Dyskinesia–hyperpyrexia syndrome: Another Parkinson's disease emergency

Parkinsonism–hyperpyrexia syndrome, also known as neuroleptic malignant-like syndrome, is a rare though life-threatening complication of Parkinson's disease (PD).1-4 It is clinically characterized by hyperthermia, autonomic dysfunction, disturbances of the level of consciousness, muscle rigidity, and elevated serum creatinekinase (CK) levels. In many cases, this syndrome is triggered by an infection, changes in the antiparkinsonian drug treatment, hot weather or dehydratation. A prompt recognition of this emergency and treatment with intravenous fluids, antipyretic measures, antiparkinsonian drugs—particularly levodopa and dopamine agonists—, and sometimes the use of dantrolene are crucial for a favorable outcome.2, 5 We report on a patient with advanced PD who experienced a dyskinesia–hyperpyrexia syndrome. Severe dyskinesias causing exhaustion and, rarely, rhabdomyolisis have been considered in some reviews of emergencies in parkinsonism.2, 4 To our knowledge, however, no PD patients with a dyskinetic status—instead of severe muscle rigidity—associated with hyperthermia, rhabdomyolysis, and a confusional state have been previously described in the English literature. A 68-year-old woman had a twelve-year history of PD complicated with motor fluctuations and peak-of-dose and biphasic dyskinesias. Apart from PD, her past medical history was irrelevant. She was treated with levodopa/carbidopa/entacapone (five daily doses of 150/50/200 mg), pramipexole (4 mg/day), and amantadine (200 mg/day). She experienced transient visual hallucinations that became more frequent over the last months. Two days before her admission to the Gregorio Marañón University Hospital severe disabling continuous generalized dyskinesias appeared followed by a confusional state, drowsiness, and fever. There had been no change in her usual antiparkinsonian treatment. On examination, she was conscious but disoriented. Her speech was incoherent, and she experienced vivid visual and auditory hallucinations (children playing around her, animals attacking her). No meningeal signs were found. Severe generalized choreatic dyskinesias were observed, more intense in the lower limbs. As a consequence of the amplitude and violence of these leg involuntary movements, that resembled ballism, the patient was unable to stand or walk. Only a mild bilateral akinetic-rigid syndrome was detected. Her temperature was 41.2°C, and her heart rate 110 beats per minute. The remainder of the neurological and general examinations was unremarkable. Routine blood tests showed 7,300 leukocytes. Plasma CK levels rose to 1,455 IU/L (normal values: 26–192 IU/L), LDH was 311 U/L (normal values: 135–214 U/L) and AST 53 U/L (normal values: 10–31 U/L). The rest of biochemical parameters were within normal range. The exam of the cerebrospinal fluid obtained by lumbar puncture was normal. A cranial computerized tomography and a chest radiography showed no abnormalities. Bacteriological cultures of blood, urine, and cerebrospinal fluid were sterile. Treatment was started with intravenous fluids, I.V. paracetamol and physical antipyretic measures. Pramipexol was tapered and withdrawn within five days and a small dose of quetiapine (25 mg/day) was added. Levodopa/carbidopa/entacapone and amantadine were kept unchanged. The patient's clinical situation progressively improved. Temperature and CK levels normalized in few days (Fig. 1), and the severity of dyskinesias was greatly reduced. Hallucinations remitted almost completely. The kidney function was closely monitored during her hospitalization but remained normal. Two months after being discharged from the hospital, dyskinesias remained non-disabling but the patient noticed motor fluctuations, with several off periods of variable duration every day. A neuropsychological evaluation found out mild cognitive impairment. The patient was proposed to undergo an enteral infusion of levodopa. Temperature and CK plasma levels during the patient's hospitalization. This case illustrates a new movement disorder emergency in PD. The patient here described shares some of the clinical characteristics of the parkinsonism-hyperpyrexia syndrome, such as hyperthermia, rhabdomyolysis, and a confusional state, but differs in that severe dyskinesias, instead of rigidity, dominate the clinical picture. The dyskinesia-hyperpyrexia syndrome probably reflects the most severe complication that continuous violent generalized dyskinesias may induce in patients with PD. In our patient, the massive dyskinetic movements likely led to rhabdomyolysis and hyperthermia, which consequently aggravated her mental state. Rhabdomyolysis has been described in patients with ballism,6 but very rarely in dyskinetic PD patients,2, 7 in whom neither hyperthermia nor related alterations of their mental state have so far been reported. However, the confusional state observed in this case, as well as the prominent hallucinations, could be related not only to hyperthermia, but chiefly to excessive dopaminergic stimulation, also responsible for the dyskinetic status. Thus, an abnormally high dopaminergic stimulation of the brain, involving the striatum and other dopaminergic structures, such as the mesocorticolimbic system, may be the main pathophysiological mechanism underlying the clinical picture of this patient. The dyskinesia-hyperpyrexia syndrome, contrarily to the parkinsonism-hyperpyrexia syndrome, should be treated by reduction of dopaminergic drugs, particularly dopamine agonists. A rapid recognition and treatment of this potentially ominous disorder is of the foremost importance. Financial Disclosure: Grandas received honoraria from serving on the scientific advisory board of UCB and served as a consultant for Shering Plough. Author Roles: Gil-Navarro provided clinical care and wrote the first draft of the manuscript. Grandas supervised clinical care, reviewed and wrote the final version of the manuscript. Silvia Gil-Navarro MD*, Francisco Grandas MD, PhD*, * Movement Disorders Research Unit Hospital Universitario Gregorio Marañón Madrid, Spain.