Meyung Kug Kim

Emergence of Myasthenia Gravis with Myositis in a Patient Treated with Pembrolizumab for Thymic Cancer

Dear Editor, A 34-year-old woman presented with a 4-week history of diplopia, dysphagia, and dyspnea. She had no previous history of a neuromuscular disorder. However, she had been diagnosed with thymic cancer (squamous cell carcinoma) 2 years previously, with metastasis to the pericardium, pleura, and lung, which had not been successfully treated with conventional chemotherapy (cyclophosphamide, vincristine, doxorubicin, and cisplatin). She had been treated with four cycles of 100-mg pembrolizumab every 2 weeks, which reduced the size of the tumor. A physical examination revealed bilateral ptosis, ophthalmoplegia, dysarthria, facial diplegia, hypophonia, and weakness of the palatal and neck flexor muscles. Her deep tendon reflexes were symmetrically decreased. Laboratory studies showed a markedly elevated serum creatine kinase (CK) level of 2,125 U/L and seropositivity for acetylcholine-receptor antibodies (0.86 nmol/L). The findings of nerve conduction studies, repetitive nerve stimulation, and brain MRI were normal. Electromyography findings were suggestive of active myopathy. Based on the clinical and laboratory findings, we made a clinical diagnosis of myasthenia gravis (MG) with myositis associated with pembrolizumab. Pembrolizumab was discontinued and the patient underwent a 5-day course of intravenous immunoglobulin (IVIg). She was then subsequently treated with a 3-day course of 1-g intravenous methylprednisolone (IVMP), followed by prednisolone (1 mg/kg). The CK level normalized (230 U/L) and her neck weakness improved after IVMP treatment. However, five cycles of plasmapheresis were applied due to aggravation of dyspnea. The dysphagia and ptosis had improved at the 6-month follow-up, but ophthalmoplegia and mild dyspnea persisted even though she was on continuous prednisolone treatment. Additionally, the thymic cancer remained the same even without additional chemotherapy. Pembrolizumab is a monoclonal antibody targeting the programmed cell death 1 (PD-1) that is clinically beneficial in the treatment of malignancies such as metastatic melanoma and other advanced solid tumors, for which conventional therapies are only weakly effective.1 Pembrolizumab binds to PD-1, which is an inhibitory signaling receptor expressed on the surface of activated T cells, resulting in pembrolizumab preventing the binding of PD-1 to other ligands, thereby increasing the effectiveness of the T-cell-mediated immune response against tumor cells. However, enhanced immune activation by a PD-1 inhibitor may induce adverse side effects. It is particularly notable that autoimmune events in the neuromuscular system have also been reported in patients with metastatic melanoma who were treated with pembrolizumab (Table 1).2-9 Unlike the previously published cases in which metastatic melanoma was the underlying cancer, our patient had a thymic carcinoma. It is well known that thymic abnormalities and So-Young Huh Seong-Hoon Shin Meyung Kug Kim So-Young Lee Ki Hun Son Ha Young Shin

Status Epilepticus as an Unusual Manifestation of Heat Stroke

Heat stroke (HS) is a medical emergency and life threatening condition, characterized by body temperature over 40°C. This can lead to dysfunction of multiple organs such as the heart, liver, kidneys, lungs, blood coagulation system, and central nervous system. Neurological complications include change in consciousness, cerebellar dysfunction, convulsions, aphasia, muscular weakness, and parkinsonism. Cerebellar syndrome is the most common neurological finding in HS. We report a case of HS presenting with status epilepticus, without any other neurological manifestations. A 42 year old man, previously diagnosed with bipolar disorder, was admitted to the emergency room with high fever and repetitive generalized tonic-clonic seizures. He had been found unconscious after 4 hours of heavy physical work under extremely hot weather conditions. He was diagnosed with HS accompanied by status epilepticus, and treated with emergency body cooling and antiepileptics. Five days after admission, he regained consciousness and the laboratory parameters that were initially abnormal returned to normal values. On day 14, he was discharged without any neurological complications.