Anatomical connectivity and efficacy of electro-therapy for seizure control: A SANTE's single-center regression analyses.

OBJECTIVE: To assess based on a single-center data from a multicenter trial (Stimulation of the Anterior Nucleus for the Thalamus for Epilepsy (SANTE)), the role of anatomical connectivity and other factors (e.g., stimulating electrode placement) on efficacy of electro-therapy of the anterior thalamic nuclei (ATN), a node in Papez network, on pharmaco-resistant seizures. DATA SOURCE: Adults with at least 6 seizures /month were enrolled in this trial. Percent seizure reduction was compared between subjects with seizures emerging inside Papez's network (IPN) to those with seizures outside it (OPN). Statistical analyses were performed on the first year of the trial. RESULTS: Data from 11 subjects were analyzed. At Year 1, median seizure reduction was 80.5% (-100% to -40.3%) in 8/11 subjects with seizures IPN, vs. 52.8% (-61.4% to -23.7%) for 3/11 subjects with seizures OPN (2-sided Wilcoxon p = 0.08). At year 7, 3/11 subjects with seizures IPN had been seizure free for several years vs. 0/11 subjects with seizures OPN. Addition of 4 subjects from a pilot trial with nearly identical protocol to SANTE's, increased to 12/15 the number of subjects with seizures IPN. A 2-sided Fisher's exact test applied to seizure frequency reduction in the 12/15 cohort compared to the 3/15 with seizures OPN, showed significant (p = 0.04) differences in efficacy at the 70% seizure reduction rate. Median quality of life (QOL) scores for subjects with seizures IPN improved by 81% vs. 53% for subjects with seizures OPN. No other factors (e.g., current intensity) had a statistically significant effect on efficacy. CONCLUSIONS: Degree of anatomical connectivity between stimulation targets and epileptogenic networks (ENs) plays an important role in therapeutic efficacy. This may be explained by the minimization of signal attenuation inherent in impulse transmission in nervous tissue partly as a function of fiber tract length, tissue anisotropy, and number of synaptic relays between stimulation target and epileptogenic networks.

Programming parameters of subthalamic deep brain stimulators in Parkinson's disease from a controlled trial.

BACKGROUND: Programming algorithms have never been tested for outcome. The EARLYSTIM study showed superior outcomes of deep brain stimulation of the subthalamic nucleus (STN-DBS) over best medical treatment in early Parkinson's disease (PD). Patients were programmed according to common guidelines but customized for each patient. METHODS: Stimulation parameters were systematically documented at 1, 5, 12, and 24 month in the cohort of 114 patients who had bilateral STN-DBS at 24 month. We investigated the influence of atypical programming, changes of stimulated electrode contacts and stimulation energy delivered. Outcomes were the Unified Parkinson's Disease Rating Scale (UPDRS) motor and ADL-subscores, health-related quality of life (PDQ-39) summary index and mobility- and ADL-subscores. RESULTS: At 1/5/12/24 months follow up, mean amplitude (1.8/2.5/2.6/2.8 V), impedance (1107/1286/1229/1189 Ω) and TEED (33.7/69.0/84.4/93.0 V2*µs*Hz/Ω) mainly increased in the first 5 months, while mean pulse width (60.0/62.5/65.1/65.8 µs), frequency (130/137.7/139.1/142.7 Hz) remained relatively stable. Typical programming (single monopolar electrode contact) was used in 80.7% of electrodes. Double monopolar (11/114) and bipolar (2/114) stimulation was only rarely required. There was no significant difference in clinical outcomes between the patient groups requiring contact changes (n = 32/28.1%) nor between typical (n = 83/72.8%) versus non-typical programming. Energy used for STN-DBS was higher for the dominant side of PD. CONCLUSION: In the first 5 months an increase in amplitude is required to compensate for various factors. Monopolar stimulation is sufficient in 80% of patients at 24 months. Homogeneous stimulation strategies can account for the favorable outcomes reported in the Earlystim study.

Precipitous exit block with epicardial steroid-eluting leads.

Between January 1990 and October 1992, we implanted 16 steroid-eluting ventricular epicardial pacing leads (Medtronic 10295A and 10295B/4965) in 12 patients. There were 8 males and 4 females ranging in age from 3 months to 49 years (mean 8.7 +/- 13.2, median 6.0 years). Structural cardiac disease was present in 11 of 12 patients. Follow-up ranged from 3-73 months postimplant (mean 35.7 +/- 22.3, median 28.5 months). Lead fracture (10295A) occurred in 1 of 12 patients. Of the remaining 11 patients, 8 of 11 have very low long-term pacing thresholds. Unexpectedly, 3 patients demonstrated precipitous threshold increases from 3 months to 3.5 years postimplant. Although no deaths resulted in these exit block patients, 1 of 3 exit block patients developed marked worsening of congestive heart failure. We reviewed and analyzed the data obtained at 4 weeks postimplant for all of the 10295A and 4965 patients in the entire Medtronic clinical study database. Using the criterion of a 4 week postimplant pacing threshold > or = 0.12 ms (5 V), we found that the long-term risk of eventual exit block was 27.3% for the 10295A lead (P = 0.005) and 7.5% for the 10295B/4965 lead (P = 0.03). We, therefore, recommend that in patients implanted with the 4965 steroid-eluting epicardial lead, ventricular pacing thresholds > or = 0.12 ms (5 V) measured at 4 weeks postimplant should prompt frequent threshold testing to detect late and potentially sudden ventricular pacing threshold increases.

Steroid elution improves the stimulation threshold in an active-fixation atrial permanent pacing lead. A randomized, controlled study. Model 4068 Investigators.

BACKGROUND: Prior work suggests that the addition of a steroid-eluting reservoir to a passive-fixation permanent pacemaker lead improves the stimulation threshold; however, no large randomized study has addressed this tissue. Over the last several years, there has been an increase in enthusiasm for the use of active-fixation permanent pacemaker leads for various reasons in spite of the generally accepted notion that active-fixation leads have higher stimulation thresholds. METHODS AND RESULTS: This multicenter, randomized, controlled study examined the difference in performance between a standard active-fixation atrial lead (Medtronic model 4058) and a steroid-eluting lead (Medtronic model 4068). Stimulation thresholds were obtained in a four-point strength-duration fashion. Evaluations of sensing and impedance were performed as well. These evaluations were performed at implantation, at weeks 1 through 4, and at weeks 6, 12, 24, and 52. Stimulation thresholds were significantly better in the steroid lead than in the nonsteroid lead at each measurement point from 1 week to 12 months. The mean 1.6-V stimulation threshold at 12 months was 0.19 +/- 0.2 ms in the steroid lead and 0.41 +/- 0.30 ms in the control lead. No acute peaking was observed with the steroid lead, whereas significant peaking was observed with the control lead. There was no difference in long-term sensing or impedance. CONCLUSIONS: Inclusion of a steroid-eluting reservoir in an active-fixation permanent pacing lead improved stimulation thresholds in both the subacute and chronic periods and therefore should extend pulse-generator longevity.