Acute lymphoblastic leukemia (ALL) is a hema-topoietic disease, associated with progressive bone marrow failure and accounts for 15-20% of adult acute leukemia cases. Leukemic infiltration and viral infections are associated with the pathogenesis of cranial nerve palsy in ALL. Although previous lite-rature has introduced vagus nerve involvement with dysphagia in leukemic patients¹, facial nerve, espe-cially bilateral facial nerve palsy inducing oropha-ryngeal dysphagia is very rare. We report a rare case of bilateral facial palsy with oropharyngeal dysphagia in a patient with ALL.

A 48-year-old man with a history of diabetes was admitted to the hospital on January 18, 2021, due to general weakness, a palpable mass on his neck, and uncontrolled blood sugar.

He had unstable vital signs. He had low blood pre-ssure (81/54 mmHg) and high fever (up to 39.6°C). Initial laboratory analysis showed low hemoglobin levels (7.0 g/dL), low platelet count (35×10³/μL), and low white blood cell (WBC) count (2.74×10³/μL, with a differential of 9% neutrophils, 29% lymphocytes, 3% atypical lymphocytes, 2% band neutrophils, and 57% immature cells). Gram-negative bacilli were found in his blood culture. Peripheral blood smears revealed normocytic normochromic red blood cells, anisocytosis, and poikilocytosis. Bone marrow aspiration biopsy showed 90% blasts with hypercellular marrow with a diffuse proliferation of immature precursors. He was positive for CD10, CD20, TdT, and PAX5 in tumor cells. He was also positive for BCR-ABL1 in the marrow via a polymerase chain reaction. Brain magnetic reso-nance imaging (MRI) showed bone marrow enhan-cement of the skull base, suggestive of tumor infil-tration or hematopoietic marrow reconversion. How-ever, definite brain metastases were not found. Neck computed tomography (CT) showed acute lympha-denitis in the right retroauricular area, while abdo-minal CT showed left acute pyelonephritis with renal abscess. He was diagnosed to have B lymphoblastic leukemia with BCR-ABL1. Hyperfractionated cyclo-phosphamide, vincristine, doxorubicin, and dexame-thasone were initiated. In addition, antibiotic therapy (cefepime) was initiated to control sepsis. On March 2, 2021, the patient could not completely close his eyes and lips and could not move his forehead.(Fig. 1) Physical examination revealed dysarthria and decreased taste. However, the bilateral facial sen-sation was intact. Other neurological tests of the cranial nerves were unremarkable. A follow-up brain MRI showed no significant changes. A cerebrospinal fluid study noted a few lymphocytes showing hyper-chromasia, with severe dry artifacts. Based on this finding, ALL with central nervous system (CNS) invol-vement was suspected, and intrathecal chemotherapy (methotrexate, hydrocortisone, and cytarabine) was initiated to treat CNS involvement. A neurologist was consulted for further evaluation and management of bilateral facial palsy. The neurologist recommended antiviral therapy since a viral infection could not be ruled out.

Figure 1. The patient developed house-brackmann grade IV bilateral facial palsy.

Despite chemotherapy and antiviral therapy, his facial palsy persisted. Pneumonia was also noted in March; however antibiotic treatment failed to alle-viate this. In May, a videofluoroscopic swallowing study (VFSS) was done to rule out dysphagia causing aspiration pneumonia. VFSS revealed oropharyngeal phase dysfunction. Severe drooling was observed due to poor lip sealing in the oral phase. Tongue move-ment was normal, but he had difficulty controlling dense food between the teeth and tongue, and under the tongue. He used his fingers to dig up the food to swallow. In addition, poor bolus formation and pre-mature bolus spillage were observed in the liquid test. In the pharyngeal phase, his swallowing reflex was normal but decreased elevation and closure of the larynx were observed. After swallowing, food rem-nants in the vallecular space were observed. Pene-tration and aspiration were observed during liquid tests.(Fig. 2) A 5 cc liquid penetration corresponds to a penetration aspiration scale (PAS) of 5. On the other hand, 10 cc liquid aspiration corresponds to a PAS of 8, representing aspiration without coughing. A food thickener was prescribed, and swallowing rehabilitation was initiated, to address his dysphagia. Rehabilitation included tongue movement exercises to increase oro-motor function, and the Mendelsohn maneuver and Shaker exercise to improve laryngeal elevation.

Figure 2. Videofluoroscopic swallowing study showed food remnants between lips and teeth and under the tongue (red arrow). (A) During liquid swallowing, aspiration is observed (black arrow). (B) During solid food swallowing, food remnants are observed in the vallecula (green arrow). (C) He used his finger to dig up food in the oral cavity (blue arrow).

A nerve conduction study (NCS) revealed decreased amplitudes of less than 0.1 mV on both sides of his facial muscles. Further, a blink reflex study showed no response on both side. The results were com-patible with severe peripheral neuropathy of the bilateral facial nerve (VII).(Table 1)

Table 1 . Electrodiagnostic test for bilateral facial palsy.

NCS	Nerve	Stimulation	Muscle	Latency (ms)	Amplitude (mV)
	Left facial nerve	Postauricular	Orbicular oculi	2.45	0.1*
			Nasalis	3.23	<0.1*
	Right facial nerve	Postauricular	Orbicular oculi	3.07	0.1*
			Nasalis	2.60	<0.1*
Blink reflex	Stimulation site	Ipsilateral R1 (ms)	Ipsilateral R2 (ms)		Contralateral R2 (ms)
	Left	NR*	NR*		NR*
	Right	NR*	NR*		NR

NR: no response.

*Abnormal finding.

On June 16, 2021, pneumonia developed, and subsequent septic shock occurred due to immuno-suppression. Because he was confined in the inten-sive care unit, VFSS follow-up could not be perfor-med. He died on July 14, 2021.

Bilateral simultaneous facial palsy has an incidence of 1 per 5 million populations per year. The causes of bilateral facial palsy include congenital, neo-plastic, infectious, traumatic, and toxic material². There have been previous works of literature pre-senting facial palsy in leukemia patients^3-8. However, only three cases have been reported with bilateral facial palsy^5-7. Furthermore, there is only one report that showed dysphagia in leukemia patient with facial palsy which was unilataeral⁴. In this case, the patient complained of difficulty swallowing, but dysphagia symptom was not evaluated or confirmed by VFSS. In our case, the patient had bilateral facial palsy and dysphagia, and these were evaluated by nerve con-duction study, electromyography, and VFSS. Accor-dingly, our case is the first report of dysphagia with bilateral facial palsy in ALL confirmed by VFSS and NCS findings.

The CNS involvement in leukemia is related to the expression of specific molecules by a subpopulation of leukemic cells. The cells, called “sticky cells” have the ability to interact and adhere to endothelial cells. In addition, the microenvironment becomes hypoxic, and together with the secretion of VEFG-A by ALL or AML cells, the permeability of vasculature in the bone marrow increases resulting in disruption of the blood-brain barrier⁹. On the other hand, paralysis of the facial nerve, the peripheral nervous system, is caused by the infiltration of leukocytes into the nerve fibers of the perineural and endoneurial sheath of the facial nerve, causing bleeding and physical compre-ssion in the tissue, and degenerative changes in the nerve¹⁰. Leukemic infiltration of the tympanic cavity and the temporal bone has also been suggested as causes of peripheral facial nerve involvement in leukemic patients⁸.

In our case, CNS involvement of leukemia was first suspected, but the patient’s facial nerve palsy was considered peripheral type, given the symptoms affe-cting both the lower and upper face and the results of NCS.

The function of the facial nerve is important to swallowing. Welby et al.¹¹ reported the effects of facial nerve injury on the swallowing process in rats. The study result showed slower lick, decreased swa-llow rates, and longer inter-swallow intervals¹¹. The bucci-nator, orbicularis oris muscles innervated by the facial nerve are important for the oral phase of swallowing. These muscles close the mouth to prevent drooling and food from escaping. Suprahyoid muscles (stylo-hyoid and posterior digastric muscles, innervated by facial nerve) are important for the oropharyngeal phase of swallowing. These muscles elevate the hyoid bone which causes laryngeal elevation. The posterior digastric also contracts in coordination with the ante-rior digastric muscle to open the jaw during chewing, and bolus formation. Therefore, abnormal stylohyoid and digastric muscle causes restricted hyoid movement, which indirectly hinders tongue movement and affec-ted the pharyngeal phase of swallowing^2,11.

In VFSS, our patient showed oropharyngeal phase dysfunction. Drooling is observed during both liquid and thick food because he could not close his lips due to facial palsy. He had difficulty controlling the thick food located between his teeth and lip with his tongue. In the pharyngeal phase, decreased elevation and closure of the larynx, food remnants in vallecular space, penetration, and aspiration during liquid tests were observed. It seems that due to bilateral facial palsy, decreased stylohyoid muscle and digastric muscle function affected hyoid movement, which indirectly disturbs tongue and pharyngeal movement^2,11.

In our case, it took nearly two months from the onset of pneumonia to the evaluation of dysphagia by VFSS, because bilateral facial palsy had not been suspected to be the reason for dysphagia. Eventually, the patient died of pneumonia and sepsis. Our case highlights that since the facial nerve plays an impor-tant role in the oropharyngeal phase of swallowing, it is important to evaluate swallowing function early in patients with dysphagia in the presence of bilateral facial palsy, especially immunosuppressed patients.

This work was supported by Inha University Resea-rch Grant.

The authors declare no conflict of interest.