Accumulation of axonal damage in multiple sclerosis (MS) patients results in central pain syndromes, motor deficiencies, and spasticity. Recent studies suggest that disease severity is associated with the amount of axonal damage.1 Current pharmacological, immunomodulatory, and immunosuppressive therapies are only effective in patients with active inflammatory disease. This offers little benefit to patients with primary or secondary progressive disease. Focus has since moved to axonoprotection; however, no agents are currently available for clinical usage.1
Aside from curative therapies, symptomatic relief is another important aspect of MS treatment. Originally used to address lower extremity or chronic back pain, spinal cord stimulation (SCS) has found success in treating neurological conditions, including MS.2,3 Traditional SCS offers a means to manage many late-stage MS symptoms. Electrodes placed in the epidural space evoke paresthesias to modulate pain signaling, coinciding with areas where patients experience most of their pain. Results range from successful pain control to improved urinary incontinence and spasticity.3
Novel advances in SCS technology offers paresthesia-free SCS (PF-SCS) as an alternative means for neuromodulation. This technology has been successfully used to treat many chronic pain syndromes, including chronic back and leg pain. However, successful PF-SCS usage has yet to be shown in MS. Here, we present a case of PF-SCS utilization for central pain and spasticity treatment in a late-stage MS patient.
Written consent was obtained from the patient and her daughter for publication of this case report and accompanying figures.
A 54-year-old woman with a 13-year history of MS presented for evaluation of a spinal cord stimulator trial. Before disease onset, she could ambulate and had no pain or neurological deficits. Her initial symptoms included balance difficulties, urinary incontinence, and upper and lower extremity paresthesias. With disease progression, she became wheelchair bound. Furthermore, she suffered from mild dysarthria, neurogenic bladder, neck pain, shoulder pain, low back pain with spasm, and lower extremity pain with spasm. Intravenous steroid treatment improved her shoulder and neck pain. However, her low back and lower extremity pain with spasm persisted. The lower extremity pain evolved where placing her feet on the ground for transfer resulted in excruciating pain. Her back and leg pain were 6–9 of 10 on visual analog score (VAS) with sharp shooting quality.
Teriflunomide was ineffective in relieving her symptoms, and she was switched to dimethyl fumarate with plans to start rituximab in the future. Despite trials of various agents including antidepressants (venlafaxine and amitriptyline), muscle relaxants (baclofen and cyclobenzaprine), gabapentin, and nonsteroidal anti-inflammatory drugs, her symptoms progressively worsened without significant pain relief. Pregabalin was not trialed due to prohibitive cost. She had some symptomatic improvement with the medications she was already on.
Her brain magnetic resonance imaging (MRI) scan revealed periventricular, subcortical, left pontine, right cerebellar, and right pontine lesions, which had been stable compared to previous imaging (Figure 1). A cervical spine MRI scan showed discrete multifocal nonenhancing lesions at C2 (midline and left), C3 (midline and right), C4 (posterior midline), C5 (right), C6 (right), and C7 (left posterior lateral). Furthermore, her cervical spine MRI scan showed multilevel degenerative disk disease and mild spinal stenosis without significant neural foraminal narrowing (Figure 2). A lumbar spine MRI scan revealed L4–5 mild canal narrowing with mild bilateral foraminal narrowing and L5–S1 mild-to-moderate bilateral foraminal narrowing (Figure 3). Considering her MRI scan findings, an electromyogram was not ordered by neurology. Given the extent of her disease, she was deemed an appropriate candidate for a trial of PF-SCS.
Intraoperative tonic testing with paresthesia was provoked to match regions where the patient was experiencing back and lower extremity pain. Adequate coverage was obtained once the lead was placed at the top of T8 (Figure 4). The leads (Abbott BurstDR, St. Paul, MN) were sterilely attached to the battery and programmed by the representative with patient feedback to confirm satisfactory coverage.
In the recovery unit, the patient underwent an uneventful course reporting 6/10 pain on VAS at discharge. Device programming was optimized for burst parameters before safe discharge home. On trial completion, she reported ≥80% pain relief in her back and lower extremities. Furthermore, she had successfully placed her feet on the ground twice to move from her bed to wheelchair with 2-person assist. Before this, she required a lift. In addition, she regained the ability to sense the urge to void.
The patient’s experience with SCS was discussed, and the decision was made to undergo a permanent MRI-compatible paddle lead system placement. A paddle system was selected due to institutional practice. She underwent general anesthesia with inhaled anesthetic for the procedure. T10–T11 and T9–T10 laminotomies were performed intraoperatively for paddle placement over T9 to replicate the coverage from the percutaneous single-lead trial (Figure 5). The patient tolerated the procedure well, with an uneventful recovery.
At 1-month follow-up, she reported continued functional improvement and adequate pain control. Her pain was reported at 2/10 on VAS without supplementary medication usage for breakthrough pain control. She could stand with a walker, ambulate independently for short distances, sit without falling, and place herself on a bedpan when she felt the urge to void. At 4-month follow-up, she reported 100% back and lower extremity pain relief, with resolution of her lower extremity spasms, rating the pain at 0/10 on VAS. At 5-month follow-up, her pain continued to be well controlled. At 10 months, she continued to report 0/10 pain. Although her back pain and spasms remained controlled, her left lower extremity weakness returned to preimplantation levels. Her right lower extremity continued to have increased strength. Combined with continued balance difficulties, she could not ambulate independently and remained largely wheelchair bound. Currently, her bladder dysfunction could not be accurately assessed due to several episodes of urinary tract infections resulting in hospitalizations.
Traditional SCS functions on the premise that paresthesia mapping coincides with the patient’s region of pain. According to gate control theory, it is thought that preferential activation of large diameter axons, such as Aβ fibers of the dorsal column, modulates pain signaling from Aδ and C fibers.4 Once implanted, the presence of paresthesias acts as a surrogate to indicate dorsal column activation and effective neuromodulation. Aside from bioelectrical stimulation, SCS was thought to reduce extracellular glutamate and increase dorsal horn gamma-aminobutyric acid release by both segmental and supraspinal pathways.5 SCS has been shown to reduce long-term potentiation and modulated hyperexcitability in mice.6
PF-SCS is a relatively novel modality for pain modulation for which the mechanism of action and efficacy has yet to be definitively defined. Current PF-SCS options involve devices that elicit burst pattern or high-frequency stimulation to prevent the sensation of paresthesias. The Success Using Neuromodulation With BURST study was the first large, prospective, multicenter randomized crossover study on burst stimulation.7 Patients were randomized to traditional or PF-SCS for 12 weeks each before crossing over. In that study, 70% of patients preferred burst stimulation after the 24-week period due to better pain relief (45.6%) or lack of paresthesia (47.1%). At 1-year follow-up, of the 88 patients who provided preference data, 7 patients had no preference, 60 preferred burst stimulation, and 21 patients preferred tonic stimulation.
Studies have shown that low-frequency paresthesias generated by high-frequency spinal cord stimulators do not overlap with pain regions treated by the same device when using high frequencies, indicating a different mechanism of action than traditional SCS.8 Nevertheless, it has been shown to treat most chronic pain conditions just as effectively as paresthesia-inducing SCS and is potentially better at treating chronic low back pain.9 Similar findings of improved pain relief were found in patients using burst pattern PF-SCS compared to traditional paresthesia-inducing SCS.7
Our patient’s pain and spasms were successfully treated by burst pattern PF-SCS with permanent paddle lead placement. North et al10 found that paddle leads offer improved pain scores up to 1.9 years after implantation, but this difference disappears at 2.9 years. Aside from pain and spasm relief, our patient regained some previously lost strength due to improved pain relief, allowing for increased physical activity. However, our results are limited as they only reflect the 10-month follow-up experiences of 1 patient.
Traditional paresthesia-inducing SCS has been used to successfully provide symptomatic relief in MS patients. Patient results varied from pain control to increased strength. Since 2000, there have been 4 published reports of patients with MS treated with traditional paresthesia-inducing SCS, and none have involved PF-SCS.3 Given the necessity of repeat MRI scans to monitor disease progression, our patient received an MRI-compatible system.
MS is a difficult-to-manage, devastating neurological disease. Current options for management slow but do not reverse the demyelinating process. Late-stage MS symptoms are difficult to treat and range from pain to spasticity. Paresthesia-inducing SCS has been used for MS treatment, although the role of PF-SCS is less defined. Given the success in symptom management in our patient, there may be a potential role for PF-SCS in treating central pain and spasticity in MS patients.
Name: Christopher M. Lam, MD.
Contribution: This author helped review the literature and write the manuscript.
Name: Brian R. Monroe, MD.
Contribution: This author helped review the literature and write the manuscript.
This manuscript was handled by: BobbieJean Sweitzer, MD, FACP.
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