Spontaneous Middle Cerebral Artery Reperfusion in Ischemic Stroke
A Follow-up Study With Transcranial Doppler
Background and Purpose The aim of this study was to investigate by means of transcranial Doppler (TCD) ultrasonography how many spontaneous reperfusions of the middle cerebral artery (MCA) occurred during the first week after onset of acute ischemic stroke in the carotid territory.
Methods TCD examination, computed tomographic scan, and arterial digital angiography were performed in 56 patients with acute ischemic stroke within 6 hours of the onset of symptoms. The TCD examination was repeated within 24 hours, 48 hours, and 7 days after stroke; a further TCD examination was performed within 3 to 9 months in 27 patients.
Results At 6 hours, 33 patients presented abnormal TCD findings in the symptomatic MCA (16 “no flows” and 17 asymmetries). Of these, 4 patients (3 no flows and 1 asymmetry) died before the 7-day follow-up was completed, whereas of the 29 remaining patients undergoing all the TCD control examinations, only 14 presented permanently abnormal TCD findings (7 asymmetries and 7 no flows). These data are consistent with an MCA reperfusion occurring at any level of the MCA, although most frequently in the distal part, and in the majority of cases during the first 48 hours. One patient who showed MCA asymmetrical flow velocity at the day-7 TCD examination was normal at the TCD follow-up at 3 to 9 months.
Conclusions TCD examination offers an easy and reliable way of monitoring MCA reopening and might be useful to identify subgroups of patients who may benefit most from pharmacological reperfusion.
The predominantly embolic origin of ischemic stroke is now an accepted concept; this opinion derives above all from the numerous observations of occlusions of intracranial arteries detected by angiography in the acute phase of stroke, which are no longer evident in subsequent angiographic or autoptic examinations.
Several single-case observations or studies on small series of patients seem to confirm this fact.1 2 3 4 5 In these studies, the first angiographic examination generally was performed 1 to 3 days after stroke and the second one at a time ranging from some days to some weeks. In recent years, following the introduction of thrombolytic therapy, a number of angiographic studies have been conducted before and after the infusion of recombinant tissue plasminogen activator to assess the reperfusion of previously occluded arteries. However, the angiographic follow-up of these cases was never performed later than 24 hours after the administration of therapy,6 7 even in the placebo-treated cases.8 So far, a longer follow-up using transcranial Doppler (TCD) ultrasonography has been conducted in studies of patients either treated9 or not treated10 with thrombolytic agents.
We report our experience regarding spontaneous reperfusion of the middle cerebral artery (MCA) observed by means of TCD during the first week after ischemic stroke. We also consider the type of arterial occlusion that was most frequently reopened and the timing of arterial reperfusion.
Subjects and Methods
Sixty-nine patients (35 men and 34 women; mean age, 65.9±9.4 years) presenting with an acute ischemic stroke in the carotid territory were considered in this study. This series of patients is part of a multimodal study of acute cerebral hemispheric ischemia.11 The following examinations were performed in all patients within 6 hours of the onset of symptoms: quantitative neurological evaluation by means of the Canadian Neurological Scale12 ; standard cerebral computed tomographic (CT) scan, repeated at 1 week; TCD examination, repeated at 24 hours, 48 hours, and 7 days after the onset of symptoms (27 patients underwent a further TCD examination 3 to 9 months after the stroke); and arterial digital angiography of the symptomatic carotid axis within 30 minutes of TCD, either by direct injection or through the humoral route with a nonionic water-soluble contrast medium. In 12 patients with an occlusion of the symptomatic internal carotid artery or carotid siphon, the contralateral carotid axis was explored as well to study the symptomatic territory via collateral pathways of the circle of Willis. MCA occlusions were classified in four categories13 : type I, MCA main-stem occlusion proximal to the origin of the lenticulostriate branches; type II, MCA occlusion distal to the lenticulostriate arteries but proximal to the temporal branches; type III, MCA occlusion distal to the origin of the temporal branches (more than three branches involved); and type IV, peripheral MCA branch occlusion.
The TCD examination was performed using TC 2-64 EME equipment with a 2-MHz probe. The anterior cerebral artery (ACA), the MCA, and the posterior cerebral artery (PCA) were explored through the temporal window,14 15 and the time-mean flow velocity of each artery was considered. Carotid compression was not performed on these patients, given the acute phase of their illness. TCD findings of the symptomatic MCA were classified as follows16 : (1) absence of any flow signal from the symptomatic MCA, when the ipsilateral ACA and/or PCA were detectable through the same acoustic window; (2) asymmetry of the MCAs, when the asymmetry index was below −21%, for lower velocity in the symptomatic one; and (3) normal MCA. During the follow-up period, a reopening of the symptomatic MCA was defined as a previously absent signal that reappeared, even if an asymmetry between the MCAs was still present, or when a previous MCA asymmetry was within the normal range. In addition, we also took into account an asymmetry index higher than +21% as an index of hyperperfusion. A collateral blood flow through pial anastomosis from the ipsilateral ACA and/or PCA to the symptomatic MCA territory was considered to be present when an asymmetry index higher than 27% for the ACA and 28% for the PCA was observed.
A clinical evaluation and, when indicated, transthoracic echocardiography were performed to look for potential embolic sources.17
A χ2 test was applied to correlate angiographic and 6-hour TCD findings.
The following data refer to 56 of the 69 enrolled patients (32 men and 24 women; mean age, 65.4±9.9 years), since the remaining 13 (19%; 3 men and 10 women; mean age, 68.0±6.5 years) did not have an adequate temporal acoustic window.
The TCD examination performed within 6 hours showed abnormal findings in 33 patients (59%): in 16 patients (29%) the symptomatic MCA was not detected, and in 17 (30%) an MCA asymmetry below −21% was found. All the patients with normal angiography (n=13) had normal TCD findings. The 4 patients with extracranial internal carotid artery occlusion showed either asymmetry (n=2) or had a normal TCD (n=2) on the ipsilateral MCA. Of the 11 patients with type IV MCA occlusion, 3 showed MCA asymmetry, whereas 8 had a normal TCD; 9 of the 10 cases of type III MCA were asymmetrical, whereas 1 presented an absence of MCA signal. Finally, of the 18 patients with siphon (n=4), type I (n=10), and type II (n=4) MCA occlusions, the MCA flow signal was absent in 15, whereas 3 showed MCA asymmetry (P<.001, χ2). Angiographic and TCD findings are synoptically shown in Table 1⇓.
The 7-day follow-up was completed in 48 patients, since 8 patients died during the first week. Of the 16 patients with an absence of the symptomatic MCA flow signal, 7 (44%) showed a reappearance of the artery signal at the times shown in Table 1⇑. In 6 of these patients, the reappeared MCA was initially asymmetrical; in 4 of these, the artery became symmetrical by the seventh day. Of the initially “asymmetrical” 15 cases of MCA occlusion, 10 (67%) became normal, whereas one patient with type III MCA occlusion showed no flow at the 48-hour control examination.
A symptomatic MCA higher than the contralateral one (asymmetry index >+21%) was detected at the 6-hour TCD examination in 3 patients with normal arterial digital angiography, with it persisting in one case throughout the 7-day follow-up. This phenomenon also occurred at 48 hours in 1 patient with type IV occlusion with a normal 6-hour TCD and at the 7-day examination in 2 patients (1 type II and 1 type IV MCA occlusion) who had shown a lower symptomatic MCA mean velocity at 6 hours.
All the patients who underwent the 3- to 9-month TCD examination showed the same findings as at the 7-day examination, except for 1 patient in whom there was no flow in the symptomatic MCA at 6 hours, asymmetry at 48 hours and at 7 days, and normal TCD results at this last examination.
At the first examination, possible TCD collateral pathways, either through the ipsilateral ACA (13 cases), PCA (6 cases), or both these arteries (2 cases), were observed in 21 patients with prevailing type II or type III MCA occlusion (n=14, 67%). These TCD collateral pathways tended to disappear in concomitance with MCA reperfusion.
The rate and percentage of reperfusion according to the site of arterial occlusion at angiography are summarized in Table 2⇑, which shows that the more distal the occlusion, the higher the frequency of reperfusions.
Four patients underwent a second arterial digital angiography, which confirmed the TCD results: reperfusion in 2 patients with type II and 1 with type III MCA occlusion and nonreperfusion in 1 patient with type I MCA occlusion.
This study confirms the good correlation between TCD and angiographic data that had already been found in a previous study.16 A proximal MCA occlusion is indicated by the absence of the MCA flow signal at TCD, and a more distal occlusion is reflected in an asymmetrical MCA flow velocity, whereas the occlusion of few MCA branches is only episodically detectable.10 16
During the first week after stroke, the main-stem MCA occlusion spontaneously disappeared in 44% of cases, whereas the distal MCA occlusion was no longer present in 67% of patients. In 86% of reperfused patients with a main-stem MCA occlusion, the reopening of the artery was initially characterized by a phase of asymmetrical MCA flow velocity, with lower values in the symptomatic MCA. This data may be interpreted as a migration and a more distal location of the clot, or of its fragments, occluding the vessel lumen. The occurrence of this phenomenon was demonstrated by angiographic studies on spontaneous reperfusion of intracranial arterial occlusions.1 3 18
The reappearance of a previously absent MCA or the disappearance of the MCA asymmetry occurred in 41% of patients at 24 hours, in 47% of patients at 48 hours, and in the remaining 12% of patients at 7 days. The time-related changes in the TCD pattern observed in our study are similar to those reported in studies that used cerebral blood flow techniques19 20 or TCD.9 10
In our series, the spontaneous reperfusion seemed to show a proximal to distal gradient of frequency, ie, the more distal the occlusion, the higher the frequency of reperfusion. Interestingly, distal MCA occlusions are the ones that seem to benefit most from thrombolytic treatment.6 7 21
Regarding carotid siphon occlusions, it is worth noting that only those located in the supraclinoid tract reopened, as opposed to those located in the intracavernous tract, which did not. Pathological studies suggest that this may be due to the fact that supraclinoid tract occlusions are more frequently of embolic origin.22
The MCA reperfusion was also less frequent (33%) in cases of tandem occlusion, a finding that was also observed in patients undergoing thrombolysis.7 This might be explained by the fact that the embolic material, presumably of arterial origin, was probably less prone to lysis. This hypothesis comes from the observation that nonreperfusion was more frequent among the patients who had an exclusively carotid source (57%) compared with patients with an exclusively cardiac source (22%) or those with both sources possible (14%) or not identified (7%). Furthermore, according to Ringelstein et al,9 we could also hypothesize that the presence of good collateral circulation might be decisive insofar as it allows the intravascular clot to be washed out by the intrinsic thrombolytic system.7 23 In fact, in 1 of the 2 tandem occlusion patients who showed an MCA reopening, we detected an important leptomeningeal collateral pathway through the ipsilateral PCA throughout the first week, and collateral leptomeningeal pathways were inferred in 10 of the 15 remaining reperfused patients and in only 5 of the 14 nonreperfused ones. In our patients, TCD examination was never able to detect a flow signal through the distal branches of the occluded MCA, which could be supplied by angiographically detected collateral pathways, although this event has been described by other authors.24
We also mentioned the fact that some patients showed higher flow velocity in the symptomatic MCA. This relatively high velocity was neither detectable in confined tracts of the MCA nor accompanied by spectral abnormalities of the Doppler signal that might suggest the presence of MCA stenosis. Therefore, this phenomenon was probably due to reactive postischemic hyperemia, which in the 3 patients in whom it was present at 6 hours could indicate that reperfusion had occurred before admission to this study; both the CT scan and clinical outcome of these patients showed very mild cerebral damage.
Incidentally, we found that the reperfusion was not related to the occurrence of hemorrhagic infarction, since this event was observed in 7 reperfused and 6 nonreperfused patients, which is in agreement with the mechanisms of hemorrhagic infarction proposed in the literature.25 26
The possible distal migration of the embolus discussed earlier in this work implies that the location of the arterial occlusion may vary considerably during the first week, since an M1 tract occlusion may subsequently become an M2 and then an M3 or an M4 occlusion. Had we first studied our patients at 24 or 48 hours after stroke onset, many TCD findings would have been different from the 6-hour examination. This might explain why different series of patients, studied at different time intervals after stroke, show inconsistencies between the location of the occlusion and the site and size of the infarct.
In conclusion, our study suggests that TCD is a reliable means of monitoring the types of MCA occlusion that are most likely to reopen and the time in which this event takes place. It could therefore be of use in studies of pharmacological reperfusion to identify subgroups that may benefit most from the treatment.
We gratefully acknowledge Professor Cesare Fieschi and Professor Gian Luigi Lenzi for their criticism and suggestions in reviewing the manuscript and Dr Antonio Salerno and Dr Marco Solaro for their helpful assistance in collecting data.
- Received August 12, 1994.
- Revision received October 14, 1994.
- Accepted December 19, 1994.
- Copyright © 1995 by American Heart Association
Bladin PF. A radiologic and pathologic study of embolism of the internal carotid-middle cerebral arterial axis. Radiology. 1964;82: 615-624.
Fieschi C, Bozzao L. Transient embolic occlusion of the middle cerebral and internal arteries in cerebral apoplexy. J Neurol Neurosurg Psychiatry. 1969;32:236-240.
Zatz LM, Iannone AM, Eckmann PB, Hecker SP. Observation concerning intracerebral vascular occlusions. Neurology. 1965;15: 389-401.
del Zoppo GJ, Poeck K, Pessin MS, Wolpert SM, Furlan AJ, Ferbert A, Albert MJ, Zivin AJ, Wechsler L, Busse O, Greenlee R, Brass L, Mohr JP, Feldmann E, Hacke W, Kase CS, Biller J, Daryl G, Otis MS. Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke. Ann Neurol. 1992;32:78-86.
von Kummer R, Hacke W. Safety and efficacy of intravenous tissue plasminogen activator and heparin in acute middle cerebral artery stroke. Stroke. 1992;23:646-652.
Mori E, Yoneda Y. Early spontaneous recanalization of thromboembolic stroke. In: del Zoppo GJ, Mori E, Hacke W, eds. Thrombolytic Therapy in Acute Ischemia Stroke, II. Berlin/Heidelberg: Springer-Verlag; 1993:129-137.
Ringelstein EB, Biniek R, Weiller C, Ammeling B, Nolte PN, Thron A. Type and extent of hemispheric brain infarctions and clinical outcome in early and delayed middle cerebral artery recanalization. Neurology. 1992;42:289-298.
Kaps M, Damian MS, Teschendorf U, Dorndorf W. Transcranial Doppler ultrasound findings in middle cerebral artery occlusion. Stroke. 1990;21:532-537.
Cote R, Hachinski V, Shurvell BL, Norris JV, Wolfon C. The Canadian Neurological Scale: a preliminary study in acute stroke. Stroke. 1986;17:731-737.
Bozzao L, Bastianello S, Fantozzi LM, Angeloni U, Argentino C, Fieschi C. Correlation of angiographic and sequential CT findings in patients with evolving cerebral infarction. AJNR. 1989;10: 1215-1222.
Zanette EM, Fieschi C, Bozzao L, Roberti C, Toni D, Argentino C, Lenzi GL. Comparison of cerebral angiography and transcranial Doppler sonography in acute stroke. Stroke. 1989;20:899-903.
Kittner SJ, Sharkness CM, Price TR, Plotnick GD, Dambrosia JM, Wolf PA, Mohr JP, Hier DB, Kase CS, Tuhrim S. Infarcts with a cardiac source of embolism in the NINCDS Stroke Data Bank: historical features. Neurology. 1990;40:281-284.
Caplan L. Brain embolism, revisited. Neurology. 1993;43:1281-1287.
Olsen TS, Lassen NA. A dynamic concept of middle cerebral artery occlusion and cerebral infarction in the acute state based on interpreting severe hyperemia as a sign of embolic migration. Stroke. 1984;15:458-468.
Mori E, Yoneda Y, Tabuchi M, Yoshida T, Ohkawa S, Ohsumi Y, Kitano K, Tsutsumi A, Yamadori A. Intravenous recombinant tissue plasminogen activator in acute carotid artery territory stroke. Neurology. 1992;42:976-982.
Torvik A, Jörgensen L. Thrombotic and embolic occlusion of the carotid arteries in an autopsy material, I: prevalence, location and associated diseases. J Neurol Sci. 1964;1:24-29.
Ueda S, Fujitsu K, Inomori S, Kuwbara T. Thrombotic occlusion of the middle cerebral artery. Stroke. 1992;23:1761-1766.
Hennerici M, Rautenberg W, Schwartz A. Transcranial Doppler ultrasound for the assessment of intracranial arterial flow velocity, II: evaluation of intracranial arterial disease. Surg Neurol. 1987;27: 523-532.
Hornig CR, Bauer T, Simon C, Trittmacher S, Dorndorf W. Hemorrhagic transformation in cardioembolic cerebral infarction. Stroke. 1993;24:465-468.
Ogata J, Yutani C, Imakita M, Ishibashi-Ueda H, Saku Y, Minematsu K, Sawada T, Yamaguchi T. Hemorrhagic infarct of the brain without a reopening of the occluded arteries in cardioembolic stroke. Stroke. 1989;20:876-883.