Multicentre European study of thalamic stimulation for parkinsonian tremor: a 6 year follow-up.

AIM: To evaluate the results of ventral intermediate (Vim) thalamic deep brain stimulation (DBS) in patients with tremor predominant Parkinson's disease (PD) at 6 years post surgery. METHODS: This was a prolonged follow-up study of 38 patients from eight centres who participated in a multicentre study, the 1 year results of which have been published previously. Total scores as well as scores for individual items of the motor part and the disability part of the Unified Parkinson's Disease Rating Scale were used for evaluation. RESULTS: Tremor was still effectively controlled by DBS and appendicular rigidity and akinesia remained stable compared with baseline. Axial scores (speech, gait and postural instability), however, worsened, and in parallel the initial improvement in activities of daily living scores at the 1 year follow-up had disappeared at 6 years, despite sustained improvement of tremor. Remarkably, neither daily doses of dopaminergic medication nor fluctuations and dyskinesias had changed at 6 years compared with baseline in this particular patient group. CONCLUSION: This study confirms that patients with tremor dominant PD who do not present with fluctuations and dyskinesias may have a relatively benign progression of the disease. Vim DBS, although having no effect on akinesia and rigidity, is a relatively lenient surgical procedure and may still have a place for long term symptomatic control of PD tremor in selected patients.

[Spinal cord stimulation in angina pectoris--what is the current situation?]. / Ryggmärgsstimulering vid angina--var står vi idag?

Spinal cord stimulation has been used to treat intractable angina pectoris since 1985 with good results. Several studies have shown the treatment to yield both anti-anginal and antiischaemic effects. The mechanisms underlying these effects have been investigated in a number of studies, but remain unclear. In a recent randomised prospective study, where spinal cord stimulation was compared to coronary artery bypass surgery, both treatments yielded adequate relief of symptoms, and there was no subgroup difference in this respect. The article consists in a review of current trends in this field.

Evaluation of refractory epilepsy treated with vagus nerve stimulation for up to 5 years.

We assessed the long-term efficacy of vagus nerve stimulation (VNS) in 64 refractory epilepsy patients. After implantation, intermittent stimulation was delivered and seizure frequency and severity were counted. Average treatment time was 20 months. Nineteen of 47 patients with partial seizures, five of nine patients with idiopathic generalized seizures, and five of eight patients with Lennox-Gastaut syndrome had >50% seizure reduction. Side effects were mild. VNS is a safe and effective treatment for refractory epilepsy.

Effects of spinal cord stimulation on coronary blood flow velocity.

BACKGROUND: Spinal cord stimulation (SCS) has been used in the treatment of severe angina pectoris since the 1980s. Several studies have shown both an antianginal and an anti-ischaemic effect. There are several theories about the mechanism behind the anti-ischaemic effect of SCS, including the possibility that it is dependent on an increase in coronary flow velocity. OBJECTIVE: To determine if there were effects of SCS on coronary flow velocity during cardiac stress. METHOD: Eight patients with severe anginal pain secondary to coronary artery disease who had been implanted with an SCS device were included in the study. In addition, four patients with syndrome X were examined. If possible, a Doppler guidewire was placed in the vessel corresponding to the ischaemic area revealed on a prior myocardial scintigram. A temporary pacemaker electrode was placed in the right atrium. Atrial pacing started at 80 beats/min and increased by 10 beats/min every 2 min until the patient experienced moderate angina; the pacing frequency was then maintained at the same level. After 2 min of pacing at this frequency, SCS treatment commenced; after a further 5 min, pacing was stopped. Throughout the procedure, coronary flow velocity, assessed as average peak velocity (APV), was monitored continually. RESULTS: APV increased during pacing in all the patients with coronary artery disease (mean increase 53%; P < 0.02). There were no significant changes in APV during maximum pacing frequency when stimulation was introduced. CONCLUSIONS: The results of this study do not support the theory that the anti-ischaemic effect of SCS is dependent on an increase in coronary flow velocity.

Myocardial turnover of endogenous opioids and calcitonin-gene-related peptide in the human heart and the effects of spinal cord stimulation on pacing-induced angina pectoris.

Earlier studies have shown that spinal cord stimulation (SCS) has antianginal and anti-ischemic effects in severe coronary artery disease. In the present study, 14 patients were subjected to right-sided atrial catheterization and atrial pacing. The patients were paced to angina during a control session and during spinal cord stimulation. Myocardial extraction of beta-endorphin (BE) during control pacing (8 +/- 22%) changed to release at the maximum pacing rate during treatment (-21 +/- 47%, a negative value representing release). Furthermore, the results indicate local myocardial turnover of leuenkephalin, BE and calcitonin-gene-related peptide. In addition, it is implied that SCS may induce myocardial release of BE which could explain the beneficial effects in myocardial ischemia.

Electrical stimulation versus coronary artery bypass surgery in severe angina pectoris: the ESBY study.

BACKGROUND: Spinal cord stimulation (SCS) has been shown to have antianginal and anti-ischemic effects in severe angina pectoris. The present study was performed to investigate whether SCS can be used as an alternative to coronary artery bypass grafting (CABG) in selected patient groups, ie, patients with no proven prognostic benefit from CABG and with an increased surgical risk. METHODS AND RESULTS: One hundred four patients were randomized (SCS, 53; CABG, 51). The patients were assessed with respect to symptoms, exercise capacity, ischemic ECG changes during exercise, rate-pressure product, mortality, and cardiovascular morbidity before and 6 months after the operation. Both groups had adequate symptom relief (P<.0001), and there was no difference between SCS and CABG. The CABG group had an increase in exercise capacity (P=.02), less ST-segment depression on maximum (P=.005) and comparable (P=.0009) workloads, and an increase in the rate-pressure product both at maximum (P=.0003) and comparable (P=.03) workloads compared with the SCS group. Eight deaths occurred during the follow-up period, 7 in the CABG group and 1 in the SCS group. On an intention-to-treat basis, the mortality rate was lower in the SCS group (P=.02). Cerebrovascular morbidity was also lower in the SCS group (P=.03). CONCLUSIONS: CABG and SCS appear to be equivalent methods in terms of symptom relief in this group of patients. Effects on ischemia, morbidity, and mortality should be considered in the choice of treatment method. Taking all factors into account, it seems reasonable to conclude that SCS may be a therapeutic alternative for patients with an increased risk of surgical complications.

Intracerebroventricular administration of GM1 ganglioside to presenile Alzheimer patients.

We have conducted a preliminary study of the optimum conditions for a therapeutic effect of ganglioside GM1 in Alzheimer's disease. Five patients with the early onset form of Alzheimer's disease (AD type I) received the ganglioside by intracerebroventricular administration for 12 months. Bilateral stereotactic punction of the frontal horns of the ventricular system was performed, and shunt catheters were implanted and connected to a programmable pump. The optimum GM1 dose varied between 20 and 30 mg/24 h. Neurological neuropsychological, psychiatric and neurochemical examinations were performed 7 days before surgery and on days 30, 90, 180 and 360. No patient found the surgery difficult and no patient or relative regretted that they participated in the study. The patients became more active and safer in relation to others and to performance of various activities from day 90. The cerebrospinal fluid level of the monoamine metabolites homovanillic acid and 5-hydroxyindoleacetic acid and the neuropeptide somatostatin increased.

Effects of pacing-induced myocardial stress and spinal cord stimulation on whole body and cardiac norepinephrine spillover.

AIMS: Spinal cord stimulation has been used in the treatment of intractable angina pectoris since the beginning of the 1980s. This study was designed to investigate whether the documented anti-ischaemic effects of spinal cord stimulation are mediated through a decrease in sympathetic activity. METHODS AND RESULTS: Ten patients with a spinal cord stimulator implanted as anti-anginal treatment were included in the study. Atrial pacing until the patient experienced moderate angina was performed and after 50 min rest the procedure was repeated during spinal cord stimulation. Total body and cardiac norepinephrine spillover was calculated and the former was found to have increased during pacing (47%, P = 0.02). When spinal cord stimulation was applied, total body norepinephrine spillover decreased at a comparable pacing rate (18%, P = 0.02). Cardiac norepinephrine spillover was not affected during the procedure. CONCLUSION: The results of this study indicate that the anti-ischaemic effect of spinal cord stimulation is not due to reduced cardiac sympathetic activity. However, spinal cord stimulation decreases overall sympathetic activity which may benefit the heart, possibly by reducing oxygen demand.

Effects of spinal cord stimulation (SCS) in patients with inoperable severe lower limb ischaemia: a prospective randomised controlled study.

OBJECTIVES: This study was designed to test the hypothesis that spinal cord stimulation (SCS) improves limb salvage in patients with inoperable severe leg ischaemia. DESIGN: Prospective randomised controlled study with 18 months follow-up. SETTING: Vascular surgical units in two university hospitals. MATERIALS: Atherosclerotic (n = 41) and diabetic (n = 10) patients having chronic leg ischaemia with rest pain and/or ischaemic ulcerations due to technically inoperable arterial occlusions. CHIEF OUTCOME MEASURES: Limb salvage and amount of tissue loss within 18 months, pain relief. MAIN RESULTS: Twenty-five patients were randomized to SCS and 26 to analgesic (control) treatment. Macrocirculatory parameters were not different in the two groups during follow-up. Long-term pain relief was observed only in the SCS group. At 18 months, limb salvage rates in the SCS and control groups were 62% and 45% (N.S.). Tissue loss was less (p = 0.05) in the SCS group. A subgroup analysis of patients without arterial hypertension showed a significantly lower amputation rate in the SCS vs the control group. CONCLUSIONS: SCS provided long-term pain relief but limb salvage at 18 months was not significantly improved by SCS in this rather small study. The results suggest that SCS may reduce amputation levels in patients with severe inoperable leg ischaemia and be most effective in patients without arterial hypertension.

Spinal cord stimulation in cardiovascular disease.

Spinal cord stimulation in ischemic pain conditions has proved to be an effective method of treatment for many patients. The indications are ischemic pain in the extremities from peripheral vascular disease and angina pectoris. The long-term results show that the response rate for ischemic pain is 70% to 90%, while the corresponding results for neuropathic pain average approximately 50% to 70%, which actually makes ischemic pain a very good indication for SCS. SCS system implantation is a safe and quick operation performed under local anesthesia and well tolerated by the patient. A total implant of the lead and the pulse-generator in one stage seldom takes more than 1 hour. High sterility and prophylactic antibiotics are prerequisites to avoid postoperative problems. In atherosclerosis, SCS should be regarded as a method supplementary to vascular surgery, to be used for symptom recurrence after treatment or when there are technical obstacles to reconstructive surgery. SCS has proven to be extremely effective for the relief of ischemic rest pain, which constitutes the most severe problem for these patients. Today it is estimated that more than 7000 implants for PVD have been done in Europe. In a prospective randomized study, Jivegård et al have shown that SCS is a limb-saving treatment. For angina pectoris, SCS by now has become a routine supplementary method to conventional medical and surgical treatment. The technique is clinically effective, and several studies have shown decreased myocardial ischemia and decreased anginal pain during treatment. It is probable that the use of SCS in refractory angina will increase considerably in the 1990s.

Spinal cord stimulation in severe angina pectoris.

Since 1985, 225 patients suffering from severe pectoris due to New York Heart Association classes III-IV have been treated with spinal cord stimulation (SCS). All patients have been considered not suitable for open heart surgery by technical reasons. The long-term follow-up has shown a very good positive response to stimulation with pain relief, less intake of medication and increased quality of life. Several invasive studies with catheters in the coronary sinus and peripheral arteries have shown a significant improvement with stimulation regarding heart muscle lactate metabolism, blood flow in the coronary sinus and oxygen demand. Recordings with the so-called Holter technique have demonstrated that SCS does not create arrhythmias, and pacing studies that SCS does not mask ischemia at extreme workload. In conclusion, apart from the positive effect on the quality of life, SCS in angina pectoris has demonstrated antianginal and anti-ischemic effects. The clinical results and the physiological and hemodynamic measurements will be presented in detail.

Safety aspects of spinal cord stimulation in severe angina pectoris.

BACKGROUND: Spinal cord stimulation has been used over the past decade for the treatment of patients suffering from intractable angina pectoris, despite having received optimal medical therapy, and who are unsuitable for further surgical intervention. The clinical results are promising and several studies have shown that the antianginal effect of the treatment is associated with a reduction in myocardial ischemia. It has been suggested, however, that spinal cord stimulation may only attenuate the transmission of pain from the heart, without influencing myocardial ischemia. This is a major safety concern when applying this treatment strategy. METHODS: The aim of this study was to assess the potentially unfavourable aspects of spinal cord stimulation in patients with severe coronary artery disease and angina pectoris by means of repeated long-term ECG recordings. Nineteen patients who had been accepted for implantation of spinal cord stimulators for the treatment of severe angina pectoris were included. RESULTS: No increases were noted in the frequency of ischemic episodes, the total ischemic burden, or the number of arrhythmic episodes during treatment. CONCLUSION: The results of this study do not indicate any unfavourable effects of spinal cord stimulation in severe angina pectoris in terms of an increase in the frequency or severity of myocardial ischemia during treatment with spinal cord stimulation.

[Spinal cord stimulation in severe angina pectoris. Reduced ischemia and increased quality of life]. / Ryggmärgsstimulering vid svår angina pectoris. Minskad ischemi och ökad livskvalitet.

Promising clinical results have been obtained with spinal cord stimulation which in recent years has been used for treating the subgroup of patients with angina pectoris that has proved intractable to conventional medical and surgical treatment strategies. According to recent reports, the anti-angina effect of spinal cord stimulation is associated with a reduction in myocardial ischaemia due to decreased myocardial oxygen consumption. Candidates for the treatment require careful screening. It is important to ensure that the patient is capable of full co-operation, and that the chest pain is due to true reversible myocardial ischaemia. Results in the 206 patients given implants to date have been encouraging, with reductions both in the frequency of angina attacks and in the consumption of short-acting nitroglycerin.

Vagus nerve stimulation for treatment of partial seizures: 2. Safety, side effects, and tolerability. First International Vagus Nerve Stimulation Study Group.

Vagus nerve stimulation (VNS) significantly reduces the frequency of partial seizures in refractory epilepsy patients. We examined the serious adverse events, side effects, and tolerability as they relate to the surgical implant procedure and the stimulating device. We also reviewed potential drug interactions, device output complications, and impact of the therapy on overall health status. We analyzed the first 67 patients to exist the acute phase of the EO3 VNS trial comparing high (therapeutic) VNS to low (less or noneffective) VNS. Data were collected from case report forms used at each of the four visits during the 12-week baseline and at each of the four visits during the 14-week randomized phase of the trial. No significant complications were reported as a result of the implant procedure. Serious adverse events included 1 patient who experienced direct current to the vagus nerve owing to generator malfunction resulting in left vocal cord paralysis and withdrawal of the patient from the study. No clinically significant effects on vital signs, cardiac function, or gastric function were detected. Side effects associated with VNS in the high group were hoarseness (35.5%), coughing (13.9%), and throat pain (12.9%). In the low group, only hoarseness (13.9%) and throat pain (13.9%) were associated with VNS. These effects generally wrre not considered clinically significant and occurred primarily during the stimulation pulses. No patients discontinued VNS therapy during the acute phase because of side effects associated with normal stimulation. Except for the one instance of a short circuit in the system resulting in a direct current, stimulating system complications were minor, limited to programming, unscheduled stimulation, and high lead impedance. Patients, investigators, and patient companions rated patients receiving high stimulation as more "improved" than those receiving low stimulation in regards to overall health status. Antiepileptic drug (AED) plasma concentrations were not affected by VNS. The implant procedure, stimulating system, and therapy proved safe and tolerable during the study. The high percentage (67 of 68) of patients completing the study reflects patient acceptance and tolerability of this mode of therapy.

Spinal cord stimulation in angina pectoris with normal coronary arteriograms.

BACKGROUND: Patients with angina pectoris with normal coronary arteriograms, also known as Syndrome X (typical exercise-induced angina pectoris, positive exercise testing, and normal coronary arteriograms), are often difficult to treat with conventional forms of medical therapy. Spinal cord stimulation has been used in recent years for the treatment of severe angina pectoris refractory to conventional medical and surgical therapy in coronary artery disease. The aim of this study was to investigate the effects of spinal cord stimulation on angina pectoris with normal coronary arteriograms. METHODS: Twelve patients underwent five bicycle exercise tests, three tests without (control), and two tests with spinal cord stimulation treatment. RESULTS: The exercise tolerance of the patients increased (108 +/- 22 W versus 96 +/- 21 W; P < 0.001), the magnitude of ST-segment depression at comparable work load decreased (1.0 +/- 0.6 mm versus 1.5 +/- 0.9 mm; P < 0.01), time to angina increased (5.4 +/- 2.2 min versus 2.7 +/- 1.9 min; P < 0.01), and time to the appearance of ST-segment depression increased (3.5 +/- 1.9 min versus 2.4 +/- 1.6 min; P < 0.01). The rate-pressure product at maximum work load during treatment increased, compared with the maximum work load during the control session (28,038 +/- 6124 mmHg x bpm versus 25,222 +/- 4519 mmHg x bpm; P < 0.05) and the comparable work load during treatment (28,038 +/- th 6124 mmHg x bpm versus 24,795 +/- 5022 mmHg x bpm; P < 0.01). CONCLUSIONS: Spinal cord stimulation has beneficial effects in angina pectoris with normal coronary arteriograms in terms of relief of symptoms of angina pectoris and improvement of exercise tolerance. These effects may be associated with a reduction in myocardial ischemia.

Assessment of the influence of spinal cord stimulation on left ventricular function in patients with severe angina pectoris: an echocardiographic study.

Patients with severe, widespread coronary atherosclerosis and patients who have undergone several coronary artery bypass operations are often poor candidates for coronary bypass surgery (CABG). Spinal cord stimulation (SCS) has been shown to have an anti-anginal effect that is probably associated with an anti-ischaemic effect. In the present investigation, 15 patients with severe angina (mean age 64 years, range 49-71) were studied. All patients had a history of intractable angina pectoris despite optimal medical treatment and previous coronary bypass operation. The patients had multi-vessel disease and graft occlusion or graft stenosis on postoperative coronary angiograms. Left ventricular function was assessed echocardiographically at rest and during provocation with adenosine infusion in a control session without treatment and during treatment with SCS. The recovery time was at least 3 h. The decrease in the ejection fraction during adenosine infusion was more pronounced in the control situation (44 to 37%; P < 0.05) than during SCS (48 to 44%; ns), and the time to echocardiographic signs of dysfunction and to anginal pain during adenosine infusion was significantly prolonged during SCS (P < 0.001). In addition, the recovery time for these parameters was shorter during SCS (P < 0.001). It is concluded that the deterioration in left ventricular function during adenosine provocation was less pronounced with SCS than without. This possible anti-ischaemic effect is in agreement with results from earlier studies.