John E. Adams

Treatment of chronic pain by deep brain stimulation: long term follow-up and review of the literature.

Since the senior authors (J.E.A.) first report in 1972 of the use of deep brain stimulation (DBS) to control chronic pain, electrodes for DBS have been implanted in 141 patients. Of reported series, this one has the largest number of patients and the longest period of follow-up. The mean age of patients in this study was 51.2 years. The mean length of follow-up was 80 months. Patients had experienced pain for a mean period of 65 months before DBS was attempted; all patients had exhausted other medical and surgical therapies. For the purposes of this study, pain states were characterized as being either nociceptive or deafferentation in nature. Nociceptive pain was treated primarily by stimulation of the periaqueductal or periventricular gray, and deafferentation pain was treated primarily by stimulation of the sensory thalamus. Eighty-four patients were treated for deafferentation pain, which included the thalamic pain syndrome (25 cases), peripheral neuropathic pain (16 cases), anesthesia dolorosa (12 cases), paraplegia pain (11 cases), postcordotomy dyesthesia (5 cases), phantom limb pain (5 cases), thoracic neuralgia (4 cases), and miscellaneous pain states (6 cases). We treated 57 patients with nociceptive pain states, 51 for low back and skeletal pain and 6 for pain from the invasion of cancer. Initial relief of pain was obtained by 83 patients (59%). After the mean follow-up period of 80 months, 42 patients (31%) continued to obtain significant pain relief with DBS. Some pain states, particularly anesthesia dolorosa and paraplegia pain, did not seem to respond to DBS. Major complications of therapy included wound infection (12%) and intracranial hemorrhage (3.5%); there was one death in the series (0.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Naloxone reversal of analgesia produced by brain stimulation in the human

&NA; The analgesia resulting from electrical stimulation in the periventricular grey matter at the level of the posterior commissure in the human patient has been reversed by naloxone. This finding raises the possibility that such stimulation is effective because morphine receptor cells may be activated.

Naloxone-reversible analgesia produced by microstimulation in the rat medulla

Using microstimulation of the rostral medulla in the barbiturate-anesthetized rat, a map was constructed of loci for inhibition of the tail-flick response to noxious heat. Low threshold sites (less than or equal to 10 microA) were found in both the nucleus raphe magnus and the nucleus reticularis paragigantocellularis. Chronaxie determinations indicate that analgesia was not produced by activation of large myelinated axons of passage. Systemic naloxone only antagonized the inhibition generated from stimulation at low threshold sites. Inhibition from higher threshold sites, for example from the nucleus reticularis gigantocellularis, was not naloxone reversible. Depending on the area stimulated, either an opioid-or a non-opioid-mediated inhibition results from microstimulation within the rat medulla.

Lumbar intrathecal naloxone blocks analgesia produced by microstimulation of the ventromedial medulla in the rat

In lightly barbiturate-anesthetized rats. low threshold (less than 10 micro A) electrical stimulation within the rostral ventromedial medulla inhibited the tail-flick response to noxious heat. Naloxone applied intrathecally at the lumbar level reversed this inhibition, but the same dose of naloxone applied to the cervical intrathecal space had no effect. Doses of naloxone 1- to 4-fold greater than the intrathecal dose did not antagonize tail-flick suppression when given systemically. Because neither systemic nor intrathecal naloxone had any effect on base-line tail-flick latencies, we conclude that the inhibition of the tail-flick response resulting from microstimulation in the ventromedial medulla is mediated by a spinal opioid synapse.

Angiographie Demonstration and Nonsurgical Embolization of Spinal Cord Angioma

The value of arteriography in the diagnosis of angioma of the spinal cord has been stressed recently (3–11). This technic permits an exact definition of the position and extent of the malformation as well as of the location of its afferent and efferent vessels. The demonstration of the feeding vessels also allows a more logical approach to therapy. Before the advent of arteriography, angiomas of the spinal cord were usually treated by laminectomy with decompression alone, or by laminectomy combined with local excision or coagulation of the malformation. The results of these surgical efforts were often disappointing and were frequently associated with a deterioration in the neurologic state of the patient. More recently, ligation of the feeding arteries has been recommended (3, 5, 9). This surgical management has improved the neurologic deficit markedly in many instances and, at least, has not worsened it. Nonsurgical embolization of arteriovenous malformations of the spinal cord has not been proposed prev...

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.

Cryohypophysectomy for Acromegaly Factors Associated with Altered Endocrine Function and Carbohydrate Metabolism

Abstract After Cryohypophysectomy, fasting levels of growth hormone (GH) fell to less than 10 ng/ml in 38 (76 per cent) of 50 patients with acromegaly. Effects, including lowered serum insulin levels and improved glucose tolerance, were rapid and long-lasting. Optimal endocrine-metabolic results, defined as lowering of the GH level to 10 ng/ml or less and normal glucose tolerance (attained in 60 per cent of patients), were most often achieved when preoperative glucose tolerance was normal or mildly abnormal. Factors that favored optimal lowering of GH were preoperative GH level below 50 ng/ml and moderately, rather than greatly, enlarged sellae turcica. Factors that favored normal carbohydrate balance after treatment were postoperative fasting GH level of 10 ng/ml or less and preoperative symptom duration of 10 years or less. A family history of diabetes was not an important over-all factor in glucose intolerance. Although postoperative reduction in 24-hour urinary excretion of 17-hydroxycorticosteroids was associated with adequate GH reduction, adrenal reserve and thyroid function remained normal in most patients. In contrast to the prognostic significance of high GH levels, adrenal and thyroid function could not be related to eventual GH response or to carbohydrate metabolism.

Reduced Anesthetic Requirement after Electrical Stimulation of Periaqueductal Gray Matter

To determine whether electrical stimulation of the periaqueductal gray region decreases anesthetic requirement, the authors studied the effect of such stimulation on the MAC of halothane and 60% nitrous oxide in 33 patients. These patients, who were undergoing implantation of a radio-frequency-coupled receiver and connection of that receiver to electrodes previously implanted in the periaqueductal gray area, were assigned randomly to receive (n = 16) or not receive (n = 17) electrical stimulation 1 h before surgery. The mean value (±SEM) for the minimum alveolar concentration of halothane combined with 60% nitrous oxide was significantly less (P, < 0.001) for patients who were stimulated preoperatively (0.15 ± 0.05%) than for those who were not (0.51 ± 0.02%). The authors conclude that stimulation of the periaqueductal gray region decreases anesthetic requirements and believe that at least three mechanisms are possible: a nonspecific narcotic-like effect, a specific effect on a pain pathway, or an effect on specific neural pathways that affect anesthetic requirements secondary to changes in regional concentrations of neurotransmitters.

Familial hemangioblastoma of the cerebellum; pedigree of two families.

Case 1. M.V., a ~-year-old married woman of Hawaiian extraction, was first admitted to the San Francisco Hospital on Aug. 1, 1948, complaining of occipital and frontal headaches accompanied by nausea and vomiting for the previous 3 months. Physical and neurological examinations were negative. The family history obtained from the patient indicated only that her father had died of a brain tumor of unknown type. Subsequently, it was revealed that several members of the paternal branch of the family in the preceding two generations had had brain tumors (Fig. 1).

Deep Brain Stimulation for Chronic Pain: Long-Term Results and Complications

Electrical stimulation of brain structures in an attempt to produce analgesia in humans was first reported by Heath in 1954 [6] and by Pool and co-workers in 1956 [15]. Acute thalamic stimulation was reported to suppress the aversive properties of pain in patients with facial postherpetic neuralgia [26] and in patients with anesthesia dolorosa [9]. Based upon the hypothesis that chronic stimulation of denervated thalamic neurons would suppress deafferentation pain, further clinical trials of deep brain stimulation (DBS) for pain relief were undertaken. Hosobuchi, Adams, and coworkers [9] in the United States and Mazars and colleagues [12] in Europe published the first reports on the relief of deafferentation pain with chronic electrical stimulation of sensory thalamic nuclei. The technique of DBS for chronic pain was expanded after the observation that central gray matter stimulation in animals initiated the release of endogenous opioid peptides and resulted in analgesia [2, 13, 17]. Soon thereafter, Hosobuchi and associates and Richardson and Akil [19, 20] reported that chronic pain in humans was believed by longterm electrical stimulation of the periaqueductal gray matter.