Leukomalacia With Ruptured Saccular Aneurysm Iftekhar Ahmed, MD, Joanna Sher, MD \s=b\ A 42-year-old woman with a ruptured saccular aneurysm of the internal carotid artery developed large areas of cerebral leukomalacia, resulting in hemiparesis and an obtunded mental state. A significant factor in the development of the white matter lesions was episodic hypotension, leading to reduced cerebral blood flow in a patient whose cerebral circulation was already compromised by vasospasm secondary to the subarachnoid hemorrhage. This case illustrates yet another clinical situation associated with the development of white matter necrosis. (Arch Neurol 36:231-232, 1979) or necrosis localized to Teukomalacia, ^ the white matter of the central nervous system, is a relatively unusual lesion that has been described in cases of congestive heart failure and drug addiction coma12 as well as in carbon monoxide intoxication and severe hy¬ poxia.35 Focal neurological deficit may occur as a result.2·3 The roles of hypoxemia, acidosis, and hypotension have been stressed as important in the pathogenesis.6 Destructive lesions of white matter are also known to occur as a result of local vascular disease with severe cerebral arteriolar sclero¬ sis (Bingswanger's subcortical en¬ cephalopathy) and with vasculitis as¬ sociated with bacterial meningitis.7 This report describes yet another group of clinical circumstances resultAccepted for publication March 3, 1978. From the Department of Pathology, Downstate Medical Center, Brooklyn, NY. Reprint requests to Department of Pathology, Downstate Medical Center, Brooklyn, NY 11203 (Dr Sher). ing in large areas of white matter necrosis, ie, ruptured saccular aneu¬ rysm of an artery of the circle of Willis with associated vasospasm and hypotension. REPORT OF A CASE A 42-year-old woman was hospitalized with complaints of severe generalized headaches and mental confusion for one day. There was a history of hypertension of several years' duration. The patient had had diabetes mellitus for 16 years. Blood pressure was 200/100 mm Hg; pulse rate, 92 beats per minute; temperature, 37 °C; and respirations, 25/min. The patient was alert but disoriented for time, place, and person. She responded to questions and was slightly restless. No focal neurological find¬ ings were demonstrable, except for nuchal rigidity. A lumbar puncture showed gross¬ ly bloody cerebrospinal fluid. Arterial blood gas values at this time were as follows: pH, 7.30; Po2, 55 mm Hg; Pco,„ 46 mm Hg. The patient was treated with methyldopa, hydralazine, hydrochlorothiazide (Hydrodiuril), and aminocaproic acid. During the first few days after admission, the patient's BUN level rose to 35 mg/dl and creatinine value to 4.6 mg/dl. On the fourth day, periods of hypotension with blood pressure as low as 80 mm Hg systolic were recorded on several occasions. Neurological examination at this time disclosed a leftsided weakness of the body, left central facial paresis, and papilledema. Decreased mental alertness was noted. Corticoste¬ roids were added to the regimen. The next day, a cerebral angiogram showed an aneu¬ rysm of the right internal carotid artery at the level of the origin of the posterior communicating artery, measuring 6x4 mm. The patient's general condition con¬ tinued to deteriorate. It was difficult to control her diabetes because of stress and corticosteroid therapy. Two days before her death, she had a large melanotic bowel Downloaded From: http://archneur.jamanetwork.com/ by a Oakland University User on 06/07/2015 Section of cingulate gyri, corpus callosum, and periventricular white matter, showing well-circumscribed areas of leukomalacia (Weil, x4). movement that was guaiac positive, and became hypotensive with a systolic blood pressure of 70 to 80 mm Hg. Despite treat¬ ment with isoproterenol, she remained hypotensive. Neurological examination at this time disclosed coma with left-sided weakness. On doll's eye maneuver, the eyes did not pass to the left of midline. Arterial blood gas values were as follows: pH, 7.28; Po„, 52 mm Hg; Pco,, 48 mm Hg. The hemoglobin level dropped from 13.2 to 10 g/dl. She developed cardiorespiratory ar¬ rest and died. At autopsy, a chronic duodenal ulcer was found, surrounded by a few adherent small blood clots. The heart was enlarged due to moderate left ventricular hypertrophy. Examination of the brain disclosed exten¬ sive subarachnoid hemorrhage over the base of the brain. There was a 4-mm ruptured saccular aneurysm of the right internal carotid artery adjacent to the origin of the posterior communicating artery. Cross sections of the cerebral hemi¬ spheres showed many well-demarcated areas of softening in the frontal and parie- tal white matter, bilaterally, measuring up to 3 cm in greatest diameter (Figure). There were similar white matter lesions in the right optic radiation adjacent to the lateral ventricle. Microscopically, the leukomalacic areas appeared pale staining and necrotic, with edematous borders. Acute inflammatory infiltrates were present, surrounding many of the small blood vessels within the necrotic areas. Microglial cells were not prominent. Only rare macrophages were noted in a few foci at the edges of the lesions. COMMENT Most commonly, the cerebral lesions associated with ruptured saccular aneurysms are infarctions of the cortex and basal ganglia. In a series of 159 cases reported by Crompton,8 necrosis of white matter was found only as a part of areas of encephalomalacia that were primarily cortical. Isolated areas of leukomalacia in such apparently rare. general, leukomalacia is cases are In uncommon an lesion, known to occur in some cases of congestive heart failure and in coma associated with excessive ingestion of drugs such as heroin and barbiturates. Carbon monoxide intox¬ ication is known to produce leukomal¬ acia. Such white matter lesions in carbon monoxide intoxication are at¬ tributed to the anoxia, edema, and local hemodynamic changes in the white matter, as well as to disturbed glycogen metabolism.911 In some cases, acidosis and hypoxia have been thought to act synergistically in the production of white matter edema and subsequent necrosis.612 Hypotension, resulting in reduced cerebral blood flow, and associated hypoxemia, were found to be the common clinical features in three cases reported by Ginsberg et al.1 Similarly, in the case reported by DeReuck and Schaum¬ burg,2 there was decreased cerebral blood flow secondary to an acute decrement in cardiac output, in a patient with a cerebral circulation already compromised by arteriosclero¬ sis. In our case, the large areas of leuko¬ malacia apparently resulted from the reduced cerebral blood flow during the hypotensive episodes in a patient whose cerebral circulation was already compromised by vasospasm secondary to subarachnoid hemorrhage. Changes in her cardiovascular status may have been secondary to the subarachnoid hemorrhage. The effects of subarach¬ noid hemorrhage on the cardiovascu¬ lar system have been well describ¬ ed1314 and are attributed to the altered autonomie tone to the heart.151B The acidosis, which was verified several times during her hospital course, may have acted as a contributing factor. DeReuck and Schaumburg2·17 de¬ scribed three different vascular ar¬ rangements supplying the periventri¬ cular regions, all of which are in arte¬ rial end zones. The arterial supply of the white matter surrounding the anterior horns and bodies of the later¬ al ventricles is provided by long per¬ forating branches of leptomeningeal vessels that turn away from the ventricular wall in a "ventriculofugal" pattern. The significance of this pattern of vascular supply is that the last white matter area to receive the arterial flow is therefore at a short distance from the ventricular wall. By contrast, a "ventriculopetal" pattern is found in the anterior corpus callo¬ sum and brain stem, whereas a combi¬ nation of both types is seen in areas adjacent to the choroid plexus. The pattern of lesions noted in our case, with frequent sparing of a rim of white matter immediately adjacent to the ventricle, is consistent with these observations. Downloaded From: http://archneur.jamanetwork.com/ by a Oakland University User on 06/07/2015 References 1. Ginsberg MD, Hedley-Whyte ET, Richardson EP: Hypoxic ischemic leukoencephalopathy. Arch Neurol 33:5-14, 1976. 2. DeReuck J, Schaumburg HH: Periventricular atherosclerotic leukoencephalopathy. Neurology 22:1094-1097, 1972. 3. Lapresle J, Fardeau M: Les leuco-enc\l=e'\phalopathies de l'intoxication oxycarbon\l=e'\e.Acta Neuropathol 6:327-348, 1966. 4. Schwedenberg TH: Leukoencephalopathy following carbon monoxide asphyxia. J Neuropathol Exp Neurol 18:597-601, 1959. 5. 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