https://orcid.org/0000-0003-3040-6434
Introduction
Idiopathic small fiber neuropathy (SFN) is a slowly progressively debilitating and painful illness without disease modifying treatments.1 It is not a rare condition with an incidence of 12 per 100 000 and prevalence of 53 cases per 100 000.2 A typical presentation is numbness, burning, tingling, and pain in a stocking glove distribution. It may involve both the unmyelinated C-fibers as well as thinly myelinated Aδ fibers.3 Diagnosis is primarily made by clinical presentation and can be confirmed with skin biopsy to measure intraepidermal nerve fiber density.4 Management of SFN consists of treating any underlying condition, then the application of gabapentinoids, antidepressants, tramadol or other opioids to modulate the pain. However, many of the medications cause significant side effects, and none of the medications used to treat this condition or similar neuropathies have much impact on numbness.5,6 More effective and better tolerated treatments are needed.
Scrambler Therapy (ST) is a Food and Drug Administration approved form of cutaneous electrostimulation for neuromodulation of pain that is sometimes effective in chronic neuropathic cancer and non-cancer pain, as well as numbness and tingling.7 It is remarkably safe with an adverse event rate of only 0.03%, consisting at most of a bruise or slight redness under the electrodes.8 We report here the use of ST to treat 3 consecutive patients with documented idiopathic SFN. All patients gave written permission to use their information, and Investigational Review Board permission is not needed for case reports of 3 or less persons.
Cases
Case 1: This 70-year-old female had a 7-year history of small fiber neuropathy (SNF). Symptoms started in 2016 with above the ankle burning sensation that radiated above the knee, associated with stabbing pinching nerve pain. Skin biopsy obtained in 2017 confirmed SFN. The patient started intravenous immunoglobulins (IVIg) for 3 months but developed hemolytic anemia with minimal improvement, so it was discontinued. In 2019, burning pain spread to her arms, from 1” above the wrists to 4” below the shoulders. She tried Gabapentin, antidepressants, Duloxetine, IV Ketamine, and Methadone with no symptom control. She used Tramadol 100 mg 24-hour Extended Relief and 50 mg immediate release as needed with partial relief. Prior to initiating her first session of scrambler therapy, the patient noted her pain was 7.5/10 in her legs and 6/10 in her arms.
Following 5 daily consecutive sessions lasting 40 minutes each, she noted an improvement to 2–3 out of 10 in her legs and 1–2 out of 10 in her arms. Because of persistent pain in her legs, she afterward increased her Tramadol ER to 100 twice a day with more improvement. She had 7 additional sessions in April 2021, and 3 sessions in July 2021. Pain worsened in her legs and arms in March 2023, and starting April 2023 she underwent 4 sessions. The electrode placement is shown in Figure 1. The pain in the arms was reduced from 6–7 to 0/10 on the pain scale, but her legs remained at 8/10 despite treatments. Throughout this period of multiple treatments on 2 separate treatment days the leg pain went to 0/10 and lasted over 12 hours. This could not be replicated, however. Overall, she judged the treatment to be very successful in her arms, with less effect on the legs. Unfortunately, her SFN has progressed with more numbness, fatigue, postural orthostatic tachycardia syndrome, and dyspnea making it too difficult to continue treatment.
Placement of the arm electrode set 2 cm below and above the pain.
Case 2: This 70-year-old male had a history of type 2 diabetes (A1c 7.0%) complicated with diabetic small fiber neuropathy (DSFN). Symptoms started in 2012. He developed a burning sensation in both feet, which gradually evolved into a feeling of cold. The coldness moved up his legs, to the mid-thighs, recently associated with cramps. His left hand and forearm also became affected. His right hand was relatively spared. These symptoms had been relatively stable for the past 8 years. Sweat test in 2017–2019 confirmed SNF, as did a skin biopsy showing reduced intraepidermal nerve fiber density. He attempted Gabapentin, Duloxetine, and Tramadol with only minor improvement of symptoms. Acupuncture, dry needling, and traction did not help either. Before the first therapy in 2022, right leg pain, left leg, left hand pain were all reported at 3/10, and his balance was impaired. After 5 consecutive daily treatments, each lasting 40 minutes, his pain improved to 0 out of 10 in all regions and his balance improved. Symptoms recurred 4 months later and after two additional sessions his pain improved from 5 out of 10 to 1–2 out of 10 in all regions, and patient was able to ambulate normally, as shown in Figure 2. However, further treatments failed to relieve the pain for more than a few days and he judged the treatment unsatisfactory for pain relief; however, his balance remained improved. Another series of 3 consecutive treatments 3 months later reduced his pain to zero, which has continued, but he still experiences uncomfortable coldness in all 4 extremities.
Graph showing pre- Scrambler Therapy (ST) and post-ST numerical pain scores, by day.
Case 3: This 96-year-old man had biopsy-documented small fiber neuropathy, and pain in his legs from the toes to the mid-thigh region, progressive over 20 years. He had an extensive workup for causes but no diagnosis was found. He was treated with 2 sets of electrodes on each leg (L5 to L5, and L4 anteriorly to S1 posteriorly) and 1 set across the shoulders at the C6 level. His pain reduced with each session from 3 out of 10 to 1 out of 10, but relief only lasted 1 hour. After 10 treatments the patient stopped due to only transient effect; although he was enthusiastic to do more treatments, transportation to the center was an issue.
Discussion
Treatment of small fiber neuropathy remains unsatisfactory. There is 1 case report of a patient with SFN successfully treated with 2 spinal cord stimulators using both cervical and lower thoracic leads, but that treatment is invasive, expensive, and carries risks like infection and spinal fluid leakage. We were hopeful that scrambler therapy, a non-invasive means of cutaneous neuromodulation, would be helpful in reducing the pain and numbness of SFN, but results so far have been mixed. The mechanism of action of scrambler therapy is still under active investigation, but each set of electrodes acts as an artificial neuron, capturing the surface receptors of the c-fibres and replaces the pain signal with a “non-pain signal.”7 This may reset central sensitization. Scrambler therapy also redirects cerebral blood flow from the pain centers to the frontal inhibitory centers9 and restores the serum balance of pain-activating and inhibitory mRNAs, and their proteins.10 Compared to other neuropathies that have responded to Scrambler Therapy, SFN appears to take more sessions and lose effectiveness sooner. The partial relief of some patients is encouraging that further research and the development of a portable device may allow better more consistent treatment.
Board type questions. Correct
1. Which of the following best describes the symptoms of small fiber neuropathy?
o It affects mostly muscle function. (Sensory deficits)
o Autonomic dysfunction is the most common presenting symptom. (Occurs late in the disease.)
o Sensory function is affected first and foremost
o None of the above
2. Which of the following statements about small fiber neuropathy are true?
o Spinal cord stimulation is nearly universally effective. (Has only been tested in handful of patients.)
o Drug management can help some of the symptoms of most patients.
o Treatment with anti-inflammatory drugs like steroids often resolves the neuropathy. (There is minimal if any effect in most cases.)
o Intravenous immunoglobulin has been proven to be effective in randomized controlled trials. (Definitive negative trial: Neurology 2021 May 18; 96(20):e2534-e2545. doi: 0.1212/WNL.0000000000011919. Epub 2021 Mar 25. Intravenous Immunoglobulin Therapy in Patients With Painful Idiopathic Small Fiber Neuropathy.)
Acknowledgments
Contributions: K.T.S. and T.J.S., treatment of subjects, writing, review of final manuscript. Supported by grants 1 R01 CA245054-01A1; 1 R01 CA177562-01A1, PCORI IHS 1609–36518; PCORI 2020C3-21247-el-Jawari (T.J.S.); the Harry J. Duffey Family Fund for Palliative Care; The Lerner Foundation, Washington, DC (all T.J.S.); the Ben and Esther Rosenbloom Foundation, Baltimore MD (T.J.S.).
Funding
None declared.
Conflicts of interest: None declared.
