1H MRS in acute traumatic brain injury.

The objective of this study was to demonstrate 1H MR spectroscopy (MRS) changes in cerebral metabolites after acute head trauma. Twenty-five patients (12 children, 13 adults) were examined with quantitative 1H MRS after closed head injury. Clinical grade (Glasgow Coma Scale [GCS]) and outcome (Rancho Los Amigos Medical Center Outcome Score [ROS]) were correlated with quantitative neurochemical findings. N-acetylaspartate (NAA), a neuronal and axonal marker, was reduced (P < .03-.001). In children, a reduced NAA/creatine plus phosphocreatine (Cr) level and the presence of detectable lipid/lactate predicted bad outcome (sensitivity, 89%; specificity, 89%). The first MRS examination of all patients correlated with ROS versus NAA (r = .65, P < .0001). Although most patients showed MRS abnormalities, striking heterogeneity of 1H MRS characterized the individual patients. 1H MRS identifies multiple patterns of diffuse brain injury after blunt head trauma. There was a strong correlation between MRS and outcome. Future prospective studies will be needed to determine the clinical usefulness of MRS in predicting outcome from closed head injury.

Immunotherapy for recurrent malignant glioma: an interim report on survival.

We present interim survival data for a group of 83 adult patients with recurrent malignant glioma treated by implanting stimulated autologous lymphocytes into the tumour bed following surgical debulking. The patients were treated 6 months or more prior to data analysis. Fifty-nine patients were male and 24 female. The mean age for the entire group was 48.4 years and the mean Karnofsky rating (KR) was 67.2. Eight of the patients had grade II tumours, 33 had grade III tumours and 42 had grade IV tumours. Statistical analysis focuses on tumour grade, KR and patient age, factors that have been shown to affect survival in previous studies. Multifactorial analyses are employed to identify interrelationships among factors related to survival. Seven patients (8%) did not respond to immunotherapy, 76 (92%) had a good initial response. Twenty-five patients (30.1%) are living and 18 (22%) have shown no evidence of recurrence. Results are evaluated in the light of those obtained in trials of other experimental therapies for recurrent malignant gliomas. It is concluded that the present protocol offers a safe and comparatively effective treatment option.

Salvage immunotherapy of malignant glioma.

We present the preliminary results of a phase I trial of adoptive immunotherapy for recurrent or residual malignant glioma. The protocol is based on surgical debulking followed by implantation into the tumor bed of autologous lymphocytes that have been stimulated with phytohemagglutinin-P and then cultured in vitro in the presence of interleukin 2. Fifty-five patients with a mean Karnofsky rating of 64 were treated between February 1985 and March 1987. No significant toxicity was associated with the immunotherapy. Fifty patients had a positive initial response to therapy, nine patients had early recurrence (two to four months after treatment), and 22 patients died. We comment on major differences between the protocol described and other immunotherapy protocols.

Preliminary clinical trial of immunotherapy for malignant glioma.

An immunotherapy protocol based on intracranial implantation of stimulated, autologous lymphocytes into the tumor bed following surgical debulking of malignant glioma is described. Phase I clinical trials in human patients are now in progress. Preliminary data representing the first 39 patients treated are presented briefly.

Phototoxicity of brain tissue in hematoporphyrin derivative treated mice.

Photoradiation therapy conditions which have been used to treat subcutaneous and breast tumors are lethal when applied to the head of mice. Treatment of control mice with laser light at 631 nm over an energy density range of 0-90j/cm2 had no measurable effect but mice photosensitized with 5 mg HPD/kg 72 hrs prior to laser treatment showed a threshold for brain damage at 56j/cm2, above which the mice developed cerebral edema and died. Laser treatment caused the same rate and magnitude of temperature rise in both control and HPD-photosensitized mice. Moreover, studies using mice whose brain temperature was kept below 37 degrees C during laser treatment showed a greater phototoxicity than mice without temperature regulation. Therefore, temperature rise in cerebral tissue was not associated with phototoxicity in the brain. In contrast the oxygen consumption rate in a brain cell suspension from an HPD-treated mouse was only 54% of that from a control mouse following treatment with laser light. This observation, when taken with supporting data from other investigations, suggests that one mechanism for the phototoxic response in brain tissue is oxygen deprivation resulting from mitochondrial damage.

Nuclear magnetic resonance imaging. Review of early clinical experience.

Nuclear magnetic resonance tomography is a powerful new imaging modality which produces cross-sectional images similar to those obtained by computerized tomography. However, unlike computerized tomography, nuclear magnetic resonance imaging does not use ionizing radiation but rather utilizes an apparently safe interaction between magnetic fields, radio waves, and atomic nuclei. Basic principles of nuclear magnetic resonance imaging are discussed briefly and promising early clinical applications are reviewed. The two magnetic relaxation times, T1 and T2, provide discrimination between tissues based on differences in fat and water content. Tumors are readily differentiated from normal tissue on the basis of the increased water content, primarily due to edema and hypervascularity. Although nuclear magnetic resonance imaging is very sensitive in the detection of these abnormalities, it is not yet able to provide a specific diagnosis.

Development of a protocol for photoradiation therapy of malignant brain tumors: part 1. Photosensitization of normal brain tissue with hematoporphyrin derivative.

The successful application of phototherapy to subcutaneous tumors has suggested that a similar procedure should be developed for treating gliomas. As a result, attempts are being made to determine a set of conditions that would optimize the destruction of tumor cells while minimizing injury to surrounding brain tissue. To initiate this task, we developed a novel assay method to assess the amount of phototoxicity induced in normal brain by light exposure of mice treated with hematoporphyrin derivative (HPD). The application of this procedure demonstrated that a sufficient amount of HPD was retained in brain tissue, even 72 hours after injection, to cause severe cerebral damage in light-treated mice.

A three-dimensional and volume determination of tumors of the cerebellopontine angle.

We propose a new technique to accurately determine the volume of cerebellopontine angle (CPA) tumors. It has been determined that the measurement of the long axis in a slice plane of the CPA tumor does not adequately measure the total growth of the tumor. Volume measurements are more accurate indicators of the mass of the tumor.

Computerized three-dimensional stereotaxic removal of small central nervous system lesions in patients.

The authors describe the results of their recently reported computer-based stereotaxic surgical technique for the indentification, enhancement, three-dimensional reconstruction, localization, and removal of small central nervous system lesions. This technique has been applied to patients with various types of central nervous system pathology, and representative cases are reported.

A microstereotactic approach to small CNS lesions. Part II; Adjuvant therapy. Clinical potential and toxicity of intraventricular lymph infusion.

A technique is described for adjuvant therapy of small central nervous system tumors after their removal. The feasibility of direct application of lymphocytes from the thoracic duct to the ventricular system of cats has been explored. Reduction of the antigenic mass by techniques described in part I of this paper is probably crucial. Patients with gliomas are known to have circulating tumor-specific lymphocytes which may not have direct access to the CNS. This study demonstrated no toxicity from the chronic intraventricular infusion of thoracic duct lymph in cats.

A microstereotactic approach to small CNS lesions. Part I. Development of CT localization and 3-D reconstruction techniques.

The authors describe a newly designed and utilized stereotactic methodology for the removal of central nervous system lesions as small as a few millimeters in diameter. These small lesions are detected and localized by non-invasive computerized axial tomography (GE 8800 scanner) with additional computer processing of the digital data by means of a PDP-1145 computer. Multiple computer algorithms have been developed to enhance regions of interest on CT scans by three-dimensional reconstruction and magnification techniques. This same data can then be used to calculate a stereotactic approach to a small CNS lesion. The stereotactic approach coordinates are then mated to a head fixation system modified from the Reichert-Mundinger stereotactic apparatus enabling information transfer from CT scan to the stereotactic surgical system. These small CNS lesions, as small as 5 mm, can be removed with the apparatus described herein under direct binocular 3-D vision with minimal tissue damage, through a small trephine craniotomy or burr hole. Newly designed instruments and instruments in the process of being developed are mounted on a micromanipulator attached to the Riecher-Mundinger frame for guidance at surgery. These new instruments include stereoendoscopes with xenon arc illumination, multiple tissue expanders for exposing the operative site, a radiation tracer probe, a rotary-sucker extractor, and multiple other small instruments for operating and removal of blood and tissue from small CNS lesions. The stereotactic frame accurately defines all areas of the cranium in three-dimensional coordinates, and its combination with the micromanipulator-instrument assembly enables the site of any small CNS lesion, the three-dimensional coordinates of which have been located by additional computer processing of the CT digital data, to be accurately approached by the stereotactic guide micromanipulator assembly. The instrument described herein allows removal of very small tumor burdens, and opens the possibility for successful secondary application of adjuvant immunotherapy to a CNS tumor site as described in part II of this paper.

Development of a new implantable bio-telestimulator.

The authors describe preliminarily an implantable bio-stimulating device for stimulation of peripheral nerves and the central nervous system. The receiving unit is totally implantable. The system works on radiofrequency transcutaneous coupling across the skin. This new telestimulating device has a wider band width and more flexibility than units currently being used in neurosurgery. The unit is independent of coupling efficiency and is designed to accept any symmetrical or nonsymmetrical waveform within limits listed in this presentation. The unit is designed so as to provide this waveform as a constant current signal at the output of the receiver.

A computerized microstereotactic method to approach, 3-dimensionally reconstruct, remove and adjuvantly treat small CNS lesions.

The authors update a novel method recently utilized in humans with various CNS pathology for stereotactic localization, removal, and adjuvant therapy of small CNS lesions using additional computer processing of the date from a GE 8800 CT Scanner. Multiple computer algorithms developed at Cal Tech enhance regions of interest by filtering, magnifying, color-coding and 3-dimensional reconstruction based on routine CT scans. This stereotactic approach is calculated by the computer and coordinates are mated to a modified head fixation system; small lesions can be removed with the apparatus described herein under direct binocular vision with minimal tissue damage. This technique may offer the possibility of successful secondary application of adjuvant therapy to, particularly, a CNS glioma site.

Microsurgical cannulation of the thoracic duct in cats. Technical note.

The authors describe a new technique for the microsurgical cannulation of the thoracic duct. A small silastic tube is utilized which can be joined to a subcutaneously implanted one-way flow, CSF, Ommaya-type reservoir. Extended drainage is avoided. No deletion or alteration of major venous channels occurs. Lymph collection is accomplished by tapping the subcutaneous reservoir with a small-bore needle.

Adverse effects of electrical energy applied to the nervous system.

Neural prostheses activated by radiofrequency transmission are currently being implanted to treat a variety of clinical problems. It is essential that neither the materials used in these prostheses, particularly the electrodes, nor the stimulus parameters that are employed will cause neural damage. The experiences of investigators engaged in both the experimental laboratory and clinical studies of the effects of electrical stimulation are reported herein.