Intrathecal baclofen for dystonia of complex regional pain syndrome.

Dystonia in complex regional pain syndrome (CRPS) responds poorly to treatment. Intrathecal baclofen (ITB) may improve this type of dystonia, but information on its efficacy and safety is limited. A single-blind, placebo-run-in, dose-escalation study was carried out in 42 CRPS patients to evaluate whether dystonia responds to ITB. Thirty-six of the 38 patients, who met the responder criteria received a pump for continuous ITB administration, and were followed up for 12 months to assess long-term efficacy and safety (open-label study). Primary outcome measures were global dystonia severity (both studies) and dystonia-related functional limitations (open-label study). The dose-escalation study showed a dose-effect of baclofen on dystonia severity in 31 patients in doses up to 450 microg/day. One patient did not respond to treatment in the dose-escalation study and three patients dropped out. Thirty-six patients entered the open-label study. Intention-to-treat analysis revealed a substantial improvement in patient and assessor-rated dystonia scores, pain, disability and quality-of-life (Qol) at 12 months. The response in the dose-escalation study did not predict the response to ITB in the open-label study. Eighty-nine adverse events occurred in 26 patients and were related to baclofen (n=19), pump/catheter system defects (n=52), or could not be specified (n=18). The pump was explanted in six patients during the follow-up phase. Dystonia, pain, disability and Qol all improved on ITB and remained efficacious over a period of one year. However, ITB is associated with a high complication rate in this patient group, and methods to improve patient selection and catheter-pump integrity are warranted.

Diagnostic criteria used in studies of reflex sympathetic dystrophy.

OBJECTIVE: Assessment of the diagnostic criteria of reflex sympathetic dystrophy (RSD) and evaluation of the impact of the introduction of the diagnostic criteria of complex regional pain syndrome (CRPS) on the international application of diagnostic criteria of RSD. METHODS: Randomized controlled trials and clinical investigations, published between January 1980 and June 2000, were evaluated with regard to the applied diagnostic criteria of RSD. RESULTS: One hundred seven studies were identified. Thirty-four of these studies were excluded because of inadequate reporting of diagnostic criteria. The 73 included studies were not homogeneous with regard to the diagnostic criteria because they applied many different aspects of sensory and autonomic features. Only 12% of the studies considered the presence of motor features, mostly vaguely described, as mandatory for the diagnosis RSD. Although 10 of the 23 studies published since the introduction of CRPS have applied this term, only 3 used the exact criteria without additions or other modifications. CONCLUSION: Diagnostic criteria sets of RSD focus on many different aspects of sensory and autonomic features that generally are described vaguely. This has not changed since the introduction of the CPRS criteria. These findings question whether the current criteria adequately define RSD.

Intrathecal baclofen for the treatment of dystonia in patients with reflex sympathetic dystrophy.

BACKGROUND AND METHODS: Patients with reflex sympathetic dystrophy (also known as the complex regional pain syndrome) may have dystonia, which is often unresponsive to treatment. Some forms of dystonia respond to the intrathecal administration of baclofen, a specific gamma-aminobutyric acid-receptor (type B) agonist that inhibits sensory input to the neurons of the spinal cord. We evaluated this treatment in seven women who had reflex sympathetic dystrophy with multifocal or generalized tonic dystonia. First, we performed a double-blind, randomized, controlled crossover trial of bolus intrathecal injections of 25, 50, and 75 microg of baclofen and placebo. Changes in the severity of dystonia were assessed by the woman and by an investigator after each injection. In the second phase of the study, six of the women received a subcutaneous pump for continuous intrathecal administration of baclofen and were followed for 0.5 to 3 years. RESULTS: In six women, bolus injections of 50 and 75 microg of baclofen resulted in complete or partial resolution of focal dystonia of the hands but little improvement in dystonia of the legs. During continuous therapy, three women regained normal hand function, and two of these three women regained the ability to walk (one only indoors). In one woman who received continuous therapy, the pain and violent jerks disappeared and the dystonic posturing of the arm decreased. In two women the spasms or restlessness of the legs decreased, without any change in the dystonia. CONCLUSIONS: In some patients, the dystonia associated with reflex sympathetic dystrophy responds markedly to intrathecal baclofen.

Clinimetric issues of screening for responsiveness to intrathecal baclofen in dystonia.

OBJECTIVES: In this study we address clinimetric issues that pertain to the screening of responsiveness to intrathecal baclofen (ITB) in dystonia. METHODS: Eight patients with severe dystonia, who did not respond to oral medication, were evaluated in a double-blind placebo controlled ascending dose screening procedure, which included a randomised sequence of injections of 25, 50 and 75 microg baclofen and placebo. Self-assessments of dystonia severity on a visual analogue scale (VAS) and the Dyskinesia Rating Scale (DRS) were carried out at baseline 1, 4 and 8 hours after a bolus injection. RESULTS: Compared to the VAS, the DRS lacked responsiveness in all patients. Baseline scores of the VAS scores varied considerably between and within patients and underscore the need to express response scores in relation to the baseline. After placebo administration some patients showed a persistent improvement of about 30% across the day, while at some assessments improvements of >50% were noted. Based on the aforementioned findings, a responsiveness coefficient was used which relates the baclofen effect size to the non-specific score changes that may occur as a placebo effect or as random fluctuations in dystonia. Four patients with a responsiveness coefficient >2 received pump implantation and did well on continuous infusion of ITB. Several side effects occurred during the screening procedure, but none interfered with the execution of the screening procedure. CONCLUSIONS: This study demonstrates important clinimetric issues that need to be taken into account when screening for responsiveness to ITB.

Extradural and subarachnoid catheterization using the Seldinger technique.

The Seldinger technique was developed using a plastic introducer through which introduction and manipulations of a silicone spinal catheter, an extradural stimulation lead or a small diameter fibreoptic scope are possible without the risk of damage to the vulnerable devices. It is not intended as a replacement of the standard technique of introducing a spinal catheter through a Tuohy needle in general anaesthetic practice. Silicone spinal catheters and stimulation leads are used for long-term therapy in intractable chronic pain and spasticity. A fibreoptic scope is used for endoscopic examination of the subarachnoid or extradural space. Using a standard Tuohy needle the soft silicone extradural lead can be damaged easily by manipulations during insertion. For this reason the manufacturer modified the Tuohy needle for extradural silicone lead introduction. The disadvantages of this modified Tuohy needle are: first, difficulty in localization of the extradural space, second, the needle is unsuitable for a subarachnoid catheter or introduction of a fibreoptic scope. The Seldinger technique was performed 25 times in 18 patients, introducing a spinal silicone catheter (n = 14), an extradural silicone stimulation lead (n = 2) or a small diameter fibreoptic endoscope (n = 9). Paraesthesiae caused by neural irritation occurred in awake patients. This did not differ from the technique using a Tuohy needle only. Neural damage or trauma did not occur with the Seldinger technique. The incidence of post-spinal headache was the same for both techniques. No further complications were noted.

Pregnancy in a quadriplegic patient treated with continuous intrathecal baclofen infusion to manage her severe spasticity. Case report.

A report on pregnancy in a quadriplegic patient treated with a high dose of 1000 mcg/24 h continuous intrathecal baclofen infusion using an implanted drug delivery system (Synchromed, Medtronic, USA). Spasticity could be managed up to the 35th week of gestation. However, uterine contractions evoke enormous spastic symptoms which we, even with maximum values of the spasticity scales, could not classify. The recurrence of spasticity was associated with autonomic dysregulation. With continuous epidurally infused bupivacaine (11.25 mg/h) adequate relaxation could be reached and gestation was terminated by a primary caesarean section. A healthy girl was born (2040 g, Apgar 9 and 10).

Technical complications during long-term subarachnoid or epidural administration of morphine in terminally ill cancer patients: a review of 140 cases.

The type and incidence of technical complications (e.g., obstruction and dislocation of the catheter and infection) in long-term (ten to 366 days) spinal morphine administration in terminally ill cancer patients by means of an epidural or subarachnoid catheter are presented. Total treatment time was 8650 days, of which patients spent 6175 at home. Portable external mini infusion pumps were used with satisfactory results in 15 patients of the epidural group (n = 110) and in all patients receiving subarachnoid morphine (n = 30). In the other 95 patients of the epidural group, intermittent bolus injections were used. During the first 20 days of treatment, a significant difference (chi-square test, p = 0.02) in the incidence of complications was observed between the epidural group (8%) and the subarachnoid group (25%). During the remainder of the treatment period the complication rate rose to 55% in patients receiving epidural morphine and declined to 5% in the subarachnoid group, a significant difference (chi-square test, p = 0.001). The most frequent complication in the epidural group was obstruction and dislocation of the catheter, probably due to the development of epidural fibrosis. This problem became apparent in 50% of patients during the treatment period from Day 20 to 366. In patients receiving subarachnoid morphine, the prevalent complication was CSF leakage, which was observed only during the first two weeks of treatment. The subarachnoid route is preferred for patients expected to live longer than one month. For patients with a shorter life expectancy, epidural administration can yield acceptable results.

Intrathecal baclofen overdose: report of 7 events in 5 patients and review of the literature.

This study is intended to alert the clinician to the insidious symptoms of baclofen overdose, its prevention and treatment. In a group of 43 patients suffering from previously intractable spasticity and a total treatment time of 2,422 weeks, 7 events of intrathecal baclofen overdose happened in 5 patients. On two occasions, a bolus injection caused an overdose (dose 50 and 280 micrograms). The 5 events during continuous infusion intoxication only happened in high dosed patients. The overdose symptoms occurred in one patient when she was lying in supine position (800 micrograms/24 h), in another patient after repair of CSF leakage by an autologous epidural bloodpatch (1,920 micrograms/24 h) and in tolerant patients, once during maximal dose adjustments (2,400 micrograms/24 h) and twice ca. 6 hours following reinitiation of the intrathecal baclofen infusion after a "drug holiday" treatment (27 and 55 micrograms/h). We could not confirm the reported similarity of baclofen overdose with the anticholinergic syndrome. Especially, the bradycardia and hypotension are more in accord with the reported clinical picture of oral baclofen overdose. In the absence of a pure baclofen antagonist and the varying symptoms of intrathecal baclofen, intoxication make rational treatment difficult. We observed that the advised physostigmine therapy is not always effective and safe. The occasionally doubtful antidotal benefits of physostigmine must be weighted against major side-effects. The classical approach of decreasing the absorption of a drug by lowering baclofen levels in the CSF by lumbar puncture drainage was successful. This approach together with conservative symptomatic treatment in an intensive care environment is probably a better and safer alternative than physostigmine alone as an antidote.