Descending trigeminal tractotomy for trigeminal neuralgia after surgical failure.

Percutaneous rhizotomy, microvascular decompression or rhizotomy by suboccipital craniotomy often cures medically untreatable trigeminal neuralgia with an acceptable complication rate. However, pain involving the same trigeminal distribution persists in a few patients despite both rhizotomies. For 7 patients with such surgically 'failed' trigeminal neuralgia, we performed descending trigeminal tractotomy. In all patients, neuralgia ceased immediately postoperatively and has not recurred during 9 months to 15 years follow-up. Descending trigeminal tractotomy provides a satisfactory solution to this relatively rare but paroxysmal pain syndrome.

Control of the transition from sensory detection to sensory awareness in man by the duration of a thalamic stimulus. The cerebral 'time-on' factor.

A 'time-on' theory to explain the cerebral distinction between conscious and unconscious mental functions proposes that a substantial minimum duration ('time-on') of appropriate neuronal activations up to about 0.5 s is required to elicit conscious sensory experience, but that durations distinctly below that minimum can mediate sensory detection without awareness. A direct experimental test of this proposal is reported here. Stimuli (72 pulses/s) above and below such minimum train durations (0-750 ms) were delivered to the ventrobasal thalamus via electrodes chronically implanted for the therapeutic control of intractable pain. Detection was measured by the subject's forced choice as to stimulus delivery in one of two intervals, regardless of any presence or absence of sensory awareness. Subjects also indicated their awareness level of any stimulus-induced sensation in each and every trial. The results show (1) that detection (correct greater than 50%) occurred even with stimulus durations too brief to elicit awareness, and (2) that to move from mere detection to even an uncertain and often questionable sensory awareness required a significantly larger additional duration of pulses. Thus simply increasing duration ('time-on') of the same repetitive inputs to cerebral cortex can convert an unconscious cognitive mental function (detection without awareness) to a conscious one (detection with awareness).

Treatment of cerebral ischemia with electrical stimulation of the cervical spinal cord.

We observed an increase in cerebral blood flow (CBF) for control of pain but were otherwise normal. Based on that observation, we implanted stimulators for cervical spinal cord stimulation (cSCS) in three patients who had symptomatic cerebral ischemia. Two had severe basivertebral occlusive disease and one had bilateral carotid occlusive disease. In all three cases, cSCS alleviated the symptoms of ischemia. Xenon-CBF studies or single-photon emission computer tomography (SPECT) showed increased CBF in response to cSCS. Although no mechanism clearly responsible for this remarkable therapeutic efficacy can be proposed yet, further clinical trials of cSCS for inoperable cerebral ischemia may be justified.

Cerebrospinal fluid concentrations of laudanosine after administration of atracurium.

The concentration of laudanosine in cerebrospinal fluid (CSF) was measured in four patients undergoing brain electrode placement after the administration of atracurium. CSF: plasma laudanosine concentration ratios ranged from less than 1 to 14%, with a range of CSF laudanosine concentrations of less than 2-14 ng ml-1. One patient had no detectable laudanosine in CSF, but sampling in this patient was possible for only 30 min. There was no atracurium detectable in the CSF of any patient. We conclude that laudanosine crosses the blood-brain barrier and further study of its central nervous system effects in man is warranted.

Beneficial effects of cervical spinal cord stimulation (cSCS) on patients with impaired consciousness: a preliminary report.

Electrical stimulation of the spinal cord can be used for treatment of intractable pain and spasticity. Based on our experimental findings cervical spinal cord stimulation (cSCS) was performed on eight patients with severe brain dysfunction due to traffic accidents, pronounced vasospasm caused by subarachnoid hemorrhage or surgery of huge cerebral tumors (chordoma). After a 1 to 2 month period of stimulation, two patients became conscious and began to speak. It remains unclear whether cSCS induced the restoration of consciousness and improved neurological deficits. Although the successful results might be due to chance, cSCS might have stimulated brain function. This preliminary report shows such excellent results that further studies are warranted.

The effects of cervical spinal cord stimulation (cSCS) on experimental stroke.

Cervical spinal cord stimulation (cSCS) has been employed as a treatment for intractable pain for the past 20 years. Recently, we reported that cSCS increased regional cerebral blood flow (rCBF) in cats and humans. The present study was designed to examine the effects of cSCS on experimental cerebral strokes, using a cat middle cerebral artery occlusion model (MCAO). A total of 31 cats were randomly assigned to three groups; Group 1: control, Group 2: sham operation, Group 3: cSCS. Mortality of the control group was 92% as long as 4 days after MCAO. Groups 2 and 3 showed a prolongation of survival rate (44% and 56%, respectively). CSCS reduced the rate of death within 24 hours after MCAO. There was no alteration of infarct size, which was estimated by the TTC method and measured by computer technique (PDP-11/23), was found in dead cats of all groups. In cats that survived in Group 3, however, drastic prevention of an infarct progression was found, compared to Group 2. The results provide a clinical application of cSCS for stroke patients, although no evident mechanism was obtained.

Brachytherapy of recurrent tumors of the skull base and spine with iodine-125 sources.

Thirteen patients with recurrent, previously irradiated tumors of the skull base or spine were reirradiated with 125I sources implanted interstitially using microsurgical or stereotactic techniques. Patients harbored difficult, end-stage recurrences of chordoma, meningioma, malignant meningioma, fibrosarcoma, invasive pituitary adenoma, and malignant schwannoma. In two other patients with malignant meningioma, the dose of external radiation was augmented by implanting 125I sources during the initial operation for excision of the lesion or at a separate surgical procedure after conventional teletherapy. Microsurgical implantation of 125I sources into basal tumors was limited by the difficulties inherent in operating in this region; it is not possible to visualize the entire tumor that requires implantation. Three of five chordomas stabilized or regressed; these patients probably benefited from the procedure. Two patients with recurrent malignant meningiomas had long term remission after interstitial brachytherapy. Interstitial 125I brachytherapy for recurrent tumors at the base of skull or adjacent to the spine can be more successful only if more aggressive surgical exposures of these regions are attempted. Implantation of sources for a "boost" dose, either microsurgically during the initial surgical resection of the lesion before conventional teletherapy or stereotactically after conventional teletherapy, may be a valuable adjunct to external irradiation for the control of potentially devastating tumors (such as chordomas and malignant meningiomas) before they recur with the severe consequences seen in the patients reported here.

Consequence of dynorphin-A administration on anterior pituitary hormone concentrations in the adult male rhesus monkey.

This study examines the role of dynorphin-A(1-13) and dynorphin-A(1-10)-amide in the neuroendocrine regulation of anterior pituitary hormones in nonrestrained, adult male rhesus monkeys. The effects of these opioids on plasma concentrations of prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyrotropin (TSH) and growth hormone (GH) were assessed. Intravenous administration of dynorphin-A(1-13), 1-120 micrograms/kg, significantly increased plasma PRL levels. Average maximal increases of 90-230% occurred within 5 min and levels remained significantly elevated for up to 120 min. PRL response reached a plateau following the 30 micrograms/kg dose. Dynorphin-A(1-13) had no observable effects on plasma concentrations of LH, FSH, TSH or GH at any dose level studied. Administration of dynorphin-A(1-10)-amide produced significant dose-dependent increases in plasma PRL concentrations. Dose levels of 1-120 micrograms/kg produced mean peak increases from 100 to 230%, 5-10 min postadministration. Dynorphin-A(1-10)-amide had no significant effect on plasma concentrations of LH, FSH, TSH or GH. The increases in plasma PRL concentrations induced by dynorphin-A were naloxone-reversible. These results indicate a selective effect of dynorphin-A on the regulatory mechanisms of PRL secretion over that of other anterior pituitary hormones.

Dorsal periaqueductal gray-matter stimulation in humans.

Seven patients suffering intractable pain from head and neck cancer (age 48-73, mean 57.5 years) underwent acute stimulation of dorsal periaqueductal gray matter (PAG) with immediate cessation of pain. Two patients received chronic PAG stimulation with relief of pain during stimulation. The effect was not reversed by naloxone and there were no changes in CSF peptides.

Stereotactic heavy-particle irradiation of intracranial arteriovenous malformations.

Stereotactic irradiation appears to be effective in causing partial or complete thrombosis of AVM that are not surgically resectable. Use of heavy particles generated in a cyclotron allows better spatial definition and dose distribution than do other methods, allowing larger AVM to be treated. From these preliminary results, it is evident that heavy-particle irradiation therapy, like proton beam therapy, does not offer protection from recurrent hemorrhage for at least 12 months, nor is it devoid of major complications; it does offer a noninvasive mode of therapy for AVM that are difficult to treat surgically, however.

Dynorphin effects on plasma concentrations of anterior pituitary hormones in the nonhuman primate.

The role of dynorphin-(1-13) and dynorphin-(1-10)-amide in the neuroendocrine control of primate anterior pituitary hormones was studied in nonrestrained, ovariectomized rhesus monkeys. The effects of these opioids on plasma concentrations of prolactin (PRL), luteinizing hormone (LH), follicle stimulating hormone (FSH) and thyrotropin (TSH), and interactions with naloxone are reported here. Intravenous administration of dynorphin-(1-13), 30 to 120 micrograms/kg, significantly increased plasma PRL levels 3- to 4-fold. These PRL increases occurred within 5 min and levels remained elevated for at least 60 min. Administration of naloxone (1.0 mg/kg i.v.) antagonized the rise in PRL levels. Dynorphin-(1-13) had no significant effect on plasma LH, FSH or TSH levels. Dynorphin-(1-10)-amide (30-120 micrograms/kg) increased plasma PRL levels 2- to 4-fold at 5 to 40 min after administration. Plasma LH levels were significantly depressed 100 to 120 min postdrug. Dynorphin-(1-10)-amide produced no change in plasma FSH or TSH levels. These results indicate that dynorphin is involved in the modulation of PRL and perhaps LH secretion, although not affecting TSH or FSH release.

Effects of dynorphin1-13 on opiate binding and dopamine and GABA uptake in stroked cat brain.

We previously reported that the opioid peptide dynorphin1-13 improves survival chances in stroked cats. Some evidence also suggests that changes in dopamine and gamma-aminobutyric acid (GABA) uptake may be associated with stroke. In the present study, therefore, we determined binding of the opiate [3H]ethylketocyclazocine (EKC), as well as dopamine and GABA uptake in various brain regions of control, stroked and dynorphin1-13-treated stroked cats. Cats were stroked by middle cerebral artery occlusion. In the EKC binding study, the Kd of the high-affinity site of the occluded cortex was significantly increased, relative to that of both the unoccluded side and control cortex. Dynorphin1-13 treatment reversed this effect, lowering the Kd to control level. In the dopamine uptake study, the Km was decreased and Vmax was increased significantly in unoccluded cortex, compared with that in the occluded cortex or in control cortex. Again, dynorphin1-13 reversed these effects, raising the Km and lowering the Vmax. However, the Km of occluded cortex was also increased so that it became significantly higher than that of control cortex. The Km of unoccluded subcortex in stroked cats treated with dynorphin1-13 was significantly reduced compared with control. In the GABA uptake study, there was no significant change in any parameter. The change in opioid binding observed here and its reversal by dynorphin1-13 are consistent with the notion that the peptide's beneficial effect on stroke is mediated through opiate receptors. Since opioid systems in the brain are known to have association with dopaminergic ones, the change in dopamine uptake could also be the result of an opioid effect.

Subcortical electrical stimulation for control of intractable pain in humans. Report of 122 cases (1970-1984).

Chronic electrical stimulation of the subcortical area of the brain by implanted electrodes provides satisfactory control of a number of intractable pain syndromes that are refractory to medication. This series of 122 patients who underwent electrode implantation for the control of severe chronic pain was evaluated over a follow-up period of 2 to 14 years. Of the 65 patients with pain of peripheral origin, who were treated with stimulation of the periaqueductal gray region (PAG), 50 obtained successful pain control. Of 76 patients with a deafferentation pain syndrome, 44 obtained control of the dysesthesia with stimulation of the subcortical somatosensory region. Nineteen patients with both leg and back pain received electrodes in the PAG and the somatosensory regions; whereas back pain was relieved by PAG stimulation, dysesthetic leg pain was controlled more effectively by somatosensory region stimulation. The electrical stimulation technique appears to provide long-term pain control safely, with few side effects or complications.

Autopsy analysis of the safety, efficacy and cartography of electrical stimulation of the central gray in humans.

Electrical brain stimulation is effective in controlling certain intractable chronic pain syndromes in humans, but the specific target site(s) for stimulation producing a maximal analgesic effect is (are) not well defined. This prospective study correlates the clinical results of chronic stimulation of the periaqueductal gray (PAG) and periventricular gray (PVG) matter in humans with the anatomic site of electrode placement as determined at autopsy, and documents the histologic reactions to electrode implantation and electrical stimulation of the area. Seven patients underwent electrode implantation to control their chronic pain; two had electrodes implanted bilaterally. All patients obtained complete analgesia with stimulation, although 3 subsequently found the stimulation to have diminished efficacy. The opiate antagonist naloxone reversed the analgesia in the 4 patients so tested. All 7 patients later died of causes unrelated to electrode implantation or stimulation. Postmortem analysis showed that, for 6 of the 9 electrodes implanted, the electrode tip was located in the ventrolateral PAG at the level of the posterior commissure; the other 3 electrodes were found in the white matter adjacent to the PAG. No evidence of gliosis or parenchymal reaction was observed along the tracts and tips of the electrodes. The results indicate that the ventrolateral PAG and PVG matter at the level of the posterior commissure is the optimal site for therapeutic electrical brain stimulation for opiate-responsive pain in humans.