Key Paper Summaries Neurostimulation

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• The paper reviews the history, theoretical basis and evolution of neuromodulation techniques.
• Since its introduction in 1967, the main method of neuromodulation for the management of chronic, intractable pain of neuropathic origin has been the stimulation of the DCs by electrodes in the epidural space. This is based on the rationale that it should be possible to target nerve fibers of all painful dermatomes by a single electrode when placed at the proper cephalocaudal level.
• In clinical practice, however, it is very difficult to consistently target multiple dermatomes and in a substantial number of patients, single-electrode stimulation is only segmental and long-term success has been generally limited.
• Computer modeling studies in the 1990s indicated changes in electrode geometry to improve coverage and methods to focus the stimulation at the proper region of the DCs:
  • The introduction of dual-electrode stimulation improved clinical outcome, but much variability between patients remained. This led to a new approach in which partly overlapping regions of the painful area are stimulated alternately by different anode-cathode configurations on the same electrodes.
  • Particular pain areas remain difficult to stimulate with SCS, such as the occiput, the low back and lower sacral dermatomes. For these areas, a different approach was introduced by which corresponding Ab fibers were stimulated in the proper spinal nerve either intraspinally or extraspinally

• Newer approaches to the management of chronic pain will continue to evolve and achieve increasing success with the development of new technical innovations. These innovations will undoubtedly involve selective cannulation methods and electrical field steering by both multiple-electrode programming and tuning a 'stereo' stimulator. In addition, automatisation of the parameter selection procedures will increasingly become a patient-interactive process.
  
  
• The development of new stimulation systems to manage neuropathic pain in the future will evolve directly from today's trends.

• The aim of the study was to investigate the efficacy of SCS in postherpetic neuralgia (PHN) and acute herpes zoster (HZ) in patients with preserved sensory function refractory to conventional drug therapy.
  
  
• The study involved the prospective investigation of 28 patients with PHN over a median period of 29 months and 4 patients with acute HZ pain over a median period of 1.8 months. All patients were referred to a pain clinic due to ineffective pain medication and increasing pain.
  
  
• Following preliminary screening and trial stimulation, patients were implanted with an SCS device:
  
  • PHN patients were supplied with a quadripolar lead and INTREL II or III device
  • Patients with acute HZ were supplied with a bipolar lead and an external temporary transmitter (Medtronic Screener 3625)
    
    
• Patients were assessed at quarterly intervals. Pain and impairment of quality of life were assessed using a visual analog scale and pain disability index. The efficacy of treatment was assessed by SCS inactivation tests to objectify the existence of pain-free intervals or spontaneous improvement with complete resolution of pain
  

Postherpetic neuralgia

• After intractable pain for more than 2 years, significant long-term pain relief was achieved in 82% of PHN patients during SCS treatment, confirmed by a median decrease of 9 to 1 on the VAS (p<0.001).
• In 5 patients with serious comorbidity, the initial pain alleviation could not be stabilized.
• 8 patients discontinued SCS permanently because of complete pain relief after stimulation periods of 3-66 months. Two patients re-established SCS at 2 and 6 months due to gradually worsening pain.
• Amongst the responders, there was a significant improvement in quality of life as measured by the pain disability index (p<0.001). Pre-existing pain medication was completely removed or significantly reduced in the majority of patients.

Acute herpes zoster

• All 4 patients who had experienced unbearable pain for a median period of 1.8 months reported immediate relief of pain with SCS (reduction of pain intensity from 9 to 1 on the VAS).
  
  
• SCS could be terminated after a median period of 2.5 months (quartiles 2.0-3.1) due to complete pain cessation.
  

• A major finding of this study is the favorable long-term outcome of SCS treatment in patients with PHN and acute HZ pain.
  
  
• The investigators concluded that SCS treatment of PHN and unbearable acute HZ pain may offer a worthwhile option in the treatment of pharmacological non-responders with anatomically intact neural pathways, providing that the patients accept an invasive approach.

• Malignant brain tumors have been shown to decrease oxygen and blood flow, resulting in hypoxia and low perfusion. These in turn reduce radiation sensitivity and access by chemotherapeutic agents and diminish the efficacy of these treatments.
  
  
• Modification of hypoxia can improve local tumor control and overall patient survival, depending on the stage of the tumor.
  
  
• Spinal cord stimulation (SCS) has been used successfully in the treatment of pain and ischemic syndromes and increases in cerebral blood flow have been demonstrated.
  
  
• Thus, the aim of this study was to assess the effect of cervical SCS (using Pisces-Quad electrodes) on tumor tissue oxygenation in malignant tumors.
  
  
• Three patients with high grade astrocytomas (brain tumors) were assessed and the effects of SCS measured using the polarographic probe system, the 'gold standard' for measuring changes in tissue oxygenation (PO2) and hypoxia.

• The results of SCS indicated that the overall tumor tissue oxygenation increased by 90% (from 13.2 ± 9.4 mmHg to 25.1 ± 9.6 mmHg, p=0.013).
  
  
• The percentage of moderately hypoxic values (<10 mmHg) decreased by 55% (from 48.6 ± 20.1% to 22 ± 3.3%, p=0.026).
  
  
• The percentage of considerably hypoxic values (<5 mmHg) decreased by 45% (from 28 ± 20.3% to 15.5 ± 15.0%, p=0.018).

• In this report, the authors describe a potential novel application of SCS.
  
  
• The preliminary results suggested that SCS significantly increased tumor tissue oxygenation (by 90%) and decreased the percentage of hypoxia (by 45-55%).
  
  
• Benefits include an increased access to the tumor tissue for chemo- and radiotherapeutic agents and increased radiosensitivity.
  
  
• The authors suggest that SCS may be applicable as an adjuvant to radio- and chemotherapy regimens.
  
  
  • SCS can be activated or deactivated at any time once the electrodes are in situ and can be activated to fit within the chemotherapy or radiotherapy schedule.
  • Furthermore, when implanted subcutaneously the neurostimulation can continue over a period of months or even years.

• This paper reviews the three neurostimulation methods currently used in clinical practice for management of neuropathic pain: spinal cord stimulation (SCS), peripheral nerve stimulation (PNS) and deep brain stimulation (DBS).
  
  
• Neurostimulation for the control of chronic neuropathic pain has gained in popularity for a number of reasons:
  • In contrast to nerve ablation, the techniques are minimally invasive and reversible.
  • Improvements in hardware design, simplified implantation techniques and prolonged equipment longevity have made therapy more accessible.
  • Stimulation trials have become less invasive, allowing patients to be pre-screened before implantation.
  • Scientific evidence has shown good outcomes of neurostimulation methods for chronic neuropathic pain control.
• Recent research has revealed new potential mechanisms of action for neurostimulation. Whereas action was explained by gate control theory in the past, it now appears that neuromodulation acts by modulation of neurotransmitters in the central nervous system.
• SCS and PNS are excellent treatment choices for certain forms of neuropathic pain:
  • New indications for SCS include end-stage peripheral vascular disease and ischaemic heart disease.
  • PNS is used for the treatment of occipital neuralgia and chronic pelvic pain.
  • DBS is reserved for carefully selected patients in whom the other treatment modalities have failed.
• A small minority of patients may develop a 'tolerance' to neurostimulation after long-term use.

• Neurostimulation has become a mainstream modality for treatment of certain neuropathic pain conditions. It is minimally invasive and reversible and its efficacy is widely documented in the literature.
  
  
• Neuromodulation may provide superior pain relief to other treatment methods in carefully selected patients.
  
  
• Further clinical trials should identify better outcome predictors in order to further improve long-term success rates of neuromodulation for chronic neuropathic pain.
  
  
• Note: This is a useful review article for new users of Neurostimulation and/or for referral physicians.

• This paper reviews the proposed underlying mechanisms, indications and contraindications for spinal cord and peripheral nerve stimulation for the relief of chronic intractable pain, along with patient selection criteria and a review of implantable systems currently available.
  
  
• Early frustrations with the use of peripheral and spinal nerve stimulation due to difficulties with patient selection criteria and equipment have diminished as a result of carefully controlled clinical studies and improvements in equipment design.
  
  
• Efficacy studies consistently show an overall 50% improvement in long-term pain control in patients who have failed conservative or other invasive modalities.
  
  
• It is well accepted that SCS has been more successful for the treatment of neuropathic pain than for nociceptive pain. Current indications for SCS include lumbar arachnoid fibrosis, CRPS I, CRPS II, peripheral nerve injury or neuralgia, post-amputation pain syndromes, peripheral vascular disease, persistent ischaemic rest pain, spinal cord lesions, postherpetic neuralgia, peripheral neuropathy, spasmodic torticollis and chronic intractable angina pectoris.
  
  
• Evidence shows that devices that support 'multi-channel' electrodes are clearly superior to early single electrode devices. The use of a transverse tripolar stimulation electrode in combination with a dual-pulse generator allows parasthesia to be directed in a predictable manner without having to reposition the electrode.
  
  
• The Synergy System by Medtronic has made possible dual-channel stimulation with an implantable lithium-powered pulse generator.
  

• Spinal cord stimulation can be effective in the treatment of chronic intractable pain and is indicated if an optimal drug regimen and less invasive procedures fail to produce adequate pain relief, or do so with unacceptable side effects. SCS is not, however, the treatment of choice for all patients with intractable pain. The use of defined selection criteria and sound clinical judgement are required to identify those patients who may benefit from treatment.
  
  
• Note: This is a useful review article for new users of Neurostimulation and/or for referral physicians.

• This is a review of the physiology of spinal cord stimulation (SCS), focussing on its possible mode of action on neuropathic pain.
  
  
• Data from experimental models in animals and from electrophysiological studies of humans indicate that SCS predominantly exerts its effects on pain that is related to abnormal functioning of the Ab fibre system.
  
  
• There is no evidence for an involvement of opioid mechanisms in the effects of SCS. However, there is evidence for the involvement of other neurotransmitter/modulator systems.
  
  
• There is some evidence that the extracellular release of substance P and serotonin may be influenced by SCS, but these findings are difficult to evaluate.
  
  
• Development of allodynia after peripheral nerve injury appears to be related to dysfunction of the spinal GABA systems, and SCS may act by restoring normal GABA levels in the dorsal horn.
  
  
• The effects of SCS could be enhanced by the GABAB agonist, baclofen, and counteracted by a GABAB antagonist whereas drugs acting at the GABAA receptor had much smaller effects.
  
  
• Adenosine and an adenosineA agonist had a potentiating effect on SCS, and there was a synergistic effect of this agonist and baclofen.
  
  
• There are also early indications that gabapentin has a potentiating effect on SCS.
  
  
• These results indicate that adjuvant pharmacological treatment may, in the future, enhance the efficacy of SCS in patients who do not respond or have insufficient pain relief.

• This paper reviews current concepts of pain.
  
  
• The perception of pain is generated by the output of a neural pattern-generating mechanism (the 'neuromatrix') resulting from sensory inputs and information from areas of the brain involved in affective and cognitive activities. Conditioning from previous environmental cues or expectation of pain can also lead to pain behaviours.
  
  
• The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage."
  
  
• The existence of different types of pain is reflected in four broad categories of response:
  • nociception: the detection of tissue damage by specialized receptors
  • perception of pain, which is frequently triggered by noxious stimuli (e.g. diabetic neuropathy or spinal cord injury)
  • suffering - a negative response induced by pain or other psychological states such as fear or stress
  • pain behaviours, such as grimacing or limping, in response to pain.
    
    
• The principal types of pain are:
  • transient pain - elicited by the activation of nociceptors in the skin or other tissues in the absence of tissue damage
  • acute pain - elicited by substantial tissue damage and activation of nociceptors at sites of local tissue damage
  • chronic pain, which is commonly triggered by injury or disease but may be perpetuated by factors other than the original cause.
    In contrast to acute pain, chronic pain continues after treatment stops.
    
    
• Cognitive or behavioural treatments may be used to modify the effect of pain on the patient's life.

• The aim of this study was to retrospectively assess patient's impressions of two spinal cord stimulation (SCS) systems (implantable pulse generators (IPG) and radio frequency (RF) systems) on quality of life, function and pain relief.
  
  
• Two groups of 250 patients, fitted with either a Medtronic Model 7425 Itrel 3 neurostimulation system (IPG system) or a Medtronic Model 3470/3425 Xtrel neurostimulation system (RF system), were enrolled in the study. All 500 patients had at least 16 months experience with the system implants.
  
  
• Information regarding levels of pain, quality of life and functional capacity were sought from each patient via a questionnaire. Patients were asked to retrospectively rate their experience of these factors immediately before implantation of the SCS system, and again at the time of the questionnaire.

• SCS provides significant improvements in pain relief, quality of life and function, regardless of age, sex or the type of SCS device used.
  
  
• In this study, patients with totally implantable SCS systems routinely experience improved quality of life and higher activity levels compared to patients with RF systems.
  
  
• Previous studies have shown that of most concern to patients with chronic pain is their ability to walk and stand. In this study, improvements in these parameters were significantly greater with IPG devices compared to RF systems.
  
  
• In terms of practicality and convenience, RF systems proved unsatisfactory for a number of reasons, including antenna-related discomfort, their impact on clothing choices and interference with personal grooming. Such problems are not associated with IPG devices, as all components are fully internalised.
  
  
• The choice of SCS system clearly influences patient outcome. Fully internalised systems, such as the Medtronic Model 7425 Itrel 3 neurostimulation system, are not only effective, but substantially more convenient than their partially internalised counterparts.

• The aim of this study was to determine the value of specific prognostic parameters in the prediction of successful SCS.
  
  
• A total of 235 patients with an average age of 51.4 years were included in the study. All patients had chronic intractable pain of various aetiologies, including failed back syndrome, peripheral vascular disease and peripheral neuropathy. All patients had used narcotic medication and were found to be refractory to conservative modalities of pain relief.
  
  
• Following a successful trial period using Pisces-Sigma or later in the study Pisces-Quadripolar electrodes implanted percutaneously or Resume electrodes, 189 patients received a permanent, multipolar Medtronic Itrel I, Itrel II, or X-trel system. Subjective pain assessments were conducted at 6-monthly intervals, with a mean follow-up period of 66 months.

• Multipolar, Medtronic Itrel I, Itrel II, or X-trel system implants provide satisfactory relief from chronic pain of various aetiologies, regardless of patient age or sex, and significantly increase patients' activities of daily living.
  
  
• The most responsive syndromes to SCS include failed back syndrome, reflex sympathetic dystrophy and peripheral vascular disease.
  
  
• Patients with fewer previous surgeries and a shorter duration of time between surgeries and SCS implantation had a more favourable response to SCS.
  
  
• Possible prognostic factors for successful SCS include: (i) the aetiology of the pain syndrome; (ii) the number of previous surgical procedures; and (iii) the duration of time between surgical interventions and SCS implantation.
  

• The aim of this study was to evaluate whether using a strict selection protocol and uniform technique can improve the outcome of SCS.
  
  
• A total of 27 patients were selected for the trial using the following protocol:
  • a recognised pain syndrome with a plausible aetiology was identified
  • a corrective surgical procedure was considered not feasible
  • patients had a lack of satisfactory response to noninterventional multidisciplinary pain management
  • patients had no contra-indicated psychological conditions
  • patients intolerable to transcutaneous electrical nerve stimulation (TENS) were not included
    
    
• Apart from one patient, all cases were of non-malignant pain. Following a successful trial, 24 patients were fitted with a permanent Medtronic Itrel II system implant with Medtronic Pisces-Quad or Medtronic Resume leads. Patients were followed up for a mean of 19 months, during which the effectiveness of the SCS implant was assessed by an impartial third party and by the neurosurgeon involved in the trial.

• A rigid selection protocol can maximise the proportion of patients with intractable pain who are successfully treated with SCS.
  
  
• In carefully selected patients, SCS is effective in relieving chronic pain of both benign and malignant origin. SCS may also improve autonomic function in patients with RSD.
  
  
• In this study, the Medtronic Itrel II System proved to be extremely effective, safe and technically very reliable.
  

• This paper reviews various philosophical and practical issues relating to psychological evaluation in patients being considered for spinal cord stimulation (SCS).
  
  
• Evaluation of patients with chronic pain must take into account numerous factors, including the sensation of pain, associated behaviours and the emotional impact of pain. This is reflected in current models, which emphasise the multidimensional and dynamic aspects of pain.
  
  
• Most studies reporting psychological 'predictors' in SCS therapy have involved patients with failed back surgery syndrome (FBSS). However, these data should not be generalized to other patient populations. It is necessary for the mental health practitioner to have a basic understanding of the proposed mechanisms of SCS therapy.
  
  
• The clinical interview can identify factors that may influence the patient's experience and demonstration of pain.
  
  
• Various psychological tests have been used to screen potential candidates for SCS, including the Minnesota Multiphasic Personality Inventories, measures of mood states such as the Beck Depression Inventory, the McGill Pain Questionnaire, pain drawings, the Coping Strategies Questionnaire, measures of functional disability, and 'gut feelings interviews.' None of these have consistently identified specific, statistically significant, psychological factors that predict the outcome of SCS therapy.

• The authors conclude that as much emphasis should be given to identifying potential adjunct therapies (e.g. treating major depression or drug dependence) that could enhance the success of SCS therapy as to identifying 'predictors' of success.

• The aim of this study was to determine whether psychological test instruments had any prognostic value in selecting patients for trials of spinal cord stimulation (SCS) for chronic, intractable pain.
  
  
• Fifty-eight patients selected for SCS were tested prospectively with a battery of psychological tests. Patients were suffering from chronic pain of various aetiologies, including failed back surgery syndrome (FBSS), spinal cord injury and peripheral neuropathic pain syndromes.
  
  
• Each patient proceeded to a trial with a temporary, Medtronic model 3487A or a Neuromed model ERE-4, epidural electrode. Thirty-five of these patients went on to receive a permanent implant.
  
  
• The 2 major endpoints in this trial were: (i) the probability of achieving a successful result with a temporary electrode and proceeding with a permanent implant, and (ii) the probability of long-term success as measured by a patient questionnaire.

• Simple univariate statistical tests found certain associations between psychological test results and successful long-term outcomes of permanent implants. However, using more rigorous multivariate analysis, no significant association was found.
  
  
• This study provides little evidence for selecting patients for SCS on the basis of psychological testing. In the sub-population chosen for this study, psychological testing is of only modest value and explains little of the observed variance in outcome.
  
  
• Psychological methods of evaluation may make their greatest contribution in the timing of intervention and in the selection of adjuvant psychological or behavioural treatments.

• Peripheral neuropathy is a common long-term complication of diabetes. Conventional drugs are often ineffective and complicated by side-effects. Therefore spinal cord stimulation (SCS) was tested for the treatment of chronic diabetic neuropathic pain that did not respond to conventional drugs.
  
  
• Trial and placebo stimulators were tested for 2 days each in a crossover design. Patients who responded to the trial stimulation were then given an implanted stimulator (Medtronic X-trel, model 3470 with Pisces-Quad Plus, model 3888 lead).

• This is the first study to have demonstrated the efficacy of SCS on chronic diabetic neuropathic pain.
  
  
• Patient selection is obviously important: patients were carefully selected for the presence and severity of neuropathy, and for their psychological status.
  
  
• The results demonstrated that SCS offers a new and effective treatment for chronic diabetic neuropathic pain for some patients, improves exercise tolerance, and should be considered in patients who do not respond to drug treatment.
  

• This paper presents the results of a nation-wide survey of the use of spinal cord stimulation (SCS) in Belgium between 1983 and 1992. The survey was prompted by the growing healthcare expenditure associated with SCS.
  
  
• The results of three studies that evaluated outcome by different criteria are reviewed.
  

• The subjective pain relief reported here is comparable with that in other studies which used third party evaluation.
  
  
• Psychiatric assessment can significantly improve the outcome of SCS.
  

• This paper reviews the experience in 205 patients with chronic, intractable, pain (153 with failed back surgery syndrome, 11 with spinal cord injury, and 41 with pain of peripheral origin) who received temporary or permanent Medtronic spinal cord stimulators between 1972 and 1990. Of 171 patients who received permanent implants, electrodes were placed percutaneously in 134 and by laminectomy in 37.
  
  
• Clinical outcome (standard analogue pain ratings, employment status, ability to undertake everyday activities, use of analgesics) was assessed by third-party interview at intervals from 2-20 years (mean 7.1 years).

• Technical improvements in spinal cord stimulation have led to enhanced system reliability and improved clinical outcome.
  
  
• Since a majority of patients continued to report at least 50% pain relief at an average time of 7 years after implantation, spinal cord stimulation compares favourably with other treatment modalities for chronic, intractable, pain.
  

• This paper describes the outcome of spinal cord stimulation (SCS) in 43 patients with intractable lower trunk and/or lower extremity pain of various causes.
  
  
• All patients underwent implantation of a Medtronic Resume electrode via laminectomy. Patients were asked to rate their pain during an initial trial period, and those obtaining more than 50% pain relief received permanent implants of either a Medtronic SE 4 or Medtronic Itrel system.
  
  
• Follow-up was performed by telephone interview at various intervals (mean duration of follow-up 13 months).

• These results are consistent with others in the literature, suggesting that SCS can produce success rates of 45% or more in patients with chronic intractable pain.
  
  
• "State of the art" equipment should be used. In particular, the Resume electrode appears to have a very low technical failure rate.
  

• This paper reviews the indications and use of spinal cord stimulation (SCS) in patients with intractable pain.
  
  
• SCS is indicated in patients in whom:
  • pain has an objective basis and is amenable to stimulation coverage
  • alternative therapies have been exhausted, or are unacceptable, and psychiatric clearance has been obtained.
    
    
• Specific indications are:
• lumbar arachnoiditis or polyradiculopathy
• spinal cord lesions
• phantom limb or stump pain
• peripheral neuropathy
• peripheral vascular disease.
  
  
• A trial with a temporary percutaneous system is useful before the decision is made to implant a permanent system. This requires technically satisfactory coverage over most of the affected area for at least 3 days.
  
  
• Permanent implantation is performed with the patient sedated, under fluoroscopic guidance, sterile conditions and local anaesthesia. Test stimulation is performed during implantation to optimize electrode placement. Antibiotic prophylaxis should be given preoperatively and for 24 hours postoperatively.
  
  
• Hardware for permanent implants includes percutaneous electrode arrays, laminectomy electrode arrays (for patients with previous laminectomy or epidural scarring) and radiofrequency receivers.