Comparison of tonic spinal cord stimulation, high-frequency and burst stimulation in patients with complex regional pain syndrome: a double-blind, randomised placebo controlled trial.

BACKGROUND: Complex Regional Pain Syndrome (CRPS) is a disabling disease that is sometimes difficult to treat. Although spinal cord stimulation (SCS) can reduce pain in most patients with CRPS, some do not achieve the desired reduction in pain. Moreover, the pain reduction can diminish over time even after an initially successful period of SCS. Pain reduction can be regained by increasing the SCS frequency, but this has not been investigated in a prospective trial. This study compares pain reduction using five SCS frequencies (standard 40 Hz, 500 Hz, 1200 Hz, burst and placebo stimulation) in patients with CRPS to determine which of the modalities is most effective. DESIGN: All patients with a confirmed CRPS diagnosis that have unsuccessfully tried all other therapies and are eligible for SCS, can enroll in this trial (primary implantation group). CRPS patients that already receive SCS therapy, or those previously treated with SCS but with loss of therapeutic effect over time, can also participate (re-implantation group). Once all inclusion criteria are met and written informed consent obtained, patients will undergo a baseline assessment (T0). A 2-week trial with SCS is performed and, if successful, a rechargeable internal pulse generator (IPG) is implanted. For the following 3 months the patient will have standard 40 Hz stimulation therapy before a follow-up assessment (T1) is performed. Those who have completed the T1 assessment will enroll in a 10-week crossover period in which the five SCS frequencies are tested in five periods, each frequency lasting for 2 weeks. At the end of the crossover period, the patient will choose which frequency is to be used for stimulation for an additional 3 months, until the T2 assessment. DISCUSSION: Currently no trials are available that systematically investigate the importance of variation in frequency during SCS in patients with CRPS. Data from this trial will provide better insight as to whether SCS with a higher frequency, or with burst stimulation, results in more effective pain relief. TRIAL REGISTRATION: Current Controlled Trials ISRCTN36655259.

Barriers to investigator-initiated deep brain stimulation and device research.

The success of device-based research in the clinical neurosciences has overshadowed a critical and emerging problem in the biomedical research environment in the United States. Neuroprosthetic devices, such as deep brain stimulation (DBS), have been shown in humans to be promising technologies for scientific exploration of neural pathways and as powerful treatments. Large device companies have, over the past several decades, funded and developed major research programs. However, both the structure of clinical trial funding and the current regulation of device research threaten investigator-initiated efforts in neurologic disorders. The current atmosphere dissuades clinical investigators from pursuing formal and prospective research with novel devices or novel indications. We review our experience in conducting a federally funded, investigator-initiated, device-based clinical trial that utilized DBS for thalamic pain syndrome. We also explore barriers that clinical investigators face in conducting device-based clinical trials, particularly in early-stage studies or small disease populations. We discuss 5 specific areas for potential reform and integration: (1) alternative pathways for device approval; (2) eliminating right of reference requirements; (3) combining federal grant awards with regulatory approval; (4) consolidation of oversight for human subjects research; and (5) private insurance coverage for clinical trials. Careful reformulation of regulatory policy and funding mechanisms is critical for expanding investigator-initiated device research, which has great potential to benefit science, industry, and, most importantly, patients.

Simplifying the assessment of the recovery from surgical injury to the lingual nerve.

OBJECTIVE: To determine the sensitivity of conventional sensory assessment in monitoring lingual nerve recovery subsequent to third molar surgery and to evaluate if the assessment methods can be predictive of injury outcome. METHOD: A prospective case series of 94 patients presenting with lingual nerve injuries evaluated using objective mechanosensory and subjective methods during the recovery period of up to 12 months. RESULTS: The conventional tests were often unable to diagnose the presence of injury due to variability and they were not predictive of outcome. As a result of this study, we are able to identify patients more likely to have permanent rather than temporary lingual nerve injury at four to eight weeks post injury, using patient reported subjective function. The subjective function test also minimises the requirements for specialist training or equipment providing an ideal method for general dental practice. CONCLUSIONS: The development of these simple subjective tests may enable us to identify which patients are at risk of permanent lingual nerve injuries in the early post injury phase, thus allowing expeditious therapy when indicated.

Clinical evaluation criteria for the assessment of impaired pain sensitivity by thulium-laser evoked potentials.

OBJECTIVES: Cortical potentials evoked by carbon dioxide laser pulses have been applied in clinical practice to study nociceptive pathways for several years. In this study, we evaluate the properties of an infrared laser (thulium-YAG) with a penetration depth in the skin that matches the intracutaneous depth of nociceptors. METHODS: Temperature measurements and modelling showed that the thulium laser generates painful intracutaneous temperatures with less surface heating than the carbon dioxide laser and with no side effects (up to 600 mJ pulse energy). To develop clinical evaluation criteria, laser-evoked potentials (LEPs) were recorded from 3 midline positions (Fz, Cz, Pz) versus linked earlobes in 23 healthy subjects. Within a session, two skin areas were studied twice in a balanced sequence using randomized interstimulus intervals and two intensities in randomized order. RESULTS: After hand and foot stimulation with 540 mJ pulses, all subjects showed reproducible biphasic vertex potential, consisting of a negativity (hand: 210 ms, foot: 250 ms) and a positivity (hand: 330 ms, foot: 380 ms). Mean habituation of the vertex potential amplitude across runs was 25% (hand) or 16% (foot); due to the balanced sequence it did not affect the other comparisons. Following foot stimulation, peak latencies were significantly longer (by 40-50 ms) and amplitudes were significantly smaller than following hand stimulation (22.5+/-6.7 vs. 30.3+/-10.9 microV, mean+/-SD). Using 2. 5 standard deviations from the mean as a cut-off, absolute normative values were determined for peak latencies and amplitudes. In addition, relative normative values were determined for paired comparisons (hand-hand, foot-foot, hand-foot). CONCLUSIONS: The thulium-YAG laser is a useful tool for assessment of impaired pain sensitivity. Representative case reports illustrate that unlike for early SEP components, the most frequent LEP abnormalities were amplitude differences.

Assessment of the carpal tunnel outcome instrument in patients with nerve-compression symptoms.

The outcome movement in medicine has encouraged the development of patient-answered questionnaires as measures of well-being. A disease-specific questionnaire for carpal tunnel syndrome (CTS) was introduced by Levine et al. in 1993. We evaluated this questionnaire in 156 consecutive new patients presenting with pain, numbness, or tingling of the upper extremity. Of these, 114 correctly filled out the carpal tunnel outcome instrument. In addition, these patients completed the self-administered hand diagram developed by Katz and Stirrat for the diagnosis of CTS. The 114 patients were classified according to their hand diagram as classic or probable CTS (n = 47), possible CTS (n = 31), and unlikely CTS (n = 36). The mean symptom severity score in patients classified as classic or probable CTS was significantly higher than the mean score in patients classified as possible or unlikely CTS (p < .01). The mean scores of items regarding sensory symptoms were significantly higher in patients with classic or probable CTS compared to patients with possible or unlikely CTS (p < .0001). The scores were similar for CTS and non-CTS patients on the functional status subscale.

Neurosensory disturbances of the trigeminal nerve: a long-term follow-up of traumatic injuries.

PURPOSE: This study assesses the physical and psychosocial consequences of trigeminal nerve damage. MATERIAL AND METHODS: A questionnaire consisting of 33 questions, 30 of which had fixed alternatives, was mailed to 300 persons who had received compensation from a syndicate of several insurance companies (Konsortiet för Patientförsäkring) because of trigeminal nerve damage. One question with no alternative reply gave the respondents an opportunity to comment on their problems and to rate them on a visual analogue scale. The questionnaire was answered by 226 recipients, 72 men and 153 women. RESULTS: Most of the patients had sensory disturbances resulting from damage to the inferior alveolar nerve, the mental nerve, or the lingual nerve. More than 70% of the respondents complained about paresthesia. No fewer than one of five patients suffered from pain in the affected area. The altered sensation caused functional disturbances in speech and eating which, in turn, had social and psychological consequences. CONCLUSIONS: This study shows that mainly women and older persons have the most severe discomfort after oral nerve damage.