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Douglas Chyatte and Rebecca Porterfield

Object. Repair of unruptured aneurysms is a reasonable course of action if their expected natural history is worse than the predicted risks of treatment. The purpose of this study was to examine the presenting symptoms of unruptured aneurysms and to test the hypothesis that unruptured intracranial aneurysms can be repaired without significant functional worsening. A second hypothesis was also examined—that is, that the experience of the surgeon, the aneurysm size, and the patient age can be used to predict functional outcome.

Methods. Consecutive patients who underwent repair of an unruptured intracranial aneurysm at a single institution between 1980 and 1998 were studied. Clinical and radiographic data were collected in all patients. Their modified Rankin Scale (mRS) score was determined before treatment (baseline), at 6 weeks, and at 6 months. The primary endpoint for analysis was the mRS score.

Four hundred forty-nine aneurysms were repaired in 366 patients by 10 surgeons. The mean size of the primary lesion repaired was 14.6 + 10.4 mm and 27% were judged to be symptomatic. Aneurysm treatment involved either microsurgical clipping (78%), wrapping (4%), trapping with or without bypass (5%), hunterian ligation with or without bypass (9%), or other methods (4%). The mRS scores at 6 weeks were worse than at baseline (p < 0.0001), but there was no significant difference between the baseline and 6-month mRS score. At 6 months, 94% of patients showed no significant functional worsening as a result of treatment. The number of aneurysms treated by a specific surgeon was a strong predictor of better functional outcome (r = 0.99, p = 0.05). Increasing patient age (r = 0.16, p = 0.003) and increasing aneurysm size (r = 0.15, p = 0.004) were predictors of worsened functional outcome.

Conclusions. Many unruptured aneurysms produce symptoms. Unruptured intracranial aneurysms can be treated without significant permanent functional worsening. The surgeon's experience, aneurysm size, and patient age are predictors of functional outcome.

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John C. Andrefsky, Jeffrey I. Frank and Douglas Chyatte

Object. This study was conducted to delineate the ciliospinal reflex (CSR), which is defined as pupillary dilation caused by a noxious stimulus to the face or head. The authors anecdotally observed that patients in a pentobarbital coma have a CSR that can mimic pathological conditions. A pentobarbital coma obscures the results of the neurological examination in patients with potentially life-threatening cerebral edema; pupil size and reactivity are the only readily monitored signs. Any condition that incorrectly suggests evolving intracranial pathological processes can lead to unnecessary clinical actions.

Methods. The authors evaluated six consecutive patients in the neurointensive care unit in whom a pentobarbital coma had been induced, documenting the presence and duration of the CSR. The CSR was always bilateral and symmetrical, manifesting as enlarged (6–8 mm), seemingly nonreactive pupils continuing from 1 to 6 minutes and was usually seen after routine nursing maneuvers. The pupils appeared nonreactive to short flashes of direct light but did react if longer flashes were used.

Conclusions. Recognition of the CSR can potentially lead to reduction of unnecessary transportation and complicating medical interventions in critically neurologically ill patients in whom a pentobarbital coma has been induced.

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Gerard Bruno, Roxanne Todor, Isabel Lewis and Douglas Chyatte

Object. The occurrence of cerebral aneurysms has been linked to alterations in the extracellular matrix and to matrix-degrading proteases. The purpose of the present study was to determine whether active extracellular matrix remodeling occurs within cerebral aneurysms.

Methods. Aneurysm tissue was collected from 23 patients (two of whom had a ruptured aneurysm and 21 of whom had an unruptured aneurysm) and compared with 11 control basilar arteries harvested at autopsy. Active proteinases capable of gelatin lysis were identified by performing in situ zymography in the presence and absence of a metalloproteinase inhibitor (ethylenediamine tetraacetic acid) and a serine proteinase inhibitor (phenylmethylsulfonyl fluoride). Immunohistochemical analysis was used to localize plasmin, tissue-type (t)—plasminogen activator (PA), urokinase-type (u)—PA, membranetype (MT1)—matrix metalloproteinase (MMP), MMP-2, MMP-9, and tenascin.

Focal areas of gelatin lysis occurred in most cerebral aneurysm tissue samples (17 of 21), but rarely in control arteries (two of 11) (p = 0.002). Both serine proteinases and MMPs contributed to gelatin lysis; however, the MMPs were the predominant enzyme family. Plasmin (p = 0.04) and MT1-MMP (p = 0.04) were expressed in the aneurysm tissue but were unusual in control tissue. The MMP-2 was also expressed more commonly in aneurysm than in control tissue (p = 0.07). The MMP-9 and t-PA were expressed in both groups; however, different staining patterns were observed between aneurysm and control tissue. Tenascin staining was commonly present in both groups, whereas u-PA staining was rarely present.

Conclusions. Aneurysm tissue demonstrates increased proteolytic activity capable of lysing gelatin and increased expression of plasmin, MT1-MMP, and MMP-2 when compared with normal cerebral arteries. This activity may contribute to focal degradation of the vascular extracellular matrix and may be related to aneurysm formation and growth.

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R. L. Patrick Rhoten, Youssef G. Comair, Daniel Shedid, Douglas Chyatte and Michael S. Simonson

✓ Cerebrovascular arteriovenous malformations (AVMs) display abnormal vascular development and dysautoregulation of blood flow. Genetic mechanisms that contribute to the pathogenesis and phenotype of cerebral AVMs are unknown. As a first step in understanding the pathophysiology of AVMs, the authors investigated the hypothesis that endothelial dysfunction—specifically, deregulation of endothelin-1 (ET-1) secretion—contributes to the abnormal vascular phenotype and the lack of hemodynamic autoregulation elaborated by these lesions. Endothelin-1 peptide and preproendothelin-1 (ppET1) messenger RNA were not detected in the intranidal vasculature of all 17 patients with AVMs studied, but were prominently expressed in human control subjects with normal cerebrovasculature (p < 0.01). Although AVM vasculature lacked ET-1, its expression was prominent in vasculature distant from these lesions, suggesting local repression of the ppET-1 gene. Local repression of ET-1 was specific to AVMs; ET-1 in vascular malformations of patients with Sturge—Weber disease was actually elevated compared to normal controls (p < 0.01). Repression of the ppET-1 gene was an intrinsic phenotype of AVM endothelial cells and was not due to factors in the AVM microenvironment. The authors also showed that ETA receptor expression was low in AVM vasculature compared to normal controls. Together, these results demonstrate that the ppET-1 gene is locally repressed in AVM lesions and suggest a role for abnormal ppET-1 gene regulation in the pathogenesis and clinical sequelae of cerebral AVMs.

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Douglas Chyatte, Terence L. Chen, Kathryn Bronstein and Lawrence M. Brass

✓ Seasonal and climatic variations have been linked to the occurrence of some types of cerebrovascular disease; however, the conditions that lead to intracranial aneurysm rupture are not known. The purpose of the present study was to determine whether seasonal and climatic conditions are related to intracranial aneurysm rupture.

Data provided by the Connecticut Health Information Management and Exchange were analyzed for all patients with a primary diagnosis of aneurysmal subarachnoid hemorrhage (SAH) for the fiscal years 1981, 1983, 1985, 1987, 1988, and 1989. Patient records were correlated with climatic conditions for the years 1981 to 1989 obtained from the National Climatic Data Center, National Oceanic and Atmospheric Administration, National Environmental Satellite Data, and Information Service.

During the time periods studied, 1487 patients with a primary diagnosis of aneurysmal SAH were treated by reporting hospitals. Seasonal variation in the incidence of aneurysmal SAH and admission clustering were observed but differed significantly between men and women. Men showed a single large peak in late fall (Roger's r = 11.5, p < 0.005), whereas women had an annual peak occurring in late spring (Roger's r = 10.3, p < 0.01). Substantial climatic change occurred during the 72 hours prior to 10 of the 14 clusters of men who were admitted (p < 0.01, Yates' corrected chi-square 7.33, df = 1). In contrast, clusters of women admitted were not related to preceding climatic change (p > 0.25, Yates' corrected chi-square 0.06, df = 1).

Hospital admissions for aneurysmal SAH display seasonal fluctuation, with women showing a different seasonal pattern from men. Changing climatic conditions precede aneurysm rupture in men but not in women, which suggests that weather is causally related to aneurysm rupture in men, and that factors that lead to aneurysm rupture in women may be different from those in men. These data do not explain why weather fronts or gradients are associated with aneurysm rupture in men.

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John Strugar and Douglas Chyatte

✓ Spinal dural arteriovenous malformations (AVM's) are the most common type of AVM involving the spinal cord in adults. Direct obliteration of the fistula nidus located in the dura is the preferred method of treatment. Five cases of spinal dural AVM were treated by open surgical exposure, microsurgical disconnection of the dural nidus from the coronal venous plexus, and in situ obliteration of the nidus using the Nd:YAG laser. Use of the Nd:YAG laser reduced nidus obliteration to a simple 10-minute technical exercise. All patients improved neurologically following surgery, and complete obliteration of all lesions was verified by delayed angiography. There were no permanent complications related to either the surgical exposure or the use of the Nd:YAG laser. Open surgical treatment of spinal dural AVM's using the Nd:YAG laser appears to be a safe, effective, and durable method of treating these lesions. Photocoagulation is discussed in the context of the other treatment modalities available.