Website Edition: December 2013/January 2014

Clinical Vignette & Commentary

Malignant deep brain stimulation-withdrawal syndrome in a patient with Parkinson's disease

Authors: Janina Neuneier MD1,*, Michael T. Barbe MD1,2, Christian Dohmen MD1, Mohammad Maarouf MD3, Jochen Wirths MD3, Gereon R. Fink MD1,2, Lars Timmermann MD1,*

Article first published online: 15 JUL 2013
DOI: 10.1002/mds.25494

© 2013 International Parkinson and Movement Disorder Society

Author Information

1 Department of Neurology, University Hospital Cologne, Cologne, Germany
2 Institute for Neuroscience and Medicine (INM-3), Cognitive Neuroscience, Research Center Juelich, Juelich, Germany
3 Department of Stereotaxy and Functional Neurosurgery, University Hospital Cologne, Cologne, Germany

*Correspondence to: Dr. J. Neuneier, Department of Neurology, University Hospital Cologne, Kerpener Str. 62, 50937 Cologne, Germany;; and Dr. L. Timmermann, Department of Neurology, University Hospital Cologne, Kerpener Str. 62, 50937 Cologne, Germany;

Relevant conflicts of interest/financial disclosures: Nothing to report.

Deep brain stimulation (DBS) is a well established therapeutic option for patients with advanced Parkinson's disease (PD).[1] Recent publications report promising long-term results concerning the efficacy and safety of DBS after 5 years.[2] Furthermore, a sustainable stimulation-induced improvement of motor functions and an enduring reduction of dopaminergic medication were reported in a single-center, 10-year follow-up study.[3] However, complications, such as hardware infection, psychiatric side effects, technical problems, or battery depletion, may occur in a considerable number of patients.[4] Here, we report a previously undescribed “malignant DBS-withdrawal syndrome” after battery depletion as a possible complication of DBS therapy in a patient with PD.


A man aged 77 years with advanced PD was admitted to our center because of a subacute aggravation of tremor and rigidity. He had been diagnosed with PD in 1994 and had been treated with bilateral DBS of the subthalamic nuclei (STN) since February 2007. An excellent effect on motor symptoms, especially tremor, was observed after implantation of the electrodes (United Parkinson's Disease Rating Scale, part III [motor subscale]: DBS off and medication off, 43 of 108 points; DBS on and medication on, 29 of 108 points). Subsequently, the symptoms remained almost stable for 60 months. Further diagnoses comprised essential hypertension and coronary heart disease (myocardial infarction, 1992; coronary stenting, 2002; coronary bypasses, 2009).

At the most recent admission, a total battery depletion of the impulse generator (IPG) was detected. Because of an increased risk of bleeding associated with co-medication with aspirin 100 mg daily, the exchange of the IPG was postponed. Hence, the dose of dopaminergic medication was sharply increased (levodopa [l-dopa] 150–1000 mg daily) over the following days. On day 6, small erysipelas appeared on the right leg, associated with slightly elevated C-reactive protein (CRP) (see Fig. 1), but the leukocyte count and procalcitonin levels were normal. This minor skin infection was treated immediately with systemic antibiotics (piperacillin plus tazobactam 4.5 g 3 times daily) to ensure that no systemic infection could adversely affect the urgent need to change the IPG. The clinically visible inflammation as well as the CRP level promptly decreased. Nevertheless, the clinical condition worsened dramatically over the days that followed: tremor and rigidity could no longer be controlled by oral dopaminergic medication, the patient developed hyperthermia up to 41°C and elevated serum creatine kinase (up to 1642 U/L; reference value, < 190 U/L) was detected. In addition to fluid management, intravenous amantadine (600 mg daily) and paracetamol (acetaminophen)/metamizole were added to the treatment, which still did not sufficiently control the symptoms. In particular, the hyperthermia was barely controlled either pharmacologically or by external cooling with ice packs. At day 10, the IPG was exchanged and activated using the former stimulation parameters; however, stimulation was unable to stabilize the clinical course. The patient kept developing high temperatures despite pharmacologic and physical interventions. No other reasons for the hyperthermia, e.g. a persistent systemic infection or medication-induced fever, could be detected. On the following day, the condition deteriorated to multiorgan failure with disseminated intravascular coagulation, finally resulting in a lethal outcome despite intensive care treatment.

image Figure 1. Body temperature and C-reactive protein (CRP) are illustrated over time. The start of antibiotics was on day 6 (arrow).


Severe complications may occur with DBS, especially around the time of the IPG exchange, and must be considered carefully.[5] A dramatic worsening in PD symptoms after acute DBS failure has been described previously as a rebound phenomenon, with poor response to a compensatory increase of oral dopaminergic medication. However, further clinical deterioration can usually be prevented by early surgical intervention.[6] In this case report, we present the tragic full picture of a novel syndrome after acute withdrawal of DBS, defined by a refractory akinetic crisis with massive impairment of motor function as well as central hyperthermia and rhabdomyolysis (elevated serum creatine kinase). A similar combination of symptoms with an equally dramatic course has been described as a malignant l-dopa withdrawal syndrome, which was observed after a drastic reduction in dopaminergic medication.[7, 8] To date, a full understanding of the pathophysiology is lacking; nevertheless the 2 syndromes seem to be closely related, because both involve the sudden removal of external stimulation of central dopaminergic pathways. Because of this analogy, we suggest calling this novel syndrome “malignant DBS-withdrawal syndrome.”

Sudden DBS withdrawal is a rare but life-threatening complication in patients with PD who are receiving DBS. In our patient, all symptoms, especially the hyperthermia, responded very poorly to medication and physical treatment, eventually leading to multiorgan failure with a lethal outcome. It seems unlikely that the fever was caused by a sepsis, because the leukocyte count and procalcitonin levels were normal throughout the course, whereas the CRP level and the clinical appearance of the minor skin infection quickly decreased under appropriate antibiotic treatment. Furthermore, a medication-induced fever is rather unlikely, because we only introduced antibiotics and increased the dopaminergic medication. We hypothesize that the lethal course of our patient was eventually caused by a heatstroke-like multiorgan failure due to the refractory high fever.

An early exchange of the IPG seems to be the best treatment. Our case strongly suggests that any postponement because of co-medication with antithrombotic agents or anticoagulants or a concomitant infection should be considered with great caution, and the decision should be made on an individual basis. It emphasizes that potential complications from excessive bleeding because of aspirin or clopidogrel intake are clearly outweighed by the potential worsening of the PD status if no surgical intervention is performed. An early involvement of intensive care seems advisable, especially to cope with the hyperthermia, for example by endovascular cooling of the body.

In summary, we suggest that the malignant DBS-withdrawal syndrome may be considered a rare but severe complication in patients with PD who receive STN-DBS. Because the current long-term experience in this field is still limited, we suspect that this syndrome may occur more frequently in the future.


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Jens Volkmann MD, PhD*

Article first published online: 25 OCT 2013
DOI: 10.1002/mds.25666

© 2013 International Parkinson and Movement Disorder Society

Author Information

Department of Neurology, University Clinic of Würzburg, Germany

*Correspondence to: Prof. Jens Volkmann, Department of Neurology, University Clinic of Würzburg, Josef-Schneider-Strasse 11, D-97080 Würzburg, Germany;

Relevant conflicts of interest/financial disclosures: Nothing to report.

This patient had an excellent response to DBS therapy for the initial 4 years, but experienced a first episode of status dystonicus after depletion of the left internal pulse generator (IPG), which was successfully terminated by an immediate IPG exchange. One year later, battery failure of the right IPG resulted in another status dystonicus with subsequent complications, which required intensive care treatment. Unfortunately, the patient never returned to his independant postoperative state despite immediate surgical restoration of bilateral DBS. This case is remarkable for two reasons: (1) Dystonic storm is the most relevant serious adverse event of long-term neurostimulation in dystonia, because it may result in permanent disability after a complicated course despite rapid restitution of effective DBS therapy. (2) The case illustrates that even unilateral failure of DBS in patients with generalized dystonia can result in life-threatening dystonic storm. This observation questions the common clinical practice of implanting two single-channel DBS systems in patients with severe dystonia to avoid a possible simultaneous bihemispheric failure of dual-channel systems. Any uncontrolled cessation of stimulation, even unilateral, should be avoided in these patients, and regular monitoring of the battery status is essential in the long-term care of DBS-treated dystonia patients to plan IPG exchanges.