Electromyography findings in radiation-induced unilateral tongue immobility.

BACKGROUND: We used electromyography to characterize hypoglossal nerve function among radiation-treated head and neck cancer survivors with later onset unilateral tongue immobility. METHODS: Patients with unilateral tongue immobility without evidence of recurrent cancer were seen at a tertiary academic institution between February and September 2021. All patients were at least 2 years post-treatment with radiation therapy for head and neck squamous cell carcinoma. Participants were under annual surveillance and displayed no evidence of operative injury to the hypoglossal nerve. RESULTS: The median symptom-free interval for the 10 patients included in this study was 13.2 years (range 2-25 years). Myokymia alone was present in 3 of 10 patients, fibrillation potentials alone were present in 3 of 10 patients, and 1 subject displayed both fibrillation and myokymia. Three out of 10 patients had normal hypoglossal nerve function. DISCUSSION: These findings highlight how disparate mechanisms may underlie similar clinical presentations of radiation-induced neuromuscular dysfunction.

Characterization of very late dysphagia after chemoradiation for oropharyngeal squamous cell carcinoma.

OBJECTIVES: Improved prognosis for p16+ oropharyngeal squamous cell carcinoma (OPSCC) has led to efforts to mitigate long-term complications of treatment, which remains poorly defined in late survivors. Here we characterize very late dysphagia in OPSCC. MATERIALS AND METHODS: Long-term review of 93 p16+ OPSCC patients treated with chemoradiation was performed. We scored videofluoroscopic swallow studies (VFSS) according to the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) scale. Very late dysphagia was defined >2.5 years from end of treatment. Fine-Gray regression models were used to assess dysphagia with competing risk of death. RESULTS: Median follow up was 10.5 years. 402 total VFSS were assessed (median 4 per patient, range 0-8). 15.1% of patients had a DIGEST score ≥2 very late after treatment. Very late DIGEST score ≥2 correlated with T-stage (HR 1.7, p = 0.049), second cancer (HR 6.5, p = 0.004), superior pharyngeal constrictor dose (HR 1.11, p = 0.050), total tongue dose (HR 1.07, p = 0.045), but not hypoglossal nerve dose (p > 0.2). Seven patients (7.5%) had late progressive dysphagia, defined as DIGEST score that increased by ≥2 beyond one year after treatment, and this correlated with higher ipsilateral hypoglossal nerve D1cc dose (75 vs 72 Gy, p = 0.037). CONCLUSION: In p16+ OPSCC patients treated with definitive chemoradiation, at least 7.5% developed late progressive dysphagia, and 15.1% experienced moderate dysphagia >2.5 years from treatment. Our study suggests that dose to tongue musculature may be associated with very late dysphagia, and hypoglossal nerve dose may be associated with late progressive dysphagia. More intensive long-term dysphagia survivorship monitoring is suggested.

Incidence and outcomes of radiation-induced late cranial neuropathy in 10-year survivors of head and neck cancer.

OBJECTIVES: To characterize the late cranial neuropathy among 10-year survivors of head and neck cancer treatment. MATERIALS AND METHODS: We retrospectively evaluated patients treated with curative-intent radiation for HNC between 1990 and 2005 at a single institution with systematic multidisciplinary follow-up ≥ 10 years. New findings of CNP were considered radiation-induced when examination, imaging and/or biopsy did not demonstrate a structural or malignant cause. Cox proportional hazards modeling was used for univariable analysis (UVA) and multivariable analysis (MVA) for time to CNP after completion of radiation. RESULTS: We identified 112 patients with no evidence of disease and follow-up ≥ 10 years (median 12.2). Sixteen (14%) patients developed at least one CNP. The median time to CNP was 7.7 years (range 0.6-10.6 years). Most common was CN XII deficit in eight patients (7%), followed by CN X deficit in seven patients (6%). Others included CN V deficit in three, and CN XI deficit in two. Eight of the thirteen patients with a CN X and/or CN XII deficit required a permanent gastrostomy tube. On UVA, site of primary disease, post-radiation neck dissection, chemotherapy, and radiation dose were significantly associated with increased risk of CNP. CONCLUSION: Iatrogenic CNP may develop years after head and neck cancer treatment and often leads to swallowing dysfunction. Long-term follow up is essential for these patients receiving head and neck radiation.

Isolated Unilateral Tongue Atrophy: A Possible Late Complication of Juxta Cephalic Radiation Therapy.

BACKGROUND Isolated unilateral hypoglossal nerve injury is extremely rare. It may be caused by radiation therapy targeting neoplasms of the cephalic region. CASE REPORT A 51-year-old man with synovial sarcoma of the left upper arm status post extensive radiation therapy in 1980 presented in late 2014 with gradual onset of speech difficulty and difficulty moving his tongue for a couple of weeks. Neurological examination revealed isolated left-sided unilateral tongue atrophy. Postradiation residual extensive cicatrix with erythema over the whole left upper extremity extending to the neck on the affected side was noticed. On head magnetic resonance imaging (MRI) before and after administration of gadolinium, he was found to have asymmetrically fatty striations, atrophy, and fibrosis in the left tongue consistent with radiation toxicity. The patient's tongue weakness persisted without improvement. CONCLUSIONS The diagnosis of unilateral hypoglossal nerve injury is usually difficult. Detailed neurological examinations and thorough investigations including head MRI are very helpful. Previous exposure to radiation therapy is a potential cause of hypoglossal nerve injury. To our knowledge, this is the first case report that presents isolated unilateral tongue atrophy as a late complication of juxta cephalic radiation therapy.

One hour of tongue-task training is associated with plasticity in corticomotor control of the human tongue musculature.

Corticomotor control of the human tongue has been reported to undergo neuroplastic changes following several days of training in a tongue-protrusion task. The aims of the present study were to determine if a 1 h tongue-task training is sufficient to induce signs of neuroplastic changes in the corticomotor pathways, and to obtain preliminary information on the time course of such changes. Corticomotor excitability was assessed by changes in electromyographic activity evoked by transcortical magnetic stimulation (TMS) in 11 healthy subjects. Motor evoked potentials (MEPs) recorded in the tongue musculature and the first dorsal interosseous (FDI) muscle were assessed at four sessions: at baseline before training, 30 min after training, and 1 and 7 days after training. All subjects performed successfully the task (success rate: 38+/-4%). Thresholds for evoking MEPs by TMS in the tongue were decreased at 30 min, 1 and 7 days after training compared with baseline (ANOVA: P<0.001). Tongue MEP amplitudes were significantly increased at 1 day follow-up and had returned to baseline values at 7 days follow-up (ANOVA: P<0.001). No significant effect of tongue-task training on FDI MEPs was observed (ANOVA: P=0.160). Corticomotor topographic maps revealed increases (ANOVA: P<0.001) in area at the 1 day follow-up. The success rate was significantly correlated to the net increases in tongue MEPs at 1 day follow-up (Spearman: 0.615; P=0.0039). The present findings confirm that tongue task training is associated with plasticity of corticomotor excitability specifically related to the tongue musculature and further document that plasticity is evident within 30 min post-training and may last up to at least 7 days.

The effects of prenatal X-irradiation on hypoglossal nucleus: a GFAP immunohistochemical study.

The effects of prenatal X-irradiation on hypoglossal (XII) nucleus were investigated in the rat. Pregnant animals were exposed to a single whole body X-irradiation on day 11 and 16 of gestation at a does of 1.3 Gy. The offspring were killed at 7-14 days of age for the histological and immunohistochemical observations. Nissl staining revealed no significant changes of XII motoneurons in these experimental animals. In the control case it was of interest that expression of glial fibrillary acidic protein-immunoreactivity (GFAP-IR) is largely confined to the dorsomedial region including the XII nucleus at the level caudal to the obex. Exposure of X-irradiation on day 16 of gestation led to similar expression of GFAP-IR in the nucleus at the same level. However, exposure on day 11 of gestation apparently led to strong expression of GFAP-IR in the XII nucleus at the level caudal to the obex and the expression was observed to extend rostrally. The GFAP-IR cells showed hypertrophy of cell bodies and longer cytoplasmic processes. Horse-radish peroxidase (HRP) injection into the tip of the tongue including the intrinsic muscles resulted in retrograde labeling in the ventromedial portion of the XII nucleus bilaterally from +0.30 to -1.25 mm. The present study would indicate that motoneurons of the XII nucleus supplying mainly the intrinsic and partly the extrinsic tongue muscles are more sensitive to X-ray exposure before the formation of the XII nucleus.

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.

MR features of the denervated tongue in radiation induced neuropathy.

The MR features of the denervated tongue have been described following nerve injury from radical neck dissection and tumour invasion. The purpose of the study was to determine whether similar features are present in the tongue following radiation induced neuropathy (RIN). The clinical records and MR images of 12 patients with RIN of the hypoglossal nerve were reviewed retrospectively. T1 weighted SE images were performed in 12, T2 weighted TSE images in 11, fat suppressed images in 10 and contrast enhanced T1 weighted images in nine patients. The denervated tongue revealed "oedemalike" changes in five, fatty infiltration in six, atrophy in 11 and pseudohypertrophy in one patient. Abnormal enhancement was not identified, and in five patients the signal intensity was normal on all sequences. The oedemalike changes, fatty infiltration and normal signal intensity were seen 2-48, 2-48, and 6-63 months, respectively, after the onset of RIN. In conclusion, there was no discernible relationship between the duration of RIN and the MR appearance of the denervated tongue. Oedemalike changes, previously described in the acute/subacute phase of denervation, were also seen in long-standing disease and there was no associated abnormal enhancement in any case. Furthermore, the signal intensity may be normal, the MR diagnosis relying on asymmetry of the size of the tongue. It is postulated that radiation causes incomplete and ongoing damage of the nerve, the course of which is unpredictable.

Transient cranial neuropathy in prostatic cancer with bone metastases after rhenium-186-HEDP treatment.

Rhenium-186 (tin) hydroxyethylidene diphosphonate (186Re-HEDP), a bone-seeking radiopharmaceutical, has been successfully used in the treatment of patients with painful bone metastases. Toxicity is usually limited to reversible thrombocytopenia. An infrequent but clinically significant side effect is the occurrence of transient cranial neuropathy. We report on two prostatic cancer patients with metastatic bone cancer. Both patients developed transient cranial neuropathy shortly after treatment with 186Re-HEDP. Transient neuropathy of cranial nerves needs to be distinguished from neurological abnormalities caused by disease progression.

Vocal cord palsy: possible late complication of radiotherapy for head and neck cancer.

Cranial nerve palsies are uncommon complications of radiotherapy for head and neck cancer. A review of the literature reveals that cranial nerve damage after radiotherapy has been reported for the optic, oculomotor, trigeminal, abducens, cochlear, vagus, spinal accessory, and hypoglossal nerves. The hypoglossal nerve appears to be the most commonly affected, and the recurrent laryngeal nerve is seldom involved. The case histories of three patients who developed vocal cord palsy from 21 to 34 years after a course of curative or postoperative radiotherapy for carcinoma of the head and neck are presented. Two patients had bilateral palsy, and in the third patient, bilateral damage cannot be excluded. Physical examination and radiographic investigations on admission and on follow-up did not demonstrate any evidence of tumor recurrence, cervical or distant metastases, or second primary tumors. The distinction between irradiation-induced palsy and that due to malignancies is emphasized.

Myokymia and neuromyotonia of the tongue: a case report of complication of irradiation.

A 51-year-old man has suffered from progressive dysarthria since 1989. He himself noted slight weakness and tightness of the tongue, so that he was unable to perform motor tasks in a normal fashion. He was diagnosed as having nasopharyngeal carcinoma and had irradiation 70 Gy in 32 divided doses in 1979. Neurological examination revealed left-sided tongue atrophy and myokymia sparing of facial muscles involvement. Electrical discharges of myokymia and neuromyotonia were observed in the tongue muscles, suggesting hypoglossal nerve lesion with hyperexcitability of the axon membrance. Computed tomogram of brain did not show any evidence of recurrence of tumor; indicating that irradiation was the pathologic basis. Our report revealed that myokymia and neuromyotonia of the tongue was an unusual complication of irradiation.

Radiation-induced cranial nerve palsy: hypoglossal nerve and vocal cord palsies.

Cranial nerve palsies are an unexpected complication of radiotherapy for head and neck tumours. We present a case of this radiation-induced cranial palsy. An 18-year-old female with nasopharyngeal carcinoma developed a right hypoglossal nerve palsy 42 months after cancericidal doses of radiotherapy. In addition, she developed a bilateral vocal cord palsy 62 months after therapy. Follow-up over four years has demonstrated no evidence of tumour recurrence and no sign of neurological improvement.

Bilateral hypoglossal palsies: a late complication of curative radiotherapy.

A 57 year old man developed bilateral hypoglossal nerve palsies 6 years after radiotherapy for carcinoma of the uvula. Follow-up over 2 years has demonstrated no evidence of tumour recurrence and no sign of neurological improvement. Reactive fibrosis and vascular insufficiency secondary to radiation and may have lead to hypoglossal nerve compression and infarction.

Neoplasms induced by megavoltage radiation in the head and neck region.

Radiation-induced cancer, although fortunately a rare complication of radiotherapy, is nonetheless observed occasionally even after megavoltage radiation has been used. Over a 22-year period at the Curie Institute, four patients were found to have malignant neoplasms within the fields of megavoltage treatment given for various cancers of the head and neck region. Three of the neoplasms were sarcomas, two osteogenic and one fibrosarcoma, and the other tumor was a sarcomatoid epithelioma. The latent period ranged from 3 1/2-15 years. Although the evidence is strong that the neoplasms were causally related to the precedent irradiation, it is acknowledged that rare examples of the "double primary" phenomenon exist, even separated by five or more years, and that only one such instance would induce a large error in the estimated frequency of postirradiation neoplasms. Because clinical estimates after megavoltage irradiation are usually compounded by an association with a relatively high total absorbed dose, the issue of the incidence of postirradiation neoplasms as a function of the type of external beam (orthovoltage vs. megavoltage) may require resolution by experimental means. Another rare sequela of radiotherapy is injury to a peripheral nerve. One of the four patients with a second neoplasm after radiation also developed left hypoglossal nerve palsy 2 1/2 years post-therapy, and left optic nerve atrophy seven years postradiation treatment of a squamous cell carcinoma of the ethmoid and maxillary sinuses. The 51-year-old patient had received a tumor dose of 6800 rads (2043 rets).

Bilateral hypoglossal nerve paralysis after irradiation therapy.

Cancericidal doses of irradiation therapy to be the head and neck may be followed by paralysis of cranial nerves due to fibrosis of tissue about the nerves and infiltration of the nerves with fibrous tissue. The hypoglossal nerve is particularly prone to this delayed effect of irradiation therapy and a case is presented here in which there was bilateral hypoglossal paresis appearing three years after therapy.

Radiation-induced cranial nerve palsy.

Twenty-five patients with 35 cranial nerve palsies were seen at the Fondation Curie during follow-up after radical radiotherapy for head and neck tumors. The twelfth nerve was involved in 19 cases, the tenth in nine, and the eleventh in five; the fifth and second nerves were involved once each and in the same patient. The twelfth nerve was involved alone in 16 patients and the tenth nerve alone in three, with multiple nerves involved in the remaining six patients. The palsy was noted from 12 to 145 months after diagnosis of the tumor. The latency period could be correlated with dose so that the least square fit equation representing NSD vs delay in NSD = 2598 - Delay (in months) X 4.6, with a correlation coefficient of -0.58. The distinction between tumor recurrence and radiation-induced nerve palsy is critical. It can often be inferred from the latency period but must be confirmed by observation over a period of time.