Charles J. Fontana

Cranioplasty using gentamicin-loaded acrylic cement: A test of neurotoxicity

Cranioplasty represents a formidable challenge for neuro-surgeons, with a significant morbidity from both early and late wound infections. Polymethylmethacrylate (PMMA) is one of the most widely used materials in this setting. Despite the advantages of this material, such as ease of handling and inert biochemical properties, it is still a foreign body that is prone to infection. We present an animal model using a gentamicin-impregnated PMMA patch to assess the neurotoxicity as well as the efficacy of using this as an alternative material to lessen the infectious morbidity in this clinical setting. In part two of our experiment, we used a PMMA patch of similar weight and surface area in a physiological saline solution to determine the rate of gentamicin elution from the patch. The results obtained appear promising with no evidence of neurotoxicity and warrant further study to assess the clinical efficacy of PMMA in this setting.

Stereotaxic Implantation of Electrodes in the Human Brain: A Method for Long-Term Study and Treatment

A stereotaxic method for placement of electrodes in the human brain is described. Radiographic visualization of subcortical targets are discussed and error correction formulas are developed. Electrodes and fixation methods for long-term human implantation are described. Multiple stainless steel or silver bail electrodes have been implanted in 75 patients with schizophrenia, epilepsy, depression, Parkinsons disease, narcolepsy, and intractable pain. The silver ball electrode is more satisfactory for recording and stimulation. Biphasic 0.25-ms duration currents from 2-7 mA have been applied to animals and humans without evidence of structural damage.

A sympathoinhibitory area in cat rostral medulla: its role in cardiovascular tone regulation and baroreflex.

We have found a medullary vasodepressor area in cat centered 3 mm rostral to the obex and just lateral to the compact division of the ambiguus nucleus. The area is compact, extending at most 1 mm in any direction. Microinjection of L-glutamate into this rostral depressor area (RDA) elicited acute hypotension and bradycardia. These responses were not reduced by either peripheral atropine blockade or bilateral vagotomy, but they were nearly abolished by peripheral phentolamine/propranolol blockade or high cervical cord transection. Bilateral reversible blockade of the RDA by local microinjection of the neuronal hyperpolarizing agent muscimol yielded chronic hypertension and tachycardia. Sympathetically mediated baroreflex, observed as a bradycardic response to a peripherally administered phenylephrine bolus in atropinized animals, was partially (50%) abolished during this same blockade. We conclude that the RDA contains sympathoinhibitory cells which are involved in the regulation of cardiovascular tone and in the expression of the sympathetic component of baroreflex.

Cardiovascular sympathoinhibitory neurons form an extended longitudinal column in cat lateral medulla

A search for vasomotor depressor sites in the lateral medullary brainstem of anesthetized cat using microinjections of AMPA has delineated a longitudinal column of sympathoinhibitory neurons consisting of the rostral depressor area, the caudal ventrolateral medulla, and a new intermediate depressor area. Systematic blockade of these three subregions with bilateral microinjections of kynurenic acid indicates a uniform involvement of the entire column with sympathetic baroreflex, but a slightly greater involvement of the anterior portion, over the posterior, with regulation of cardiovascular tone.

EEG activation with chloralosane.

Abstract In 39 studies on 37 patients with behavioral disorders requiring hospitalization on a psychiatric ward, only 3 patients failed to show electroencephalographic abnormalities after they had received 500 mg. of chloralose plus 1 2 mg. of scopolamine. Six of this group showed EEG abnormalities during baseline recordings with hyperventilation. Only 7 of the 37 had a history of grand mal or psychomotor seizures. In 15 voluntary controls with no evidence of either epilepsy or severe behavior disorder, only 4 were activated. All activated controls had some irregularities in the baseline recording which, although they might not have been considered abnormal were, nevertheless, deviations from the expected pattern. Activation, which, with one exception, started within the first hour and reached a maximum within the second, consisted of theta-delta activity that was often focal at first but tended to generalize later. Occasionally sharp waves or spikes would be seen. The abnormality would be continuous or paroxysmal and was often associated with an increase in symptoms or behavioral abnormalities. In 8 patients with subcortical chronically implanted electrodes, there was no consistent pattern of subcortical activation before involvement of the cortical areas. Like the clinical studies, the activation often occurred focally then became generalized. Only one patient lost consciousness, and although she showed focal rhythmic clonic movements there was no generalized tonic-clonic convulsion. In view of the fact that only 7 of the 34 patients who were activated had a history of seizures, one should be extremely cautious in interpreting scopolamine-chloralose activation as evidence of epilepsy. Whether this procedure will be useful in identifying a specific group of behavior disorders can only be determined by extending activations to much larger series of patients and controls.

Sympathetically-mediated cardiovascular responses induced by neurochemical microinjection in the brainstem lateral tegmental field of cat

This study examines sympathetically-mediated cardiovascular responses arising from microinjections of AMPA and kynurenic acid in the medullary lateral tegmental field (LTF). The resulting behavior, which is predominantly inhibitory, is nearly identical to that reported for the para-ambiguual area lying just lateral to the LTF, and suggests that the two regions may share other cardiovascular control functions.

Lateral tegmental field neurons with activity correlated to the 10-Hz rhythm in sympathetic nerve discharge.

Neurons in the lateral tegmental field (FTL) has been previously reported to have activity only minimally correlated (< 1% of neurons tested) with the 10-Hz rhythm of the slow wave of the sympathetic nerve discharge. We report here that 10% of the neurons recently tested in the FTL could be shown to correlate with the 10-Hz rhythm. The neuron-to-nerve coherence is weaker than in other medullary areas, but is nonetheless significant.

Neurons of the rostral para-ambiguual field have activity correlated to the 10-Hz rhythm in sympathetic nerve discharge of urethane-anesthetized cat.

Using the techniques of time domain correlation (mid-signal spike-triggered averaging) and frequency domain correlation (neuron-to-nerve coherence), 24% (54) of a sample of 229 neurons of the rostral para-ambiguual field have shown to have activity correlated to the 8- to 13-Hz rhythm in the inferior cardiac sympathetic nerve discharge (SND) of urethane-anesthetized cat. This correlation existed in both baroreceptor-innervated and -denervated animals. Of the correlated neurons, 37% (20) were non-rhythmically firing and displayed flat autospectra, while 63% (34) fired rhythmically and contained well-defined peaks in their autospectra. The group firing rate of these neurons was 4.3 +/- 0.4 spikes/s, indicating that they are not pacemaker neurons for the 10-Hz SND rhythm. The group time of firing of these neurons to the next peak of the SND slow wave was 52 +/- 4 ms. Correlation of the activity of medullary neurons with the 8-13-Hz rhythm of the SND was previously claimed only for rostral ventrolateral medulla, caudal raphe, and rostral caudal ventrolateral medulla. This present finding suggests that this behavior may be more widely spread throughout the medulla.

Pulmonary vascular responses to forebrain stimulation in the cat.

The effects of forebrain stimulation on the pulmonary vascular bed were investigated in the intact-chest cat under conditions of controlled blood flow and constant left atrial pressure. When pulmonary vascular tone was raised to a high steady level, direct electrical stimulation of the forebrain elicited a biphasic change in lobar arterial pressure. The response was characterized by an initial transient increase in lobar arterial pressure that was followed by a prolonged secondary decrease in pressure. When a delay coil was added to the extracorporeal perfusion circuit, the secondary vasodilator response was separated into initial brief and delayed prolonged components, suggesting that it was mediated in part by the release of a humoral factor. The entire response to forebrain stimulation was abolished by cervical cord section or freezing. The initial constrictor response and early brief dilator response were not blocked by classic pharmacological blocking agents. The delayed humorally mediated vasodilator response was blocked by propranolol or ICI 118551, indicating that it was mediated by a circulating factor with beta 2-stimulating properties. The delayed vasodilator response was associated with a large increase in arterial epinephrine levels, and this rise in plasma epinephrine was not altered by propranolol. The present data suggest that electrical stimulation of the forebrain causes a prolonged pulmonary vasodilator response that is mediated by way of a descending pathway, which results in a large rise in arterial epinephrine levels.