Delayed radiation-induced bulbar palsy

The late effects of ionizing radiation on the nervous system can begin months to years after the exposure and are generally divided into those syndromes caused by damage to the peripheral nerves and plexuses and those caused by CNS damage. ^[1-6] Peripheral nerve and plexus damage occur most often in the upper extremities secondary to radiation involving the chest or thorax. ^[1,4] There are clear descriptions of the electrophysiology of these syndromes. ^[7,8] Postradiation CNS syndromes include myelopathy, encephalopathy, and a lower motor neuron syndrome described almost exclusively in the lower extremities and thought to be secondary to either anterior horn cell or motor root damage. ^[1-3,5,9] There are rare reports of the late effects of radiation on the cranial nerves, ^[10-13] and the electrophysiologic attributes have not been well characterized. We report an unusual case of severe delayed radiation-induced bulbar palsy in a patient 14 years after receiving treatment for a nasopharyngeal carcinoma. Electrodiagnostic studies revealed diffuse electromyographic evidence of myokymia and neuromyotonia in cranial-nerve-innervated muscles.

Case report.

A 41-year-old Cambodian man developed the insidious onset of difficulty with swallowing and speech and recurrent aspiration pneumonia over 2 years, resulting in severe cachexia and a 40-pound weight loss. There was no associated ophthalmoplegia, ptosis, or facial or focal limb weakness. Medical history was significant for malaria and a positive PPD, with no history of active tuberculosis or treatment. Between August and October of 1981 he had received 70 Gy cobalt radiation in 32 fractions for treatment of a nasopharyngeal carcinoma, stage T2 N2 M0, resulting in complete remission. He had previously suffered lacerations about the neck while attempting escape from a Cambodian prison camp. The patient was initially admitted to another hospital with aspiration pneumonia and a diagnosis of bulbar palsy variant of amyotrophic lateral sclerosis (ALS) was made. He was treated with high-dose steroids for respiratory distress and transferred to a rehabilitation hospital, where he subsequently developed worsening respiratory compromise. He was transferred to this institution for further evaluation.

Physical examination revealed a cachectic man with generalized loss of muscle bulk. Fibrotic skin changes were noted about the neck secondary to the previous radiation, as well as several well-healed scars secondary to his old neck lacerations. Speech was nasal and dysarthric, with most difficulty with guttural sounds. The palate did not elevate and gag response was absent on the left, depressed on the right. There was diffuse atrophy of the anterior cervical musculature, more prominent on the left, with continuous undulating movements of the tongue at rest and deviation to the left on attempted protrusion Figure 1. Taste and light touch sensation of the tongue were preserved. Weakness was limited to the palate, tongue, sternocleidomastoids, and neck flexors, and was more pronounced on the left side. Tone was normal in the upper and lower extremities bilaterally with no evidence of fasciculations in the limbs or trunk. Strength, sensation, and coordination were normal in the upper and lower extremities bilaterally. Deep tendon reflexes were depressed in the upper extremities, slightly more so on the right, but normal and symmetric in the lower extremities. Plantar responses were flexor bilaterally. There was no snout, jaw jerk, or Myerson's sign.

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Figure 1. Delayed radiation-induced atrophy of the anterior cervical musculature, with tongue deviation to the left on attempted protrusion.

Laboratory studies.

Serum electrolytes, calcium, magnesium, phosphorus, creatine kinase, liver function studies, glucose, CEA level, cortrosyn stimulation test, and angiotensin converting enzyme were normal. DNA testing for X-linked bulbospinal muscular atrophy was negative, as were antibody titers to HIV-1 and 2, acetylcholine receptors, GM-1 ganglioside, and lyme borreliosis. Spinal fluid was acellular with normal glucose (68 mg/dl) and protein (21 mg/dl). Gadolinium-enhanced MRI of the brain and cervicomedullary junction with sagittal and axial T₁ and fast-spin echo T₂-weighted images was normal. Direct laryngoscopy revealed normal vocal cord abduction, but incomplete glottic closure with abnormal adduction. Modified barium swallow examination of the upper GI tract revealed very poor pharyngeal movement.

Electrodiagnostic testing.

Motor and orthodromic sensory conduction studies, F wave studies, blink responses, and concentric needle EMG were performed using standard techniques. Motor and sensory studies of the right median and ulnar nerves, including segmental stimulation to Erb's point, were normal, as were bilateral tibial motor and sural sensory studies. Right median and ulnar F responses were absent. Axon reflexes were noted with median nerve stimulation. Bilateral tibial F responses and gastrocnemius-soleus H reflex studies were normal. Blink studies revealed normal R1 and R2 latencies bilaterally, with a contralateral R1 reflex noted with stimulation on either side. Concentric needle EMG showed diffuse myokymic discharges in the tongue bilaterally, more prominent on the left side Figure 2. A combination of complex repetitive discharges, neuromyotonia, and myokymic discharges was noted in the left sternocleidomastoid, bilateral mentalis, and right trapezius muscles. Motor-unit readings in these muscles were generally of high amplitude and prolonged duration, with reduced recruitment. No fibrillations or positive sharp waves were noted on needle examination. EMG examination of frontalis and masseter muscles as well as selected proximal and distal muscles of the right upper and lower extremities was normal.

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Figure 2. Diffuse myokymic discharges in the tongue, firing at approximately 3 Hz, resulting in continuous undulating movements of the tongue at rest.

Discussion.

Cranial neuropathy as a late complication of head and neck radiation is poorly documented both clinically and electrophysiologically. Whereas much has been written on the electrophysiologic characteristics of radiation-induced peripheral nerve and plexus damage, ^[7,8,14] previous reports of delayed radiation-induced cranial nerve damage are scarce. ^[10-13] Earlier reports have implicated cranial nerves I, II, V, VI, X, XI, and XII, although twelfth nerve damage is most frequent. ^[10-13,15] Only one previous report, published in the Chinese literature, ^[13] describes the electrophysiology of a patient with delayed radiation-induced bulbar palsy, consisting of diffuse myokymia and neuromyotonia in the tongue and sparing the facial muscles. In the case reported here, electromyographic evaluation revealed widespread myokymia and neuromyotonia primarily affecting the lower cranial-nerve-innervated musculature. Myokymia is most often recognized clinically as continuous, involuntary, rippling or undulating movement of muscle. Electrically, myokymic discharges consist of bursts of rhythmic grouped repetitive discharges of single motor unit potentials firing spontaneously approximately every 0.25 to 5 seconds. The duration of individual bursts may be up to 2 seconds, with firing frequencies within the burst of 5 to 60 Hz. ^[16] Neuromyotonia presents clinically as stiffness and delayed muscle relaxation, and affects limb as well as ocular muscles. ^[17-19] Electrically, the discharges are also repetitive single motor unit potentials that fire spontaneously at a high frequency (150 to 250 Hz) with a characteristic decrementing amplitude and frequency.

Delayed radiation-induced nerve damage is thought to be due to either direct damage to the nerve cells themselves or damage to the vascular endothelium, which results in ischemia to adjacent tissues, connective tissue fibrosis, and secondary compromise of neural tissue. ^{[1,3,6,10,11]} The degree of damage incurred appears to be directly related to the dose of radiation received, while the time of onset of neurologic signs appears to be inversely related to the dose received. ^[1,6,10] In patients with post-radiation-induced plexus lesions, there is prominent fibrosis as well as loss of axons and myelin sheaths in the field of radiation, with Wallerian degeneration more distally. ^[6] Both myokymia and neuromyotonia are thought to originate along segments of the motor axon, and are presumed to derive from spontaneous depolarization or ephaptic transmission along segments of demyelinated nerve, secondary to altered membrane excitability. ^[16,19] Myokymia occurs in a variety of disorders, including pontine tumors, multiple sclerosis, acute inflammatory demyelinating polyneuropathy, entrapment neuropathies, timber rattlesnake envenomation, and chronic peripheral nerve or root lesions. ^[16,20] It occurs frequently in delayed radiation-induced brachial plexopathy, and thus serves as a valuable electromyographic finding to help distinguish between neoplastic and radiationinduced brachial plexopathy. ^[7,8,14] The myokymia noted electromyographically in post radiation syndromes is likely secondary to demyelinative changes.

The prominent electromyographic findings of myokymic and neuromyotonic discharges in the bulbar muscles of this patient excluded the diagnosis of the progressive bulbar palsy variant of ALS. Although fasciculations are common in ALS and double discharges are occasionally seen, myokymia and neuromyotonia do not occur. Other than post-radiation, isolated bulbar myokymia occurs only in unusual cases of pontine glioma and multiple sclerosis. ^[20,21] The differentiation of delayed radiation-induced bulbar palsy from bulbar ALS has important implications for prognosis as well as potential treatment. Abnormal movements secondary to myokymia and neuromyotonia can be abolished with the use of anticonvulsants. This patient attempted a trial of phenytoin and then carbamazepine, but was unable to tolerate the side effects of either medication at a very low dose. There was no effect on speech or swallowing noted. He underwent placement of a J-tube, gained 20 pounds over the course of 2 months, and was referred for a possible pharyngeal narrowing procedure and cricopharyngeal myotomy. Glantz et al ^[22] recently reported the successful use of anticoagulation in a small group of patients with radiationinduced nervous system injury, including patients with myelopathy and brachial plexopathy. Whether such treatment would be useful in delayed radiationinduced bulbar syndromes remains unknown. This patient declined such treatment.

Addendum.

As this article went to press, a report appeared in Neurology describing two similar patients with delayed radiation-induced bulbar dysfunction and tongue myokymia. Poncelet AN, Auger RG, Silber MH. Myokymic discharges of the tongue after radiation to the head and neck. Neurology 1996;46:259-260.