Case Report

Muscle-specific tyrosine kinase-antibody-positive myasthenic crisis with detailed electrophysiologic studies

Abstract

A 69-year-old male who presented in a coma due to sudden respiratory arrest was transferred to our hospital. After endotracheal intubation with manual ventilation, he became alert and his neurologic findings were within the normal range, except for palsy of the respiratory muscles. Biochemical analyses of the blood and brain computed tomography failed to indicate the cause of the respiratory arrest. An edrophonium test did not improve the respiratory arrest. An urgent electromyogram at the dorsal interossei, biceps, and sternocleidomastoideus muscle and a repetitive nerve stimulation test at the trapezius and deltoid muscle were also negative on the first hospital day. However, on the 16th day in the hospital, a repetitive nerve stimulation test at the levator labii superioris alaeque nasi showed a waning phenomenon. This result indicated a diagnosis of myasthenia gravis. Anti-muscle-specific tyrosine kinase antibody was found to be positive. After treatment with plasmapheresis and prednisolone, he regained normal Respiratory function.

Anti-muscle-specific tyrosine kinase (MuSK)-antibody-

positive myasthenia gravis (MG) (MuSK-MG) tends to be associated with a lower incidence of a positive edrophonium test, a lower incidence of a positive electrophysiologic study excluding the face, and a higher incidence of respiratory failure in comparison to anti-acetylcholine receptors (AchR)-antibody-positive MG (AchR-MG). Respiratory failure is curable with treatment. Accordingly, in addition to obtaining a precise diagnosis, an emergency physician should recommend an electrophysiologic study including the face to make a differential diagnosis for respiratory arrest when biochemical and radiologic studies fail to indicate the cause of the respiratory arrest.

Muscle-specific kinase is expressed at the postsynaptic membranes of neuromuscular junctions and forms com- plexes with AChR [1]. The presence of anti-MuSK antibody appears to define a subgroup of generalized MG patients

characterized by a younger onset age; weakness predominant in the bulbar, facial, and neck muscles; and more frequent myasthenic crises, such as respiratory failure (22%-46%) in comparison to anti-AchR-MG [2]. Most patients with anti- MuSK-MG have a good response to simple plasma exchange and prednisolone [3], and therefore, a correct and Timely diagnosis is important.

A 69-old male presenting with a coma due to sudden respiratory arrest was transferred to the hospital. His elder brother and sister had a history of cerebral infarction, and his younger brother had died of cardiac disease. On examination, the patient was in a deep coma. His vital signs were stable. The arterial blood gas analysis under a 10 L/min oxygen mask showed pH of 7.115; PCO2, 157 mm Hg; PO2, 181 mm Hg; HCO^- , 50.9 mmol/L; and base excess, 21.3 mmol/L, thus indicating respiratory acidosis. After endotracheal intubation with manual ventilation, he became alert and his neurologic findings were within the normal range except for palsy of the respiratory muscles. His biochemical analyses of the blood, chest x-ray, electrocardiogram, and brain computed tomogra- phy were normal. An edrophonium test did not improve the palsy of the respiratory muscles. An urgent electromyogram at the dorsal interossei, biceps, and sternocleidomastoideus muscles was negative. In addition, a repetitive nerve stimula- tion test at the trapezius and deltoideus muscles was also negative. He was admitted and underwent mechanical ventilation without a precise diagnosis for the respiratory arrest. After obtaining his Detailed history that revealed Double Vision at 57 years old, weakness of muscle strength of the neck, dysphagia, and Sleep apnea at 67 years old, he was suspected to have a neuromuscular junction abnormality. On the 16th day in the hospital, the repetitive nerve stimulation tests at the levator labii superioris alaeque nasi showed a waning phenomenon (Fig. 1). Moreover, single fiber electromyography showed an increasing and blocking jitter at the frontal muscle. He was thus diagnosed to have MG. His anti-AChR antibody was found to be negative, but the anti-MuSK antibody was positive. After treatment with plasmapheresis and prednisolone, he dramati- cally regained normal respiratory function. He was discharged after 72 days without any neurologic deficits with continued treatment with steroids and tacrolimus.

3

In comparison to AChR-MG, MuSK-MG tends to have a

lower incidence of a positive finding on an edrophonium test.

0735-6757/$ - see front matter (C) 2009

754.e6

and radiologic studies fail to indicate the cause of respiratory arrest.

Youichi Yanagawa MD, PhD Department of Traumatology and Critical Care Medicine National Defense Medical College (NDMC)

Tokorozawa, Saitama 359-8513, Japan E-mail-address: [email protected]

Yu Hongo MD Hiroshi Shiozaki MD Keiko Kamakura MD, PhD Division of Neurology

Department of Internal Medicine, NDMC Tokorozawa, Saitama 359-8513, Japan

Fig. 1 Repetitive nerve stimulation test at the levator labii superioris alaeque nasi showed a waning phenomenon on the 16th hospital day (+ indicates waning).

Hatanaka et al [4] report the edrophonium test to be positive in 5 (50%) of 10 tested patients in the MuSK-MG, whereas the edrophonium test was positive in 32 (97%) of 33 tested patients in the AChR-MG. Accordingly, the edrophonium test is not considered to be a suitable test for detecting MuSK-MG.

The MuSK-MG tends to have a lower incidence of a positive electrophysiologic study of the extremities, excluding the face in comparison to AChR-MG. Oh et al [5] found that a repetitive nerve stimulation test in the orbicularis oculi were more common and severe in MuSK-MG than in the AChR-MG group. Farrugia et al

[6] found that more than 70% of the patients with AChR- MG had an abnormal jitter in both the extensor digitorum communis and orbicularis oculi, but the most patients with MuSK-MG had a normal jitter in the extensor digitorum communis despite an abnormal jitter in the orbicularis oculi. Accordingly, an electrophysiologic study including the face muscle is an important test for detecting the MuSK-MG.

In addition to determining the precise present illness, an emergency physician should recommend an electro- physiologic study including the face to make a differ- ential diagnosis for respiratory arrest when biochemical

Masahiro Sonoo MD, PhD

Department of Internal Medicine

University Hospital Teikyo University School of Medicine

Tokyo 173-8605, Japan

Masakatsu Motomura MD, PhD First Department of Internal Medicine Graduate School of Biomedical Science Nagasaki University, Nagasaki 852-8523, Japan

doi:10.1016/j.ajem.2008.10.005

References

1. Shigemoto K, Kubo S, Jie C, et al. Myasthenia gravis experimentally induced with muscle-specific kinase. Ann N Y Acad Sci 2008;1132:93-8.
2. Kuwabara S, Nemoto Y, Misawa S, et al. Anti-MuSK-positive myasthenia gravis: neuromuscular transmission failure in facial and limb muscles. Acta Neurol Scand 2007;115:126-8.
3. Ohta K, Shigemoto K, Fujinami A, et al. Clinical and experimental features of MuSK antibody positive MG in Japan. Eur J Neurol 2007;14:1029-34.
4. Hatanaka Y, Hemmi S, Morgan MB, et al. Nonresponsiveness to anticholinesterase agents in patients with MuSK-antibody-positive MG. Neurology 2005;65:1508-9.
5. Oh SJ, Hatanaka Y, Hemmi S, et al. Repetitive nerve stimulation of facial muscles in MuSK antibody-positive myasthenia gravis. Muscle Nerve 2006;33:500-4.
6. Farrugia ME, Kennett RP, Newsom-Davis J, et al. Single-fiber electromyography in limb and facial muscles in muscle-specific kinase antibody and acetylcholine receptor antibody myasthenia gravis. Muscle Nerve 2006;33:568-70.