Neuromodulation: Technology at the Neural Interface Received: October 14, 2014
Revised: January 14, 2015
Accepted: January 21, 2015
(onlinelibrary.wiley.com) DOI: 10.1111/ner.12281
Novel High-Frequency Peripheral Nerve Stimulator Treatment of Refractory Postherpetic Neuralgia: A Brief Technical Note Imanuel R. Lerman, MD, MS*; Jeffrey L. Chen, MD, MHS*; David Hiller, MD*; Dmitri Souzdalnitski, MD, PhD†; Geoffrey Sheean, MD*; Mark Wallace, MD*; David Barba, MD* Objectives: The study aims to describe an ultrasound (US)-guided peripheral nerve stimulation implant technique and describe the effect of high-frequency peripheral nerve stimulation on refractory postherpetic neuralgia. Materials and Methods: Following a cadaver pilot trial using US and confirmatory fluoroscopic guidance, a 52-year-old man with refractory left supraorbital neuralgia underwent combined US and fluoroscopic-guided supraorbital peripheral nerve stimulator trial. The patient was subsequently implanted with a percutaneous lead over the left supraorbital and supratrochlear nerve utilizing a high-frequency stimulation paradigm. Results: At 9 months follow-up, the pain intensity had declined from a weekly average of 8/10 to 1/10 on the pain visual analog scale (VAS). After implant, both nerve conduction and blink reflex studies were performed, which demonstrated herpetic nerve damage and frequency-specific peripheral nerve stimulation effects. The patient preferred analgesia in the supraorbital nerve distribution accomplished with high-frequency paresthesia-free stimulation (HFS) at an amplitude of 6.2 mA, a frequency of 100–1200 Hz, and a pulse width of 130 μsec, to paresthesia-mediated pain relief associated with low-frequency stimulation. Conclusion: We report the implant of a supraorbital peripheral nerve stimulating electrode that utilizes a high-frequency program resulting in sustained suppression of intractable postherpetic neuralgia. Keywords: Blink reflex, cadaver study, case report, chronic pain, herpes zoster, high frequency, nerve conduction study, neuromodulation, neuropathic pain, peripheral nerve stimulation, postherpetic neuralgia, shingles, supraorbital neuralgia, technical report Conflict of Interest: Dr. Mark Wallace is a consultant for Boston Scientific.
INTRODUCTION
www.neuromodulationjournal.com
Address correspondence to: Imanuel R. Lerman, MD, MS, Anesthesiology, University of California San Diego, 9444 Medical Center Drive, MC: 7651, La Jolla, CA 92093, USA. Email: [email protected] * University of California San Diego, San Diego, CA, USA; and † Western Reserve Hospital, Cuyahoga Falls, OH, USA For more information on author guidelines, an explanation of our peer review process, and conflict of interest informed consent policies, please go to http:// www.wiley.com/bw/submit.asp?ref=1094-7159&site=1 Financial support: This was an unsupported study.
© 2015 International Neuromodulation Society
Neuromodulation 2015; ••: ••–••
1
Postherpetic neuralgia (PHN) is a painful and often debilitating cutaneous condition caused by reactivation of latent varicella zoster virus (VZV). It typically affects the elderly and immunocompromised. PHN is defined as pain in a dermatomal distribution persisting four months after the initial herpes zoster rash, and possibly for years (1). There is an incidence of 1 million episodes of VZV in the United States per year, while one in three people will develop herpes zoster in their lifetime. The incidence is five to ten times greater for those persons older than 80 years (2). Of those affected by herpes zoster, there is a 10–18% risk in developing PHN (3). In a population-based study, the annual medical care cost of treating herpes zoster cases in the United States is estimated at $1.1 billion (4). Tricyclic antidepressant medications are known to be effective in the treatment of pain in PHN (5). There is also strong evidence that supports the use of antiepileptic drugs such as gabapentin and pregabalin with pain intensity reduction by 30–50% in PHN (6). Outside of these agents, opioids have also been shown to be superior to placebo (7). If medication management is not successful, other interventional therapies may be tried, such as peripheral
nerve blockade or as in this case, subcutaneous botox injection therapy (8). If a patient has failed both traditional oral pain therapies and interventional procedures, other neuromodulation techniques may be an option. Peripheral nerve stimulation (PNS) developed 40 years ago has since its inception undergone a continued evolution in the efficacy and efficiency of nerve stimulation and pain treatment (9). PNS, utilizing low-frequency ranges, has been established as a successful treatment of medically refractory neuropathic pain (10). High-frequency PNS is stimulation above the physiological fre-
LERMAN ET AL. quency range, which can result in nerve block as demonstrated in preclinical models and in the clinical setting (11–15). This technical note presents the use of ultrasound (US) with confirmatory fluoroscopic image guidance for the implant of a high-frequency peripheral nerve stimulator (1200 Hz at 6 mA, and 130 μsec pulse width) as a treatment paradigm for supraorbital PHN.
Report of an Illustrative Case A 52-year-old man with a history of PHN, HIV, obstructive sleep apnea, type 2 diabetes, and obesity was referred to the University of California San Diego (UCSD) pain clinic for refractory (five years) PHN pain, localized to the left forehead in the first branch of the trigeminal nerve. The patient reported such severe pain, that at times he was suicidal, leading to multiple emergency room evaluations for suicidal ideation. The patient reported an average pain score of 8–10/10 daily constant pain prior to being evaluated at the UCSD center for pain medicine. The patient failed multiple medication trials, including antidepressants, anticonvulsants, topical agents, as well as several opioid analgesics. Physical examination was pertinent for ulcerations and trophic changes on the left upper forehead/scalp, tactile cutaneous allodynia, hyperalgesia, and temporal summation noted in the left ophthalmic nerve distribution, including supraorbital and supratrochlear nerve distribution. An US-guided left supraorbital nerve block with anesthetic and Botox was performed with injection solution of Botox type A (5 units/injection site) and lidocaine 1% (1 mL/injection site) in close approximation to both the supraorbital and supratrochlear nerve, in addition to four injection sites spread between the frontalis and temporal area. For this US-guided injection and all subsequent procedures, a linear array (L12-5 50 mm 12-5 MHZ, Phillips, Waltham MA, USA) US probe was used. The patient reported 100% pain relief for approximately one day after the injection, but subsequently pain returned to baseline levels. As the patient was refractory to medical management and did demonstrate significant relief with local anesthetic medications, the patient then underwent a peripheral nerve stimulator lead trial. After a combined US fluoroscopic (CUF)-guided technique was tested on a cadaver provided by the UCSD anatomy lab, the patient was readied for CUF-guided peripheral nerve trial. A Boston Scientific 8 contact lead (Marlborough, MA, USA) was placed with CUF image guidance over the left supraorbital foramen. The next day, mapping was carried out with paresthesia-mediated low frequency (40 Hz pulse width at 100 μsec and amplitude of 6 mA), at which time the patient reported a 50% decrease in pain from 9–10/10 on visual analog scale (VAS) to 5/10. Next, 1200 Hz (high frequency) stimulation at an amplitude of 6.2 mA and pulse width of 130 μsec
was then tested, at which point the patient reported pain level of 2/10, accounting for 80% pain relief resulting in 100% anesthesia of his supraorbital nerve while only reporting slight pain in the most lateral edge of the supraorbital ridge. After completion of the trial period (four days later), the patient continued to report 80% pain relief with preferred continuous use of the 1200 Hz program. After this successful trial, the patient then underwent CUF-guided peripheral nerve stimulator implant over left supraorbital and supratrochlear nerve. The patient was given three programs utilizing high-frequency stimulation (ranging from 100 hz to 1200 Hz) that captured all of his painful areas, resulting in 100% pain relief utilizing contacts 1–8, with pain reports of VAS decreasing from 6–9/10 to 0/10. At subsequent follow-up appointments, including his most recent 9-month follow-up appointment, the patient continued to report excellent pain relief, with high-frequency stimulation with pain scores of 1/10, rated as a 95% improvement in his pain. On exam, the prior ulcerative trophic changes had resolved in the left ophthalmic nerve distribution. Blink reflexes (BRs) are commonly employed to diagnose PHN or other facial pain syndromes such as trigeminal neuralgia. Because high-frequency PNS resulted in significant pain relief in this patient with PHN, postimplantation, BRs were performed to further measure the effect of high-frequency PNS. Technical Description Cadaver Implant An initial cadaver study was performed before implantation on our patient to study and plan the modified CUF-guided approach for the PNS trial and implant. In order to perform this study, we used a cadaver (provided by the UCSD Anatomy Lab). A high-frequency linear probe was used to visualize the supraorbital foramen in transverse scan and then a longitudinal scan, after which the probe position was marked with a sterile pen (16). This allowed marking of both the medio-lateral and cephalo-caudad orientation of the supraorbital foramen. A slightly bent 14-gauge Tuohy needle was inserted 1–2 cm posterolateral to the junction of the frontal and zygomatic portion of the orbital rim. The Tuohy needle was then advanced (in-plane) under direct US guidance in an in-plane approach from lateral to medial, and aimed at the line of the superficial temporal fascia, superficial to the temporoparietal fascia and deep to the overlying subcutaneous tissue (Fig. 1). The Tuohy needle was then advanced 1 cm over the supramuscular fascia overlying frontalis muscle and deep to subcutaneous tissue. US guidance allowed real-time direct visualization of the Tuohy bevel tip, allowing the operator to avoid engaging or scraping subcutaneous tissue. The Tuohy needle was fixed at this point and the 8 contact (Linear ST Percutaneous, Boston Scientific) lead was advanced in the
2
Figure 1. Cadaver implant of supraorbital peripheral nerve stimulator. a. The Tuohy needle slightly bent was advanced (1 cm) under direct ultrasound guidance in an in-plane approach within the superficial temporal fascial line just superficial to the temporoparietal fascia and deep to the subcutaneous tissue, and then the lead was advanced further above the supramuscular fascia overlying frontalis muscle. Panels b and c demonstrate methylene blue which was injected as the lead was advanced (red arrows, Tuohy needle; yellow arrows, peripheral nerve stimulator lead). www.neuromodulationjournal.com
© 2015 International Neuromodulation Society
Neuromodulation 2015; ••: ••–••
NOVEL HIGH-FREQUENCY PNS TREATMENT OF POSTHERPETIC NEURALGIA
Figure 2. Cadaver implant of supraorbital nerve stimulator. a. The Tuohy needle slightly bent was advanced (1 cm) under direct ultrasound guidance in an in-plane approach (b). Under ultrasound image guidance, the Tuohy needle tip is easily visualized with bevel directed downward, then advanced in real time, taking care to avoid contact with the subcutaneous tissue. The Tuohy needle tip (red arrows) was kept stationary (a, c, e). c. The Tuohy needle was kept stationary and the lead was then advanced under combined ultrasound (d) and flouoroscopic imaging (e, f ).
subcutaneous tissue plane. The lead was advanced continuously superficial to the supramuscular fascia overlying the frontalis muscle and deep to the subcutaneous tissue. As the lead was advanced the contacts (hyperechoic) and inter-contact spaces (hypoechoic) were directly visualized under US guidance in an in-plane view with confirmatory fluoroscopic imaging (Fig. 2). The lead was perforated at the tip to allow visualization of a colored injectate (methylene blue) (Fig. 1). Methylene blue was injected through the perforated tip incrementally as the lead was advanced. The placement of the lead was then confirmed by fluoroscopic imaging, as previously described (17). Upon further dissection, methylene blue injectate was localized directly over the supraorbital nerve, deep to the subcutaneous tissue and superficial to the supramuscular fascia overlying the frontalis muscle (Fig. 1).
www.neuromodulationjournal.com
Patient Supraorbital Peripheral Stimulation Implant Peripheral nerve stimulator implant was performed with placement of peripheral nerve stimulator electrode using the same CUF trial approach. After the peripheral nerve stimulator electrode was successfully positioned over the supraorbital and supratrochlear nerves, the lead was then tunneled to a generator pocket created in infraclavicular location. After permanent peripheral nerve stimulator implantation, nerve conduction studies (NCS) (Fig. 4) and blink reflex study (BRS) (Figs 5 and 6) were carried out on both left and right supraorbital nerve. NCS demonstrated a normal right supraorbital sensory action potential waveform. Left supraorbital sensory nerve conduction study demonstrated an absent sensory nerve action potential indicative of large fiber supraorbital nerve dysfunction. BR tests demonstrated normal right-sided response. BR tests of the left
© 2015 International Neuromodulation Society
Neuromodulation 2015; ••: ••–••
3
Patient Supraorbital Peripheral Stimulation Trial The patient underwent a peripheral nerve stimulator trial and implant using CUF guidance. The patient was placed in the supine position with the head turned to right. A pre-US scan was carried out with the US probe oriented in the transverse plane to visualize the level of the supraorbital foramen and then in a longitudinal plane to visualize the temporal artery and the lateral edge of the supraorbital ridge. The skin and soft tissues were anesthetized with a 10 mL solution of lidocaine 1% that was infiltrated 2 cm lateral to the orbit at the level of the supraorbital ridge and the superficial temporal fascia. After the supraorbital foramen was identified, the probe was placed in transverse orientation over the roof of the orbital rim. The bone was scanned until a hypoechoic break identifying the foramen was located. Color doppler was used to visualize and confirm the presence of the supraorbital artery in short axis as it exited the supraorbital foramen. A 14-gauge bent Tuohy needle was inserted 1–2 cm posterolateral to the junction of the frontal and zygomatic portion of the orbital rim. The Tuohy needle was then advanced (in-plane) under direct US guidance from lateral to medial, and aimed at the line of the superficial temporal fascia, superficial to the temporoparietal fascia and deep to the overlying subcutaneous tissue (Fig. 3). Real-time US imaging demonstrated that the needle tip and shaft remained below the subcutaneous tissue layer and above the temporoparietal fascia, then the tip was advanced above the supra-muscular fascia overlying the frontalis muscle. Real-time US imaging of the Tuohy tip ensured avoidance of
penetration or trauma to the subcutaneous tissue. The frontalis muscle was identified as deep palisading longitudinal fibers just underneath the supramuscular fascia (Fig. 3). No vasculature was encountered as the needle was advanced confirmed with color doppler US imaging. After the Tuohy needle was fixed at the lateral edge of the orbital rim, the lead was visualized under US guidance as it was advanced and exited the needle tip remaining between subcutaneous tissue and the supramuscluar fascia overlying the frontalis muscle (Fig. 3d). Further fluoroscopic images in the AP view demonstrated the 8 contact lead overlying the supraorbital ridge (Fig. 3a,c). After the electrode lead was placed in the desired location, the needle was removed. Dermabond (Ethicon, Somerville, NJ, USA) and a Biopatch (Johnson and Johnson, New Brunswick, NJ, USA) were placed over the lead entry point. Steri-strips (3M, St Paul, MN, USA) were placed over the electrode lead. Bacitracin was then placed under a one loop coil behind the ear. Tegaderm (3M) was used to cover the steri-strips overlying the lead. The lead was taped to the side of the patient’s neck and secured for further programming. The lead was checked to ensure all contacts were viable and verified by the Boston Scientific representative. The day after trial lead placement, the patient returned to clinic to initiate programming including low-frequency (40 Hz pulse width at 100 μsec and amplitude of 6 mA) paresthesia mapping, followed by the initiation of a high-frequency stimulation program.
LERMAN ET AL.
Figure 3. Intraoperative implant of supraorbital nerve stimulator. a. Intraoperative technique of lead advancement using the in-plane ultrasound-guided approach. Panel b demonstrates the Tuohy needle advanced into the loose aeorolar tissue plane, deep to the subcutaneous tissue. The Tuohy needle is only advanced approximately 1 cm at which time the lead is advanced over the supramuscular fascia overlying the frontalis muscle. c. After the lead is appropriately placed, the Tuohy needle is withdrawn. d. 1 indicates the epidermal layer; 2 indicates the dermal layer; 3 indicates the subcutaneous peripheral nerve stimulator lead; 4 indicates the supramuscular fascia; 5 indicates the frontalis muscle layer which demonstrates longitudinal fiber layers (black lines); 6 indicates the skull periosteum. e. Corresponding tissue layers under ultrasound imaging, using high-frequency linear array (L12-5 50 mm 12–5 MHZ, Phillips, Waltham, MA, USA) ultrasound probe. a. Photograph has been presented in poster format at the 2013 NANS (18).
stimulation (HFS) (1200 Hz) of the left supraorbital nerve, the amplitude of left R2 was markedly suppressed and the left R2 latency was increased, while low frequency (40 Hz) had less of an effect (Fig. 6). The patient has had sustained pain relief of his severe, intractable left supraorbital herpetic neuralgia over a 9-month follow-up period. His reported pain intensity over the left supraorbital nerve distribution declined from a weekly average of 8/10 to 1/10 on the pain intensity scale. The patient’s exam demonstrated decreased left forehead hyperalgesia, decreased left forehead allodynia, and decreased left frontalis activity on eye brow raise. Postimplantation, the program that the patient preferred to use to obtain this analgesia was frequency at 1200 Hz, amplitude 6.2 mAmp (25.5 max mAmp), and pulse width 130 μsec. In addition, the patient utilized a 100 Hz, amplitude 15.2 mAmp, and pulse width of 400 μsec.
Figure 4. Nerve conduction study of right and left supraorbital nerve. a. Right supraorbital sensory action potential visualized demonstrates a normal peripheral nerve conduction waveform (green bar) with functional large fibers of the right supraorbital nerve. b. Left supraorbital sensory nerve conduction study demonstrates an absent sensory nerve action potential (orange bar) indicative of large fiber supraorbital nerve dysfunction.
4
supraorbital nerve did not produce a clear ipsilateral R1 response, but produced bilateral R2 responses with a significantly shorter latency and larger amplitudes when compared with the unaffected right-side waveform (Fig. 5). After high-frequency paresthesia-free www.neuromodulationjournal.com
DISCUSSION PNS utilizing percutaneously inserted electrodes has been shown to be effective for a variety of indications, including: occipital neuralgia (19–23), trigeminal neuropathic pain (24–27), cervicogenic headache (28–32), and as in our case, PHN (10,33). This technical note demonstrates: 1) US-guided peripheral nerve stimulator lead implant over the supraorbital and supratrochlear nerve; and 2) the use of high-frequency PNS in the treatment of PHN facial pain. The use of US guidance allowed us to place the Tuohy needle and then advance the lead subcutaneously. The main advantage of the
© 2015 International Neuromodulation Society
Neuromodulation 2015; ••: ••–••
NOVEL HIGH-FREQUENCY PNS TREATMENT OF POSTHERPETIC NEURALGIA
Figure 5. Left and right blink reflex (BR) with peripheral nerve stimulator off (a and b). Panel a demonstrates left-sided BR with an absent R1 thought to be due to herpetic nerve damage. The red bars in Panel a demonstrate a wide and large amplitude R2 waveform that represents central hyperexcitability of the polysynaptic left trigeminal sensory pathways involved in this reflex. Panel b demonstrates right-sided (unaffected) BR, with smaller R2 amplitude (red bars) than the left side (a). In addition, the R2 latency (blue bars) is increased (b) when compared with the short R2 latency on the left (a).
www.neuromodulationjournal.com
Figure 6. Left blink reflex with implanted supraorbital peripheral stimulator off (a), the implanted supraorbital peripheral stimulator turned on at a 40 Hz frequency (b), and the implanted supraorbital peripheral stimulator turned on at a 1200 Hz frequency (c). Red vertical bars (a–c) demonstrate sequential decrement in amplitude of the R2 complex, with increasing frequency of supraorbital stimulation at 40 Hz (b) and 1200 Hz (c). Blue bars demonstrate sequential increased latency of R2, with higher frequency at 40 Hz (b) and 1200 Hz (c).
nerve block (13). Solomonow et al. utilized a monophasic waveform similar to the current controlled waveform used in this case thought to maintain a net charge on the nerve membrane that can result in nerve block. As demonstrated postoperatively, the patient likely had motor nerve block given decreased left frontalis activity. This case demonstrates supraorbital nerve stimulation-mediated changes to the BR. Abnormal BRs are apparent in trigeminal neuropathy (TNP) and PHN, and are employed as part of the diagnostic algorithm of both TNP (38,39) and PHN (39), demonstrative of shortened R2 latency and increased R2 amplitude (or area under the curve [AUC]) (35), and small or abolished R1 waveform. This patient with left-sided PHN had a BR that was consistent with the prior literature, including: 1) a shortened left side R2 latency; 2) an increase in the left-side R2 AUC; and 3) an absent left side R1. R1 waveforms are thought to largely represent A-beta fibers while the R2 waveforms represent combined afferent A-Beta, A-delta, and C-fiber activation (40). This is supported by R2 (but not R1) activation with supraorbital laser stimulation known to activate only afferent C-fibers (41). Similar to PHN patients, chronic migraine patients who are given capsaicin injection consistently demonstrate an increase in R2 AUC (42). Occipital nerve block employed for headache therapy is known to modulate the trigeminocervical complex and has been shown to alter BR by: 1) decreasing R2 AUC; and 2)
© 2015 International Neuromodulation Society
Neuromodulation 2015; ••: ••–••
5
US technique is that it avoids further tissue trauma by blindly advancing a Tuohy needle, which is likely to damage underlying fascia, muscle layers, and most importantly the superficial subcutaneous tissue, all of which may cause lead erosion. Lead erosion through subcutaneous tissue is one of the most common complications of PNS procedures (34). Advancing the Tuohy needle under US guidance allows the operator to immediately detect if the needle is in close proximity to subcutaneous tissue and then redirect the needle course. US-guided Tuohy visualization may decrease trauma to subcutaneous tissue as well as risk of lead erosion. Advancing the lead easily visualized under US guidance in the potential space between the supramuscular fascia and the subcutaneous tissue may further decrease the risk of tissue injury. A total of two confirmatory fluoroscopic images were obtained to further verify proper lead placement over the supraorbital foramen. Using the CUF approach may reduce exposure of both the patient and physician to unnecessary x-ray irradiation. PHN is caused by small and large fiber dysfunction, which is thought to originate from varicella-zoster-induced degeneration of the dorsal root ganglion cells (35). Prior studies show A-delta and C-fiber specific damage as well as demyelination of A-beta fibers (35–37). This combined nociceptive fiber type dysfunction contributes to the severe pain experienced by patients with PHN. In this case, the patient’s pain was so severe and debilitating that at times the patient was actively suicidal. The patient, however, did not have a history of depression or any other mental health disorder. Nine months after successful implantation, both personal interview and a review of the chart demonstrate no evidence of mental health issues related to major depression disorder. This patient chose an amplitude of 6 mA with a 130 μsec pulse width when utilizing 1200 Hz stimulation. These stimulation parameters are within close range to high frequency 600–1200 Hz and amplitude described by Solomonow et al. that resulted in motor
LERMAN ET AL. increasing the R2 latency (43). It is thought that the amplitude and duration of the R2 is mediated by wide dynamic range neurons in the trigeminal nucleus caudalis (40,42). In clinical studies, R2 amplitude decreases in response to procaine injection (44), fentanyl and diazepam administration, which is reversible with naloxone and flumazenil, respectively (45). Nonpharmacological electroacupuncture (EA) and transcutaneous electrical nerve stimulation (TENS) demonstrate an attenuation of the R2 amplitude at both 2 Hz and 100 Hz (46). At 2 Hz, the TENS and EA-mediated decrease in R2 amplitude was reversed with the administration of naloxone (46), suggesting that there is a frequency-specific (2 Hz) opiodergicmediated effect on R2. This patient had a subcutaneous implantation of the peripheral nerve stimulator that resulted in excellent pain relief at the preferred high-frequency programs of 1200 Hz and 100 Hz. Similar to the R2 amplitude decrement described in prior studies with the use of EA, TENS, procaine, fentanyl, and diazepam, this case of subcutaneous supraorbital PNS resulted in a decrease of the R2 amplitude. To our knowledge, we demonstrate for the first time that high-frequency (1200 Hz) subcutaneous PNS decreased the R2 amplitude significantly more than at 40 Hz. Prior studies demonstrate that peripheral nerve block of A-Beta and or C-fibers is frequency dependent (47). This technical note demonstrates a frequency-dependent incremental decrease (1200 Hz larger decrease than 40 Hz) in the R2 waveform known to be preferentially activated by afferent C-fibers (41). The decrease in R2 amplitude at high frequency (1200 Hz) likely represents a frequency-specific afferent C-fiber block that was not as apparent at low-frequency (40 Hz) stimulation. Taken together, the R2 amplitude decrease after high-frequency stimulation seen in this case suggests an effect on afferent C-fibers and wide dynamic range neurons that contributed to the sustained pain relief in this patient.
CONCLUSION This technical note demonstrates: 1) a CUF technique for subcutaneous supraorbital and supratrochlear peripheral nerve stimulator trial and implant; 2) that high-frequency stimulation (1200 Hz) of the subcutaneous supraorbital/supratrochlear nerves alters the BR by modulating wide dynamic range neurons found within the trigeminal nucleus caudalis; and 3) that this high-frequency stimulation can result in long-standing pain relief.
Authorship Statements Drs. Lerman, Hiller, and Souzdsalnitski carried out the cadaver study; Dr. Sheean carried out the blink reflex study and the nerve conduction studies. Drs. Barba, Lerman, and Hiller carried out the patient trial and implant using the combined ultrasound and fluoroscopic technique. Drs. Lerman, Chen, Hiller, Souzdalnitski, Wallace, and Barba prepared the manuscript draft and provided important intellectual input. All authors have approved this manuscript.
How to Cite this Article: Lerman I.R., Chen J.L., Hiller D., Souzdalnitski D., Sheean G., Wallace M., Barba D. Novel High-Frequency Peripheral Nerve Stimulator Treatment of Refractory Postherpetic Neuralgia: A Brief Technical Note. Neuromodulation 2015; E-pub ahead of print. DOI: 10.1111/ner.12281
6 www.neuromodulationjournal.com
REFERENCES 1. Dworkin RH, Portenoy RK. Pain and its persistence in herpes zoster. Pain 1996;67:241–251. 2. Glynn C, Crockford G, Gavaghan D, Cardno P, Price D, Miller J. Epidemiology of shingles. J R Soc Med 1990;83:617–619. 3. Harpaz R, Ortega-Sanchez IR, Seward JF. Advisory Committee on Immunization Practices (ACIP) Centers for Disease Control and Prevention (CDC). Prevention of herpes zoster: recommendations of the advisory committee on immunization practices (ACIP). MMWR Recomm Rep 2008;57 (RR–5):1–30. quiz CE2-4. 4. Yawn BP, Itzler RF, Wollan PC, Pellissier JM, Sy LS, Saddier P. Health care utilization and cost burden of herpes zoster in a community population. Mayo Clin Proc 2009;84:787–794. 5. Argoff CE. Review of current guidelines on the care of postherpetic neuralgia. Postgrad Med 2011;123:134–142. 6. Wiffen PJ, Derry S, Moore RA et al. Antiepileptic drugs for neuropathic pain and fibromyalgia—an overview of cochrane reviews. Cochrane Database Syst Rev 2013;(11):CD010567. 7. Khadem T, Stevens V. Therapeutic options for the treatment of postherpetic neuralgia: a systematic review. J Pain Palliat Care Pharmacother 2013;27:268–283. 8. Apalla Z, Sotiriou E, Lallas A, Lazaridou E, Ioannides D. Botulinum toxin A in postherpetic neuralgia. Clin J Pain 2013;29:857–864. 9. Slavin KV. Peripheral nerve stimulation for neuropathic pain. Neurother 2008;5:100– 106. 10. Dunteman E. Peripheral nerve stimulation for unremitting ophthalmic postherpetic neuralgia. Neuromodulation 2002;5:32–37. 11. Tanner J. Reversible blocking of nerve conduction by alternating-current excitation. Nature 1962;195:712–713. 12. Bowman BR, McNeal DR. Response of single alpha motoneurons to high-frequency pulse trains. firing behavior and conduction block phenomenon. Appl Neurophysiol 1986;49:121–138. 13. Solomonow M, Eldred E, Lyman J, Foster J. Fatigue considerations of muscle contractile force during high-frequency stimulation. Am J Phys Med 1983;62:117–122. 14. Kilgore KL, Bhadra N. Reversible nerve conduction block using kilohertz frequency alternating current. Neuromodulation 2014;17:242–254, discussion 254–5. 15. Williamson RP, Andrews BJ. Localized electrical nerve blocking. IEEE Trans Biomed Eng 2005;52:362–370. 16. Tsui BC. Ultrasound imaging to localize foramina for superficial trigeminal nerve block. Can J Anaesth 2009;56:704–706. 17. Slavin KV, Vannemreddy PS. Repositioning of supraorbital nerve stimulation electrode using retrograde needle insertion: a technical note. Neuromodulation 2011;14:160–163, discussion 163–4. 18. Sein M, Lerman I. Peripheral nerve stimulator placement with ultrasound guidance for the treatment of post herpetic neuralgia: a case report (poster #267). Las Vegas, NV: Presented at the 17th Annual Meeting of the North American Neuromodulation Society, 2013. 19. Weiner RL, Reed KL. Peripheral neurostimulation for control of intractable occipital neuralgia. Neuromodulation 1999;2:217–221. 20. Hammer M, Doleys DM. Perineuromal stimulation in the treatment of occipital neuralgia: a case study. Neuromodulation 2001;4:47–51. 21. Johnstone CS, Sundaraj R. Occipital nerve stimulation for the treatment of occipital neuralgia-eight case studies. Neuromodulation 2006;9:41–47. 22. Slavin KV, Nersesyan H, Wess C. Peripheral neurostimulation for treatment of intractable occipital neuralgia. Neurosurgery 2006;58:112–119, discussion 112–9. 23. Skaribas I, Aló K. Ultrasound imaging and occipital nerve stimulation. Neuromodulation 2010;13:126–130. 24. Johnson MD, Burchiel KJ. Peripheral stimulation for treatment of trigeminal postherpetic neuralgia and trigeminal posttraumatic neuropathic pain: a pilot study. Neurosurgery 2004;55:135–141, discussion 141–2. 25. Slavin KV, Wess C. Trigeminal branch stimulation for intractable neuropathic pain: technical note. Neuromodulation 2005;8:7–13. 26. Reverberi C, Dario A. The treatment of trigeminal neuralgia and atypical facial pain with peripheral nerve field stimulation (PNfS): a clinical case report. Neuromodulation 2011;14:552. 27. Amin S, Buvanendran A, Park KS, Kroin JS, Moric M. Peripheral nerve stimulator for the treatment of supraorbital neuralgia: a retrospective case series. Cephalalgia 2008;28:355–359. 28. Popeney CA, Alo KM. Peripheral neurostimulation for the treatment of chronic, disabling transformed migraine. Headache 2003;43:369–375. 29. Melvin EA Jr, Jordan FR, Weiner RL, Primm D. Using peripheral stimulation to reduce the pain of C2-mediated occipital headaches: a preliminary report. Pain Physician 2007;10:453–460. 30. Rodrigo-Royo MD, Azcona JM, Quero J, Lorente MC, Acin P, Azcona J. Peripheral neurostimulation in the management of cervicogenic headache: four case reports. Neuromodulation 2005;8:241–248. 31. Slavin KV, Colpan ME, Munawar N, Wess C, Nersesyan H. Trigeminal and occipital peripheral nerve stimulation for craniofacial pain: a single-institution experience and review of the literature. Neurosurg Focus 2006;21:E5. 32. Zhou L, Abad M, Ashkenazi A. Occipital and supraorbital nerve stimulation for refractory cervicogenic headache—a comparison study. Neuromodulation 2011;14. 33. Stidd DA, Wuollet AL, Bowden K et al. Peripheral nerve stimulation for trigeminal neuropathic pain. Pain Physician 2012;15:27–33. 34. Rasskazoff SY, Slavin KV. Neuromodulation for cephalgias. Surg Neurol Int 2013; 4 (Suppl. 3):S136–S150.
© 2015 International Neuromodulation Society
Neuromodulation 2015; ••: ••–••
NOVEL HIGH-FREQUENCY PNS TREATMENT OF POSTHERPETIC NEURALGIA 35. Truini A, Galeotti F, Haanpaa M et al. Pathophysiology of pain in postherpetic neuralgia: a clinical and neurophysiological study. Pain 2008;140:405–410. 36. Cruccu G, Leandri M, Iannetti GD et al. Small-fiber dysfunction in trigeminal neuralgia: carbamazepine effect on laser-evoked potentials. Neurology 2001;56:1722– 1726. 37. Kimura J. Electrically elicited blink reflex in diagnosis of multiple sclerosis. review of 260 patients over a seven-year period. Brain 1975;98:413–426. 38. Cruccu G, Biasiotta A, Galeotti F, Iannetti GD, Truini A, Gronseth G. Diagnostic accuracy of trigeminal reflex testing in trigeminal neuralgia.Neurology 2006;66:139–141. 39. Cruccu G, Leandri M, Feliciani M, Manfredi M.Idiopathic and symptomatic trigeminal pain. J Neurol Neurosurg Psychiatry 1990;53:1034–1042. 40. Esteban A. A neurophysiological approach to brainstem reflexes. Blink reflex. Neurophysiol Clin 1999;29:7–38. 41. Ellrich J, Bromm B, Hopf HC. Pain-evoked blink reflex. Muscle Nerve 1997;20:265– 270.
42. de Tommaso M, Sardaro M, Pecoraro C et al. Effects of the remote C fibres stimulation induced by capsaicin on the blink reflex in chronic migraine. Cephalalgia 2007;27:881–890. 43. Busch V, Jakob W, Juergens T, Schulte-Mattler W, Kaube H, May A. Functional connectivity between trigeminal and occipital nerves revealed by occipital nerve blockade and nociceptive blink reflexes. Cephalalgia 2006;26:50–55. 44. Shahani B. The human blink reflex. J Neurol Neurosurg Psychiatry 1970;33:792–800. 45. Cruccu G, Ferracuti S, Leardi MG, Fabbri A, Manfredi M. Nociceptive quality of the orbicularis oculi reflexes as evaluated by distinct opiate- and benzodiazepineinduced changes in man. Brain Res 1991;556:209–217. 46. Willer JC, Roby A, Boulu P, Boureau F. Comparative effects of electroacupuncture and transcutaneous nerve stimulation on the human blink reflex. Pain 1982;14:267– 278. 47. Joseph L, Butera RJ. High-frequency stimulation selectively blocks different types of fibers in frog sciatic nerve. IEEE Trans Neural Syst Rehabil Eng 2011;19:550–557.
7
www.neuromodulationjournal.com
© 2015 International Neuromodulation Society
Neuromodulation 2015; ••: ••–••
Revised: January 14, 2015
Accepted: January 21, 2015
(onlinelibrary.wiley.com) DOI: 10.1111/ner.12281
Novel High-Frequency Peripheral Nerve Stimulator Treatment of Refractory Postherpetic Neuralgia: A Brief Technical Note Imanuel R. Lerman, MD, MS*; Jeffrey L. Chen, MD, MHS*; David Hiller, MD*; Dmitri Souzdalnitski, MD, PhD†; Geoffrey Sheean, MD*; Mark Wallace, MD*; David Barba, MD* Objectives: The study aims to describe an ultrasound (US)-guided peripheral nerve stimulation implant technique and describe the effect of high-frequency peripheral nerve stimulation on refractory postherpetic neuralgia. Materials and Methods: Following a cadaver pilot trial using US and confirmatory fluoroscopic guidance, a 52-year-old man with refractory left supraorbital neuralgia underwent combined US and fluoroscopic-guided supraorbital peripheral nerve stimulator trial. The patient was subsequently implanted with a percutaneous lead over the left supraorbital and supratrochlear nerve utilizing a high-frequency stimulation paradigm. Results: At 9 months follow-up, the pain intensity had declined from a weekly average of 8/10 to 1/10 on the pain visual analog scale (VAS). After implant, both nerve conduction and blink reflex studies were performed, which demonstrated herpetic nerve damage and frequency-specific peripheral nerve stimulation effects. The patient preferred analgesia in the supraorbital nerve distribution accomplished with high-frequency paresthesia-free stimulation (HFS) at an amplitude of 6.2 mA, a frequency of 100–1200 Hz, and a pulse width of 130 μsec, to paresthesia-mediated pain relief associated with low-frequency stimulation. Conclusion: We report the implant of a supraorbital peripheral nerve stimulating electrode that utilizes a high-frequency program resulting in sustained suppression of intractable postherpetic neuralgia. Keywords: Blink reflex, cadaver study, case report, chronic pain, herpes zoster, high frequency, nerve conduction study, neuromodulation, neuropathic pain, peripheral nerve stimulation, postherpetic neuralgia, shingles, supraorbital neuralgia, technical report Conflict of Interest: Dr. Mark Wallace is a consultant for Boston Scientific.
INTRODUCTION
www.neuromodulationjournal.com
Address correspondence to: Imanuel R. Lerman, MD, MS, Anesthesiology, University of California San Diego, 9444 Medical Center Drive, MC: 7651, La Jolla, CA 92093, USA. Email: [email protected] * University of California San Diego, San Diego, CA, USA; and † Western Reserve Hospital, Cuyahoga Falls, OH, USA For more information on author guidelines, an explanation of our peer review process, and conflict of interest informed consent policies, please go to http:// www.wiley.com/bw/submit.asp?ref=1094-7159&site=1 Financial support: This was an unsupported study.
© 2015 International Neuromodulation Society
Neuromodulation 2015; ••: ••–••
1
Postherpetic neuralgia (PHN) is a painful and often debilitating cutaneous condition caused by reactivation of latent varicella zoster virus (VZV). It typically affects the elderly and immunocompromised. PHN is defined as pain in a dermatomal distribution persisting four months after the initial herpes zoster rash, and possibly for years (1). There is an incidence of 1 million episodes of VZV in the United States per year, while one in three people will develop herpes zoster in their lifetime. The incidence is five to ten times greater for those persons older than 80 years (2). Of those affected by herpes zoster, there is a 10–18% risk in developing PHN (3). In a population-based study, the annual medical care cost of treating herpes zoster cases in the United States is estimated at $1.1 billion (4). Tricyclic antidepressant medications are known to be effective in the treatment of pain in PHN (5). There is also strong evidence that supports the use of antiepileptic drugs such as gabapentin and pregabalin with pain intensity reduction by 30–50% in PHN (6). Outside of these agents, opioids have also been shown to be superior to placebo (7). If medication management is not successful, other interventional therapies may be tried, such as peripheral
nerve blockade or as in this case, subcutaneous botox injection therapy (8). If a patient has failed both traditional oral pain therapies and interventional procedures, other neuromodulation techniques may be an option. Peripheral nerve stimulation (PNS) developed 40 years ago has since its inception undergone a continued evolution in the efficacy and efficiency of nerve stimulation and pain treatment (9). PNS, utilizing low-frequency ranges, has been established as a successful treatment of medically refractory neuropathic pain (10). High-frequency PNS is stimulation above the physiological fre-
LERMAN ET AL. quency range, which can result in nerve block as demonstrated in preclinical models and in the clinical setting (11–15). This technical note presents the use of ultrasound (US) with confirmatory fluoroscopic image guidance for the implant of a high-frequency peripheral nerve stimulator (1200 Hz at 6 mA, and 130 μsec pulse width) as a treatment paradigm for supraorbital PHN.
Report of an Illustrative Case A 52-year-old man with a history of PHN, HIV, obstructive sleep apnea, type 2 diabetes, and obesity was referred to the University of California San Diego (UCSD) pain clinic for refractory (five years) PHN pain, localized to the left forehead in the first branch of the trigeminal nerve. The patient reported such severe pain, that at times he was suicidal, leading to multiple emergency room evaluations for suicidal ideation. The patient reported an average pain score of 8–10/10 daily constant pain prior to being evaluated at the UCSD center for pain medicine. The patient failed multiple medication trials, including antidepressants, anticonvulsants, topical agents, as well as several opioid analgesics. Physical examination was pertinent for ulcerations and trophic changes on the left upper forehead/scalp, tactile cutaneous allodynia, hyperalgesia, and temporal summation noted in the left ophthalmic nerve distribution, including supraorbital and supratrochlear nerve distribution. An US-guided left supraorbital nerve block with anesthetic and Botox was performed with injection solution of Botox type A (5 units/injection site) and lidocaine 1% (1 mL/injection site) in close approximation to both the supraorbital and supratrochlear nerve, in addition to four injection sites spread between the frontalis and temporal area. For this US-guided injection and all subsequent procedures, a linear array (L12-5 50 mm 12-5 MHZ, Phillips, Waltham MA, USA) US probe was used. The patient reported 100% pain relief for approximately one day after the injection, but subsequently pain returned to baseline levels. As the patient was refractory to medical management and did demonstrate significant relief with local anesthetic medications, the patient then underwent a peripheral nerve stimulator lead trial. After a combined US fluoroscopic (CUF)-guided technique was tested on a cadaver provided by the UCSD anatomy lab, the patient was readied for CUF-guided peripheral nerve trial. A Boston Scientific 8 contact lead (Marlborough, MA, USA) was placed with CUF image guidance over the left supraorbital foramen. The next day, mapping was carried out with paresthesia-mediated low frequency (40 Hz pulse width at 100 μsec and amplitude of 6 mA), at which time the patient reported a 50% decrease in pain from 9–10/10 on visual analog scale (VAS) to 5/10. Next, 1200 Hz (high frequency) stimulation at an amplitude of 6.2 mA and pulse width of 130 μsec
was then tested, at which point the patient reported pain level of 2/10, accounting for 80% pain relief resulting in 100% anesthesia of his supraorbital nerve while only reporting slight pain in the most lateral edge of the supraorbital ridge. After completion of the trial period (four days later), the patient continued to report 80% pain relief with preferred continuous use of the 1200 Hz program. After this successful trial, the patient then underwent CUF-guided peripheral nerve stimulator implant over left supraorbital and supratrochlear nerve. The patient was given three programs utilizing high-frequency stimulation (ranging from 100 hz to 1200 Hz) that captured all of his painful areas, resulting in 100% pain relief utilizing contacts 1–8, with pain reports of VAS decreasing from 6–9/10 to 0/10. At subsequent follow-up appointments, including his most recent 9-month follow-up appointment, the patient continued to report excellent pain relief, with high-frequency stimulation with pain scores of 1/10, rated as a 95% improvement in his pain. On exam, the prior ulcerative trophic changes had resolved in the left ophthalmic nerve distribution. Blink reflexes (BRs) are commonly employed to diagnose PHN or other facial pain syndromes such as trigeminal neuralgia. Because high-frequency PNS resulted in significant pain relief in this patient with PHN, postimplantation, BRs were performed to further measure the effect of high-frequency PNS. Technical Description Cadaver Implant An initial cadaver study was performed before implantation on our patient to study and plan the modified CUF-guided approach for the PNS trial and implant. In order to perform this study, we used a cadaver (provided by the UCSD Anatomy Lab). A high-frequency linear probe was used to visualize the supraorbital foramen in transverse scan and then a longitudinal scan, after which the probe position was marked with a sterile pen (16). This allowed marking of both the medio-lateral and cephalo-caudad orientation of the supraorbital foramen. A slightly bent 14-gauge Tuohy needle was inserted 1–2 cm posterolateral to the junction of the frontal and zygomatic portion of the orbital rim. The Tuohy needle was then advanced (in-plane) under direct US guidance in an in-plane approach from lateral to medial, and aimed at the line of the superficial temporal fascia, superficial to the temporoparietal fascia and deep to the overlying subcutaneous tissue (Fig. 1). The Tuohy needle was then advanced 1 cm over the supramuscular fascia overlying frontalis muscle and deep to subcutaneous tissue. US guidance allowed real-time direct visualization of the Tuohy bevel tip, allowing the operator to avoid engaging or scraping subcutaneous tissue. The Tuohy needle was fixed at this point and the 8 contact (Linear ST Percutaneous, Boston Scientific) lead was advanced in the
2
Figure 1. Cadaver implant of supraorbital peripheral nerve stimulator. a. The Tuohy needle slightly bent was advanced (1 cm) under direct ultrasound guidance in an in-plane approach within the superficial temporal fascial line just superficial to the temporoparietal fascia and deep to the subcutaneous tissue, and then the lead was advanced further above the supramuscular fascia overlying frontalis muscle. Panels b and c demonstrate methylene blue which was injected as the lead was advanced (red arrows, Tuohy needle; yellow arrows, peripheral nerve stimulator lead). www.neuromodulationjournal.com
© 2015 International Neuromodulation Society
Neuromodulation 2015; ••: ••–••
NOVEL HIGH-FREQUENCY PNS TREATMENT OF POSTHERPETIC NEURALGIA
Figure 2. Cadaver implant of supraorbital nerve stimulator. a. The Tuohy needle slightly bent was advanced (1 cm) under direct ultrasound guidance in an in-plane approach (b). Under ultrasound image guidance, the Tuohy needle tip is easily visualized with bevel directed downward, then advanced in real time, taking care to avoid contact with the subcutaneous tissue. The Tuohy needle tip (red arrows) was kept stationary (a, c, e). c. The Tuohy needle was kept stationary and the lead was then advanced under combined ultrasound (d) and flouoroscopic imaging (e, f ).
subcutaneous tissue plane. The lead was advanced continuously superficial to the supramuscular fascia overlying the frontalis muscle and deep to the subcutaneous tissue. As the lead was advanced the contacts (hyperechoic) and inter-contact spaces (hypoechoic) were directly visualized under US guidance in an in-plane view with confirmatory fluoroscopic imaging (Fig. 2). The lead was perforated at the tip to allow visualization of a colored injectate (methylene blue) (Fig. 1). Methylene blue was injected through the perforated tip incrementally as the lead was advanced. The placement of the lead was then confirmed by fluoroscopic imaging, as previously described (17). Upon further dissection, methylene blue injectate was localized directly over the supraorbital nerve, deep to the subcutaneous tissue and superficial to the supramuscular fascia overlying the frontalis muscle (Fig. 1).
www.neuromodulationjournal.com
Patient Supraorbital Peripheral Stimulation Implant Peripheral nerve stimulator implant was performed with placement of peripheral nerve stimulator electrode using the same CUF trial approach. After the peripheral nerve stimulator electrode was successfully positioned over the supraorbital and supratrochlear nerves, the lead was then tunneled to a generator pocket created in infraclavicular location. After permanent peripheral nerve stimulator implantation, nerve conduction studies (NCS) (Fig. 4) and blink reflex study (BRS) (Figs 5 and 6) were carried out on both left and right supraorbital nerve. NCS demonstrated a normal right supraorbital sensory action potential waveform. Left supraorbital sensory nerve conduction study demonstrated an absent sensory nerve action potential indicative of large fiber supraorbital nerve dysfunction. BR tests demonstrated normal right-sided response. BR tests of the left
© 2015 International Neuromodulation Society
Neuromodulation 2015; ••: ••–••
3
Patient Supraorbital Peripheral Stimulation Trial The patient underwent a peripheral nerve stimulator trial and implant using CUF guidance. The patient was placed in the supine position with the head turned to right. A pre-US scan was carried out with the US probe oriented in the transverse plane to visualize the level of the supraorbital foramen and then in a longitudinal plane to visualize the temporal artery and the lateral edge of the supraorbital ridge. The skin and soft tissues were anesthetized with a 10 mL solution of lidocaine 1% that was infiltrated 2 cm lateral to the orbit at the level of the supraorbital ridge and the superficial temporal fascia. After the supraorbital foramen was identified, the probe was placed in transverse orientation over the roof of the orbital rim. The bone was scanned until a hypoechoic break identifying the foramen was located. Color doppler was used to visualize and confirm the presence of the supraorbital artery in short axis as it exited the supraorbital foramen. A 14-gauge bent Tuohy needle was inserted 1–2 cm posterolateral to the junction of the frontal and zygomatic portion of the orbital rim. The Tuohy needle was then advanced (in-plane) under direct US guidance from lateral to medial, and aimed at the line of the superficial temporal fascia, superficial to the temporoparietal fascia and deep to the overlying subcutaneous tissue (Fig. 3). Real-time US imaging demonstrated that the needle tip and shaft remained below the subcutaneous tissue layer and above the temporoparietal fascia, then the tip was advanced above the supra-muscular fascia overlying the frontalis muscle. Real-time US imaging of the Tuohy tip ensured avoidance of
penetration or trauma to the subcutaneous tissue. The frontalis muscle was identified as deep palisading longitudinal fibers just underneath the supramuscular fascia (Fig. 3). No vasculature was encountered as the needle was advanced confirmed with color doppler US imaging. After the Tuohy needle was fixed at the lateral edge of the orbital rim, the lead was visualized under US guidance as it was advanced and exited the needle tip remaining between subcutaneous tissue and the supramuscluar fascia overlying the frontalis muscle (Fig. 3d). Further fluoroscopic images in the AP view demonstrated the 8 contact lead overlying the supraorbital ridge (Fig. 3a,c). After the electrode lead was placed in the desired location, the needle was removed. Dermabond (Ethicon, Somerville, NJ, USA) and a Biopatch (Johnson and Johnson, New Brunswick, NJ, USA) were placed over the lead entry point. Steri-strips (3M, St Paul, MN, USA) were placed over the electrode lead. Bacitracin was then placed under a one loop coil behind the ear. Tegaderm (3M) was used to cover the steri-strips overlying the lead. The lead was taped to the side of the patient’s neck and secured for further programming. The lead was checked to ensure all contacts were viable and verified by the Boston Scientific representative. The day after trial lead placement, the patient returned to clinic to initiate programming including low-frequency (40 Hz pulse width at 100 μsec and amplitude of 6 mA) paresthesia mapping, followed by the initiation of a high-frequency stimulation program.
LERMAN ET AL.
Figure 3. Intraoperative implant of supraorbital nerve stimulator. a. Intraoperative technique of lead advancement using the in-plane ultrasound-guided approach. Panel b demonstrates the Tuohy needle advanced into the loose aeorolar tissue plane, deep to the subcutaneous tissue. The Tuohy needle is only advanced approximately 1 cm at which time the lead is advanced over the supramuscular fascia overlying the frontalis muscle. c. After the lead is appropriately placed, the Tuohy needle is withdrawn. d. 1 indicates the epidermal layer; 2 indicates the dermal layer; 3 indicates the subcutaneous peripheral nerve stimulator lead; 4 indicates the supramuscular fascia; 5 indicates the frontalis muscle layer which demonstrates longitudinal fiber layers (black lines); 6 indicates the skull periosteum. e. Corresponding tissue layers under ultrasound imaging, using high-frequency linear array (L12-5 50 mm 12–5 MHZ, Phillips, Waltham, MA, USA) ultrasound probe. a. Photograph has been presented in poster format at the 2013 NANS (18).
stimulation (HFS) (1200 Hz) of the left supraorbital nerve, the amplitude of left R2 was markedly suppressed and the left R2 latency was increased, while low frequency (40 Hz) had less of an effect (Fig. 6). The patient has had sustained pain relief of his severe, intractable left supraorbital herpetic neuralgia over a 9-month follow-up period. His reported pain intensity over the left supraorbital nerve distribution declined from a weekly average of 8/10 to 1/10 on the pain intensity scale. The patient’s exam demonstrated decreased left forehead hyperalgesia, decreased left forehead allodynia, and decreased left frontalis activity on eye brow raise. Postimplantation, the program that the patient preferred to use to obtain this analgesia was frequency at 1200 Hz, amplitude 6.2 mAmp (25.5 max mAmp), and pulse width 130 μsec. In addition, the patient utilized a 100 Hz, amplitude 15.2 mAmp, and pulse width of 400 μsec.
Figure 4. Nerve conduction study of right and left supraorbital nerve. a. Right supraorbital sensory action potential visualized demonstrates a normal peripheral nerve conduction waveform (green bar) with functional large fibers of the right supraorbital nerve. b. Left supraorbital sensory nerve conduction study demonstrates an absent sensory nerve action potential (orange bar) indicative of large fiber supraorbital nerve dysfunction.
4
supraorbital nerve did not produce a clear ipsilateral R1 response, but produced bilateral R2 responses with a significantly shorter latency and larger amplitudes when compared with the unaffected right-side waveform (Fig. 5). After high-frequency paresthesia-free www.neuromodulationjournal.com
DISCUSSION PNS utilizing percutaneously inserted electrodes has been shown to be effective for a variety of indications, including: occipital neuralgia (19–23), trigeminal neuropathic pain (24–27), cervicogenic headache (28–32), and as in our case, PHN (10,33). This technical note demonstrates: 1) US-guided peripheral nerve stimulator lead implant over the supraorbital and supratrochlear nerve; and 2) the use of high-frequency PNS in the treatment of PHN facial pain. The use of US guidance allowed us to place the Tuohy needle and then advance the lead subcutaneously. The main advantage of the
© 2015 International Neuromodulation Society
Neuromodulation 2015; ••: ••–••
NOVEL HIGH-FREQUENCY PNS TREATMENT OF POSTHERPETIC NEURALGIA
Figure 5. Left and right blink reflex (BR) with peripheral nerve stimulator off (a and b). Panel a demonstrates left-sided BR with an absent R1 thought to be due to herpetic nerve damage. The red bars in Panel a demonstrate a wide and large amplitude R2 waveform that represents central hyperexcitability of the polysynaptic left trigeminal sensory pathways involved in this reflex. Panel b demonstrates right-sided (unaffected) BR, with smaller R2 amplitude (red bars) than the left side (a). In addition, the R2 latency (blue bars) is increased (b) when compared with the short R2 latency on the left (a).
www.neuromodulationjournal.com
Figure 6. Left blink reflex with implanted supraorbital peripheral stimulator off (a), the implanted supraorbital peripheral stimulator turned on at a 40 Hz frequency (b), and the implanted supraorbital peripheral stimulator turned on at a 1200 Hz frequency (c). Red vertical bars (a–c) demonstrate sequential decrement in amplitude of the R2 complex, with increasing frequency of supraorbital stimulation at 40 Hz (b) and 1200 Hz (c). Blue bars demonstrate sequential increased latency of R2, with higher frequency at 40 Hz (b) and 1200 Hz (c).
nerve block (13). Solomonow et al. utilized a monophasic waveform similar to the current controlled waveform used in this case thought to maintain a net charge on the nerve membrane that can result in nerve block. As demonstrated postoperatively, the patient likely had motor nerve block given decreased left frontalis activity. This case demonstrates supraorbital nerve stimulation-mediated changes to the BR. Abnormal BRs are apparent in trigeminal neuropathy (TNP) and PHN, and are employed as part of the diagnostic algorithm of both TNP (38,39) and PHN (39), demonstrative of shortened R2 latency and increased R2 amplitude (or area under the curve [AUC]) (35), and small or abolished R1 waveform. This patient with left-sided PHN had a BR that was consistent with the prior literature, including: 1) a shortened left side R2 latency; 2) an increase in the left-side R2 AUC; and 3) an absent left side R1. R1 waveforms are thought to largely represent A-beta fibers while the R2 waveforms represent combined afferent A-Beta, A-delta, and C-fiber activation (40). This is supported by R2 (but not R1) activation with supraorbital laser stimulation known to activate only afferent C-fibers (41). Similar to PHN patients, chronic migraine patients who are given capsaicin injection consistently demonstrate an increase in R2 AUC (42). Occipital nerve block employed for headache therapy is known to modulate the trigeminocervical complex and has been shown to alter BR by: 1) decreasing R2 AUC; and 2)
© 2015 International Neuromodulation Society
Neuromodulation 2015; ••: ••–••
5
US technique is that it avoids further tissue trauma by blindly advancing a Tuohy needle, which is likely to damage underlying fascia, muscle layers, and most importantly the superficial subcutaneous tissue, all of which may cause lead erosion. Lead erosion through subcutaneous tissue is one of the most common complications of PNS procedures (34). Advancing the Tuohy needle under US guidance allows the operator to immediately detect if the needle is in close proximity to subcutaneous tissue and then redirect the needle course. US-guided Tuohy visualization may decrease trauma to subcutaneous tissue as well as risk of lead erosion. Advancing the lead easily visualized under US guidance in the potential space between the supramuscular fascia and the subcutaneous tissue may further decrease the risk of tissue injury. A total of two confirmatory fluoroscopic images were obtained to further verify proper lead placement over the supraorbital foramen. Using the CUF approach may reduce exposure of both the patient and physician to unnecessary x-ray irradiation. PHN is caused by small and large fiber dysfunction, which is thought to originate from varicella-zoster-induced degeneration of the dorsal root ganglion cells (35). Prior studies show A-delta and C-fiber specific damage as well as demyelination of A-beta fibers (35–37). This combined nociceptive fiber type dysfunction contributes to the severe pain experienced by patients with PHN. In this case, the patient’s pain was so severe and debilitating that at times the patient was actively suicidal. The patient, however, did not have a history of depression or any other mental health disorder. Nine months after successful implantation, both personal interview and a review of the chart demonstrate no evidence of mental health issues related to major depression disorder. This patient chose an amplitude of 6 mA with a 130 μsec pulse width when utilizing 1200 Hz stimulation. These stimulation parameters are within close range to high frequency 600–1200 Hz and amplitude described by Solomonow et al. that resulted in motor
LERMAN ET AL. increasing the R2 latency (43). It is thought that the amplitude and duration of the R2 is mediated by wide dynamic range neurons in the trigeminal nucleus caudalis (40,42). In clinical studies, R2 amplitude decreases in response to procaine injection (44), fentanyl and diazepam administration, which is reversible with naloxone and flumazenil, respectively (45). Nonpharmacological electroacupuncture (EA) and transcutaneous electrical nerve stimulation (TENS) demonstrate an attenuation of the R2 amplitude at both 2 Hz and 100 Hz (46). At 2 Hz, the TENS and EA-mediated decrease in R2 amplitude was reversed with the administration of naloxone (46), suggesting that there is a frequency-specific (2 Hz) opiodergicmediated effect on R2. This patient had a subcutaneous implantation of the peripheral nerve stimulator that resulted in excellent pain relief at the preferred high-frequency programs of 1200 Hz and 100 Hz. Similar to the R2 amplitude decrement described in prior studies with the use of EA, TENS, procaine, fentanyl, and diazepam, this case of subcutaneous supraorbital PNS resulted in a decrease of the R2 amplitude. To our knowledge, we demonstrate for the first time that high-frequency (1200 Hz) subcutaneous PNS decreased the R2 amplitude significantly more than at 40 Hz. Prior studies demonstrate that peripheral nerve block of A-Beta and or C-fibers is frequency dependent (47). This technical note demonstrates a frequency-dependent incremental decrease (1200 Hz larger decrease than 40 Hz) in the R2 waveform known to be preferentially activated by afferent C-fibers (41). The decrease in R2 amplitude at high frequency (1200 Hz) likely represents a frequency-specific afferent C-fiber block that was not as apparent at low-frequency (40 Hz) stimulation. Taken together, the R2 amplitude decrease after high-frequency stimulation seen in this case suggests an effect on afferent C-fibers and wide dynamic range neurons that contributed to the sustained pain relief in this patient.
CONCLUSION This technical note demonstrates: 1) a CUF technique for subcutaneous supraorbital and supratrochlear peripheral nerve stimulator trial and implant; 2) that high-frequency stimulation (1200 Hz) of the subcutaneous supraorbital/supratrochlear nerves alters the BR by modulating wide dynamic range neurons found within the trigeminal nucleus caudalis; and 3) that this high-frequency stimulation can result in long-standing pain relief.
Authorship Statements Drs. Lerman, Hiller, and Souzdsalnitski carried out the cadaver study; Dr. Sheean carried out the blink reflex study and the nerve conduction studies. Drs. Barba, Lerman, and Hiller carried out the patient trial and implant using the combined ultrasound and fluoroscopic technique. Drs. Lerman, Chen, Hiller, Souzdalnitski, Wallace, and Barba prepared the manuscript draft and provided important intellectual input. All authors have approved this manuscript.
How to Cite this Article: Lerman I.R., Chen J.L., Hiller D., Souzdalnitski D., Sheean G., Wallace M., Barba D. Novel High-Frequency Peripheral Nerve Stimulator Treatment of Refractory Postherpetic Neuralgia: A Brief Technical Note. Neuromodulation 2015; E-pub ahead of print. DOI: 10.1111/ner.12281
6 www.neuromodulationjournal.com
REFERENCES 1. Dworkin RH, Portenoy RK. Pain and its persistence in herpes zoster. Pain 1996;67:241–251. 2. Glynn C, Crockford G, Gavaghan D, Cardno P, Price D, Miller J. Epidemiology of shingles. J R Soc Med 1990;83:617–619. 3. Harpaz R, Ortega-Sanchez IR, Seward JF. Advisory Committee on Immunization Practices (ACIP) Centers for Disease Control and Prevention (CDC). Prevention of herpes zoster: recommendations of the advisory committee on immunization practices (ACIP). MMWR Recomm Rep 2008;57 (RR–5):1–30. quiz CE2-4. 4. Yawn BP, Itzler RF, Wollan PC, Pellissier JM, Sy LS, Saddier P. Health care utilization and cost burden of herpes zoster in a community population. Mayo Clin Proc 2009;84:787–794. 5. Argoff CE. Review of current guidelines on the care of postherpetic neuralgia. Postgrad Med 2011;123:134–142. 6. Wiffen PJ, Derry S, Moore RA et al. Antiepileptic drugs for neuropathic pain and fibromyalgia—an overview of cochrane reviews. Cochrane Database Syst Rev 2013;(11):CD010567. 7. Khadem T, Stevens V. Therapeutic options for the treatment of postherpetic neuralgia: a systematic review. J Pain Palliat Care Pharmacother 2013;27:268–283. 8. Apalla Z, Sotiriou E, Lallas A, Lazaridou E, Ioannides D. Botulinum toxin A in postherpetic neuralgia. Clin J Pain 2013;29:857–864. 9. Slavin KV. Peripheral nerve stimulation for neuropathic pain. Neurother 2008;5:100– 106. 10. Dunteman E. Peripheral nerve stimulation for unremitting ophthalmic postherpetic neuralgia. Neuromodulation 2002;5:32–37. 11. Tanner J. Reversible blocking of nerve conduction by alternating-current excitation. Nature 1962;195:712–713. 12. Bowman BR, McNeal DR. Response of single alpha motoneurons to high-frequency pulse trains. firing behavior and conduction block phenomenon. Appl Neurophysiol 1986;49:121–138. 13. Solomonow M, Eldred E, Lyman J, Foster J. Fatigue considerations of muscle contractile force during high-frequency stimulation. Am J Phys Med 1983;62:117–122. 14. Kilgore KL, Bhadra N. Reversible nerve conduction block using kilohertz frequency alternating current. Neuromodulation 2014;17:242–254, discussion 254–5. 15. Williamson RP, Andrews BJ. Localized electrical nerve blocking. IEEE Trans Biomed Eng 2005;52:362–370. 16. Tsui BC. Ultrasound imaging to localize foramina for superficial trigeminal nerve block. Can J Anaesth 2009;56:704–706. 17. Slavin KV, Vannemreddy PS. Repositioning of supraorbital nerve stimulation electrode using retrograde needle insertion: a technical note. Neuromodulation 2011;14:160–163, discussion 163–4. 18. Sein M, Lerman I. Peripheral nerve stimulator placement with ultrasound guidance for the treatment of post herpetic neuralgia: a case report (poster #267). Las Vegas, NV: Presented at the 17th Annual Meeting of the North American Neuromodulation Society, 2013. 19. Weiner RL, Reed KL. Peripheral neurostimulation for control of intractable occipital neuralgia. Neuromodulation 1999;2:217–221. 20. Hammer M, Doleys DM. Perineuromal stimulation in the treatment of occipital neuralgia: a case study. Neuromodulation 2001;4:47–51. 21. Johnstone CS, Sundaraj R. Occipital nerve stimulation for the treatment of occipital neuralgia-eight case studies. Neuromodulation 2006;9:41–47. 22. Slavin KV, Nersesyan H, Wess C. Peripheral neurostimulation for treatment of intractable occipital neuralgia. Neurosurgery 2006;58:112–119, discussion 112–9. 23. Skaribas I, Aló K. Ultrasound imaging and occipital nerve stimulation. Neuromodulation 2010;13:126–130. 24. Johnson MD, Burchiel KJ. Peripheral stimulation for treatment of trigeminal postherpetic neuralgia and trigeminal posttraumatic neuropathic pain: a pilot study. Neurosurgery 2004;55:135–141, discussion 141–2. 25. Slavin KV, Wess C. Trigeminal branch stimulation for intractable neuropathic pain: technical note. Neuromodulation 2005;8:7–13. 26. Reverberi C, Dario A. The treatment of trigeminal neuralgia and atypical facial pain with peripheral nerve field stimulation (PNfS): a clinical case report. Neuromodulation 2011;14:552. 27. Amin S, Buvanendran A, Park KS, Kroin JS, Moric M. Peripheral nerve stimulator for the treatment of supraorbital neuralgia: a retrospective case series. Cephalalgia 2008;28:355–359. 28. Popeney CA, Alo KM. Peripheral neurostimulation for the treatment of chronic, disabling transformed migraine. Headache 2003;43:369–375. 29. Melvin EA Jr, Jordan FR, Weiner RL, Primm D. Using peripheral stimulation to reduce the pain of C2-mediated occipital headaches: a preliminary report. Pain Physician 2007;10:453–460. 30. Rodrigo-Royo MD, Azcona JM, Quero J, Lorente MC, Acin P, Azcona J. Peripheral neurostimulation in the management of cervicogenic headache: four case reports. Neuromodulation 2005;8:241–248. 31. Slavin KV, Colpan ME, Munawar N, Wess C, Nersesyan H. Trigeminal and occipital peripheral nerve stimulation for craniofacial pain: a single-institution experience and review of the literature. Neurosurg Focus 2006;21:E5. 32. Zhou L, Abad M, Ashkenazi A. Occipital and supraorbital nerve stimulation for refractory cervicogenic headache—a comparison study. Neuromodulation 2011;14. 33. Stidd DA, Wuollet AL, Bowden K et al. Peripheral nerve stimulation for trigeminal neuropathic pain. Pain Physician 2012;15:27–33. 34. Rasskazoff SY, Slavin KV. Neuromodulation for cephalgias. Surg Neurol Int 2013; 4 (Suppl. 3):S136–S150.
© 2015 International Neuromodulation Society
Neuromodulation 2015; ••: ••–••
NOVEL HIGH-FREQUENCY PNS TREATMENT OF POSTHERPETIC NEURALGIA 35. Truini A, Galeotti F, Haanpaa M et al. Pathophysiology of pain in postherpetic neuralgia: a clinical and neurophysiological study. Pain 2008;140:405–410. 36. Cruccu G, Leandri M, Iannetti GD et al. Small-fiber dysfunction in trigeminal neuralgia: carbamazepine effect on laser-evoked potentials. Neurology 2001;56:1722– 1726. 37. Kimura J. Electrically elicited blink reflex in diagnosis of multiple sclerosis. review of 260 patients over a seven-year period. Brain 1975;98:413–426. 38. Cruccu G, Biasiotta A, Galeotti F, Iannetti GD, Truini A, Gronseth G. Diagnostic accuracy of trigeminal reflex testing in trigeminal neuralgia.Neurology 2006;66:139–141. 39. Cruccu G, Leandri M, Feliciani M, Manfredi M.Idiopathic and symptomatic trigeminal pain. J Neurol Neurosurg Psychiatry 1990;53:1034–1042. 40. Esteban A. A neurophysiological approach to brainstem reflexes. Blink reflex. Neurophysiol Clin 1999;29:7–38. 41. Ellrich J, Bromm B, Hopf HC. Pain-evoked blink reflex. Muscle Nerve 1997;20:265– 270.
42. de Tommaso M, Sardaro M, Pecoraro C et al. Effects of the remote C fibres stimulation induced by capsaicin on the blink reflex in chronic migraine. Cephalalgia 2007;27:881–890. 43. Busch V, Jakob W, Juergens T, Schulte-Mattler W, Kaube H, May A. Functional connectivity between trigeminal and occipital nerves revealed by occipital nerve blockade and nociceptive blink reflexes. Cephalalgia 2006;26:50–55. 44. Shahani B. The human blink reflex. J Neurol Neurosurg Psychiatry 1970;33:792–800. 45. Cruccu G, Ferracuti S, Leardi MG, Fabbri A, Manfredi M. Nociceptive quality of the orbicularis oculi reflexes as evaluated by distinct opiate- and benzodiazepineinduced changes in man. Brain Res 1991;556:209–217. 46. Willer JC, Roby A, Boulu P, Boureau F. Comparative effects of electroacupuncture and transcutaneous nerve stimulation on the human blink reflex. Pain 1982;14:267– 278. 47. Joseph L, Butera RJ. High-frequency stimulation selectively blocks different types of fibers in frog sciatic nerve. IEEE Trans Neural Syst Rehabil Eng 2011;19:550–557.
7
www.neuromodulationjournal.com
© 2015 International Neuromodulation Society
Neuromodulation 2015; ••: ••–••
