Godtfredsen Syndrome

From EyeWiki
Assigned editor:
Review:
Assigned status Update Pending
.


Article summary goes here.

Disease Entity

Disease

Godtfredsen syndrome is a rare clinical manifestation composed of concomitant cranial nerve six and cranial nerve twelve palsy. It was first reported by Eric Godtfredsen in 1946 relating to metastatic nasopharyngeal carcinoma. Modern imaging modalities reveal clival lesions are most commonly related in causing such a rare presentation.

History and Subtype

In 1946, Dr. Erik Godtfredsen, a Danish Ophthalmologist, presented a case series of 9 patients of nasopharyngeal carcinoma with unique neuro-ophthalmic signs [1]. These patients had concurrent CNVI and CNXII palsy, which was later named as Godtfredsen syndrome. He postulated that this was caused by both direct intracranial tumor invasion and metastatic retropharyngeal lymphadenopathy overlying the hypoglossal canal [1]. This discovery was intended to be used in diagnosing metastatic nasopharyngeal carcinomas in the age before modern imaging techniques [1]. Since the original description, Godtfredsen syndrome has been reported in several other case series with various etiologies other than nasopharyngeal carcinoma including but not limited to, metastatic malignancies and hematomas [2][3][4].

Pathophysiology

Erik Godtfredsen’s original syndrome definition of “an invasive tumor of the cavernous sinus causing ipsilateral blindness, trigeminal neuralgia, paralysis of the 12th cranial nerve, and ophthalmoplegia” has since been expanded to include any lesion or combination of lesions which result in CNVI and XII palsy secondary nerve compression [5]. With modern imaging modalities, Godtfredsen syndrome can be localized to a lesion of the clivus as this is the anatomical location in which CNVI and XII run in closest proximity to one another [2].

Etiology

While the etiology can be any lesion that causes the local compression of CNVI and CNXII, the most commonly reported causes are:

  • Nasopharyngeal tumor – 13 cases [1][2]
  • Primary tumors – 9 case [2]
  • Metastatic Disease – 8 cases [2][3]
  • Subdural Hematoma – 1 case [4]

This should prompt any clinician who observes this syndrome to consider it an oncological complication and order appropriate imaging.

Epidemiology

The exact epidemiology of Godtfredsen syndrome is unknown but it is considered uncommon given its scares reporting in the literature. However, this could be a result of under-reporting, in which case it is more prevalent than current literature would indicate.

Diagnosis

Signs and Symptoms

Signs and symptoms are primarily dependent on the primary etiology of the Godtfredsen, but most commonly consist of binocular horizontal diplopia that worsens on directional gaze towards the affected side. This is due to the abduction deficit caused by paresis of the lateral rectus muscle. On primary gaze, the unopposed medial rectus can cause the patient to appear esotropic in the affected eye when the non-affected eye is the primary fixating eye.

Evaluation of the CNXII palsy produces the result of tongue deviation towards the affected side when the patient protrudes their tongue. This is due to the loss of innervation of the genioglossus on the affected side leading to the unopposed action of the genioglossus on the contralateral side causing unopposed deviation.

Physical examination

A joint CNVI and CNXII palsy are relatively easy to appreciate on physical exam. As previously mentioned, the patient will appear esotropic on primary gaze. It is important to perform a cover-uncover test to differentiate primary vs secondary deviation.

Diagnostic procedures

MRI should be the primary means of imaging as it provided the highest level of resolution. A PET scan to evaluate more active metastasis may also be useful, and if there is reason that time is an issue then CT head can be used. Attention shall be focused on clivus for any signs of malignancy. Chronic CNXII palsy can lead to hemitongue atrophy, which will show up on T2 weighted image.

Management

Given that Godtfredsen is caused secondary to a primary lesion, intervention is guided by the etiology of the primary lesion.

Symptomatic management can be achieved through patching the affected eye or by the administration of Botulinum toxin to temporarily paralyze the medial rectus of the affected eye until the primary lesion can be addressed.

References

[1] Godtfredsen, E. (1947). Ophthalmo-Neurological Symptoms in Malignant Nasopharyngeal Tumours.[Summary]. Proceedings of the Royal Society of Medicine, 40(3), 131–135. https://doi.org/10.1177/003591574704000313

[2] James R. Keane. Combined VIth and XIIth cranial nerve palsies: A clival syndrome. Neurology Apr 2000, 54 (7) 1540-1541; DOI: 10.1212/WNL.54.7.1540

[3] Thapa, Lekhjung & Paudel, Raj & Chhetri, Pramod & Rana, P. (2011). Eye twist and tongue twist: A rare neurological syndrome. BMJ case reports. 2011. 10.1136/bcr.06.2011.4366.

[4] Amalnath SD. Teaching NeuroImages: Godtfredsen syndrome due to retroclival subdural hematoma. Neurology. 2018;91(10):e999. doi:10.1212/WNL.0000000000006125

[5] Godtfredsen, Erik. (n.d.) Medical Eponyms. (2012). Retrieved August 10 2020 from https://medical-dictionary.thefreedictionary.com/Godtfredsen%2c+Erik

[6] Azarmina M, Azarmina H. The six syndromes of the sixth cranial nerve. J Ophthalmic Vis Res. 2013;8(2):160-171.