Neurofibromatosis is an autosomal dominant, genetically inherited disease first described in 1882 by the German pathologist Friedrich Daniel von Recklinghausen. It belongs to the family of phakomatoses and is subcategorized into two types: NF-1 (von Recklinghausen's disease) and NF-2 (bilateral acoustic neurofibromatosis). Our patient had classic NF-1, which is characterized predominately by neurofibromas of the peripheral nervous system .
According to the National Institutes of Health, a definitive diagnosis of NF-1 is made when two of seven cardinal clinical features of the disease are present : (1) six or more café au lait macules that measure >5 mm in the greatest diameter in prepubertal individuals and >15 mm in the greatest diameter in postpubertal individuals; (2) two or more neurofibromas of any type or one plexiform neurofibroma; (3) freckles in the axillary or inguinal region; (4) optic nerve glioma; (5) two or more iris hamartomas (Lisch nodules); (6) a distinctive osseous lesion, such as sphenoid dysplasia or thinning of the long-bone cortex with or without pseudoarthrosis; and (7) a first-degree relative with NF-1 diagnosed on the basis of the preceding six criteria.
There are many complications of NF-1, including chronic hypertension, pheochromocytomas, brain tumors, malignant peripheral nerve tumors, and a high incidence of learning disabilities . The most significant complications are dermal and plexiform neurofibromas, malignant peripheral nerve sheath tumors, and other malignant tumors [10, 11]. The known mechanisms by which tumor cells evade detection by the human immune system are thought to play a role in the progression to malignancy in patients with NF-1 .
Chronic headaches are among the most common neurological manifestations of NF-1. In a hospital-based series of 158 patients with NF-1 , headache was one of the most common neurological manifestations. Twenty-eight (28%) of the patients were found to have chronic idiopathic headaches and migraines. Although headaches are common in patients with NF-1, the frequency has varied between studies. In one study of 181 patients with NF-1 , headache was present in 55 patients (30%). This frequency was not statistically significantly different from that found in the general population, leading the study investigators to conclude that headache is not a specific feature of NF-1. This conclusion, however, was contradicted by the findings of another study  that comprised 132 patients with NF-1. Eighty-one (45%) of these patients were found to have headaches, a frequency that led the study investigators to conclude that patients with NF-1 are at greater risk for headaches than the general population. Another interesting finding of the study was that 38 (47%) of the 81 patients had recurrent headaches .
Although an association between NF-1 and distinct neurological syndromes, such as the Arnold-Chiari I malformation, has been reported , no association has been found between NF-1 and occipital neuralgia. The most common skull manifestations of NF-1 involve the orbit, with very few reports of occipital defects in patients with NF-1 . Such occipital defects have been found in a 54-year-old woman with a massive plexiform neurofibroma that extended from the auricular region to the shoulder and was associated with large left occipital and left petrous bone defects .
No neurofibromatous lesions were visualized sonographically during the placement of the stimulating leads in our patient, but multiple small neurofibromata were found during creation of the implant pocket at the posterior neck site, and they were dissected. A subsequent computed tomographic scan of her head revealed subcutaneous nodules in the tissue surrounding the stimulating leads in both occipital areas, which were consistent with neurofibromas. The histological diagnosis of these nodules is unknown, since the nodules were not sent for pathological analysis. The clinical significance of these nodules is also unknown, since they could interfere with the surrounding branches of the greater and lesser occipital nerves and create most of the symptomatology reported by our patient.
Of interest is the fact that during ultrasound guidance for OPNS, the greater occipital nerve was visualized both medially (Figure 2) and laterally (Figure 3) to the greater occipital artery. The variable course of the greater occipital nerve as it relates to the greater occipital artery, as well as the ability of ultrasonography to accurately identify both structures, makes a strong argument for the utilization of ultrasound guidance.
Only one other study has reported the use of neurostimulation as a treatment for neurofibromatosis . In that study, three patients who had headaches that were refractory to conventional treatment were treated, respectively, with cutaneous neurostimulation, spinal cord neurostimulation, and cortical stimulation. Our patient responded very well to OPNS, achieving an 80% reduction in symptoms initially and a persistent >60% reduction at 10 months after electrode implantation. This outcome is in agreement with the outcomes of OPNS in studies of patients without NF-1 and is independent of the etiology of occipital neuralgia [7, 20–23].
Our patient's recovery from implantation of the leads was complicated with infection at the implantation site approximately two months after the initial implantation. It is unusual for any implant to become infected after such a prolonged period and could possibly be a consequence of NF-1, since patients with neurofibromatosis are thought to be prone to infections because of a compromised immune system resulting from mast cell infiltration around neurofibromata .