Faculty Bibliography

BACKGROUND:While transcranial magnetic stimulation (TMS) has been studied for the treatment of psychiatric disorders, emerging evidence supports its use for pain and headache by stimulating either motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC). However, its clinical implementation is hindered due to a lack of consensus in the quality of clinical evidence and treatment recommendation/guideline(s). Thus, working collaboratively, this multinational multidisciplinary expert panel aims to: 1) assess and rate the existing outcome evidence of TMS in various pain/headache conditions; 2) provide TMS treatment recommendation/guidelines for the evaluated conditions and comorbid depression; and 3) assess the cost-effectiveness and technical issues relevant to the long-term clinical implementation of TMS for pain and headache. METHODS:Seven task groups were formed under the guidance of a 5-member steering committee with four task groups assessing the utilization of TMS in the treatment of Neuropathic Pain (NP), Acute Pain, Primary Headache Disorders, and Posttraumatic Brain Injury related Headaches (PTBI-HA), and remaining three assessing the treatment for both pain and comorbid depression, and the cost-effectiveness and technological issues relevant to the treatment. RESULTS:The panel rated the overall level of evidence and recommendability for clinical implementation of TMS as: 1) high and extremely/strongly for both NP and PTBI-HA respectively; 2) moderate for postoperative pain and migraine prevention, and recommendable for migraine prevention. While the use of TMS for treating both pain and depression in one setting is clinically and financially sound, more studies are required to fully assess the long-term benefit of the treatment for the two highly comorbid conditions, especially with neuronavigation. CONCLUSIONS:After extensive literature review, the panel provided recommendations and treatment guidelines for TMS in managing neuropathic pain and headaches. In addition, the panel also recommended more outcome and cost-effectiveness studies to assess the feasibility of the long-term clinical implementation of the treatment.

BACKGROUND:Chronic pelvic pain (CPP) represents a group of poorly understood disorders that are often refractory to conventional treatment. Referral to pain management typically occurs later in the continuum of care; as such, many of the injections and nerve blocks commonly prescribed for such patients are potentially limited in efficacy. While neuromodulation is conventionally considered the next algorithmic step in the treatment of chronic pain after injections fail, there is a common perception that neuromodulation is largely ineffective for CPP conditions. However, there is evidence that suggests neuromodulation may in fact be a viable treatment option for this particular patient population when utilized properly. OBJECTIVES/OBJECTIVE:To provide a basic overview of the pathophysiology of CPP and the relevant neuroanatomy as it pertains to various available treatment options, as well as the techniques and potential targets for neuromodulation. STUDY DESIGN/METHODS:Literature review. SETTING/METHODS:Private practice, academic and hospital setting. METHODS:A comprehensive review of the available literature was performed targeting publications focused on CPP and various techniques for utilizing neuromodulation to treat it. RESULTS:Neuromodulation is an established treatment modalities, however its usefulness as it relates to treating CPP has typically been drawn into question. In this literature review, we discuss the efficacy of various techniques for treating CPP with neuromodulation. LIMITATIONS/CONCLUSIONS:Evidence to support the various treatments, while encouraging, is based on small studies and case series. Large-scale randomized, placebo-controlled clinical trials are warranted to evaluate the clinical efficacy and safety of the different treatments described, particularly neuromodulation. CONCLUSIONS:In addition to the percutaneous, injection-based treatments described herein, neuromodulation remains a plausible option for recalcitrant cases that fail to respond to more conventional means. KEY WORDS/UNASSIGNED:Chronic pelvic pain, neuromodulation, spinal cord stimulation, CRPS, complex regional pain syndrome, neuropathic pain.

INTRODUCTION: Spinal cord stimulation (SCS) devices are cost effective and improve function as well as quality of life. Despite the demonstrated benefits of SCS, some patients have the device explanted. We are interested in exploring the patient characteristics of those explanted. METHODS: This is a retrospective chart review of neurostimulation patients who underwent explantation at 18 centers across the United States within the previous five years. RESULTS: Data from 352 patients were collected and compiled. Failed Back Surgery syndrome was the most common diagnosis (38.9%; n = 136/350) and over half of the patients reported numerical rating scale (NRS) scores >/=8 prior to implant (64.3%; n = 207/322). All patients reported changes in NRS scores across time, with an initial decrease after implant followed by a pre-explant increase (F (2, 961) = 121.7, p < 0.001). The most common reason for device explant was lack or loss of efficacy (43.9%; 152/346) followed by complications (20.2%; 70/346). Eighteen percent (18%; 62/343) of patients were explanted by a different physician than the implanting one. Rechargeable devices were explanted at a median of 15 months, whereas primary cell device explants occurred at a median of 36 months (CI 01.434, 2.373; median endpoint time ratio = 2.40). DISCUSSION: Loss or lack of efficacy and complications with therapy represent the most frequent reasons for neurostimulation explantation. Of the devices that were explanted, therapy was terminated earlier when devices were rechargeable, when complications occurred, or when pain relief was not achieved or maintained. Furthermore, in nearly 20% of the cases, a different provider than the implanting physician performed device removal. CONCLUSIONS: SCS is largely a safe and efficacious strategy for treating select chronic refractory pain syndromes. Further prospective data and innovation are needed to improve patient selection, maintain SCS therapeutic efficacy and reduce the reasons that lead to device explant.

Reports an error in "Safety and efficacy of peripheral nerve stimulation of the occipital nerves for the management of chronic migraine: Results from a randomized, multicenter, double-blinded, controlled study" by Stephen D. Silberstein, David W. Dodick, Joel Saper, Billy Huh, Konstantin V. Slavin, Ashwini Sharan, Ken Reed, Samer Narouze, Alon Mogilner, Jerome Goldstein, Terrence Trentman, Julien Vaisma, Joseph Ordia, Peter Weber, Timothy Deer, Robert Levy, Roni L. Diaz, Stephanie N. Washburn and Nagy Mekhail (Cephalalgia, 2012[Dec], Vol 32[16], 1165-1179). In the print version of this article, the author name Julien Vaisman was mis-spelled as Julien Vaisma. The correction was present in the erratum. (The following abstract of the original article appeared in record 2012-30866-002). Background: Chronic migraine (CM) is a debilitating neurological disorder with few treatment options. Peripheral nerve stimulation (PNS) of the occipital nerves is a potentially promising therapy for CM patients. Methods: In this randomized, controlled multicenter study, patients diagnosed with CM were implanted with a neurostimulation device near the occipital nerves and randomized 2:1 to active (n = 105) or sham (n = 52) stimulation. The primary endpoint was a difference in the percentage of responders (defined as patients that achieved a >50% reduction in mean daily visual analog scale scores) in each group at 12 weeks. Results: There was not a significant difference in the percentage of responders in the Active compared with the Control group (95% lower confidence bound (LCB) of -0.06; p = 0.55). However, there was a significant difference in the percentage of patients that achieved a 30% reduction (p = 0.01). Importantly, compared with sham-treated patients, there were also significant differences in reduction of number of headache days (Active Group = 6.1, baseline = 22.4; Control Group = 3.0, baseline = 20.1; p = 0.008), migraine-related disability (p = 0.001) and direct reports of pain relief (p = 0.001). The most common adverse event was persistent implant site pain. Conclusion: Although this study failed to meet its primary endpoint, this is the first large-scale study of PNS of the occipital nerves in CM patients that showed significant reductions in pain, headache days, and migraine-related disability. Additional controlled studies using endpoints that have recently been identified and accepted as clinically meaningful are warranted in this highly disabled patient population with a large unmet medical need.

Background: Chronic migraine (CM) is a debilitating neurological disorder with few treatment options. Peripheral nerve stimulation (PNS) of the occipital nerves is a potentially promising therapy for CM patients. Methods: In this randomized, controlled multicenter study, patients diagnosed with CM were implanted with a neurostimulation device near the occipital nerves and randomized 2:1 to active (n = 105) or sham (n = 52) stimulation. The primary endpoint was a difference in the percentage of responders (defined as patients that achieved a >/=50% reduction in mean daily visual analog scale scores) in each group at 12 weeks. Results: There was not a significant difference in the percentage of responders in the Active compared with the Control group (95% lower confidence bound (LCB) of -0.06; p = 0.55). However, there was a significant difference in the percentage of patients that achieved a 30% reduction (p = 0.01). Importantly, compared with sham-treated patients, there were also significant differences in reduction of number of headache days (Active Group = 6.1, baseline = 22.4; Control Group = 3.0, baseline = 20.1; p = 0.008), migraine-related disability (p = 0.001) and direct reports of pain relief (p = 0.001). The most common adverse event was persistent implant site pain. Conclusion: Although this study failed to meet its primary endpoint, this is the first large-scale study of PNS of the occipital nerves in CM patients that showed significant reductions in pain, headache days, and migraine-related disability. Additional controlled studies using endpoints that have recently been identified and accepted as clinically meaningful are warranted in this highly disabled patient population with a large unmet medical need. Trial registration: Clinical trials.gov (NCT00615342).

OBJECTIVE: To develop guidelines for selection of antiepileptic drugs (AEDs) among people with HIV/AIDS. METHODS: The literature was systematically reviewed to assess the global burden of relevant comorbid entities, to determine the number of patients who potentially utilize AEDs and antiretroviral agents (ARVs), and to address AED-ARV interactions. Results and Recommendations: AED-ARV administration may be indicated in up to 55% of people taking ARVs. Patients receiving phenytoin may require a lopinavir/ritonavir dosage increase of ~50% to maintain unchanged serum concentrations (Level C). Patients receiving valproic acid may require a zidovudine dosage reduction to maintain unchanged serum zidovudine concentrations (Level C). Coadministration of valproic acid and efavirenz may not require efavirenz dosage adjustment (Level C). Patients receiving ritonavir/atazanavir may require a lamotrigine dosage increase of approximately 50% to maintain unchanged lamotrigine serum concentrations (Level C). Coadministration of raltegravir/atazanavir and lamotrigine may not require lamotrigine dosage adjustment (Level C). Coadministration of raltegravir and midazolam may not require midazolam dosage adjustment (Level C). Patients may be counseled that it is unclear whether dosage adjustment is necessary when other AEDs and ARVs are combined (Level U). It may be important to avoid enzyme-inducing AEDs in people on ARV regimens that include protease inhibitors or nonnucleoside reverse transcriptase inhibitors, as pharmacokinetic interactions may result in virologic failure, which has clinical implications for disease progression and development of ARV resistance. If such regimens are required for seizure control, patients may be monitored through pharmacokinetic assessments to ensure efficacy of the ARV regimen (Level C).

OBJECTIVES: We intend to review the importance of appropriately recognizing and managing attention deficit/attention deficit hyperactivity disorder (ADD/ADHD) in the acute psychiatric hospital setting. METHODS: We demonstrate the management of three patients with associated ADD/ADHD diagnosis in the hospital setting. This case series is followed by a review of the literature on the treatment of ADD/ADHD with particular focus on inpatient treatment. RESULTS: Given that the core symptoms of ADD/ADHD are inattention, hyperactivity, poor concentration, impulsivity, poor organization and emotional instability, it follows that a comprehensive inpatient treatment plan should address these issues in order to obtain sustained, focused participation on the part of the patient. Suppression of ADD/ADHD symptoms with stimulants greatly enhanced our patients' ability to more productively and actively participate in the treatment of the acute psychiatric problems which led to their admission. CONCLUSIONS: Currently, no published data exist on prevalence of ADD/ADHD in psychiatric hospitals, rates of treatment and outcome of treatment with regard to recovery and quality of aftercare. Nonetheless, the benefits of treating ADD/ADHD among psychiatric inpatients may be seen in case examples and are also apparent in the data concerning treatment of ADD/ADHD in the dually diagnosed

A subgroup of adults in private treatment for cocaine dependence in remission reported a therapeutic effect from cocaine during the initial phases of cocaine addiction and, also, met DSM-IV criteria for ADHD. We report evidence that study subjects probably medicated their ADHD symptoms with cocaine and describe a 1-year treatment algorithm featuring long-acting stimulants that was effective in the management of their ADHD and cocaine dependence. Nineteen stable patients in full remission from all substance dependence were entered into an open label, prospective, treatment trial for ADHD. The treatment schedule consisted of the progressive introduction-and discontinuation of ineffective medication-of each of several medications in the following order: fluoxetine, bupropion, pemoline, sustained-release methylphenidate, dextroamphetamine spansules, and methamphetamine gradumets. Treatment of ADHD was successful. Several treatment regimens, especially those including long-acting stimulants, alone or in combination with other agents, were highly effective. All but 1 of the 19 subjects had a fully effective response for at least 1 full year. Mean UTAH scale scores were 7.4 before any medications were administered and 1.6 at the end of the study. Treatment proved successful in suppressing ADHD symptoms, with minimal cocaine slips or side effects