C2 Nerve Field Stimulation for the Treatment of Fibromyalgia: A Prospective, Double-blind, Randomized, Controlled Cross-over Study

Highlights

• Occipital nerve field stimulation exerts a beneficial and lasting effect on fibromyalgia.

• Could be considered as a treatment modality in medically intractable patients.

• 6 week trial phase of the study, patients had an overall decrease of 36%.

• 6 months follow up an improvement in life quality of 50%.

Abstract

Background

Fibromyalgia is a condition characterized by widespread chronic pain. Due to the high prevalence and high costs, it has a substantial burden on society. Treatment results are diverse and only help a small subset of patients. C2 nerve field stimulation, aka occipital nerve stimulation, is helpful and a minimally invasive treatment for primary headache syndromes. Small C2 pilot studies seem to be beneficial in fibromyalgia.

Methods

Forty patients were implanted with a subcutaneous electrode in the C2 dermatoma as part of a prospective, double-blind, randomized, controlled cross-over study followed by an open label follow up period of 6 months. The patients underwent 2 week periods of different doses of stimulation consisting of minimal (.1 mA), subthreshold, and suprathreshold (for paresthesias) in a randomized order. Twenty seven patients received a permanent implant and 25 completed the 6 month open label follow up period.

Results

During the 6 week trial phase of the study, patients had an overall decrease of 36% on the fibromyalgia impact questionnaire (FIQ), a decrease of 33% fibromyalgia pain and improvement of 42% on the impact on daily life activities and quality. These results imply an overall improvement in the disease burden, maintained at 6 months follow up, as well as an improvement in life quality of 50%. Seventy six percent of patients were satisfied or very satisfied with their treatment. There seems to be a dose–response curve, with increasing amplitudes leading to better clinical outcomes.

Conclusion

Subcutaneous C2 nerve field stimulation seems to offer a safe and effective treatment option for selected medically intractable patients with fibromyalgia.

Introduction

Fibromyalgia is pain syndrome characterized by widespread chronic pain, consisting of axial pain, left- and right-sided pain, and upper and lower segment pain lasting for at least three months [1]. Fibromyalgia symptoms are not restricted to pain, but include also non-restorative sleep, fatigue, headaches and mood disorders. Since there are no consistent findings on physical or technical examinations, the diagnosis is mainly clinical [2]. The American College of Rheumatologists (ACR) recognized fibromyalgia as a diagnostic disorder and proposed diagnostic criteria in 1990 [3] with a proposal for revision in 2010 [4] which focused on a self-report questionnaire taking into account 18 pain areas and questions concerning fatigue, memory disturbances, lower abdominal cramps, depressive mood, and headache as diagnostic criteria. The previously required tender point examination was removed from the original criteria in the proposed revision [4]. Epidemiological studies show a prevalence up to 8%, with a female to male ratio of between 7:1 and 9:1 [5]. Since the health care utilization in this patient population is high, the syndrome carries a high economic burden. The estimated direct medical costs are up to €10.087 per year per patient in France and up to $11,049 per patient per year in the United States [6], [7].

The exact mechanism underlying this pathology is not known, however clinical functional imaging and neurophysiological testing suggests it is related to central sensitization with decreased inhibitory descending pain control [8]. Treatment options are as diverse as their outcomes. Both pharmacological and non-pharmacological modalities are used [2]. Physical therapy, both active and passive, and psychological treatment tends to improve symptoms [9]. Concerning the pharmacological treatment, analgesics, opioids, antidepressant drugs, and anticonvulsants have shown some usefulness [9], [10]. However, a group of patients remains refractory to treatment. In various pathologies this is the point in which surgical treatments like neuromodulation find their place. One new treatment option could be neuromodulation for patients intractable to conservative medical practice [11], [12], [13], [14], [15]. Stimulation via a subcutaneous implant of an electrode in the area of the greater occipital nerve can be performed in a minimally invasive way which has been described by Weiner and Reed for the treatment of medically intractable headache syndromes [16]. Since its inception it has been investigated as a potential treatment for many different head and facial pain syndromes [17], [18], [19]. It delivers electrical pulses in the area supplied by the greater occipital nerves, which arise from the second cervical nerve complex, and is described as nerve field stimulation [20]. The mechanism of action is uncertain, but supposed to be due to the connections at the trigeminal–cervical complex, a connection between the greater occipital nerve and brainstem structures including the nuclei of the trigeminal nerve and autonomic nervous system [14], [21]. Subcutaneous nerve field stimulation of the area supplied by the greater occipital (C2) nerve modulates brain activity in several important regions involved in pain perception as shown by functional imaging including fMRI and PET techniques [22], [23], [24].

A serendipitous finding by Thimineur is that in patients with fibromyalgia, who also had headaches, and were treated for the headaches by C2 nerve stimulation, showed that not only the headaches improved, but also the associated wide spread bodily pain and fatigue, leading to an increased quality of life [13]. This was followed up by a small pilot study in a placebo-controlled way [15], supporting the initial non-placebo-controlled study [13]. Guided by these positive results the authors performed a randomized double blinded controlled trial, with different doses in randomized order for periods of 2 weeks, and concluding with an open label follow-up. The study goals were to determine the safety and efficacy of C2 nerve stimulation in the treatment of fibromyalgia. The primary outcome parameter was a reduction in fibromyalgia related disease burden as measured by the Fibromyalgia Impact Questionnaire.