Douglas A. Nichols

Stereotactic radiosurgery and particulate embolization for cavernous sinus dural arteriovenous fistulae.

OBJECTIVE To evaluate the safety and efficacy of stereotactic radiosurgery, either with or without transarterial embolization, in the treatment of patients with dural arteriovenous fistulae (DAVFs) of the cavernous sinus. METHODS We reviewed the findings, from a prospectively established database, for 20 patients with cavernous sinus DAVFs who were treated with either radiosurgery alone (n = 7) or radiosurgery and transarterial embolization (n = 13) in a 7-year period. The median follow-up period after radiosurgery was 36 months (range, 4-59 mo). RESULTS Nineteen of 20 patients (95%) experienced improvement of their clinical symptoms. Fourteen of 15 patients (93%) experienced either total (n = 13) or nearly total (n = 1) obliteration of their DAVFs, as documented by angiography performed a median of 12 months after radiosurgery. No patient experienced a recurrence of symptoms after angiography showed DAVF obliteration. Two patients developed new neurological deficits after embolization procedures. One patient exhibited temporary aphasia secondary to a venous infarction; another patient exhibited permanent VIth cranial nerve weakness related to acute cavernous sinus thrombosis. Two patients experienced recurrent symptoms and underwent repeat transarterial embolization at 7 and 12 months; both patients achieved clinical and angiographic cures (5 and 10 mo later, respectively). One patient experienced recurrent visual symptoms and underwent transvenous embolization 4 months after radiosurgery. CONCLUSION Staged radiosurgery and transarterial embolization provided both rapid symptom relief and long-term cures for patients with cavernous sinus DAVFs. Radiosurgery alone was effective for patients with DAVFs whose arterial supply was not accessible via a transarterial approach, although the time course of symptom improvement was longer, compared with patients who also underwent embolization.

Intra-arterial Thrombolysis in Acute Basilar Artery Thromboembolism: The Initial Mayo Clinic Experience

OBJECTIVE To investigate the feasibility of intra-arterial thrombolysis in acute basilar artery thrombosis. DESIGN We reviewed a consecutive series of patients in whom intra-arterial thrombolysis was performed during the period from 1994 to 1996. MATERIAL AND METHODS Intra-arterial thrombolysis with urokinase was done in an attempt to recanalize the basilar artery in a series of nine patients with basilar artery thrombosis admitted to the neurologic intensive care unit. At the time of initial assessment, all nine patients had major neurologic deficits attributable to brain-stem ischemia, including two patients with locked-in syndrome. RESULTS Recanalization of the basilar artery system was successful in seven of the nine patients (a range of 2 to 13 hours after the ictus). Failure to recanalize the basilar artery occurred in two patients, who died after progressing to coma. Complete recovery or only minimal neurologic deficits were demonstrated in five of the nine patients. Despite recanalization of the basilar artery, two patients had no major change in their neurologic function, and both ultimately had severe ataxia and were fully dependent on others. A cerebellar hemorrhage occurred in one patient but without clinical worsening. Two patients had a retroperitoneal hematoma. CONCLUSION Intra-arterial thrombolysis with urokinase in acute basilar artery occlusion resulted in recanalization in seven of the nine patients (78%). Five of the nine patients recovered fully, including two patients who had had locked-in syndrome. In light of the devastating natural course of acute basilar artery occlusion, these initial results are encouraging and indicate that intra-arterial thrombolysis may be a useful emergency treatment, even in patients with prolonged symptoms of ischemia (up to 12 hours).

Postoperative radiotherapy of supratentorial low-grade gliomas

Forty-nine patients with supratentorial low-grade gliomas underwent surgery (biopsy or subtotal resection) and postoperative radiotherapy at the Mayo Clinic between 1976 and 1983. The median, 5-, and 10-year overall survivals for the total group were 6.5 years, 62%, and 14%, respectively. Nine prognostic variables were examined for their possible association with survival, including age, sex, site, size, CT enhancement, histologic type, extent of resection, radiation volume, and radiation dose. Of these variables, only histologic type was significantly associated with survival. The estimated 5-year survival was 100% for the 5 patients with pilocytic astrocytomas, 83% for the 20 patients with oligodendrogliomas or mixed oligo-astrocytomas, and 40% in the 24 patients with ordinary astrocytomas (log rank p = 0.001). Other possible prognostic variables, such as radiation volume or total dose, showed no association with survival. Twenty-seven patients had a documented treatment failure. For the 20 patients in whom the pattern of failure could be determined, all failed within their radiation portals. Eleven patients had additional tissue obtained following suspected disease recurrence. Tumor was found in ten of these patients, and radionecrosis in one.

Radiation-associated atheromatous disease of the cervical carotid artery: report of seven cases and review of the literature

The natural history of postirradiation extracranial cerebrovascular disease is uncertain. Previous reported cases spanning 20 years of carotid surgery are difficult to evaluate, because patients may sometimes have unspecified symptoms, physical examinations, postoperative results, and follow-up. Also, the evolution of carotid surgery over the past two decades makes it impossible to compare earlier operative technique with the state-of-the-art technique of today. Our series of 7 patients underwent 9 carotid endarterectomies with an average follow-up period of 46 months. The number of patients is small, and although technically this is a more difficult operation, we feel the results are favorable and may be comparable with endarteerctomy procedures in nonirradiated patients. These patients should be approached as if radiation changes are not a major factor when they are considered for reconstructive arterial surgery.

Preliminary report: effects of high dose methylprednisolone on delayed cerebral ischemia in patients at high risk for vasospasm after aneurysmal subarachnoid hemorrhage.

Mounting evidence suggests that chronic cerebral vasospasm may be linked to the inflammatory response that follows subarachnoid hemorrhage. Twenty-one patients judged to be at high risk for vasospasm because of either poor admitting grade or a large amount of subarachnoid blood shown by computed tomography were treated with a course of high dose methylprednisolone, and management results were compared to those of a cohort of contemporary control patients matched for grade, number of hemorrhages, time from hemorrhage to admission, time from hemorrhage to operation, aneurysm location, age, and sex. Patients treated with high dose methylprednisolone were twice as likely to have an excellent result and half as likely to die as those who were not treated. The incidence and severity of delayed cerebral ischemia were reduced in treated patients when compared to control patients. None of the treated patients developed a serious side effect that could be attributed to steroid treatment. These findings are consistent with the conclusion that chronic vasospasm is an inflammatory vasculopathy and suggest that early treatment with high dose methylprednisolone may benefit this high risk group of patients.

Computed Tomographic Determinants of Neurologic Deterioration in Patients With Large Middle Cerebral Artery Infarctions

OBJECTIVE To identify specific radiographic features on computed tomographic (CT) imaging that can predict neurologic deterioration in patients with large middle cerebral artery (MCA) infarctions. PATIENTS AND METHODS We performed a 10-year retrospective review from January 1, 1991, through December 31, 2001, of medical records and CT scans of patients with large MCA infarctions. Neurologic deterioration was defied as progressive drowsiness or signs of herniation. The CT scans were grouped into 3 periods according to time after ictus. Radiographic features reviewed included hyperdense middle cerebral artery sign (HMCAS), more than a 50% loss of MCA territory, sulcal effacement, loss of lentiform nucleus or insular ribbon, and septal and pineal shift. Demographic and radiographic variables were compared by using t tests and the Fisher exact test. Prognostic values were calculated for all significant radiographic variables. RESULTS Thirty-four CT scans in 22 patients before neurologic deterioration were compared with 47 scans obtained in 14 patients without neurologic worsening. There were no demographic differences between groups. Initial analysis revealed that early (<12 hours) involvement of more than 50% of the MCA territory (P=.047; odds ratio [OR], 14.02; 95% confidence interval [CI], 1.04-189.42) and the HMCAS at any time (P<.001; OR, 21.6; 95% CI, 3.54-130.04) were independent predictors of neurologic deterioration. The positive predictive power for early involvement of more than 50% of the MCA and the HMCAS was 0.75 and 0.91, respectively. CONCLUSION The HMCAS and early CT evidence of more than 50% MCA involvement are predictive of neurologic deterioration in patients with large MCA infarcts.

Coils or clips in subarachnoid haemorrhage

In this issue of the Journal of Cerebrovascular Diseases and Stroke, the International Subarachnoid Aneurysm Trial (ISAT) collaborators report their multicenter randomized trial comparing the safety and efficacy of endovascular coiling versus neurosurgical clipping in patients with a ruptured intracranial saccular aneurysm. Both the ISAT report and this editorial were previously published in The Lancet. The primary outcome measure was the proportion of patients dead or disabled, defined by a modified Rankin scale (mRS) score between 3 and 6, at 1 year. Recruitment was halted after randomization of 2143 eligible patients selected from 9278 patients with subarachnoid hemorrhage (SAH). A planned interim analysis demonstrated a relative risk reduction of 22.6% and an absolute risk reduction of 6.9% of dependency or death at 1 year with endovascular treatment. The patients randomized in ISAT represent a selected subgroup of patients with SAH seen in clinical practice. Eighty-eight percent were of good clinical status, 93% of the target aneurysms were 10 mm or smaller in diameter, and 97% of target aneurysms were in the anterior circulation. These three characteristics have historically been thought to predict a good neurological outcome after neurosurgical clipping. The better neurological outcome after endovascular coiling in ISAT is thus noteworthy. Despite no prospective study demonstrating superior safety of one treatment over another, a relatively small number of assessed patients were randomized in ISAT. Apparently, clinical equipoise did not exist in 80% of 9278 patients with aneurysmal SAH assessed for eligibility. Almost thirty percent (2737) of the patients were considered to be better candidates for endovascular coiling, 3615 patients for neurosurgical clipping, and 1064 were treated in some other unknownmanner. Any pre-existing bias is likely to be multifactorial, including personal experiences at the individual centers, knowledge of the results of previous retrospective reviews of treatment of aneurysms with particular characteristics, patient’s preference, and clinical status after SAH. Given that so many patients were deemed ineligible for randomization by the participating interventional neuroradiologists and neurosurgeons, it is difficult to generalize the results of this study to the entire population of patients with aneurysmal SAH. Application to practice must be limited to those whose characteristics match those randomized in ISAT. The clinical follow-up data are limited. Dependency and death were assessed by postal questionnaire. The differences in outcome between treatments were mainly in the mRS3 (significant restriction in lifestyle) and mRS2 (some restriction in lifestyle) groups, and there was no difference in mortality between treatments. The ability of a questionnaire to reliably differentiate moderate from moderately severe functional disability is uncertain. Activities-of-daily-living, or deficit-delineation scales were not reported. Evaluation of cognitive outcome is an important contributor to assessment of disability after surgery for unruptured aneurysm. The comprehensive neuropsychometric data collected on a subset of the ISAT patients will greatly help to clarify cognitive outcomes after aneurysmal SAH treatment. In the neurosurgical group, 23 patients rebled before the first procedure, compared with 14 in the endovascular group. This result may be secondary to the small but statistically significant difference in the time between randomization and the first procedure (1.7 days for neurosurgery compared with 1.1 days for endovascular), and underscores the importance of early treatment of ruptured cerebral aneurysms. More than 3% (3.4%) of neurosurgical cases and 13.0% of endovascular cases required a second procedure—higher than might be expected given the characteristics of the patients. In those patients allocated to endovascular treatment, 5 who had failed endovascular coiling rebled while awaiting neurosurgical clipping. The ongoing debate about what constitutes definitive treatment of a ruptured cerebral aneurysm and durability of treatment remains unanswered. If definitive treatment is defined as prevention of post-treatment rebleeding, then definitive treatment was not attained in 2.4% (26/ 1048) of endovascular cases and in 1.0% (10/994) of those treated surgically, as indicated by target aneurysm rebleeding within a year. These data suggest an increased early rebleeding risk among endovascularly treated patients. The early rebleeding rates in this study for both endovascularly and surgically treated patients are higher From the *Departments of Radiology, †Neurology, and Neurologic Surgery, Mayo Clinic, Rochester, MN. Reprinted from The Lancet 360:1262-1263, 2002; copyright by Elsevier Science Ltd. All rights reserved. Address reprint requests to: Douglas A. Nichols, MD, Department of Radiology, Mayo Clinic, Rochester, MN 55905. Copyright

Endovascular Coil Embolization of Cerebral Aneurysm Remnants After Incomplete Surgical Obliteration

Introduction— The presence of an aneurysm remnant after incomplete or unsuccessful surgical clipping is associated with persistent risk of regrowth and rupture, and additional treatment is generally recommended. Attempts at surgical re-exploration are technically difficult and carry significant risk. Endovascular therapy can represent a valuable therapeutic alterative in these cases. Methods— We reviewed the information on 21 patients with postsurgical aneurysm remnants treated at our institution with endovascular coil occlusion between 1991 and 2000. Clinical outcome was measured using the modified Rankin scale. Statistical analysis of outcome predictors was performed using the two-tailed Fisher exact test. Results— Sixty-seven percent of the aneurysms were located in the anterior circulation. The median aneurysm size at the time of surgery was 9.9 mm (range 3 to 35 mm). The mean size of the aneurysm remnants before coiling was 6.4 mm (range 3 to 14 mm). Endovascular coiling resulted in total occlusion of the remnants in 81% of the cases. No major complications were associated with the endovascular treatment. Seventy-two percent of patients left the hospital without any functional impairment (modified Rankin scale 0 to 1). No cases of subarachnoid hemorrhage or symptomatic aneurysmal regrowth were noted after endovascular treatment over a mean follow-up of 22 months. Presence of disability or death was associated with an initial (presurgical) presentation with subarachnoid hemorrhage (P =0.04) and an interval between incomplete clipping and endovascular coil embolization ≤1 month (P = 0.0005). Conclusion— Endovascular coil occlusion of postsurgical aneurysm remnants is a safe and efficacious therapeutic alternative in selected cases. Postoperative angiography to identify aneurysm remnants that may be amenable to endovascular treatment should be considered in all patients.

Medical and Surgical Management of Intracranial Aneurysms

OBJECTIVE To examine the medical and surgical aspects of intracranial aneurysms, including the pathogenesis, clinical manifestations, management of subarachnoid hemorrhage (SAH), and indications for surgical intervention. DESIGN This review presents the classification of intracranial aneurysms, defines specific aneurysms, and analyzes the Mayo Clinic experience with surgical treatment of cerebral aneurysms. MATERIAL AND METHODS Intracranial aneurysms are classified by cause, size, site, and shape. The clinical grading systems for SAH, the most common manifestation, are as follows: modified Botterell, Hunt and Hess, and World Federation of Neurological Surgeons. Surgical options are direct clipping, interventional neuroradiologic treatment, proximal ligation or trapping of aneurysms, and wrapping or coating of aneurysms. Although the timing of surgical intervention after SAH is controversial, it should be based on the clinical grade, site of the aneurysm, and patients medical condition. RESULTS The frequency of intracranial aneurysms is estimated to be 1 to 8% in the general population, and 90% of patients have SAH. After SAH, 8 to 60% of patients die before they get to a hospital. After hospitalization, the mortality rate is 37%, severe disability is 17%, and outcome is favorable in 47%. The current trend for surgical treatment is early after SAH. The Mayo Clinic experience with 1,947 patients who underwent surgical treatment because of aneurysmal SAH or for aneurysmal repair between 1969 and 1990 is as follows: 1,445 had an excellent outcome, 231 had a good outcome, 171 had a poor outcome, and 100 died. CONCLUSION Aggressive management can be beneficial for many patients with severe neurologic injury after SAH by preventing rerupture of the aneurysm, attenuating the severity and sequelae of vasospasm, and decreasing the surgical complications.

Perimesencephalic subarachnoid hemorrhage. Additional perspectives from four cases.

Background Nonaneurysmal perimesencephalic hemorrhage, a distinct form of subarachnoid hemorrhage, is a recently described variant of intracranial hemorrhage. We describe two patients who presented with unusual features of this type of subarachnoid hemorrhage and also two patients who had a perimesencephalic pattern of hemorrhage due to a ruptured posterior circulation aneurysm. Case Descriptions The first patient, a 41‐year‐old woman with perimesencephalic hemorrhage, underwent an exploratory craniotomy because angiography had suggested an anomaly of the basilar tip. No source of hemorrhage could be identified at the time of surgery. The second patient was a 3‐year‐old boy who presented with opisthotonos and who was found to have a perimesencephalic hemorrhage. Angiography revealed no source for the hemorrhage. The third patient, a 54‐year‐old man, had a perimesencephalic pattern of subarachnoid hemorrhage from a vertebrobasilar junction aneurysm associated with a fenestration that was missed on the initial angiographic study. The fourth patient, a 43‐year‐old man, suffered a perimesencephalic pattern of subarachnoid hemorrhage from a small posterior cerebral artery aneurysm, which had not been recognized on two angiograms. Conclusions These patients elaborate on the clinical spectrum of subarachnoid hemorrhage with a perimesencephalic pattern. First, a negative exploratory craniotomy suggests that the source of nonaneurysmal perimesencephalic hemorrhage may not be arterial. Second, nonaneurysmal perimesencephalic hemorrhage may also occur in children. Finally, the index of suspicion for a posterior circulation aneurysm should remain high in patients who present with a perimesencephalic pattern of subarachnoid hemorrhage, and these aneurysms may rise from unusual locations. (Stroke. 1994;25:1507‐1511.)