Chun-Lei Han, Yan Ge, Da-Wei Meng, Jian-Guo Zhang and Fan-Gang Meng
Background: Parkinsonism-hyperpyrexia syndrome (PHS) is a rare but potentially fatal condition in patients with Parkinson’s disease. Deep brain stimulation (DBS) is a widely used and efficacious treatment for advanced Parkinson’s disease.
Case presentation: Here, we report a case of PHS in a patient who first underwent withdrawal of antiparkinsonian medications and then bilateral subthalamic nucleus DBS.
Conclusions: Patients should be advised to gradually decrease rather than suddenly stop antiparkinsonian medications when they must stop taking a medication and antiparkinsonian medications should be reintroduced as soon as possible after surgery.
Keywords: Parkinson’s disease, Deep brain stimulation, Parkinsonism-hyperpyrexia syndrome
Parkinsonism-hyperpyrexia syndrome (PHS) is a rare but potentially fatal condition in patients with Parkinson’s disease (PD) and is manifested by pyrexia, muscle rigidity, a reduced level of consciousness, and autonomic instability. It is generally believed that rapid withdrawal of antiparkinsonian drugs or abrupt changes in medication regimens is the primary cause of this syndrome [1, 2]. Deep brain stimulation (DBS) is a widely used and efficacious treatment for advanced Parkinson’s disease. Antiparkinsonian drugs are transiently stopped before the procedure to check the patient’s response during the procedure when the patient is in the “off” state. However, sudden discontinuation of medications before or after DBS surgery had been reported to provoke PHS [3, 4]. In addition, the surgery itself may also provoke the condition. Here, we reported a case of PHS in a patient who firstly underwent withdrawal of antiparkinsonian medications and then bilateral subthalamic nucleus (STN) DBS.
Fig. 1 The antiparkinsonian medication adjustment process of a 69-year-old woman diagnosed with Parkinson’s disease and treated with DBS of the STN. WBC, white blood cells. Row 1 indicates the date in “day/month” format.
A 69-year-old woman with a 24-year history of Parkinson’sdisease and the use of a variety of antiparkinsonian drugswas admitted on February 27, 2014. Her disease had grad-ually progressed, and the drugs were less effective, despiteincreased dosages and changes in drug families. Before ad-mission, she had been experiencing serious motor compli-cations, including wearing-off and dyskinesia, and she wastaking levodopa/benserazide 500 mg/day, carbidopa/levo-dopa 500 mg/day, selegiline 12.5 mg/day, trastal 150 mg/day and amantadine 100 mg/day. After admission, thedrugs were gradually discontinued in order to alleviate thedyskinesia (Fig. 1). However, it had no effect. A levodopatest, which compared the Unified Parkinson Disease RatingScale Part III (motor score) before and after oral intake oflevodopa, showed a more than 30% improvement, whichindicated that the patient was a suitable candidate forSTN-DBS. Bilateral STN stimulation was commenced 5days after admission. Eight hours before surgery, all PDmedications were stopped. Bilateral STN-DBS was per-formed as described in the literature . During the pro-cedure, the patient was cooperative but exhausted. Afterrecovering from the general anesthesia, the patient was un-able to communicate properly. During the night, the pa-tient developed severe muscle rigidity, tremors, continuouslimb shaking, head tremor and trismus. She was febrile,with a temperature of 39.8°C, and had diaphoresis, a pulserate of 132 beats/min, a respiratory rate of 24 breaths/min,and sustained increasing in blood pressure up to 178/117mmHg. Her consciousness gradually declined approxi-mately 11 h after DBS. Laboratory tests were normal withthe exception of an elevated white blood cell count (18.0 ×109/L). A computed tomography (CT) scan of the brainshowed correct placement of the electrodes without evi-dence of blood or other abnormalities. The next day, thepatient was admitted to the intensive care unit. Intravenousfluid replacement and cooling of the body were initiated,and complications were managed. In the next 7 days, aseries of tests were run to determine the cause of her con-dition. An evaluation to determine potential sources of in-fection was unrevealing. The evaluation of her febrilecondition included a chest x-ray, thyroid function tests,routine stool tests, routine urine tests and a bacterial cul-ture analysis; however, causative factors were not identified.A cerebrospinal fluid (CSF) examination was also normal.On the day of surgery and on postoperative days 1, 2, 3, 6,and 12, brain CT showed normal postoperative changes;however, a left frontal cerebral infarction occurred on the2nd day after the operation (Fig. 2). On day 7 postopera-tively, when infection, cerebral infarction and intracerebralhemorrhage were all excluded, the diagnosis of PHS wasmade. Antiparkinsonian medications were immediately re-instated, and the patient’s symptoms began to improve.Levodopa/benserazide was initiated at 250 mg/day and in-creased to 500 mg/day, trastal was initiated at 25 mg/dayand increased to 150 mg/day, and amantadine 100 mg/day per day was initiated (Fig. 1). By the 28th day aftersurgery, the patient’s condition had gradually returned toher preoperative status. Her consciousness recovered, andher vital signs and laboratory tests returned to baselinelevels (Fig. 3).
Fig. 2 Postoperative CT showed correct placement of the electrodes (a-b) and a suspicious left frontal cerebral infarction on the 2nd, 3rd, 6th and 12th days after operation (c-f).
It has been reported repeatedly that acute withdrawal ofantiparkinsonian drugs in PD patients is considered tobe the sole cause of PHS. Apart from these medication-related causes, physiological stressors, such as surgery, in-jury, may also precipitate PHS . Overnight withdrawal ofantiparkinsonian drugs in PD patients is widely performedbefore DBS surgery to aid in the identification of the opti-mal macrostimulation response site during surgery. Thus,withdrawal of antiparkinsonian drugs combined with fur-ther surgery is more likely to cause the complication thaneither factor alone. Until now, about 5 cases of PHS afterDBS surgery have been documented; 3 of these cases oc-curred due to perioperative drug cessation [4, 6, 7], while,the other 2 cases occurred 6 and 8 days after antiparkinso-nian drug dosages were reduced abruptly when the DBSsystem was activated [3, 8]. In our case, the patient first ex-perienced rapid reduction of antiparkinsonian drugs due todyskinesia. However, there was no improvement, whicheventually made her received DBS surgery. After surgery,PHS happened and a left frontal cerebral infarction oc-curred on the 2nd day after surgery. However, it isuncertain whether the occurrence of cerebral infarc-tion precipitated PHS or not. PHS occurred eventuallyand was characterized by hyperthermia, extreme musclerigidity, autonomic instability, and altered consciousness.At first, the patient’s condition was not considered to bePHS because of a lack of experience with this disorderand confounding factors such as the possibility of infec-tion and cerebral infarction. The differential diagnosis in-cluded infection, cerebral infarction and intracerebral hemorrhage. Infection was excluded based on CSF ana-lysis, an x-ray, routine stool tests, routine urine tests andbacterial culture analysis. CT of the brain revealed no intra-cerebral hemorrhage but showed a left frontal cerebral in-farction. Thus, in the first 7 days after surgery, onlysymptomatic treatment was administered. Finally, when in-fection, cerebral infarction and intracerebral hemorrhagewere all excluded, the diagnosis of PHS was made, and anti-parkinsonian medications were gradually prescribed. Thepatient’ condition returned to her preoperative status withclear consciousness and stable vital signs when discharged.
In summary, patients should be advised to gradually re-duce rather than suddenly stop antiparkinsonian medica-tions when they must stop taking a medication due tosignificant side effects. Once a patient is seen to have veryhigh fever, extreme muscle rigidity, autonomic instability, and altered consciousness, PHS should be considered.Moreover, antiparkinsonian medications should be rein-troduced as soon as possible after surgery. In the eventthat a patient develops PHS, it should be treated as aneurological emergency. The key to success is early diagno-sis and initiation of treatment. Finally, we should considerthe possibility that DBS surgery itself, as a physiologicalstressor, may precipitate PHS.
Fig. 2 The patient’s temperature (a) and white blood cell (WBC) counts during treatment (b). Her temperature and WBC counts increased after the withdrawal of antiparkinsonian drugs and deep brain stimulation surgery but returned to normal after reinstatement of the medication.
CT: Computed tomography; DBS: Deep brain stimulation; PD: Parkinson’s disease; PHS: Parkinsonism-hyperpyrexia syndrome; STN: Subthalamic nucleus
This work was supported partly by Beijing Health System Advanced HealthTechnology Talent Cultivation Plan (Grant No. 2011-3-032), China NationalClinical Research Center for Neurological Diseases (Grant No. NCRC-ND),Beijing Municipal Administration of Hospitals Clinical medicine Developmentof Special Funding Support (Grant No. ZYLX201305) and National NaturalScience Foundation of China (Grant No. 81527901).
Availability of data and materials
CH contributed to the data collection and writing. YG and DM were involvedin the surgery and participated the data collection. JZ and FM were thesurgeons who performed the surgery. FM conceived of the study, andparticipated in its design and coordination and helped to draft themanuscript. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
Ethics approval and consent to participate
Written, informed consent was obtained from the patient for publication of this case report and accompanying images.
1Beijing Neurosurgical Institute, Capital Medical University, No. 6 Tiantan Xili, Dongcheng District, Beijing 100050, China. 2Department of Neurosurgery, Beijing Fengtai Hospital, Beijing 100071, China. 3Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
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Post time: Nov-11-2019