Neurostimulation For Complex Regional Pain Syndrome Literature Review Summary

2 | MDT Confidential The second most common use of spinal cord stimulation (SCS) in the United States is for the symptomatic management of complex regional pain syndrome (CRPS). CRPS is a neuropathic pain syndrome precipitated most commonly by minor limb trauma. 1,2,3,4 Continuous, severe pain, disproportionate to the inciting event, occurs in the limb and may be accompanied by allodynia, hyperalgesia, skin color changes, edema, joint stiffness, and bone demineralization. 1,4,5 This literature review summary highlights results of studies to demonstrate the clinical and cost-effectiveness of SCS for CRPS. Background

3 | MDT Confidential Effectiveness Study Kemler MA, et al , Prospective, randomized, controlled study of 54 type I CRPS patients randomized to receive SCS plus PT or PT alone. At the 2-year follow-up, pain intensity in the SCS group had decreased by a mean of 3.0 cm on the VAS, vs. 0 cm for PT-only patients (P < 0.001). At 24 months, global perceived effect (GPE) was much improved in 63% of SCS patients vs. 9% of PT-only patients (P < 0.001). At 24 months, as compared to PT-only patients, SCS patients had significant improvement in health-related quality of life (HRQoL) (P = 0.02 affected hand, P = foot).

4 | MDT Confidential Effectiveness Study Harke H, et al Prospective study of 29 patients with type I CRPS. At 12 months after implant, deep pain and allodynia on the VAS were reduced from a mean of 10 cm to 1.7 cm and from a mean of 10 cm to 0.03 cm, respectively (P < 0.01). Disability scores decreased > 50% (P < 0.01). At a mean follow-up of 35 months, 59% of patients did not require analgesics and 70% had returned to work.

5 | MDT Confidential Effectiveness Studies Forouzanfar T, et al Prospective study of 36 type I CRPS patients. At 24 months: HRQoL (EQ-5D) significantly improved (P < 0.02). The number of patients reporting “extreme problems” for the categories “usual activities” and “pain and discomfort” decreased for both cervical (Figure A) and lumbar (Figure B) patients (P < 0.01). The percent of patients reporting “no problems” in the “anxiety/depression” dimension increased (P < 0.02).

6 | MDT Confidential Effectiveness Studies Bennett DS, et al Retrospective, multicenter study of 101 CRPS patients. The mean improvement in VAS was 6.0 cm for patients with dual- octapolar systems and 3.70 cm for patients with single-lead quadripolar systems (P < ). Overall patient satisfaction scores were 70% in single-lead patients at 18.7 months mean follow-up and 91% in dual-octapolar patients at 23.5 months mean follow-up (P < 0.05).

7 | MDT Confidential Effectiveness Study Kemler MA, et al Retrospective study of 23 consecutive patients with type I CRPS (n = 18 implanted). At a mean follow-up of 32 months, mean VAS for implanted patients had improved from 7.9 cm to 5.4 cm (P < 0.001). 87% of patients reported a Global Perceived Effect (GPE) of “much improved” or “improved” and therapy was regarded as a success.

8 | MDT Confidential Cost Study Kemler MA, et al Calculated health care costs (1998 Euros) for 54 CRPS patients randomized to SCS plus physical therapy (PT) or PT alone. Costs shown for SCS implanted patients are minus the cost of PT.

9 | MDT Confidential Cost Study Kumar K, et al

10 | MDT Confidential Summary The referenced effectiveness studies 4,5,7,8,9 found that at long-term follow-up, SCS provided significant pain relief and has been associated with substantial long-term success as measured by global perceived effect. 5,7,9 One study demonstrated that SCS led to a reduction in medication use. 4 Two studies have shown improvements in function and daily living 4,9, and enabled patients to return to work. 4 The referenced cost studies show that mean first-year cost of SCS became substantially less in the second year. This was also found in three studies of SCS for FBSS. 12,13,14 SCS has become increasingly successful due to refined patient selection criteria, greater accuracy in electrode placement, and improvement in multipolar and multichannel systems. 1 However, complications still occur. The most frequent complication of SCS system implantation has been electrode migration. 5,7,8,9 Various complications have also led to surgical revision of the pulse generator, lead and/or system explantation. 5,7,9

11 | MDT Confidential Conclusions The referenced long-term clinical studies have shown that SCS provides statistically significant pain relief in patients with CRPS. Despite a high cost the first year, SCS has been shown to be more effective and less expensive than conventional treatment in the long term.

12 | MDT Confidential Neurostimulation Therapy for Chronic Pain Truck and/or Limbs: Product manuals must be reviewed prior to use for detailed disclosure. Indications: Implantable neurostimulation systems: A Medtronic implantable neurostimulation system is indicated for spinal cord stimulation (SCS) system as an aid in the management of chronic, intractable pain of the trunk and/or limbs—including unilateral or bilateral pain associated with the following conditions: Failed Back Syndrome (FBS) or low back syndrome or failed back, radicular pain syndrome or radiculopathies resulting in pain secondary to FBS or herniated disk, postlaminectomy pain, multiple back operations, unsuccessful disk surgery, degenerative Disk Disease (DDD)/herniated disk pain refractory to conservative and surgical interventions, peripheral causalgia, epidural fibrosis, arachnoiditis or lumbar adhesive arachnoiditis, Complex Regional Pain Syndrome (CRPS), Reflex Sympathetic Dystrophy (RSD), or causalgia. Contraindications: Diathermy: Do not use shortwave diathermy, microwave or therapeutic ultrasound diathermy (all now referred to as diathermy) on patients implanted with a neurostimulation system. Energy from diathermy can be transferred through the implanted system and cause tissue damage at the locations of the implanted electrodes, resulting in severe injury or death. Warnings: Sources of strong electromagnetic interference (e.g., defibrillation, diathermy, electrocautery, MRI, RF ablation, and therapeutic ultrasound) can interact with the neurostimulation system, resulting in serious patient injury or death. These and other sources of EMI can also result in system damage, operational changes to the neurostimulator or unexpected changes in stimulation. Rupture or piercing of the neurostimulator can result in severe burns. An implanted cardiac device (e.g., pacemaker, defibrillator) may damage a neurostimulator, and the electrical pulses from the neurostimulator may result in an inappropriate response of the cardiac device. Precautions: The safety and effectiveness of this therapy has not been established for pediatric use (patients under the age of 18), pregnancy, unborn fetus, or delivery. Patients should be detoxified from narcotics prior to lead placement. Clinicians and patients should follow programming guidelines and precautions provided in product manuals. Patients should avoid activities that may put undue stress on the implanted neurostimulation system components. Patients should not scuba dive below 10 meters of water or enter hyperbaric chambers above 2.0 atmosphere absolute (ATA). Electromagnetic interference, postural changes, and other activities may cause shocking or jolting. Adverse Events: Adverse events may include undesirable change in stimulation described by some patients as uncomfortable, jolting or shocking; hematoma, epidural hemorrhage, paralysis, seroma, CSF leakage, infection, erosion, allergic response, hardware malfunction or migration, pain at implant site, loss of pain relief, chest wall stimulation, and surgical risks. For further information, please call Medtronic at and/or consult Medtronic’s website at Rx only

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