A rare case of neuroleptic malignant syndrome without elevated serum creatine kinase
A 51-year-old man had experienced repetitive manic and delirious episodes since he was 17 years old and was previously diagnosed with schizoaffective disorder. He had to be psychiatrically hospitalized six times for recurrent psychotic episodes after discontinuing his medications. He did not have a history of drug allergies. In 1996, at the age of 34, he was admitted to a psychiatric hospital, where he remained until the time of the current report. At the time of admission, his height and weight was 172 cm and 63 kg, respectively. His body mass index (BMI) was 21.3 Kg/m2. Throughout the first year of admission, he suffered repeated manic episodes with excitement and delusion. During these episodes, he often had to be taken into a private room because of his violent behavior towards other patients. Since he often refused to take medications, he was given fluphenazine decanoate (25 mg), injected intramuscularly, every month. Additionally, he was given lithium carbonate (600 mg), zotepine (150 mg), haloperidol (9 mg), and biperiden (6 mg) daily. While being treated with lithium carbonate, the serum lithium levels were within the therapeutic range. Furthermore, during periods when he became manic and excited, his dietary intake decreased, leading to large decreases in body weight. As a result, his body weight ranged from 63 to 53 kg.\nHis body weight was about 55 kg in the first half of 2011 but was 63 kg in January of 2012. After this, his body weight decreased gradually along with the deterioration of his mental state, and by December of 2012, he weighed 49 kg. His changes in BMI are shown in . There were no complaints from the patient, but he was suspected of having malignant disease. However, blood tests showed no abnormalities: white blood cell (WBC) count 7,900/mm3, red blood cell (RBC) count 344 × 104/mm3, total protein 7.6 g/dL, total cholesterol 169 mg/dL, aspartate aminotransferase (AST) 12 mU/mL, alanine aminotransferase (ALT) 9 mU/mL, and CK 51 mU/mL (normal range 48–248).\nOn January 31, 2013, the patient weighed 48 kg. Upon evaluation, his blood pressure was 96/60 mmHg, his pulse rate was 58 bpm, and his body temperature was 35.5°C. At that time, valproic acid (600 mg), lithium carbonate (800 mg), zotepine (150 mg), and risperidone (6 mg) were administered. On February 11, he became excited and was physically violent towards other patients and was transferred to a private ward. On February 12, the patient received fluphenazine decanoate (25 mg) by intramuscular injection. On February 13, he was physically able to have a meal by himself. On February 14, when a nurse went for her rounds in the morning, she noticed that he could not raise himself up. He did not show headaches, meningeal signs, or focal neurological signs. Upon evaluation, his blood pressure was 106/72 mmHg, his pulse rate was 102 bpm, and his body temperature was 36.0°C but rose to 38.5°C in the afternoon (day 1 of NMS). Since he had difficulty swallowing, all medications were discontinued, and he received intravenous fluid replacement. At that time, an antibiotic was administered intravenously upon suspicion of an infection. On February 17, it was noted that he was unable to speak due to marked muscle rigidity, but he did not show diaphoresis. His chest X-rays were normal. On February 18, blood tests showed the following: WBC count 10,800/mm3 and CK 74 mU/mL. On February 20, diaphoresis was observed. Since fever, generalized “lead pipe rigidity”, and dysphagia were also found, NMS was suspected. Only supportive therapy, including intravenous fluid replacement and cooling, was sustained. Because his serum CK was within the normal range, we were hesitant to administer dantrolene; thus, dantrolene was not given. In addition, since the patient had been mute during the disease, the administration of benzodiazepines or electroconvulsive therapy (ECT) was not planned. Although the patient’s serum CK was measured two more times, the levels were within normal range. On February 24, the patient’s body temperature was 38.4°C, and hypersalivation and tachypnea (respiratory rate 34/min) became prominent. On February 25, his oxygen saturation was noted to be 89% with room air, and 100% O2 was immediately given via face mask. However, he suddenly died of respiratory failure on February 26 (day 13). An autopsy was not performed.\nThe profile of the clinical course, including body temperature, the degree of muscle rigidity, and laboratory findings consisting of the levels of serum CK and WBC, is shown in . Muscle rigidity was rated using the NMS evaluation scale proposed by Sachdev.