Albert W. Cook

Somatosensory far field potentials: Studies in normal subjects and patients with multiple sclerosis ☆ ☆☆

Abstract Somatosensory evoked potentials to median nerve stimulation which arise in subcortical structures were recorded from the scalp of 15 normal subjects and 26 patients with definite multiple sclerosis (McAlpines criteria) in non-cephalic reference leads. In normal subjects, these subcortical events consisted of 3 positive potentials which were distributed widely over the scalp and were of similar amplitude at all scalp recording locations. In some subjects, these potentials were followed by another positive potential which was recorded predominantly over frontal central scalp regions. These potentials were followed by a larger negative potential which was most prominent over the somesthetic cortex contralateral to the side of stimulation. This negative potential is thought to reflect the arrival of the afferent volley in cerebral cortical elements. The criteria for abnormality in the patient group were (a) absence of components consistently recorded in normal subjects, (b) statistically significant component peak latency differences in patients compared to normal subjects, and (c) statistically significant differences in the amplitudes of the third positive and first negative potentials to stimulation of the left median nerve as compared with right median nerve stimulation. The response in all but one of the patients was judged to be abnormal. Absent components were observed in 17 patients, prolonged peak latency differences in 13 patients and component amplitude measurements were abnormal in 3 patients. Sequential recordings obtained in 5 of 9 patients revealed loss of components or latency changes. Evoked potential abnormalities were often found in the absence of either brain stem signs or clinically evident disturbances of specific sensory systems.

Electrical stimulation in multiple sclerosis.

When electrodes were implanted in the spinal cord of a patient with MS--for dorsal column stimulation to relieve intractable pain--she regained considerable movement in her legs. Subsequently such stimulation has been employed in more than 70 other patients, and many have regained voluntary control over their arms, legs, and sphincters. The procedure is detailed and its implications are explored.

Results of Spinal Cord Stimulation in Multiple Sclerosis

The results of spinal cord stimulation by various methods in 204 patients with multiple sclerosis are presented.

Functional stimulation of the spinal cord in multiple sclerosis

The authors describe the effect of electrical stimulation of the spinal cord in multiple sclerosis. After considering the nature of multiple sclerosis, the authors describe the background, character, mode and method of delivering electrical fields to the spinal cord. The results of this form of treatment and the implications of these observations in terms of physiologic mechanisms are discussed.

Sitting Prone Position for the Posterior Surgical Approach to the Spine and Posterior Fossa

The sitting prone position is compared with the standard laminectomy prone position and the sitting up position for posterior fossa surgery. We measured central venous pressure and airway pressure with the patient in different positions to determine the comparative efficacy of the sitting prone position. On a linear average, the central venous pressure increased by 6.83 cm H2O and the airway pressure increased by 3.16 cm H2O when the patient was changed from the supine to the standard prone position under general anesthesia; with a change from the standard prone position to the sitting prone position, the central venous pressure decreased by 10.45 cm H2O and the airway pressure decreased by 3.66 cm H2O. However, comparing the sitting prone position for posterior fossa surgery with the sitting up position, there was no statistically significant difference in central venous or airway pressure.

Growth of astrocytomas in the human tumor clonogenic assay and sensitivity to mismatched dsRNA and interferons

Nine astrocytoma specimens were received from seven patients and processed for testing in the human tumor clonogenic assay (HTCA). Cells derived from these specimens were challenged with human natural alpha-interferon (α-IFN) and beta interferon (β-IFN), recombinant beta interferon (βser-IFN), and mismatched double-stranded (ds) RNA (Ampligen). Six of the astrocytoma specimens formed adequate colonies for drug sensitivity testing (≥30 colonies/plate), and all were high-grade (III—IV) tumors. Sensitivity was denned as a ≥50% decrease in tumor colony formation following drug exposure and was observed with α-IFN (2/4), β-IFN (3/4), and mismatched dsRNA (4/5) exposure. No decrease in colony growth was observed after recombinant βser-IFN exposure, and in 2 of 3 cases, colony formation was stimulated. The sensitivity of 75 non-CNS solid tumors to mismatched dsRNA was compared to the high-grade astrocytomas in the HTCA. Of the 10 additional histologic tumor types studied, carcinoid and renal cell carcinomas exhibited the greatest sensitivity to mismatched dsRNA: 63% and 52%, respectively. However, in comparison, 80% of the high-grade astrocytomas were sensitive, demonstrating that these gliomas are among the most sensitive of human tumors to mismatched dsRNA in vitro. Clinical trials of interferons and mismatched dsRNA, coupled with in vitro sensitivity studies, should further define their therapeutic potential.

Human non-malignant and malignant brain tumor derived cell cultures: proliferation and sensitivity to natural human fibroblast (beta) interferon

Twenty-one human brain tumor biopsies were processed by mechanical and enzymatic methods to produce mixed cell suspensions. Cultures were prepared in small plastic flasks, and primary outgrowth occurred in 16/21 cultures. The period required for primary outgrowth ranged from 3 days to 14 days. We established serial propagation with 15/16 of the primary cultures. Sensitivity to HuIFN-β was determined between passages 3 to 12, using a microassay based on cell viability (uptake of a supravital stain, netural red). Extracted dye was quantified in acidic-methanol using the MR580 Microelisa Autoreader (Dynatech). We observed a broad range of responsiveness to the drug among the 12 cell-strains tested. Thus, 4 cell strains were relatively sensitive; 4 were resistant to 104 IRU/ml of purified HuIFN-β. Four cell strains exhibited a level of responsiveness that was intermediate to that of these two groups.During propagation of these biopsies, cytopathology suggestive of paramyoxvirus-infection appeared in 4 of the cell-strains. This characteristic was not uniformly associated with high sensitivity to human beta interferon which is a very potent, naturally occurring antiviral substance.Our results support the concept that information concerning sensitivity to HuIFN-β and other cytostatic agents may be rapidly obtained using microcultures of brain tumor cultures in conjunction with supravital stain uptake studies. Additionally, these results suggest that further clinical studies with β interferon should be undertaken to define the parameters which determine successful in vivo application.