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The clinical efficacy of neuroendoscope in surgical treatment for deafferentation pain.

Spinal cord stimulation (SCS) is one of the most minimally invasive and effective treatments for intractable pain. We report the efficacy of a very small diameter neuroendoscope on setting the electrode to the proper site in the epidural space. Our cases include thalamic hemorrhage, and each patient had unilateral intractable pain on L1 or less as the main complaint. They had been treated for over two years in other hospitals, but no significant relief was achieved. Because each patient had been given frequent epidural blocks, the adhesion in the epidural space was expected. In Group A (3 cases), we used very small diameter neuroendoscope to dissect adhesion in the epidural space and to make optimal space for lead placement under direct vision. Conventional lead placement under fluoroscopy was performed in Group B (3 cases). Medtronic's PISCES lead system was used for SCS. In Group A, stimulation and pain regions matched in all cases, and good pain relief was also achieved. In Group B, however, stimulation and pain regions matched incompletely and the increase in stimulation caused stimulation on the pain-free side.

Aged↗

Treatment of diabetic neuropathy with pentoxifylline: case report.

Diabetic neuropathy includes a heterogenous group of neuropathic syndromes associated with diabetes mellitus. One form of diabetic neuropathy is distal symmetric polyneuropathy, which is characterized at a late stage by intractable pain. This pain is generally refractory to present modalities of therapy except for narcotics. Pentoxifylline offers a new approach to therapy, reducing the blood viscosity and improving perfusion of ischemic microcirculation. A case report will be presented of intractable painful peripheral neuropathy responding dramatically to pentoxifylline therapy.

Aged↗

Ziconotide (Elan Pharmaceuticals).

Elan Pharmaceuticals (formerly Neurex) is developing ziconotide, a neuron-specific N-type calcium channel blocker, for the potential treatment of severe pain and ischemia. A US NDA for the use of the compound in intractable pain is under review [351606,357600] and phase III trials for ischemia are ongoing [261455,292579]. Elan received an approvable letter from the FDA for pain in June 2000, and by October 2000, was responding to questions raised by the FDA in the letter [372580,386279]. In December 2000, DRAXIS filed an NDS for ziconotide with the Therapeutic Products Programme of Health Canada [393773]. The drug has Priority Review status in Canada [387218]. PAIN: In pivotal studies, ziconotide showed a significant reduction in pain compared to placebo. In the two trials, completed by December 1999, more than 700 patients received the drug for the treatment of intractable pain intrathecally. This included patients who had failed morphine therapy, or who had become intolerant of therapy due to side-effects. The drug was safe and well tolerated over periods as long as 3 years [351606]. ISCHEMIA: Elan and Pfizer (formerly Warner-Lambert) are also developing ziconotide for the treatment of ischemia associated with head trauma and stroke [292579]. In September 1997, Neurex and Warner-Lambert restarted a pivotal phase III head trauma study with no changes in the study design. In July 1997, patient enrollment had been halted pending analysis of clinical data from earlier studies to determine the relative risk/benefits of administering ziconotide with the current protocol [261455]. By April 1999, Parke-Davis (now Pfizer) was also working on the development of nonpeptide analogs of ziconotide, with the aim of developing an orally available agent for the treatment of chronic pain [325613,324954]. In July 2000, Merrill Lynch predicted FDA approval and launch in the third or fourth quarter of 2000 [375966], but in January 2001, the prediction of approval was revised to be in 2001 [395423].

Journal Article↗

Patients with persistent pain after enucleation studied by MRI dynamic color mapping and histopathology.

PURPOSE: To study possible causes of persistent pain in patients who underwent enucleation of the globe and in whom all other noninvasively detectable causes of pain had been ruled out. METHODS: Twenty patients were studied, 10 with intractable pain (score >5 on a 0-to-9 self-reporting pain scale) persisting for more than 6 months after enucleation (for various reasons) and 10 without pain (score <4) at least 6 months after enucleation. Magnetic resonance imaging (MRI) with dynamic color mapping (MRI-DCM) was used to quantify the motion of the optic nerve in millimeters per degree of gaze, 2 to 3 mm behind the implant. Histopathologic study of biopsy specimens was used to verify imaging findings. RESULTS: The optic nerve was attached to the implant in almost all (19/20) patients. On average, the motion was significantly less in patients with persistent intractable pain (0.04 mm/deg) than in patients without pain (0.08 mm/deg; normal orbit, 0.13 mm/deg). A biopsy specimen was available in 5 of 10 patients with persistent pain, and in 4 of those 5, microscopic neuroma was found close to the optic nerve-implant junction. CONCLUSIONS: In the enucleated orbit, the optic nerve is usually attached to the implant and soft tissue motion is decreased. In patients who have persistent pain after enucleation, motion is decreased even more, and a high percentage of microscopic amputation neuromas are found. Increased stiffness of orbital soft tissue and optic nerve attachment after enucleation are detectable using MRI-DCM, and may play a role in susceptible patients in the development of microscopic amputation neuroma and pain.

Adult↗

Kyphoplasty: indications, contraindications and technique.

PURPOSE: Percutaneous Kyphoplasty is an emerging Interventional Radiology technique consisting in injecting polymethylmethacrylate (PMMA) into collapsed vertebral bodies under fluoroscopic guidance, after compaction of the cancellous bone with two dedicated balloon catheters. The purpose of our study was to assess the indications, contraindications, technique and results of our initial study. MATERIALS AND METHODS: Between January and May 2003 we treated 11 patients (5 men, 6 women) with vertebral collapse occurred up to three months earlier and due to osteoporosis or myeloma (mean age: 68.9), with pain refractory to medical therapy. All patients underwent treatment on a single vertebra (1 D7; 1 D8; 2 D12; 3 L1; 3 L2; 1 L4). Patient selection was based on clinical and instrumental criteria: conventional radiography, CT and MR were performed on all patients before the procedure. The Visual Analogue Scale (VAS) for pain assessment was used to evaluate the post-procedure results. RESULTS: All patients showed an increase in the height of the collapsed vertebral body, associated with partial or complete pain relief (VAS score decreasing from a pre-treatment score of 8 to a score of 2 after treatment). No complications related to the procedure were recorded. CONCLUSIONS: The indications for kyphoplasty include recent vertebral compression fractures due to osteoporosis, myeloma, metastasis and vertebral angioma with intractable pain and with no neurological symptoms. The main contraindications are coagulation disorders, unstable fractures or complete vertebral collapse (vertebra plana). Kyphoplasty proved to be a safe and effective method for the treatment of intractable pain due to vertebral collapse that allows for shorter hospital stays and an immediate improvement in the patient's quality of life.

Aged↗

A brief trial of phenytoin therapy for thalamic pain.

Phenytoin was given in full dosage to eight patients with thalamic pain and two others with intractable pain resistant to other forms of treatment. Serum levels were monitored and correlated with dosage levels. Three patients improved markedly, two improved only minimally, two were unchanged, and three were worse. Those patients who had improved noted return of original pain on stopping phenytoin. The results indicate the need for a further study of the drug in thalamic and other chronic pain states.

Adult↗

Daily scheduled opioids for intractable head pain: long-term observations of a treatment program.

BACKGROUND: Daily scheduled opioids (DSO) have been employed in some instances to remediate intractable headache. However, long-term studies of effectiveness, sequelae over several years, predictors of long-term benefit, comparisons of pain-related outcome measures, and prevalence of problematic drug behavior are not available. METHODS: The authors evaluated the results of a treatment program at their institution designed to treat and monitor intractable headache patients administered DSO. Of 160 sequential patients participating in the program, 70 who remained on DSO for at least 3 years qualified for inclusion in an efficacy analysis. Patients completed structured questionnaires at each medical visit as part of routine clinical care. The authors assessed medical records during treatment, and during the 2 years before starting DSO. The primary clinical efficacy variable was percentage improvement in the severe headache index (frequency x severity of severe headaches/week). RESULTS: Analysis of the medical records found 41 (26%) of the original 160 patients with >50% improvement. Patients reported larger improvements on a visual analog scale (mean improvement = 70%) than shown by the medical record (mean improvement = 46%), p < 0.00001. Problem drug behavior (dose violations, lost prescriptions, multisourcing) occurred in 50% of patients, usually involving dose violations. CONCLUSIONS: For a select group of intractable headache patients, DSO can offer significant benefit. However, 74% of those treated either failed to show significant improvement or were discontinued from the program for clinical reasons. The relatively low percentage of patients with demonstrated efficacy and unexpectedly high prevalence of misuse have clinical relevance.

Adult↗

Percutaneous trigeminal thermorhizotomy in treatment of malignant facial pain.

Fifty-eight patients suffering from intractable pain in the trigeminal distribution due to neoplasms of the intracranial or facial regions underwent controlled percutaneous coagulation of the Gasserian ganglion (trigeminal thermorhizotomy). Of them, 35 were evaluated at varying time intervals from the intervention (mean: 7 months). While pain was completely relieved in 71 per cent of cases at discharge, the follow-up examination was consistent with 49 per cent of analgesias. The rationale of percutaneous thermocoagulation in malignant facial pain is given and the pertinent literature summarized.

Dermatologic Surgical Procedures↗

[Modulating mechanism of the dorsal column stimulation for pain relief (author's transl)].

The neural mechanism of the modulating effects of spinal cord stimulation upon intractable pain was studied in cats under local anaesthesia. The electrical activity at the centre median nucleus of the thalamus (CEM), which responded to noxious stimuli and was inhibited by nitrous oxide inhalation, was recorded as an indicator of the degree of pain sensation. The suppressed effect upon the evoked potential responding to sciatic stimulation (1 Hz) was recorded during and after train stimulation of various parts of the spinal cord by means of silver ball bipolar electrode. Whenever inhibitory modulating effect upon CEM response was observed by spinal cord stimulation, the bilateral dorsal tractotomy cranial, caudal or both to the stimulating point in order to examine the influence upon the CEM potential. The results are as follows: 1) The CEM evoked potential responding to sciatic stimulation is inhibited by about 30-45% of its amplitude by dorsal column stimulation. This effect corresponds to the inhibitory effect by 75% N2O gas inhalation. Upon dorsal column stimulation, the intraspinal electrical activity is found in the central gray matter the antero-lateral quandrants of the spinal cord as well as the dorsal column. 2) Following lateral or anterior column stimulation as well as dorsal column stimulation, the CEM evoked potential responding to sciatic stimulation is inhibited by about 50% of its amplitude. 3) Following bilateral dorsal tractotomy cranial, caudal or both to the stimulating point, the CEM evoked potentials responding to sciatic stimulation are inhibited by dorsal column stimulation. According to the experimental results, it may be concluded that the inhibitory modulating mechanism by dorsal column stimulation for pain relief is not only mediated through the dorsal column, but also through other ascending spinal pathways.

Animals↗

Spinal cord stimulation in the treatment of paraplegic pain.

Twenty-five patients suffering from intractable pain due to a chronic spinal cord lesion underwent a percutaneous test of spinal cord stimulation. At the end of the test period, 40.9% of the patients reported a mean of 65% pain relief and these patients were selected for ongoing stimulation. At a mean follow-up time of 37.2 months the success rate, based on the number of patients with more than 50% pain relief, had fallen to 18.2%. Pain relief rates were analyzed in relation to quality of pain, neurological status, level and extent of the lesion, and electrode level to identify prognostic factors that could improve the clinical usefulness of spinal cord stimulation. Patients experiencing painful spasms or a constrictive type of pain and with incomplete thoracic lesions were found to be the best candidates for spinal cord stimulation.

Adult↗

Major amputations done with palliative intent in the treatment of local bony complications associated with advanced cancer.

Palliative amputations were performed on 11 patients (7 men, 4 women) with disseminated disease to control local bony complications. The average patient age was 54 years (range 14-78 years). The primary diseases were melanoma/sarcoma (seven patients) and carcinoma (four patients). All had pain; eight had intractable pain that could not be controlled by analgesics. All 11 patients had additional severe local complications, which included recurrent pathological fracture (4), sepsis (2), hemorrhage (2), radiation necrosis (2), and iliofemoral thrombosis secondary to tumor (1). Previous attempts of palliation had been made in all 11 patients, and 8 had undergone previous operative procedures (5 had undergone two or more) prior to amputation. Three anterior hemipelvectomies, five posterior hemipelvectomies, two hip disarticulations, and one forequarter amputation were performed. All patients survived the surgery, and there were no intraoperative complications. All patients received dramatic relief of pain. Postoperative complications included two cases of flap necrosis and two infections; all resolved satisfactorily. The six patients who were nonambulatory before surgery ambulated postoperatively, and two eventually ambulated with a prosthesis. Six of 11 patients survived 1 year or longer, with a median postoperative survival period of 13 months (average 16 months). Although major amputations are viewed at times as offering little to already-compromised patients, they can improve dramatically the quality of life in selected patients.

Adolescent↗

Severe toxic damage to the rabbit spinal cord after intrathecal administration of preservative-free S(+)-ketamine.

BACKGROUND: Ketamine and S(+)-ketamine have been advocated for neuraxial use in the management of postoperative pain and severe intractable pain syndromes unresponsive to opioid escalation. Although clinical experience has accumulated with S(+)-ketamine, safety data on toxicity in the central nervous system after neuraxial administration of S(+)-ketamine are conflicting. In this study, neurologic and toxicologic effects on the spinal cord from repeated daily intrathecal administration of commercially available, preservative-free S(+)-ketamine were evaluated against placebo in a randomized, blinded design. METHODS: Eighteen white New Zealand rabbits were assigned to two groups receiving either 0.5 ml intrathecal S(+)-ketamine, 0.5% solution (12 rabbits), or 0.5 ml saline (6 rabbits) once a day for 7 consecutive days. During general anesthesia, an intrathecal catheter was placed between the fifth and sixth spinous processes (lumbar). Neurologic (according to Tarlov criteria) and histopathologic assessments were performed after 7 days of treatment. RESULTS: Postmortem investigation of the spinal cord and nerve roots revealed histopathologic lesions suggestive of toxic damage in 11 rabbits, from the group of 12 animals receiving S(+)-ketamine. These results were significantly different compared with 5 control animals (no histologic changes observed). There was no significant difference in neurologic status between the two groups after 7 days of intrathecal treatment. CONCLUSIONS: The authors conclude that repeated intrathecal administration of preservative-free S(+)-ketamine in a clinically relevant concentration and dosage has, considering the extent and severity of the lesions, a toxic effect on the central nervous system of rabbits.

Anesthesia, Spinal↗

Five-year results from chemonucleolysis with chymopapain or collagenase: a prospective randomized study.

STUDY DESIGN: A 5-year clinical follow-up assessment of a prospective randomized study of chemonucleolysis using chymopapain (4000 IU) or collagenase (400 ABC units) was performed. SUMMARY OF BACKGROUND DATA: Intradiscal therapy can be performed for patients with contained discs by chemonucleolysis, percutaneous discectomy, or laser ablation. The oldest intradiscal therapy is chemonucleolysis with chymopapain. OBJECTIVE: The purpose of this study was to compare prospectively the efficacy of chymopapain and collagenase for intradiscal injection. METHODS: In this study, 100 patients with indication for intradiscal therapy were prospectively randomized to treatment with either chymopapain or collagenase. All the injections were performed by the double-needle technique with the patient under general anesthesia. The mean age of the patients was 35.5 years in the chymopapain group and 38 years in the collagenase group. An equal number of injections was performed at L4-L5 and L5-S1. RESULTS: After 5 years, good and excellent results were observed in 72% of the chymopapain group and 52% of the collagenase group when the surgically treated and lost patients were graded as poor. Using a scale of 0 (no pain) to 10 (intractable pain), the pain level dropped from 8.5 to 0.7 in the chymopapain group and from 8.6 to 0.9 in the collagenase group. Microdiscectomy at the injected level was required for 23 patients (14 in the collagenase group and 9 in the chymopapain group). CONCLUSIONS: After 5 years, no deterioration had occurred, as compared with the 1-year follow-up assessment. Chymopapain has proved to be safe, with one minor anaphylactic reaction, and effective even over the long term. Collagenase may need further study and cannot be recommended at this time.

Adult↗

Sacroplasty and iliac osteoplasty under combined CT and fluoroscopic guidance.

STUDY DESIGN: We postulate that osteoplasty of osteolytic metastases of the pelvic region performed by computed tomography (CT)-guided insertion of Kirschner wires into the lesions is effective and more feasible. OBJECTIVE: To determine whether osteoplasty of osteolytic metastases of the pelvic region can be performed by a more feasible lesion access, increasing patient compliance and reducing patient radiation exposure. SUMMARY OF BACKGROUND DATA: Treatment of osteolytic bone metastases is palliative and relies mainly on the elimination of pain. When pain is medically intractable, this can be effectively treated by osteoplasty. MATERIALS AND METHODS: A 61-year-old man with medically intractable pain from osteolytic lesions of the sacral ala and left iliac alum from pulmonary adenocarcinoma underwent osteoplasty. The lesions were accessed using Kirschner wires under CT guidance. Subsequently, under high-resolution fluoroscopic guidance, 13-G biopsy needles were advanced coaxially over the Kirschner wires and polymethyl methacrylate (PMMA) was injected into the lesions. RESULTS: No peri-procedural complications were observed. The patient experienced an immediate and substantial pain relief that was persistent during a 4-month follow-up. CONCLUSIONS: This technique is safe and effective and requires fewer CT scans, thus reducing the patient's radiation exposure. The shorter procedure correlates to a better patient tolerance.

Adenocarcinoma↗

Neurologic pain syndromes in patients with cancer.

Recognizing and treating the cause of pain in the patient with cancer should be the initial approach to the management of this common symptom. Careful analysis of patients with cancer and pain has led to the elucidation of common neurologic pain syndromes unique to this disease process. Pain in patients with cancer is commonly the presenting symptom of neurologic involvement. Changes in the pattern of pain or neurologic deficits should be carefully evaluated to rule out the possibility that metastatic disease may be exacerbating existing neuropathic pain. This chronic intractable pain syndrome can markedly debilitate the patient and needs an aggressive approach with drug therapy as the first-line approach.

Chronic Disease↗

[Pain following traumatic lesions of the brachial plexus (radicular avulsions and truncular lesions)].

Pain in avulsions lesions of the brachial plexus is related with deafferentation; experimental studies demonstrate that spontaneous discharges can be recorded with micro electrodes in the dorsal horn, after division of the dorsal roots. These discharges ("firing") are related with the loss of control of the inhibitory effects of the large caliber sensory fibers. This pathophysiological concept drawn from the Melzack and Wall's theory (gate control) allows a good meaning of the paradoxical results observed after neurotization (via accessory or intercostal nerves), namely immediate relief of pain, observed in several cases after surgery. This theory helps to explain the efficiency of the neurostimulation techniques (by inhibition of the "firing") and of the technique of "dorsal root entry zone coagulation" in the avulsed area, on the spinal cord, by direct destruction of the hyperactive cells in the posterior horn. These technical advances and early return to work and to community offer the best prospect of relief of pain. Incidence of intractable pain problem is less than 10% after 10 years.

Brachial Plexus↗

Thoracoscopic splanchnicolysis for the relief of chronic pancreatitis pain: experience of a group of pneumologists.

Intractable pain is the most invalidating symptom in patients suffering from chronic pancreatitis. Anatomical interruption of the major afferent pain nerves is indicated in severe refractory cases. Among the various techniques and sites of interruption, thoracoscopic splanchnicectomy has emerged as an efficient alternative for the more aggressive open surgical splanchnicectomy, and for the (solely temporarily efficacious) transcutaneous neural blocks, which moreover bear some serious complications. Until now, all reports on thoracoscopic splanchnicectomy were typically surgical, using video-assisted thoracoscopic surgery techniques, double-lumen intubation, and so on. In analogy with thoracoscopic upper dorsal T2-T3 sympathicolysis for essential hyperhidrosis, a simplified thoracoscopic splanchnicolysis technique used in 8 patients suffering from either severe refractory chronic pancreatitis pain (7 patients) or postsurgical epigastric pain is described. Pain control was achieved in 5 of the 7 patients with chronic pancreatitis with a short (20+/-8 min) intervention, short hospitalization (2 days), and simple (single-lumen intubation, no chest drains) procedure. Thus, this simplified thoracoscopic splanchnicolysis technique may represent a valid alternative in the often difficult treatment of refractory chronic pancreatitis pain or other upper abdominal pain.

Abdominal Pain↗

[Motor cortex stimulation therapy in patients with thalamic pain].

Seven patients with thalamic pain were treated by electrical stimulation of the motor cortex. Patients ranged from 55 to 71 years of age. There were six men and one woman. Causes of thalamic pain were thalamic infarction in 2 patients and thalamic hemorrhage in five. Six patients had intractable pain associated with dysesthesia in the upper and lower limb (upper limb dominant). One patient had intractable pain in the face contralateral to the lesion. Magnetic resonance images (MRI) were performed in 5 patients and showed the deposit of hemosiderin in the internal capsule, posterolateral nucleus and pulvinar. Electrodes were placed on the motor cortex epidurally in seven patients. Electrodes were implanted permanently in six patients and removed in one patient after an unsatisfactory result of test stimulation. Motor cortex stimulation provided satisfactory pain relief in all six patients for a month after the beginning of stimulation, however, by the time three months had passed, pain relief had become gradually unsatisfactory in five patients. We compared pain relief between 10 Hz and 100 Hz of stimulus rate in four patients and observed that all patients complained of fatigue in the upper extremity at the 100 Hz of stimulus rate, though no differences in pain relief was obtained according to which of these two stimulus rates were used. We concluded that motor cortex stimulation brought about pain inhibition in patients with thalamic pain, but pain control tended to become less gradual within several months after the beginning of stimulation.

Aged↗