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C A S E R E P O R T Open Access
Parkinsonism-hyperpyrexia syndrome after
withdrawal of antiparkinsonian drugs and
deep brain stimulation surgery
Chun-Lei Han
1
, Yan Ge
2
, Da-Wei Meng
3
, Jian-Guo Zhang
3
and Fan-Gang Meng
1*
Abstract
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
Background
Parkinsonism-hyperpyrexia syndrome (PHS) is a rare but
potentially fatal condition in patients with Parkinson’sdis-
ease (PD) and is manifested by pyrexia, muscle rigidity, a
reduced level of consciousness, and autonomic instability.
It is generally believed that rapid withdrawal of antiparkin-
sonian 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 treat-
ment 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 discon-
tinuation of medications before or after DBS surgery had
been reported to provoke PHS [3, 4]. In addition, the sur-
gery itself may also provoke the condition. Here, we re-
ported a case of PHS in a patient who firstly underwent
withdrawal of antiparkinsonian medications and then bi-
lateral subthalamic nucleus (STN) DBS.
Case presentation
A 69-year-old woman with a 24-year history of Parkinson’s
disease and the use of a variety of antiparkinsonian drugs
was admitted on February 27, 2014. Her disease had grad-
ually progressed, and the drugs were less effective, despite
increased dosages and changes in drug families. Before ad-
mission, she had been experiencing serious motor compli-
cations, including wearing-off and dyskinesia, and she was
taking 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, the
drugs were gradually discontinued in order to alleviate the
dyskinesia (Fig. 1). However, it had no effect. A levodopa
test, which compared the Unified Parkinson Disease Rating
Scale Part III (motor score) before and after oral intake of
levodopa, showed a more than 30% improvement, which
indicated that the patient was a suitable candidate for
STN-DBS. Bilateral STN stimulation was commenced 5
days after admission. Eight hours before surgery, all PD
medications were stopped. Bilateral STN-DBS was per-
formed as described in the literature [4]. During the pro-
cedure, the patient was cooperative but exhausted. After
recovering from the general anesthesia, the patient was un-
able to communicate properly. During the night, the pa-
tient developed severe muscle rigidity, tremors, continuous
* Correspondence: fgmeng@ccmu.edu.cn
1
Beijing Neurosurgical Institute, Capital Medical University, No. 6 Tiantan Xili,
Dongcheng District, Beijing 100050, China
Full list of author information is available at the end of the article
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CHINESE NEUROSURGICAL SOCIETY
CHINESE NEUROSURGICAL SOCIETY
CHINESE MEDICAL ASSOCIATION
© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Han et al. Chinese Neurosurgical Journal (2017) 3:10
DOI 10.1186/s41016-016-0067-y
limb shaking, head tremor and trismus. She was febrile,
with a temperature of 39.8°C, and had diaphoresis, a pulse
rate of 132 beats/min, a respiratory rate of 24 breaths/min,
and sustained increasing in blood pressure up to 178/117
mmHg. Her consciousness gradually declined approxi-
mately 11 h after DBS. Laboratory tests were normal with
the exception of an elevated white blood cell count (18.0 ×
10
9
/L). A computed tomography (CT) scan of the brain
showed correct placement of the electrodes without evi-
dence of blood or other abnormalities. The next day, the
patient was admitted to the intensive care unit. Intravenous
fluid replacement and cooling of the body were initiated,
and complications were managed. In the next 7 days, a
series 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 febrile
condition 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 the
2nd day after the operation (Fig. 2). On day 7 postopera-
tively, when infection, cerebral infarction and intracerebral
hemorrhage were all excluded, the diagnosis of PHS was
made. 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/day
and increased to 150 mg/day, and amantadine 100 mg/
day per day was initiated (Fig. 1). By the 28th day after
surgery, the patient’s condition had gradually returned to
her preoperative status. Her consciousness recovered, and
her vital signs and laboratory tests returned to baseline
levels (Fig. 3).
Discussion
It has been reported repeatedly that acute withdrawal of
antiparkinsonian drugs in PD patients is considered to
be the sole cause of PHS. Apart from these medication-
related causes, physiological stressors, such as surgery, in-
jury, may also precipitate PHS [5]. Overnight withdrawal of
antiparkinsonian drugs in PD patients is widely performed
before 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 than
either factor alone. Until now, about 5 cases of PHS after
DBS 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 DBS
system was activated [3, 8]. In our case, the patient first ex-
perienced rapid reduction of antiparkinsonian drugs due to
dyskinesia. However, there was no improvement, which
eventually 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 is
uncertain whether the occurrence of cerebral infarc-
tion precipitated PHS or not. PHS occurred eventually
and was characterized by hyperthermia, extreme muscle
rigidity, autonomic instability, and altered consciousness.
At first, the patient’s condition was not considered to be
PHS because of a lack of experience with this disorder
and confounding factors such as the possibility of infec-
tion and cerebral infarction. The differential diagnosis in-
cluded infection, cerebral infarction and intracerebral
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
Han et al. Chinese Neurosurgical Journal (2017) 3:10 Page 2 of 4
hemorrhage. Infection was excluded based on CSF ana-
lysis, an x-ray, routine stool tests, routine urine tests and
bacterial 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, only
symptomatic treatment was administered. Finally, when in-
fection, cerebral infarction and intracerebral hemorrhage
were all excluded, the diagnosis of PHS was made, and anti-
parkinsonian medications were gradually prescribed. The
patient’condition returned to her preoperative status with
clear consciousness and stable vital signs when discharged.
Conclusions
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 to
significant side effects. Once a patient is seen to have very
high fever, extreme muscle rigidity, autonomic instability,
Fig. 3 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
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)
Han et al. Chinese Neurosurgical Journal (2017) 3:10 Page 3 of 4
and altered consciousness, PHS should be considered.
Moreover, antiparkinsonian medications should be rein-
troduced as soon as possible after surgery. In the event
that a patient develops PHS, it should be treated as a
neurological emergency. The key to success is early diagno-
sis and initiation of treatment. Finally, we should consider
the possibility that DBS surgery itself, as a physiological
stressor, may precipitate PHS.
Abbreviations
CT: Computed tomography; DBS: Deep brain stimulation; PD: Parkinson’s
disease; PHS: Parkinsonism-hyperpyrexia syndrome; STN: Subthalamic nucleus
Acknowledgements
Not applicable.
Funding
This work was supported partly by Beijing Health System Advanced Health
Technology Talent Cultivation Plan (Grant No. 2011-3-032), China National
Clinical Research Center for Neurological Diseases (Grant No. NCRC-ND),
Beijing Municipal Administration of Hospitals Clinical medicine Development
of Special Funding Support (Grant No. ZYLX201305) and National Natural
Science Foundation of China (Grant No. 81527901).
Availability of data and materials
Not applicable.
Authors’contributions
CH contributed to the data collection and writing. YG and DM were involved
in the surgery and participated the data collection. JZ and FM were the
surgeons who performed the surgery. FM conceived of the study, and
participated in its design and coordination and helped to draft the
manuscript. All authors read and approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Consent for publication
Not applicable.
Ethics approval and consent to participate
Written, informed consent was obtained from the patient for publication of
this case report and accompanying images.
Author details
1
Beijing Neurosurgical Institute, Capital Medical University, No. 6 Tiantan Xili,
Dongcheng District, Beijing 100050, China.
2
Department of Neurosurgery,
Beijing Fengtai Hospital, Beijing 100071, China.
3
Department of Neurosurgery,
Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
Received: 2 June 2016 Accepted: 8 December 2016
References
1. Newman EJ, Grosset DG, Kennedy PG. The parkinsonism-hyperpyrexia
syndrome. Neurocrit Care. 2009;10:136–40.
2. Arora A, Fletcher P. Parkinsonism hyperpyrexia syndrome caused by abrupt
withdrawal of ropinirole. Br J Hosp Med. 2013;74:698–9.
3. Urasaki E, Fukudome T, Hirose M, Nakane S, Matsuo H, Yamakawa Y.
Neuroleptic malignant syndrome (parkinsonism-hyperpyrexia syndrome)
after deep brain stimulation of the subthalamic nucleus. J Clin Neurosci.
2013;20:740–1.
4. Kim JH, Kwon TH, Koh SB, Park JY. Parkinsonism-hyperpyrexia syndrome after
deep brain stimulation surgery: case report. Neurosurgery. 2010;66, E1029.
5. Hashimoto T, Tokuda T, Hanyu N, Tabata K, Yanagisawa N. Withdrawal of
levodopa and other risk factors for malignant syndrome in Parkinson’s
disease. Parkinsonism Relat Disord. 2003;9 Suppl 1:S25–30.
6. Linazasoro G, Van Blercom N, Castro A, Dapena MD. Subthalamic deep brain
stimulation masking possible malignant syndrome in Parkinson disease.
Neurology. 2004;63:589–90.
7. Govindappa ST, Abbas MM, Hosurkar G, Varma RG, Muthane UB.
Parkinsonism Hyperpyrexia Syndrome following Deep Brain Stimulation.
Parkinsonism Relat Disord. 2015;21:1284–5.
8. Factor SA. Fatal Parkinsonism-hyperpyrexia syndrome in a Parkinson’s
disease patient while actively treated with deep brain stimulation. Mov
Disord. 2007;22:148–9.
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