Epidural Spinal Cord Electrical Stimulation Research Articles

Improvement of brain perfusion in patients with chronic brain ischemia at epidural spinal cord electrical stimulation.

ObjectiveIncreasing life expectancy and aging of the population is accompanied by a steady increase in the number of elderly patients with chronic cerebral ischemia and age-related cognitive impairment associated with cerebral hypoperfusion and microangiopathy. The aim of this study was to identify long-term changes in cerebral blood flow (CBF) in patients with chronic cerebral ischemia at the epidural electrical stimulation of the spinal cord (SCS).Materials and methodsChanges in cerebral blood flow were studied according to CT perfusion in 59 patients (aged 55–78 years) with vertebrogenic pain syndromes and chronic cerebral ischemia during epidural electrical stimulation of the spinal cord at the cervical (C3–C5) and lower thoracic (Th9–Th10) levels.ResultsIn all patients, on the 5th day of trial SCS, an increase in cerebral blood flow by from 58.6 ± 1.13 ml/100 ml/min to 64.8 ± 1.21 ml/100 ml/min (p < 0.01) with stimulation at the Th9-Th10 level and from 58.8 ± 1.12 ml/100 ml/min to 68.2 ± 1.42 ml/100 ml/min (p < 0, 01) with stimulation at the C3-C5 level. These changes in brain perfusion were preserved during the follow-up examination 1 year after the implantation of chronic SCS system. The greatest increase in CBF was registered in the frontotemporal regions, subcortical structures and white matter of the brain. Changes in cerebral perfusion did not correlate with the degree of reduction in the severity of the accompanying pain syndrome. The change in CBF in the control group (32 patients) in all periods was not statistically significant.ConclusionOur results show that SCS is accompanied by a persistent improvement in brain perfusion, which may be potentially useful for developing methods for reducing age-related vascular disorders in the elderly.

A Fully Integrated Wireless SoC for Motor Function Recovery After Spinal Cord Injury.

This paper presents a wirelessly powered, fully integrated system-on-a-chip (SoC) supporting 160-channel stimulation, 16-channel recording, and 48-channel bio-impedance characterization to enable partial motor function recovery through epidural spinal cord electrical stimulation. A wireless transceiver is designed to support quasi full-duplex data telemetry at a data rate of 2Mb/s. Furthermore, a unique in situ bio-impedance characterization scheme based on time-domain analysis is implemented to derive the Randles cell electrode model of the electrode-electrolyte interface. The SoC supports concurrent stimulation and recording while the high-density stimulator array meets an output compliance voltage of up to ±10V with versatile stimulus programmability. The SoC consumes 18mW and occupies a chip area of 5.7mm × 4.4mm using 0.18μm high-voltage CMOS process. In our in vivo rodent experiment, the SoC is used to perform wireless recording of EMG responses while stimulation is applied to enable the standing and stepping of a paralyzed rat. To facilitate the system integration, a novel thin film polymer packaging technique is developed to provide a heterogeneous integration of the SoC, coils, discrete components, and high-density flexible electrode array, resulting in a miniaturized prototype implant with a weight and form factor of 0.7g and 0.5cm3, respectively.

Flexible active electrode arrays with ASICs that fit inside the rat’s spinal canal

Epidural spinal cord electrical stimulation (ESCS) has been used as a means to facilitate locomotor recovery in spinal cord injured humans. Electrode arrays, instead of conventional pairs of electrodes, are necessary to investigate the effect of ESCS at different sites. These usually require a large number of implanted wires, which could lead to infections. This paper presents the design, fabrication and evaluation of a novel flexible active array for ESCS in rats. Three small (1.7 mm2) and thin (100 μm) application specific integrated circuits (ASICs) are embedded in the polydimethylsiloxane-based implant. This arrangement limits the number of communication tracks to three, while ensuring maximum testing versatility by providing independent access to all 12 electrodes in any configuration. Laser-patterned platinum-iridium foil forms the implant’s conductive tracks and electrodes. Double rivet bonds were employed for the dice microassembly. The active electrode array can deliver current pulses (up to 1 mA, 100 pulses per second) and supports interleaved stimulation with independent control of the stimulus parameters for each pulse. The stimulation timing and pulse duration are very versatile. The array was electrically characterized through impedance spectroscopy and voltage transient recordings. A prototype was tested for long term mechanical reliability when subjected to continuous bending. The results revealed no track or bond failure. To the best of the authors’ knowledge, this is the first time that flexible active electrode arrays with embedded electronics suitable for implantation inside the rat’s spinal canal have been proposed, developed and tested in vitro.

An Implantable Versatile Electrode-Driving ASIC for Chronic Epidural Stimulation in Rats.

This paper presents the design and testing of an electrode driving application specific integrated circuit (ASIC) intended for epidural spinal cord electrical stimulation in rats. The ASIC can deliver up to 1 mA fully programmable monophasic or biphasic stimulus current pulses, to 13 electrodes selected in any possible configuration. It also supports interleaved stimulation. Communication is achieved via only 3 wires. The current source and the control of the stimulation timing were kept off-chip to reduce the heat dissipation close to the spinal cord. The ASIC was designed in a 0.18- μm high voltage CMOS process. Its output voltage compliance can be up to 25 V. It features a small core area (<;0.36 mm(2)) and consumes a maximum of 114 μW during a full stimulation cycle. The layout of the ASIC was developed to be suitable for integration on the epidural electrode array, and two different versions were fabricated and electrically tested. Results from both versions were almost indistinguishable. The performance of the system was verified for different loads and stimulation parameters. Its suitability to drive a passive epidural 12-electrode array in saline has also been demonstrated.

Effects of epidural spinal cord electrical stimulation with varying voltage and frequency on spinal cord refle-xes

Objective To investigate the effects of epidural spinal cord electrical stimulation (ESCES) on spinal cord reflexes in normal adult rats, and to find out where and how the spinal cord reflexes are generated. Methods Ten adult female Sprague Dawley rats were anaesthetized and an electrode was placed at the S, spinal cord segment. Single electric pulses with 200 μs pulse width and voltages of 400 mV, 600 mV and 1200 mV were used in the ESCES. 1200 mV voltages with 50 Hz, 60 Hz, 80 Hz, 100 Hz frequency were also tested. EMG signals were re-corded with concentric needle electrodes in the rats' semitendinosus muscles to observe the characteristics of spinal cord reflexes. Results The voltage threshold for generating semitendinosus muscle response was 300 mV. The three ESCES voltages induced 2 kinds of spinal cord reflexes. The 400 mV and 600 mV stimulation induced spinal cord reflexes with short latency (5.27±0.36 ms and 5.19±0.67 ms respectively). The 1200 mV stimulation volt-age induced spinal cord reflexes with long latency (2.57±0.23 ms). Spinal cord reflexes could be generated by 50 Hz, 60 Hz, 80 Hz, and 100 Hz ESCES. At the higher frequencies, spinal cord reflexes declined late in the ex-periments and then appeared irregular. In some of the rats, spinal cord reflexes vanished entirely late in the stimula-tion experiments. The latency and duration of the spinal cord reflexes induced by 50 Hz ESCES were (4.46 ± 1.07) ms and (7.33±1.00)ms respectively. These were significantly different from the latency and duration initia-ted by 60 Hz, 80 Hz or 100 Hz ESCES. Conclusions Different ESCES voltages induce different spinal cord refle-xes generated differently. The long latency reflexes might be monosynaptic responses mediated by dorsal root excite-ment, while the short latency reflexes might be sarcous exciting electric activity mediated by direct excitement of mo-tor neurons or motor fibers. The irregular spinal cord reflexes induced by higher frequency ESCES might be one kind of monosynaptic response. Irregularly appearing spinal cord reflexes induced by higher frequency stimulation might due to the inhibitory effect of higher frequency stimulation. Key words: Epidural spinal cord electrical stimulation; Voltage ; Frequency; Spinal cord ; Spinalcord reflexes

The response of brain with chronic pain during spinal cord stimulation, using FDG-PET

To evaluate the effect of epidural spinal cord electrical stimulation (SCS), the response of the brain with chronic pain was examined “before” and “during” stimulation, using fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET). The thalamus was considered to have an important role for the response.

Design issues of a randomised controlled clinical trial on spinal cord stimulation in critical limb ischaemia

Review of the design of a clinical study to evaluate of the efficacy of epidural spinal cord electrical stimulation (ESES) as compared to best medical treatment in patients with nonreconstructible critical limb ischaemia. Randomised controlled clinical trial of pragmatic type, which will be analysed according to the intention-to-treat principle. The treatment strategies are ESES, in addition to best medical treatment, and best medical treatment alone. Patients are followed-up for at least 18 months. The ESES-trial is an ongoing multicentre trial in 17 hospitals in The Netherlands. Patients with critical limb ischaemia, nonsuitable for either primary intervention or reintervention after failing reconstructions. Limb survival, patient survival, quality of life and cost-effectiveness. From November 1991 until May 1994 120 patients had been enrolled. Using life-table analysis, at one year 76% of these randomised patients were alive: 41% without amputation and 35% with amputation. Quality of life of the trial patients was low, even compared to other severely ill patient groups, such as liver and heart transplant candidates. Considering the high incidence of death and amputation, 18 months of follow-up seems adequate to detect a clinically relevant outcome improvement from ESES-treatment, if present. We hope to present the results of this study at the end of 1995.

Clinical results of epidural spinal cord electrical stimulation in patients affected with limb-threatening chronic arterial obstructive disease.

Between 1982 and 1990, 76 patients (33 women, 43 men, mean age 71.4 +/- 10 years) affected with limb-threatening peripheral vascular disease (claudication < 20 m: 3 patients; rest pain: 10 patients; necrosis1 smaller than 3 cm2: 28 patients; necrosis2 larger than 3 cm2: 35 patients) not amenable to medical and/or surgical therapy, were treated by epidural spinal cord electrical stimulation (ESES). Effectiveness of ESES was evaluated by consideration of pain control, walking distance, and healing of ischemic lesions. At a mean follow-up of twenty-six months (range: one to seventy-six) 44 limbs (58%) were amputated (rest pain 2; necrosis1 13; necrosis2 29) and 39% of necrotic lesions smaller than 3 cm2 healed. The overall limb salvage rate was 42%. Pain control was obtained in 80% of patients at the one-year and 75% at the two-year follow-up, with infrequent use of pain relievers. Despite the poor clinical results observed, the limb salvage rate testifies to the effectiveness of ESES in limb-threatening ischemia. Moreover, the authors noticed a good ESES effect on pain relief, maximal in the early and intermediate postimplant periods. In conclusion ESES must be considered the last resort in peripheral vascular disease in patients in whom medical and/or surgical therapies are ineffective or impossible. Necrotic lesions larger than 3 cm2 contraindicate, in their opinion, ESES implant.

Indices of Sympathetic Vascular Innervation in Scleroderma Patients Treated by Epidural Spinal Cord Electrical Stimulation (ESES)

In an attempt to explain the epidural spinal cord electrical stimulation (ESES) mechanism of action on microcirculation, the authors measured arterial and venous plasma concentration of norepinephrine (NE), by chromatography, in 17 patients (16 women - 1 man, mean age forty-seven years, range: twenty- four to sixty-four years) affected by scleroderma (15 patients) and Raynaud's disease (2 patients), treated by ESES (mean follow-up 29.3 months, range: one to forty-nine months). Blood was sampled with the patient in the supine position, resting at least for thirty minutes, in environmental standard conditions, from a brachial vein (without tourniquet) and a radial artery, with pacemaker off for twelve hours and pacemaker on for thirty minutes. Microcirculatory modifications induced by ESES were also evaluated in all patients by transcutaneous oxygen tension (TcPO2) and laser Doppler flow (LDF), simultaneously measured with the pa tient in the supine position, on the palm (thenar and hypothenar eminences) during three thirty-minute consecutive phases at 42 ° C and 45°C (phase I: pace maker off for twelve hours; phase II: pacemaker on; phase III: pacemaker off). For technical reasons, NE dosages were available in only 12 patients. Cate gorizing the patients on the basis of clinical results (group A, excellent-good, 9 patients; group B, poor-null, 3 patients) the authors noted after the ESES stim ulation: 1. The vasodilatation index (TcPO2 42°C/TcPO2 45 ° C) increased in phase II and phase III (phase I vs phase II, p &lt; 0.001; phase I vs phase III, p &lt; 0.01). 2. The LDF flow differences between 42°C and 45°C were statistically sig nificant in responders between phase I and phase III (p &lt; 0.01). 3. The physiologic norepinephrine arteriovenous ratio was inverted in 7 of 9 patients of group A and in none of group B (p &lt; 0.05). TcPO2 and LDF are useful noninvasive techniques to evaluate microcircula tory modifications induced by ESES. Moreover, the arteriovenous ratio de crease in plasma norepinephrine may explain the ESES effect on microcircula tion and the reduced vasomotor tone.

Laser Doppler Flowmetry and Transcutaneous Oxygen Tension in Patients with Severe Arterial Insufficiency Treated by Epidural Spinal Cord Electrical Stimulation

Six patients (3 men, 3 women, mean age 74.2 years) affected by severe arterial insufficiency with rest pain and/or necrosis (smaller than 3 cm2) have been studied simultaneously by means of transcutaneous oxygen tension (Tcp02) and laser Doppler flowmetry (LDF) measurements. They had been submitted to epidural spinal cord electrical stimulation (ESES) device implant from one week to thirteen months previously. Tcp02 vasodilation index and LDF flow and LDF volume increased in 5 patients in whom the ESES was effective in pain relief and ulcer healing. In 1 diabetic patient the clinical result was poor and neither Tcp02 nor LDF showed any improvement. The LDF flow and LDF volume increase, coupled with the simultaneous Tcp02 vasodilation index increase, testify to the amelioration of the cutaneous microcir culation, related to a diminished vasomotor tone (sympathetic activity), induced by ESES . In diabetic patients with neuropathy (autonomic sympathectomy) a high vasodilation index contraindicates ESES implant.

Foot salvage and improvement of microvascular blood flow as a result of epidural spinal cord electrical stimulation

Epidural spinal cord electrical stimulation has been suggested as an alternative treatment in patients with limb-threatening ischemia in whom vascular reconstructive surgery is not possible anymore. We studied the effects of epidural spinal cord electrical stimulation on microcirculatory blood flow in 20 patients with ischemic rest pain and ulcers. Angiography showed occluded crural arteries technically unsuitable for reconstructive surgery. Intravital capillary microscopy was used to assess capillary density and diameter and red blood cell velocity before and after a 1-minute period of arterial occlusion. After epidural spinal cord electrical stimulation 18 patients claimed immediate pain relief, which was confirmed by intravital capillary microscopy. Capillary density increased from 10 to 19/mm2 (p < 0.001), red blood cell velocity increased from 0.088 to 0.496 mm/sec (p < 0.001), and peak red blood cell velocity after arterial occlusion increased from 0.092 to 0.548 mm/sec (p < 0.001). Two patients had no immediate pain relief; they did not show improvement of microcirculatory perfusion, and amputation was necessary. During the follow-up period (3 months to 3 years, mean 27 months), six other patients had recurrent ischemic pain, and amputation was necessary. In 12 patients pain relief continued, and ischemic ulcers healed; capillary microscopy confirmed improved microcirculatory blood flow. Microcirculatory parameters were significantly higher in respondents than in nonrespondents (p < 0.001). Life-table analysis revealed a cumulative foot salvage of 80% and 56% after 1 and 2 years, respectively. In conclusion, under special conditions in most of a short series of patients epidural spinal cord electrical stimulation relieved rest pain, improved skin nutritional flow leading to healing of ulcers of moderate size, and thus increased the salvage of feet with limb-threatening ischemia. Use of epidural spinal cord electrical stimulation can be considered when indicated by the results of capillary microscopy as an alternative treatment in patients with nonreconstructable occlusive arterial disease.

Foot salvage and improvement of microvascular blood flow as a result of epidural spinal cord electrical stimulation

Foot salvage and improvement of microvascular blood flow as a result of epidural spinal cord electrical stimulation

Is epidural spinal cord electrical stimulation indicated in patients with severe lower limb ischaemia?

Is epidural spinal cord electrical stimulation indicated in patients with severe lower limb ischaemia?

Epidural Spinal Cord Electrical Stimulation Improves Microvascular Blood Flow in Severe Limb Ischemia

Epidural spinal cord electrical stimulation (ESES) was performed on 10 patients with severe limb ischemia due to atherosclerotic disease. Microcirculatory parameters were assessed before and after ESES. Bright field microscopy was used to assess capillary diameters and red blood cell (RBC) velocity in the dorsum of the foot. Fluorescein microscopy was used with intravenously injected sodium fluorescein to study capillary density and sodium fluorescein appearance time in the dorsum of the toe. The systolic ankle/arm pressure ratio and toe pressure measurements were used as macrocirculatory parameters. After ESES, clinical improvement was confirmed by intravital microscopy. Capillary density increased (p less than 0.001), RBC velocity in capillaries already perfused before ESES increased from 0.054 mm/sec to 0.762 mm/sec (p less than 0.001), and sodium fluorescein appearance time decreased from 72 to 45 seconds (p less than 0.001). Capillary diameter did not change significantly so that the increase in RBC velocity may be interpreted as enhanced volume flow. Systolic ankle/arm pressure ratios and digital arterial pressure did not change significantly. The current results show that in patients with severe occlusive arterial disease of the lower limbs, ESES recruits capillaries not perfused in the control situation and enhances skin blood flow, improvements that may explain the beneficial clinical effects of ESES.