that the decrease in lesion volume was more favorable in patients undergoing restoration of carotid flow, whereas the Barthel index improved to the same extend in the two groups (Table 3).

During the spontaneous course of the disease reinfarction rates of 12%34 and a mortality of 19%35 within the first year after onset of symptoms have been reported. In our patients, reinfarction within the former symptomatic hemisphere related to the reconstructed ICA did not occur and the 1 and 2 year survival rates were 92 and 90%.

In conclusion, on the one hand, the criteria for patient selection in urgent carotid surgery will have to follow traditional aspects such as extracranial carotid artery involvement, minor clinical and intracerebral deficit, and whether the patient is conscious or not. On the other, the preservation of an open MCA, and the PWI/DWI mismatch reflecting the brain tissue at risk (i.e., penumbra) must also be reconsidered. Although in an expert stroke team the necessary information can be obtained within a few hours, even in a university hospital, the time frames are still long, as we have found that there is a median of 2 days from hospital admission until surgery. Recently, however, this time interval has shown a decrease.

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Acknowledgements 

The study was supported by grants from the Federal Government (Kompetenznetzwerk Schlaganfall) and the German Research Council (SFB 194). We are also grateful to H. Stuetzer, IMSIE University of Cologne, for help with the statistical analysis.

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References 

  1. Blaisdell WF, Clauss RH, Galbraith JG, Imparato AM, Wylie EJ. Joint study of extracranial carotid occlusion. IV. A review of surgical considerations. JAMA. 1969;209:1889–1895
  2. Bruetman ME, Fields WS, Crawford ES, DeBakey ME. Cerebral hemorrhage in carotid artery surgery. Arch Neurol. 1963;9:458–467
  3. Rob CG. Operations for acute completed stroke due to thrombosis of the internal carotid artery. Surgery. 1969;65:862–865
  4. Thompson JE, Austin DJ, Patman PD. Endarterectomy of the totally occluded internal carotid artery for stroke, results in 100 operations. Arch Surg. 1967;95:791–801
  5. Ballotta E, Da Giau G, Saladini M, Abbruzzese E, Renon L, Toniato A. Carotid endarterectomy with patch closure versus carotid eversion endarterectomy and reimplantation: a prospective randomized study. Surgery. 1999;125:271–279
  6. Gasecki AP, Ferguson GG, Eliasziw M, et al.  Early endarterectomy for severe carotid artery stenosis after nondisabling stroke: results from the North American Symptomatic Carotid Endarterectomy Trial. J Vasc Surg. 1994;27:288–295
  7. Parrino PE, Lovelock M, Shockey KS, King C, Tribble CG, Kron IL. Early carotid endarterectomy after stroke. Cardiovasc Surg. 2000;8:116–120
  8. Pritz MB. Timing of carotid endarterectomy after stroke. Stroke. 1997;28:2563–2567
  9. Neumann-Haefelin T, Wittsack HJ, Wenserski F, et al.  Diffusion- and perfusion weighted MRI. The DWI/PWI mismatch region in acute stroke. Stroke. 1999;30:1591–1597
  10. Schwamm LH, Koroshetz WI, Sorensen AG, et al.  Time course of lesion development in patients with acute stroke. Stroke. 1998;29:2268–2276
  11. Baird AE, Benfield A, Schlaug G, et al.  Enlargement of human cerebral ischemic lesion volumes measured by diffusion weighted magnetic resonance imaging. Ann Neurol. 1997;41:581–589
  12. Neumann-Haefelin T, Wittsack HJ, Fink GR, et al.  Diffusion- and perfusion weighted MRI. Influence of severe carotid artery stenosis on the DWI/PWI mismatch in acute stroke. Stroke. 2000;31:1311–1317
  13. Bath P, Butterworth RJ, Soo J, Kerr JE. The King's College Hospital Acute Stroke Unit. J R Coll Physicians London. 1996;30:13–17
  14. Futrell N, Millikan CH. Stroke is an emergency. Dis Mon. 1996;42:199–264
  15. Raithel D. Carotid eversion endarterectomy: a better technique than the standard operation?. Cardiovasc Surg. 1999;5:471–472
  16. Wittsack HJ, Ritzl A, Fink GR, et al.  Magnetic resonance imaging in acute stroke: DWI and PWI parameters predicting infarct size. Radiology. 2002;222:397–403
  17. Rankin J. Cerebral vascular accidents in patients over the age of 60. Prognosis. Scott Med J. 1957;2:200–215
  18. Mahoney FI, Barthel DW. Functional evaluation: the Barthel index. Md State Med J. 1965;14:61–65
  19. Hantson L, De Weerdt W, De Keyser J, et al.  The European stroke scale. Stroke. 1994;25:2215–2219
  20. Sandmann W, Willeke F, Kolvenbach R, Benecke R, Godehard E. Shunting and neuromonitoring: a prospective randomized study. In:  Greenhalgh RM editors. Surgery for stroke. London-Philadelphia-Toronto-Sydney-Tokyo: WB Saunders,; 1993;p. 287–296
  21. European Carotid Surgery Trialists' Collaborative Group . Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet. 1998;351:1379–1386
  22. European Carotid Surgery Trialists' Collaboratory Group . MRC European carotid surgery trial: interim results for symptomatic patients with severe (70-90%) or with mild (0-29%) carotid stenosis. Lancet. 1991;337:1235–1243
  23. North American Symptomatic Carotid Endarterectomy Trial Collaborators Group . Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med. 1991;325:445–453
  24. Hacke W, Kaste M, Olsen TS, Bogousslavsky J, Orgogozo JM. Acute treatment of ischemic stroke. Cerebrovasc Dis. 2000;10:22–33
  25. Kniemeyer HW, Aulich A, Schlachetzki F, Steinmetz H, Sandmann W. Pseudo- and segmental occlusion of the internal carotid artery: a new classification, surgical treatment and results. Eur J Vasc Endovasc Surg. 1996;12:310–320
  26. Barber PA, Davis SM, Darby DG, et al.  Absent middle cerebral artery flow predicts the presence and evolution of the ischemic penumbra. Neurology. 1999;52:1125–1132
  27. von Arbin M, Britton M, de Faire U. Mortality and recurrences during eight years following stroke. J Intern Med. 1992;231:43–48
  28. Hennerici M, Hulsbomer HB, Rautenberg W, Hefter H. Spontaneous history of asymptomatic internal carotid occlusion. Stroke. 1986;17:718–722
  29. Klijn CJM, Kappelle JK, van der Grond J, Algra A, Tulleken CAF, van Gijn J. Magnetic resonance techniques for the identification of patients with symptomatic carotidartery occlusion at high risk of cerebral ischemic events. Stroke. 2000;31:3001–3007
  30. Ommer A, Dziewanowski M, Pillny M, Huber R, Siebler M, Sandmann W. Langzeitergebnisse nach Carotisrekonstruktion im Defektstadium der cerebrovaskulären Verschluβkrankheit. Dtsch Med Wochenschr. 2002;127:370–375
  31. Sandercock P, Tangkanakul C. Very early prevention of stroke recurrence. Cerebrovasc Dis. 1997;7:10–15
  32. Astrup J, SiesjÖ BK, Symon L. Thresholds of cerebral ischemia: the ischemic penumbra. Stroke. 1981;12:723–725
  33. Lassen NA. Pathophysiology of brain ischemia as it relates to the therapy of acute ischemic stroke. Clin Neuropharmacol. 1990;13:S1
  34. Easton DJ. Epidemiology of stroke recurrence. Cerebrovasc Dis. 1997;7:2–4
  35. Dennis MS, Burn JPS, Sandercock PAG, Bamford JM, Wade DT, Warlow CP. Long term survival after first ever stroke: the oxfordshire community stroke project. Stroke. 1993;24:796–800

PII: S1078-5884(03)70187-7

doi:10.1053/ejvs.2002.1774

European Journal of Vascular & Endovascular Surgery
Volume 25, Issue 1 , Pages 60-67, January 2003

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