Cranial Nerve Abnormalities in Oculo-Auriculo-Vertebral Spectrum

Discussion

This neuroradiologic study showed the strikingly common involvement of CNs among patients with oculo-auriculo-vertebral spectrum, especially among those presenting with the more severe phenotype (Goldenhar syndrome). In our series, at MR imaging, 17/29 patients (59%) displayed 57 abnormal CNs ranging from hypoplasia/aplasia to protean morphologic abnormalities; moreover, at CT, 4 patients showed isolated hypoplasia of the foramen ovale and/or of the inferior alveolar nerve bone canal, consistent with trigeminal branch hypo-/aplasia, thus disclosing also a possible distal CN involvement.

CN involvement in OAVS has been previously clinically and radiologically described in case reports or small series studies.^{13⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓–26} In 1975, a pathologic study on a child affected with Goldenhar syndrome¹⁷ showed the absence of the cisternal portion of the right trigeminal nerve along with the absence of its intra-axial nuclei, providing direct evidence of CN and central nervous system involvement in patients with OAVS. Moreover, because skull base foramina development is influenced by the existence of the corresponding CN branches,²⁷ CN abnormalities might be also be indirectly inferred by skull evaluation. The presence of hypoplastic and deformed foramina ovalia and rotundum in a paleopathologic case affected with Goldenhar syndrome²⁸ seems to confirm the possible concomitant distal involvement of the trigeminal branches (S. Panzer, MD, personal e-mail communication, January 1, 2013). Similar evaluation can be performed by CT, which allows the precise visualization of the bone foramina. In the present study, 11/26 (42%) patients with OAVS with adequate bone CT showed foramina abnormalities, suggesting that the distal involvement of the trigeminal branches is not uncommon.

In the past few years, MR imaging has provided high-resolution images suitable for the evaluation in vivo of the CNs, especially at the cisternal portion, thus contributing, in some cases, to the explanation of their absent or impaired function.^29,30 Although CNs IV and XII might be inconstantly recognizable at 1.5T and CNs IX–XI appear as an indistinguishable group of roots originating from the retro-olivary sulcus, MR imaging reliably assesses the absence or the relative hypoplasia of the remaining CNs. Thus, MR imaging has become a cornerstone in the diagnostic work-up of children with profound congenital deafness, helping in cochlear or brain stem implantation decision-making.³¹ In fact, the absence of the cisternal segment of the eighth CN or the intrameatal absence of the cochlear nerve is considered, to date, a major contraindication to cochlear implantation.

At MR imaging, besides CN aplasia (absence of the cisternal segment) or hypoplasia (significant side-to-side asymmetry of the nerve diameter), in our study population, we recognized protean morphologic changes never reported in previous publications. One patient showed a nodular thickening of the fifth CN close to its origin (On-line Fig 3). Because the distal part of the nerve was recognizable and the mass diagnosis could not be supported by histology, this patient with Goldenhar syndrome was, as a precaution, not included among those with CN abnormalities. In some patients, a single nerve was rooted from the brain stem and was divided subsequently into different CNs. In 2 patients, for example, we did not detect the cisternal portion of the facial nerve concomitant to an enlarged ipsilateral trigeminal nerve and partially preserved facial nerve function. While direct pathologic evidence was not available, these cases likely represent the abnormal fusion of the cisternal segments of the facial and trigeminal nerves. Indeed, in one of these cases, an abnormal facial bone canal/internal acoustic meatus seemed to be recognizable close to the site where the abnormal CN V reached the upper surface of the petrous bone apex (Fig 2). Similarly, in 2 patients, there was only 1 CN in the internal acoustic meatus, a condition that is considered indicative of a preserved facial nerve with CN VIII aplasia³¹; nonetheless, both patients had partially preserved auditory function. The presence of nerve fibers within a different nerve or nerve branch has been suggested in some cases in which the absence of the cochlear nerve did not correspond to a complete loss of hearing function.³² Therefore, these cases seem to increase the body of evidence against the “dogmatic” indication toward auditory brain stem implantation whenever cranial VIII or the cochlear nerves are missing at MR imaging investigation,³³ unless concomitant and coherent functional data are obtained.

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Fig 2.

Brain MR imaging. A, Contiguous T2-weighted axial images show the common origin of the left fifth and seventh/eighth cranial nerves from the anterior profile of the middle cerebellar peduncle (arrow). The common trunk runs in the cisternal space and subdivides into 2 nerves entering the Meckel cave (asterisk) and, slightly caudally, the internal acoustic meatus (arrowheads). B, Oblique multiplanar reconstruction shows the common nerve origin and the subsequent subdivision.

In the current study, anomalies of CN II were not further considered because hypoplasia of the optic nerve was the rule when the patients presented with microphthalmia or anophthalmia. In contrast, abnormalities of the nerves that control eye movements did not correlate with abnormal eye development. Globe abnormalities were not significantly more frequent among patients with CN III or VI abnormalities (2/8 versus 3/18); this finding confirms that eye and oculomotor apparatus follow different development pathways. From a functional point of view, the association between Goldenhar syndrome and extrinsic ocular-movement impairment has been frequently noted. Duane syndrome type I has been reported in patients with Goldenhar syndrome.^{15,20⇓⇓⇓⇓⇓–26} Among our patients with functional evaluation, 4/18 had oculomotor impairment (all Goldenhar phenotypes), while 8/28 with MR imaging evaluation presented with CN III or VI abnormalities. Considering that this study did not evaluate CN IV morphologic abnormalities and that hypoplasia of CN VI is difficult to ascertain because the nerve is very thin, our data confirm the frequent involvement of the oculomotor nerves in OAVS and explain the frequent oculomotor impairment in these patients. On the other hand, the recurrent observation of preserved oculomotor function despite CN VI aplasia seems to support the hypothesis that nerve fibers might run along alternative routes to innervate the extrinsic ocular muscles.

From a pathogenic point of view, involvement of the CNs in OAVS is likely due to the common embryologic origin of facial bones, soft tissues, and peripheral neural structures from the first and second pharyngeal arches. These structures are contiguous to the corresponding neural crests and central nervous system structures. Whatever the nature of the lesion leading to OAVS (ischemic, hemorrhagic, infectious, and so forth), CN development might be concomitantly affected: In fact, most CN abnormalities were ipsilateral to facial abnormalities. On the other hand, in our cohort, a few patients showed bilateral CN involvement despite unilateral facial involvement. This observation suggests that neural structures in OAVS might be even more vulnerable than contiguous bone and soft tissues or that the clinical evaluation of microsomia (which is based on side-to-side comparison) might be less sensitive than the neuroradiologic or functional evaluation of the CNs.

Notably, the present study showed a strong association between Goldenhar phenotype (severe cases among the OAVS) and CN involvement. This might appear obvious because among the OAVS, Goldenhar syndrome criteria imply a more extensive involvement (facial and auricular involvement plus ocular or vertebral involvement). Nonetheless, we did not find within the Goldenhar subgroup an association between the number of fulfilled criteria and the number of involved CNs. Patients with Goldenhar syndrome with both ocular and vertebral involvement did not show an increased number of abnormal CNs compared with patients with Goldenhar syndrome with isolated ocular or vertebral involvement. A likely explanation is that the inclusion criteria for Goldenhar syndrome do not take into account the severity of ocular or vertebral abnormalities. Besides anophthalmia and microphthalmia, coloboma, epibulbar dermoid, or even epicanthus are considered among the inclusion criteria for ocular involvement in Goldenhar syndrome, though their clinical impact and severity are clearly different.

The clinical impact of CN abnormalities in patients with OAVS has been underlined in previous studies^{13⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓–26}; the present study on a relatively large sample shows that MR imaging and CT might provide the explanation of nerve impairment. Moreover, because neonates and infants might be difficult to evaluate and CN dysfunction might imply serious complications (eg, corneal lesions or abnormal masticatory dynamic), neuroimaging-focused evaluation might help when CN impairment is suspected in the early phases of the life of a patient with OAVS, thus helping to prevent irreversible damage. For this purpose, MR imaging is certainly the preferred tool, but in some cases, the evaluation of the foramen ovale and the inferior alveolar nerve bone canal might disclose CN abnormalities, even when the cisternal portion of the trigeminal nerve appears normal.