Vagus nerve stimulation in refractory epilepsy: effects on pro- and anti-inflammatory cytokines in peripheral blood.

OBJECTIVE: The vagus nerve has important immunological functions that may be relevant for its anticonvulsive action. We postulate that this anticonvulsive action is activated by a shift in the immune system resulting in a reduction of neurotoxic and an increase of neuroprotective tryptophan metabolites. METHODS: Eleven patients with refractory epilepsy and 11 controls matched for age and gender were included in this study. The primary outcome measure was a 50% seizure reduction. Other variables were pro-inflammatory cytokines IL-6 and TNF-α, anti-inflammatory cytokine IL-10, cortisol, and the tryptophan metabolites 3-hydroxykynurenine (3-OH-KYN), kynurenic acid (KYNA), kynurenine, serotonin (5-HT) and 5-hydroxyindol acetic acid (5-HIAA). Blood samples were scheduled during baseline, and in week 28 of add-on treatment. RESULTS: IL-6 levels were higher in the responders than in the control group, and decreased after vagus nerve stimulation (VNS), whereas IL-10 was low and increased after VNS. In nonresponders, VNS resulted in an increase of IL-6 plasma levels and in a decrease of IL-10. Cortisol concentrations are higher in the epilepsy group than in the control group. After VNS, these concentrations decreased. The concentrations of the tryptophan metabolites were lower in the epilepsy group than in the control group. The KYNA ratios are defined as the ratio of neuroprotective KYNA versus neurotoxic 3-OH-KYN and KYNA versus neurotoxic kynurenine: these ratios were lower in epilepsy patients than in controls, and they both moderately increased after VNS. CONCLUSION: The outcome of this preliminary study indicates that VNS causes a rebalancing of the immune system. This results in: (1) a reduction of neurotoxic and an increase of neuroprotective kynurenine metabolites and (2) in the normalization of cortisol levels.

Hardware failure in vagus nerve stimulation therapy.

A 20 year old male patient who had been successfully treated for epilepsy with vagus nerve stimulation (VNS) for 7 years (50% seizure frequency reduction), had experienced multiple episodes of severe hoarseness, throat pain and impaired breathing during physical exercise. As malfunctioning of the pulse generator was suspected, it was decided to replace the device. During surgery, the pulse generator was found to have broken in two, due to an unstable connection between the battery subunit and the connector subunit. With a new pulse generator seizure frequency reduction was restored. No side effects occurred.

Vagus nerve stimulation in patients with catastrophic childhood epilepsy, a 2-year follow-up study.

PURPOSE: To establish the long-term efficacy and tolerability of vagus nerve stimulation (VNS) in children with a Lennox-like syndrome. METHOD: This study was a longitudinal observational prospective cohort analysis. Baseline: 6 months. FOLLOW-UP: 24 months. Screening (baseline and every 6 months): MRI (baseline only), EEG, neuropsychological evaluation, ECG and blood sampling for antiepileptic drug levels. Nineteen children are included. RESULTS: A seizure frequency reduction of 20.6% was found at the end of the follow-up period. No relationship was detected between the length of the stimulation period and the reduction in the seizure frequency. 21% of the patients showed a reduction in seizure frequency of 50% or more. The seizure severity showed improvement in the first 12 months of treatment. The largest seizure reduction was found in the patients with highest frequency of background activity at the baseline EEG. Neuropsychological findings: no negative impact on behaviour, moderate improvement in function, behaviour and mood. Largest seizure reduction was found in the group with the highest baseline mental function. The scores for mental age improved independently of the seizure control. Twelve patients (63%) experienced minor side effects, which subsided after 1 month. CONCLUSION: (1) There was a significant reduction in seizure frequency and severity. (2) No serious side effects were recorded. (3) No negative effects on cognition or quality of life were apparent. (4) Patients with highest baseline mental functioning showed the highest seizure reduction. (5) Those patients with less disturbed EEG (high background activity and less interictal epileptic activity) showed the highest seizure reduction.

Effectiveness of behavioral graded activity after first-time lumbar disc surgery: short term results of a randomized controlled trial.

Behavioral approaches to treating patients following lumbar disc surgery are becoming increasingly popular. The treatment method is based on the assumption that pain and pain disability are not only influenced by somatic pathology, if found, but also by psychological and social factors. A recent study highlighted the effectiveness of cognitive-behavioral interventions, as compared to no treatment, for chronic low back patients. However, to the authors' knowledge, there is no randomized controlled trial that evaluates a behavioral program for patients following lumbar disc surgery. The purpose of this study was to assess the effectiveness of a behavioral graded activity (BGA) program compared to usual care (UC) in physiotherapy following first-time lumbar disc surgery. The BGA program was a patient-tailored intervention based upon operant therapy. The essence of the BGA is to teach patients that it is safe to increase activity levels. The study was designed as a randomized controlled trial. Assessments were carried out before and after treatment by an observer blinded to treatment allocation. Patients suffering residual symptoms restricting their activities of daily living and/or work at the 6 weeks post-surgery consultation by the neurosurgeon were included. The exclusion criteria were: complications during surgery, any relevant underlying pathology, and any contraindication to physiotherapy or the BGA program. Primary outcome measures were the patient's Global Perceived Effect and the functional status. Secondary measures were: fear of movement, viewing pain as extremely threatening, pain, severity of the main complaint, range of motion, and relapses. Physiotherapists in the BGA group received proper training. Between November 1997 and December 1999, 105 patients were randomized; 53 into the UC group and 52 into the BGA group. The unadjusted analysis shows a 19.3% (95% CI: 0.1 to 38.5) statistically significant difference to the advantage of the UC group on Global Perceived Effect. This result, however, is not robust, as the adjusted analyses reveal a difference of 15.7% (95% CI: -3.9 to 35.2), which is not statistically significant. For all other outcome measures there were no statistically significant or clinically relevant differences between the two intervention groups. In general, the physiotherapists' compliance with the BGA program was satisfactory, although not all treatments, either in the BGA or the UC group, were delivered exactly as planned, resulting in less contrast between the two interventions than had been planned for. There was one re-operation in each group. The BGA program was not more effective than UC in patients following first-time lumbar disc surgery. For Global Perceived Effect there was a borderline statistically significant difference to the advantage of the UC group. On functional status and all other outcome measures there were no relevant differences between interventions. The number of re-operations was negligible, indicating that it is safe to exercise after first-time disc surgery.

Long-term effects of 24-month treatment with vagus nerve stimulation on behaviour in children with Lennox-Gastaut syndrome.

The long-term effects of vagus nerve stimulation (VNS) on behaviour were studied in 19 children with Lennox-Gastaut syndrome. We used the following stimulation parameters: output current: 112 to 2mA; signal frequency: 30Hz frequency; signal pulse width: 500&mgr;s; signal 'on and off' time: 30s 'on,' 3min 'off.' The test battery consisted of cognitive tests assessing mental age and quality of life measurements assessing independency, behavioural problems, and mood. The results show relatively small changes in the behavioural outcomes, concurrent with the modest effects of VNS on seizure frequency (an average of 20.6% seizure reduction). When baseline measurements are compared with the follow-up measures, neither the cognitive measure nor the quality of life measures show any deterioration and the cognitive measure (mental age) showed mild positive changes (gain of 4.2 months mental age during the follow-up period). None of the changes were statistically significant. Treatment effect was most prominent in the group with the highest mental age at baseline, which suggests that mental retardation is a negative prognostic factor for VNS treatment. Moreover, in this specific patient group, treatment effect did not increase with treatment duration. Some evidence during follow-up suggests a direct positive effect of VNS on behavioural function, independent of changes in seizure frequency. Long-term treatment with VNS is not associated with adverse behavioural effects. Mental retardation is a negative prognostic factor for the efficacy of VNS.

Vagus nerve stimulation in children with therapy-resistant epilepsy diagnosed as Lennox-Gastaut syndrome: clinical results, neuropsychological effects, and cost-effectiveness.

We studied the clinical efficacy and tolerability, neuropsychological effects, and cost-effectiveness (direct medical costs, direct nonmedical costs, and indirect costs) of vagus nerve stimulation (VNS) in children with Lennox-like syndrome (n = 16). The situation 6 months before implantation of the device is compared with that 6 months after surgery. Seizure frequency and severity are significantly reduced during VNS: 25% of the patients show a reduction in seizure frequency of 50% or greater; overall seizure reduction is 26.9%. Measures of neuropsychological outcome show a moderate improvement in mental functioning, behavior, and mood. The scores for mood and mental age improve independently of seizure control. Side effects are minor and transient. There is a significant reduction in direct non-health care costs, ergotherapy, and the number of days of sub-optimal functioning of the child. The costs during the 6 postoperative months are 2,876.06 Euros less than the costs during the 6 months before VNS; the payback period is 2.3 years.

Effects of 6 months of treatment with vagus nerve stimulation on behavior in children with lennox-gastaut syndrome in an open clinical and nonrandomized study.

The effect of vagus nerve stimulation (VNS) on behavior outcomes was studied in 16 children with Lennox-Gastaut syndrome. We used the following stimulation parameters: output current, 11 2 to 2 mA; signal frequency, 30 Hz; signal pulse width, 500 microseconds; signal on and off times, 30 seconds on and 3 minutes off. The test battery consisted of cognitive tests measuring mental age, attention, language, psychomotor function, and cognitive style, and quality-of-life measurements assessing independence, behavioral problems, symptoms of pervasive development disorders (PDDs) and mood. The results show relatively small changes in behavioral outcomes concurrently with modest effects on seizure frequency (an average of 26.9% seizure reduction). When baseline and endpoint measurements are compared none of the cognitive measures show any deterioration and three of five cognitive measures show slight positive changes. Among the quality-of-life measures, one measure showed a slight worsening of scores and three showed slight improvement. When the group is divided into subgroups on the basis of treatment effect the most prominent improvements are observed in the group without any effects of VNS on seizure frequency. These patients gained, on average, 9.5 months in mental age and showed more independent behavior, mood improvements and fewer PDD symptoms. This suggests an effect of VNS on behavioral function independent of changes in seizure frequency.

Behavioral-graded activity compared with usual care after first-time disk surgery: considerations of the design of a randomized clinical trial.

OBJECTIVE: To present the design of a trial on the effectiveness of a behavioral-graded activity model. DESIGN: Randomized clinical trial. PATIENTS: Patients undergoing first-time lumbar disk surgery who still have low-back pain at the 6-week neurosurgical consultation. INTERVENTIONS: A patient-tailored behavioral-graded activity program that is based on operant therapy. The key elements of this program are baseline measurements, goal-setting, and time-contingency. This program is compared with usual care in physiotherapy, which is pain-contingent. OUTCOME MEASURES: Primary measures are the patient's global impression of the effect and their functional status. Secondary measures are kinesiophobia, catastrophizing, pain, main complaint, range of motion, and relapses. The direct and indirect costs will also be assessed. The effect measures are rated before randomization and 3, 6, and 12 months later. DISCUSSION: Several trials have been conducted on the effectiveness of behavioral treatments. Subjects were always patients with chronic low-back pain. In this trial, we apply such a treatment in patients after first-time disk surgery in a primary care setting.

A unique case of intracranial metastasis from lung carcinoma.

We describe a case of an intracranial metastasis from a lung carcinoma in the same location from which an intracranial meningioma had been completely removed surgically eleven months earlier. It is demonstrated that the metastasis originated in the scar of the first operation.

The R-zero line: a new kinematic concept of the lumbar spine.

A new kinematic concept is described that relates to the notion that the lumbar spine behaves as a complete structure. This concept is called the "R-zero line" and represents kinematically the neutral position of the lumbar spine between anteflexion and retroflexion. The clinical significance of this parameter is evaluated in normal individuals and in patients with a symptomatic herniated disc at L4-5, with a symptomatic herniated disc at L5-S1, and with spondylolysis/spondylolisthesis. The results of this study show that the R-zero line has a characteristic configuration in all four test groups.

Computed tomography-guided and stereotactic techniques in the diagnosis and treatment of cerebral tuberculoma.

The advantages of computed tomography-guided preoperative localization of brain lesions are illustrated in four cases of solitary tuberculoma and in one case of tuberculous abscess of both the cerebrum and the cerebellum. The role of stereotactic diagnostic techniques is emphasized. The clinical presentation and the computed tomography findings in these patients were equivalent to those from glial or metastatic tumors. Synchronous pulmonary tuberculosis was not present in these patients, but in three patients there was metachronous tuberculosis. Tuberculous meningitis had not developed in any of the patients.

Chemonucleolysis versus discectomy: a randomized multicenter trial.

A randomized clinical trial was carried out to compare the results of open discectomy with those of chemonucleolysis in 151 patients suffering from a disc herniation at L4-5 or L5-S1. All patients fulfilled strict entry criteria; 78 patients underwent open discectomy and 73 were subjected to chemonucleolysis. An increase in radicular pain immediately after treatment was encountered in 16 patients (22%) in the chemonucleolysis group, as compared to none in the discectomy group. The efficacy of discectomy appeared to be definitely superior to that of chemonucleolysis. Within a follow-up period of 1 year, 18 patients (25%) required open discectomy following failed chemonucleolysis; two patients (3%) in the discectomy group needed a second operation. Open discectomy following previous chemonucleolysis was successful in only 44% of cases. Comparison of the final results of the two modes of treatment 12 months after the last intervention (including second treatment) did not reveal any significant differences. The duration of the preoperative symptoms, the level of disc herniation, and the leakage of contrast medium out of the disc appeared to be of no relevance to the final outcome. The complication rates in both treatment groups were low.

Chemonucleolysis or discectomy? Results of a randomized multicentre trial in patients with a herniated lumbar intervertebral disc (a preliminary report).

A randomized trial was carried out to compare the results of discectomy and chemonucleolysis in 151 patients, suffering from lumbar disc herniation L4-L5 or L5-S1. All patients fulfilled strict entry criteria. Seventy eight patients underwent surgical discectomy, 73 were treated with chemonucleolysis. Within one year of follow-up 18 patients (25%) required surgery after chemonucleolysis, whereas 2 patients (3%) in the surgery group underwent re-operation. Increase of radicular pain within 30 days after treatment was encountered in 16 patients (22%) in the chemonucleolysis group, as compared to none in the surgery group. The results of open surgery after preceding chemonucleolysis was successful in 44% and unsuccessful in 56%. The final result of chemonucleolysis, including second treatment, was still slightly less favourable (73%) the result of primary surgery (79%).

The Rotterdam teletransducer. A telemetric device for measuring epidural pressure.

A discussion on the clinical value of telemetric measurements of intracranial pressure is presented. The technical improvements of an earlier described implantable epidural transducer are reported. Furthermore, the results are given of an in vivo study in dogs of the relation between epidural pressure as measured by this device and ventricular fluid pressure for variable physiologic conditions. An evaluation of the implantation technique is included and a justification for the selection of the constituting materials is given. Clinical results obtained in a patient are illustrated.

Epidural pressure monitoring with the so-called Rotterdam transducer. Further in vivo results.

Results of measurements in vivo of intracranial pressure obtained with a new telemetric epidural pressure transducer are described. The relations of epidural pressure to ventricular fluid pressure are studied in acute experiments and found to be linear, but variable. The functioning of 18 transducers was studied over many months of implantation.