Changes in Ventricular and Cortical Volumes following Shunt Placement in Patients with Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND AND PURPOSE: While changes in ventricular and extraventricular CSF spaces have been studied following shunt placement in patients with idiopathic normal pressure hydrocephalus, regional changes in cortical volumes have not. These changes are important to better inform disease pathophysiology and evaluation for copathology. The purpose of this work is to investigate changes in ventricular and cortical volumes in patients with idiopathic normal pressure hydrocephalus following ventriculoperitoneal shunt placement. MATERIALS AND METHODS: This is a retrospective cohort study of patients with idiopathic normal pressure hydrocephalus who underwent 3D T1-weighted MR imaging before and after ventriculoperitoneal shunt placement. Images were analyzed using tensor-based morphometry with symmetric normalization to determine the percentage change in ventricular and regional cortical volumes. Ventricular volume changes were assessed using the Wilcoxon signed rank test, and cortical volume changes, using a linear mixed-effects model (P < .05). RESULTS: The study included 22 patients (5 women/17 men; mean age, 73 [SD, 6] years). Ventricular volume decreased after shunt placement with a mean change of -15.4% (P < .001). Measured cortical volume across all participants and cortical ROIs showed a mean percentage increase of 1.4% (P < .001). ROIs near the vertex showed the greatest percentage increase in volume after shunt placement, with smaller decreases in volume in the medial temporal lobes. CONCLUSIONS: Overall, cortical volumes mildly increased after shunt placement in patients with idiopathic normal pressure hydrocephalus with the greatest increases in regions near the vertex, indicating postshunt decompression of the cortex and sulci. Ventricular volumes showed an expected decrease after shunt placement.

Psychiatric co-morbidity in 75 patients undergoing epilepsy surgery: lack of correlation with pathological findings.

BACKGROUND: Psychiatric disorders may occur in patients with intractable partial epilepsy after surgical treatment. Previous reports attributed the presence of psychological adverse events to specific pathological entities such as dysembryoplastic neuroepithelial tumors (DNETs) and gangliogliomas. The rationale for the present study is to evaluate the importance of the surgical pathology in individuals undergoing epilepsy surgery. METHODS: The patients were separated into three groups based on the surgical pathology: group I ganglioglioma (N=25), group II DNETs (N=25), and group III mesial temporal sclerosis (N=25). Thirteen of the 75 patients (17.3%) had a preexisting psychiatric disorder. The most common preoperative psychiatric diagnosis was depression (N=4). Sixty-three of the lesions (84%) were restricted to the temporal lobe. The operative strategy included resection of the lesion and epileptogenic cortex. Sixty-two of the 75 patients (83%) were rendered seizure-free. RESULTS: Eight of the 75 patients (10.7%) had an acquired psychiatric illness following surgical treatment. A mood disorder developed in three patients after surgery. No statistical difference emerged in preoperative psychiatric co-morbidity (no group difference; p=1.0) or in newly diagnosed postoperative psychiatric disease (group I vs. II, p=0.67; group I vs. III, p=1.0; and group II vs. III, p=0.67) within the three surgical pathology groups. CONCLUSION: This study indicates that the presence of psychiatric disease before and after surgery for intractable partial epilepsy, predominantly of temporal lobe origin, was independent of the pathological findings.

Surgical outcome and predictive factors in adult patients with intractable epilepsy and focal cortical dysplasia.

OBJECTIVES: To determine the surgical outcome and prognostic factors in adult patients with intractable epilepsy and focal cortical dysplasia (FCD). MATERIALS AND METHODS: We retrospectively studied the operative outcome in 21 consecutive adult patients with FCD who underwent surgical treatment for intractable partial epilepsy. RESULTS: The mean age at surgery was 32.7 years (range, 18-58 years). The median post-operative follow-up was 2.5 years. The FCD was extratemporal in 11 patients, involved the temporal lobe in 10 patients, and was multilobar in eight patients. Eleven patients (52%) were rendered seizure-free, four patients (19%) had >95% reduction in seizures, and two patients (10%) had an 80-94% reduction in seizures. A seizure-free outcome was associated with shorter duration of epilepsy (P = 0.02). CONCLUSION: Adult patients with FCD may be candidates for surgical treatment of intractable partial epilepsy. Most individuals have neocortical, extrahippocampal seizures and approximately 50% of patients are rendered seizure-free.

Adult-onset epilepsy in focal cortical dysplasia of Taylor type.

Focal cortical dysplasia of Taylor type (FCDT) usually presents with seizures at an early age, whereas adult onset of epilepsy is uncommon. We reviewed the medical records of 213 patients with FCDT. In 21 patients (10%), age at seizure onset ranged from 18 to 55 years (mean 25.3). The outcome of seizures in patients with FCDT and adult-onset epilepsy seems favorable vs childhood-onset seizures.

Resective reoperation for failed epilepsy surgery: seizure outcome in 64 patients.

OBJECTIVE: To determine the surgical outcome and factors of predictive value in patients undergoing reoperation for intractable partial epilepsy. METHODS: The authors retrospectively studied the operative outcome in 64 consecutive patients who underwent reoperation for intractable partial epilepsy. Demographic data, results of comprehensive preoperative evaluations, and the seizure and neurologic outcome after reoperation were determined. All patients were followed a minimum of 1 year subsequent to their last operative procedure. RESULTS: Fifty-three patients had two surgeries, and 11 patients had three or more operations. The first surgery involved a lesionectomy (n = 33), "nonlesional" temporal lobe resection (n = 28), and a "nonlesional" extratemporal resection (n = 3). The mean duration between the first and second procedure was 5.5 years. Fifty-five patients underwent an intralobar reoperation, whereas nine had a resection of a different lobe. After reoperation, 25 patients (39%) were free of seizure, 6 patients (9%) had rare seizures, 12 patients (19%) had a worthwhile improvement, and 21 patients (33%) failed to respond to surgery. Predictors of seizure-free outcome were age at seizure onset >15 years (p = 0.01), duration of epilepsy < or =5 years at the time of initial surgery (p = 0.03), and focal interictal discharges in scalp EEG (p = 0.03). Using a logistic regression model, two significant predictors emerged: duration of epilepsy < or =5 years (odds ratio, 3.18; p = 0.04) and preoperative focal interictal discharge (odds ratio, 4.45; p = 0.02). Complications of reoperation included visual field deficits (n = 9), wound infection (n = 2), subdural hematoma (n = 1), and hemiparesis (n = 1). CONCLUSION: Reoperation may be an appropriate alternative form of treatment for selected patients with intractable partial epilepsy who fail to respond to initial surgery.

Long-term follow-up of temporal lobectomy in children.

Temporal lobectomy is an effective treatment for medically intractable seizures. The change in seizure status with prolonged postoperative follow-up is unclear. The authors followed 37 patients who underwent first time temporal lobectomy during childhood for at least 15 years. This study is the longest follow-up of children who have had a temporal lobectomy for intractable seizures. It demonstrates that seizure recurrence can increase with longer duration of follow-up.

Endoscopic transnasal pituitary surgery: report on 180 cases.

The endoscopic transnasal approach is an evolving technique for treating lesions in the sella turcica. Since this method was introduced at our institution 4 years ago, the majority of transsphenoidal procedures are performed with it. The records of all patients having endoscopic transnasal hypophysectomy at the Mayo Clinic during the last 4 years were reviewed retrospectively. The criteria analyzed were safety, functional and cosmetic outcome, and complications. During the 4-year period, the operative procedure was modified to improve operative exposure and safety. The results of our review showed a significant decrease in length of hospital stay, reduced operative time, reduced need for nasal packing, and elimination of a sublabial incision. The complication rate was equivalent to that reported for the traditional transseptal transsphenoidal approach. As the neurosurgeons at our institution gained experience with this approach, an increasing number of pituitary microadenomas were resected safely and successfully. In addition, because of the limited septal dissection, this approach is particularly helpful for revision operations. This approach also can be used for the full range of pituitary lesions and in conjunction with adjunctive techniques, including frontal craniotomy and gamma-knife irradiation. Currently, the endoscopic transsphenoidal approach is the method preferred for surgically treating pituitary lesions in adults at our institution.

Awake craniotomy for aggressive resection of primary gliomas located in eloquent brain.

OBJECTIVE: To determine with intraoperative neurologic and language examinations the maximal tumor resection achievable with acceptable postoperative neurologic dysfunction in patients undergoing awake stereotactic glial tumor resection in eloquent regions of the brain. PATIENTS AND METHODS: Between October 1995 and December 2000, 65 patients underwent frameless stereotactic resection of glial tumors located in functioning tissue. During the resection, continuous examinations by a neurologist and speech pathologist were performed. The goal of surgery was to resect the maximum neurologically permissible tumor volume defined on preoperative T2 imaging. Tumor resection was stopped at the onset of neurologic dysfunction. Novel segmentation software was used to measure tumor cytoreduction based on pre- and postoperative magnetic resonance imaging. All patients underwent 3-month postoperative neurologic examinations to determine functional outcomes. RESULTS: The cortical and subcortical white matter tracts at risk for injury were the left frontal operculum in 15 patients, the central lobule in 38, the insula in 11, and the left angular gyrus in 1. Thirty-four (52%) had a greater than 90% reduction in T2 signal postoperatively. In 26 patients thought to have low-grade tumors based on preoperative imaging, 12 proved to have grade 3 gliomas. Forty-eight patients (74%) developed intraoperative deficits; 34 (71%) recovered to a modified Rankin grade of 0 or 1 at 3 months postoperatively, 11 (23%) achieved a modified Rankin grade of 2, and 3 patients (6%) achieved a modified Rankin grade of 3 or 4 at 3-month follow-up. There was no operative mortality; 17 patients (26%) died from tumor progression during the follow-up period. CONCLUSIONS: Combining frameless computer-guided stereotaxis with cortical stimulation and repetitive neurologic and language assessments facilitates tumor resection in functioning brain regions. Resecting tumor until the onset of neurologic deficits allows for a good functional recovery. Imaging software can objectively and accurately measure preoperative and postoperative tumor volumes.

Pituitary carcinoma: an ultrastructural study of eleven cases.

Pituitary carcinomas are very rare. Defined as adenohypophysial tumors that undergo craniospinal and/or systemic metastasis, most are PRL- or ACTH-producing. Their ultrastructural features, particularly relative to benign adenomas of similar functional type, have not been sufficiently explored. Eleven cases of immunohistochemically characterized pituitary carcinoma with documented cerebrospinal and/or systemic metastases were collected from various institutions and studied by transmission electron microscopy. The tumors were surgically removed from 7 women and 4 men ranging in age between 28 and 74 years (mean, 50 years). All were endocrinologically functioning. Six tumors secreted PRL; three were ACTH-producing; one each was GH/PRL- and TSH-producing. The patients with the ACTH-producing tumors had all presented with Cushing's disease and two of them had undergone adrenalectomy (Nelson syndrome). In most cases significant cellular atypia and mitotic activity were observed. In terms of morphologic features of functional differentiation, electron microscopy revealed that in 9 cases the tumor cells maintained at least some ultrastructural markers of their basic phenotype. A unique feature in 2 ACTH carcinomas was the variable admixture of smooth endoplasmic reticulum with intermediate (cytokeratin) filaments. In 2 cases, both PRL-producing carcinomas, the cell type comprising the tumor could not be identified on an ultrastructural basis alone. Ultrastructural investigation of pituitary carcinomas confirms their endocrine nature and, in most but not all cases, reveals their functional differentiation. Despite the diagnostic utility of electron microscopy in the assessment of these rare tumors, the distinction of pituitary carcinoma from pituitary adenoma cannot be firmly made on ultrastructural grounds alone.

Fatal progression of posttraumatic dural arteriovenous fistulas refractory to multimodal therapy. Case report.

The authors report the case of a man who suffered from progressive, disseminated posttraumatic dural arteriovenous fistulas (DAVFs) resulting in death, despite aggressive endovascular, surgical, and radiosurgical treatment. This 31-year-old man was struck on the head while playing basketball. Two weeks later a soft, pulsatile mass developed at his vertex, and the man began to experience pulsatile tinnitus and progressive headaches. Magnetic resonance imaging and subsequent angiography revealed multiple AVFs in the scalp, calvaria, and dura, with drainage into the superior sagittal sinus. The patient was treated initially with transarterial embolization in five stages, followed by vertex craniotomy and surgical resection of the AVFs. However, multiple additional DAVFs developed over the bilateral convexities, the falx, and the tentorium. Subsequent treatment entailed 15 stages of transarterial embolization; seven stages of transvenous embolization, including complete occlusion of the sagittal sinus and partial occlusion of the straight sinus; three stages of stereotactic radiosurgery; and a second craniotomy with aggressive disconnection of the DAVFs. Unfortunately, the fistulas continued to progress, resulting in diffuse venous hypertension, multiple intracerebral hemorrhages in both hemispheres, and, ultimately, death nearly 5 years after the initial trauma. Endovascular, surgical, and radiosurgical treatments are successful in curing most patients with DAVFs. The failure of multimodal therapy and the fulminant progression and disseminated nature of this patient's disease are unique.

Ischemic complications of surgery for anterior choroidal artery aneurysms.

OBJECT: Anterior choroidal artery (AChA) aneurysms account for 4% of all intracranial aneurysms. The surgical approach is similar to that for other supraclinoid carotid artery lesions, but surgery may involve a higher risk of debilitating ischemic complications because of the critical territory supplied by the AChA. METHODS: Between 1968 and 1999, 51 AChA aneurysms in 50 patients were treated using craniotomy and clipping at the Mayo Clinic. There were 22 men (44%) and 28 women (56%) whose average age was 53 years (range 27-79 years). Twenty-four AChA aneurysms (47%) had hemorrhaged; nine patients (18%) had subarachnoid hemorrhage from another aneurysm. Three AChA aneurysms (6%) were associated with symptoms other than rupture. Forty-one patients (82%) achieved a Glasgow Outcome Scale (GOS) score of 4 or 5 at long-term follow up. The surgical mortality rate was 4%, and major surgical morbidity (GOS < or = 3) was 10%. Eight patients (16%) had clinically and computerized tomography-demonstrated AChA territory infarcts. Five of these strokes manifested in a delayed fashion 6 to 36 hours after the operation, and progressed from mild to complete deficit over hours. In 41 patients the aneurysm arose from the internal carotid artery adjacent to the AChA, and in nine patients the aneurysm arose directly from the origin of the AChA itself; four of these nine patients had postoperative infarction. CONCLUSIONS: Surgical treatment of AChA aneurysms involves a significant risk of debilitating ischemic complications. Most postoperative strokes occur in a delayed fashion, offering a potential therapeutic window. Patients with aneurysms arising from the AChA itself have an extremely high risk for postoperative stroke.

Surgical repair of clinoidal segment carotid artery aneurysms unsuitable for endovascular treatment.

OBJECTIVE: Clinoidal segment carotid artery aneurysms are surgically challenging lesions. The aneurysm neck originates proximal to the distal dural ring, and the aneurysms typically are larger. Therefore, endovascular techniques are often considered to be the primary treatment option. Treatment techniques and results for 40 clinoidal segment carotid artery aneurysms that were considered unsuitable for contemporary endovascular intervention are analyzed in this report. METHODS: Forty aneurysms in 33 female and 3 male patients were treated surgically. Fifteen patients had bilateral aneurysms; of these patients, four underwent bilateral craniotomies. Twenty-seven aneurysms were 10 to 14 mm in size, eight were 15 to 24 mm, and five were more than 25 mm. The most common presentation was visual loss, which occurred in 13 patients. Seven patients presented with subarachnoid hemorrhage. RESULTS: Thirty-seven aneurysms were directly repaired with clipping, two were trapped with bypass, and one was trapped without bypass. The complication rate was 10%, with one major stroke, two minor strokes, and one successfully treated brain abscess. CONCLUSION: Surgical treatment of clinoidal segment carotid artery aneurysms can produce acceptable outcomes. Specific preoperative and intraoperative techniques facilitate improved surgical results for aneurysms that are not treatable with contemporary endovascular techniques.

Spontaneous intracranial hypotension mimicking aneurysmal subarachnoid hemorrhage.

OBJECTIVE: An excruciating headache of instantaneous onset is known as a thunderclap headache. A subarachnoid hemorrhage is the prototypical cause, but other serious disorders may also present with a thunderclap headache, including cerebral venous sinus thrombosis, carotid artery dissection, and pituitary apoplexy. We report a group of patients with thunderclap headaches as the initial manifestation of spontaneous intracranial hypotension caused by a spinal cerebrospinal fluid leak. METHODS: Among 28 patients with spontaneous intracranial hypotension due to a documented spinal cerebrospinal fluid leak, four (14%) initially experienced an excruciating headaches of instantaneous onset. RESULTS: The mean age of the four patients (two men and two women) was 35 years (range, 24-45 yr). Nuchal rigidity was present in the three patients who sought early medical attention, and they underwent emergency computed tomographic scanning, lumbar puncture, and cerebral angiography to rule out an aneurysmal subarachnoid hemorrhage. The delay between the onset of headache and diagnosis of intracranial hypotension ranged from 4 days to 5 weeks. A fourth patient did not seek medical attention until 1 month after the ictus. CONCLUSION: Spontaneous intracranial hypotension should be included in the differential diagnosis of thunderclap headache, even when meningismus is present.

Carotid artery: elliptic centric contrast-enhanced MR angiography compared with conventional angiography.

PURPOSE: To determine the accuracy of elliptic centric contrast material-enhanced magnetic resonance (MR) angiography by using conventional angiography as the reference standard. MATERIALS AND METHODS: Fifty patients were examined prospectively with contrast-enhanced MR angiography and conventional angiography. The two examinations were performed within 1 week of each other. Two patients underwent conventional angiography of only one carotid artery, which yielded 98 arteries for comparison. RESULTS: With conventional angiography as the reference standard and by using a 70% threshold for internal carotid arterial diameter stenosis, maximum intensity projection (MIP) images had a sensitivity of 93.3%, specificity of 85.1%, and accuracy of 87.6%, whereas reformatted transverse source images had a sensitivity of 83.3%, specificity of 97.0%, and accuracy of 92.8%. Interobserver variability for conventional angiograms was 0.97, for MIP images was 0.91, and for source images was 0.90. The contrast-enhanced MR angiographic technique had a sensitivity of 88.9% and specificity of 58.1% for the presence of irregularity and/or ulceration. All 50 examinations were triggered appropriately so that minimal or no venous signal intensity was depicted. CONCLUSION: Contrast-enhanced elliptic centric three-dimensional MR angiography offers high-spatial-resolution, venous-suppressed images of the carotid arteries that appear to be adequate to replace conventional angiography in most patients examined prior to carotid endarterectomy.

Refractory idiopathic intracranial hypertension treated with stereotactically planned ventriculoperitoneal shunt placement.

OBJECT: Ventriculoperitoneal (VP) shunts have not been widely used for idiopathic intracranial hypertension (IIH) because of the difficulty of placing a shunt into normal or small-sized ventricles. The authors report their experience with stereotactic placement of VP shunts for IIH. METHODS: The authors reviewed the clinical records of all patients in whom stereotaxis was used to guide the placement of a VP shunt for IIH at their institution. All shunts were placed using stereotactic guidance to target the frontal horn of the lateral ventricle. Patients were contacted at a mean postoperative interval of 15.1 months. No patients were lost to follow up. The authors identified 13 patients who underwent placement of a stereotactically guided VP shunt for IIH over a 6-year period. A trial of either acetazolamide or steroid therapy had failed in all patients. Prior surgical treatments included optic nerve sheath fenestrations in seven patients and cerebrospinal fluid diversionary procedures, other than stereotactic VP shunt procedures, in nine patients. Twelve patients reported excellent or good durable symptomatic relief at the time of follow up. No patient suffered progression of visual deficits. Four patients experienced persistent headaches following the procedure. Three patients required a revision of the VP shunt for technical failure. CONCLUSIONS: Stereotactically guided VP shunt placement is an effective and durable treatment option in many cases of IIH that are refractory to more traditional medical and surgical approaches.

Subtraction peri-ictal SPECT is predictive of extratemporal epilepsy surgery outcome.

OBJECTIVES: To determine whether localization of extratemporal epilepsy with subtraction ictal SPECT coregistered with MRI (SISCOM) is predictive of outcome after resective epilepsy surgery, whether SISCOM images provide prognostically important information compared with standard tests, and whether blood flow change on SISCOM images is useful in determining site and extent of excision required. BACKGROUND: The value of SISCOM in predicting surgical outcome for extratemporal epilepsy is unknown, especially if MRI findings are nonlocalizing. METHODS: SISCOM images in 36 consecutive patients were classified by blinded reviewers as "localizing and concordant with site of surgery," "localizing but nonconcordant with site of surgery," or "nonlocalizing." SISCOM images were coregistered with postoperative MRI, and reviewers visually determined whether cerebral cortex underlying the SISCOM focus had been completely resected, partially resected, or not resected. RESULTS: Twenty-four patients (66.7%) had localizing SISCOM, including 13 (76.5%) of those without a focal MRI lesion. Eleven of 19 patients (57.9%) with localizing SISCOM concordant with the surgical site, compared with 3 of 17 (17.6%) with nonlocalizing or nonconcordant SISCOM, had an excellent outcome (p < 0.05). With logistic regression analysis, SISCOM findings were predictive of postsurgical outcome, independently of MRI or scalp ictal EEG findings (p < 0.05). The extent of resection of the cortical region of the SISCOM focus was significantly associated with the rate of excellent outcome (100% with complete resection, 60% with partial resection, and 20% with nonresection, p < 0.05). CONCLUSION: SISCOM images may be useful in guiding the location and extent of resection in extratemporal epilepsy surgery.

Redefined duplex ultrasonographic criteria for diagnosis of carotid artery stenosis.

OBJECTIVE: To evaluate duplex ultrasonographic criteria for the determination of 50% or more and 70% or more stenosis of the diameter of the internal carotid artery based on conventional angiography in order to align ultrasonographic diagnostic categories with current clinical management schemes. PATIENTS AND METHODS: Between January 1, 1995, and June 30, 1999, 915 patients underwent both carotid duplex ultrasonography and cerebral angiography within 30 days at Mayo Clinic, Rochester, Minn. Of these patients, 294 were excluded from this study because of occlusion of one or both of the internal carotid arteries or atypical flow characteristics. In the remaining 621 patients (61 % male, 39% female; mean age, 67.7 years [range, 14-88 years]), 1218 vessels were available for correlation. Several Doppler ultrasonographic velocity variables were compared with the angiographic findings by use of receiver operating characteristic curve analysis. The primary end point was verification of optimal ultrasonographic criteria to diagnose 70% or more internal carotid artery stenosis. The secondary end point was establishment of threshold values to detect stenosis of 50% or more. RESULTS: At angiography, 382 patients had internal carotid arteries with 70% or more stenosis. Peak systolic and end diastolic velocities of the internal carotid artery and internal carotid artery:common carotid artery peak systolic velocity ratios were measured. For an internal carotid artery stenosis of 70% or more, a peak systolic velocity of 230 cm/s or more resulted in a sensitivity of 86.4%, a specificity of 90.1%, a positive predictive value of 82.7%, a negative predictive value of 92.3%, and an accuracy of 88.8%. An end diastolic velocity of 70 cm/s or more and an internal carotid artery:common carotid artery ratio of 3.2 or more yielded similar values. For an internal carotid artery stenosis of 50% or more, a peak systolic velocity of 130 cm/s or more resulted in a sensitivity of 92.1 %, a specificity of 89.5%, a positive predictive value of 90.3%, a negative predictive value of 91.3%, and an overall accuracy of 90.8%. An internal carotid artery:common carotid artery ratio of 1.6 or more yielded similar values. CONCLUSION: In our ultrasonography laboratory, a carotid artery stenosis of 70% or more (for which carotid endarterectomy is typically recommended in symptomatic patients) is diagnosed reliably with the following duplex ultrasonographic criteria: a peak systolic velocity of 230 cm/s or more, an end diastolic velocity of 70 cm/s or more, or an internal carotid artery:common carotid artery ratio of 3.2 or more.

Adenovirus-mediated gene transfer to human cerebral arteries.

Gene therapy is being investigated as a putative treatment option for cardiovascular diseases, including cerebral vasospasm. Because there is presently no information regarding gene transfer to human cerebral arteries, the principal objective of this study was to characterize adenovirus-mediated expression and function of recombinant endothelial nitric oxide synthase (eNOS) gene in human pial arteries. Pial arteries (outer diameter 500 to 1,000 microm) were isolated from 30 patients undergoing temporal lobectomy for intractable seizures and were studied using histologic staining, histochemistry, electron microscopy, and isometric force recording. Gene transfer experiments were performed ex vivo using adenoviral vectors encoding genes for bovine eNOS (AdCMVeNOS) and Escherichia coli beta-galactosidase (AdCMVLacZ). In transduced arteries, studied 24 hours after exposure to vectors, expression of recombinant beta-galactosidase and eNOS was detected by histochemistry, localizing mainly to the adventitia (n = 4). Immunoelectron microscopy localized recombinant eNOS in adventitial fibroblasts. During contractions to U46619, bradykinin-induced relaxations were significantly augmented in AdCMVeNOS-transduced rings compared with control and AdCMVLacZ-transduced rings (P < 0.01; n = 6). The NOS inhibitor L-nitroarginine methylester (L-NAME) caused significantly greater contraction in AdCMVeNOS-transduced rings (P < 0.001; n = 4) and inhibited bradykinin-induced relaxations in control and transduced rings (P < 0.001; n = 6). The current findings suggest that in AdCMVeNOS-transduced human pial arteries, expression of recombinant eNOS occurs mainly in adventitial fibroblasts where it augments relaxations to NO-dependent agonists such as bradykinin. Findings from the current study might be beneficial in future clinical applications of gene therapy for the treatment or prevention of cerebral vasospasm.