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[American Association of Neurological Surgeons] The American Association of
Neurological Surgeons 1998 Annual Meeting
The American Association of Neurological Surgeons (AANS) held its 66th Annual Meeting April 25 - 30, 1998 at the Pennsylvania Convention Center in Philadelphia, Pennsylvania. NOTICE: The AANS meeting program information is available from the AANS. Users are responsible for complying with all copyright and licensing restrictions associated with the program information. Copyright © 1998; The American Association of Neurological Surgeons / Congress of Neurological Surgeons


    POSTER #1002
    Intraarterial Papaverine Therapy for Vasospasm: Does It Really Work?

    Frank R. Huang-Hellinger, MD, PhD
    Christopher M. Putman, MD (Boston, MA)
    Pearse Morris, MD (Burlington, VT)
    Ronald F. Budzik, Jr., MD
    Christopher S. Ogilvy, MD (Boston, MA)

    KEY WORDS: cerebral vasospasm, papaverine therapy, subarachnoid hemorrhage

    Cerebral vasospasm remains a significant cause of morbidity and mortal-ity among patients surviving aneurysmal SAH. Intraarterial papaverine infusion has been shown to have angiographic efficacy and is presumed to prevent new strokes among these patients.

    We reviewed our experience with 33 patients to determine the CT inci-dence of vasospasm-induced stroke, clinical outcome, and complications following intraarterial papaverine therapy to evaluate safety and efficacy of treatment. The clinical, angiographic, and CT data of the 33 patients who were treated between December, 1993, and June, 1997, in 85 procedures (2.6 patients) with a total of 125 infusions (3.8 patient, 1.5 procedures) were reviewed. Two additional patients were excluded because pre- and post-treatment CTs were unavailable. Another patient developed severe hypertension (SBP 230) during infusion and no further papaverine was given. All patients had failed a trial of hemodynamic augmentation with hemodilution, hypervolemia, and hypertension prior to papaverine therapy.

    Pretreatment and long-term follow-up head CTs were compared for the presence of new strokes. Long-term clinical outcome was noted. The dose varied up to 300 mg per infusion position (vascular territory). New strokes were seen in 12 patients (36%); of these, 8 had watershed or branch occlusions. Four developed multiple large strokes, intractably elevated intracranial pressure, and died. Complications were seen in 6 patients: 1 embolus with stroke, 4 dissections, 2 of which contributed to strokes, and 1 extended and hemorrhaged into a developing infarct (symptomatic complication rate 4 (12%) of the 33 patients, 5% of procedures). Despite the fact that 14 patients had new strokes, functional outcome was excellent in 14, good in 7, poor in 1, and 11 patients died.

    Therefore, while papaverine was not effective in preventing all strokes in patients suffering from severe cerebral vasospasm, most patients (64%) did not develop new strokes and had excellent or good outcomes.


    POSTER #1015
    TPA Following Aneurysmal Subarachnoid Hemorrhage Is Not Effective in Reducing Incidence of Severity of Vasospasm

    Oscar Szentirmai, BA
    Christopher Ogilvy, MD
    Nicholas Zervas, MD (Boston, MA)

    KEY WORDS: aneurysm, subarachnoid hemorrhage, transcranial Doppler

    The administration of fibrinolytics intracisternally has been reported to be beneficial in a number of nonrandomized clinical trials. In one randomized study safety was demonstrated without significant efficacy.

    Between 1992 and 1997, we managed 411 patients with SAH. Of this group, 31 patients were selected for treatment with intracisternal tPA (10 mg) after aneurysm clipping. We compared the incidence of vasospasm based on transcranial Doppler ultrasound (TCD) to the group of patients who did not receive tPA (380 patients). The incidence and severity of vasospasm in each group was compared to the patients’ density of blood on CT scan (Fisher scale).

    In the treated group, there were no Fisher Grade I patients who received tPA; in Grade II, 1 patient was treated; in Grade III, 15; and in Grade IV, 15. TCD-detected vasospasm was as follows: Grade II, 0%; Grade III, 4 (27%) out of 15 ; Grade IV, 6 (40%) out of 15; given an overall incidence of 10 (32%) of 31. In the nontreated group, TCD vasospasm was diagnosed in Fisher Grade I, 4 (14%) out of 28; Grade II, 26 (35%) out of 74; Grade III, 71 (47%) out of 152; Grade IV, 45 (36%) out of 126; and an overall incidence of 146 (38%) out of 380. There was not a significant difference in the incidence of TCD vasospasm in treated and untreated patients (p = 0.15). In addition, the severity of spasm was not less in the tPA group. Severe spasm was present in 1 (3%) of 31 tPA patients compared to 35 (9%) of 380 of non-tPA patients.

    Therefore, we conclude that tPA is not effective in reducing the inci-dence or severity of TCD spasm in patients with SAH.


    POSTER #1048
    Magnesium and Mexiletine Combined, Administered During Ischemia, Results in a Significantly Better Recovery of Neuronal Function in the In Vitro Rabbit Retina

    Christopher Ogilvy, MD
    David Chen, BA
    Kenneth Maynard, PhD (Boston, MA)

    KEY WORDS: cerebral ischemia, magnesium, stroke

    Both magnesium (Mg 2+ ) and mexiletine (Mex) individually have been shown to be neuroprotective. These agents block the untoward activities of Ca 2+ and Na + , respectively, each of which plays a major role in the induction of processes leading to irreversible ischemic damage. We therefore examined the effect of Mg 2+ (1 mM), Mex (300 µM), and Mg 2+ & Mex, compared with control (untreated) preparations, during 2 hours of simulated ischemia, on the recov-ery of light-evoked compound action potentials (CAPs) recorded from the optic nerve of isolated retinas.

    lschemia was induced by the reduction of oxygen (from 95% to 15%) and glucose (from 6 to 1 mM), which abolished the CAPs within 10 mm. The table shows the percent recovery of the CAPs over time, relative to the preischemia light-evoked CAPs for each retina (mean ± sem, ** = p <0.01).

    
    Time (h)	0.5	1	2	3	4	#of retinas
    Control		3±3	2±2	6±3	2±2	2±2	3
    Mg 2+ (1 mM)	8±4	14±11	47±14	24±8	16±7	3
    Mex (300 µM)	31±8	34±5	42±4	31±9	38±6	3
    Mg 2+ & Mex	34±8**	85±35**	79±31**	82±62**	55±25**	3

    Although Mg 2+ and Mex individually improved the average recovery of neuronal functional outcome after returning to control conditions following ischemia, the recovery in each case was not significantly different from the control group using repeated measures ANOVA1 followed by Fisher’s Pro-tected LSD posthoc tests. Retinas treated with both Mg 2+ & Mex, however, showed significantly (p <0.01) better recovery of function compared with control (untreated) retinas.

    We conclude that Mg 2+ & Mex combined, rather than either agent indi-vidually, administered during ischemia, leads to a significantly better recovery of neuronal function in this preparation. The mechanism of action of the effect remains to be examined, but it is probably related to Mg 2+ blocking various Ca 2+ -mediated events, combined with Mex acting as a Na + channel blocker.


    POSTER #1108
    Spinal Cord Concussion: Clinical Presentation, Radiographic Features, and Long-Term Outcome

    Gordon Tang, MD (Barstow, CA)
    Alfredo Quinones, BA
    Griffith Harsh IV, MD (Boston, MA)

    KEY WORDS: central cord syndrome, spinal cord concussion, spinal cord injury

    Spinal cord concussion remains a vague clinical syndrome with ill-de-fined features and no clear management strategy. We aim to characterize the syndrome, describe radiographic findings, particularly with MRI, and determine long-term outcome.

    We have defined spinal cord concussion as neurologic deficits consis-tent with spinal cord injury following spinal trauma that resolve completely within 72 hours. Twenty-one patients meeting this criteria have been retrospec-tively reviewed. All patients underwent evaluation by MRI within a week of injury. Follow-up averaged 27.8 months.

    Sixteen males and 5 females ranging in age from 9 to 71 years (mean 28 years) made up the study group. The cervical region accounted for 76% of the injuries, with the remaining at the thoracolumbar junction. Sports-related activi-ties (38%) and motor-vehicle acccidents (29%) were the most frequent causes. Hyperextension (62%) was the most common mechanism. Central cord syn-drome and complete spinal level accounted for most presentations. Motor deficts were noted in 71% of the patients, including 6 cases with transient quadripleiga. Sensory deficits were found in all 21 patients. Half of the patients demonstrated reflex abnormalities. All patients were initially immobilized and 15 received a course of solumedrol. Cervical spine radiographs did not demon-strate fractures or dislocations. One patient demonstrated ligamentous insta-bility on flexion/extension films. MRIs were normal in 13 patients, with the remaining 8 demonstrating mild spinal stenosis. Two patients had signal changes within the cord consistent with contusion. Symptoms and signs returned to normal in most patients within 24 hours. Six patients were treated with rigid external immobilization for 12 weeks. Immobilization was reserved for patients in the pediatric age group or those demonstrating cord contusion.

    In follow-up, all patients have been free from neurologic deficit without evidence of late instability. No recurrent injuries have been reported.


    POSTER #1395
    Comparison of Mutant Strains of Herpes Simplex Virus (HSV 1) as Potential Future Gene Therapy Vectors for Brain Tumors

    Nazer H. Qureshi, MD, DS*
    Keiro Ikeda, MD, PhD
    Kristin M. Suling, BS
    Ennio A. Chiocca, MD, Ph.D (Charlestown, MA)
    Griffith R. Harsh IV, MD (Boston, MA)

    KEY WORDS: gene therapy, herpes simplex virus, mutant strains

    Two mutants of HSV-1, hrR3 and MGH-1, were compared for their potential as future gene therapy vectors. The hrR3, derived from wild-type KOS strain, is inactivated in the ribonucleotide reductase (rR) gene function, while MGH-1 (from wild-type F strain) in addition also has deletions in the gamma 34.5 gene. Both mutants were tested in vitro for the extent of tumor cell lysis, yield of progeny viruses, and marker gene delivery in rodent (9L) and human (U87 & T98) glioma cell lines, and primary human pilocytic astrocytoma cells (Hy-QC). Stereotaxic injection of mutant and wild-type viruses in the right frontal lobe of nude mice (nu/nu) was done to assess toxicity (n = 72).

    The hrR3 was more efficient than the MGH-1 in producing oncolysis at all multiplicities of infection (MOI: 0.01, 0.1, and 1) and in all cell lines except Hy-QC. Maximal difference was seen in T98 (MOI = 0.1; p <0.02). Yield of progeny viruses was in agreement with oncolytic effects, i.e., lower progeny virus of MGH-1. Marker gene delivery was not significantly different. Strain difference could not account for the observed results, for the F strain was more efficient than the KOS in cell lysis (MOI="0.01;" p < 0.02). There were no animal deaths with MGH-1 even with inoculation of 2 × 10 7 pfus, while the hrR3 had an LD50 of < 2 × 10 5 pfus. The LD50 for KOS and F strain were < 10 and 10 pfus, respectively.

    Single rR-mutant of HSV-1 is a more effective oncolytic agent, but the double rR- and gamma 34.5-mutant are less toxic. These studies should have relevance in designing mutants of HSV-1 for gene therapy of brain tumors.


    POSTER #1156
    Brain Surgery as Physiology Lab: The History of Intraoperative Functional Localization

    Fred G. Barker, MD
    G.R. Cosgrove, MD (Boston, MA)

    KEY WORDS: functional mapping, optical imaging, trephination

    Modern neurosurgeons often use intraoperative functional mapping when resecting lesions close to functional areas. We reviewed the use of these techniques in the 19th and early 20th centuries. We conducted a systematic review of North American publications on trephinations for open brain injuries (1800-1880) and epilepsy (1800-1900) with directed review of later intraopera-tive functional mapping literature (1900-1945).

    The earliest North American examples of intraoperative functional map-ping dated from the early 19th century, when surgeons produced temporary aphasia by pressing on the frontal cortex through the cranial defects while dressing wounds. This period also saw substantial interest in dural movements in response to stimulation. Bartholow of Cincinnati first reported electrical stimulation of the human brain (1874), following European experiments in dogs (1870). Bartholow’s patient suffered subsequent convulsions and died of sep-sis, prompting criticism that his experiments had been unethical.

    Formal intraoperative electrical cortical stimulation for motor response was reported in the late 1880s and 1890s during trephinations for epilepsy and was significantly associated with cortical resections (versus simple elevation of depressed bone; p <0.001, multivariate logistic regression corrected for the decade of the surgery). Motor stimulation was used both in academic centers and in community practice. Although some early subjects reported sensory responses during awake motor stimulation, Cushing (1909) was the first to report pure sensory stimulation in awake patients. This work attracted notice in the contemporary lay press ( Popular Science Monthly). Penfield employed electrical stimulation for speech mapping in the early 1930s and Gardner (1941) reported direct injection of procaine into putative speech cortex in apparently isolated work. Penfield’s later reports of experiential stimulation for complex formed memories again captured popular attention.

    Although initially lagging behind animal physiologists, neurosurgeons have had unique advantages in exploring the physiology of the awake human brain. Developments in real-time optical imaging of the human cortex are likely to extend these advantages into the next century.

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