The incidence and management of tolerance in intrathecal baclofen therapy.

STUDY DESIGN: Retrospective study. OBJECTIVES: To study the incidence and management of tolerance in patients treated with intrathecal baclofen (ITB) therapy. SETTING: Department of neurology and neurosurgery, University Medical Center Groningen, The Netherlands. METHODS: Medical records of all patients who had received an implantable ITB pump at our clinic during 1991-2005 were reviewed. RESULTS: A total of 37 patients (representing 116 pump years) were included. Mean follow-up time was 38 months (range 3-120 months). Baclofen dose increased in the first 18 months after implantation (P<0.05), and then stabilized around a mean dose of 350 microg per day. Eight patients (22%) developed tolerance, defined as a dose increase of >100 microg per year. No predictive factors for development of tolerance could be determined. Three different treatment regimens for tolerant patients were analyzed. Altering the infusion mode from simple to complex continuous (n=6) had no effect on the development of tolerance. Pulsatile bolus infusion (n=1) and a drug holiday (n=2) were both effective in reducing the daily baclofen dose. Patients who needed surgical revision of the pump system because of mechanical failures (n=11) showed a significant dose decrease during the first month after revision, indicating that the preoperative dose increase most likely had been caused by the pump failure. Pump-related complications occurred once per 10.5 years of ITB treatment. Drug-related side effects had an annual risk of 13.8%. The reported events were mostly mild. CONCLUSIONS: ITB therapy is effective and safe, also in the long term and causes tolerance in only 22% of the treated patients.

Intraoperative neurophysiological assessment of disabling symptoms in DBS surgery.

INTRODUCTION: Neurophysiological assessment can provide quantitative measures for the selected motor signs that have been targeted for surgery and may be helpful in predicting the therapeutic effects of deep brain stimulation (DBS) on pathological tremor, motor performance, and rigidity. OBJECTIVE: To present a survey and demonstrate the contribution of neurophysiological assessment of side effects and effects on disabling motor symptoms at various steps of DBS surgery, and to confirm its role for optimal target localization, as an adjuvant to anatomic imaging. MATERIAL AND METHODS: The data result from 192 nuclei in 118 procedures on patients with Parkinson's disease (84), essential tremor (24), Hallenvorder Spatz dystonia (4), multiple sclerosis (4), and Holmes tremor (2). The intraoperative neurophysiological monitoring (IOM) protocol consists of semimicroelectrode recording (for subthalamic nuclei), whereas accelerotransducers and spectral analysis allow assessment of tremor, finger tapping (FT), diadochokinesis (DDK), and determination of the distance between DBS electrodes and internal capsule (IC). Rigidity is assessed by surface EMG recordings in combination with a goniometer. RESULTS: The determination of the functional distance between the DBS electrode and the IC is based on the activation functions of axons in the IC. We show the high sensitivity of accelerometers for tremor over a large part of the body, the relationship between clinical scores and spectral frequencies of FT and DDK. Parkinsonian rigidity can be assessed from surface EMG (sEMG) by means of a balance coefficient, which can detect negative rigidity, for low unified Parkinson's disease rating scale (UPDRS) scores (0-2) and quantified EMG when negative rigidity is excluded. CONCLUSION: Accelerometer and sEMG recording have shown their value for intraoperative assessment of disabling motor symptoms and side effects during surgery, to optimize the target position electrodes for DBS. The combination with contemporary signal analyzing techniques permit intraoperative monitoring without a significant delay. IONM improves sensitivity and adds objective neurophysiological data.

Cost analysis of the treatment of severe spinal spasticity with a continuous intrathecal baclofen infusion system.

OBJECTIVE: The purpose of our study was to analyse and evaluate the costs of continuous intrathecal baclofen administration as a modality in the treatment of severe spasticity in the Netherlands. DESIGN: A cost analysis was conducted as part of a prospective, multicentre, multidisciplinary, randomised and placebo-controlled clinical trial. The study covered the period from December 1991 to September 1995. The data on medical consumption and costs were collected over a 3-year period from different sources: administrative databases of health insurance companies, hospital registries and a patient survey. These data were structured by means of a flowchart analysis of the medical decision-making by specialists and general practitioners (GPs). They included data on in- and outpatient care, home care and care in nursing homes. The cost analysis was conducted using data from 18 patients included in the trial and from 15 so-called 'match' patients. The latter group are patients with comparable diseases leading to spasticity and living in comparable circumstances. Next to absolute costs (direct and indirect) of care and treatment for the 2 groups of patients, cost differences between the 2 groups were considered (differential cost analysis). SETTING: Per patient cost data, collected prospectively for 2 years during the phase of clinical evaluation, and retrospectively 1 year before implantation. The data were collected on patients from in- and outpatient care, home care and care in nursing home settings. PATIENTS AND PARTICIPANTS: The trial patients (8 men) had a mean age of 46 years; 11 patients had multiple sclerosis and 7 patients had spinal cord injuries. The match patients (7 men) had a mean age of 48 years; 9 patients had multiple sclerosis and 6 patients had spinal cord injuries. INTERVENTIONS: Trial patients were treated with a subcutaneously implanted programmable continuous infusion pump (SynchroMed, Medtronic), filled with baclofen (a muscle relaxant) to treat patients with chronic disabling spasticity who did not respond to a maximum dose of oral baclofen, dantrolene and tizanidine. MAIN OUTCOME MEASURES AND RESULTS: An analysis of hospital stay between both groups showed a significant difference during the implantation year. The average number of hospital days per patient in the year in the treated group was 31.5 days and in the match group was 18.7 days. Significant cost differences between both groups in the year that started with pump implantation and the following year can be attributed mostly to the costs of implantation of the pump and related hospitalisation days. The total costs of patient selection, testing, implanting the pump and follow-up amounted to $US28,473 for the first year. Savings must be taken into consideration as well. The savings of direct costs were due to withdrawal of oral medication (estimated annual total of between $US1950 and $US2800 per patient). Indirect savings on employment and nursing home costs, amounted annually to $US1047 and $US5814, respectively. Scenarios make it possible to consider policy consequences. The case of 'extending' the indications for this treatment to a larger population has been calculated and visualised. CONCLUSIONS: The costs of the therapy (continuous intrathecal infusion of baclofen) can be attributed mostly to implantation of the pump and related hospitalisation days. Savings originated from withdrawal of oral medication, job preservation and avoidance or delay of admission to a nursing home.

Spinal cord stimulation in chronic pain syndromes.

Spinal cord stimulation (SCS) has been used for more than 30 years now, and although it has shown to be effective under certain well-described conditions of chronic pain, conclusive evidence on its effectiveness is still sparse. There is a need for more prospective and methodological good studies, in order to prove SCS efficacy for new or still questionable indications and to reveal prognostic factors for successful application. Especially at this moment, when governments are trying to control and reduce their health care expenses, studies on the cost-effectiveness of SCS are important. In contrast to the early years when SCS was applied by independent physicians exploring the field of neurostimulation, the importance of information exchange and coordination of studies has now been recognized. Recent technical improvements of SCS devices may positively influence clinical outcome.

Effects of spinal cord stimulation on myocardial ischaemia during daily life in patients with severe coronary artery disease. A prospective ambulatory electrocardiographic study.

BACKGROUND: Spinal cord stimulation (SCS) may be a useful additional therapy for pain in patients with therapeutically refractory angina pectoris. But doubts remain about whether it also relieves ischaemia. METHODS: Indices of ischaemia were studied with and without SCS in 10 patients with otherwise intractable angina and evidence of myocardial ischaemia on 48 h ambulatory electrocardiographic (ECG) recording. Primary end points assessed by 48 h ECG recordings were total ischaemic burden, number of ischaemic episodes, and duration of ischaemic episodes. In addition, symptoms were assessed by a diary of glyceryl trinitrate intake and angina attacks. RESULTS: During SCS the total ischaemic burden of the entire group was significantly reduced from a median of 27.9 (1.9-278.2) before SCS to 0 (0-70.2) mm x min with SCS (p < 0.03). In six out of the 10 patients there was no myocardial ischaemia during 48 h ambulatory ECG monitoring with SCS. The number of ischaemic episodes was reduced from a median of 3 (1-15) before SCS to 0 (0-9) with SCS (p < 0.04). The duration of ischaemic episodes decreased from a median of 20.6 (1.7-155.4) min before SCS to 0 (0-48.3) min with SCS (p < 0.03). This was accompanied by a significant improvement in symptoms with a reduction in daily glyceryl trinitrate intake from a median of 3.0 (0-10) before SCS to 0.3 (0-10) tablets per 48 h (p < 0.02) and a decrease in the frequency of anginal attacks from a median of 5.5 (2-14) before SCS to 1.0 (0-10) per 48 h with SCS (p < 0.03). CONCLUSIONS: SCS not only reduced symptoms but also myocardial ischaemia. Therefore, SCS appears to be both a safe and an effective therapy for patients with refractory angina.