The American Association of
Neurological Surgeons 1998
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
Intraarterial Papaverine Therapy for Vasospasm: Does It Really Work?
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
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.
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
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.
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.
TPA Following Aneurysmal Subarachnoid Hemorrhage Is Not Effective
in Reducing Incidence of Severity of Vasospasm
Christopher Ogilvy, MD
Nicholas Zervas, MD (Boston, MA)
KEY WORDS: aneurysm,
subarachnoid hemorrhage, transcranial Doppler
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.
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.
conclude that tPA is not effective in reducing the inci-dence
or severity of TCD spasm in patients with SAH.
Magnesium and Mexiletine Combined, Administered During Ischemia,
Results in a Significantly Better Recovery of Neuronal Function
in the In Vitro Rabbit Retina
David Chen, BA
Kenneth Maynard, PhD (Boston, MA)
KEY WORDS: cerebral
ischemia, magnesium, stroke
(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.
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
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 Fishers 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)
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.
Spinal Cord Concussion: Clinical Presentation, Radiographic Features,
and Long-Term Outcome
MD (Barstow, CA)
Alfredo Quinones, BA
Griffith Harsh IV, MD (Boston, MA)
KEY WORDS: central
cord syndrome, spinal cord concussion, spinal cord injury
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.
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.
all patients have been free from neurologic deficit without evidence
of late instability. No recurrent injuries have been reported.
Comparison of Mutant Strains of Herpes Simplex Virus (HSV 1) as
Potential Future Gene Therapy Vectors for Brain Tumors
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
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.
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
Brain Surgery as Physiology Lab: The History of Intraoperative
G.R. Cosgrove, MD (Boston, MA)
KEY WORDS: functional
mapping, optical imaging, trephination
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
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). Bartholows
patient suffered subsequent convulsions and died of sep-sis, prompting
criticism that his experiments had been unethical.
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.
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.