Capsular Infarcts The Underlying Vascular Lesions C. Miller Fisher, MD \s=b\In ten patients, 11 infarcts involving mainly the internal capsule have been examined pathologically. Serial sections of the involved basal ganglia were studied in ten infarcts and only a gross dissection was made in the other. The implicated penetrating arteries were traced throughout their length and obstructive vascular lesions were found in nine instances. In two of the nine there was an atheromatous plaque with a superimposed thrombus, in four an atheromatous plaque had caused severe stenosis, in one a destructive arterial process lipohyalinosis had occurred, in one case the nature of the obstruction remained "uncertain," and in the penetrating arteries were obstructed at their orifices by an atheroma in the superior division of the middle cerebral artery. In two cases the vessels were patent, suggesting embolism. The atheromas consisted almost exclusively of a conglomerate of fat-filled macrophages. The clinical correlate was a pure motor hemiplegia or hemiparesis involving the face, arm, and leg without sensory deficit, one homonymous hemianopia, receptive aphasia, or apractognosia. Confusion was prominent in one patient. (Arch Neurol 36:65-73, 1979) Accepted for publication Feb 15, 1978. From the Neurology Service, Massachusetts General Hospital, and the Department of Neurol- ogy, Harvard Medical School, Boston. Reprint requests to Neurology Service, Massachusetts General Hospital, Boston, MA 02114 (Dr Fisher). Although infarcts in the internal capsule are not an uncommon cause of stroke, their underlying vascular disease is usually not investi¬ gated. This is because the infarcts are the result of blockage of penetrating deep branches of the middle cerebral ** artery rather than of the middle cere¬ bral artery itself or the internal carot¬ id artery, and attempting to find a lesion in the system of penetrating branches and demonstrate accurately its relationship to the infarct requires uninterrupted serial sections of the basal ganglia. Also, it is necessary to section the brain horizontally, leave the middle cerebral artery undissected lest small branches be torn, and process the involved basal ganglia largely as one block. It is therefore impractical to investigate these ves¬ sels at routine autopsy. CASE MATERIAL Eleven capsular infarcts have been stud¬ ied in ten cases (nine unilateral and one bilateral). Ten infarcts were investigated using serial sections of blocks of the basal ganglia while one infarct was dissected only grossly (case 10). Ten specimens were embedded in paraffin, one in celloidin. Phosphotungstic acid-hematoxylin and hematoxylin-eosin were the main stains used, to which were added in some instances Verhoeff's elastic, Van Gieson, Loyez myelin, and azocarmine stains. The number of sections in each case varied from 1,000 to 4,000. Starting superiorly in the infarct, the small arteries within the ischemie tissue were traced inferiorly to their origin from a parent vessel whose Downloaded From: http://archneur.jamanetwork.com/ by a University of Iowa User on 06/10/2015 territory of supply accounted for the entire of infarction without extending to zone normal tissue. This artery to the infarct then traced proximally until an occlu¬ sion was found or, if none was present, until the artery joined the middle cerebral artery or another large branch that supplied intact regions in addition to the infarct. To conserve space, the clinical data and often the pathological findings are pre¬ sented in abbreviated form, but in each case information omitted was not crucial to the presentation. was Clinicopathologic Findings The cavities left as the residuum of small infarcts in the deep parts of the brain are generally referred to as lacunar infarcts or lacunes. The infarcts described here are among the larger of the type and may be designated capsular infarcts. Occurring as isolated lesions, these infarcts are the result of blockage of penetrating arteries or branches by either local vascular disease '·' or embolus.1 The occlusive vascular dis¬ ease causing capsular infarction is usually either atherosclerosis or lipohyalinosis and is almost wholly dependent on the presence of systemic hypertension; that is, capsular infarcts resulting from occlusive vascular disease are almost always accompanied by high blood pressure. In the present study, vascular occlusion was found in relation to nine of the capsu¬ lar infarcts, while in two, convincing obstructive disease was not identified. In six, the vascular disease consisted of ather¬ osclerotic plaques remarkable for their almost pure content of fat-filled macro¬ phages. In two instances there was total occlusion of the lumen, and in four, only severe stenosis. In one case lipohyalinosis was responsible, in another the arterial was uncertain, and in one the blockage lay in the superior division of the middle cerebral artery. The penetrating process vessels involved were 300 to 800 µ in diam¬ eter and the vascular events to be de¬ scribed were on a miniature scale. Occlu¬ sion of the internal carotid and main middle cerebral arteries was excluded on clinical, angiographie, or pathological ex¬ amination, except in case 2. REPORT OF CASES Case 1.—A hypertensive man, aged 54, awakened at 6 am one day and walked about his bedroom. He returned to bed, slept, and on awakening at 8 am and trying to walk, fell down because of weakness of the right leg. On admission to the hospital shortly thereafter, examination showed a total paralysis of the face, arm, and leg on the right side. There had been no headache or transient ischemie attack. Slight im¬ provement occurred and neurological ex¬ amination nine days later showed extreme¬ ly severe paralysis of the right side of the face and almost no teeth on the right side being uncovered on showing the teeth. The visual fields were full on confrontation to finger movement and a 3-mm white bead. The extraocular movements were full with¬ out nystagmus. There was no sensory deficit on the face. Dysarthria was so severe that unless the patient spoke slowly speech was unintelligible. There was no aphasia. With great effort the right elbow flexed slightly. The tip of the right index finger could be moved through an excursion of about 7 mm without power. The right leg could be lifted high in the air, but there was only very slight motion of the toes and ankle. Sensation was intact to pinprick, vibration, touch, joint-position, numberwriting, and stereo-naming. The tendon reflexes were increased on the right and there was a right Babinski's sign. There was no cerebellar ataxia in the left limbs. The blood pressure was 170/100 mm Hg. A diagnosis of pure motor hemiparesis of capsular origin was made. An electroencephalogram showed a slight generalized abnormality. The blood showed an eosinophilia of 45% (5,840/cu mm absolute). The sedimentation rate was 58 mm/hr. Computed tomography (CT) on day 14 was normal. Convalescence was complicated by the development of a pure sensory stroke on the left side on the 11th day of illness and mononeuritis multiplex on the 23rd day. Recovery was proceeding satisfactorily when the patient died from pulmonary embolism six months after the onset of the illness. The general pathological examination, both gross and microscopic, showed no definite abnormality except for pulmonary embolism. The gross examination of the brain after fixation in 10% formaldehyde disclosed only one lesion in the left hemisphere. It was a small irregular cavity measuring 4 by 5 mm in the posterior limb of the internal capsule at about the junction of the anterior two thirds and posterior one third (Fig 1). The lesion was revealed by shaving razor-thin slices from the region of the internal capsule, starting superiorly and progressing inferiorly until the cavity was uncovered. The right half of the thala¬ showed a lacunar infarct that mus accounted for the pure sensory stroke. The brain stem was intact. Microscopically, the left capsular lesion was an infarct cavity containing abundant lipid-filled macrophages. On reconstruct¬ ing the infarct from the sections, it measured 1.6 cm vertically, 10 mm anteroposteriorly, and 8 mm transversely. The small arteries supplying the infarcted territory were traced back to their origin from a single artery that at the inferior level of the infarct was the site of a focal unusually hemorrhagic lesion. The artery, which was about 300 µ in diameter, was almost totally destroyed, with little re¬ maining of the original structure. Replac¬ ing it were fragments of collagenous connective tissue in a mass of hemosiderinfilled macrophages (Fig 2). The lesion was typical of lipohyalinosis1 except for the large number of hemosiderin-filled macro¬ phages, which indicated that extravasation was greater than usual. Proximal to the lipohyalinotic lesion the artery resumed its normal appearance and was traced to its junction with neighboring arteries that were then followed downward approxi¬ mately 13 mm to the origin of the parent branch from the middle cerebral artery. No other vascular lesions were found. It was concluded that the lacunar infarct was the result of occlusion of an artery by a hemor¬ rhagic lipohyalinotic lesion. Fig 1.—Case 1. Infarct in posterior limb of internal capsule. Fig 2.—Case 1. Hemorrhagic lipohyalinotic occlusion of penetrat¬ ing artery (phosphotungstic acid-hematoxylin, 200). Downloaded From: http://archneur.jamanetwork.com/ by a University of Iowa User on 06/10/2015 Case 2.—A mildly hypertensive woman, aged 67, on arising one morning, noted incoordination, uncertainty, and shuffling of the left leg when she stood on it, a tendency to veer to the left, and a feeling the knee might buckle. The left fingers felt "a little cold." Examination 24 hours later showed slight weakness of the face and arm on the left side and slightly more prominent weakness of the left leg both proximally and distally, greater distally. The patient did not support herself on the left heel and toes as well as on the right. There was no dysarthria. Sensation was intact. The visual fields were full. The tendon reflexes were brisker and there was a Babinski's sign on the left side. On holding the left leg out with the knee straight, there was an up-and-down waver¬ ing motion of 3 to 4 cm in amplitude. On the heel-knee-tibia test, the left leg was slow and incoordinate. The patient walked slowly without danger of falling, carefully placing the left foot. The Romberg test was negative. The blood pressure was 176/80 mm Hg. An electroencephalogram and CT scan were normal. The patient was much improved in four days and fully recovered in about one month except for a persisting left Babinski's sign. She died six years later from primary pulmonary carcinoma. Gross sectioning of the brain showed only one lesion, a small cavity 5x4 mm in the upper medial part of the left putamen abutting on the internal capsule at the junction of the anterior three fourths and posterior one fourth (Fig 3). The pons showed no lesion. Examination of serial sections of the region showed an old infarction extending approximately 1 mm into the internal capsule, which was pale over an anteroposterior distance of approximately 4 mm. A small artery, 300 µ in diameter, supplying the territory of the infarct was accurately traced and although its wall was thickened here and there, nowhere was the lumen Fig 3.—Case 2. Infarct (marker) in putamen at edge of internal capsule. Fig 4.—Case 3. Old cavitating lesion in left internal capsule. Superficial infarct (ar¬ row) is recent. Fig 6.—Diagram of sites of vascular obstruction: 1, case 5, right and left; 2, case 7; 3, case 6; 4, case 8; 5, case 3; 6, case 8; 7, cases 1 Fig 5.—Case 3. Penetrating artery (PA) at origin from middle cerebral artery (MCA) showing atheromatous plaque (hematoxy¬ lin-eosin, 39). Downloaded From: http://archneur.jamanetwork.com/ by a University of Iowa User on 06/10/2015 and 9. narrowed by more than 50%. More proximally this artery was joined by arterial branches supplying intact tissue, an indica¬ tion that any obstruction must have lain distal to these branches. No occlusion was found in the more proximal penetrating arteries down to the stem of the middle cerebral artery. In the absence of an occlu¬ sion, it was concluded that either a very small embolus had entered the penetrating artery and undergone subsequent lysis or that in the six years since the stroke, a thrombotic occlusion had partially resolved with restoration of the lumen, a sequence of events that is of uncertain occurrence. There was no obvious source of an embolus. The cerebral arteries were minimally atherosclerotic. The cervical segment of the internal carotid artery was not exam¬ ined at autopsy. Case 3.—A hypertensive woman, aged 77, suffered a right hemiparesis without impairment of speech or mind. Recovery was imperfect and although the patient could walk with assistance the right arm remained useless. She maintained an active interest, conversed with her friends, read the newspaper, and listened to the radio. She was occasionally incontinent of urine. The patient died three years later, following amputation for incipient gan¬ grene of the right leg. Examination in the final illness showed moderate residual paresis of the face, arm, and leg on the right side. There was no intellectual impairment, dysphasia, visual field defect, or sensory loss. General pathological examination showed recent myocardial infarction and mural thrombus in both atrial appendages. On neuropathologic examination there were five recent superficial infarcts, three in the right cerebral hemisphere, one in the left, and one, 7 x 12 mm, in the left cere¬ bral hemisphere. In each instance the artery of supply was blocked by gray embolie material. These softenings ac¬ counted for the postoperative coma. The only old infarct was a trabeculated cavity, measuring 25 mm vertically, 15 mm anteroposteriorly, and 7 mm transversely, in the posterior limb of the left internal capsule involving the adjacent body of the caudate nucleus, the posterior putamen, the posterior part of the globus pallidus, the external capsule, claustrum, and extreme capsule (Fig 4). The left cortico¬ spinal system was atrophie in the pons. On examination of serial sections of the left basal ganglia, the artery supplying the territory of the infarct was identified and traced downward through the inferior Fig 7.—Case 4. Capsular infarct. Fig 8.—Case 5, right side. Infarct in posterior limb of internal capsule (Loyez myelin, 2). Fig 9.—Case 5, right side. Atheromatous stenosis of penetrating branch (Verhoeff's elastic stain, 230). Downloaded From: http://archneur.jamanetwork.com/ by a University of Iowa User on 06/10/2015 putamen and subarachnoid space to the middle cerebral artery. The only signifi¬ cant lesion lay at the junction of the pene¬ trating artery with the middle cerebral artery, where an atheromatous plaque 2 mm long narrowed the lumen to about 40 µ or less (Fig 5 and 6). The artery at this point was about 750 µ in external diameter. No mural thrombus was present and all parts of the vessel contained blood, indicat¬ ing that the main lesion, at least at the time of death, was stenotic rather than occlusive. A striking feature of the plaque was its composition, which consisted almost entirely of large fat-filled macro¬ month later. Examination of the brain showed a large cavitating infarct involving the posterior limb of the left internal capsule and the adjacent putamen and body of the caudate nucleus. The infarct measured 2.5 cm verti¬ cally, 2 cm anteroposteriorly, and 1.2 cm transversely (Fig 7). The only other lesion was a 1-cm area of destruction of the sylvian cortex of the left midtemporal lobe. Microscopic examination of serial sec¬ tions of the left basal ganglia clearly iden- phages. Case 4.—A normotensive right-handed man, aged 68, suddenly developed a right hemiplegia and speech difficulty. Exami¬ nation showed flaccid paralysis of the right limbs, weakness of the right side of the face, thickness of speech, and dysphagia. Fifteen minutes after arrival in the emer¬ gency room, he said indistinctly, "I hope I will be all right." The blood pressure was 150/90 mm Hg. Swallowing improved in two days. The patient had had a myocardial infarction two years before. Neurological examination two months after the stroke showed slurring of speech without dyspha¬ sia. The visual fields were full. There was no motion of the fingers or toes on the right side, but the leg could be lifted in the air. Pinprick was slightly less painful on the right side. The patient could take a few steps unassisted. An electroencephalogram showed slowing in the left centrotemporal region. The patient died suddenly one Fig 10.—Case 6. Capsular infarct (mark¬ er). tified the arteries supplying the territory of the infarct. As the two main arteries were followed inferiorly, they remained separate until 0.5 mm from the middle cerebral artery when they united to form a common trunk 800 µ in diameter. Through¬ out the entire penetrating branch system from the infarct to the middle cerebral artery, there was no obstructive lesion and the vessels were remarkably free of any trace of atherosclerosis. The middle cere¬ bral artery itself was also free of atheroma. These findings suggest embolism, and in this regard it is significant that the cere¬ bral cortex on the same side showed a superficial lesion of about the same age as the capsular infarct. It is remarkable that the patient had no dysphasia despite the large infarct and severe right hemiplegia. Case 5.—A man, aged 71, over a period of half an hour developed complete paralysis of the left arm and leg. He recovered by the third day, only to have total paralysis recur. There was gradual recovery in two weeks, leaving only slight clumsiness of the fingers. There had been no sensory or visual loss. The blood pressure varied from 150/95 to 200/120 mm Hg. Three months later, the patient devel¬ oped a right hemiparesis from which he slowly recovered. One month still later, the right hemiparesis recurred and was asso¬ ciated with complete speechlessness. Ex¬ amination showed aphonia and total paral¬ ysis of the lips and tongue. The right arm and leg were moderately weak in the absence of sensory loss, visual field deficit, or aphasie errors. There was a Babinski's Fig 11.—Case 6. Atheromatous stenosis with organizing clot extending proximally (Verhoeff's elastic stain, 95). Fig 12.—Case 7. Capsular infarct involving genu and anterior limb. Downloaded From: http://archneur.jamanetwork.com/ by a University of Iowa User on 06/10/2015 Fig 13.—Case 7. Atheromatous plaque in pene¬ trating artery with superimposed recent fibrinplatelet thrombus (phosphotungstic acid-hema¬ toxylin, X130). Fig 14.—Case 8. Capsular infarct in anterior limb. Fig 15.—Case 8. Atheromatous stenosis of 400-µ penetrating 290). artery (phosphotungstic acid-hematoxylin, Fig 16.—Case 9. Myelin stain of section across uppermost internal capsule, showing infarct (I) in posterior segment of internal capsule (IC). PT indicates putamen. Adjacent segment of cortex is missing. sign bilaterally. The blood pressure was 170/105 mm Hg. The blood cholesterol level was 250 mg/dl. The patient died two months later. Microscopic examination of large blocks of each basal ganglia showed bilateral capsular infarcts. On the right side, the infarct lay in the midportion of the poste¬ rior limb of the internal capsule and measured 12 mm vertically, 10 mm antero- posteriorly, and 3 mm transversely (Fig 8). The infarct lay in close relation to a small atheroma that severely narrowed the artery of supply, normally 425 µ in diame¬ ter, to about 50 µ (Fig 9). The plaque that lay at the lowest extremity of the infarct, just within the brain substance (Fig 6), was situated at the origin of its artery from another penetrating artery of similar size that originated from the anterior choroidal Downloaded From: http://archneur.jamanetwork.com/ by a University of Iowa User on 06/10/2015 artery. The atheroma consisted of large, round, reticulated cells typical of fat-filled macrophages. The wall of the artery, while not necrotic, was split into several layers forming a latticework. Abundant hemosiderin-filled macrophages lay perivascularly, a picture reminiscent of the lipohyalinotic lesions that affect smaller arteries, but on larger scale. On the left side, there was an irregular a infarct 4x4x5 mm lying at the genu of the internal capsule. The lesion was similar to that on the right side. The artery of supply, measuring about 400 µ in diameter, was narrowed to about 40 µ by a plaque of fat-filled macrophages. There was no superimposed thrombus and a few hemosiderin-filled macrophages lay nearby. The arterial lesion lay at the lowest extremity of the infarct in a vessel whose parent artery had traversed the optic tract and appeared to be a branch of the anterior choroidal artery. In this case, the capsular infarcts were traced to sites of arterial stenosis rather than occlusion. There were no other vascu¬ lar lesions of any severity, and the location of the stenoses accurately corresponded to the territory of the infarcts. No other softenings were found along the corticospi¬ nal systems, and the combination of lesions on the two sides probably explains the presence of bilateral pure motor hemipare¬ sis with facial-buccal-lingual palsy. Case 6.—A hypertensive woman, aged 84, while in the hospital receiving vigorous antihypertensive therapy, suddenly devel¬ oped a complete left hemiplegia. A sensory examination was not recorded. The pulse was regular. In the next three months, the patient slowly recovered, but then died suddenly of a pulmonary embolus. General pathologic examination showed evidence of old and recent pulmonary emboli. The foramen ovale was patent, having a 5-mm aperture. The fixed brain when sectioned horizon¬ tally showed three lesions. The main lesion was a trabeculated cavity, measuring 1.5 in a vertical axis, 1.5 cm anteroposteriorly, and 0.5 cm transversely, lying just posterior to the midpoint of the posterior limb of the internal capsule on the right side (Fig 10). The other two lesions involved the right frontal cortex: The first, measuring about 1 cm in diameter, lay on the anterior wall of the precentrai sulcus, while the second, 2x1x4 mm, lay in the cm middle frontal gyrus. Microscopic examination of serial sec¬ tions of the right basal ganglia disclosed that the artery supplying the territory of the infarct was stenosed almost to the point of occlusion by an atheroma lying just inferior to the lower limit of the infarct (Fig 11). The plaque lay 2 mm from the middle cerebral artery at a point where the penetrating artery turned abruptly upward from a horizontal to a vertical plane (Fig 6). The lumen, which was narrowed to about 30 µ, was completely occluded by an organizing clot for 1 mm proximal to the region of greatest stenosis. The involved artery, which was about 500 µ in diameter, was traced proximally to its origin from the middle cerebral artery without finding a further obstructive lesion. It is possible that rapid drastic treat¬ ment of the patient's hypertension precipi¬ tated ischemia distal to a severe stenosis. Case 7.—A hypertensive man, aged 55, awakened from a nap with slurred speech and weakness of the face, arm, and leg on the right side. Examination disclosed severe dysarthria, marked weakness of the right side of the face, and slight weakness of the right arm and leg without sensory loss. There was a right Babinski's sign. Speech was sparse and halting, each three or four words being followed by a pause, as if the patient were searching for a word. Words were occasionally mispronounced but immediately corrected. The patient followed complex commands, repeated the words of the examiner, named ten objects, wrote, read, and calculated satisfactorily. Gait was slightly broad-based. Retinal hemorrhages were present. The blood pres¬ sure was 240/120 mm Hg. Vigorous antihy¬ pertensive therapy was instituted. The next day the patient was lethargic and complained of a left frontal headache. There was no spontaneous speech, and the patient uttered only single syllables and unintelligible sounds. He followed oral and written commands. There was slight weak¬ ness of the right arm and leg. Sensation was intact. On day 3 the right hand was paralyzed, but the right leg still moved well. Although motor power improved on days 4 to 7, there was still no return of speech and dysphagia was troublesome. The patient developed pneumonitis and died on day 10. On pathological examination the main lesion was a recent infarct that involved the superior portion of the genu and ante¬ rior limb of the internal capsule and extended downward through the lateral putamen to within 2 mm of the middle cerebral artery (Fig 12). In its superior part the infarct, which measured 23 mm anteroposteriorly, involved 17 mm of the anterior limb of the internal capsule and 6 mm of the posterior limb, as well as the adjacent body of the caudate nucleus. The infarct measured 19 mm transversely at this level and narrowed to a few millime¬ ters in its most inferior extent. The infarct reached to within 18 mm of the cerebral cortex laterally, but did not involve the motor cortex or Broca area or the white matter beneath them. There were four additional lesions. The first and the one that may have played a part in the clinical picture consisted of an infarct, old and trabeculated, in approxi¬ mately the mirror position of the lesion described above, involving, on the right side, the anterior limb of the internal capsule, the anterior part of the body of the caudate nucleus, and the upper part of the putamen. It measured 12 mm vertically, 6.5 mm anteroposteriorly, and 4 mm trans¬ versely. The other lesions were a 2 2-mm lacune in the right upper putamen, a 4-mm lacune in the white matter of the left temporal lobe, and a narrow scar 12 mm long in the right parieto-occipital region, probably an old hemorrhage. Microscopic examination of serial sec¬ tions of the assembled blocks of the left basal ganglia identified the responsible vascular lesion. A medial penetrating branch of the middle cerebral artery, 500 µ in diameter, was totally occluded at a point 1.2 mm within the brain substance (Fig 6) by an atherosclerotic mass that narrowed the lumen to 20 µ and on which was super- Downloaded From: http://archneur.jamanetwork.com/ by a University of Iowa User on 06/10/2015 imposed an organizing, fibrin thrombus (Fig 13). The lumen immediately proximal to the obstruction contained a recent fibrin-platelet thrombus. The segment of total occlusion measured only about 0.13 mm in length. The stenosing athero¬ sclerotic plaque lay just distal to a rightangle bend in the artery and was no more than 1 mm in length. The atheroma consisted mainly of fat-filled macro¬ phages. The occluding thrombus immediately proximal to the point of greatest stenosis origin and raised the ques¬ tion whether vigorously lowering the blood pressure had not created ischemia distal to the stenosis. Case 8.—A mildly hypertensive diabetic man, aged 72, who had previously been mentally sound was found in a greatly altered state after being alone for about eight hours. His conversation was "inco¬ herent," and he did not know that he was at home. The left side of the face sagged. The patient staggered when he walked, knock¬ ing objects from the table. He attempted to cook meat for supper whereas in the past he had never been known to engage in cooking. He was described as "like drunk." That night he fell out of bed. On examina¬ tion the next day, the patient's speech made good sense and there was no dysar¬ thria. On the left side there was slight weakness of the face, arm, and leg, the tendon reflexes were brisker and a Babin¬ ski's sign was present. On attempting to walk the patient staggered, tending to fall to the left and backward. There was no cerebellar ataxia in the arms or legs. Sensation was intact to light touch, hot and was of recent cold, vibration, joint position, stereognosis, and number writing. Sensitivity to pin¬ prick was less on the dorsum of the left foot than on the right. Copying and drawing excellent. The blood pressure was 160/90 mm Hg. The patient's condition improved in two weeks, but there persisted a slight impairment of memory and judg¬ ment that in the following months gradual¬ ly merged with a progressive senile demen¬ tia. The patient died of congestive heart failure approximately three years after the were original ictus. Gross pathologic examination of the brain showed only one vascular lesion, a trabeculated cavity in the anterior limb of the right internal capsule extending poste¬ riorly to the genu (Fig 14). It measured 1.5 cm vertically, 1 cm anteroposteriorly, and 1 cm transversely. It extended slightly into the caudate nucleus medially, into the medial putamen laterally and within 2 mm of the surface of the brain inferiorly. There was no surface lesion in the right hemi¬ sphere. There was an advanced degree of frontal convolutional atrophy. On microscopic examination of serial sections of the right basal ganglia, the artery of supply to the infarcted territory was traced proximally through the puta¬ men and the subarachnoid space to its origin from the middle cerebral artery, where it measured 400 µ in diameter. At a distance of 2.5 mm from the middle cere¬ bral artery and just before leaving the subarachnoid space to enter the brain tissue, the vessel changed direction acutely from vertical to horizontal. Immediately proximal to this angulation, the lumen was narrowed to about 50 µ by a plaque of atheroma 750 µ in length consisting almost totally of compartments of lipid (Fig 6 and 15). There was no superimposed thrombus. One cannot be certain that this ather¬ omatous plaque was responsible for the infarct, but it was correctly situated and the other penetrating branches of the middle cerebral artery were free of disease. The degree of stenosis at which flow in a penetrating artery becomes reduced is not known, but judging from observations in the present series of cases, severe narrowing is not tolerated as well as it is in larger cerebral arteries. In this case the clinicopathologic correla¬ tion is made with some reservation. It is tempting to suggest that the lacune in the anterior limb of the internal capsule resulted not only in slight weakness of the left side but also in behavioral change. It is possible, however, that the patient was entering on senile dementia and a strategi¬ cally placed lesion evoked a greater effect than it would have otherwise. Case 9.—A severely hypertensive man, aged 59, on going to the bathroom at 3 am noted weakness and clumsiness of the right limbs and slurring of speech. Two days before, at 6 pm, the patient had noted weakness of the right hand for about one hour. Examination at 10 am showed moder¬ ate slurring of speech, drooping of the right side of the face, almost complete paralysis of the right arm and fingers, and severe weakness of the right leg although the patient could feebly lift it in the air and move the toes slightly. The extraocular movements were full without nystagmus. On the right side, the tendon reflexes were increased and there was a Babinski's sign. One examiner described involuntary spasms of laughter and crying. Sensation was intact to routine tests. There was no dysphasia or visual field defect. Intellec¬ tual function was intact. The blood pres¬ sure was 210/145 mm Hg. An electroen¬ cephalogram was normal. Recovery began in a few days but was incomplete. Eighteen months later, movements of the right limbs were full but slow. Power of abduction and adduction of the fingers was 7/10, and the patient walked with a moderately severe limp. He returned to full-time employ¬ ment. Death occurred 6% years later due to uremia. Gross examination of the brain disclosed a cavity 5x5 mm involving the left inter¬ nal capsule and the adjacent putamen and body of the caudate nucleus. In addition, there was a 3-mm infarct in the head of the caudate nucleus bilaterally. An 11-mm yellow slit marked the site of a small old hemorrhage in the anterior limb of the left internal capsule, estimated to be 4 months of age, too recent to account for the hemi¬ plegia. Microscopic examination of serial sec¬ tions of the left basal ganglia showed a well-trabeculated infarct cavity involving the putamen and adjacent posterior limb of the internal capsule and extending inferiorly to within 8 mm of the middle cerebral artery (Fig 16). The territory of the infarct was supplied by a penetrating artery branch about 400 µ in diameter that at the inferior margin of the infarct was narrowed by atherosclerosis to about 150 µ. No point of greater narrowing was found although several small branches within the infarct were totally occluded by fine connective tissue. As a satisfactory expla¬ nation of the infarct was not at hand, the vascular lesion is classed as "uncertain" although embolism is a possibility. Study of this case was hindered in that in dividing the block in two for processing the knife passed directly through the crucial vascular zone. Case 10.-A mildly hypertensive man, aged 77, who had been progressively more forgetful for three years, underwent resec¬ tion of a large abdominal aortic aneurysm. Postoperative recovery was good and the patient was again able to walk. On the seventh postoperative day, the left arm and left leg were slightly weak and in the next four days became totally paralyzed. The patient was unaware of the paralysis. Examination, which was complicated by the patient's mental state, showed weak¬ ness of the face and complete paralysis of the arm and leg on the left side. Pinprick was felt on the left leg but not on the face and hand. Recovery was poor and the patient died of myocardial infarction six weeks later. Neuropathologic examination showed a large pale infarct involving the internal capsule and putamen on the right side. The only superficial lesions were a few small infarcts, 3 to 10 mm in diameter and several weeks old, scattered in the white matter of the right premotor region. Examination of the right middle cere¬ bral artery showed severe atherosclerotic stenosis at the origin of the superior divi¬ sion with extension distally for about 7 mm. From this diseased segment of artery arose two lateral penetrating branches that ran through the lateral putamen to the territory of the infarct (Fig 6). Although serial microscopic studies were not made, it appeared certain that the obvious vascular lesion was the cause of the putamenocapsular softening. The scattered hemispheral lesions lay in the superficial territory of the stenosed superior division but would not account for the hemiplegia. COMMENT Pathological Findings In summary, of the 11 capsular infarcts eight can be classed as large and three as small (two in case 5 and one in case 9). They were located in the posterior limb of the internal capsule in eight instances and mainly in the genu or anterior limb in three instances (cases 5, 7, and 8). Five were on the right side of the brain and six on the left. In ten instances the vessels were traced out microscopical¬ ly, while in the 11th (case 10) only a Downloaded From: http://archneur.jamanetwork.com/ by a University of Iowa User on 06/10/2015 gross dissection was made. A vascular lesion that accounted for the infarct was found in nine; in the other two, the penetrating arterial system was either free of occlusive disease or stenosis was not severe. The size of the involved arteries determined in ten instances was as follows: 800, 750, 500 (twice), 425, 400 (three times), and 300 (twice) µ. The vascular obstruction was in a penetrating artery eight times, while in the other (case 10), an atherosclerotic occlusion of the first part of the superior division of the middle cerebral artery probably blocked the mouth of one or two later¬ al penetrating arteries. The eight lesions in the penetrating arteries lay 2 to 13 mm from the origin of the vessels except in case 3, where the lesion lay at the very origin of the penetrating artery from the middle cerebral artery. In seven instances, the penetrating branch lesion con¬ sisted of a small highly localized atheromatous plaque, while in one, lipohyalinosis was the process.4 Two of the atheromatous plaques were asso¬ ciated with a superimposed microthrombus, while the other four had produced severe stenosis with reduc¬ tion of the lumen to one tenth or less of normal but the residual lumen remained patent. In cases 6 and 7, the superimposed thrombus consisted of a small fibrin-platelet mass at the prox¬ imal end of the plaque. In several cases, the vascular lumen distal to the occlusion and particularly within the infarct contained fine fibrillar connec¬ tive tissue enclosing small channels of recanalization. In two cases (No. 2 and 4) in which the arteries supplying the infarct were patent and intact, embolism is postulated as the mechanism of infarction. It is well established that embolie material disappears in the hours and days following embolism, leaving no trace at the expected site of block. Just as embolie material enters the retinal circulation from both known and unknown sources, it is expected that material—platelet, fi¬ brin-platelet, cholesterol, or coagulum-enters the penetrating branches of the middle cerebral artery. No remnants of cholesterol material were found in the present cases. An embolie source was not found at routine necropsy, but an inobvious source in the carotid system, aorta, or heart would have to be considered. In case 4, the patient had had a myocardial infarction in the past. In these cases it is difficult to entertain seriously a mechanism other than embolism. Vasospasm and complete resolution of an atheroma are unlikely possibilities. Normal vessels have also been found in a personal case of basilar branch infarction of the pons studied with serial sections. In case 9, the nature of the vascular occlusion was left "uncertain" al¬ though an atherosclerotic plaque nar¬ rowed the appropriate artery by one third. The patient survived his stroke for 6V2 years and the findings at autopsy may not have reflected the acute state. The term "atheroma" is hardly appropriate for the miniature plaques because, for the most part, they of fat-filled great size and macrophages, many with indistinct boundaries. consisted of a mass some of "Lipid macrophage" plaque or "lipophage" plaque would be a more accu¬ rate designation. Fibrillar connective tissue proliferation, mural thrombus, cholesterol clefts, and hemorrhage into plaques were absent or minimal. Apart from the individual occlusive plaques described, the penetrating arteries were sometimes free of disease. The plaques lay at the site of a sharp change in direction of an artery in four instances and at the very origin of a branch in two, illus¬ trating the influence of physical forces in the deposition of atheroma. Clinical Findings The clinical findings that were accu¬ rate in cases 1, 2, 7, 8, and 9 and adequate in the other cases support the concept that capsular infarction is characterized by a purely motor hemi¬ plegia or hemiparesis involving the face, arm, and leg without sensory deficit, homonymous hemianopia, aphasia, or apractognosia.1 Weakness of the limbs was profound in six instances and moderate in five. Case 8 may illustrate the occurrence of men¬ tal change with lacunar infarction, an aspect of small-vessel disease not fully defined. The speech disorder in case 7, although not described in detail, suggested a Broca motor aphasia approaching anarthria. The strokes usually developed suddenly, and in only one case were there prodromal transient ischemie attacks. Hyperten¬ sion was severe in three cases and only moderate in the others; in the latter, mainly the systolic level was elevated, illustrating that systolic hypertension may cause vascular damage. One patient was mildly diabetic and anoth¬ er had an abnormal glucose tolerance curve. Of interest was the occurrence of capsular infarcts bilaterally in two cases (No. 5 and 7), the lesions lying in mirror positions in one. Several addi¬ tional cases have been seen clinically in which pure motor hemiplegia has occurred first on one side and within a few months on the other. In case 5, with bilateral lesions, speech, swallowing, and movements of the tongue were unimpaired with the left hemiplegia, yet persistent apho¬ nia and paralysis of the tongue resulted from the later development of infarction at the genu of the oppo¬ site internal capsule. This suggests either that control was so completely bilateral that the right corticobulbar tract subserving the buccal region could be unobtrusively put out of action or, less likely, that control normally resided wholly in the left hemisphere. The neurological deficit in cases 1, 3, 4, and 9 deserves a brief comment in that a lesion of the internal capsule on the dominant side caused a distur¬ bance of speech that was only tempo¬ rary. This might indicate that either the nondominant motor system is capable of assuming speech function with relatively complete bilateral con¬ trol of the speech apparatus or the Downloaded From: http://archneur.jamanetwork.com/ by a University of Iowa User on 06/10/2015 corticobulbar fibers subserving speech function are located further forward in the internal capsule, perhaps at the genu, thus escaping injury. Yet in each case the right side of the face was weak. A case of bilateral capsular infarction in which the dominant side was involved first would be informa¬ tive in this regard. Does this study have any therapeu¬ tic implications? It is our experience that atheromatous disease of small penetrating arteries is strictly a func¬ tion of hypertension, prevention of which should therefore largely abolish capsular infarcts. In the realm of prophylaxis, the strikingly pure lipid nature of the small-artery plaques points to a dyscrasia of fat metabo¬ lism and possibly the need to reduce dietary fats. In two of the present cases, the blood pressure was abruptly lowered at an early stage of the stroke with untoward results, a warning that such management is to be avoided. Anticoagulant therapy, for example intravenous administration of hepa¬ rin, might prevent the late thrombotic closure of the residual arterial lumen, and we recommend such therapy in the early stage of a pure motor hemi¬ plegia, particularly if transient is¬ chemie attacks of pure motor hemiple¬ gia are occurring. This investigation was supported in part by grant NS05152 from the National Institute of Neurological and Communicative Disorders and Stroke. References 1. Fisher CM, Descarries L, Zeiper I: Capsular infarcts: The underlying vascular lesions. Trans Am Neurol Assoc 91:227-229, 1966. 2. Fisher CM: The arterial lesions underlying lacunes. Acta Neuropathol 12:1-15, 1969. 3. Fisher CM: Cerebral miliary aneurysms in hypertension. Am J Pathol 66:313-324, 1972. 4. Fisher CM, Curry HB: Pure motor hemiplegia of vascular origin. Arch Neurol 13:130-140, 1965.