Max E. Ots, Tony L. Yaksh, Robert E. Anderson and Thoralf M. Sundt Jr.
✓ Nimodipine, a dihydropyridine that interacts with a Ca++ channel-associated binding site, when delivered (30 to 150 µg/kg) intra-arterially (ia) to enflurane-anesthetized cats, produced a dose-dependent suppression of seizures evoked by pentylenetetrazol. A comparable suppression was produced by clonazepam (1 to 30 µg/kg, ia). Phenytoin was maximally effective only at nearly lethal doses (90 mg/kg, ia). Verapamil, a diphenyl-alkylamine that interacts with a separate Ca++ channel-associated site, at the maximum nonlethal dose (6 mg/kg, ia) resulted in a mild facilitation of seizure activity. The drug vehicle used in these studies (50% polyethylene glycol-400) had no effect when given alone. Regional cerebral blood flow (rCBF) as measured by the clearance of xenon-133 was markedly elevated immediately after the onset of seizure activity (89 ± 3 to 168 ± 4 ml/100 gm/min). Concurrent with their resolution of the seizure activity, both nimodipine and clonazepam reduced rCBF to near preseizure levels and preserved the rCBF response to hypercarbia which would otherwise have been abolished following prolonged seizure activity. Moreover, the effect of nimodipine on rCBF and seizures occurred without any prominent alterations in mean arterial blood pressure as compared to preseizure levels. These data support the proposition that a dihydropyridine Ca++ channel binding site may play a role in modulating paroxysmal neuronal activity, and suggest that this class of agents may reflect a novel group of antiepileptic drugs.
Thoralf M. Sundt Jr., David G. Piepgras, O. Wayne Houser and J. Keith Campbell
✓ The authors report their initial experience with the use of interposition saphenous vein grafts between the external carotid artery and the proximal posterior cerebral artery. The indications, results, and technical aspects of the operation are reviewed. All patients accepted for surgery were at high risk for a posterior circulation infarct, and all patients with ischemic symptomatology had continued to progress while on anticoagulant drugs or anti-platelet agents. Thus, all patients were at high risk, and 11 of the 14 patients operated on were confined to bed before surgery. Intraoperative graft flows varied from 35 to 170 ml/min, and postoperative graft flows ranged from 75 to 311 ml/min in the patent grafts. There were three early graft occlusions and two late graft occlusions; these all occurred in patients with relatively low flows at the time of surgery (40 ml/min or lower). Subdural hygroma was the next most frequent complication to graft occlusion. It was thought to be caused by the pulsating graft anastomosed to a major vessel through a small opening in the basal arachnoid, which provided a new path for cerebrospinal fluid flow in patients with a degree of preexisting atrophy. One patient with a large aneurysm in the posterior circulation underwent proximal intracranial clipping of the vertebral artery and bypass grafting simultaneously. There were seven excellent results and two good results in nine patients in whom the graft remained patent. In the five patients with graft occlusion, there were two minor strokes, two major strokes, and one death.
An experimental study in monkeys
John R. Little, Thoralf M. Sundt Jr. and Frederick W. L. Kerr
✓ The sequential neuronal alterations that occur during the early phase of developing cortical infarction in the squirrel monkey were studied by light and electron microscopy. A technique used to select ischemic tissue based on spectrophotometry is described. Neuronal shrinkage, characterized by angularity, cytoplasmic eosinophilia, and nuclear pyknosis on light microscopy and by an increase in electron density of the cytoplasmic and nucleoplasmic matrix on electron microscopy, was the predominant reaction. The increased electron density of the cytoplasm and nucleoplasm suggested a diffuse alteration at the molecular level and the appearance of this abnormality between 3 and 6 hours corresponded with the development of an irreversible neurological deficit. In contrast, approximately 10% of the neurons became very swollen and pale. The pattern of perineuronal astrocytic alterations suggested that some form of interaction involving fluid transfer may exist between astrocyte and neuron and that shrinkage or swelling of neurons may depend in part upon the presence or absence of direct fluid exchange with astrocytes. Most terminal boutons became progressively shrunken and dense resembling the changes which occur in anterograde axonal degeneration. Swelling and fragmentation of large lysosomes occurred at 12 hours. Disruption of neural membranes was widespread by 24 hours and was more severe in swollen neurons.
Fredric B. Meyer, Thoralf M. Sundt Jr., Nicolee C. Fode, Michael K. Morgan, Glen S. Forbes and James F. Mellinger
✓ In this study, 24 aneurysms occurring in 23 patients under the age of 18 years (mean 12 years) are analyzed. The male:female ratio was 2.8:1, and the youngest patient was 3 months old. Mycotic lesions and those associated with other vascular malformations were excluded. Forty-two percent of the aneurysms were located in the posterior circulation, and 54% were giant aneurysms. Presenting symptoms included subarachnoid hemorrhage in 13 and mass effect in 11. Several of these aneurysms were documented to rapidly increase in size over a 3-month to 2-year period of observation. All aneurysms were surgically treated: direct clipping was performed in 14; trapping with bypass in four; trapping alone in four; and direct excision with end-to-end anastomosis in two. The postoperative results were excellent in 21 aneurysms (87%), good in two (8%), and poor in one. The pathogenesis of cerebral aneurysms is reviewed.
Jack P. Whisnant, Sara E. Sacco, W. Michael O'Fallon, Nicolee C. Fode and Thoralf M. Sundt Jr.
✓ The objective of this study was to assess the effect of referral bias on survival in patients with subarachnoid hemorrhage (SAH). The characteristics of 49 patients with aneurysmal SAH from a single community were compared with those of 328 patients referred from outside the community, all treated in the same medical care setting. In addition, referral patients who received surgery were compared by differential survival analysis with those still awaiting surgery at Days 1 to 3, Days 4 to 10, and Days 11 to 15.
There was a dramatic difference in the 30-day survival rate between referral patients (83%) and community patients (59%), but most of the difference had occurred by the 2nd day after SAH. In the referral patients, the variables present at first medical attention that were found to have an independent effect on survival were clinical grade, presence of coma, number of days from SAH to referral, diastolic blood pressure, and patient age. There was a higher survival rate at 1 year for patients who were surgically treated compared with those awaiting surgery for each of the three time periods. Patients who underwent early surgical treatment had a 1-year survival rate almost identical to that of patients with late surgery.
Referral patients had a better early survival rate than did community patients because the referral group did not include patients who died and some who were in poor clinical condition before the opportunity for referral. The differential survival analysis described provides a new method for estimating survival for treated and untreated patients with SAH.
Nayef R. F. Al-Rodhan, Thoralf M. Sundt Jr., David G. Piepgras, Douglas A. Nichols, Daniel Rßfenacht and Lorna N. Stevens
✓ An alternative theory is proposed to explain the brain edema and hemorrhage that may occur after resection of high-flow intracerebral arteriovenous malformations (AVM's). This theory, termed “occlusive hyperemia,” is based on a retrospective analysis of operative dictations along with postoperative imaging studies (191 angiograms and 273 computerized tomography scans) in 295 cases of intracerebral AVM's operated on at the Mayo Clinic between 1970 and 1990. In this series, 34 cases (12%) of postoperative deterioration were documented, of which 15 were due to incomplete resection of the AVM. Of the remaining 19 cases, six had brain edema alone and 13 had hemorrhage with edema, despite complete excision of the AVM. In these 19 cases, the AVM's were greater than 6 cm in diameter in 10 patients, between 3 and 6 cm in six, and less than 3 cm in three. Obstruction of the venous drainage system was observed in 14 (74%) of the 19 cases. Ten of these 14 were due to obstruction of the primary venous drainage of the brain parenchyma immediately surrounding the lesions, while four were due to obstruction of other venous structures. In no case was a rapid circulation identified on postoperative angiograms. The flow pattern was slow or stagnant in former AVM feeders and their parenchymal branches. It is proposed that postoperative intracranial hemorrhage and/or brain edema in AVM patients may be due to: 1) obstruction of the venous outflow system of brain adjacent to the AVM, with subsequent passive hyperemia and engorgement; and 2) stagnant arterial flow in former AVM feeders and their parenchymal branches, with subsequent worsening of the existing hypoperfusion, ischemia, and hemorrhage or edema into these areas. Supportive hemodynamic evidence for this theory was derived from the literature.