Electrode alignment of transverse tripoles using a percutaneous triple-lead approach in spinal cord stimulation.

The aim of this modeling study is to determine the influence of electrode alignment of transverse tripoles on the paresthesia coverage of the pain area in spinal cord stimulation, using a percutaneous triple-lead approach. Transverse tripoles, comprising a central cathode and two lateral anodes, were modeled on the low-thoracic vertebral region (T10-T12) using percutaneous triple-lead configurations, with the center lead on the spinal cord midline. The triple leads were oriented both aligned and staggered. In the staggered configuration, the anodes were offset either caudally (caudally staggered) or rostrally (rostrally staggered) with respect to the midline cathode. The transverse tripolar field steering with the aligned and staggered configurations enabled the estimation of dorsal column fiber thresholds (I(DC)) and dorsal root fiber thresholds (I(DR)) at various anodal current ratios. I(DC) and I(DR) were considerably higher for the aligned transverse tripoles as compared to the staggered transverse tripoles. The aligned transverse tripoles facilitated deeper penetration into the medial dorsal columns (DCs). The staggered transverse tripoles always enabled broad and bilateral DC activation, at the expense of mediolateral steerability. The largest DC recruited area was obtained with the rostrally staggered transverse tripole. Transverse tripolar geometries, using percutaneous leads, allow for selective targeting of either medial or lateral DC fibers, if and only if the transverse tripole is aligned. Steering of anodal currents between the lateral leads of the staggered transverse tripoles cannot target medially confined populations of DC fibers in the spinal cord. An aligned transverse tripolar configuration is strongly recommended, because of its ability to provide more post-operative flexibility than other configurations.

Cathodal, anodal or bifocal stimulation of the motor cortex in the management of chronic pain?

The conditions of motor cortex stimulation (MCS) applied with epidural electrodes, in particular monopolar (cathodal or anodal) and bipolar stimulation, are discussed. The results of theoretical studies, animal experiments and clinical studies lead to similar conclusions. Basically, cortical nerve fibres pointing at the epidural electrode and those normal to this direction are activated by anodal and cathodal stimulation, respectively. Because MCS for the relief of chronic pain is generally applied bipolarly with electrodes at a distance of at least 10 mm, stimulation may actually be bifocal. The polarity and magnitude of a stimulus needed to recruit cortical nerve fibres varies with the calibre and shape of the fibres, their distance from the electrode and their position in the folded cortex (gyri and sulci). A detailed analysis of intra-operative stimulation data suggests that in bipolar MCS the anode of the bipole giving the largest motor response in the pain region is generally the best electrode for pain management as well, when connected as a cathode. These electrode positions are most likely confined to area 4.

Motor cortex stimulation: role of computer modeling.

Motor cortex stimulation (MCS) is a promising clinical technique used to treat chronic, otherwise intractable pain. However, the mechanisms by which the neural elements that are stimulated during MCS induce pain relief are not understood. Neither is it known which of the main neural elements, i.e. cell bodies, dendrites or fibers are immediately excited by the electrical pulses in MCS. Moreover, it is not known what are the effects of MCS on fibers which are parallel or perpendicular to the cortical layers, below or away from the electrode. The therapy and its efficacy are less likely to be improved until it is better understood how it may work. In this chapter, we present our efforts to resolve this issue. Our computer model of MCS is introduced and some of its predictions are discussed. In particular, the influence of stimulus polarity and electrode position on the electrical field and excitation thresholds of different neural elements is addressed. Such predictions, supported with clinical evidence, should help to elucidate the immediate effects of an electrical stimulus applied over the motor cortex and may ultimately lead to optimizations of the therapy.

Modelling motor cortex stimulation for chronic pain control: electrical potential field, activating functions and responses of simple nerve fibre models.

This computer modelling study on motor cortex stimulation (MCS) introduced a motor cortex model, developed to calculate the imposed electrical potential field characteristics and the initial response of simple fibre models to stimulation of the precentral gyrus by an epidural electrode, as applied in the treatment of chronic, intractable pain. The model consisted of two parts: a three-dimensional volume conductor based on tissue conductivities and human anatomical data, in which the stimulation-induced potential field was computed, and myelinated nerve fibre models allowing the calculation of their response to this field. A simple afferent fibre branch and three simple efferent fibres leaving the cortex at different positions in the precentral gyrus were implemented. It was shown that the thickness of the cerebrospinal fluid (CSF) layer between the dura mater and the cortex below the stimulating electrode substantially affected the distribution of the electrical potential field in the precentral gyrus and thus the threshold stimulus for motor responses and the therapeutic stimulation amplitude. When the CSF thickness was increased from 0 to 2.5 mm, the load impedance decreased by 28%, and the stimulation amplitude increased by 6.6 V for each millimetre of CSF. Owing to the large anode-cathode distance (10 mm centre-to-centre) in MCS, the cathodal fields in mono- and bipolar stimulation were almost identical. Calculation of activating functions and fibre responses showed that only nerve fibres with a directional component parallel to the electrode surface were excitable by a cathode, whereas fibres perpendicular to the electrode surface were excitable under an anode.

Application of a dual channel peroneal nerve stimulator in a patient with a "central" drop foot.

Dropped foot is a common mobility problem amongst patients after a cerebro vascular accident. The condition arises from paresis of the muscles that control the foot movement during the swing phase of gait. If the abnormal movement is not compensated for, it results in a significant decrease in the mobility and hence quality of life. Compensation for the drop foot can be achieved through the application of functional electrical stimulation. To date, in the clinical environment, the stimulation has been applied through electrodes placed on the skin over the common peroneal nerve, and using a single channel implant device. It is well known that with these techniques it is difficult to establish a balanced response of the foot. An implantable dual channel system for stimulation of the deep and superficial peroneal nerve has now been developed for patients with a drop foot following a stroke. By stimulation of the two branches of the common peroneal nerve separately it is possible to achieve a precisely balanced dorsal flexion and eversion of the foot. Stimulation occurs via small bipolar electrodes which are placed subepineural. After successful tests on animals we have now started the two channel peroneal nerve stimulator implantation in patients. The preliminary results of the first implants are presented.

Morphometry of human superficial dorsal and dorsolateral column fibres: significance to spinal cord stimulation.

In spinal cord stimulation (SCS) large diameter cutaneous (Abeta) fibres in the dorsal columns (DCs) are activated and have an inhibiting effect on the transmission of pain signals by Adelta and C fibres from the corresponding dermatome(s). The largest Abeta fibres can be activated up to a maximum depth of about 0.25 mm in the DCs. No data are available on the distribution of the large fibres in this superficial human DC layer at the common SCS levels Th(10-11). Such data are indispensable to improve the predictive capability of a computer model of SCS. The whole myelinated fibre population in the superficial 300 microm of the dorsal column (DC(0-300)) at Th(10-11 )of two human subjects was morphometrically analysed. Some data was obtained from a third subject. The superficial dorsolateral column (DLC(0-300)) was included in this analysis because it was hypothesized that large dorsal spinocerebellar tract fibres could also be activated by SCS. Only very few fibres larger than 10.7 microm were found: a mean of 68 (0.5%) in DC(0-300) and 114 (2%) in DLC(0-300). Considering that the effect of SCS is primarily attributed to activation of these largest fibres, it is concluded that a surprisingly small average amount of 2.4 fibres per running 0.1 mm width and 6 fibres per segmental division of the DC is involved. Distinct mediolateral heterogeneity in fibre composition was found in both DC(0-300) and DLC(0-300). In the DC(0-300), the mean diameter of fibres > or =7.1 microm increases significantly by 5% from medial to lateral. Density (i.e. number of fibres per 1000 microm(2)) and frequency (i.e. percentage of a fibre size group compared to its parent population) of the large fibres increase significantly from medial to lateral in the DC(0-300). For fibres > or =10.7 microm, these parameters increase by 200 and 269%, respectively. It is concluded that the difference in stimulation threshold of large Abeta fibres in the median and lateral DC can be mainly attributed to the absence and presence, respectively, of collaterals at the stimulation site. Marked differences were found between DC(0-300) and DLC(0-300). The largest DLC(0-300) fibres (> or =10.7 microm) have a 320% higher frequency and a 473% higher density. Their mean diameter is, however, only 2% larger. The largest DLC(0-300) fibres are not likely to be recruited by SCS, since they are not larger than their DC(0-300) counterparts, they lack collaterals (which would reduce the threshold stimulus substantially) and they are more remote from the stimulation electrode.

The effect of subthreshold prepulses on the recruitment order in a nerve trunk analyzed in a simple and a realistic volume conductor model.

The influence of subthreshold depolarizing prepulses on the threshold current-to-distance and the threshold current-to-diameter relationship of myelinated nerve fibers has been investigated. A nerve fiber model was used in combination with both a simple, homogeneous volume conductor model with a point source and a realistic, inhomogeneous volume conductor model of a monofascicular nerve trunk surrounded by a cuff electrode. The models predict that a subthreshold depolarizing prepulse will desensitize Ranvier nodes of fibers in the vicinity of the cathode and thus cause an increase in the threshold current of a subsequent pulse to activate these fibers. If the increase in threshold current of the excited node is large enough, the excitation will be accompanied by a strong hyperpolarization of adjacent nodes, preventing the propagation of action potentials in these fibers. As fibers close to the electrode are more desensitized by prepulses than more distant ones, it is possible to stimulate distant fibers without stimulating such fibers close to the electrode. Moreover, as larger fibers are more desensitized than smaller ones, smaller fibers have lower threshold currents than larger fibers up to a certain distance from the electrode. The realistic model has provided an additional condition for the application of this method to invert nerve fiber recruitment, i.e., real or virtual anodes should be close to the cathode. When using a cuff electrode for this purpose, in the case of monopolar stimulation the cuff length (determining the position of the virtual anodes) should not exceed twice the internodal length of the fibers to be blocked. Similarly, the distance between cathode and anodes should not exceed the internodal length of these fibers when stimulation is to be applied tripolarly.

A nerve stimulation method to selectively recruit smaller motor-units in rat skeletal muscle.

Electrical stimulation of peripheral nerve results in a motor-unit recruitment order opposite to that attained by natural neural control, i.e. from large, fast-fatiguing to progressively smaller, fatigue-resistant motor-units. Yet animal studies involving physiological exercise protocols of low intensity and long duration require minimal fatigue. The present study sought to apply a nerve stimulation method to selectively recruit smaller motor-units in rat skeletal muscle. Two pulse generators were used, independently supplying short supramaximal cathodal stimulating pulses (0.5 ms) and long subthreshold cathodal inactivating pulses (1.5 s) to the sciatic nerve. Propagation of action potentials was selectively blocked in nerve fibres of different diameter by adjusting the strength of the inactivating current. A tensile-testing machine was used to gauge isometric muscle force of the plantaris and both heads of the gastrocnemius muscle. The order of motor-unit recruitment was estimated from twitch characteristics, i.e. peak force and relaxation time. The results showed prolonged relaxation at lower twitch peak forces as the intensity of the inactivating current increased, indicating a reduction of the number of large motor-units to force production. It is shown that the nerve stimulation method described is effective in mimicking physiological muscle control.

Electrical stimulation of the trigeminal tract in chronic, intractable facial neuralgia.

In this paper the treatment of patients with chronic, intractable trigeminal neuralgia by invasive electrical stimulation of the Gasserion ganglion is reviewed. Two different surgical techniques are employed in this treatment. Most frequently, a method similar to the traditional technique for percutaneous glycerol and radiofrequency trigeminal rhizolysis is used: a small percutaneous stimulation electrode is advanced under fluoroscopic control through a thin needle via the foramen ovale to the Gasserian cistern. Some neurosurgeons use an open surgical technique by which the Gasserian ganglion is approached subtemporally and extradurally, and the bipolar pad electrode is sutured to the dura. When percutaneous test stimulation is successful (at least 50% pain relief) the electrode is internalized and connected to a subcutaneous pulse generator or RF-receiver. Data from 8 clinical studies, including 267 patients have been reviewed. Of all 233 patients with medication-resistant atypical trigeminal neuralgia 48% had at least 50% long term pain relief. The result of test stimulation is a good predictor of the long term effect, because 83% of all patients with successful test stimulation had at least 50% long term relief, and 70% had at least 75% long term relief. Patients generally preferred this invasive method over TENS. The success rate in patients with postherpetic trigeminal neuralgia was very low (less than 10%). It is suggested that the likelihood of pain relief by electrical stimulation is inversely related to the degree of sensory loss. It is concluded that invasive stimulation of the Gasserian ganglion is a promising treatment modality for patients with chronic, intractable, atypical trigeminal neuralgia.

Identification of the target neuronal elements in electrical deep brain stimulation.

The aim of this study is to identify the primary neuronal target elements in electrical deep-brain stimulation, taking advantage of the difference in strength-duration time constant (tau(sd)) of large myelinated axons ( approximately 30-200 micros), small axons ( approximately 200-700 micros) and cell bodies and dendrites ( approximately 1-10 ms). Strength-duration data were measured in patients suffering from Parkinson's disease or essential tremor and treated by high-frequency stimulation in the ventral intermediate thalamic nucleus or the internal pallidum. Threshold voltages for the elimination of tremor were determined at various pulsewidths and a pulse rate of 130 pulses per second. The tau(sd) was calculated using Weiss's linear approximation. Its mean value was 64.6+/-25.4 micros (SD) for the thalamic nucleus and 75.3+/-25.5 micros for the internal pallidum. Corrections to the mean values were made because the tau(sd) values were based on voltage-duration measurements using polarizable electrodes. Apart from this systematic error, a resolution error, due to the relatively large increment steps of the pulse amplitude, was taken into account, resulting in mean tau(sd) estimates of 129 and 151 micros for the thalamic nucleus and the internal pallidum, respectively. It is concluded that the primary targets of stimulation in both nuclei are most probably large myelinated axons.

Nerve stimulation with a multi-contact cuff electrode: validation of model predictions.

The recruitment characteristics of muscle selective nerve stimulation by a multi-contact nerve cuff electrode, as predicted by computer modeling, have been investigated in acute experiments on rabbits. A nerve cuff containing five or six dot electrodes was placed around the sciatic nerve in five rabbits. M-waves were recorded with wire electrodes from the lateral gastrocnemius, soleus, tibialis anterior, and extensor digitorum longus muscles. The muscle recruitment performances of three contact configurations (monopole, transverse bipole, transverse tripole) were compared. The selectivity was quantified by the recruitment of two muscles (one extensor and one flexor) in response to a particular stimulus. The results showed that only in a few cases, transverse bi- and tripolar stimulation provided a better selectivity than monopolar stimulation. Neither of the two extensors, nor of the two flexors could be stimulated separately. In accordance with the results of the modeling studies, bi- and tripolar stimulation required higher stimulus currents than monopolar stimulation, whereas maximum recruitment and slopes of recruitment curves were lower. The rabbit sciatic nerve appears to be a less suitable preparation for reproducible selectivity experiments, due to the variability in the number and size of the fascicles and their position in this nerve.

Chronaxie calculated from current-duration and voltage-duration data.

To determine the rheobase and the chronaxie of excitable cells from strength-duration curves both constant-current pulses and constant-voltage pulses are applied. Since the complex impedance of the electrode-tissue interface varies with both the pulsewidth and the stimulation voltage, chronaxie values estimated from voltage-duration measurements will differ from the proper values as determined from current-duration measurements. To allow a comparison of chronaxie values obtained by the two stimulation methods, voltage-duration curves were measured in human subjects with a deep brain stimulation electrode implanted, while the current and the load impedance of the stimulation circuit were determined in vitro as a function of both stimulation voltage and pulsewidth. Chronaxie values calculated from voltage-duration data were shown to be 30-40% below those estimated from current-duration data. It was also shown that in the normal range of stimulation amplitudes (up to 7 V) the load impedance increases almost linearly with the pulsewidth. This result led us to present a simple method to convert voltage-duration data into current-duration data, thereby reducing the error in the calculated chronaxie values to approximately 6%. For this purpose voltage-duration data have to be measured for pulses up to 10-20 times the expected chronaxie.

A model of the electrical behaviour of myelinated sensory nerve fibres based on human data.

Calculation of the response of human myelinated sensory nerve fibres to spinal cord stimulation initiated the development of a fibre model based on electrophysiological and morphometric data for human sensory nerve fibres. The model encompasses a mathematical description of the kinetics of the nodal membrane, and a non-linear fibre geometry. Fine tuning of only a few, not well-established parameters was performed by fitting the shape of a propagating action potential and its diameter-dependent propagation velocity. The quantitative behaviour of this model corresponds better to experimentally determined human fibre properties than other mammalian, nonhuman models do. Typical characteristics, such as the shape of the action potential, the propagation velocity and the strength-duration behaviour show a good fit with experimental data. The introduced diameter-dependent parameters did not result in a noticeable diameter dependency of action potential duration and refractory period. The presented model provides an improved tool to analyse the electrical behaviour of human myelinated sensory nerve fibres.

Quantitative aspects of the clinical performance of transverse tripolar spinal cord stimulation.

A multicenter study was initiated to evaluate the performance of the transverse tripolar system for spinal cord stimulation. Computer modeling had predicted steering of paresthesia with a dual channel stimulator to be the main benefit of the system. The quantitative analysis presented here includes the results of 484 tests in 30 patients. For each test, paresthesia coverage as a function of voltage levels was stored in a computerized database, including a body map which enabled calculation of the degree of paresthesia coverage of separate body areas, as well as the overlap with the painful areas. The results show that with the transverse tripolar system steering of the paresthesia is possible, although optimal steering requires proper placement of the electrode with respect to the spinal cord. Therefore, with this steering ability as well as a larger therapeutic stimulation window as compared to conventional systems, we expect an increase of the long-term efficacy of spinal cord stimulation. Moreover, in view of the stimulation-induced paresthesia patterns, the system allows selective stimulation of the medial dorsal columns.

Estimation of fiber diameters in the spinal dorsal columns from clinical data.

Lack of human morphometric data regarding the largest nerve fibers in the dorsal columns (DC's) of the spinal cord has lead to the estimation of the diameters of these fibers from clinical data retrieved from patients with a new spinal cord stimulation (SCS) system. These patients indicated the perception threshold of stimulation induced paresthesia in various body segments, while the stimulation amplitude was increased. The fiber diameters were calculated with a computer model, developed to calculate the effects of SCS on spinal nerve fibers. This computer model consists of two parts: 1) a three-dimensional (3-D) volume conductor model of a spinal cord segment in which the potential distribution due to electrical stimulation is calculated and 2) an electrical equivalent cable model of myelinated nerve fiber, which uses the calculated potential field to determine the threshold stimulus needed for activation. It is shown that the largest fibers in the medial DC's are significantly smaller than the largest fibers in the lateral parts. This finding is in accordance with the fiber distribution in cat, derived from the corresponding propagation velocities. Moreover, it is shown that the mediolateral increase in fiber diameter is mainly confined to the lateral parts of the DC's. Implementation of this mediolateral fiber diameter distribution of the DC's in the computer model enables the prediction of the recruitment order of dermatomal paresthesias following increasing electrical stimulation amplitude.

Multigrid solution of the potential field in modeling electrical nerve stimulation.

In this paper, multilevel techniques are introduced as a fast numerical method to compute 3-D potential field in nerve stimulation configurations. It is shown that with these techniques the computing time is reduced significantly compared to conventional methods. Consequently, these techniques greatly enhance the possibilities for parameter studies and electrode design. Following a general description of the model of nerve stimulation configurations, the basic principles of multilevel solvers for the numerical solution of partial differential equations are briefly summarized. Subsequently, some essential elements for successful application are discussed. Finally, results are presented for the potential field in a nerve bundle induced by tripolar stimulation with a cuff electrode surrounding part of the nerve.

Theoretical performance and clinical evaluation of transverse tripolar spinal cord stimulation.

A new type of spinal cord stimulation electrode, providing contact combinations with a transverse orientation, is presented. Electrodes were implanted in the cervical area (C4-C5) of two chronic pain patients and the stimulation results were subsequently simulated with a computer model consisting of a volume conductor model and active nerve fiber models. For various contact combinations a good match was obtained between the modeling results and the measurement data with respect to load resistance (less than 20% difference), perception thresholds (16% difference), asymmetry of paresthesia (significant correlation) and paresthesia distributions (weak correlation). The transversally oriented combinations provided the possibility to select either a preferential dorsal column stimulation, a preferential dorsal root stimulation or a mixed stimulation. The (a)symmetry of paresthesia could largely be affected in a predictable way by the selection of contact combinations as well. The transverse tripolar combination was shown to give a higher selectivity of paresthesia than monopolar and longitudinal dipolar combinations, at the cost of an increased current (more than twice).

Computer modelling of spinal cord stimulation and its contribution to therapeutic efficacy.

An overview of computer models developed since the late seventies, which enable the simulation of the primary effects of spinal cord stimulation (SCS) on nerve fibres, is presented. These models consist of a 3-dimensional volume conductor model, representing anatomical structures and their electrical conductivities, and cable models representing the electrical behaviour of nerve fibres. The characteristics of these models and their relation to anatomy and physiology, as well as the calculation of stimulation-induced electrical fields and their effect on nerve fibre models, are reviewed. It is shown that most characteristics of SCS as predicted by computer modelling correspond well with empirical data. Accordingly, a theoretical framework describing the relations between relevant parameters in SCS is presented. Finally, it is shown how theory and computer modeling are applied to improve the efficacy of SCS by the optimization of its technique, primarily by the design of new epidural electrodes.

Transverse tripolar stimulation of peripheral nerve: a modelling study of spatial selectivity.

Various anode-cathode configurations in a nerve cuff are modelled to predict their spatial selectivity characteristics for functional nerve stimulation. A 3D volume conductor model of a monofascicular nerve is used for the computation of stimulation-induced field potentials, whereas a cable model of myelinated nerve fibre is used for the calculation of the excitation thresholds of fibres. As well as the usual configurations (monopole, bipole, longitudinal tripole, 'steering' anode), a transverse tripolar configuration (central cathode) is examined. It is found that the transverse tripole is the only configuration giving convex recruitment contours and therefore maximises activation selectivity for a small (cylindrical) bundle of fibres in the periphery of a monofascicular nerve trunk. As the electrode configuration is changed to achieve greater selectivity, the threshold current increases. Therefore threshold currents for fibre excitation with a transverse tripole are relatively high. Inverse recruitment is less extreme than for the other configurations. The influences of several geometrical parameters and model conductivities of the transverse tripole on selectivity and threshold current are analysed. In chronic implantation, when electrodes are encapsulated by a layer of fibrous tissue, threshold currents are low, whereas the shape of the recruitment contours in transverse tripolar stimulation does not change.