Symptomatic Middle Cerebral Artery Stenosis R. C . Hinton, M D , J. P. Mohr, M D , R. H. Ackerman, MD, L. B. Adair, MD, and C. M. Fisher, MD
The clinical course of 16 consecutive patients with stenosis of the middle cerebral artery angiographically diagnosed between 1970 and 1977 was reviewed. All were managed nonsurgically with medical treatment including anticoagulation. Prior to therapy, transient ischemic attacks had occurred in 15 and cerebral infarction in 1 1 . Initially, none exhibited more than a minor neurological deficit. Follow-up from one month to six years showed a benign course in 14 patients: 13 experienced no subsequent transient attacks or new stroke; 1 had repeated transient attacks for two years but not in the following four years. Two of t h e 16 developed a severe stroke early in the course, before medical therapy was started. No distinctive clinical or radiographic features were identified that permitted prediction of the outcome. This small series supports the need for a randomized study of bypass efficacy in these patients. Hinton RC, Mohr JP, Ackerman RH, et al: Symptomatic middle cerebrai artery stenosis. Ann Neurol 5:152-157, 1979
Middle cerebral artery stenosis associated with atherosclerosis is a much less common cause of symptomatic ischemia than is middle cerebral embolism 11, 5, 7, 9-11]. Stenosis is important in that it often presents as transient ischemic attacks and provides an opportunity for therapeutic intervention before total occlusion and severe stroke occur. Patients with stenosis also provide information regarding the interrelation between hemodynamic factors and ischemic symptoms. T h e present review of 16 medically managed patients with symptomatic stenosis of the middle cerebral artery encountered at o u r institution between 1970 and 1977 has been prompted by recent innovations in the surgical management of cerebral arterial stenoses. T h e favorable outcome in this group points u p the need for a randomized study of surgical versus medical therapy for patients with intracranial stenosis, an investigation that is currently underway.
teriogram: site of stenosis, degree of stenosis, evidence of local thrombus formation, abnormality of flow distal to the stenosis, position of the border zone between the middle and anterior and middle and posterior cerebral territories, and evidence of peripheral embolization. Because the magnification factor varied from study to study, the degree of stenosis was reported as the percentage reduction in the lumen diameter compared to an adjacent, ostensibly normal segment. The diameters of the normal and involved segments were determined by two examiners, using a graticule. Delay in flow distal to the stenosis was judged by comparing the relative filling time of the middle and anterior cerebral arteries. Retrograde flow from the anterior or posterior cerebral circulation into the middle cerebral circulation was considered evidence of border zone shift. Stenosis was considered hemodynamically significant in the presence of delayed filling of [he middle cerebral vessels, a border zone shift, or both. Delayed filling or emptying in focal regions o f the cortical branches was taken as an index of peripheral embolization.
Material and Methods Sixteen patients with middle cerebral artery stenosis were collected from the angiogram reports of t h e Department of Neuroradiology at the Massachusetts General Hospital from 1970 to 1977. Patients in whom severe ipsilateral carotid artery disease was present or a revascularization procedure was performed were excluded. Twenty angiograms were available for review, as 4 of the patients had second studies. Three of the angiograms were performed by direct carotid puncture, 15 by the transfemoral route, and 2 by carotid puncture, transfemoral route, or brachial artery injection, or a combination of these. The following information was sought from each ar-
Results Angiogruphic Findings
From the Stroke Service, Departments of Neurology and Neuroradiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
Accepted for publication June 30, 1978.
152
T h e angiographic data appear in Table 1. T h e stenosis involved the main stem of the middle cerebral artery in 13 patients and the proximal segment of the superior division of the middle cerebral artery in the other 3. T h e middle cerebral vascular defect was less than 5 m m long in all but 3 patients. In 1 it was 12 m m long; in another the stenosis extended from the origin of t h e middle cerebral artery to the first bifurcation; and in the third a 7 m m segment of the
Address reprint requests to Dr Hinton, 82 10 Walnut Hill La, Suite 905, Dallas, TX 75231.
0364-5134/79/020152-06$01.25@ 1978 by R. C. Hinton
~
~~
Patient
~~
''[
Stenosis
Site o f Stenosis
Hcmod ynamicdl y Significant
Seconcl Irsion Distal ICA ancl ACA
1
85
Origin o f MCA
Yes
2
85 85 '5
Lcnticulostriatc segments Origin of MCA Origin o f MCA Origin of MCA
Yes
Distal to lenticulostriatc segments Superior division of MCA
Yes Ycs Yes Yes Yes Yes Yes No Yes No Yes
3 .i 5
70
6
70
7
65 65
x 0 10 11 I'? 13 1 .I
I5 10
65 60
55 50 50 45 40 65
Lcnticulostriate segments Distal to lenticulostriatc segments D i s d to lenticulostriatc segments Origin o f MCA Superior &vision o f MCA Lenticulostriatc segments Lenticulostriatc segments Distal to lenticulostriate segments Superior division of MCA
Yes Yes Yes
IM(;A distal segments
to
Icnticulostriatc
Proximal segment o f ACA
lrontal branch of h1CA
Frontal branch o f IMCA
'Length ot stenosis was greater rhan 5 nim in Paricnts 1 , l,l, ancl 16. Thrombus tormation occurred in Patient 5 . Distal emhilism was found i n Paricnts 1 , 8. 1 1 . a d 12. Angiography was repcared in Paticnts 2, 6, 10. and 14.
MCA = middle cerebral artery; ICA = internal caroriJ artery; A C A = anterior cerebral artery.
proximal superior division was involved. Stenosis occurred in the middle cerebral artery stem at its origin proximal to the Icnticulostriate segments in 5 patients, in the region of rhe lenticulostriate segments in 4 , and distal to those segments in 5 , and it involved the superior division in 3 . Included in this tabulation is a patient who had two lesions in the middle c u e bra1 stem, o n c proximal and o n e distal to the Ienticulostriate segments. T h e patient with a stenosis extending the entire lcngth of the middle cerebral stem is included in the 4 with thc lesion involving t h e Icnticulostriates. Stenoses occurred in additional arteries in 5 patients: l subject had slight stenosis of the ipsilateral distal internal carotid artery and moderate stenosis of the proximal anterior cerebral vessel; another had severe stcnosis of the proximal segment of the ipsilateral anterior ccrebral artery; and 2 had stenosis of the frontal branches of the ipsilateral middle cerebral artery. N o n e of the patients had severe disease in the ipsilateral cervical internal carotid artery. Hemodynamic effects, evidenced by border t o n e shift or delaycd flow, were present in all but 2 patients. T h e degree of stenosis in the hcmodynamically positive cases ranged from 45 to 85%, while in the 2 hernodynamically negative cases the narrowing was 50f'; and 30 t o 4Oci ( t h e long segment), respectively. A filling defect suggesting in situ thrombosis was seen in 2 patients, neither of whom had peripheral
emboli. Evidence suggesting peripheral embolism was found in 4 patients. O n repeat angiography, 1 patient showed a decrease in stenosis from 85"i to 60';; over a two-year period and a second showed a decrease t'rom 70 t o 605; with a loss of hemodynamic effect over a fiveyear period; both patients were taking sodium warfarin. O n e other patient showed progression o f stcnosis from 45 t o 55/'; over a one-year period o n sodium warfarin, although the previously dcmonstratcd hcmodynamic changes were no longer prcsent. T h e fourth patient showed occlusion at the point o f stenosis later o n the same day of the initial angiogram.
CII" iicrl I:indin,p T h e left middle cerebral artery was involved in 1 1 patients and the right in 5. T h e clinical presentation was rather typical. Transient ischemic attacks (TIAS) occurred in 15 of the 16 patients. Four had o n e attack; 1 patient each had two, three, four, and hvc attacks, respectively; and 7 patients had more than tive attacks. O f the 11 patients with dominant hemisphere involvement, 10 had TlAs consisting of a combination of spcech disorder (~lysphasia)with weakness and numbness of the right side, while only 1 had weakness without spccch alteration. O f the 5 patients with involvemcnc of the nondominant hemisphere, 1 had weakness of the left arm and leg, 1 had
Hinton
et
d: Symptomatic MCA Stcnosis
153
weakness and numbness of the left side, 1 had weakness of the left leg, and 2 had a combination of dysarthria with weakness and numbness of the left side. At the time of admission, 5 patients had had TIAs only and the neurological examination was normal, 9 patients who had had TIAs showed a slight neurological deficit, and 2 patients had a moderate neurological deficit. Eleven of the patients received heparin intravenously as the initial therapy while 1 received sodium warfarin. A total of 12 were discharged on a regimen of sodium warfarin. Another 2 patients were not anticoagulated initially and were discharged on aspirin. In all these cases the neurological course was benign, and the patients experienced no further neurological deficit related to the involved middle cerebral artery. One patient was anticoagulated with heparin and warfarin initially but not discharged on these agents. Although she remained neurologically asymptomatic, she died of a pulmonary embolus after one month. Follow-up data ranged from four months to six years in the other patients in this group with benign disease, and all remained asymptomatic on various modes of therapy (Table 2). Two of the patients who had shown a moderate neurological deficit initially recovered almost completely. Two patients developed a severe stroke shortly after admission. Neither was anticoagulated initially. In each case there had been only one TIA, and the course of events differed greatly from the others in the study. In the first patient, a relative had reported slurred speech and weakness of one side of the face but was uncertain which side. Angiograms showed very severe stenosis of the left internal carotid artery, which was treated surgically. Three days postoperatively 1 patient developed a severe left hemiplegia. Review of the preoperative angiograms showed severe stenosis of the right middle cerebral artery, which accounted for the acute postoperative stroke. In the second instance, the patient developed a severe left hemiplegia a few hours after angiography. Repeat angiogram hours after the stroke revealed complete occlusion of the left middle cerebral artery at the point of the previous stenosis. Heparin was begun, but deterioration continued and the patient died. Bloody spinal fluid on lumbar puncture raised the possibility of a hemorrhagic infarct consistent with embolism. The diagnosis of stenosis of the middle cerebral artery at the stage of minor symptoms carried with it an exceptionally good prognosis, possibly related to the use of anticoagulant therapy. These results contrast with those reported in a study of unselected patients with complete occlusion of the middle cerebral artery, in which 87.5% had a permanently disabling or unacceptable neurologlcal deficit [71. Dis-
154 Annals of Neurology
Vol 5
No 2
February 1979
ability and deficit occurred regardless of the frequency of TIAs, the time span over which they occurred, or the severity of their associated neurological deficit. Patient Reports The following 5 patients illustrate the typical clinical features of middle cerebral artery stenosis. A 77-year-old right-handed man experienced five TI AS over a five-day period. Each lasted approximately five minutes and consisted of paresis o r paralysis of the left arm and leg. The general physical examination revealed a 4/6 systolic ejection murmur suggestive of aortic stenosis. The blood pressure was 160/80.The neurolo~calexamination was normal. Angiography showed 85% stenosis of the right middle cerebral artery with delay in flow and a striking border zone shift. The patient was given heparin followed by sodium warfarin. He remained asymptomatic for two and a half years, when anticoagulation was discontinued because of a retrograde peritoneal hemorrhage. A repeat angiogram showed reduction in the stenosis to 60?, but the hemodynamic changes were still present. H e continued asymptomatic for two years on aspirin therapy. A 56-year-old right-handed woman experienced four TIAs over a two-year period. Each attack lasted five to six minutes and was characterized by inability to speak and weakness of the right arm and leg. O n admission the general and neurological examinations were normal and blood pressure was 1l0/65. A technetium brain scan and electroencephalogram were normal. Angiography revealed 5 5% stenosis of the main stem of the left middle cerebral artery at its origin, with delayed flow distally and a shift of the border zone. The patient received heparin intravenously shortly after admission and was then put o n an anticoagulation regimen with sodium warfarin for the next year. Two years later she was asymptomatic without anticoagulation. A 58-year-old man had had as many as three or four TIAs per day over a three-week period. The attacks lasted two to three minutes and consisted of muteness with or without right arm weakness. O n the day before admission his speech suddenly became incoherent and he experienced drooping of the right lower face, followed shortly by right arm weakness. His physician noted hypertension and prescribed a diuretic. The deficit was worse the next day, and by noon the patient’s speech was incoherent, his right arm was paralyzed, and walking was difficult. Improvement occurred in the next half-hour. O n admission the general physical examination was unremarkable and the blood pressure was 170/100. The patient made paraphasic errors in reading and perseverated in following verbal and written commands. There was mild dysnomia, right-left confusion, dyscalculia, and finger agnosia. The visual fields were full and the right lower face was weak. Strengh was 8/10 in the right arm and hand with 9/10 strength in the right leg. Sensation was normal. The reflexes were slightly brisker on the right side but the plantar response was flexor. Left carotid angiography demonstrated (152 stenosis of the left middle cerebral artery in the lenticulostriate segment with delay in flow distally. Sodium warfarin wdS
Table 2. Clinical Findings in I 6 Patients with Middle Cerebral Artery Stenosis" Patient No., Sex, and Age (yr)
N o . and Nature of TlAs
Early Course
FoIIow-~P
1. M, 53
Multiple; dysphasia, right side weak
Asymptomatic 6 mo later on warfarin
2. M, 77
Five; weak left arm and leg
O n admission slight right-sided weakness; normal neurological exam at discharge TIAs only
3. M, 64
One; dysphasia and "funny feeling" in right face One; slurred speech and drooping left face
4. F, 55
5. M, 4 9
6. F, 6 3
Multiple; dysphasia, right side weak and numb Two; dysphasia, right side weak
7 . F, 7 5
Three; slurred speech and weak right side
8. M, 56
Multiple; dysphasia, weak right side One; left side weak
9. M, 62
10. M, 47
Multiple; dysphasia, right hand numb and weak
1 1 . F, 56
Four; dysphasia, right arm and leg weak None
O n e TIA only O n admission slight droop of left face; right carotid endarterectomy followed by right hemiplegia corresponding to left MCA stenosis Only slight flattening of right nasolabial fold Mild drift of right arm
Slight drift of right arm and leg; discharged without sodium warfarin TIAs only Severe left hemiplegia several hours after admission; repeat angiogram showed occlusion at previous site of stenosis Mild trouble with word finding and slight weakness of right face and arm Occasional paraphasic errors
13. M, 79
One; dysphasia and right side weak
14. M, 58
Multiple; dysphasia, right side weak
15. M, 60
Multiple; left leg weak
Dysarthia with 6/10 strength in left limbs on discharge 7/10 strength on right side at time of admission; 4 days later 9/10 strength Occasional paraphasic errors with 9/10 right-sided weakness at time of discharge TIAs only
16. M, 70
Multiple; dysphasia and weak right side
Very mild drift of right arm and right Babinski sign
12. M, 72
Asymptomatic 25'2 yr later on warfarin Asymptomatic 5 yr later on aspirin Severe left hemiplegia
N o n e available Asymptomatic with normal neurological exam 5 yr later on warfarin Died of pulmonary embolus 1 mo later Symptomatic 3 yr later on warfarin Died of stroke
Asymptomatic 2$4 yr later on warfarin Asymptomatic 2 yr later, off warfarin for 1 yr Asymptomatic with minimal deficit 31/2 yr later off medication Asymptomatic 2 yr later on aspirin Asymptomatic 6 yr later off warfarin Asymptomatic 3 y r later on warfarin but then suffered embolic stroke in opposite hemisphere Asymptomatic 4 mo later on warfarin
"Hypertension present in all except Patient 11.
TlAs
=
transient ischemic attacks; MCA = middle cerebral artery
begun, and ten days later speech was greatly improved and full strength had returned to the right side. There was still minimal right-left confusion. He was well for one year, when he was admitted again with multiple TIAs manifested by numbness and weakness of the right leg. These continued in spite of heparin and sodium warfarin, but at times were terminated by having the patient lie flat. Electroencephalograms were normal.
Another carotid angiogram showed progression of stenosis to 55% but resolution of the hemodynamic changes. The attacks eventually stopped but recurred two months later. They later subsided, and six years later he was asymptomatic without anticoagulation. Over two and a half years, a 47-year-old right-handed man experienced multiple episodes of transient numbness of the right hand, involving mainly the fourth and fifth
Hinton et al: Symptomatic MCA Stenosis
155
fingers. The numbness occurred every 3 to 4 months, and each attack lasted seconds to minutes. Radiographs of the cervical spine were normal. About 36 hours prior to admission the patient noted the sudden onset of numbness and weakness of the right hand and difficulty speaking. Twenty-four hours later speech had improved and numbness involved only the medial three fingers. His general physical examination was normal and the blood pressure was 160/100. Neurological examination revealed mild word-finding difficulties, slighc clumsiness of the right hand and arm, and mild impairment of all forms of sensation in the right hand. Strength was full except for slight weakness of flexion of the third, fourth, and fifth fingers of the right hand. There was flattening of the right nasolabial fold. The reflexes were symmetrical and the plantar responses flexor. An electroencephalogram was normal. The angiogram showed 60% stenosis of the left middle cerebral artery with delayed flow distally and a border zone shift. Sodium warfarin was prescribed, and the patient was asymptomatic two and a half years later. Two weeks prior to admission a 56-year-old righthanded man had a twenty-minute attack of inability to speak and right hand weakness. One week later h e had a fifteen-minute episode of aphasia and dragging of the right leg. During the week prior to admission, three similar episodes of aphasia occurred, two of which were accompanied by numbness of the lips or tip of the tongue. His TlAs continued despite heparin therapy. Physical examination was normal. A n angiogram revealed 65% stenosis of the left middle cerebral artery. Heparin was continued and the spells ceased. Long-term anticoagulation with sodium warfarin was begun, and the patient was asymptomatic three years later.
Discussion The clinical features of symptomatic middle cerebral artery stenosis already mentioned are almost the same as those of stenosis of the internal carotid artery, except for the absence of transient monocular blindness. In this series of patients, the prognosis was good regardless of the clinical or radiological findings. Our preliminary conclusions suggest that medical therapy, including anticoagulation, should be initiated early, before the occurrence of complete occlusion. Complete occlusion and infarction occurred shortly after angiography in I of o u r patients, and an angiographic complication is possible in this case. It is for these patients that external carotid-middle cerebral artery bypass anastomotic surgery is most often recommended. O u r findings that the prognosis on long-term anticoagulant therapy can be remarkably good demands that such therapy be considered as an alternative to surgery. The literature contains some support for the favorable clinical course of middle cerebral artery stenosis. Allcock [ 11 reported “good or fair” results in 1 0 of 11 patients with middle cerebral artery stenosis, but the clinical details were not given, nor were the treat-
156 Annals of Neurology Vol 5 No 2 February 1979
ment and period of follow-up. Lascelles and Burrows [7] found “recovery or improvement” in 7 of 9 patients with stenosis, but detailed information was nor provided. The poor results in complete thrombotic occlusion reported by Fisher [3] were mentioned earlier. In complete occlusion, Lascelles and Burrows [7] found no change or death in half of their patients, and Kaste and Waltimo [6] found that 25 of their 78 patients required assistance with daily activities, were totally dependent, or had died. Pathological data o n symptomatic middle cerebral artery stenosis or recent thrombotic occlusion of the middle cerebral artery are sparse or nonexistent. This lack of information is partly d u e to the relative infrequency of the lesion and the tendency of the patient to survive even a severe deficit. Further detailed pathological study would no doubt help to guide therapy. Our experience that middle cerebral artery stenosis is an uncommon cause of cerebral ischemia corroborates other studies. It was present in 7 % of angiograms in the cooperative study [5], and its incidence in several studies o n occlusive disease of the middle cerebral artery ranged from 1.6 to 28% [ 1, 7 , 9-1 11. Presumably, stenotic lesions in most cases are regions of atherosclerotic narrowing that provide a setting for potential thrombotic occlusion of the artery. Thrombotic occlusion of the middle cerebral artery is much less common at autopsy than is embolic occlusion [2, 4 , 8, 121, and embolic occlusion with partial recanalitation cannot be completely excluded as a cause of stenosis. Although some degree of resolution of stenosis was evident o n repeat angiograms in 2 of our patients, the stenosis by no means disappeared completely. These findings agree with other reports from the literature [ 1, 71 except for one report of a patient in whom the area of stenosis had resolved completely when angiography was repeated ten days later [I]. This single patient, however, suggests that an embolus produced incomplete occlusion, mimicking stenosis. Atherosclerotic involvement of the intracranial vessels correlates well with the degree of systemic hypertension, although the disease process usually is more advanced in the extracranial vessels [4]. In our study, only 1 patient with middle cerebral artery stenosis had comcomitant narrowing of the ipsilateral carotid artery. This case was excluded from the series. Included in o u r series was a patient with middle cerebral artery stenosis with a patent ipsilateral carotid artery but severe stenosis of the contralateral carotid artery. These findings are in keeping with the view that carotid stenosis “protects” the intracranial vessels from disease secondary to hypertension [4]. T h e site of stenosis was in the main stem of the middle cerebral artery in 13 patients and in the
proximal part of the superior division of the middle cerebral artery in 3 patients. Thrombosis, and therefore symptomatic stenosis, is rarely described as occurring in the peripheral cortical branches of the middle cerebral artery. The proximal segment of the superior or inferior divisions of the middle cerebral artery is the furthest distal site that symptomatic atherothrombosis is generally found [4]. We limited our study to the patient material available since modern magnification neuroradiology has come into general use. As increasing numbers of cases of stenosis are now being discovered, these patients illustrate the potentially benign course of the condition when treated with medical therapy alone. The clinical randomized trial underway will, we hope, clarify the value of and indications for medical versus surgical therapy in this condition. Supported by Grants H S 10088 and N S 10828-01A1 from the National Institutes of Health.
3.
4.
5.
6.
7.
8.
9.
10. 11.
References 1. Allcock JM: Occlusion of the middle cerebral artery: serial angiography as a guide to conservative therapy. J Neurosurg 27~353-363, 1967 2. Blackwood W, Bratty P. Mair WGP: Observations o n occlu-
12.
sive vascular disease of the brain, in Jakob H (ed): Proceedings of the International Congress of Neumpathology. Stuttgart, Thieme, 1962, vol 3, p 146 Fisher CM: The natural history of middle cerebral artery trunk occlusion, in Austin G M (ed): Microneurosurgical Anastomosis for Cerebral Ischemia. Springfield, IL, Thomas, 1976 Fisher CM, Gore I, Okabe N , et al: Atherosclerosis of the carotid and vertebral arteries. J Neuropathol Exp Neurol 24:455, 1965 Hass WK, Fields WS, North RR, e t al: Joint study of exrracranial arterial occlusion: 11. Arteriography, techniques, sites, and complications. JAMA 203:159-166, 1968 Kaste M, Waltirno 0: Prognosis of patients with middle cerebral artery occlusion. Stroke 7:482-485, 1976 Lascelles RG, Burrows EH: Occlusion of the middle cerebral artery. Brain 88:85-96, 1965 Lhermitre F, Gautier JC, Derouesne C: Nature of occlusions of the middle cerebral artery. Neurology (Minneap) 20:82-88, I 9 7 0 Lhermitte F, Gautier JC, Derouesne C, e t al: Ischemic accidents in the middle cerebral artery territory. Arch Neurol 19:248-256, 1968 Silverstein A, Hollin S: Internal carotid vs middle cerebral artery occlusions. Arch Neurol 12:468-47 1, 1965 Sindermann F, Dichgans J, Bergleiter R: Occlusion of the middle cerebral artery and its branches. Angiographic and clinical correlates. Brain 92:607-620, 1969 Y a m PO, Hutchinson EC: Cerebral Infarction: The Role of Stenosis of the Extracranial Cerebral Arteries (Medical Research Council Special Report Series N o . 300). London, H e r Majesty's Stationery Office, 1961
Hinton et al: Symptomatic MCA Stenosis
157
The clinical course of 16 consecutive patients with stenosis of the middle cerebral artery angiographically diagnosed between 1970 and 1977 was reviewed. All were managed nonsurgically with medical treatment including anticoagulation. Prior to therapy, transient ischemic attacks had occurred in 15 and cerebral infarction in 1 1 . Initially, none exhibited more than a minor neurological deficit. Follow-up from one month to six years showed a benign course in 14 patients: 13 experienced no subsequent transient attacks or new stroke; 1 had repeated transient attacks for two years but not in the following four years. Two of t h e 16 developed a severe stroke early in the course, before medical therapy was started. No distinctive clinical or radiographic features were identified that permitted prediction of the outcome. This small series supports the need for a randomized study of bypass efficacy in these patients. Hinton RC, Mohr JP, Ackerman RH, et al: Symptomatic middle cerebrai artery stenosis. Ann Neurol 5:152-157, 1979
Middle cerebral artery stenosis associated with atherosclerosis is a much less common cause of symptomatic ischemia than is middle cerebral embolism 11, 5, 7, 9-11]. Stenosis is important in that it often presents as transient ischemic attacks and provides an opportunity for therapeutic intervention before total occlusion and severe stroke occur. Patients with stenosis also provide information regarding the interrelation between hemodynamic factors and ischemic symptoms. T h e present review of 16 medically managed patients with symptomatic stenosis of the middle cerebral artery encountered at o u r institution between 1970 and 1977 has been prompted by recent innovations in the surgical management of cerebral arterial stenoses. T h e favorable outcome in this group points u p the need for a randomized study of surgical versus medical therapy for patients with intracranial stenosis, an investigation that is currently underway.
teriogram: site of stenosis, degree of stenosis, evidence of local thrombus formation, abnormality of flow distal to the stenosis, position of the border zone between the middle and anterior and middle and posterior cerebral territories, and evidence of peripheral embolization. Because the magnification factor varied from study to study, the degree of stenosis was reported as the percentage reduction in the lumen diameter compared to an adjacent, ostensibly normal segment. The diameters of the normal and involved segments were determined by two examiners, using a graticule. Delay in flow distal to the stenosis was judged by comparing the relative filling time of the middle and anterior cerebral arteries. Retrograde flow from the anterior or posterior cerebral circulation into the middle cerebral circulation was considered evidence of border zone shift. Stenosis was considered hemodynamically significant in the presence of delayed filling of [he middle cerebral vessels, a border zone shift, or both. Delayed filling or emptying in focal regions o f the cortical branches was taken as an index of peripheral embolization.
Material and Methods Sixteen patients with middle cerebral artery stenosis were collected from the angiogram reports of t h e Department of Neuroradiology at the Massachusetts General Hospital from 1970 to 1977. Patients in whom severe ipsilateral carotid artery disease was present or a revascularization procedure was performed were excluded. Twenty angiograms were available for review, as 4 of the patients had second studies. Three of the angiograms were performed by direct carotid puncture, 15 by the transfemoral route, and 2 by carotid puncture, transfemoral route, or brachial artery injection, or a combination of these. The following information was sought from each ar-
Results Angiogruphic Findings
From the Stroke Service, Departments of Neurology and Neuroradiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
Accepted for publication June 30, 1978.
152
T h e angiographic data appear in Table 1. T h e stenosis involved the main stem of the middle cerebral artery in 13 patients and the proximal segment of the superior division of the middle cerebral artery in the other 3. T h e middle cerebral vascular defect was less than 5 m m long in all but 3 patients. In 1 it was 12 m m long; in another the stenosis extended from the origin of t h e middle cerebral artery to the first bifurcation; and in the third a 7 m m segment of the
Address reprint requests to Dr Hinton, 82 10 Walnut Hill La, Suite 905, Dallas, TX 75231.
0364-5134/79/020152-06$01.25@ 1978 by R. C. Hinton
~
~~
Patient
~~
''[
Stenosis
Site o f Stenosis
Hcmod ynamicdl y Significant
Seconcl Irsion Distal ICA ancl ACA
1
85
Origin o f MCA
Yes
2
85 85 '5
Lcnticulostriatc segments Origin of MCA Origin o f MCA Origin of MCA
Yes
Distal to lenticulostriatc segments Superior division of MCA
Yes Ycs Yes Yes Yes Yes Yes No Yes No Yes
3 .i 5
70
6
70
7
65 65
x 0 10 11 I'? 13 1 .I
I5 10
65 60
55 50 50 45 40 65
Lcnticulostriate segments Distal to lenticulostriatc segments D i s d to lenticulostriatc segments Origin o f MCA Superior &vision o f MCA Lenticulostriatc segments Lenticulostriatc segments Distal to lenticulostriate segments Superior division of MCA
Yes Yes Yes
IM(;A distal segments
to
Icnticulostriatc
Proximal segment o f ACA
lrontal branch of h1CA
Frontal branch o f IMCA
'Length ot stenosis was greater rhan 5 nim in Paricnts 1 , l,l, ancl 16. Thrombus tormation occurred in Patient 5 . Distal emhilism was found i n Paricnts 1 , 8. 1 1 . a d 12. Angiography was repcared in Paticnts 2, 6, 10. and 14.
MCA = middle cerebral artery; ICA = internal caroriJ artery; A C A = anterior cerebral artery.
proximal superior division was involved. Stenosis occurred in the middle cerebral artery stem at its origin proximal to the Icnticulostriate segments in 5 patients, in the region of rhe lenticulostriate segments in 4 , and distal to those segments in 5 , and it involved the superior division in 3 . Included in this tabulation is a patient who had two lesions in the middle c u e bra1 stem, o n c proximal and o n e distal to the Ienticulostriate segments. T h e patient with a stenosis extending the entire lcngth of the middle cerebral stem is included in the 4 with thc lesion involving t h e Icnticulostriates. Stenoses occurred in additional arteries in 5 patients: l subject had slight stenosis of the ipsilateral distal internal carotid artery and moderate stenosis of the proximal anterior cerebral vessel; another had severe stcnosis of the proximal segment of the ipsilateral anterior ccrebral artery; and 2 had stenosis of the frontal branches of the ipsilateral middle cerebral artery. N o n e of the patients had severe disease in the ipsilateral cervical internal carotid artery. Hemodynamic effects, evidenced by border t o n e shift or delaycd flow, were present in all but 2 patients. T h e degree of stenosis in the hcmodynamically positive cases ranged from 45 to 85%, while in the 2 hernodynamically negative cases the narrowing was 50f'; and 30 t o 4Oci ( t h e long segment), respectively. A filling defect suggesting in situ thrombosis was seen in 2 patients, neither of whom had peripheral
emboli. Evidence suggesting peripheral embolism was found in 4 patients. O n repeat angiography, 1 patient showed a decrease in stenosis from 85"i to 60';; over a two-year period and a second showed a decrease t'rom 70 t o 605; with a loss of hemodynamic effect over a fiveyear period; both patients were taking sodium warfarin. O n e other patient showed progression o f stcnosis from 45 t o 55/'; over a one-year period o n sodium warfarin, although the previously dcmonstratcd hcmodynamic changes were no longer prcsent. T h e fourth patient showed occlusion at the point o f stenosis later o n the same day of the initial angiogram.
CII" iicrl I:indin,p T h e left middle cerebral artery was involved in 1 1 patients and the right in 5. T h e clinical presentation was rather typical. Transient ischemic attacks (TIAS) occurred in 15 of the 16 patients. Four had o n e attack; 1 patient each had two, three, four, and hvc attacks, respectively; and 7 patients had more than tive attacks. O f the 11 patients with dominant hemisphere involvement, 10 had TlAs consisting of a combination of spcech disorder (~lysphasia)with weakness and numbness of the right side, while only 1 had weakness without spccch alteration. O f the 5 patients with involvemcnc of the nondominant hemisphere, 1 had weakness of the left arm and leg, 1 had
Hinton
et
d: Symptomatic MCA Stcnosis
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weakness and numbness of the left side, 1 had weakness of the left leg, and 2 had a combination of dysarthria with weakness and numbness of the left side. At the time of admission, 5 patients had had TIAs only and the neurological examination was normal, 9 patients who had had TIAs showed a slight neurological deficit, and 2 patients had a moderate neurological deficit. Eleven of the patients received heparin intravenously as the initial therapy while 1 received sodium warfarin. A total of 12 were discharged on a regimen of sodium warfarin. Another 2 patients were not anticoagulated initially and were discharged on aspirin. In all these cases the neurological course was benign, and the patients experienced no further neurological deficit related to the involved middle cerebral artery. One patient was anticoagulated with heparin and warfarin initially but not discharged on these agents. Although she remained neurologically asymptomatic, she died of a pulmonary embolus after one month. Follow-up data ranged from four months to six years in the other patients in this group with benign disease, and all remained asymptomatic on various modes of therapy (Table 2). Two of the patients who had shown a moderate neurological deficit initially recovered almost completely. Two patients developed a severe stroke shortly after admission. Neither was anticoagulated initially. In each case there had been only one TIA, and the course of events differed greatly from the others in the study. In the first patient, a relative had reported slurred speech and weakness of one side of the face but was uncertain which side. Angiograms showed very severe stenosis of the left internal carotid artery, which was treated surgically. Three days postoperatively 1 patient developed a severe left hemiplegia. Review of the preoperative angiograms showed severe stenosis of the right middle cerebral artery, which accounted for the acute postoperative stroke. In the second instance, the patient developed a severe left hemiplegia a few hours after angiography. Repeat angiogram hours after the stroke revealed complete occlusion of the left middle cerebral artery at the point of the previous stenosis. Heparin was begun, but deterioration continued and the patient died. Bloody spinal fluid on lumbar puncture raised the possibility of a hemorrhagic infarct consistent with embolism. The diagnosis of stenosis of the middle cerebral artery at the stage of minor symptoms carried with it an exceptionally good prognosis, possibly related to the use of anticoagulant therapy. These results contrast with those reported in a study of unselected patients with complete occlusion of the middle cerebral artery, in which 87.5% had a permanently disabling or unacceptable neurologlcal deficit [71. Dis-
154 Annals of Neurology
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ability and deficit occurred regardless of the frequency of TIAs, the time span over which they occurred, or the severity of their associated neurological deficit. Patient Reports The following 5 patients illustrate the typical clinical features of middle cerebral artery stenosis. A 77-year-old right-handed man experienced five TI AS over a five-day period. Each lasted approximately five minutes and consisted of paresis o r paralysis of the left arm and leg. The general physical examination revealed a 4/6 systolic ejection murmur suggestive of aortic stenosis. The blood pressure was 160/80.The neurolo~calexamination was normal. Angiography showed 85% stenosis of the right middle cerebral artery with delay in flow and a striking border zone shift. The patient was given heparin followed by sodium warfarin. He remained asymptomatic for two and a half years, when anticoagulation was discontinued because of a retrograde peritoneal hemorrhage. A repeat angiogram showed reduction in the stenosis to 60?, but the hemodynamic changes were still present. H e continued asymptomatic for two years on aspirin therapy. A 56-year-old right-handed woman experienced four TIAs over a two-year period. Each attack lasted five to six minutes and was characterized by inability to speak and weakness of the right arm and leg. O n admission the general and neurological examinations were normal and blood pressure was 1l0/65. A technetium brain scan and electroencephalogram were normal. Angiography revealed 5 5% stenosis of the main stem of the left middle cerebral artery at its origin, with delayed flow distally and a shift of the border zone. The patient received heparin intravenously shortly after admission and was then put o n an anticoagulation regimen with sodium warfarin for the next year. Two years later she was asymptomatic without anticoagulation. A 58-year-old man had had as many as three or four TIAs per day over a three-week period. The attacks lasted two to three minutes and consisted of muteness with or without right arm weakness. O n the day before admission his speech suddenly became incoherent and he experienced drooping of the right lower face, followed shortly by right arm weakness. His physician noted hypertension and prescribed a diuretic. The deficit was worse the next day, and by noon the patient’s speech was incoherent, his right arm was paralyzed, and walking was difficult. Improvement occurred in the next half-hour. O n admission the general physical examination was unremarkable and the blood pressure was 170/100. The patient made paraphasic errors in reading and perseverated in following verbal and written commands. There was mild dysnomia, right-left confusion, dyscalculia, and finger agnosia. The visual fields were full and the right lower face was weak. Strengh was 8/10 in the right arm and hand with 9/10 strength in the right leg. Sensation was normal. The reflexes were slightly brisker on the right side but the plantar response was flexor. Left carotid angiography demonstrated (152 stenosis of the left middle cerebral artery in the lenticulostriate segment with delay in flow distally. Sodium warfarin wdS
Table 2. Clinical Findings in I 6 Patients with Middle Cerebral Artery Stenosis" Patient No., Sex, and Age (yr)
N o . and Nature of TlAs
Early Course
FoIIow-~P
1. M, 53
Multiple; dysphasia, right side weak
Asymptomatic 6 mo later on warfarin
2. M, 77
Five; weak left arm and leg
O n admission slight right-sided weakness; normal neurological exam at discharge TIAs only
3. M, 64
One; dysphasia and "funny feeling" in right face One; slurred speech and drooping left face
4. F, 55
5. M, 4 9
6. F, 6 3
Multiple; dysphasia, right side weak and numb Two; dysphasia, right side weak
7 . F, 7 5
Three; slurred speech and weak right side
8. M, 56
Multiple; dysphasia, weak right side One; left side weak
9. M, 62
10. M, 47
Multiple; dysphasia, right hand numb and weak
1 1 . F, 56
Four; dysphasia, right arm and leg weak None
O n e TIA only O n admission slight droop of left face; right carotid endarterectomy followed by right hemiplegia corresponding to left MCA stenosis Only slight flattening of right nasolabial fold Mild drift of right arm
Slight drift of right arm and leg; discharged without sodium warfarin TIAs only Severe left hemiplegia several hours after admission; repeat angiogram showed occlusion at previous site of stenosis Mild trouble with word finding and slight weakness of right face and arm Occasional paraphasic errors
13. M, 79
One; dysphasia and right side weak
14. M, 58
Multiple; dysphasia, right side weak
15. M, 60
Multiple; left leg weak
Dysarthia with 6/10 strength in left limbs on discharge 7/10 strength on right side at time of admission; 4 days later 9/10 strength Occasional paraphasic errors with 9/10 right-sided weakness at time of discharge TIAs only
16. M, 70
Multiple; dysphasia and weak right side
Very mild drift of right arm and right Babinski sign
12. M, 72
Asymptomatic 25'2 yr later on warfarin Asymptomatic 5 yr later on aspirin Severe left hemiplegia
N o n e available Asymptomatic with normal neurological exam 5 yr later on warfarin Died of pulmonary embolus 1 mo later Symptomatic 3 yr later on warfarin Died of stroke
Asymptomatic 2$4 yr later on warfarin Asymptomatic 2 yr later, off warfarin for 1 yr Asymptomatic with minimal deficit 31/2 yr later off medication Asymptomatic 2 yr later on aspirin Asymptomatic 6 yr later off warfarin Asymptomatic 3 y r later on warfarin but then suffered embolic stroke in opposite hemisphere Asymptomatic 4 mo later on warfarin
"Hypertension present in all except Patient 11.
TlAs
=
transient ischemic attacks; MCA = middle cerebral artery
begun, and ten days later speech was greatly improved and full strength had returned to the right side. There was still minimal right-left confusion. He was well for one year, when he was admitted again with multiple TIAs manifested by numbness and weakness of the right leg. These continued in spite of heparin and sodium warfarin, but at times were terminated by having the patient lie flat. Electroencephalograms were normal.
Another carotid angiogram showed progression of stenosis to 55% but resolution of the hemodynamic changes. The attacks eventually stopped but recurred two months later. They later subsided, and six years later he was asymptomatic without anticoagulation. Over two and a half years, a 47-year-old right-handed man experienced multiple episodes of transient numbness of the right hand, involving mainly the fourth and fifth
Hinton et al: Symptomatic MCA Stenosis
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fingers. The numbness occurred every 3 to 4 months, and each attack lasted seconds to minutes. Radiographs of the cervical spine were normal. About 36 hours prior to admission the patient noted the sudden onset of numbness and weakness of the right hand and difficulty speaking. Twenty-four hours later speech had improved and numbness involved only the medial three fingers. His general physical examination was normal and the blood pressure was 160/100. Neurological examination revealed mild word-finding difficulties, slighc clumsiness of the right hand and arm, and mild impairment of all forms of sensation in the right hand. Strength was full except for slight weakness of flexion of the third, fourth, and fifth fingers of the right hand. There was flattening of the right nasolabial fold. The reflexes were symmetrical and the plantar responses flexor. An electroencephalogram was normal. The angiogram showed 60% stenosis of the left middle cerebral artery with delayed flow distally and a border zone shift. Sodium warfarin was prescribed, and the patient was asymptomatic two and a half years later. Two weeks prior to admission a 56-year-old righthanded man had a twenty-minute attack of inability to speak and right hand weakness. One week later h e had a fifteen-minute episode of aphasia and dragging of the right leg. During the week prior to admission, three similar episodes of aphasia occurred, two of which were accompanied by numbness of the lips or tip of the tongue. His TlAs continued despite heparin therapy. Physical examination was normal. A n angiogram revealed 65% stenosis of the left middle cerebral artery. Heparin was continued and the spells ceased. Long-term anticoagulation with sodium warfarin was begun, and the patient was asymptomatic three years later.
Discussion The clinical features of symptomatic middle cerebral artery stenosis already mentioned are almost the same as those of stenosis of the internal carotid artery, except for the absence of transient monocular blindness. In this series of patients, the prognosis was good regardless of the clinical or radiological findings. Our preliminary conclusions suggest that medical therapy, including anticoagulation, should be initiated early, before the occurrence of complete occlusion. Complete occlusion and infarction occurred shortly after angiography in I of o u r patients, and an angiographic complication is possible in this case. It is for these patients that external carotid-middle cerebral artery bypass anastomotic surgery is most often recommended. O u r findings that the prognosis on long-term anticoagulant therapy can be remarkably good demands that such therapy be considered as an alternative to surgery. The literature contains some support for the favorable clinical course of middle cerebral artery stenosis. Allcock [ 11 reported “good or fair” results in 1 0 of 11 patients with middle cerebral artery stenosis, but the clinical details were not given, nor were the treat-
156 Annals of Neurology Vol 5 No 2 February 1979
ment and period of follow-up. Lascelles and Burrows [7] found “recovery or improvement” in 7 of 9 patients with stenosis, but detailed information was nor provided. The poor results in complete thrombotic occlusion reported by Fisher [3] were mentioned earlier. In complete occlusion, Lascelles and Burrows [7] found no change or death in half of their patients, and Kaste and Waltimo [6] found that 25 of their 78 patients required assistance with daily activities, were totally dependent, or had died. Pathological data o n symptomatic middle cerebral artery stenosis or recent thrombotic occlusion of the middle cerebral artery are sparse or nonexistent. This lack of information is partly d u e to the relative infrequency of the lesion and the tendency of the patient to survive even a severe deficit. Further detailed pathological study would no doubt help to guide therapy. Our experience that middle cerebral artery stenosis is an uncommon cause of cerebral ischemia corroborates other studies. It was present in 7 % of angiograms in the cooperative study [5], and its incidence in several studies o n occlusive disease of the middle cerebral artery ranged from 1.6 to 28% [ 1, 7 , 9-1 11. Presumably, stenotic lesions in most cases are regions of atherosclerotic narrowing that provide a setting for potential thrombotic occlusion of the artery. Thrombotic occlusion of the middle cerebral artery is much less common at autopsy than is embolic occlusion [2, 4 , 8, 121, and embolic occlusion with partial recanalitation cannot be completely excluded as a cause of stenosis. Although some degree of resolution of stenosis was evident o n repeat angiograms in 2 of our patients, the stenosis by no means disappeared completely. These findings agree with other reports from the literature [ 1, 71 except for one report of a patient in whom the area of stenosis had resolved completely when angiography was repeated ten days later [I]. This single patient, however, suggests that an embolus produced incomplete occlusion, mimicking stenosis. Atherosclerotic involvement of the intracranial vessels correlates well with the degree of systemic hypertension, although the disease process usually is more advanced in the extracranial vessels [4]. In our study, only 1 patient with middle cerebral artery stenosis had comcomitant narrowing of the ipsilateral carotid artery. This case was excluded from the series. Included in o u r series was a patient with middle cerebral artery stenosis with a patent ipsilateral carotid artery but severe stenosis of the contralateral carotid artery. These findings are in keeping with the view that carotid stenosis “protects” the intracranial vessels from disease secondary to hypertension [4]. T h e site of stenosis was in the main stem of the middle cerebral artery in 13 patients and in the
proximal part of the superior division of the middle cerebral artery in 3 patients. Thrombosis, and therefore symptomatic stenosis, is rarely described as occurring in the peripheral cortical branches of the middle cerebral artery. The proximal segment of the superior or inferior divisions of the middle cerebral artery is the furthest distal site that symptomatic atherothrombosis is generally found [4]. We limited our study to the patient material available since modern magnification neuroradiology has come into general use. As increasing numbers of cases of stenosis are now being discovered, these patients illustrate the potentially benign course of the condition when treated with medical therapy alone. The clinical randomized trial underway will, we hope, clarify the value of and indications for medical versus surgical therapy in this condition. Supported by Grants H S 10088 and N S 10828-01A1 from the National Institutes of Health.
3.
4.
5.
6.
7.
8.
9.
10. 11.
References 1. Allcock JM: Occlusion of the middle cerebral artery: serial angiography as a guide to conservative therapy. J Neurosurg 27~353-363, 1967 2. Blackwood W, Bratty P. Mair WGP: Observations o n occlu-
12.
sive vascular disease of the brain, in Jakob H (ed): Proceedings of the International Congress of Neumpathology. Stuttgart, Thieme, 1962, vol 3, p 146 Fisher CM: The natural history of middle cerebral artery trunk occlusion, in Austin G M (ed): Microneurosurgical Anastomosis for Cerebral Ischemia. Springfield, IL, Thomas, 1976 Fisher CM, Gore I, Okabe N , et al: Atherosclerosis of the carotid and vertebral arteries. J Neuropathol Exp Neurol 24:455, 1965 Hass WK, Fields WS, North RR, e t al: Joint study of exrracranial arterial occlusion: 11. Arteriography, techniques, sites, and complications. JAMA 203:159-166, 1968 Kaste M, Waltirno 0: Prognosis of patients with middle cerebral artery occlusion. Stroke 7:482-485, 1976 Lascelles RG, Burrows EH: Occlusion of the middle cerebral artery. Brain 88:85-96, 1965 Lhermitre F, Gautier JC, Derouesne C: Nature of occlusions of the middle cerebral artery. Neurology (Minneap) 20:82-88, I 9 7 0 Lhermitte F, Gautier JC, Derouesne C, e t al: Ischemic accidents in the middle cerebral artery territory. Arch Neurol 19:248-256, 1968 Silverstein A, Hollin S: Internal carotid vs middle cerebral artery occlusions. Arch Neurol 12:468-47 1, 1965 Sindermann F, Dichgans J, Bergleiter R: Occlusion of the middle cerebral artery and its branches. Angiographic and clinical correlates. Brain 92:607-620, 1969 Y a m PO, Hutchinson EC: Cerebral Infarction: The Role of Stenosis of the Extracranial Cerebral Arteries (Medical Research Council Special Report Series N o . 300). London, H e r Majesty's Stationery Office, 1961
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