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Histological Evaluation of Neural Damage from Electrical Stimulation: Considerations for the Selection of Parameters for Clinical Application

The relationship of charge density per phase, or QD/ph (expressed in units of microcoulombs per cm2 per phase of the charge-balanced wave form), and total charge (QDt) to neural damage has been investigated by light and electron microscopy after surface stimulation of the parietal cortex in normal cats. QD/ph values ranging from 40 to 400 were achieved by varying several stimulus parameters. The least amount of neural damage in this study was observed at QD/ph 40). The extent of neural injury at stimulated sites increased with the charge density and was evident as disruption of cell membranes, intracytoplasmic vacoulation, an increasing glycogen content, the deposition of intracellular calcium hydroxyapatite, and neuronal and astrocytic degeneration. Although individual factors contributing to neural damage are isolated with difficulty, charge density and total charge seem to be predominant among the contributing parameters. In view of these findings, recommendations have been made for the selection of electrical stimulus parameters to be used in central nervous system prostheses.

Gamma knife thalamotomy for treatment of tremor: long-term results

The purpose of this paper was to note a potential source of error in magnetic resonance (MR) imaging. Magnetic resonance images were acquired for stereotactic planning for GKS of a vestibular schwannoma in a female patient. The images were acquired using three-dimensional sequence, which has been shown to produce minimal distortion effects. The images were transferred to the planning workstation, but the coronal images were rejected. By examination of the raw data and reconstruction of sagittal images through the localizer side plate, it was clearly seen that the image of the square localizer system was grossly distorted. The patient was returned to the MR imager for further studies and a metal clasp on her brassiere was identified as the cause of the distortion.A-60-year-old man with medically intractable left-sided maxillary division trigeminal neuralgia had severe cardiac disease, was dependent on an internal defibrillator and could not undergo magnetic resonance imaging. The patient was successfully treated using computerized tomography (CT) cisternography and gamma knife radiosurgery. The patient was pain free 2 months after GKS. Contrast cisternography with CT scanning is an excellent alternative imaging modality for the treatment of patients with intractable trigeminal neuralgia who are unable to undergo MR imaging.The authors describe acute deterioration in facial and acoustic neuropathies following radiosurgery for acoustic neuromas. In May 1995, a 26-year-old man, who had no evidence of neurofibromatosis Type 2, was treated with gamma knife radiosurgery (GKS; maximum dose 20 Gy and margin dose 14 Gy) for a right-sided intracanalicular acoustic tumor. Two days after the treatment, he developed headache, vomiting, right-sided facial weakness, tinnitus, and right hearing loss. There was a deterioration of facial nerve function and hearing function from pretreatment values. The facial function worsened from House-Brackmann Grade 1 to 3. Hearing deteriorated from Grade 1 to 5. Magnetic resonance (MR) images, obtained at the same time revealed an obvious decrease in contrast enhancement of the tumor without any change in tumor size or peritumoral edema. Facial nerve function improved gradually and increased to House-Brackmann Grade 2 by 8 months post-GKS. The tumor has been unchanged in size for 5 years, and facial nerve function has also been maintained at Grade 2 with unchanged deafness. This is the first detailed report of immediate facial neuropathy after GKS for acoustic neuroma and MR imaging revealing early possibly toxic changes. Potential explanations for this phenomenon are presented.In clinical follow-up studies after radiosurgery, imaging modalities such as computerized tomography (CT) and magnetic resonance (MR) imaging are used. Accurate determination of the residual lesion volume is necessary for realistic assessment of the effects of treatment. Usually, the diameters rather than the volume of the lesion are measured. To determine the lesion volume without using stereotactically defined images, the software program VOLUMESERIES has been developed. VOLUMESERIES is a personal computer-based image analysis tool. Acquired DICOM CT scans and MR image series can be visualized. The region of interest is contoured with the help of the mouse, and then the system calculates the volume of the contoured region and the total volume is given in cubic centimeters. The defined volume is also displayed in reconstructed sagittal and coronal slices. In addition, distance measurements can be performed to measure tumor extent. The accuracy of VOLUMESERIES was checked against stereotactically defined images in the Leksell GammaPlan treatment planning program. A discrepancy in target volumes of approximately 8% was observed between the two methods. This discrepancy is of lesser interest because the method is used to determine the course of the target volume over time, rather than the absolute volume. Moreover, it could be shown that the method was more sensitive than the tumor diameter measurements currently in use. VOLUMESERIES appears to be a valuable tool for assessing residual lesion volume on follow-up images after gamma knife radiosurgery while avoiding the need for stereotactic definition.This study was conducted to evaluate the geometric distortion of angiographic images created from a commonly used digital x-ray imaging system and the performance of a commercially available distortion-correction computer program. A 12 x 12 x 12-cm wood phantom was constructed. Lead shots, 2 mm in diameter, were attached to the surfaces of the phantom. The phantom was then placed inside the angiographic localizer. Cut films (frontal and lateral analog films) of the phantom were obtained. The films were analyzed using GammaPlan target series 4.12. The same procedure was repeated with a digital x-ray imaging system equipped with a computer program to correct the geometric distortion. The distortion of the two sets of digital images was evaluated using the coordinates of the lead shots from the cut films as references. The coordinates of all lead shots obtained from digital images and corrected by the computer program coincided within 0.5 mm of those obtained from cut films. The average difference is 0.28 mm with a standard deviation of 0.01 mm. On the other hand, the coordinates obtained from digital images with and without correction can differ by as much as 3.4 mm. The average difference is 1.53 mm, with a standard deviation of 0.67 mm. The investigated computer program can reduce the geometric distortion of digital images from a commonly used x-ray imaging system to less than 0.5 mm. Therefore, they are suitable for the localization of arteriovenous malformations and other vascular targets in gamma knife radiosurgery.

Evaluation of electrode array material for neural prostheses.

Matrix support materials for brain surface electrodes used in neuroprosthetic applications were evaluated after chronic subdural implantation over the parietal cortex of the cat. Four types of array fabricated with Silastic, Dacron mesh, or platinum wire annuli were implanted for periods ranging from 5 weeks to 1 year. We evaluated the arrays by access resistance measurements and gross and histological observations of the tissue beneath both nonstimulated and stimulated electrodes. A porous type matrix constructed of Dacron mesh proved to be the superior design because of its minimal compression of the cortical surface, facility of handling during implantation and autopsy, and satisfactory electrical characteristics provided by a good electrode-brain interface. (Neurosurgery, 5: 681--686, 1979).

Therapy of recurrent high grade gliomas with surgery, and autologous mitogen activated IL-2 stimulated killer (MAK) Lymphocytes: I. Enhancement of MAK lytic activity and cytokine production by PHA and clinical use of PHA

Nineteen patients with recurrent high grade gliomas were treated in a phase I/II trial with aggressive debulking of the tumor, mitogen activated IL-2 stimulated peripheral blood lymphocytes (MAK cells), and rIL-2. Phytohemagglutin (PHA) was introduced into the tumor site in 16 patients prior to implanting MAK cells and IL-2 in an attempt to trigger more effective lysis of the tumorin vivo. In vitro both TNF bioactivity and cytolytic activity of long term cultured MAK (LMAK) cells were dramatically enhanced by adding PHA to the cultures of these activated PBL. Three of eleven patients (27%) had a decrease in size of the enhancing lesion on CT and/or MRI. Seven (37%) patients clinically improved. Median survival after therapy was 30 weeks. PHA was shown to be safein vivo and more effective than IL-2 triggering enhanced effector functionin vitro.

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.

Generation of stimulated, lymphokine activated T killer (T-LAK) cells from the peripheral blood of normal donors and adult patients with recurrent glioblastoma☆

Peripheral blood mononuclear cells (PBM) from normal donors and patients with recurrent glioma were activated initially for 48-72 h with phytohemagglutinin-P (PHA) and recombinant human interleukin-2 (IL-2), and then proliferated in vitro for up to 5 months with IL-2. These cells are termed mitogen-stimulated lymphokine-activated T killer (T-LAK) cells. We measured patterns of T-LAK cell growth, in vitro cytolytic activity on a panel of continuous and primary tumor cells, and the phenotypes of the cells in these cultures. Lymphocyte viability declined dramatically over the first 3-5 days; and then the remaining cells in these cultures began to divide and maintained a constant 30-36 h doubling time for long periods in vitro. Phenotyping revealed that cells in the initial few days of culture were heterogeneous, but became almost totally CD3 T cells after 7-10 days in culture. The T-LAK cells from individual normal donors and cancer patients demonstrated a non-genetically restricted cytolytic ability against a panel of both continuous cell lines and primary autologous and allogeneic glioblastoma cells in vitro. This technique provides a method of generating large numbers of autologous cytolytic T cells with non-restricted anti-tumor activity that can be derived from peripheral blood mononuclear cells.

Benign intracranial hypertension in pregnancy

Benign intracranial hypertension, an unusual case of headaches, was associated with pregnancy in a gravid female with the chief complaint of headache. Symptoms resolved after three days of prednisone therapy. In benign intracranial hypertension, the possibilities of intracranial mass lesions, intracranial infection, obstruction of the cerebral ventricles, and hypertensive encephalopathy are excluded by evaluation with skull films, computerized axial tomography, electroencephalography and lumbar puncture. The only symptom may be headache and the only physical sign, papilledema. Therefore, neurological examination must include visualization of the fundi.

Hereditary Hemorrhagic Telangiectasia A Case Report with Known Cerebral Involvement and Cardiac Catheterization Data

Numerous bleeding episodes, neurological signs and symptoms, and pulmonary arteriovenous malformations are well documented in reports of families with hereditary hemorrhagic telangiectasia. It is always assumed that these are due to the arteriovenous malformations. We are here reporting a case with positive cerebral angiographic findings of large arteriovenous communications, as well as catheterization data revealing pulmonary ab normalities secondary to the cerebral arteriovenous fistula, but no ab normalities within the pulmonary vasculature itself.

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.

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.