Abstract
To the Editor
Neuroleptic malignant syndrome (NMS) most commonly presents with significant changes in mental status, muscle rigidity, hyperthermia, and autonomic dysregulation (Levenson, 1985). Creatinine kinase (CK) level is typically elevated to more than 1000 IU/l and can exceed 100,000 IU/l (Levenson,1985; Velamoor, 1998). Another associated finding in most cases of NMS is high white blood cell count. It is very important to recognize NMS as the incidence of mortality is estimated at 10 % (Ahuja and Cole, 2009).
A 45-year-old male, diagnosed with schizophrenia 19 years ago, was admitted to the emergency department after he was found in an altered conscious state. He had been on clozapine for 2 years and the dose had been increased 2 months previously from 600 to 750 mg. He had presented to the emergency department 6 days before with similar complaints and he was discharged home after a CT scan of his brain was normal.
He presented with a history of unsteady gait, generalized weakness, and lightheadedness. On examination, he was drowsy and found to have myoclonic jerks in his upper limbs. There was no evidence of rigidity. He was afebrile. Initial investigations revealed dehydration with a glomerular filtration rate of 28 (>60 ml/min/1.73m2), urea of 10.8 mmol/l and creatinine of 223 µmol/l. His white cell count was mildly elevated (12.6×109/l) and CK was 445 (normal levels 46-171 IU/l).
After improvement in his glomerular filtration rate, he was transferred to the mental health unit where he was found to have fluctuations in blood pressure throughout the day (lowest was 66/29 mmHg), which responded to IV fluids. His CK level further increased to 698 U/l on the second day of admission. On the fifth day of his admission the plasma clozapine level was 2070 µg/l. Throughout this period there was no rigidity or hyperthermia noted. Clozapine was ceased the same day. His blood pressure remained stable afterwards and CK started normalizing. He appeared more alert. He was stabilized on ziprasidone before discharge.
When we consider typical NMS, the above clinical presentation makes the diagnosis difficult. The presence of muscular rigidity, temperature above 38°C and CK level exceeding 1000 IU/l are the hallmarks of the syndrome but were virtually absent in this case. However, the presence of other features such as autonomic instability, drowsiness, mild CK elevation, and the improvement in these features after cessation of clozapine supports a diagnosis of NMS.
To conclude, this case illustrates that clozapine can perhaps cause NMS with an atypical presentation (Sachdev et al., 1995). Missing the diagnosis could lead to increased mortality. Further studies are required to find out if atypical presentations are a separate entity related to atypical anti-psychotics or whether they are an alternate from of NMS.