✓ Surgical specimens from six benign and 16 malignant human gliomas were investigated immunohistochemically to correlate the degree of malignancy, the distribution of transforming growth factor-alpha (TGF-α) and epidermal growth factor (EGF) receptor, and the potential for cell proliferation using monoclonal antibodies to TGF-α, EGF receptor, and Ki-67. Fourteen (88%) of the malignant gliomas and one (17%) of the benign gliomas were found to be positive for TGF-α, and 14 (88%) of the malignant gliomas and two (33%) of the benign gliomas expressed EGF receptor. The proliferation index with Ki-67 was 18.8% ± 8.1% (mean ± standard deviation) in malignant gliomas and 1.9% ± 1.8% in benign gliomas. In general, cells positive for EGF receptor and Ki-67 were randomly distributed throughout the tumor tissue, and cells positive for TGF-α tended to be clustered without obvious relationship to areas of necrosis or blood vessels. In some tumors, cells positive for TGF-α, EGF receptor, and Ki-67 were associated in a focal distribution. The more frequent expression of TGF-α and EGF receptor in the highly proliferative malignant gliomas is compatible with a role for TGF-α and EGF receptor in the induction or stimulation of malignant gliomas.
Motohiko Maruno, John S. Kovach, Patrick J. Kelly and Takehiko Yanagihara
David G. Piepgras, Michael K. Morgan, Thoralf M. Sundt Jr., Takehiko Yanagihara and Lynn M. Mussman
✓ A series of 14 patients with intracerebral hemorrhage after carotid endarterectomy is reviewed. This complication occurred in 0.6% of 2362 consecutive carotid endarterectomies performed at the Mayo Clinic from 1972 through 1986. All hemorrhages occurred within the first 2 weeks after operation and were ipsilateral to the side of the operation. Eight patients died, and only two made a good recovery. Significant risk factors are hypertension and chronic hemispheric hypoperfusion with impaired autoregulation. The “normal pressure-hyperperfusion breakthrough” syndrome was considered to be operative in 12 of the 14 patients. Nine patients had documented hyperperfusion (at least 100% increase of baseline cerebral blood flow) at the time of surgery. In an additional three patients, normal perfusion-pressure breakthrough was inferred by the clinical course and radiological findings, as well as by the absence of alternative explanations. Patients at risk for postendarterectomy intracerebral hemorrhage include those who have a clinical history suggestive of hemodynamic cerebral ischemia, severe carotid stenosis with limited hemispheric collateral flow, and postendarterectomy hyperperfusion, as measured by intraoperative cerebral blood flow. To minimize the risk of hemorrhage in these patients, strict maintenance of blood pressure at normotensive or even relatively hypotensive levels during the intraoperative and early postoperative periods is advised.
Kazumi Yamamoto, Fumiharu Akai, Toshiki Yoshimine and Takehiko Yanagihara
✓ Progression and recovery of ischemic and postischemic damage after occlusion of the middle cerebral artery and subsequent reperfusion were investigated in the gerbil. This study was performed by immunohistochemical reaction testing for tubulin and creatine kinase BB-isoenzyme to visualize the neuronal structure and by immunohistochemical reaction testing for astroprotein (an astrocyte-specific protein) to visualize reactive astrocytes. The earliest ischemic lesion became visible in the frontoparietal cortex after 7 minutes of ischemia as a laminar loss of the reaction for tubulin involving the neuropil, neuronal perikarya, and dendrites. The earliest lesion in the caudoputamen evolved after 30 minutes of ischemia. After reestablishment of cerebral circulation, the immunohistochemical ischemic lesions in the neuronal structure disappeared if the ischemic period was 10 minutes or less and partially disappeared even after ischemia for 15 minutes in the cerebral cortex, while the postischemic lesion in the caudoputamen disappeared even after ischemia for 15 minutes. Reactive astrocytes were detected in the cerebral cortex and caudoputamen as early as 24 hours after reperfusion, both in the areas with and without the neuronal lesions. No lesion was identified in the hippocampus or thalamus. This experimental model is suitable for investigation of rapidly progressive regional ischemia in the cerebral cortex and for comparison with other regional or global cerebral ischemia in the gerbil or other animal species.
Toshiki Yoshimine, Kazuyoshi Morimoto, Joan M. Brengman, Henry A. Homburger, Heitaro Mogami and Takehiko Yanagihara
✓ Immunohistochemical methods for the determination of tubulin, creatine kinase BB-isoenzyme, and astroprotein-glial fibrillary acidic protein were used to investigate recovery of the ischemic lesion after temporary occlusion of a common carotid artery in the gerbil and the evolution of the postischemic lesion following reperfusion. One group of gerbils was followed from 15 minutes to one month after an ischemic period of 30 minutes, and another group was examined after 7 days following an ischemic period of 5 to 30 minutes. It was found that the postischemic lesion, visualized as loss of the immunohistochemical reaction for tubulin and creatine kinase BB-isoenzyme, evolved within 60 minutes after reperfusion in the hippocampus and cerebral cortex and within 3 hours in the caudoputamen and thalamus. Resolution of the preexisting ischemic lesion was possible only after an ischemic period of less than 10 minutes in the cerebral cortex and caudoputamen and less than 15 minutes in the thalamus. In the CA1-CA2 region of the hippocampus, the ischemic lesion already existed after an ischemic period of 5 minutes and was mostly irreversible. The immunohistochemical method of testing for different cellular and subcellular components was very useful for investigation of cerebral ischemia and may also be advantageous for investigation of other pathophysiological conditions of the nervous system.
Fredric B. Meyer, David G. Piepgras, Thoralf M. Sundt Jr. and Takehiko Yanagihara
✓ Twenty cases treated with emergency embolectomy for acute occlusion of the middle cerebral artery were reviewed. There were 10 males and 10 females, with an average age of 55 years. The left middle cerebral artery was involved in 17 patients and the right in three. Flow was restored in 16 patients (75%). The embolus originated in the heart in seven, the carotid artery in seven, the aorta in three, an aneurysm in one, and an indeterminate source in two. It was technically most difficult to achieve patency with atheromatous emboli from the aorta. Two patients (10%) had an excellent result with no neurological deficit, five (25%) were left with a minimal deficit but were employable, seven (35%) had a fair result but were still independent and employable, four (20%) did poorly, and two (10%) died. Patients with an associated ipsilateral carotid artery occlusion did poorly. Collateral flow, as judged from preoperative angiograms, was the best predictor of outcome.
Toshiki Yoshimine and Takehiko Yanagihara
✓ The authors have created an experimental model of regional cerebral ischemia in gerbils that is reproducible and has a low mortality rate. In gerbils, either the posterior communicating artery (PCoA) or the middle cerebral artery (MCA) was occluded, and the distribution of cerebral ischemia from each surgical procedure was compared with that produced by occlusion of the common carotid artery (CCA). In contrast to the widespread cortical and subcortical infarctions seen after occlusion of the CCA, occlusion of the PCoA caused infarction that was restricted to the hippocampus, the piriform cortex, and the posterior part of the thalamus, and occlusion of the MCA resulted in infarction that was restricted to the central part of the cerebral hemisphere and the caudate nucleus and putamen. Intracranial occlusion of the PCoA or MCA in the gerbil resulted in lesions that were reproducible with low mortality rates over a long-term period. Occlusion of the PCoA, MCA, or CCA also produces a model that is suitable for investigation of the postischemic period. A combination of these three experimental models is useful for investigation of regional vulnerability and for the study of regional metabolic differences in cerebral ischemia.
Ruben J. Saez, Burton M. Onofrio and Takehiko Yanagihara
✓ A retrospective study of 60 adult patients with Arnold-Chiari malformation revealed that certain presenting clinical syndromes, although not pathognomonic, seemed to have definite prognostic significance. Surgical management by suboccipital decompression led to remarkable and enduring improvement in 65% of patients followed for as long as 14 years. In some patients, however, the initial postoperative benefit tended to fade into an insidious progression of neurological deficit. Despite operation, 18.6% of patients eventually experienced progressive neurological deterioration. Patients who presented with paroxysmal intracranial hypertension or cerebellar dysfunction had the best prognosis. Evidence of central cord involvement was the single most detrimental factor to neurological recovery.