Jan Holsheimer

New trends in neuromodulation for the management of neuropathic pain

SINCE ITS FIRST application in 1967, the methodology and technology of spinal cord stimulation for the management of chronic, intractable pain have evolved continuously. Despite these developments and improved knowledge of the effects of spinal anatomy and epidural contact configuration on paresthesia coverage, the clinical results of spinal cord stimulation—particularly the long-term effects—are still unsatisfactory in many patients. This dissatisfaction has come primarily from the failure of single-electrode configurations to provide consistent paresthesia coverage of the entire painful area. Therefore, new approaches were developed during the late 1990s that attempted to selectively cover one or more dermatomes with paresthesia as well as to provide sequential stimulation of different anatomic sites. These approaches have been applied both intraspinally and extraspinally by stimulating either the spinal nerves or the dorsal columns. To target parts of the latter, different methods have been developed and tested using either two-dimensional contact configurations or electronic field steering. These developments hold promise for improving long-term outcomes as well as increasing the number of pain conditions that can be treated with neuromodulation therapy. In this review, the history, theoretical basis, and evolution of these methodologies, as well as the ways in which they represent new trends in neuromodulation, are discussed.

Excitation of dorsal root fibers in spinal cord stimulation: a theoretical study

In epidural spinal cord stimulation it is likely not only that dorsal column fibers are activated, but also that dorsal root fibers will be involved as well. In this investigation a volume conductor model of the spinal cord was used and dorsal root fibers were modeled by an electrical network including fiber excitation. The effects of varying some geometric fiber characteristics, as well as the influence of the dorsal cerebrospinal fluid layer and the electrode configuration on the threshold stimulus for their excitation, were assessed. The threshold values were compared with those of dorsal column fibers. The results of this modeling study predict that, besides the well known influence of fiber diameter, the curvature of the dorsal root fibers and the angle between these fibers and the spinal cord axis are a major influence on their threshold values. Because of these effects, threshold stimuli of dorsal root fibers were relatively low as compared to dorsal column fibers. Excitation of the dorsal root fibers occurred near the entry point of the fibers.<<ETX>>

Which Neuronal Elements are Activated Directly by Spinal Cord Stimulation

The purpose of this paper is to discuss which nerve fibers in the various quadrants of the spinal cord are immediately activated under normal conditions of spinal cord stimulation, ie, at voltages within the therapeutic range. The conclusions are based on both empirical and computer modeling data. The recruitment of dorsal column (DC) fibers is most likely restricted to Aβ fibers with a diameter ≥ 10.7 μm in a 0.20–0.25 mm layer under the pia mater and fibers of 9.4–10.7 μm in an even smaller outer layer when a conventional SCS lead is used. In a 0.25‐mm outer layer of the T11 segment the number of Aβ fibers ≥ 10.7 μm, as estimated in a recent morphometric study, is about 56 in each DC. Because a DC at T11 innervates 12 dermatomes, a maximum of 4–5 fibers (≥ 10.7 μm) may be recruited in each dermatome near the discomfort threshold. The dermatome activated just below the discomfort threshold is likely to be stimulated by just a single fiber, suggesting that paresthesia and pain relief may be effected in a dermatome by the stimulation of a single large Aβ fiber. The depth of stimulation in the DCs, and thereby the number of recruited Aβ fibers, may be increased 2–3 fold when stimulation is applied by an optimized electrode configuration (a narrow bi/tripole or a transverse tripole). Assuming that the largest Aβ fibers in a dorsal root have a diameter of 15 μm, the smallest ones recruited at discomfort threshold would be 12 μm. The latter are presumably of proprioceptive origin and responsible for segmental reflexes and uncomfortable sensations. Furthermore, it is shown to be unlikely that, apart from dorsal roots and a thin outer layer of the DCs, any other spinal structures are recruited when stimulation is applied in the dorsal epidural space. Finally, anodal excitation and anodal propagation block are unlikely to occur with SCS.

Recruitment of dorsal column fibers in spinal cord stimulation: influence of collateral branching

An electrical network model of myelinated dorsal column nerve fibers is presented. The effect of electrical simulation was investigated using both a homogeneous volume conductor and a more realistic model of the spinal cord. An important feature of dorsal column nerve fibers is the presence of myelinated collaterals perpendicular to the rostro-caudal fibers. It was found that transmembrane potentials, due to external monopolar stimulation, at the node at which a collateral is attached, is significantly influenced by the presence of the collateral. It is concluded that both excitation threshold and blocking threshold of dorsal column fibers are decreased up to 50% compared to unbranched fibers.<<ETX>>

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 (τsd) of large myelinated axons (≈ 30–200 µs), small axons (≈ 200–700 µs) and cell bodies and dendrites (≈ 1–10 ms). Strength–duration data were measured in patients suffering from Parkinsons 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 τsd was calculated using Weisss linear approximation. Its mean value was 64.6 ± 25.4 µs (SD) for the thalamic nucleus and 75.3 ± 25.5 µs for the internal pallidum. Corrections to the mean values were made because the τsd 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 τsd estimates of 129 and 151 µs 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.

Anodal vs cathodal stimulation of motor cortex: A modeling study

OBJECTIVE To explore the effects of electrical stimulation performed by an anode, a cathode or a bipole positioned over the motor cortex for chronic pain management. METHODS A realistic 3D volume conductor model of the human precentral gyrus (motor cortex) was used to calculate the stimulus-induced electrical field. The subsequent response of neural elements in the precentral gyrus and in the anterior wall and lip of the central sulcus was simulated using compartmental neuron models including the axon, soma and dendritic trunk. RESULTS While neural elements perpendicular to the electrode surface are preferentially excited by anodal stimulation, cathodal stimulation excites those with a direction component parallel to its surface. When stimulating bipolarly, the excitation of neural elements parallel to the bipole axis is additionally facilitated. The polarity of the contact over the precentral gyrus determines the predominant response. Inclusion of the soma-dendritic model generally reduces the excitation threshold as compared to simple axon model. CONCLUSIONS Electrode polarity and electrode position over the precentral gyrus and central sulcus have a large and distinct influence on the response of cortical neural elements to stimuli. SIGNIFICANCE Modeling studies like this can help to identify the effects of electrical stimulation on cortical neural tissue, elucidate mechanisms of action and ultimately to optimize the therapy.

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.

Paresthesia thresholds in spinal cord stimulation: a comparison of theoretical results with clinical data

The potential distributions produced in the spinal cord and surrounding tissues by dorsal epidural stimulation at the midcervical, midthoracic, and low thoracic levels were calculated with the use of a volume conductor model. Stimulus thresholds of myelinated dorsal column fibers and dorsal root fibers were calculated at each level in models in which the thickness of the dorsal cerebrospinal fluid (CSF) layer was varied. Calculated stimulus thresholds were compared with paresthesia thresholds obtained from measurements at the corresponding spinal levels in patients. The influences of the CSF layer thickness, the contact separation in bipolar stimulation and the laterality of the electrodes on the calculated thresholds were in general agreement with the clinical data. >

Position-selective activation of peripheral nerve fibers with a cuff electrode

The degree of spatial selectivity which can be obtained with longitudinal dot tripoles in an insulating cuff was quantified in terms of the overlap between fiber populations activated by different tripoles. Previous studies have failed to take into account the relative influences of transverse current and longitudinal current on position-selective activation, and furthermore have not controlled for the differing sensitivities of large and small nerve fibers to electrical stimuli. In this study, these factors were taken into account. Transverse current from an anode positioned opposite the stimulating cathode was found to improve spatial selectivity, and selectivity was enhanced when the ratio of transverse current to longitudinal current was increased. Large fibers were excited before small fibers, irrespective of fiber position, indicating a combination of position and size selectivity.

A modeling study of nerve fascicle stimulation

A nerve-stimulation model incorporating realistic cross-sectional nerve geometries and conductivities is discussed. The potential field in the volume conductor was calculated numerically using the variational method. Nerve fiber excitation was described by the model of McNeal (ibid., vol.BME-23, p.329-37, 1976). Cross-sectional geometries of small monofascicular rat common peroneal nerve and multifascicular human deep peroneal nerve were taken as sample geometries. Selective stimulation of a fascicle was theoretically analyzed for several electrode positions: outside the nerve, in the connective tissue of the nerve, and inside a fascicle. The model results predict that the use of intraneural or even intrafascicular electrodes is necessary for selective stimulation of fascicles not lying at the surface of the nerve. Model predictions correspond to experimental results on intrafascicular and extraneural stimulation of rat common peroneal nerve and to results on muscle selective stimulation in multifascicular dog sciatic nerve using an extraneural multielectrode configuration.<<ETX>>