Leptomeningeal Enhancement and Extravasation of Contrast Medium into the CSF Space?
To the Editor:
Wilkinson et al1 describe the very interesting phenomenon of abnormal leptomeningeal enhancement in the territory of the middle cerebral artery after ipsilateral carotid stent insertion. In our view, Figures 1E⇓ and 1F⇓ of the above-mentioned article not only show leptomeningeal contrast enhancement but also indicate extravasation of contrast medium into the cerebrospinal fluid (CSF) space. The authors do not believe that a reaction of leptomeningeal vessels to the x-ray contrast medium (Optiray, Mallinckrodt Medical Ltd; dosage not mentioned) was a likely cause. The phenomenon of contrast medium extravasation into the CSF space following disrupture the blood-CSF barrier, however, has been observed by using CT2 and MRI.3 During the last 10 years we have found extravasation of contrast medium into the CSF space in 11 patients, who suffered from cardiovascular and cerebrovascular arteriosclerosis often associated with severe hypoxemic brain damage (Figures 1⇓ and 2).
We believe that a latent, regional alteration of the blood-brain barrier in patients with severe stenosis of the internal carotid artery might become obvious in terms of enhancement of the leptomeninges and the adjacent subarachnoid space under certain conditions: (1) repeated intra-arterial application of x-ray contrast media; (2) short periods of hypoxemia during angioplasty; and (3) in accordance with Wilkinson et al,1 an obviously temporary reperfusion phenomenon exists, the mechanism of which is not completely understood.
Enhancement of the ventricular system (Figure 2⇓) is a result of hypoxemic damage of the “tight junctions” between the cuboidal cells resting on the basement membrane of the choroid plexus.4 Enhancement of the subarachnoid space may result from alteration of the blood-brain barrier of cortical blood vessels via “sink action” or as a direct consequence of disruption of the tight capillary junction of the outer layer of the arachnoidea.4 Neurological and psychiatric symptoms can be expected in primarily parenchymal brain lesions. Despite the possibility of contrast medium diffusion into the extracellular space of the brain parenchyma, enhancement of the CSF space is rarely associated with clinical symptoms. This observation is supported by the paucity of side effects after intrathecal application of x-ray contrast media.
We are impressed by the regularity of leptomeningeal enhancement in MRI after carotid stenting, as shown by Wilkinson et al. The authors’ diagnostic strategy enables us to study asymptomatic forms of blood-brain barrier disruption for scientific purposes and in clinical practice.
- Copyright © 2000 by American Heart Association
Wilkinson ID, Griffiths PD, Hoggard N, Cleveland TJ, Gaines PA, Venables GS. Unilateral leptomeningeal enhancement after carotid stent insertion detected by magnetic resonance imaging. Stroke.. 2000;31:848–851.
Mamourian AC, Hoopes PJ, Lewis LD. Visualization of intravenously administered contrast material in the CSF on fluid-attenuated inversion-recovery MR images: an in vitro and animal-model investigation. AJNR Am J Neuroradiol.. 2000;21:105–111.
Sage MR. Kinetics of water-soluble contrast media in the central nervous system. AJR Am J Roentergenol.. 1983;141:815–824.
Response to the Preceding 2 Letters
We thank Drs Bretschneider and Strotzer and Drs Lu, Sun, and Huang for their interest in our recently published findings.R1
We agree with the interpretation of Drs Bretschneider and Strotzer that the images in our article (along with the other 10 cases from our study that demonstrated unilateral leptomeningeal enhancement) appear to show localized extravasation of MR contrast into the CSF space. In the discussion section we defined leptomeningeal enhancement as the abnormal accumulation of contrast media in the pia and/or the arachnoid mater. Intravenous contrast media are normally prevented from entering subarachnoid CSF by tight junctions within the endothelium of the capillaries in the outermost layers of the arachnoid.R2 However, once present within the arachnoid mater, water-soluble contrast media may be free to diffuse into the CSF. It is interesting that qualitative image interpretation does not reveal enhancement of the brain extracellular fluid itself, since it is known that water-soluble substances can freely diffuse from the brain into the CSF via the pia mater.R2 Quantitative studies are indicated to exclude the presence of subtle enhancement of brain parenchyma adjacent to areas of leptomeningeal enhancement.
As set out in the discussion section of our article, we also believe that a latent, regional alteration of the blood-brain barrier in patients with severe stenosis of the internal carotid artery might become obvious in terms of enhancement of the leptomeninges (including the adjacent subarachnoid space) under certain conditions. The administration of iodinated contrast medium may be one such condition. However, our data from 2 patients who had intra-arterial angiography with repeated contrast injections but did not undergo stent insertion and did not demonstrate leptomeningeal enhancement suggest that this is not the case. Our apologies for omitting the dosage of iodinated contrast used (Optiray, Malinckrodt Medical Ltd): 30 to 50 mL was injected directly into the internal carotid artery for the stenting procedure, and approximately 150 mL was applied into the aorta for an arch angiogram. As stated in our article, we believe that more control data would be needed to further limit the possibility that x-ray contrast is the causative agent that leads to the observed enhancement.
We are most interested in the observations of Drs Bretschneider and Strotzer of extravasation of contrast into the CSF space in 11 patients who suffered from cardiovascular or cerebrovascular atherosclerosis. In the context of carotid stenting at our institution, the suggestion that short periods of hypoxemia during angioplasty are responsible relates to 2 episodes of <15 seconds of balloon inflation. This would seem to be unlikely, in view of transcranial Doppler ultrasound findings, not specifically in these patients but in others, which show that the middle cerebral artery flow is usually maintained despite balloon occlusion. None of the patients undergoing procedures in our studyR1 showed changes in consciousness at the time of balloon inflation, which suggests that the degree of hypoxemia was minimal at the time of angioplasty. This really leaves us with what we believe to be the most likely explanation: reperfusion damage to the leptomeningeal vasculature which has been put at risk from long periods of low arterial input pressure brought about by severe atherosclerotic carotid stenosis.
Drs Lu, Sun, and Huang outline the case of a patient who demonstrated enhancement throughout the territory of the middle cerebral artery on x-ray CT after carotid stenting. In contrast to the patients in our study,R1 this patient suffered neurological deficit during the interventional procedure, although it is not clear whether this represented a transient ischemic attack or a completed stroke. This is a different scenario from the cases we previously reported.R1
Drs Lu, Sun, and Huang pose the question, “How long would this phenomenon last ?” Further investigation is needed to fully address this question. However, there is some published evidence: (1) in our study, fluid-attenuated inversion-recovery images obtained after intervention and after the administration of the second bolus of MR contrast showed stronger enhancement than those obtained after intervention but before the administration of the second bolus (on average, approximately 2 hours after stenting), and (2) the study by Gillard et alR3 did not show leptomeningeal enhancement 24 hours after endarterectomy. Of course, this second point is useful only if we assume that surgery can lead to the same observation.
We thank Drs Bretschneider and Strotzer and Drs Lu, Sun, and Huang for details of their experience and thought-provoking comments. We hope that our diagnostic strategy promotes a flurry of research activity which in turn leads to a better understanding of the blood-brain, blood-CSF, and perhaps CSF-brain barriers.
Wilkinson ID, Griffiths PD, Hoggard N, Cleveland TJ, Gaines PA, Vennables GS. Unilateral leptomeningeal enhancement after carotid stent insertion detected by magnetic resonance imaging. Stroke.. 2000;31:848–851.
Sage MR. Kinetics of water-soluble contrast media in the central nervous system. AJR Am J Roentgenol. 1982; 141:815–824.
Gillard JH, Hardingham CR, Kirkpatrick PJ, Antoun NM, Freer CEL, Griffiths PD. Evaluation of carotid endarterectomy with sequential MR perfusion imaging: a preliminary report. AJNR Am J Neuroradiol. 1998:19;1747–1752.