Clinical considerations
Cases 1–3 were considered suffering from occipital neuralgia and nervus intermedius neuralgia, although not always simultaneously. In the ICHD-II classification [
7] the following diagnostic criteria are required for occipital neuralgia: (a) paroxysmal stabbing pain, with or without persistent aching between paroxysms, in the distribution(s) of the greater, lesser and/or third occipital nerves, (b) tenderness over the affected nerve and (c) pain is eased temporarily by local anaesthetic block of the nerve. Our index case clearly fulfils criteria a and b. A local anaesthetic block of the greater occipital nerve has not been performed yet. However, success of this intervention might not be specific for occipital neuralgia, since infiltration of the greater occipital nerve is effective in primary headache disorders, such as cluster headache [
8], too. Cases 2 and 3 are also very likely to suffer from occipital neuralgia, although they are less severely affected. Radiation of pain into frontal, temporal and orofacial regions, as observed in cases 1 and 2, deserves further comment. As there is evidence of more widespread headaches [
9], frontal [
10] and orofacial pain [
11] in occipital neuralgia, our observations are consistent with this diagnosis. In this context it is noteworthy that prolonged hypaesthesia [
12] has been described after greater occipital nerve block, which exemplifies convergence between cervical roots—the origin of the greater occipital nerve—and trigeminal afferents.
The ICHD-II criteria [
7] for nervus intermedius neuralgia are the following: (a) pain paroxysms of intermittent occurrence, lasting for seconds or minutes, in the depth of the ear, (b) presence of a trigger area in the posterior wall of the auditory canal and (c) not attributed to another disorder. The existence of nervus intermedius neuralgia or geniculate neuralgia as clinical entity has long been a matter of debate, since otalgia does not always originate in the nervus intermedius or the geniculate ganglion [
13]. Sensory supply of the ear involves other cranial nerves, such as for instance, the glossopharyngeal nerve. A trigger zone in the auditory canal is apparent only in a minority of patients [
13]. In our patients with neuralgiform pain deep in the ear, we assume that nervus intermedius neuralgia is the most accurate explanation.
Familial cranial neuralgias with involvement of two cranial nerves have been previously described, e.g., trigeminal and glossopharyngeal nerves [
6]. Sensory anastomoses between cranial nerves have been described, e.g., between the facial and trigeminal nerves [
14]. In addition, convergence between afferents from the intermediate nerve, descending trigeminal tracts and C2 roots—the origin of the greater occipital nerve—has been proposed [
13,
15]. Animal findings point towards extensive convergence of afferents from the face, teeth, neck and oral mucosa on the trigeminal nucleus caudalis [
16]. Therefore peripheral sensory anastomoses or central convergence of afferent pathways could explain co-occurrence of cranial neuralgia in two nerves.
Cases of familial SUNCT (short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing) have been described recently [
17]. SUNCT can clinically resemble TN but has trigemino-autonomic signs such as conjunctival injection and tearing. None of our patients reported any of these signs.
Genetic hypotheses
Considering that the father M1917 of our index patient and all his daughters (F1952, F1954 and F1944) were affected from cranial neuralgia but none of his sons (Fig.
1), an X-linked dominant inheritance can be postulated. Alternatively, an autosomal dominant inheritance, as described in TN could be assumed. M1917 had also suffered from post-herpetic neuralgia. Recently a case report with occipital neuralgia evoked by facial herpes zoster infection was described [
18] suggesting a similar trigger mechanism in this patient. Increasing age and immune suppression are well-recognised risk factors for reactivation of varicella zoster virus [
19], which causes herpes zoster. About 20% of patients with herpes zoster develop post-herpetic neuralgia and genetic susceptibility is assumed [
20]. Therefore transmission of genetic vulnerability to a spectrum of neuralgic pain disorders could be postulated in our family.
Some individuals of the present family suffer from cranial neuralgia and somnambulism, or migraine. The prevalence of somnambulism in childhood was found to be elevated in patients with migraine [
21] yielding speculations that both disorders might have common predisposition factors. Although no gene for sleep-walking has been found yet, substantial genetic effects are assumed [
22] based on population studies. Given the comorbidity of facial neuralgia and somnambulism in this family, linkage between responsible gene loci could be postulated.
Except for autosomal dominant familial hemiplegic migraine (FHM) where several gene loci have been found, genetics of migraine is complex. The majority of genetic association studies with candidate migraine genes could not be replicated [
23]. Since there is no evidence of FHM in our family, no clear hypothesis can be developed.