Visual evoked responses as a monitor of intracranial pressure during hyperosmolar blood-brain barrier disruption.

Intracarotid mannitol (HBBBD = hyperosmotic BBB disruption) as a method of transiently increasing solute/drug delivery to brain parenchyma has been associated in animals with a 1-2% increase in brain water and an increase in cisternal ICP. To determine whether these changes are clinically significant, we investigated ICP changes associated with HBBBD in 33 patients with malignant brain tumor utilizing flash VERs in which the N2 latency correlates well with ICP (N2 > 80 ms linearly corresponds to ICP > 20 cm H2O). VERs were obtained prior to, 4 and 24 h after 114 HBBBD/chemotherapy procedures. Additionally, in 10 patients (37 HBBBDs), VER monitoring was performed during the procedure. In 112/150 (75%) HBBBDs, good barrier opening was obtained (radionuclide brain scan). Postoperative mean N2 latencies did not differ significantly from pre-HBBBD values (N2 = 86 +/- 3.3 pre, 90 +/- 3.0/4 h, 87 +/- 3.6/24 h); there was no significant difference in N2 latencies in those patients with good vs poor BBBD. In the 10 patients monitored during HBBBD, peak N2 latency = 94.9 +/- 1.6, however, was significantly above pre- and post-HBBBD values (p < 0.04). We conclude that flash VERs are a useful noninvasive measure of ICP, and that HBBBD is associated with mild transient increase in ICP which is not clinically detrimental.

Dissociation of somatosensory and motor evoked potentials in a patient with an intramedullary spinal tumor.

We describe a patient with an intramedullary spinal tumor who demonstrated postoperative improvement of motor and sensory function despite the lack of somatosensory evoked potentials (SSEPs) before and after intraoperative monitoring. The motor system was evaluated by direct spinal cord stimulation across the tumor bed. The resultant evoked compound muscle action potentials and compound nerve activities were normal. Although there is sufficient clinical evidence that SSEPs are sensitive to posterior and posterolateral ischemic insults of the spinal cord, the technique should be employed with an awareness of its limitations in monitoring the descending tracts which have a different blood supply and occupy more anterior locations in the spinal cord.

Osmotic blood-brain barrier disruption and chemotherapy in the treatment of high grade malignant glioma: patient series and literature review.

In the past, chemotherapeutic treatment of patients with high grade malignant gliomas following surgery and radiation has not added significantly to the 12-14 month median survival rate. Over four years, 37 patients with high grade malignant gliomas underwent 246 treatment procedures with a combination of methotrexate, cyclophosphamide, and procarbazine given in association with hyperosmolar mannitol-induced transient breakdown of the blood-brain barrier. These patients have demonstrated a median survivorship of 22 months after considering age, Karnofsky Performance Score, and necrosis by the Cox Proportional Hazards model. The study group had a mean age of 43 years, and mean Karnofsky Performance Score of 67%. Sixty-five percent of the procedures had well-documented barrier disruption. Sixteen percent remained in complete remission while 24 patients (65%) had partial or temporary remission. Progression-free intervals after blood-brain barrier disruption/chemotherapy ranged from 1-47 (mean 15) months. Neurotoxicity has been minimal with one peri-procedural mortality and five patients suffering an increase in neurologic deficit after a procedure. The results of this study are consistent with and further extend the reported literature on this method of brain tumor therapy as described in other centers. Chemotherapy in conjunction with osmotic disruption of the blood-brain barrier may provide the pharmacokinetic advantage sufficient to significantly improve survival in patients with high grade malignant glioma.

Radionuclide assessment of blood-brain barrier disruption performed for chemotherapy of high grade malignant brain gliomas.

Compared to the conventional mode of chemotherapy of malignant brain gliomas following surgery and radiation therapy, chemotherapy after transient disruption of the blood-brain barrier coupled with intraarterial administration of methotrexate improved median survival from 12-14 to 22 months in our experience. Technetium-99m-DTPA brain scintigraphy played a unique and important role in the documentation of optimum blood-brain barrier disruption. Patients with excellent clinical outcome had significantly (P less than 0.0005) better blood-brain barrier disruption than patients with poor outcome. The results indicate that the clinical outcome is related to the degree of blood-brain barrier disruption.

The effects of anesthesia on osmotic blood-brain barrier disruption.

To evaluate the effect of various anesthetic agents on hyperosmolar blood-brain barrier disruption (BBBD), Sprague-Dawley rats were given pentobarbital (PB), ketamine-xylazine (KX), isoflurane (IF), methoxyflurane (MF), or fentanyl-droperidol (FD) before intracarotid infusion of mannitol or saline. Physiological monitoring showed that the effects of mannitol infusion differed significantly from those of saline infusion and were associated with transient bradycardia, hypotension, metabolic acidosis, and electroencephalographic depression. With PB, KX, or IF anesthesia, we obtained excellent BBBD as evidence by 3+ Evans blue staining of the mannitol-infused cerebral hemisphere. FD anesthesia was associated with tachycardia and MF anesthesia resulted in hypotension; both showed poor Evans blue staining. Radioisotope delivery to the disrupted hemisphere averaged 0.80% of the administered 125I-albumin compared to 0.03% in the contralateral and 0.06% in control (saline-infused) hemispheres. 99mTc-glucoheptonate delivery measured 0.49% of the administered dose after BBBD, 0.03% contralaterally, and 0.05% in control hemispheres. Pharmacological manipulation to normalize the cardiac index in the FD and MF groups resulted in 3+ Evans blue staining and significantly increased delivery of albumin and glucoheptonate. This study suggests that the cardiovascular changes of these specific anesthetic agents are important in obtaining optimal hyperosmolar BBBD.

Carotid endarterectomy: to shunt or not to shunt.

Because of controversies in the cerebrovascular literature regarding the use of an intraluminal shunt in carotid endarterectomy, we report a randomized prospective study of 118 consecutive symptomatic patients receiving surgery within a single neurosurgical practice. Over 4 years, 138 carotid endarterectomies were performed in the 118 patients, 63 operations with intraluminal shunting and 75 without. Standard rationale for surgery included ipsilateral cerebral infarction in 38% of the operations and ipsilateral transient ischemic attacks in 36%. Unilateral angiographic stenosis of greater than 90% was seen in 58% of the operations; there were no ipsilateral occlusions. Surgery was performed under general anesthesia with barbiturate induction and mild blood pressure elevation. The 30-day complication rate included a mortality rate of 0.7% with a 5.1% incidence of postoperative neurologic deficit and a 1.4% rate of myocardial infarction. In the 24 hours after surgery there were no cerebral infarctions in the shunted group and six in the unshunted group. This 8% rate in the unshunted group compared with 0% in the shunted group was significant at p = 0.023 with a power of 0.95 by Fisher's exact test and chi 2 analysis. This suggests that in our neurosurgical practice (resident training program) the use of an intraluminal shunt during carotid endarterectomy significantly reduces the risk of intraoperative neurologic deficit without increasing the incidence of other complications.

Comparison of CT-guided and stereotaxic cranial diagnostic needle biopsies.

Needle biopsy of the brain utilizing computerized tomography (CT) scan data is an accepted diagnostic technique that has been performed both with and without the aid of stereotaxic frames. Experience with both techniques has resulted in a specific procedure for CT-guided free-hand biopsy which is performed in the CT suite under local anesthesia. Over the last 6 years the authors have performed 64 CT-guided free-hand biopsies and 13 stereotaxic biopsies with the Brown-Roberts-Wells system. Nonspecific gliosis, tumor, infection, radiation necrosis, or vascular malformation, were diagnosed in all but one biopsy, for a clinically accurate diagnostic yield of 92%. A comparison of diagnostic yield, morbidity, and mortality has shown no significant difference between the free-hand and the stereotaxic techniques. The time required for the procedures and their cost have been compared and have been found to be significantly less for the free-hand biopsy group. Thus, CT-guided free-hand biopsy may still represent the method of choice for histological diagnosis of many intracranial lesions.

Developments in the diagnosis and treatment of primary CNS lymphoma. A prospective series.

Current experience with 12 patients studied prospectively suggests a new approach in the diagnosis and treatment of primary central nervous system (CNS) lymphoma, integrating the techniques of needle brain biopsy, immunohistochemical staining for monoclonal antibody and chemotherapeutic drug delivery in association with blood-brain barrier modification. Computed tomography (CT)-guided needle biopsy of deep parenchymal lesions contributed to the diagnosis in six patients. Immunohistochemical staining methods detected monoclonal immunoglobulins in those patients so tested. Following diagnosis, the patients have been treated with multi-agent chemotherapy in conjunction with osmotic blood-brain barrier modification (five without antecedent cranial irradiation) with an initial complete response rate by CT scan in nine patients, a median follow-up of 19 months from diagnosis, and a 1-year survival of 75%. This experience emphasizes the value of CT-guided stereotaxic or CT-guided needle biopsy, which limits the need for therapy without a diagnosis or the need for a major craniotomy in what are commonly deep, paraventricular lesions. Immunoperoxidase cytochemical stains can detect monoclonal immunoglobulin characteristic of CNS B-cell malignant lymphomas and provide an important diagnostic aid when only modest quantities of tissue or cells are obtained. Finally, chemotherapy administered in conjunction with osmotic blood-brain barrier modification results in a clinical response rate and survival that are at least as effective as radiotherapy as a primary therapeutic modality.

Late stenosis of a superficial temporal-middle cerebral artery bypass: angiographic and histological findings.

The course of a patient with an initially widely patent superficial temporal artery-middle cerebral artery (STA-MCA) bypass and an enlarged donor vessel is presented. Over 17 months, the STA became markedly stenotic. Serial angiography is correlated with autopsy histological findings showing severe atherosclerotic changes throughout the donor vessel. The potential causative factors, both medical and surgical, are discussed and the appropriate literature is reviewed. Parallels are drawn from the cardiac bypass experience. The bypass itself may have precipitated or accelerated intimal hyperplasia, which stenosed (and may have eventually occluded) the vessel. Is this phenomenon more frequent than we realize?

Can a patent extracranial-intracranial bypass provoke the conversion of an intracranial arterial stenosis to a symptomatic occlusion?

Although extracranial-intracranial (EC-IC) artery anastomosis seems to result in symptomatic improvement in certain types of cerebrovascular ischemic disease, this procedure can also be associated with significant morbidity, some of which paradoxically may be the direct result of a patent bypass. A review of the last 51/2 years at the Oregon Health Sciences University shows that 50 patients underwent 51 superficial temporal artery to middle cerebral artery bypass procedures with an angiographic patency rate of 91%. Of the 50 patients, 17 had intracranial stenotic lesions of either the middle cerebral artery (7 patients) or the internal carotid artery (10 patients). One patient had posterior cerebral artery stenosis. Five of the 18 patients with stenosis and a patent bypass developed a symptomatic occlusion of the stenotic lesion within 30 days after the anastomosis. It is hypothesized that the EC-IC bypass may have contributed to the occlusion in some of these patients by causing a change in the hemodynamic state. Possibly the bypass reversed the direction of flow distal to the stenosis to result in stasis and subsequent occlusion at the site of the stenosis or in some other manner affected hemostasis (i.e., the coagulation cascade).