Chronic Electrical Stimulation Research Articles

Chronic bilateral electrical stimulation of the subthalamic nucleus for the treatment of advanced Parkinson's disease

Preliminary reports in patients with Parkinson's disease (PD) showed that subthalamic nucleus (STN) stimulation was able to reverse parkinsonian state. Since 1998 we evaluated the safety and the efficacy of STN stimulation in 7 patients affected by advanced PD. All patients were included using CAPIT protocol. Motor functions and quality of life were evaluated, before and after surgery, with UPDRS and PDQ38, respectively. At the 6-month follow-up, the off medication/on stimulation UPDRS motor score improved by 50.6% and the on medication/on stimulation by 20.3%. Motor fluctuations were reduced by 57.2% and dyskinesias by 73.5%. The total L-dopa equivalent daily dose was reduced by 40.7%. PDQ38 ameliorated by 49.9%. We did not observe any perioperatory complication and only mild and tolerable side effects after stimulation.

Imaging Plasticity in Cochlear Implant Patients

Auditory re-afferentation by cochlear implants (CI) offers a unique opportunity to study directly from within the auditory modality plastic changes taking place at organisational levels up to the supra- or polymodal level. These plastic changes resulting from deafness and chronic electrical stimulation can be studied using modern neuroimaging techniques. In this paper, we review the available techniques and the experimental approaches to human studies of plasticity, we discuss the different forms of plasticity that are associated with cochlear implantation and we point to the interest of imaging studies for providing a prognosis of functional outcome after implantation.

Increased coronary artery blood flow with aortomyoplasty in chronic heart failure

Background. We hypothesized that diastolic counterpulsation using aortomyoplasty will increase coronary blood flow. Methods. In dogs (n = 6, 20 to 25 kg), the left latissimus dorsi muscle was isolated, wrapped around the descending thoracic aorta, and conditioned by chronic electrical stimulation. Heart failure was induced by rapid ventricular pacing. In a terminal study, left ventricular and aortic pressures, and blood flow in the left anterior descending coronary artery and descending aorta were measured. The endocardial-viability ratio was calculated. Results. Aortomyoplasty increased mean diastolic aortic pressure (70 ± 5 to 75 ± 5 mm Hg, p < 0.05) and reduced peak left ventricular pressure (86 ± 4 to 84 ± 4 mm Hg, p < 0.05), leading to a 16% increase in endocardial-viability ratio (1.29 ± 0.05 to 1.49 ± 0.05, p < 0.05). Coronary blood flow was increased by 15% (8.2 ± 1.5 to 9.4 ± 1.6 mL/min, p < 0.05). During muscle contraction, 2.7 ± 0.5 mL was ejected from the wrapped aortic segment. Conclusions. These data demonstrate that aortomyoplasty provides successful diastolic counterpulsation after muscle conditioning and heart failure.

Angiogenesis Induced by Electrical Stimulation Is Mediated by Angiotensin II and VEGF

Objective: Physiological angiogenesis in skeletal muscle is an adaptive response to physical training and electrical stimulation. This study investigated the role of angiotensin II (Ang II) in regulating both angiogenesis and vascular endothelial growth factor (VEGF) protein expression induced by electrical stimulation. Methods: The right tibialis anterior (TA) and extensor digitorum longus (EDL) muscles of Sprague-Dawley rats were stimulated for 8 hours per day for 7 days. The contralateral muscles served as controls. Two days before the surgery and throughout the stimulation protocol, the rats received either lisinopril or losartan in their drinking water. Rats without any drug treatment were used as control. Immunohistochemistry and Western blot analysis were performed to identify the source and quantify the VEGF protein expression in these muscles. The relationship between angiogenesis and VEGF expression was explored using a VEGF-neutralizing antibody. Results: Chronic electrical stimulation of the skeletal muscles led to significant increases in vessel density (14% and 30% for EDL and TA, respectively) within 7 days. In addition, stimulation increased VEGF protein levels in the stimulated muscles. Both lisinopril and losartan blocked elevation in VEGF expression and inhibited the angiogenesis induced by stimulation. VEGF neutralization also inhibited angiogenesis, confirming the relationship between Ang II, VEGF, and vessel growth. Conclusion: The current study suggests a pathway involving angiotensin II receptors (AT1) and VEGF in electrically stimulated angiogenesis.

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Use of a neuromuscular stimulator to increase anal sphincter pressure.

The objective of this study was to determine if short periods of electrical stimulation with perianal electrodes could increase anal pressures. Anorectal responses to electrical stimulation were evaluated in five healthy SCI patients. Anorectal pressures were recorded with a small pressure-recording balloon before, during, and immediately following stimulation. A battery-powered stimulator with self-adhering surface electrodes, two inches in diameter was used. Stimulating parameters consisted of 300 micros pulse duration, 35 Hz stimulating frequency. A current response study was conducted by using short periods of electrical stimulating with currents from 0-100 mA until a maximal pressure was recorded. Each current setting was conducted for 13.2+/-9.7 s before increasing to the next higher current, and fatigue was reduced by including a 5-minute rest between stimulations. Four of the five subjects had strong anal contractions with perianal stimulation. Increases in pressure ranged from 38 to 125 cm H2O based on maximal responses at currents ranges of 60 to 100 ma. Even during the short periods of stimulation used here, fatigue was apparent. There was an average drop of 11% in anal pressure over the 13 s of stimulation. Rectal pressures were unchanged with perianal stimulation. Perianal stimulation with surface electrodes is an approach that might be considered in the future for management of fecal incontinence in individuals with spinal cord injury. Further studies are needed to assess the feasibility of using chronic perianal surface electrical stimulation to sustain anal sphincter contractions.

An investigation of the effects of subthalamic nucleus stimulation on acoustic measures of voice.

Seven patients with Parkinson's disease were implanted with deep brain stimulators to provide chronic electrical stimulation to the subthalamic nucleus bilaterally. Acoustic recordings and neurologic assessments were undertaken before surgery in the medication-off and medication-on conditions and after surgery with and without electrical stimulation in the medication-off and medication-on conditions. The data showed significant improvements in limb motor performance in response to medication before surgery and when the subthalamic nucleus was stimulated after surgery. Six months after surgery, there were small but statistically significant increases in sound pressure level and fundamental frequency variability in response to stimulation in the medication-on condition. No other statistically significant speech changes were measured. These findings are consistent with several other studies that have reported disparity between limb and speech improvements after neurosurgical intervention for Parkinson's disease.

Matrix metalloproteinase activity is required for activity-induced angiogenesis in rat skeletal muscle.

Proteolysis of the capillary basement membrane is a hallmark of inflammation-mediated angiogenesis, but it is undetermined whether proteolysis plays a critical role in the process of activity-induced angiogenesis. Matrix metalloproteinases (MMPs) constitute the major class of proteases responsible for degradation of basement membrane proteins. We observed significant elevations of mRNA and protein levels of both MMP-2 and membrane type 1 (MT1)-MMP (2.9 +/- 0.7- and 1.5 +/- 0.1-fold above control, respectively) after 3 days of chronic electrical stimulation of rat skeletal muscle. Inhibition of MMP activity via the inhibitor GM-6001 prevented the growth of new capillaries as assessed by the capillary-to-fiber ratio (1.34 +/- 0.08 in GM-6001-treated muscles compared with 1.69 +/- 0.03 in control 7-day-stimulated muscles). This inhibition correlated with a significant reduction in the number of capillaries with observable breaks in the basement membrane, as assessed by electron microscopy (0.27 +/- 0.27% in GM-6001-treated muscles compared with 3.72 +/- 0.65% in control stimulated muscles). Proliferation of capillary-associated cells was significantly elevated by 2 days and remained elevated throughout 14 days of stimulation. Capillary-associated cell proliferation during muscle stimulation was not affected by MMP inhibition (80.3 +/- 9.3 nuclei in control and 63.5 +/- 8.5 nuclei in GM-6001-treated animals). We conclude that MMP proteolysis of capillary basement membrane proteins is a critical component of physiological angiogenesis, and we postulate that capillary-associated proliferation precedes and occurs independently of endothelial cell sprout formation.

Efficacy of chronic gastric electrical stimulation in the treatment of symptomatic gastroparesis: results at 6 and 12 months from the WAVESS study

Efficacy of chronic gastric electrical stimulation in the treatment of symptomatic gastroparesis: results at 6 and 12 months from the WAVESS study

Neurostimulation for lower urinary tract voiding problems.

In 1981, Tanagho and Schmidt introduced chronic electrical stimulation of the sacral spinal nerves using a permanently implanted sacral foramen electrode and a battery-powered pulse generator for treatment of different kinds of lower urinary tract dysfunction, refractory to conservative treatment. At our department, chronic unilateral electrical stimulation of the S3 sacral spinal nerve has been used for treatment of vesicourethral dysfunction in 55 patients with a mean postoperative follow-up of 44.3 months. Lasting symptomatic improvement of more than 50% was achieved in 16 of 21 patients with motor urge incontinence (76.2%) and in 22 of the 28 patients with urinary retention (78.6%). In our opinion, chronic sacral neuromodulation offers a sustained therapeutic effect to treatment responders that is not achieved by temporary neuromodulation techniques. Chronic neuromodulation should be considered predominantly in patients with urinary retention and in patients with motor urge incontinence who refuse temporary techniques or who require too much effort to achieve a sustained clinical effect.

Efficacy of chronic gastric electrical stimulation in the treatment of symptomatic gastroparesis: results at 6 and 12 months from the WAVESS study

Efficacy of chronic gastric electrical stimulation in the treatment of symptomatic gastroparesis: results at 6 and 12 months from the WAVESS study

Changes in cochlear electrical stimulation induced Fos expression in the rat inferior colliculus following deafness

Fos immunoreactive (IR) staining was used to examine changes in excitatory neuronal activity in the rat inferior colliculus (IC) between normal hearing and 21 day deaf rats evoked by basal or apical monopolar cochlear electrical stimulation. The location of evoked Fos IR neurons was consistent with expected tonotopic areas. The number of Fos IR cells increased as stimulation intensity increased in both normal and 21 day deaf animals. Stimulation at 1.5× threshold evoked fewer Fos IR cells in 21 day deafened animals compared to normal hearing animals. At 5× and above, however, significantly increased numbers of Fos IR neurons (in a larger grouping) were evoked in 21 day deafened animals compared to normal hearing animals. Another group of animals had 7 days of deafness followed by 14 days of chronic basal cochlear electrical stimulation. In this group basal monopolar stimulation at 5× evoked not only a greater number of Fos IR neurons, compared to normal hearing animals, but the location of their grouping was slightly shifted to a more dorso-lateral region in the contralateral IC, compared to the normal hearing and 21 day deaf groups. These observations indicate that both deafness and chronic electrical stimulation may alter central auditory processing.

Plasticity in central representations in the inferior colliculus induced by chronic single- vs. two-channel electrical stimulation by a cochlear implant after neonatal deafness

The goal of this research is to examine the functional consequences of patterned electrical stimulation delivered by a cochlear implant in the deafened developing auditory system. In previous electrophysiological experiments conducted in the inferior colliculus (IC), we have demonstrated that the precise cochleotopic organization of the central nucleus (ICC) develops normally in neonatally deafened unstimulated cats and is unaltered despite the lack of normal auditory input during development. However, these studies also showed that chronic electrical stimulation delivered at a single intracochlear location by one bipolar channel of a cochlear implant induces significant expansion of the central representation of the stimulated cochlear sector and degrades the cochleotopic organization of the IC. This report presents additional data from a new experimental series of neonatally deafened cats that received chronic stimulation on two adjacent bipolar intracochlear channels of a cochlear implant. Results suggest that competing inputs elicited by electrical stimulation delivered by two adjacent channels can maintain the selective representations of each activated cochlear sector within the central auditory system and prevent the expansion seen after single-channel stimulation. Alternating stimulation of two channels and use of highly controlled electrical signals may be particularly effective in maintaining or even sharpening selectivity of central representations of stimulated cochlear sectors. In contrast, simultaneous stimulation using two channels of a model analog cochlear implant processor in one experimental animal failed to maintain channel selectivity and resulted in marked expansion and fusion of the central representations of the stimulated channels. This potentially important preliminary result suggests that under some conditions the central auditory system may be unable to discriminate simultaneous, overlapping inputs from adjacent cochlear implant channels as distinct.

Predictors in the treatment of difficult-to-control seizures by electrical stimulation of the centromedian thalamic nucleus.

To evaluate the efficacy of chronic electrical stimulation of centromedian thalamic nuclei (ESCM) in the treatment of difficult-to-control seizures. Thirteen patients underwent ESCM for periods ranging from 12 to 94 months (mean, 41.2 mo) with electrodes stereotactically placed in both centromedian nuclei and connected to internalized stimulation systems. Electrode placement was guided by ventriculography and confirmed with magnetic resonance imaging before stimulation systems were internalized. Anatomic and electrophysiological confirmation of the electrodes' position was accomplished by plotting electrode position on anatomic sections of Schaltenbrand and Bailey's atlas, and testing cortical recruiting responses and electroencephalogram desynchronization elicited by acute low- or high-frequency stimulation, respectively. Improvement was highly significant for generalized tonicoclonic seizures and atypical absences. Better results were obtained for Lennox-Gastaut syndrome. These results were accompanied by a significant decrease in generalized spike-wave and secondary synchronous discharges, as well as focal spikes in the frontal regions. In contrast, ESCM reduced neither complex partial seizures nor focal spikes in temporal regions. Outcomes using ESCM for generalized epilepsy were better in patients in whom anatomic and electrophysiological confirmation of electrode placement was correct than in those in whom the target was missed bilaterally (P < 0.001). The effect was sustained during the observation period and was better for longer-term than for shorter-term stimulation periods. ESCM is an efficient and safe procedure for controlling certain seizure types, if patient selection and stereotactic placement are satisfactory.

Effect of indomethacin on capillary growth and microvasculature in chronically stimulated rat skeletal muscles.

1. Capillary proliferation and microvessel diameters were studied in rat ankle flexors subjected to chronic electrical stimulation by implanted electrodes (10 Hz, 0.3 ms pulse width, up to 6 V, 8 h day-1) for 2 or 7 days with or without concurrent indomethacin treatment ( approximately 2 mg day-1 in drinking water) to study the role of prostaglandins in the microcirculation in relation to capillary growth. 2. Diameters of terminal arterioles, capillaries and confluent venules were measured in epi-illuminated muscles, together with capillary red cell velocity, to evaluate whether changes in capillary pressure and/or shear stress participate in capillary growth via release of prostaglandins. 3. Cell proliferation was detected following bromodeoxyuridine (BrdU) incorporation and immuno-staining of frozen sections. Labelling was assessed as the percentage of all interstitial nuclei (Haematoxylin-stained) that were BrdU positive. By comparison with serial sections stained for alkaline phosphatase, from which the capillary-to-fibre ratio (C:F) was obtained, labelling was derived for nuclei colocalised either to capillaries or to other non-capillary interstitial cells. 4. C:F increased to 1.89 +/- 0.06 from 1.47 +/- 0.04 in controls only after 7 days stimulation; indomethacin reduced this to 1.55 +/- 0.07. Capillary labelling increased from 2.9 +/- 0.5 % in controls to 11.3 +/- 2.2 % after 2 days stimulation and 10.6 +/- 0.8 % after 7 days. The increase was attenuated by indomethacin at both time points (to 5.8 +/- 1.6 % and 4.2 +/- 0.5 %, respectively). 5. Non-capillary interstitial labelling (2.0 +/- 0.4 % in controls) increased to 9.5 +/- 2.7 % after 2 days stimulation and was back to normal after 7 days (3.2 +/- 0.7 %). Indomethacin depressed the increase at 2 days to 4.0 +/- 1.3 % and had no effect at 7 days (2.9 +/- 0.13 %). Labelling in sham-operated rats with or without indomethacin or in vehicle-treated animals was no different from controls. 6. Arteriolar and venular diameters were increased by 2 days of stimulation but unchanged after 7 days. Indomethacin increased diameters of arterioles after 2 days and venules after 7 days in sham-operated animals, but had no effect on diameters of either vessel type in stimulated muscles. 7. Capillary diameters did not change during acute muscle contractions whereas red cell velocity did. Calculated shear stress in capillaries was thereby increased by 75 %. 8. Thus during chronic electrical stimulation both capillary growth and the cell proliferation that precedes it were attenuated by indomethacin. Transient stimulation-induced increases in arteriolar and venular diameters, which were unaffected by indomethacin, do not implicate increased capillary pressure as a factor in prostaglandin release and capillary growth. Estimations of increases in capillary shear stress during muscle contractions and of a 45 % higher value even at rest after chronic stimulation for 7 days suggest that shear stress is a more likely stimulus for prostaglandin release in chronically stimulated muscles.

A case of severe dysexecutive syndrome consecutive to chronic bilateral pallidal stimulation

In treatment for severe Parkinson’s disease (PD), a recent procedure was developed which consists of implanting electrodes in the internal Globus Pallidus (GPi) for chronic electrical stimulation. The consequences on cognitive function of such an intervention are quite variable. Although most group studies observed no significant post-operative change, individual cases of post-operative cognitive impairment were reported. The present study reports the case of a PD patient who underwent bilateral implantation of deep brain stimulation electrodes in the GPi and who, after surgery, suffered from a severe dysexecutive syndrome. An extensive neuropsychological examination showed a selective negative effect of pallidal stimulation on tests assessing executive function. When the stimulation was turned off, the impairment was partly reversible. This observation emphasizes the role of the GPi in executive function.

Subthalamic Prelemniscal Radiation Stimulation for the Treatment of Parkinson's Disease: Electrophysiological Characterization of the Area

BackgroundPrevious reports have provided evidence of a reticulo-thalamic system, extending from the mesencephalic reticular formation (MRF) to the ventrolateral thalamus (VL), involved in the production of tremor. In humans, a funnel of fibers in the posterior subthalamus named the prelemniscal radiations (Raprl) has been described as an exquisite target to treat tremor in cases of Parkinson's disease. MethodsIn the present study, a group of 14 patients suffering from Parkinson's disease, with prominent unilateral tremor and rigidity, were implanted with tetrapolar depth brain stimulation (DBS) electrodes in Raprl to perform chronic electrical stimulation (ES) for the treatment of patient symptoms. Electrodes were left externalized to corroborate their placement throughout MRI studies and also to perform the following electrophysiological battery: (a) recording of somatosensory-evoked responses (SEP) through different electrode contacts and scalp by means of a paradigm to study the attention process; (b) evoking scalp EEG responses by stimulation with low (3 cps, 6 cps) and high (60–120 cps) frequencies with stimuli delivered through different electrode contacts, and (c) studying recovery cycle (RC) potentials in the Raprl while the upper MRF was being stimulated and, conversely, the RC in MRF while Raprl was being stimulated, before and after subacute Raprl stimulation. Thereafter, the electrodes were internalized and connected to a pulse generator (IPG) to carry on chronic ES, while the effects of stimulation were determined through a quantitative evaluation that measured phasic and tonic muscular activity with EMG recordings during different motor tasks. ResultsResults indicate the following: (a) that late, but not early, SEP components were recorded in Raprl and modulated in different attentive conditions; (b) that bilateral recruiting responses and spike and wave complexes were elicited by Raprl through low-frequency stimulation, while bilateral positive DC shifts induced by high-frequency stimulation were recorded, similar to those obtained in animals from MRF, and (c) that Raprl-ES induced RC inhibition at Raprl, but Raprl ES did not change MRF-RC. Long-term Raprl-ES induced a significant decrease in tremor and rigidity. ConclusionsIt was concluded that Raprl represents a subthalamic circuit electrophysiologically related to MRF in the genesis of tremor and rigidity and in the process of selective attention. Raprl-ES induced a significant improvement in tremor and rigidity by causing inhibition of the stimulated area.

Subacute and Chronic Electrical Stimulation of the Hippocampus on Intractable Temporal Lobe Seizures: Preliminary Report

BackgroundRecent animal experiments show that the application of an electrical stimulus to the amygdala or hippocampus following the kindling stimulus produced a significant and long-lasting suppressive effect on this experimental model of epilepsy. This is a preliminary report on the development of a surgical neuromodulatory procedure by chronic electrical stimulation of the hippocampus (CHCS) for control of intractable temporal lobe seizures in patients in whom anterior temporal lobectomy is not advisable, i.e., patients with bilateral temporal foci or a unilateral focus spreading to surrounding cerebral regions of the dominant hemisphere. MethodsThis work was divided in two main consecutive stages. In the first stage, we demonstrated that subacute hippocampal stimulation (SAHCS) blocks intractable temporal lobe epileptogenesis with no additional damage to the stimulated tissue, and in a second stage, we attempt to demonstrate that CHCS may produce a sustained, long-lasting antiepileptic condition without additional undesirable effects on language and memory. In addition, taking advantage of this unique and ethically permissible situation, we attempt to determine whether or not the antiepileptic effects of SAHCS and CHCS are due to inhibition of the stimulation of hippocampal tissue by means of a number of electrophysiological, single photon computed tomography (SPECT) perfusion, and autoradiographic techniques. ResultsSAHCS during 3–4 weeks prior to anterior temporal lobectomy applied to a critical area located either at the anterior Pes hippocampus close to the amygdala or at the parahippocampal gyrus close to the entorhinal cortex abolished clinical seizures and significantly decreased the number of interictal spikes at focus after 5–6 days. Microscopy analysis of the stimulated tissue showed no evident histopathological differences between stimulated vs. non-stimulated hippocampal tissues. Additionally, CHCS persistently blocked temporal lobe epileptogenesis for 3–4 months with no apparent additional undesirable effects on short memory. Also, inhibition of the stimulated hippocampus seems to be one of the possible mechanisms underlying the beneficial antiepileptic effects of SAHCS and CHCS. This was revealed by increased threshold and decreased duration of the afterdischarges induced by hippocampal stimulation, flattening of the hippocampal-evoked response recovery cycles, SPECT hypoperfusion of the hippocampal region, and increased hippocampal benzodiazepine receptor binding. ConclusionsFuture studies increasing the number and time of follow-up of patients under hippocampal stimulation are necessary before considering CHCS a reliable procedure for controlling intractable temporal lobe seizures.

REVIEW ARTICLE Acute and Chronic Electrical Stimulation of the Centromedian Thalamic Nucleus: Modulation of Reticulo-Cortical Systems and Predictor Factors for Generalized Seizure Control

The present report recapitulates the clinical and electrophysiologic studies we have performed on patients with certain forms of medically intractable epilepsy to investigate the basic mechanisms and predictor factors for seizure control of the electrical stimulation of the thalamic centromedian nucleus (CM) procedure. Acute electrical stimulation of CM reveals that in humans, as in other animals, CM represents a thalamic relay of a reticulo-cortical system that participates crucially in wakefulness and attentive processes and in regulation of cortical excitability, as well as in the physiopathology of genuine generalized epileptic seizures. For example, unilateral, threshold, low-frequency (6/sec) stimulation of CM produced electrocortical incremental responses, while high-frequency (60/sec) stimulation of CM produced electroencephalogram (EEG) desynchronization and electronegative DC shifts with no behavioral counterparts. In contrast, combined suprathreshold low-frequency (3/sec) stimulation of CM on one side and of mesencephalic reticular stimulation on the other produced generalized spike-wave complex discharges accompanied by the symptoms of a typical absence attack, including motionless stare, eye blinking, and unresponsiveness of patients to a series of flashes under a simple response task. Chronic bilateral, threshold, high-frequency (60/sec) stimulation of CM significantly decreased the number of primary and secondary generalized tonic-clonic seizures and atypical absence attacks and the amount of interictal generalized EEG discharges in both. In addition, it improved the psychological performance of patients and normalized the EEG by increasing the frequency of background EEG activity. In contrast, chronic stimulation of CM reduced neither the number of complex partial seizures nor the epileptic EEG activities localized in the temporal region. Good outcomes of the chronic CM stimulation procedure were achieved depending on correct selection of patients and accuracy of ventriculographic stereotactic targets, as well as on periodic clinical and EEG evaluation and electrophysiologic monitoring of CM electrical stimulation reliability. However, the presence of 3- to 6-month long-lasting effects of CM stimulation made statistical evaluation of ON-OFF effects of CM stimulation under placebo, double-masked randomized experiments difficult.

SACRAL NERVE NEUROMODULATION IN THE TREATMENT OF PATIENTS WITH REFRACTORY MOTOR URGE INCONTINENCE: LONG-TERM RESULTS OF A PROSPECTIVE LONGITUDINAL STUDY

Conservative treatment rarely results in a durable cure of patients with urge incontinence and bladder overactivity. Instrumental and surgical procedures often have significant side effects and less than optimal results. We developed a technique of sacral nerve neuromodulation using chronic unilateral electrical stimulation of the S3 sacral nerve to inhibit the micturition reflex to provide effective nondestructive alternative therapy for patients whose condition is refractory to conservative treatment. Of 85 patients 45 who responded to a test with a temporary electrode underwent implantation of a permanent S3 sacral nerve electrode coupled to a pulse generator. Treatment results were evaluated by urodynamic studies and voiding/incontinence diaries documenting pad use, incontinence episodes, voiding frequency and voided volume. Partial success and cure were defined as 50% to 90% and more than 90% improvement, respectively, in pad use and/or incontinence episodes. Of 45 patients 18 (40%) were cured at an average followup of 47.1 months and 9 (20%) achieved partial success. Median number of pads used and median number of incontinence episodes daily had decreased from 5.4 to 1.2 (p = 0.0001) and 7.1 to 1.3 (p = 0.0001), respectively, 6 months after implantation. Subsequently these results remained almost constant for 5 years. Bladder overactivity disappeared in 19 of the 44 patients (43%). The repeat intervention rate was 37.7% and there was no permanent injury or nerve damage. Sacral nerve neuromodulation is safe, effective and durable in patients with urge incontinence refractory to conservative treatment.