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The Massachusetts General Hospital

Early history and neurosurgery to 1939

Fred G. Barker

✓ The early history of the Massachusetts General Hospital (MGH) is reviewed with emphasis on the development of neurological surgery. The hospital opened in 1823. Early trephinations were performed by Dr. John Collins Warren and others for treatment of trauma and epilepsy. In the 1880's, interest in brain surgery increased, and Dr. John Elliot performed several trephinations for brain tumors, three of which were witnessed by Dr. Harvey Cushing during his years at the MGH as medical student and intern. In 1911, all brain surgery was placed in the hands of Dr. S. J. Mixter. He later shared the assignment with his son, Dr. W. J. Mixter, who described herniation of the intervertebral disc with Dr. J. S. Barr and became the first Chief of the Neurosurgical Service at MGH in 1939.

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Fred G. Barker II, Peter J. Jannetta, David J. Bissonette, Philip T. Shields, Mark V. Larkins and Hae Dong Jho

✓ The authors report the results of 782 microvascular decompression procedures for hemifacial spasm in 703 patients (705 sides), with follow-up study from 1 to 20 years (mean 8 years). Of 648 patients who had not undergone prior intracranial procedures for hemifacial spasm, 65% were women; their mean age was 52 years, and the mean preoperative duration of symptoms was 7 years. The onset of symptoms was typical in 92% and atypical in 8%. An additional 57 patients who had undergone prior microvascular decompression elsewhere were analyzed as a separate group. Patients were followed prospectively with annual questionnaires.

Kaplan-Meier methods showed that among patients without prior microvascular decompression elsewhere, 84% had excellent results and 7% had partial success 10 years postoperatively. Subgroup analyses (Cox proportional hazards model) showed that men had better results than women, and patients with typical onset of symptoms had better results than those with atypical onset. Nearly all failures occurred within 24 months of operation; 9% of patients underwent reoperation for recurrent symptoms. Second microvascular decompression procedures were less successful, whether the first procedure was performed at Presbyterian-University Hospital or elsewhere, unless the procedure was performed within 30 days after the first microvascular decompression. Patient age, side and preoperative duration of symptoms, history of Bell's palsy, preoperative presence of facial weakness or synkinesis, and implant material used had no influence on postoperative results.

Complications after the first microvascular decompression for hemifacial spasm included ipsilateral deaf ear in 2.6% and ipsilateral permanent, severe facial weakness in 0.9% of patients. Complications were more frequent in reoperated patients. In all, one operative death (0.1%) and two brainstem infarctions (0.3%) occurred. Microvascular decompression is a safe and definitive treatment for hemifacial spasm with proven long-term efficacy.

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Fred G. Barker II

✓ In 1848, Mr. Phineas Gage suffered destruction of his left frontal lobe in a unique fashion: passage of a metal rod through his head after a freak explosion. His change in character after the accident is the index case for personality change due to frontal lobe damage. Yet, from 1848 to 1868, it was widely believed among American physicians that he was mentally intact. The case was used as evidence against phrenology, a crude precursor of modern cerebral localization theories.

The two original reports of the case by Drs. John Harlow (Gage's physician) and Henry J. Bigelow show subtle differences in attitude toward Gage's posttraumatic character change. In his 1848 report, Harlow promised a further communication that would address Gage's “mental manifestations.” Bigelow's article portrayed Gage as fully recovered. Although delayed by 20 years, Harlow's second report rapidly changed the perception of the case in the medical community, as reflected by contemporary citations.

The educational backgrounds of Harlow and Bigelow are examined to explain their differing attitudes toward the case. Harlow's interest in phrenology prepared him to accept the change in character as a significant clue to cerebral function which merited publication. Bigelow had learned that damage to the cerebral hemispheres had no intellectual effect, and he was unwilling to consider Gage's deficit significant. Although Bigelow's paradigm was initially more influential, Harlow's more closely matched emerging theories of cerebral localization. His version of the case was used by David Ferrier as the keystone in the first modern theory of frontal lobe function, and this is how the case is remembered today.

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Fred G. Barker II and Christopher S. Ogilvy

✓ The authors report findings from a metaanalysis of all published randomized trials of prophylactic nimodipine used in patients who have experienced subarachnoid hemorrhage (SAH). Seven trials were included with a total of 1202 patients suitable for evaluation. Eight outcome measures were examined, including good versus other outcome, good or fair outcome versus other outcome, overall mortality, deficit and/or death attributed to vasospasm, infarction rate as judged by computerized tomography (CT), and deficit and/or death from rebleeding.

Nimodipine improved outcome according to all measures examined. The odds of good and of good plus fair outcomes were improved by ratios of 1.86:1 and 1.67:1, respectively, for nimodipine versus control (p < 0.005 for both measures). The odds of deficit and/or mortality attributed to vasospasm and CT-assessed infarction rate were reduced by ratios of 0.46:1 to 0.58:1 in the nimodipine group (p < 0.008 for all measures). Overall mortality was slightly reduced in the nimodipine group, but the trend was not statistically significant. The rebleeding rate was not increased by nimodipine. A metaregression yielded findings indicating that the treatment effect of nimodipine in individual trials was positively correlated with the severity of SAH in enrolled patients.

Although the majority of individual trials examined did not have statistically significant results at the p < 0.01 level according to most outcome measures, the metaanalyses confirmed the significant efficacy of prophylactic nimodipine in improving outcome after SAH under the conditions used in these trials.

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Fred G. Barker II, Michael D. Prados, Susan M. Chang, Philip H. Gutin, Kathleen R. Lamborn, David A. Larson, Mary K. Malec, Michael W. McDermott, Penny K. Sneed, William M. Wara and Charles B. Wilson

✓ To determine the value of radiographically assessed response to radiation therapy as a predictor of survival in patients with glioblastoma multiforme (GBM), the authors studied a cohort of 301 patients who were initially treated according to uniform clinical protocols. All patients had newly diagnosed supratentorial GBM and underwent the maximum safe resection followed by external-beam radiation treatment (60 Gy in standard daily fractions or 70.4 Gy in twice-daily fractions of 160 cGy). The radiation response and survival rates were assessable in 222 patients. The extent of resection and the immediate response to radiation therapy were highly correlated with survival, both in a univariate analysis and after correction for age and Karnofsky performance scale (KPS) score in a multivariate Cox model (p < 0.001 for radiation response and p = 0.04 for extent of resection). A subgroup analysis suggested that neuroimaging obtained within 3 days after surgery served as a better baseline for assessment of radiation response than images obtained later. Imaging obtained within 3 days after completion of a course of radiation therapy also provided valid radiation response scores. The impact of the radiographically assessed radiation response on survival time was comparable to that of age or KPS score. This information is easily obtained early in the course of the disease, may be of value for individual patients, and may also have implications for the design and analysis of trials of adjuvant therapy for GBM, including volume-dependent therapies such as radiosurgery or brachytherapy.

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Fred G. Barker II, Peter J. Jannetta, Ramesh P. Babu, Spiros Pomonis, David J. Bissonette and Hae Dong Jho

✓ During a 20-year period, 26 patients with typical symptoms of trigeminal neuralgia were found to have posterior fossa tumors at operation. These cases included 14 meningiomas, eight acoustic neurinomas, two epidermoid tumors, one angiolipoma, and one ependymoma. The median patient age was 60 years and 69% of the patients were women. Sixty-five percent of the symptoms were left sided. The median preoperative duration of symptoms was 5 years. The distribution of pain among the three divisions of the trigeminal nerve was similar to that found in patients with trigeminal neuralgia who did not have tumors; however, more divisions tended to be involved in the tumor patients. The mean postoperative follow-up period was 9 years.

At operation, the root entry zone of the trigeminal nerve was examined for vascular cross-compression in 21 patients. Vessels compressing the nerve at the root entry zone were observed in all patients examined. Postoperative pain relief was frequent and long lasting. Using Kaplan—Meier methods the authors estimated excellent relief in 81% of the patients 10 years postoperatively, with partial relief in an additional 4%.

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Susan M. Chang, Ian F. Parney, Michael Mcdermott, Fred G. Barker II, Meic H. Schmidt, Wei Huang, Edward R. Laws Jr., Kevin O. Lillehei, Mark Bernstein, Henry Brem, Andrew E. Sloan, Mitchel Berger and the Glioma Outcomes Investigators

Object. In many new clinical trials of patients with malignant gliomas surgical intervention is incorporated as an integral part of tumor-directed interstitial therapies such as gene therapy, biodegradable wafer placement, and immunotherapy. Assessment of toxicity is a major component of evaluating these novel therapeutic interventions, but this must be done in light of known complication rates of craniotomy for tumor resection. Factors predicting neurological outcome would also be helpful for patient selection for surgically based clinical trials.

Methods. The Glioma Outcome Project is a prospectively compiled database containing information on 788 patients with malignant gliomas that captured clinical practice patterns and patient outcomes. Patients in this series who underwent their first or second craniotomy were analyzed separately for presenting symptoms, tumor and patient characteristics, and perioperative complications. Preoperative and intraoperative factors possibly related to neurological outcome were evaluated.

There were 408 patients who underwent first craniotomies (C1 group) and 91 patients who underwent second ones (C2 group). Both groups had similar patient and tumor characteristics except for their median age (55 years in the C1 group compared with 50 years in the C2 group; p = 0.006). Headache was more common at presentation in the C1 group, whereas papilledema and an altered level of consciousness were more common at presentation in patients undergoing second surgeries. Perioperative complications occurred in 24% of patients in the C1 group and 33% of patients in the C2 group (p = 0.1). Most patients were the same or better neurologically after surgery, but more patients in the C2 group (18%) displayed a worsened neurological status than those in the C1 group (8%; p = 0.007). The Karnofsky Performance Scale score and, in patients in the C2 group, tumor size were important neurological outcome predictors. Regional complications occurred at similar rates in both groups. Systemic infections occurred more frequently in the C2 group (4.4 compared with 0%; p < 0.0001) as did depression (20 compared with 11%; p = 0.02). The perioperative mortality rate was 1.5% for the C1 group and 2.2% for the C2 group (p = not significant). The median length of the hospital stay was 4 days in each group.

Conclusions. Perioperative complications occur slightly more often following a second craniotomy for malignant glioma than after the first craniotomy. This should be considered when evaluating toxicities from intraoperative local therapies requiring craniotomy. Nevertheless, most patients are neurologically stable or improved after either their first or second craniotomy. This data set may serve as a benchmark for neurosurgeons and others in a discussion of operative risks in patients with malignant gliomas.

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Fred G. Barker II, William E. Butler, Sue Lyons, Ethan Cascio, Christopher S. Ogilvy, Jay S. Loeffler and Paul H. Chapman

Object. The use of radiosurgery for the treatment of cerebral arteriovenous malformations (AVMs) and other lesions demands an accurate understanding of the risk of radiation-related complications. Some commonly used formulas for predicting risk are based on extrapolation from small numbers of animal experiments, pilot human treatment series, and theoretical radiobiological considerations. The authors studied the incidence of complications after AVM radiosurgery in relation to dose, volume, and other factors in a large patient series.

Methods. A retrospective review was conducted in 1329 patients with AVM treated by Dr. Raymond Kjellberg at the Harvard Cyclotron Laboratory (HCL) between 1965 and 1993. Dose and volume were obtained from HCL records, and information about patient follow up was derived from concurrent clinical records, questionnaires, and contact with referring physicians. Multivariate logistic regression with bootstrapped confidence intervals was used.

Follow up was available in 1250 patients (94%); the median follow-up duration was 6.5 years. The median radiation dose was 10.5 Gy and the median treatment volume was 33.7 cm3. Twenty-three percent of treated lesions were smaller than 10 cm3. Fifty-one permanent radiation-related deficits occurred (4.1%). Of 1043 patients treated with a dose predicted by the Kjellberg isoeffective centile curve to have a less than 1% complication risk, 1.8% suffered radiation-related complications. Actual complication rates were 4.7% for 128 patients treated at Kjellberg risk centile doses of 1 to 1.8%, and 34% for 61 patients treated at risk centile doses of 2 to 2.5%. The fitted logistic model showed that complication risk was related to treatment dose and volume, thalamic or brainstem location, and patient age.

Conclusions. The Kjellberg isoeffective risk centile curve significantly underpredicted actual risks of permanent complications after proton beam radiosurgery for AVMs. Actual risks were best predicted using a model that accounted for treatment dose and volume, lesion location, and patient age.

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L. Dade Lunsford

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Emad N. Eskandar, Alice Flaherty, G. Rees Cosgrove, Leslie A. Shinobu and Fred G. Barker II

Object. The surgical treatment of Parkinson disease (PD) has undergone a dramatic shift, from stereotactic ablative procedures toward deep brain stimulaion (DBS). The authors studied this process by investigating practice patterns, mortality and morbidity rates, and hospital charges as reflected in the records of a representative sample of US hospitals between 1996 and 2000.

Methods. The authors conducted a retrospective cohort study by using the Nationwide Inpatient Sample database; 1761 operations at 71 hospitals were studied. Projected to the US population, there were 1650 inpatient procedures performed for PD per year (pallidotomies, thalamotomies, and DBS), with no significant change in the annual number of procedures during the study period. The in-hospital mortality rate was 0.2%, discharge other than to home was 8.1%, and the rate of neurological complications was 1.8%, with no significant differences between procedures. In multivariate analyses, hospitals with larger annual caseloads had lower mortality rates (p = 0.002) and better outcomes at hospital discharge (p = 0.007).

Placement of deep brain stimulators comprised 0% of operations in 1996 and 88% in 2000. Factors predicting placement of these devices in analyses adjusted for year of surgery included younger age, Caucasian race, private insurance, residence in higher-income areas, hospital teaching status, and smaller annual hospital caseload. In multivariate analysis, total hospital charges were 2.2 times higher for DBS (median $36,000 compared with $12,000, p < 0.001), whereas charges were lower at higher-volume hospitals (p < 0.001).

Conclusions. Surgical treatment of PD in the US changed significantly between 1996 and 2000. Larger-volume hospitals had superior short-term outcomes and lower charges. Future studies should address long-term functional end points, cost/benefit comparisons, and inequities in access to care.