Carotid Dissection: Pathophysiology of Stroke and Treatment Implications
To the Editor:
The article by Lucas et al1 in the December 1998 issue of Stroke analyzed neuroradiological data in an attempt to provide a reasonable pathophysiological approach to the treatment of carotid artery dissection. It is suggested that documentation of an embolic etiology for ischemia and infarction would provide a reasonable background from which to use antithrombotic medication in an acute setting. On the other hand, a hemodynamic cause of ischemia or infarct could be considered refractory to the effects to agents such as standard heparin or its low-molecular-weight relatives.
Is the pathophysiology of cerebral infarction in carotid artery dissection fundamentally different from that occurring in carotid and middle cerebral artery stroke in general? Is the presence of cortical or subcortical ischemia in carotid artery dissection a fundamentally different pathoanatomic sequence than would occur in the more common ischemic thromboembolic stroke syndromes? If embolic events as well as hemodynamic factors cause brain injury in either condition, the fundamental answer to both questions must be “no.” Each initiates a cascade of ischemic injury and potential tissue destruction.
A number of authors have described the lack of benefit from heparin in acute or evolving/progressing stroke.2 3 Whether subcategories are present that may respond to acute heparinization is an ongoing area of interest, with specificity concerns similar to those considered for use of tissue plasminogen activator. Treatment response groups have not been defined to this point.
Neurologists have been unsure about the effects and use of heparin in acute stroke since the drug was introduced. Studies in the last 10 to 15 years have revealed heparin to be singularly unimpressive as a primary or ancillary treatment in acute stroke. Low-molecular-weight heparin trials have been disappointing, at best.4 The September 1994 American Heart Association guidelines for the treatment of acute and progressing stroke5 were ambiguous, not based on firm data for heparin benefits, but partly based on the legal concern for standard of care. Although ambiguity in these statements may help to diffuse inappropriate expert witness testimony against those who treat and those who don’t, as well as the good and bad outcome case, the guideline regarding heparin in acute stroke does not provide an accurate reflection of the data.
Considering the long and complex background of heparin use in acute and progressive stroke, the therapeutic implication in authors’ article is that treatment of carotid artery dissection rests on documentation of pathophysiology, not on the basic usefulness (or uselessness) of antithrombotic therapy in the acute stroke setting. This is misleading, and the position could be used to support treatment dogma when it does not exist.
Currently, the overwhelming weight of evidence rules against the role of heparin as a fundamental treatment in acute stroke. Response of carotid dissection to antithrombotic therapy remains equivocal. Low-molecular-weight heparin treatment in dissection has not been evaluated.
Emboli in the setting of acute carotid artery disease or dissection should not be compared with cardiac emboli when considering the effects of heparin. Emboli are not “created equal.” Therapeutic and management options should not be expanded by implication but instead need firm support from scientific studies.
The article’s conclusions regarding the relative contributions of embolism and hemodynamic factors are interesting and provoke thought regarding management options. The practicing neurologist may feel compelled to treat carotid artery dissection with heparin because of experts’ statements, based on insufficient data, combined with pathological implications, as suggested by the authors. A large, conclusive study may never be possible because of these general treatment recommendations. However, the determination that a particular method of treatment is valid or even reasonable does not automatically follow and should not be casually accepted in view of the potential for complications and the singular lack of supportive data.
There are those that will read more than what is written. Some “experts” are willing to suspend scientific analysis in court and testify that therapeutic options for the use of heparin are instead firm standards of care. Anecdotal experience and unsupported recommendations cannot overcome the extensive contrary evidence.
- Copyright © 1999 by American Heart Association
Lucas C, Moulin T, Deplanque D, Tatu L, Chavot D, and the DONALD Investigators. Stroke patterns of interval carotid artery dissection in 40 Patients. Stroke.. 1998;29:2646–2648.
Haley EC, Kassell NF, Torner JC. Failure of heparin to prevent progression in progressing ischemic infarction. Stroke.. 1988;19:10–14.
Sandercock P, van den Belt AG, Lindley RI, Slattery J. Antithrombotic therapy in acute ischemic stroke: an overview of the completed randomized trials. J Neurol Neurosurg Psychiatry.. 1993;56:17–25.
Adams HP, Brott TG, Crowell RM. Guidelines for the management of patients with acute ischemic stroke: a statement for healthcare professionals from a Special Writing Group of the Stroke Council, American Heart Association. Stroke.. 1994;25:1901–1914.
We totally agree with the first two thirds of Dr Bound’s letter, which are general considerations about the pathophysiology of ischemic stroke and the use of heparin at the acute stage. We also totally agree with the uncertainty of usefulness of heparin at the acute stage of ischemic stroke. As many other authors, we think that when possible, treatments should be given according to the rules of evidence-based medicine.
The author consider that artery-to-artery emboli and cardiac emboli are not “created equal.” Although we agree with this statement, this is just a widely accepted opinion without any proof. In many centers in Europe, most neurologists treat cervical artery dissections by heparin at the acute stage in patients with a low risk of hemorrhagic complication, although the benefit of such a potentially dangerous treatment has never been proved by a randomized trial. The reason to prescribe heparin is that most infarcts are of embolic origin in patients with cervical artery dissection.R1 From a theoretical point of view, heparin may lead to an increased size of the mural hematoma. However, in clinical practice this is not confirmed.
The low rate of recurrent strokeR2 makes any therapeutic trial in patients with cervical-artery dissection difficult. On the basis of a recurrent rate of disabling stroke or death of 2% a year,R2 the number of patients necessary for a clinical trial to detect a 50% reduction of disabling stroke or death with α and β risks of 0.05 and 0.20, respectively, would be about 5000. According to the prevalence of cervical artery dissections,R3 R4 there are approximatively 9000 cervical artery dissections per year in the European Union. These figures explain why drug trials will probably never be conducted in such disorder.
Biousse et alR5 found that in dissections of the extracranial internal carotid artery, completed stroke usually occurs during the first few days after onset of the dissection and sometimes occurs as long as 1 month later. This finding suggests that any potential preventive treatment should be initiated as soon as possible after the onset of the first symptoms but might also be worth initiating even 1 month later.R5 Concerning hemodynamic failure, which is sometimes incriminated in cervical artery dissections,R1 it may be prevented by strict bed rest during the first days, particularly when transcranial Doppler suggests a hemodynamic failure or when transient ischemic attacks occur when the patient is standing. All these arguments lead to the opinion that heparin is probably useful at the acute stage of cervical artery dissections despite the lack of scientific evidence, which will probably never be demonstrated in such a disorder because of its rarity in the community (2 cases per 100 000 persons a year)R3 R4 and the low rate of stroke recurrence (2% a year).R2
Lucas C, Moulin T, Deplanque D, Tatu L, Chavot D, and the DONALD Investigators. Stroke patterns of internal carotid artery dissection in 40 patients. Stroke.. 1998;29:2646–2648.
Leys D, Moulin T, Stojkovic T, Begey S, Chavot D, and the DONALD Investigators. Follow-up of patients with history of cervical artery dissection. Cerebrovasc Dis.. 1995;5:43–49.
Schievink WI, Mokri B, Whisnant JP. Internal carotid artery dissection in a community: Rochester, Minnesota, 1987–1992. Stroke.. 1993;24:1678–1680.
Giroud M, Fayolle H, André N, Dumas R, Becker F, Martin D, Baudoin N, Krause D. Incidence of internal carotid artery dissection in the community of Dijon. J Neurol Neurosurg Psychiatry.. 1994;57:1443. Letter.
Biousse V, D’Anglejan-Chatillon J, Touboul PJ, Amarenco P, Bousser MG. Time course of symptoms in extracranial carotid artery dissections: a series of 80 patients. Stroke.. 1995;26:235–239.