Survival in patients with Parkinson's disease after deep brain stimulation or medical management.

OBJECTIVE: Deep brain stimulation has been shown to have a significant long-term beneficial effect on motor function. However, whether it affects survival is not clear. In this study, we compared survival rates for Parkinson's disease (PD) patients who underwent deep brain stimulation (DBS) with those who were medically managed. METHODS: A retrospective analysis of Veterans Affairs and Medicare administrative data of veterans with PD who received DBS and were propensity score matched to a cohort of veterans with PD who did not receive DBS between 2007-2013. RESULTS: Veterans with PD who received DBS had a longer survival measured in days than a matched group of veterans who did not undergo DBS (mean = 2291.1 [standard error = 46.4] days [6.3 years] vs 2063.8 [standard error = 47.7] days [5.7 years]; P = .006; hazard ratio = 0.69 [95% confidence interval 0.56-0.85]). Mean age at death was similar for both groups (76.5 [standard deviation = 7.2] vs 75.9 [standard deviation = 8.4] years, P = .67), respectively, and the most common cause of death was PD. CONCLUSIONS: DBS is associated with a modest survival advantage when compared with a matched group of patients who did not undergo DBS. Whether the survival advantage reflects a moderating influence of DBS on PD or on comorbidities that might shorten life or whether differences may be a result of unmeasured differences between groups is not known. © 2017 International Parkinson and Movement Disorder Society.

Differential effects of deep brain stimulation target on motor subtypes in Parkinson's disease.

OBJECTIVE: The Veterans Administration Cooperative Studies Program #468, a multicenter study that randomized Parkinson's disease (PD) patients to either subthalamic nucleus (STN) or globus pallidus internus (GPi) deep brain stimulation (DBS), found that stimulation at either target provided similar overall motoric benefits. We conducted an additional analysis of this data set to evaluate whether PD motor subtypes responded differently to the 2 stimulation targets. METHODS: We classified 235 subjects by motor subtype: tremor dominant (TD), intermediate (I), or postural instability gait difficulty (PIGD), based on pre-DBS baseline Unified Parkinson's Disease Rating Scale (UPDRS) scores off-medication. The primary outcome was change in UPDRS part III (UPDRS-III) off-medication scores from baseline to 24 months post-DBS, compared among subjects with particular PD motor subtypes and by DBS target (STN vs GPi). Changes in tremor, rigidity, akinesia, and gait scores were also assessed using the UPDRS. RESULTS: TD patients had greater mean overall motor improvement, measured by UPDRS-III, after GPi DBS, compared to STN DBS (17.5 ± 13.0 vs 14.6 ± 14.9, p = 0.02), with improvement in gait accounting for this difference. Regardless of stimulation target, PIGD subjects had lower mean overall improvement in UPDRS-III scores compared with I or TD subjects (8.7 ± 12.2 vs 21.7 ± 11.2 vs 16.3 ± 13.8, p = 0.001). INTERPRETATION: Our results suggest that responsiveness to both GPi and STN DBS is similar among different PD motor subtypes, although the TD motor subtype may have a greater response to GPi DBS with respect to gait. PIGD patients obtained less overall benefit from stimulation.

Neuropsychological changes following deep brain stimulation surgery for Parkinson's disease: comparisons of treatment at pallidal and subthalamic targets versus best medical therapy.

BACKGROUND: Deep brain stimulation (DBS) improves motor symptoms in Parkinson's disease (PD), but questions remain regarding neuropsychological decrements sometimes associated with this treatment, including rates of statistically and clinically meaningful change, and whether there are differences in outcome related to surgical target. METHODS: Neuropsychological functioning was assessed in patients with Parkinson's disease (PD) at baseline and after 6 months in a prospective, randomised, controlled study comparing best medical therapy (BMT, n=116) and bilateral deep brain stimulation (DBS, n=164) at either the subthalamic nucleus (STN, n=84) or globus pallidus interna (GPi, n=80), using standardised neuropsychological tests. Measures of functional outcomes were also administered. RESULTS: Comparison of the two DBS targets revealed few significant group differences. STN DBS was associated with greater mean reductions on some measures of processing speed, only one of which was statistically significant in comparison with stimulation of GPi. GPi DBS was associated with lower mean performance on one measure of learning and memory that requires mental control and cognitive flexibility. Compared to the group receiving BMT, the combined DBS group had significantly greater mean reductions at 6-month follow-up in performance on multiple measures of processing speed and working memory. After calculating thresholds for statistically reliable change from data obtained from the BMT group, the combined DBS group also displayed higher rates of decline in neuropsychological test performance. Among study completers, 18 (11%) study participants receiving DBS displayed reliable decline by multiple indicators in two or more cognitive domains, a significantly higher rate than in the BMT group (3%). This multi-domain cognitive decline was associated with less beneficial change in subjective ratings of everyday functioning and quality of life (QOL). The multi-domain cognitive decline group continued to function at a lower level at 24-month follow-up. CONCLUSIONS: In those with PD, the likelihood of significant decline in neuropsychological functioning increases with DBS, affecting a small minority of patients who also appear to respond less optimally to DBS by other indicators of QOL. TRIAL REGISTRATION NUMBER: NCT00056563 and NCT01076452.

Cost of deep brain stimulation for the treatment of Parkinson's disease by surgical stimulation sites.

OBJECTIVE: To assess costs and effectiveness of deep brain stimulation (DBS) of the internal globus pallidum (GPi) versus subthalamic nucleus (STN) from the provider and societal perspectives for Parkinson's disease (PD) patients in a multicenter randomized trial. METHODS: All costs from randomization to 36 months were included. Costs were from Department of Veterans Affairs (VA) and Medicare databases and clinical trial data. Quality adjusted life years (QALYs) were from Quality of Well Being questionnaires. RESULTS: Provider costs were similar for the 144 GPi and 130 STN patients (GPi: $138,044 vs. STN: $131,822; difference = $6,222, 95% confidence interval [CI]: -$42,125 to $45,343). Societal costs were also similar (GPi: $171,061 vs. STN: $167,706; difference = $3,356, 95% CI: -$57,371 to $60,294). The GPi patients had nonsignificantly more QALYs. CONCLUSIONS: The QALYs and costs were similar; the level of uncertainty given the sample size suggests that these factors should not direct treatment or resource allocation decisions in selecting or making available either procedure for eligible PD patients.

Pallidal versus subthalamic deep-brain stimulation for Parkinson's disease.

BACKGROUND: Deep-brain stimulation is the surgical procedure of choice for patients with advanced Parkinson's disease. The globus pallidus interna and the subthalamic nucleus are accepted targets for this procedure. We compared 24-month outcomes for patients who had undergone bilateral stimulation of the globus pallidus interna (pallidal stimulation) or subthalamic nucleus (subthalamic stimulation). METHODS: At seven Veterans Affairs and six university hospitals, we randomly assigned 299 patients with idiopathic Parkinson's disease to undergo either pallidal stimulation (152 patients) or subthalamic stimulation (147 patients). The primary outcome was the change in motor function, as blindly assessed on the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III), while patients were receiving stimulation but not receiving antiparkinsonian medication. Secondary outcomes included self-reported function, quality of life, neurocognitive function, and adverse events. RESULTS: Mean changes in the primary outcome did not differ significantly between the two study groups (P=0.50). There was also no significant difference in self-reported function. Patients undergoing subthalamic stimulation required a lower dose of dopaminergic agents than did those undergoing pallidal stimulation (P=0.02). One component of processing speed (visuomotor) declined more after subthalamic stimulation than after pallidal stimulation (P=0.03). The level of depression worsened after subthalamic stimulation and improved after pallidal stimulation (P=0.02). Serious adverse events occurred in 51% of patients undergoing pallidal stimulation and in 56% of those undergoing subthalamic stimulation, with no significant between-group differences at 24 months. CONCLUSIONS: Patients with Parkinson's disease had similar improvement in motor function after either pallidal or subthalamic stimulation. Nonmotor factors may reasonably be included in the selection of surgical target for deep-brain stimulation. (ClinicalTrials.gov numbers, NCT00056563 and NCT01076452.)

Suicide ideation and behaviours after STN and GPi DBS surgery for Parkinson's disease: results from a randomised, controlled trial.

BACKGROUND: The risk of suicide behaviours post-deep brain stimulation (DBS) surgery in Parkinson's disease (PD) remains controversial. We assessed if suicide ideation and behaviours are more common in PD patients (1) randomised to DBS surgery versus best medical therapy (BMT); and (2) randomised to subthalamic nucleus (STN) versus globus pallidus interna (GPi) DBS surgery. METHODS: In Phase 1 of the Veterans Affairs CSP 468 study, 255 PD patients were randomised to DBS surgery (n=121) or 6 months of BMT (n=134). For Phase 2, a total of 299 patients were randomised to STN (n=147) or GPi (n=152) DBS surgery. Patients were assessed serially with the Unified Parkinson's Disease Rating Scale Part I depression item, which queries for suicide ideation; additionally, both suicide behaviour adverse event data and proxy symptoms of increased suicide risk from the Parkinson's Disease Questionnaire (PDQ-39) and the Short Form Health Survey (SF-36) were collected. RESULTS: In Phase 1, no suicide behaviours were reported, and new-onset suicide ideation was rare (1.9% for DBS vs 0.9% for BMT; Fisher's exact p=0.61). Proxy symptoms of relevance to suicide ideation were similar in the two groups. Rates of suicide ideation at 6 months were similar for patients randomised to STN versus GPi DBS (1.5% vs 0.7%; Fisher's exact p=0.61), but several proxy symptoms were worse in the STN group. CONCLUSIONS: Results from the randomised, controlled phase of a DBS surgery study in PD patients do not support a direct association between DBS surgery and an increased risk for suicide ideation and behaviours.

Predictors of multi-domain cognitive decline following DBS for treatment of Parkinson's disease.

BACKGROUND: Statistically and clinically significant cognitive declines are observed in a small subset of individuals with Parkinson's Disease (PD) following treatment with Deep Brain Stimulation (DBS). OBJECTIVES: We examine the association between multi-domain cognitive decline (MCD) and demographic and baseline clinical variables and the incidence of serious adverse events (SAE) arising within a six-month interval following DBS for PD. METHOD: Study participants with PD who displayed MCD at 6-month follow-up evaluation after DBS (n = 18) were contrasted with individuals with PD from the same study who did not show cognitive decline after DBS (n = 146). Logistic regression analyses were employed to assess relationship between predictors, including age (>70 years old), pre-DBS cognitive screening test performance, SAE, and MCD. MCD+ and MCD-groups were also compared on other baseline clinical and demographic variables. RESULTS: MCD showed modest association with older age and lower baseline neurocognitive screening performance, whereas the groups did not differ on most other baseline clinical and demographic variables. SAEs during the study interval were the most robust predictor of MCD in the DBS group. A variety of SAEs were documented in study participants experiencing MCD after DBS surgery, including, but not limited to, infections and small intracranial hemorrhages. CONCLUSIONS: Older age and lower baseline cognition measured prior to treatment are associated with MCD measured at six-months after DBS. SAE occurring following DBS surgery are also predictive of MCD. These predictors may reflect aspects of "frailty" in advanced PD. Risk factors for SAE warrant careful consideration in clinical trials.

Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial.

CONTEXT: Deep brain stimulation is an accepted treatment for advanced Parkinson disease (PD), although there are few randomized trials comparing treatments, and most studies exclude older patients. OBJECTIVE: To compare 6-month outcomes for patients with PD who received deep brain stimulation or best medical therapy. DESIGN, SETTING, AND PATIENTS: Randomized controlled trial of patients who received either deep brain stimulation or best medical therapy, stratified by study site and patient age (< 70 years vs > or = 70 years) at 7 Veterans Affairs and 6 university hospitals between May 2002 and October 2005. A total of 255 patients with PD (Hoehn and Yahr stage > or = 2 while not taking medications) were enrolled; 25% were aged 70 years or older. The final 6-month follow-up visit occurred in May 2006. INTERVENTION: Bilateral deep brain stimulation of the subthalamic nucleus (n = 60) or globus pallidus (n = 61). Patients receiving best medical therapy (n = 134) were actively managed by movement disorder neurologists. MAIN OUTCOME MEASURES: The primary outcome was time spent in the "on" state (good motor control with unimpeded motor function) without troubling dyskinesia, using motor diaries. Other outcomes included motor function, quality of life, neurocognitive function, and adverse events. RESULTS: Patients who received deep brain stimulation gained a mean of 4.6 h/d of on time without troubling dyskinesia compared with 0 h/d for patients who received best medical therapy (between group mean difference, 4.5 h/d [95% CI, 3.7-5.4 h/d]; P < .001). Motor function improved significantly (P < .001) with deep brain stimulation vs best medical therapy, such that 71% of deep brain stimulation patients and 32% of best medical therapy patients experienced clinically meaningful motor function improvements (> or = 5 points). Compared with the best medical therapy group, the deep brain stimulation group experienced significant improvements in the summary measure of quality of life and on 7 of 8 PD quality-of-life scores (P < .001). Neurocognitive testing revealed small decrements in some areas of information processing for patients receiving deep brain stimulation vs best medical therapy. At least 1 serious adverse event occurred in 49 deep brain stimulation patients and 15 best medical therapy patients (P < .001), including 39 adverse events related to the surgical procedure and 1 death secondary to cerebral hemorrhage. CONCLUSION: In this randomized controlled trial of patients with advanced PD, deep brain stimulation was more effective than best medical therapy in improving on time without troubling dyskinesias, motor function, and quality of life at 6 months, but was associated with an increased risk of serious adverse events. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00056563.

Healthcare Utilization and Costs for Patients With Parkinson's Disease After Deep Brain Stimulation.

OBJECTIVE: To compare the complications, healthcare utilization and costs following DBS or medical management for patients with Parkinson's disease (PD). METHODS: We examined healthcare utilization and costs for up to 5 years between veterans with DBS and those with medical management for PD. Veterans who received DBS between 2007 and 2013 were matched with veterans who received medical management using propensity score approaches. Healthcare utilization and costs were obtained from national VA and Medicare data sources and compared using procedures to adjust for potential differences in length of follow-up. RESULTS: We identified 611 veterans who had received DBS and a matched group of 611 veterans who did not undergo DBS. Among DBS patients, 59% had the electrodes and generator implanted during separate admissions. After 5 years of follow-up, average total healthcare costs, including DBS procedures and complications, were $77,131 (95% confidence interval: $66,095-$88,168; P < 0.001) higher per person for patients who received DBS ($162,489) than patients who received medical management ($85,358). In contrast, excluding the costs of the DBS procedures and complications, average total costs were not significantly different between patients who received DBS and patients who received medical management after 5 years of follow-up. CONCLUSIONS: Healthcare costs over 5 years were higher for veterans who received DBS. These higher healthcare costs may reflect the costs of DBS procedures and any follow-up required plus greater surveillance by healthcare professionals following DBS as well as unobserved differences in the patients who received medical management or DBS.

Comparing two randomized deep brain stimulation trials for Parkinson's disease.

OBJECTIVE: Several randomized studies have compared the effect of deep brain stimulation (DBS) of the subthalamic nucleus with the best medical treatment in large groups of patients. Important outcome measures differ between studies. Two such major studies, the life-quality study of the German Competence Network for Parkinson's disease (LQ study) and the US Veterans Affairs/National Institute of Neurological Disorders and Stroke trial (VA/NINDS trial), were compared here in order to understand their differences in outcomes. METHODS: Unless otherwise noted, analyses were based on those subjects in each study who received a DBS implant (LQ study 76 patients, VA/NINDS trial 140 patients) and who had data for the measurement under consideration (i.e., no imputations for missing data), referred to hereafter as the "as-treated completers" (LQ 69 patients, VA/NINDS 125 patients). Data were prepared and analyzed by biostatisticians at the US Department of Veterans Affairs Cooperative Studies Program Coordinating Center, the Coordinating Center for Clinical Trials Marburg, and Medtronic, under the direction of two authors (G.D. and K.A.F.). Data were extracted from the respective databases into SAS data sets and analyzed using SAS software. Analyses were based on the 6-month follow-up data from both studies because this was the endpoint for the LQ study. RESULTS: Pre-DBS baseline demographics differed significantly between the studies, including greater levodopa responsiveness (LDR) in the LQ study population than in the VA/NINDS group. After DBS, LQ subjects demonstrated greater improvement in motor function (Unified Parkinson's Disease Rating Scale, Motor Examination [UPDRS-III]), activities of daily living (ADLs), and complications of therapy. Medication reduction and improvements in life quality other than ADLs were not significantly different between LQ and VA/NINDS subjects. When the two populations were compared according to pre-DBS LDR, the "full responders" to levodopa (≥ 50% improvement on UPDRS-III with medication) in the two studies showed no significant difference in motor improvement with DBS (LQ 18.5 ± 12.0-point improvement on UPDRS-III vs VA/NINDS 17.7 ± 15.6-point improvement, p = 0.755). Among levodopa full responders, ADLs improved slightly more in the LQ group, but scores on other UPDRS subscales and the Parkinson's Disease Questionnaire-39 were not significantly different between the two studies. CONCLUSIONS: This comparison suggests that patient selection criteria, especially preoperative LDR, are the most important source of differences in motor outcomes and quality of life between the two studies.

Referring Service Effect on Muscle Biopsy Diagnosis and Management in Myopathy.

Introduction Requests for muscle biopsy for evaluation of myopathy originate from a variety of different specialties. It is unknown whether the specialty of the referring service affects the likelihood of diagnostic biopsy or the therapeutic usefulness of a biopsy. Methods We reviewed 106 consecutive muscle biopsies requested by healthcare providers in neurology, rheumatology, family medicine, oncology, and gastroenterology. We tested for an association between referring service and whether the biopsy yielded a definitive pathology result or provided therapeutically useful results. Results Half of the biopsies (49%) returned definitive pathology and 88% of the biopsies provided information that contributed to therapeutic decisions. The diagnostic yield for muscle biopsies referred by different services was not statistically significant (p-value 0.1344) nor was the therapeutic yield statistically significant for muscle biopsies referred by different services (p-value 0.5525). Discussion The specialty of the service that requests a muscle biopsy does not influence the likelihood of obtaining a definitive pathological diagnosis or therapeutically useful information. Other factors may be more important in determining the likelihood of obtaining a clinically useful biopsy result.

Association of Preoperative Diagnosis with Clinical Yield of Muscle Biopsy.

BACKGROUND: Muscle biopsy is a common diagnostic marker for myopathy assessment; however, it has a relatively low pathologic yield of less than 60%. Additionally, both diagnostic and non-diagnostic muscle biopsies can provide guidance for treatment, i.e, provide therapeutic usefulness. PURPOSE: We designed a study to determine if having a documented definitive preoperative differential diagnosis would affect the pathologic yield and therapeutic usefulness of muscle biopsies for myopathy.  Methods: This was a retrospective, single institution chart review of 106 consecutive muscle biopsies in adult patients, which looked at the presence or absence of a definitive preoperative differential diagnosis and relation to diagnostic yield and therapeutic usefulness of muscle biopsies.  Results: Of 106 muscle biopsies, 50 biopsies (47%) had a definitive preoperative differential diagnosis, 52 biopsies (49%) returned definitive pathology, and 93 biopsies (88%) provided therapeutic information. The presence of a documented differential diagnosis increased the odds of pathologic yield by 3.73 (p-value < 0.01) and therapeutic usefulness by 3.40 (p-value 0.08). If pathology was diagnostic then the therapeutic usefulness of the biopsy was 4.54 times more likely (p-value < 0.01).  Conclusion: Documentation of a definitive preoperative differential diagnosis, when pursuing muscle biopsy for myopathy, is associated with an increased pathologic diagnostic yield. Definitive pathology was associated with an increase in the therapeutic usefulness of the muscle biopsy.

Rates, causes, risk factors, and outcomes of readmission following deep brain stimulation for movement disorders: Analysis of the U.S. Nationwide Readmissions Database.

OBJECTIVE: Deep brain stimulation (DBS) surgery has proven benefit for several movement disorders and medically-refractory psychiatric conditions and is considered a fairly safe procedure. We sought to determine the national rates, causes, predictors, and outcomes associated with 30-day and 90-day readmission. PATIENTS AND METHODS: The Nationwide Readmissions Database was queried (January-September 2013) using ICD-9-CM codes, identifying patients who underwent DBS for movement disorder (Parkinson's disease [PD], essential tremor [ET], or dystonia). Variables included categorical age, gender, insurance, comorbidities, type of movement disorder, length of stay (LOS), total costs, and discharge disposition. RESULTS: A total of 3392 DBS patients were identified [PD (70.7%), ET (25.6%), dystonia (3.7%)]. The mean age was 64.8 ±â€¯0.4 years old and 37% were female. The rates of unplanned readmissions was 1.9% at 30-days and 4.3% at 90 days. The overall NRD incidence (all patient populations) of 30-day readmission is 11.6%. Readmissions most frequently resulted from surgical complications including hematoma and attention to surgical wounds. Elderly, obese, and those with comorbidities such as history of stroke or CAD are at highest risk. The average LOS, mean total cost, and rate of adverse discharge were worse for 30-day (9 days, $64,520, 71.7%) compared to 90-day readmission (6 days, $52,183, 56.5%). CONCLUSION: All-cause, unplanned readmission for DBS was 1.9% within 30-days and 4.3% within 90-days. Risk factors for readmission in our study, such as advanced age and multiple medical comorbidities, are not unique to DBS. Unplanned readmissions are much rarer following DBS compared to most hospital discharges but can occasionally lead to additional costs and rare complications including hematoma, stroke, and wound infection. DBS should continue to be viewed as a safe and effective treatment modality for a wide range of neurological ailments.

Deep brain stimulation in Parkinson disease: a metaanalysis of patient outcomes.

OBJECT: Deep brain stimulation (DBS) to treat advanced Parkinson disease (PD) has been focused on one of two anatomical targets: the subthalamic nucleus (STN) and the globus pallidus internus (GPI). Authors of more than 65 articles have reported on bilateral DBS outcomes. With one exception, these studies involved pre- and postintervention comparisons of a single target. Despite the paucity of data directly comparing STN and GPI DBS, many clinicians already consider the STN to be the preferred target site. In this study the authors conducted a metaanalysis of the existing literature on patient outcomes following DBS of the STN and the GPI. METHODS: This metaanalysis includes 31 STN and 14 GPI studies. Motor function improved significantly following stimulation (54% in patients whose STN was targeted and 40% in those whose GPI was stimulated), with effect sizes (ESs) of 2.59 and 2.04, respectively. After controlling for participant and study characteristics, patients who had undergone either STN or GPI DBS experienced comparable improved motor function following surgery (p = 0.094). The performance of activities of daily living improved significantly in patients with either target (40%). Medication requirements were significantly reduced following stimulation of the STN (ES = 1.51) but did not change when the GPI was stimulated (ES = -0.02). CONCLUSIONS: In this analysis the authors highlight the need for uniform, detailed reporting of comprehensive motor and nonmotor DBS outcomes at multiple time points and for a randomized trial of bilateral STN and GPI DBS.

Biomechanical studies of an artificial disc implant in the human cadaveric spine.

OBJECT: The authors compared the biomechanical performance of the human cadaveric spine implanted with a metallic ball-and-cup artificial disc at L4-5 with the spine's intact state and after anterior discectomy. METHODS: Seven human L2-S1 cadaveric spines were mounted on a biomechanical testing frame. Pure moments of 0, 1.5, 3.0, 4.5, and 6.0 Nm were applied to the spine at L-2 in six degrees of motion (flexion, extension, right and left lateral bending, and right and left axial rotation). The spines were tested in the intact state as well as after anterior L4-5 discectomy. The Maverick disc was implanted in the discectomy defect, and load testing was repeated. The artificial disc created greater rigidity for the spine than was present after discectomy, and the spine performed biomechanically in a manner comparable with the intact state. CONCLUSIONS: The results indicate that in an in vitro setting, this model of artificial disc stabilizes the spine after discectomy, restoring motion comparable with that of the intact state.

Response of intractable pain to continuous intrathecal morphine: a retrospective study.

We have treated 37 patients with intractable pain (35 with cancer-related pain) by continuous intrathecal morphine infusion via implanted pump. These patients were carefully selected according to specific criteria, and each demonstrated a significant reduction in pain following a test dose of intrathecal morphine. All patients had good pain relief from intrathecal morphine infusion, even with pain located in cervical dermatomes. Systemic narcotics could be withdrawn from most patients. Significant side effects were rare and typically self-limited. Many patients required gradually increasing doses, seemingly related to disease progression. Two patients with non-malignant pain have had variable dose requirements over 28 and 44 months without clear tolerance. In these patients we observed a reduction in side effects associated with systemic opioids when continuous intrathecal opioid infusion was instituted. Intrathecal opioid administration may have fewer complications than ablative pain relief procedures. In properly selected patients, this method offers an effective alternative for pain relief.

Electrical stimulation of thalamic Nucleus Submedius inhibits responses of spinal dorsal horn neurons to colorectal distension in the rat.

In 78 halothane-anesthetized rats, we characterized the responses of single neurons in the dorsal horn of L(6)-S(1) spinal segments to a noxious visceral stimulus (colorectal balloon distension, CRD), and studied the effects of focal electrical stimulation of Nucleus Submedius (Sm) on these responses using standard extracellular microelectrode recording techniques. A total of 102 neurons were isolated on the basis of spontaneous activity. Eighty (78%) responded to CRD, of which 70% had excitatory and 30% had inhibitory responses. Neurons showed graded responses to graded CRD pressures (20-100 mmHg), with maximum excitation or inhibition occurring at 100 mmHg. Responses to noxious (pinch, heat) and innocuous (brush, tap) cutaneous stimuli were studied in 73 of the spinal dorsal horn neurons isolated. Fifty-seven (78%) of these neurons (46 CRD-responsive and 11 CRD-nonresponsive) had cutaneous receptive fields, of which 35 (61%) were small and ipsilateral, 14 (25%) were large and ipsilateral, 7 (12%) were large or small and bilateral, and 1 (2%) was small and contralateral. Sixty-one percent of these neurons responded to both noxious and innocuous cutaneous stimulation, 35% responded only to noxious stimulation, and 4% responded only to innocuous stimulation. Electrical stimulation (50-300 microA) of the contralateral Sm produced intensity-dependent attenuation of the CRD-evoked activities of most neurons (18/28 of CRD-excited and 7/12 of CRD-inhibited) tested. Sm stimulation produced facilitation of CRD responses of only one neuron (CRD-inhibited). Sm stimulation had no effects on spontaneous activity. These data indicate that Sm may be involved in the descending inhibitory modulation of visceral nociception at the spinal level.

Long-term outcomes during treatment of chronic pain with intrathecal clonidine or clonidine/opioid combinations.

To evaluate the effectiveness of intrathecal clonidine or clonidine/opioid admixture for the treatment of chronic pain states, a retrospective chart audit of 15 patients seen by the Pain Medicine and Neurosurgical Services was performed. Subjects included 9 men and 6 women aged 26-86 years. Diagnoses included complex regional pain syndrome, neuropathic pain, and cancer pain. All patients received a trial of single-shot and/or short-term infusion of clonidine. Those reporting a significant reduction in pain, or at least 50% reduction in their visual analog scale (VAS), received long-term therapy. Intrathecal clonidine as a single-shot dose, infusion, or as intrathecal polytherapy did not improve VAS scales from pre-treatment values in 5 patients. Ten patients reported significant pain relief or >50% decrease in VAS scores with the initial trial and received long-term therapy. Two received clonidine alone for 7-11 months before the therapy failed; others failed after just a few days. Seven of eight initially responded to clonidine alone (75-950 microg/day) before failing and requiring a second drug. Three received hydromorphone (200-8000 microg/day) and four morphine (0.15-15 mg/day) with clonidine. Four patients then failed 2-drug therapy (duration 6-21 months). Two continue with intrathecal clonidine/hydromorphone (duration 19-29 months) and 1 with clonidine/morphine (duration 21 months). After initiation of intrathecal clonidine, one patient reported good relief with clonidine/morphine until his death 5 months later. In this population, intrathecal clonidine was of limited utility for most patients. It may be of benefit for subset(s) of patients, but in our experience, duration of relief is typically <18 months.