Is Hypoglossal Nerve Palsy Caused by Craniocervical Junction Degenerative Disease an Underrecognized Entity?

Juxta-Articular Cysts

Isolated case reports have described hypoglossal palsy resulting from CCJ juxta-articular synovial^2,4,5 and ganglion^3,6⇓–8 cysts arising from either the atlanto-occipital^2⇓–4,8 or the atlantoaxial⁵ joints. Although synovial and ganglion cysts can be distinguished histologically, differentiation by imaging is neither feasible nor clinically important. Therefore, it is practical to adhere to the convention proposed by Kao et al¹¹ and simply identify either synovial or ganglion cysts as JACs. Spinal degeneration and segmental instability are thought to have an important role in JAC development, having a predilection for the most mobile levels in the cervical spine.¹² Our series included 1 patient with developmental occipitalization of C1, which might have contributed to the patient's atlantoaxial JAC formation.

Most of our patients with CCJ JAC (8/12) were women (mean age, 70.2 years; range, 52–89 years). Our findings are consistent with the female predilection¹³ and higher seventh-decade prevalence^12,13 previously reported for lumbar spinal JACs. Of interest, though the association of headache and JAC was noted previously in a case report,⁵ 10 of 12 patients with CCJ JAC reported new or worsening ipsilateral headache or suboccipital pain initiating in close relation to their hypoglossal palsy onset.

CCJ JACs appeared as well-defined extradural lesions with extension into the hypoglossal canal and narrow connections with the parent atlanto-occipital or atlantoaxial joint best visualized on thin-section, coronal T2-weighted images and oblique 2D or 3D reformations parallel to the hypoglossal canal. JACs were most conspicuous on T2-weighted images, where they uniformly showed a thin hypointense cyst wall and central hyperintensity. On postcontrast T1-weighted images, cysts showed only peripheral rim enhancement. These findings are consistent with those reported in a large imaging review of lumbar synovial cysts.¹³ On CT, CCJ JACs were mostly hypoattenuated (6/7). All CCJ JACs encroached on the hypoglossal canal internal ostium by 50% or more, with most (8/12) extending into or through the hypoglossal canal. Secondary hypoglossal canal smooth remodeling, as previously reported in lumbar JACs,¹³ was seen in 3 of 8 patients. Ten patients had follow-up MR imaging without intervening surgery, revealing JAC size to be enlarged in 4, unchanged in 2, and decreased in 4. Synovial cyst size variation has been reported previously in the lumbar spine, where decreased size¹³ or complete resolution¹⁴ might be attributed to diminished synovial inflammatory fluid production or spontaneous cyst rupture.

CCJ JACs that cause hypoglossal palsy can be treated with surgical resection via a lateral suboccipital craniotomy,^2⇓–4,7,8 posterior fusion, or conservative management.⁵ Most of our 12 patients with hypoglossal palsy caused by CCJ JAC chose conservative management because the hemiglossal palsy was clinically tolerable and considered likely irreversible. Four patients with CCJ JAC underwent surgery. Two patients with cyst resection had no change in hypoglossal palsy, though suboccipital headache decreased for 1 patient. For 2 patients who underwent occipital-C2 fusion, postoperative MRI showed that the JACs either resolved or decreased in size, though neither patient reported improvement in hypoglossal palsy symptoms or suboccipital headache. The CCJ JAC decreased size or resolution after occipital-C2 fusion supports the theory that spinal instability strongly contributes to synovial cyst formation because increased motion causes synovial inflammation and secondary fluid production.

Retro-Odontoid Fibrous Pseudotumor

Retro-odontoid soft tissue masses causing cervicomedullary compression can result from numerous diseases, including rheumatoid arthritis¹⁵ and calcium pyrophosphate deposition disease.¹⁶ Some investigators have theorized that in noninflammatory ROFP, also known as degenerative pseudopannus, soft tissue masses composed of benign fibrous granulation tissue form in response to chronic atlantoaxial subluxation.^17,18 Other investigators have reported ROFP formation in patients without overt atlantoaxial subluxation^19,20 and proposed that altered biomechanics attributable to adjacent segment ankyloses cause repeated transverse ligament injury with resulting hypertrophy. None of our 4 patients with ROFP had a systemic arthritic condition. Two had previously undergone surgical cervical fixation, with resulting altered biomechanics likely contributing to chronic, excessive atlantoaxial stress.

Although most of the previously reported patients with ROFP were men, most patients in our series were women. Our mean patient age of 82 years (range, 70–87 years) is higher than previously reported by Chikuda et al¹⁹ (mean, 72 years) and Kakutani et al²⁰ (mean, 76 years). The most common clinical manifestation of ROFP is myelopathy secondary to ventral cervicomedullary compression.^18⇓–20 To the best of our knowledge, ROFP has not been previously reported as a cause of hypoglossal palsy. Of interest, none of our 4 patients with CCJ ROFP hypoglossal palsy had myelopathy on neurologic examination, though imaging showed ventral cervicomedullary compression in 2 of the 4 patients.

ROFPs in our series showed variable MR imaging characteristics on T1- (hypointense, 2/3; isointense, 1/3) and T2-weighted (hypointense, 2/3; mixed iso-hyperintense, 1/3) sequences. Most ROFPs have been reported as iso-hypointense on T1-weighted images and hypointense on T2-weighted images,^17,19 consistent with a predominant fibrous composition. Alternatively, some ROFPs have been described on T2-weighted images as an admixture of iso-hyperintensity,^18,20 perhaps reflecting a larger component of vascular granulation tissue. ROFP enhancement, variably described as “absent” and “present” in previous reports,^18,20 was seen in 3 of our 4 patients. Prior studies have shown that CCJ pseudotumor mass volume can decrease after direct resection,¹⁷ occipital-cervical fusion,^18,19 or C1 laminectomy,²⁰ with secondary myelopathy commonly improved after either surgical approach.^18⇓–20

Atlanto-Occipital Osteophytes

Hypoglossal palsy secondary to atlanto-occipital osteophytes has been previously described in single-case reports.^9,10 In our 2 patients with hypoglossal palsy secondary to C1-occipital osteophytes, osteophyte encroachment and secondary hypoglossal canal wall erosions were observed at the external ostium. This external canal encroachment is in contrast to ROFPs and CCJ JACs, which encroach on the internal ostium, and commonly extended within and/or through the hypoglossal canal. One of our 2 patients with C1-occipital osteophytes had underlying congenital C2–C3 vertebral body nonsegmentation. Both patients were treated conservatively because unilateral hypoglossal palsy is reasonably well tolerated, requires complex surgery with substantial morbidity, and is unlikely to regress postoperatively.

Improving CCJDD Lesion Recognition and Differentiating JACs from Hypoglossal Schwannomas

In our series, CCJDD lesions causing hypoglossal palsy were often undiagnosed at initial imaging interpretation because of perceptual or interpretive errors. Among the 18 patients, perceptual errors—in which the underlying CCJ lesion was not described in the initial imaging interpretation despite radiologist notation of ipsilateral hemiglossal atrophy—were found in 4 patients (2 of 12 patients with JACs; 1 of 3 with ROFPs; 1 of 2 with osteophytes). Interpretive errors—in which the lesion was described in the initial imaging report, yet was not correctly specified within the differential diagnosis—occurred in 6 of the 12 patients with CCJ JAC. Therefore, hypoglossal palsy causative JAC was correctly included in the initial radiology report in only 33% (4/12) of our patients with JAC. The underlying lesion was correctly included in the initial radiology report's differential diagnosis in 3 of 4 ROFP cases and 1 of 2 cases of hypoglossal canal osteophyte encroachment.

Diverse MR imaging and CT techniques used at outside institutions and our tertiary medical centers during this 10-year retrospective period were seldom optimized for evaluation of twelfth cranial nerve pathologies. Contrast-enhanced CT is the most common initial imaging study for evaluating patients with hypoglossal palsy. Helical acquisition from the posterior fossa to the hyoid bone allows evaluation from the medullary hypoglossal nuclei to the end-organ intrinsic tongue, styloglossus, hyoglossus, and genioglossus muscles. Demonstration of hypoglossal canal encroachment by CCJDD lesions can be aided by small field of view, thin-section (≤2 mm) axial, coronal, and sagittal soft tissue and bone reconstructions centered at the hypoglossal canal. Oblique reformations parallel to the hypoglossal canal can be helpful in assessing intracranial extension and bony erosion. In our series, CCJ JACs, the most common CCJDD lesion to cause hypoglossal palsy, were more conspicuous on MR imaging than CT. A dedicated posterior fossa–skull base MR imaging protocol, including thin-section (≤3 mm), small field of view sequences, should be used to evaluate patients with hypoglossal palsy in whom initial enhanced neck CT is unrewarding or in whom hemiglossal atrophy is noted on routine MR imaging. Besides postcontrast T1-weighted images, T2-weighted sequences are particularly helpful in evaluating CCJ degenerative lesions. Their inclusion in all 3 planes, ideally as a high-resolution volumetric sequence, is strongly recommended.

Among our 12 patients with CCJ JACs, cystic hypoglossal schwannoma was listed within the report differential 5 times. Differentiating CCJ JACs from “cystic” hypoglossal schwannomas is challenging. In a series of 44 surgically treated hypoglossal schwannomas, Nonaka et al²¹ found clinical presentations similar to CCJ JACs, with a female predominance, mean patient age of 45.8 years, and symptoms including ipsilateral tongue atrophy (92%), headache (61%), and dysphagia (32%). Hypoglossal schwannomas can be characterized as intracranial (31.5%), extra- and intracranial “dumbbell” (50%), or extracranial (18.5%),²² with secondary hypoglossal canal enlargement reported in up to 83%.²¹ So-called cystic hypoglossal schwannomas are uncommon, with cystic foci most often developing within large tumors with necrosis or spontaneous intratumoral hemorrhage.^23,24 In a previous cystic hypoglossal schwannoma case report, preoperative MR imaging showed peripheral enhancement surrounding cystic regions, whereas the tumor solid component enhanced uniformly.²³ Thus, hypoglossal schwannomas and CCJ JACs share identical clinical presentations, might extend into and remodel the hypoglossal canal, and appear T1 hypointense and T2 hyperintense on MR imaging. However, an extradural location at the premedullary cistern, contiguity with the atlanto-occipital or atlantoaxial joints, lobular projections inconsistent with the hypoglossal nerve course, and thin peripheral contrast enhancement without solid enhancing component are helpful in distinguishing CCJ JACs from cystic hypoglossal schwannomas. This distinction is imperative because CCJ JAC misdiagnosis as a hypoglossal schwannoma can result in mistreatment and potential morbidity of stereotactic radiosurgery or in an unwarranted intradural surgical approach with possible cranial nerve injury.⁴

The present study has several limitations. It is a retrospective review of a rare entity and is limited as such. Based on our method for identifying patients for review, the potential exists for missing cases in which the neuroradiologist did not include “hypoglossal palsy” or “tongue atrophy” in the radiology report. A referral bias might be present because our institution is a tertiary care center. In addition, at our large referral center, many patients had limited or no long-term follow-up after their initial evaluation. Most patients were conservatively treated, limiting surgical confirmation.