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John R. Robinson, Issam A. Awad and John R. Little

✓ The incidence and natural history of the cavernous angioma have remained unclear in part because of the difficulty of diagnosing and following this lesion prior to surgical excision. The introduction of magnetic resonance (MR) imaging has improved the sensitivity and specificity of diagnosing and following this vascular malformation. Seventy-six lesions with an MR appearance typical of a presumed cavernous angioma were discovered in 66 patients among 14,035 consecutive MR images performed at the Cleveland Clinic between 1984 and 1989. Follow-up studies in 86% of the cases over a mean period of 26 months provided 143 lesion-years of clinical survey of this condition. The most frequent presenting features were seizure, focal neurological deficit, and headache. While most lesions exhibited evidence of occult bleeding on MR imaging, there was overt hemorrhage in seven of the 57 symptomatic patients and only one overt hemorrhage occurred during the follow-up interval. The annualized bleeding rate was 0.7%. Analysis of the hemorrhage group revealed a significantly greater risk of overt hemorrhage in females. Pathological confirmation of cavernous angioma was obtained in all 14 surgical cases. This information assists in rational therapeutic planning and prognosis in patients with MR images showing lesions suggestive of cavernous angioma.

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John R. Little, Issam A. Awad, Stephen C. Jones and Zeyd Y. Ebrahim

✓ This study was designed to investigate the hemodynamic characteristics of cavernous angiomas of the brain. Five adult patients with a cavernous angioma underwent local cortical blood flow studies and vascular pressure measurements during surgery for the excision of the cavernous angioma. Clinical presentation included headache in four patients, seizures in four patients, and recurring diplopia in one patient. Magnetic resonance imaging demonstrated the cavernous angiomas in all patients and revealed an associated small hematoma in two. Four patients with a cerebral cavernous angioma were operated on in the supine position and the remaining patient, whose lesion involved the brain stem, was operated on in the sitting position. Mean local cortical blood flow (± standard error of the mean) in the cerebral cortex adjacent to the lesion was 60.5 ± 8.3 ml/100 gm/min at a mean PaCO2 of 35.0 ± 0.6 torr. Mean CO2 reactivity was 1.1 ± 0.2 ml/100 gm/min/torr. The local cortical blood flow results were similar to established normal control findings. Mean pressure within the lesion in the patients undergoing surgery while supine was 38.2 ± 0.5 mm Hg; a slight decline in cavernous angioma pressure occurred with a drop in mean systemic arterial blood pressure and PaCO2. Mean pressure in the cavernous angioma in the patient operated on in the sitting position was 7 mm Hg. Jugular compression resulted in a 9-mm Hg rise in cavernous angioma pressure in one supine patient but no change in the patient in the sitting position. Direct microscopic observation revealed slow circulation within the lesions. The hemodynamic features demonstrated in this study indicate that cavernous angiomas are relatively passive vascular anomalies that are unlikely to produce ischemia in adjacent brain. Frank hemorrhage would be expected to be self-limiting because of relatively low driving pressures.

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Issam A. Awad, John R. Little, William P. Akrawi and Jennifer Ahl

✓ The natural history of cranial dural arteriovenous malformations (AVM's) is highly variable. The authors present their clinical experience with 17 dural AVM's in adults, including 10 cases with an aggressive neurological course (strictly defined as hemorrhage or progressive focal neurological deficit other than ophthalmoplegia). Two of these 10 patients died prior to surgical intervention and a third was severely disabled by intracerebral hemorrhage. Six patients underwent surgical resection of their dural AVM, with preparatory embolization in two cases. One patient received embolization and radiation therapy without surgery. Six of the seven cases without an aggressive neurological course were treated conservatively, and the seventh patient underwent embolization of a cavernous sinus dural AVM because of worsening ophthalmoplegia. In order to clarify features associated with aggressive behavior, a comprehensive meta-analysis was performed on 360 additional dural AVM's reported in the literature with sufficiently detailed clinical and angiographic information. The location and angiographic features of 100 aggressive cases were compared to those of 277 benign cases. No location of dural AVM's was immune from aggressive neurological behavior; however, an aggressive neurological course was least often associated with cases involving the transverse-sigmoid sinuses and cavernous sinus and most often associated with cases at the tentorial incisura. Contralateral contribution to arterial supply and rate of shunting (high vs. low flow) did not correlate with aggressive neurological behavior as defined. Leptomeningeal venous drainage, variceal or aneurysmal venous dilations, and galenic drainage correlated significantly (p < 0.05) with aggressive neurological presentation. The latter three angiographic features often coexisted in the same dural AVM. It is concluded that these features significantly increase the natural risk of dural AVM's, and warrant a more vigilant therapeutic strategy.

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Jeffrey V. Rosenfeld, Gene H. Barnett, Cathy A. Sila, John R. Little, Emmanuel L. Bravo and Gerald J. Beck

✓ Atrial natriuretic factor (ANF) is a diuretic natriuretic peptide hormone produced by both the heart and brain which has been postulated to play a role in the hemodynamic and sodium instability that frequently follows subarachnoid hemorrhage (SAH). Levels of ANF were measured in 12 patients with nontraumatic SAH and nine control patients with unruptured cerebral aneurysms. At surgery, the mean plasma ANF level (± standard deviation) of the SAH group was significantly higher than that of the control group (158.1 ± 83.8 vs. 57.8 ± 45.3 pg/ml, respectively; p = 0.01). There was no significant difference in serum sodium concentration, blood pressure, or central venous pressure between these groups. Nine patients with SAH due to aneurysm rupture had plasma ANF levels similar to those in three patients with SAH due to other causes. Four patients with moderate to severe SAH had significantly higher mean cerebrospinal fluid (CSF) ANF values (17.7 ± 12.8 pg/ml) than five patients with minimal SAH (0.6 ± 0.9 pg/ml) or the control group of nine patients (3.7 ± 1.3 pg/ml) (p < 0.05). Five patients with moderate to severe SAH had significantly higher plasma ANF values (202.6 ± 72.2 pg/ml) than five with minimal SAH (86.8 ± 29.2 pg/ml) or the control group (57.8 ± 45.3 pg/ml) (p < 0.05). Plasma ANF values were substantially higher than CSF ANF content in the SAH group (p < 0.01) and in the control group (p = 0.05).

From these data it is concluded that: 1) plasma ANF is elevated significantly after SAH; 2) this rise appears unrelated to the cause of hemorrhage, serum sodium concentration, blood pressure, or central venous pressure, but is related to the extent of the hemorrhage; 3) ANF concentrations in the CSF are significantly lower than in plasma, and are elevated after moderate to severe SAH; and 4) the source of CSF ANF is probably the plasma, and the source of plasma ANF is likely the heart.

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Gene H. Barnett, Russell W. Hardy Jr., John R. Little, Janet W. Bay and George W. Sypert

✓ Hypertrophy of the posterior spinal elements leading to compromise of the spinal canal and its neural elements is a well-recognized pathological entity affecting the lumbar or cervical spine. Such stenosis of the thoracic spine in the absence of a generalized rheumatological, metabolic, or orthopedic disorder, or a history of trauma is generally considered to be rare. Over a 2-year period the authors have treated six cases of thoracic myelopathy associated with thoracic canal stenosis. In four patients the deficits developed gradually and painlessly. The three older patients had a clinical profile characterized by complaints of pseudoclaudication, spastic lower limbs, and evidence of posterior column dysfunction. Two patients were younger adults with low thoracic myelopathy associated with local back pain after minor trauma. Both patients also had congenital narrowing of the thoracic spinal canal.

Oil and metrizamide contrast myelography in the prone position were of limited value in diagnosing this condition; in fact, myelography may be misleading and result in erroneous diagnosis of thoracic disc protrusion, when the principal problem is dorsal and lateral compression from hypertrophied facets. Magnetic resonance imaging and computerized tomography sector scanning were more useful in the diagnosis of this disorder than was myelography. Thoracic canal stenosis may be more common than is currently recognized and account for a portion of the failures in anterior and lateral decompression of thoracic disc herniations.

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Nazih A. Moufarrij, John R. Little, Victor Skrinska, Fred V. Lucas, John P. Latchaw, Robert M. Slugg and Ronald P. Lesser

✓ The purpose of this investigation was to study the effects of a selective thromboxane A2 (TXA2) synthetase inhibitor (TSI) upon the evolution of cerebral infarction in the cat. Adult cats, lightly anesthetized with nitrous oxide, underwent right middle cerebral artery (MCA) occlusion for 4 hours followed by a 2-hour period of reperfusion before sacrifice. Ten cats received 3 mg/kg TSI intravenously immediately before, and 10 cats received 3 mg/kg TSI intravenously immediately after MCA occlusion. Ten cats were used as controls receiving no treatment. The bleeding time was determined at baseline and at the end of each experiment. Electroencephalographic (EEG) recordings were obtained before and after MCA clipping and MCA release, and at hourly intervals thereafter. Regional cerebral blood flow (rCBF) was measured using the xenon-133 (133Xe) clearance technique before and after MCA occlusion, after MCA reopening, and before terminating each experiment. Thirty minutes before each cat was sacrificed, Evans blue dye and sodium fluorescein were given intravenously. The animals were then perfused with colloidal carbon and the brains removed and evaluated for midline shift, Evans blue dye and sodium fluorescein extravasation, carbon staining, and infarct size. The bleeding time, arterial blood pressure, rCBF changes, brain swelling, and vital dye extravasation were not statistically different between the three treatment groups. The EEG changes, carbon staining, and infarct size differences between the three groups also failed to reach statistical significance, but there was a suggestion that these parameters were adversely affected in the cats pretreated with TSI. Ten additional cats undergoing MCA occlusion and reperfusion were used for pharmacological studies. Five of them received 3 mg/kg TSI intravenously immediately after MCA occlusion, and serial drug and thromboxane B2 (TXB2) levels (a stable metabolite of TXA2) were determined. Another five cats were not treated and serial TXB2 levels were obtained. Production of TXA2 was inhibited by 95% in cats receiving TSI. In conclusion, thromboxane synthetase inhibition failed to modify favorably the evolution of cerebral infarction. When TSI was given before MCA occlusion, cerebral infarction tended to be more extensive.

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John R. Little, Bernadine S. Bryerton and Anthony J. Furlan

✓ The clinical data and findings on the early postoperative intravenous digital subtraction angiograms (IVDSA's) were studied in 61 patients undergoing 70 consecutive conventional carotid endarterectomies and in 46 patients undergoing 50 consecutive carotid endarterectomies with a saphenous vein patch graft (SVPG). The IVDSA's were considered normal in 50 of 70 conventional carotid endarterectomies and in 46 of 50 carotid endarterectomies with SVPG (p = 0.004). The internal carotid artery (ICA) origin was consistently larger and had a more normal configuration after carotid endarterectomy with SVPG. Ballooning at the endarterectomy site was an uncommon finding and occurred with similar frequency in both groups; that is, after three conventional carotid endarterectomies and two carotid endarterectomies with SVPG. In the conventional group, early symptomatic thrombosis occurred in the ICA in one patient and in the common carotid artery (CCA), ICA, and external carotid artery (ECA) in two patients. Silent ICA occulusion was seen in three patients in the conventional group. There were no occlusions in the SVPG group (p = 0.04). Stenosis at the distal end of the ICA arteriotomy was found after nine conventional carotid endarterectomies, and was mild (≤ 33% reduction in the lumen) in seven patients, moderate (34% to 66%) in one, and severe (≥ 67%) in one. Mild distal ICA stenosis was seen in one case after carotid endarterectomy with a SVPG (p = 0.03). Stenosis of 33% or less was found at the proximal end of the CCA arteriotomy after two carotid endarterectomies in the conventional group and one carotid endarterectomy in the SVPG group. Four patients in the conventional group suffered a postoperative cerebral infarct and one patient in the SVPG group suffered a postoperative brain-stem infarct (p = 0.28). The authors' findings have led them to routinely use a SVPG in carotid endarterectomy.

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Issam Awad, Anthony J. Furlan and John R. Little

✓ The natural history of intracranial arterial stenosis is not well understood. The lesions are pathologically quite diverse, and are subject to resolution, progression, or occlusion. The authors undertook an investigation to examine what effects, if any, extracranial-intracranial (EC-IC) bypass surgery had on the evolution of intracranial arterial stenosis in 18 patients undergoing EC-IC bypass procedures for ipsilateral hemispheric ischemia. There was inaccessible internal carotid artery stenosis in 14 patients, and middle cerebral artery stenosis in four patients. Early (within 2 weeks) and late (at 6 months) postoperative angiography was performed in all patients. During the period of the study, there was a significant change in the arterial stenosis in 50% of the patients (nine of 18). The stenotic artery became occluded in four patients while the grafts were widely patent. The occlusion occurred within a few days after the operation in three of the four cases, and was accompanied by an ischemic stroke in these patients. There was improvement or resolution of the stenotic lesion in five patients; the graft became occluded in two of these cases and was patent but showed poor cortical artery filling in the other three. All these patients remained asymptomatic and the change was detected on routine late postoperative angiograms. It is concluded that arterial stenoses should not be viewed as static or inflexible lesions, and that EC-IC bypass procedures can modify the hemodynamic parameters across stenotic lesions, predisposing them to improvement or worsening. This, in turn, may affect bypass patency. Such hemodynamic interactions are accompanied by ischemic symptoms in some patients, and contribute to the relatively higher morbidity associated with EC-IC bypass surgery in the setting of arterial stenosis.

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Andrew H. Kaye, John R. Little, Bernadine Bryerton and Michael Modic

✓ Preoperative intravenous digital subtraction angiography (IV DSA) was compared with the operative findings in 54 patients who underwent a total of 57 carotid endarterectomies, to evaluate the accuracy of preoperative IV DSA in predicting the lesion found at surgery. Four studies early in the series were technically unsatisfactory, leaving 50 patients with 53 procedures for evaluation. Severe carotid artery stenosis was accurately predicted in all cases. Deep ulceration in the absence of severe carotid stenosis was reliably shown by IV DSA, although it was not reliably demonstrated by either IV DSA or carotid angiography if severe stenosis was also present. As severe carotid stenosis or deep ulceration are the major radiological indications for carotid endarterectomy, the authors have found that technically satisfactory IV DSA is an adequate preoperative imaging technique.