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James E. Raisis, Glenn W. Kindt, John E. McGillicuddy and Carole A. Miller

✓ Cerebral metabolism in 21 hydrocephalic patients was studied. Preoperative and postoperative specimens of cerebrospinal fluid (CSF) were obtained and the cerebral perfusion pressure (CPP) was calculated in each instance. The specimens of CSF were analyzed for lactate and pyruvate and the lactate/pyruvate (L/P) ratio was calculated for each sample. The L/P ratio, which reflects the redox state of the cell, was used to determine the extent of anaerobic metabolism. An inverse relationship was noted between CPP and lactate as well as the L/P ratio. In general, the level of anaerobic metabolism was decreased after insertion of a shunt.

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John E. McGillicuddy, Glenn W. Kindt, James E. Raisis and Carole A. Miller

✓ A marked increase in intracranial pressure (ICP) produces a concomitant increase in systemic blood pressure (the Cushing response). In this study a comparison is made between this response of systemic blood pressure to increased ICP and the blood pressure responses produced by ischemia, hypoxia, and hypercarbia of the primate brain. A carotid-to-carotid cross-perfusion system was used to produce a purely cerebral hypoxia and hypercarbia. Each stimulus, except hypercarbia, produced a hypertensive response that was qualitatively and quantitatively similar. These responses were characterized by a short latent period, a rapid development, and an increase in mean arterial pressure of 60% or more. The similarity of the responses suggests that these stimuli act through a final common pathway independent of the purely mechanical effects of increased ICP upon the brain.

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J. Douglas Miller, John F. Butterworth, Steven K. Gudeman, J. Edward Faulkner, Sung C. Choi, John B. Selhorst, John W. Harbison, Harry A. Lutz, Harold F. Young and Donald P. Becker

✓ A prospective and consecutive series of 225 patients with severe head injury who were managed in a uniform way was analyzed to relate outcome to several clinical variables. Good recovery or moderate disability were achieved by 56% of the patients, 10% remained severely disabled or vegetative, and 34% died. Factors important in predicting a poor outcome included the presence of an intracranial hematoma, increasing age, abnormal motor responses, impaired or absent eye movements or pupil light reflexes, early hypotension, hypoxemia or hypercarbia, and elevation of intracranial pressure over 20 mm Hg despite artificial ventilation. Most of these predictive factors were assessed on admission, but a subset of 158 patients was identified in whom coma was present on admission and was known to have persisted at least until the following day. Although the mortality in this subset (40%) was higher than in the total series, it was lower than in several comparable reported series of patients with severe head injury. Predictive correlations were equally strong in the entire series and in the subset of 158 patients with coma. A plea is made for inclusion in the definition of “severe head injury” of all patients who do not obey commands or utter recognizable words on admission to the hospital after early resuscitation.

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Influence of the type of intracranial lesion on outcome from severe head injury

A multicenter study using a new classification system

Thomas A. Gennarelli, Gerri M. Spielman, Thomas W. Langfitt, Philip L. Gildenberg, Timothy Harrington, John A. Jane, Lawrence F. Marshall, J. Douglas Miller and Lawrence H. Pitts

✓ Recent studies attempting to define the outcome from severe head injury have implied, directly or indirectly, that the severity of injury (as determined by the Glasgow Coma Scale (GSC)) is the sole determinant of outcome. Little attention has been focused on the type of lesion that causes the low GCS score, and there exists an unstated hypothesis that the lesion type is not an important determinant of outcome. No attempt has been made to determine whether patients who have the same GCS score caused by different lesions have the same or different outcomes. Since this is impossible to test without a large number of cases, data were obtained from seven head-injury centers on patients who fulfilled the Glasgow criteria for severe head injury (GCS ≤ 8 for at least 6 hours). Patients were categorized according to a simple classification system comprising seven lesion types, each of which was further subdivided into two GCS score ranges (3 to 5 and 6 to 8). Of 1107 patients, the overall mortality was 41%, but ranged from 9% to 74% among the different lesion categories. Conversely, 26% had good recovery (at 3 months), but among the different lesion groups the range was 6% to 68%. Acute subdural hematoma with GCS scores of 3 to 5 was uniformly the worst problem (74% mortality and 8% good recovery), whereas diffuse injury coma of 6 to 24 hours with GCS scores of 6 to 8 had 9% mortality and 68% incidence of good recovery. Results of this study demonstrate marked heterogeneity within this severe head-injury group and point out that patients with the same GCS score have markedly different outcomes, depending on the causative lesion. The type of lesion is thus as important a factor in determining outcome as is the GCS score, and both must be considered when describing severely head-injured patients.

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Daniel L. Silbergeld and John W. Miller

✓ Four adults with unilateral (three cases) or bilateral (one case) closed schizencephaly, medically intractable epilepsy, and otherwise normal neurological examinations are presented. Three were examined preoperatively with magnetic resonance imaging and one with computerized tomography. Scalp electroencephalographic (EEG) studies in all four patients and electrocorticography via intracranial electrodes in two showed seizure origin in the cleft regions in two patients and in the ipsilateral temporal lobe in the other two. Temporal lobectomy was performed in the two patients with temporal lobe foci. Resection of superficial pachygyria around the cleft was performed in one patient. The authors conclude that the abnormal cortical mantle lining schizencephalic clefts may be epileptogenic. Alternatively, temporal allocortex may become the source of seizures. Therefore, these patients require careful EEG monitoring of the entire ipsilateral hemisphere as well as the cleft region.

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Gregory E. Plautz, Gene H. Barnett, David W. Miller, Bruce H. Cohen, Richard A. Prayson, John C. Krauss, Mark Luciano and Suyu Shu

Ten patients with progressive primary or recurrent malignant glioma received systemic adoptive immunotherapy to determine the feasibility, toxicity, and potential therapeutic benefits of this treatment. Adoptive immunotherapy, the transfer of immune T lymphocytes, is capable of mediating the regression of experimental brain tumors in animal models. A rich source of tumor-immune T cells are lymph nodes (LNs) draining the tumor vaccine site. In this clinical study, patients were inoculated intradermally with irradiated autologous tumor cells and granulocyte-macrophage colony stimulating factor as an adjuvant. Cells from draining inguinal LNs, surgically resected 7 days after vaccination, were stimulated sequentially with staphylococcal enterotoxin A and anti-CD3, and a low dose of interleukin-2 (60 IU/ml) was used to expand the stimulated cells. The maximum cell proliferation was 350-fold over 10 days of culture. The activated cells were virtually all T cells consisting of various proportions of CD4 and CD8 cells. These cells were given to patients by intravenous infusion at doses ranging from 9 X 108 to 1.5 X 1011. There were no Grade 3 or 4 toxicities associated with the treatment. Following T cell transfer therapy, radiographic regression that lasted at least 4 months was demonstrated in three patients with recurrent tumors, and four patients remain alive more than 11 months after surgery. The remaining patients had progressive disease, and three patients required intervention with corticosteroid agents or additional surgery approximately 1 month following cell transfer. These findings demonstrate that adoptive immunotherapy can be administered in patients with glioma without causing significant toxicity. It appears that this experimental regimen can provide therapeutic benefits for some patients.

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Gregory E. Plautz, Gene H. Barnett, David W. Miller, Bruce H. Cohen, Richard A. Prayson, John C. Krauss, Mark Luciano, Debra B. Kangisser and Suyu Shu

Object. To determine the feasibility, toxicity, and potential therapeutic benefits of systemic adoptive immunotherapy, 10 patients with progressive primary or recurrent malignant glioma received this treatment. Adoptive immunotherapy, the transfer of immune T lymphocytes, is capable of mediating the regression of experimental brain tumors in animal models. In animal models, lymph nodes (LNs) that drain the tumor vaccine site are a rich source of tumor-immune T cells.

Methods. In this clinical study, patients were inoculated intradermally with irradiated autologous tumor cells and granulocyte macrophage-colony stimulating factor as an adjuvant. Cells from draining inguinal LNs, surgically resected 7 days after vaccination, were stimulated sequentially with staphylococcal enterotoxin A and anti-CD3, and a low dose of interleukin-2 (60 IU/ml) was used to expand the stimulated cells. The maximum cell proliferation was 350-fold over 10 days of culture. The activated cells were virtually all T cells consisting of various proportions of CD4 and CD8 cells. These cells were given to patients by intravenous infusion at doses ranging from 9 × 108 to 1.5 × 1011. There were no Grade 3 or 4 toxicities associated with the treatment. Following T-cell transfer therapy, radiographic regression that lasted at least 6 months was demonstrated in two patients with recurrent tumors. One patient demonstrated stable disease that has lasted for more than 17 months. The remaining patients had progressive disease; however, four of the eight patients with recurrent tumor remain alive more than 1 year after surgery for recurrence. Three patients required intervention with corticosteroid agents or additional surgery approximately 1 month following cell transfer.

Conclusions. These intriguing clinical observations warrant further trials to determine whether this approach can provide therapeutic benefits and improve survival.

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Oral Presentations

2010 AANS Annual Meeting Philadelphia, Pennsylvania May 1–5, 2010