Radiation-induced hypoglossal nerve palsy after definitive radiotherapy for nasopharyngeal carcinoma: Clinical predictors and dose-toxicity relationship.

BACKGROUND AND PURPOSE: Radiation-induced hypoglossal nerve palsy is a debilitating and irreversible late complication after definitive radiotherapy for nasopharyngeal carcinoma (NPC) and other skull base tumors. This study sets to evaluate its incidence and clinical predictive factors, and to propose relevant dosimetric constraints for this structure to guide radiotherapy planning. MATERIALS AND METHODS: We undertook a retrospective review of 797 NPC patients who underwent definitive intensity-modulated radiotherapy (IMRT) between 2003 and 2011. Cumulative incidence and clinical predictors for radiation-induced hypoglossal nerve palsy were evaluated. Archived radiotherapy plans were retrieved and 330 independent hypoglossal nerves were retrospectively contoured following standardized atlas. Optimal threshold analyses of dosimetric parameters (Dmax, D0.5cc, D1cc, D2cc, Dmean) were conducted using receiver operating characteristic curves. Normal tissue complication probability was generated with logistic regression modeling. RESULTS: With a median follow-up of 8.1 years, sixty-nine (8.7%) patients developed radiation-induced hypoglossal nerve palsy. High radiotherapy dose, premorbid diabetes, advanced T-stage and radiological hypoglossal canal involvement were independent clinical risk factors. Maximum dose received by 1 cc volume (D1cc) was the best predictor for the development of radiation-induced nerve palsy (AUC = 0.826) at 8 years after IMRT. Hypoglossal nerves with D1cc of 74 Gy EQD2 had an estimated palsy risk of 4.7%. Nerves with D1cc <74 Gy EQD2 had significantly lower risk of palsy than those ≥74 Gy EQD2 (2.4% vs 20.8%, p <0.001). CONCLUSION: Incidence of radiation-induced hypoglossal nerve palsy was high after definitive IMRT for NPC. D1cc <74 Gy EQD2 can serve as a useful dose constraint to adopt during radiotherapy planning to limit palsy risk to <5% at 8 years after IMRT.

Hypoglossal nerve palsy after airway management for general anesthesia: an analysis of 69 patients.

Isolated hypoglossal nerve palsy (HNP), or neurapraxia, a rare postoperative complication after airway management, causes ipsilateral tongue deviation, dysarthria, and dysphagia. We reviewed the pathophysiological causes of hypoglossal nerve injury and discuss the associated clinical and procedural characteristics of affected patients. Furthermore, we identified procedural factors potentially affecting HNP recovery duration and propose several measures that may reduce the risk of HNP. While HNP can occur after a variety of surgeries, most cases in the literature were reported after orthopedic and otolaryngology operations, typically in males. The diagnosis is frequently missed by the anesthesia care team in the recovery room due to the delayed symptomatic onset and often requires neurology and otolaryngology evaluations to exclude serious etiologies. Signs and symptoms are self-limited, with resolution occurring within 2 months in 50% of patients, and 80% resolving within 4 months. Currently, there are no specific preventive or therapeutic recommendations. We found 69 cases of HNP after procedural airway management reported in the literature from 1926 to 2013.

Hypoglossal nerve dysfunction and sleep-disordered breathing after stroke.

OBJECTIVE: This cross-sectional study of acute ischemic stroke patients examined relationships between hypoglossal nerve conduction, sleep-disordered breathing (SDB), and its severity. METHODS: Patients within 7 days of stroke underwent nocturnal respiratory monitoring with the ApneaLink device and hypoglossal nerve conduction studies. RESULTS: Eighteen of 52 subjects (35% [95% confidence interval: 22%, 49%]) had an abnormal hypoglossal amplitude and 23 (44% [95% confidence interval: 30%, 59%]) had an abnormal hypoglossal latency. No differences were identified in hypoglossal nerve latency or amplitude between those with (n = 26) and without (n = 26) significant SDB, defined by an apnea-hypopnea index ≥ 15. However, hypoglossal nerve conduction latency was associated (linear regression p < 0.05) with SDB severity as reflected by the apnea-hypopnea index. CONCLUSIONS: Acute ischemic stroke patients have a high prevalence of hypoglossal nerve dysfunction. Further studies are needed to explore whether hypoglossal nerve dysfunction may be a cause or consequence of SDB in stroke patients and whether this association can provide further insight into the pathophysiology of SDB in this population.

Tongue deviation in acute ischaemic stroke: a study of supranuclear twelfth cranial nerve palsy in 300 stroke patients.

It is generally believed that the supranuclear innervation of the hypoglossal nucleus is bilateral and symmetrical. The aim of this work is to study the frequency and clinical characteristics of supranuclear tongue palsy in unilateral stroke. 300 patients with acute unilateral ischaemic motor strokes (excluding those in the lower brainstem) and an equal number of normal controls were studied for the presence of tongue deviation in a standardised manner. 29% of stroke patients and 5% of controls had tongue deviation (p < 0. 00001). Deviation was always to the side of the limb weakness. In patients with a history of stroke, it occurred more frequently in those with previous stroke on the contralateral side. Tongue deviation was most common in patients with clinical features of the non-lacunar stroke subtype (56%) or in those with cortical or large subcortical infarctions on brain CT scan (55 and 45%, respectively). All tongue deviations were associated with supranuclear 7th nerve palsy. Dysphagia and dysarthria occurred in 43 and 90% of patients with tongue deviation. Weakness of the arm was significantly associated with presence of tongue deviation. Tongue deviation in unilateral stroke most likely results from asymmetrical supranuclear control of the 12th cranial nerve in many individuals. The finding that it occurs relatively commonly in large (non-lacunar) infarcts and its association with dysphagia may have clinical utility.

Hypoglossal nerve palsy in nasopharyngeal carcinoma.

BACKGROUND: The aim of the study was to use magnetic resonance (MR) imaging to determine the cause of hypoglossal nerve palsy and the sites of injury in patients with nasopharyngeal carcinoma before radiation therapy and during postradiation therapy follow-up. METHODS: The clinical records and MR studies of 21 patients with hypoglossal nerve palsy were retrospectively studied. These 21 patients belonged to a cohort of 387 patients with nasopharyngeal carcinoma (153 with newly diagnosed disease and 234 on postradiation follow-up) who underwent MR imaging in a 2.5-year period. RESULTS: Four patients had hypoglossal nerve palsy at initial diagnosis and all of them had extensive skull base invasion from tumor extending postero-inferiorly to the level of the foramen magnum. The nerve was invaded in the carotid sheath (3), hypoglossal nerve canal (3), and premedullary cistern (1). In 17 patients developing hypoglossal nerve palsy after radiotherapy, only two (12%) had evidence of tumor recurrence. Radiation-induced neuropathy was the probable cause in 14 patients and 1 case was judged indeterminate. MR evidence of fibrosis was demonstrable along the course the nerve in four patients (29%), involving the carotid sheath (4), hypoglossal nerve canal (2), and premedullary cistern (1). No patient had MR evidence of radiation change in the brain stem. Seven patients had a history of a boost dose of radiation to the parapharyngeal region on one or both sides, and nerve palsy occurred on the boosted side in six of them. CONCLUSION: Hypoglossal nerve palsy on presentation was caused by locally advanced nasopharyngeal tumor whereas a palsy arising after radiation therapy was more frequently caused by postradiation damage rather than cancer.