N. F. Kassell

Treatment of right hemispheric cerebral infarction by hemicraniectomy.

An anecdotal series of nine patients (three men and six women with an average age of 57 years) presented with progressive neurologic deterioration while on medical therapy for large right hemispheric cerebral infarction. Clinical signs of uncal herniation (anisocoria or fixed and dilated pupils, and/or left hemiplegia with right decerebrate posturing) were present in seven of these nine patients. Computerized tomography of the head confirmed mass effect from cerebral edema. It was the clinical judgment of the treating neurologists and neurosurgeons that each of these nine patients would perish unless surgical decompression of the infarcted brain was performed. Accordingly, each was treated with right hemicraniectomy and dural augmentation. Six patients demonstrated neurologic improvement on the first postoperative day. One patient, with a postoperative diagnosis of lung cancer, died 1 month after surgery. The remaining eight patients are currently living with their families with a follow-up period ranging from 5 to 25 months. Patient outcome as evaluated by the Barthel Index indicates that three individuals are functioning with minimal assistance and that the remaining six patients are functionally dependent. After rehabilitative therapy, four patients returned for elective cranioplasty. These results suggest that hemicraniectomy can be an effective lifesaving procedure for malignant cerebral edema after large hemispheric infarction.

Impairment of endothelium-dependent vasodilation induced by acetylcholine and adenosine triphosphate following experimental subarachnoid hemorrhage.

The effect of subarachnoid hemorrhage (SAH) on endothelium-dependent vasodilation of isolated rabbit basilar artery was examined using an isometric tension recording method. Thirty-five rabbits that had 2 successive blood injections were divided into 3 groups: normal animals (control), 4 days, and 3 weeks after the first SAH. Acetylcholine (ACh) (10(-6)-10(-4) M) and adenosine triphosphate (ATP) (10(-6)-10(-4) M) were used to evoke dose-dependent vasodilation of isolated arterial rings previously contracted by 10(-6) M serotonin. In the animals killed 4 days after the first SAH, both ACh- and ATP-induced relaxation were suppressed, and the degree of relaxation of this group was 38 +/- 4.5% (mean +/- SEM) and 22 +/- 3.9% of the initial contractile tone in response to 10(-4) M ACh and 10(-4) M ATP, respectively. Suppression of the relaxation induced by ATP was seen even in the animals killed 3 weeks after the first SAH. Moreover, pretreatment with hemoglobin (10(-6) and 10(-5) M) inhibited endothelium-dependent vasodilation induced by ACh in the arterial rings from the animals killed 4 days after the first SAH. The present experiments suggest that impairment of the endothelium-dependent vasodilation following SAH may be involved in the pathogenesis of cerebral vasospasm.

Delay in referral of patients with ruptured aneurysms to neurosurgical attention.

Aneurysmal subarachnoid hemorrhage is a neurosurgical emergency. Early medical intervention is axiomatic for minimizing rebleeding and ischemia from vasospasm and achieving optimum results. The purpose of this study was to document the length and causes of the delay in referral which occur in patients following aneurysmal subarachnoid hemorrhage. The case histories of 150 consecutive patients admitted to The University of Iowa with proven ruptured aneurysms were studied. Medical records from The University of Iowa and referring hospitals were reviewed, and patients, families, and referring physicians interviewed. Overall, only 36% were referred within 48 hours of their first clear cut, recognizable sign or symptom of subarachnoid hemorrhage. Median time to referral was 3.6 days. Delay was due to physician diagnostic problems in 37%, delayed referral policy in 23%, unstable patient condition in 7%, failure of patients to recognize severity of illness in 8%, and logistical reasons in 12%. These data suggest that a large proportion of patients have a delay in achieving definitive neurosurgical care following aneurysm rupture, and that for the most part this delay is avoidable. More emphasis must be placed on public health and primary physician education regarding subarachnoid hemorrhage.

Histological changes in the normal rat brain after gamma irradiation

SummaryRadiation-induced changes in the parietal cortex of Wistar rats were observed at various time points after gamma surgery. Maximum dosages of 50, 75, and 120 Gy were given at the iso-center of the radiation using a 4-mm collimator. Conventional histochemical and immunocytochemical analyses, and computer-assisted videomicroscopy were utilized to examine perfusion-fixed brain tissue.Irradiation at a dosage of 50 Gy elicited morphological changes of astrocytes in the parietal cortex at 3 months. Vasodilatation became obvious at 12 months; fibrin deposition was observed in the dilated capillary wall. Neither leakage of Evans Blue from the vasculature into the tissue nor necrosis was observed across the 12 month observation period.Irradiation at a dosage of 75 Gy resulted in morphological changes of astrocytes within 1 month. Dilatation of vessels and capillary thickening were observed at 3 months. Evans Blue leakage and necrosis were observed at 4 months after 75 Gy irradiation. At this time, the walls of arterioles became thickened by subintimal accumulation of fibrin and hyaline substance; this sometimes resulted in occlusion of the lumen. Significant hemispheric swelling was observed at 4 months.Irradiation at a dosage of 120 Gy elicited changes in astrocytic morphology within 3 days. Evans Blue leakage into the tissue was observed by 3 weeks. Vasodilatation became marked at this time point and rarefaction was observed in the irradiated cortex. Necrosis was observed at 4 weeks, however, no significant swelling was observed.Taken together, these findings demonstrate time-dependent and dosage-dependent changes in normal cerebral tissue after Gamma Knife irradiation. These results provide a basis for gauging the impact of gamma surgery in regions of eloquent tissue. An enhanced understanding of the cellular responses to radiosurgery will contribute to developing and evaluating future applications for gamma surgery.

Failure of heparin to prevent progression in progressing ischemic infarction.

Anticoagulation with heparin is frequently recommended for patients with progressing ischemic cerebral infarction, yet little data is available detailing the acute results of treatment with this agent. We report the results of continuous intravenous heparin treatment in 36 consecutive patients admitted with progressing ischemic infarction, all of whom had computed tomography scans to exclude the diagnosis of hemorrhage prior to treatment. Overall, 18 of 36 (50%) had continued neurologic worsening despite treatment. The incidence of further worsening was greater in carotid territory infarctions (14 of 19, 74%) than in either vertebrobasilar (2 of 8, 25%) or lacunar (2 of 9, 22%) infarctions (p less than 0.05, Fishers exact test). These observations suggest that additional controlled studies of the efficacy of heparin in progressing ischemic infarction are warranted.

Hippocampal unit activity after transient cerebral ischemia in rats.

Single unit activity of CA1 and CA3 neurons in the hippocampus was recorded in rats 1, 2, or 3 days after 10 minutes of transient cerebral ischemia induced by the clamping of both carotid arteries combined with hypotension. In addition, paired pulse inhibition/facilitation of the CA1 population spike was examined on Day 2 using two successive stimuli of the contralateral CA3 region delivered at various intervals. On Day 1, the mean +/- SEM firing rate in the CA1 region was 0.91 +/- 0.42/sec (n = 5), which was not significantly different from the control value of 0.98 +/- 0.26/sec (n = 5). Firing rate increased on Days 2 and 3 to 3.96 +/- 0.69/sec (n = 5), and 6.49 +/- 0.89/sec (n = 5), respectively. In the CA3 region, the mean +/- SEM firing rate of 1.18 +/- 0.27/sec in the five control rats sharply dropped to 0.14 +/- 0.11/sec in the five Day 1 rats and gradually increased to 0.45 +/- 0.11/sec in the five Day 3 rats. Histologic examination of these rats revealed ischemic changes restricted to CA1 neurons on Days 2 and 3. The paired-pulse experiment showed no significant difference between six control and six Day 2 rats in the inhibition of the second population spike with interstimulus intervals of less than 400 msec. At interstimulus intervals of greater than 500 msec there was facilitation of the second spike, which lasted 5 seconds in Day 2 rats. This facilitation was not observed in control rats. Because CA3 neurons constitute the main input to CA1 pyramidal cells, decreased activity of CA3 neurons indicates less excitatory input to CA1 neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Oxyhemoglobin-induced cytotoxicity and arachidonic acid release in cultured bovine endothelial cells.

Background and Purpose An impairment of endothelial function is associated with vasospasm after subarachnoid hemorrhage. Oxyhemoglobin is considered to be a critical trigger in the pathogenesis of vasospasm. The present studies examined the direct effects of oxyhemoglobin on cultured endothelial cells from bovine carotid artery. Methods Confluent endothelial cells were treated with oxyhemoglobin, and the following were studied: 1) cell morphology, 2) cell density, and 3) the release of radiolabel from [3H] arachidonic acid-treated cells. Results Endothelial cells exposed to oxyhemoglobin exhibited detachment vacuoles, and cell density was significantly decreased in time- and dose-dependent manners. Superoxide dismutase, a free radical scavenger, provided partial protection against the cytotoxic effects of oxyhemoglobin. The release of radiolabel from [3H] arachidonic acid-treated cells was increased by oxyhemoglobin in time- and dose-dependent manners. Treatment with an inhibitor of phospholipase A2 or a calcium chelator inhibited the effects of oxyhemoglobin on arachidonic acid release and cellular viability. Conclusions Oxyhemoglobin exerts a direct cytotoxic effect on cultured endothelial cells, and this effect is associated with increased release from [3H] arachidonic acid-labeled cells. Phospholipase A2 and free radicals appear to participate in the pathogenesis of endothelial cell damage. Oxyhemoglobin-induced compromise of endothelial cells may contribute to cerebrovascular pathology.

A reproducible model of reversible, focal, neocortical ischemia in Sprague-Dawley rat

SummaryA reproducible model of reversible, focal ischemia was developed for use with the normotensive, Sprague-Dawley rat. Blood flow to the left cerebral hemisphere was interrupted by occluding simultaneously the left middle cerebral artery and both carotid arteries (CCA). The arterial occlusion lasted for 1, 2 or 3 hours after which animals survived for 3 days. The volume of brain infarction was determined utilizing computer-assisted measurements of serial brain sections stained with triphenyltetrazolium. Tissue infarctions of variable size were observed following arterial occlusions which persisted 1 or 2 hours. In contrast, remarkably-consistent infarction size was obtained following a three hours period of occlusion. Tissue edema was also estimated by measuring the volumes of the two hemispheres and expressing these values as a ratio for each animal. The volume ratio was significantly greater in the 3 hour ischemic group, indicating the occurrence of edema in the infarcted hemisphere.These results demonstrate that reversible vascular occlusion in the normal, Sprague-Dawley rat results in consistent amounts of tissue infarction. This approach represents an attractive model system for studying the pathophysiological effects of transient, focal ischemia and for testing the effects of putative, therapeutic strategies.

Mechanism of enlargement of major cerebral collateral arteries in rabbits.

Major cerebral collateral arteries enlarge following bilateral ligation of the common and internal carotid arteries. The purpose of this investigation was to determine the relative contribution of cellular hypertrophy versus cellular hyperplasia to this vessel change in a morphometric analysis as well as the functional properties of remodeled vessels in an in vitro study. We assessed cell number and vessel dimensions by morphometric analysis of 16 perfusion-fixed rabbit basilar arteries. Results demonstrated significant increases in luminal diameter from 761 to 946 microns (p less than 0.01), medial cross-sectional area from 5.1 x 10(4) to 7.6 x 10(4) micron2 (p less than 0.005), smooth muscle cell volume from 9.19 x 10(5) to 1.44 x 10(6) micron3 (p less than 0.0005), and overall arterial length from 17.41 to 20.36 mm (p less than 0.005) in basilar arteries from the eight ligated rabbits compared with the eight sham-operated controls. Smooth muscle cell volume fraction and cell numerical density were unchanged whereas the number of cells per unit length of artery was increased significantly from 21.5 to 31.0 cells/micron (p less than 0.05). These data indicate that smooth muscle cell hyperplasia rather than hypertrophy contributes to increases in vessel mass. Functional properties of the basilar arteries from 10 ligated and 10 normal control rabbits were analyzed in vitro. Results showed increased contraction to potassium chloride (approximately 74%) (p less than 0.01) and increased sensitivity of smooth muscle to acetylcholine (p less than 0.05) while maximal relaxation was the same as control in the ligated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriovenous malformations that rupture during pregnancy: a management dilemma

SummaryIntracranial haemorrhage due to rupture of an arteriovenous malformation (AVM) during pregnancy is a rare but serious condition that warrants prompt recognition. Once the diagnosis is made, the management is primarily based on neurosurgical rather than obstetric considerations. Due to its rarity, no definitive guidelines exist, and the best time to perform elective surgery (i.e., at presentation or at completion of the pregnancy) is ill-defined. This report describes three patients recently treated at our institution who had AVMs that ruptured during pregnancy. These cases well summarize the difficulties encountered in treating such patients. The diagnostic as well as the therapeutic implications of this condition are discussed.