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CC BY-NC-ND 4.0 · Asian J Neurosurg
DOI: 10.1055/s-0045-1811606
Case Report

Transient Perioperative Aggressive Behavior during Subthalamic Nucleus Deep Brain Stimulation for Parkinson's disease

Paulo Cataniag 
1   Movement Disorders Clinic, MakatiMed Institute of Neurological, Neurosurgical and Behavioral Sciences (M.I.N.D.S.), Makati City, Philippines
2   Department of Neurosciences, Baguio General Hospital and Medical Center, Baguio City, Philippines
,
Jed Noel Ong 
1   Movement Disorders Clinic, MakatiMed Institute of Neurological, Neurosurgical and Behavioral Sciences (M.I.N.D.S.), Makati City, Philippines
,
Rosalia Teleg
1   Movement Disorders Clinic, MakatiMed Institute of Neurological, Neurosurgical and Behavioral Sciences (M.I.N.D.S.), Makati City, Philippines
4   Cardinal Santos Medical Center, San Juan City, Metro Manila, Philippines
5   University of the Philippines, Philippine General Hospital, Manila, Philippines
,
Anthony Piano
3   Asian Brain Institute, Asian Hospital and Medical Center Muntinlupa City, Philippines
,
Carmina Charmaine Bernardo
1   Movement Disorders Clinic, MakatiMed Institute of Neurological, Neurosurgical and Behavioral Sciences (M.I.N.D.S.), Makati City, Philippines
,
Rachelle Holandez
1   Movement Disorders Clinic, MakatiMed Institute of Neurological, Neurosurgical and Behavioral Sciences (M.I.N.D.S.), Makati City, Philippines
,
Jean Quint Oropilla
1   Movement Disorders Clinic, MakatiMed Institute of Neurological, Neurosurgical and Behavioral Sciences (M.I.N.D.S.), Makati City, Philippines
3   Asian Brain Institute, Asian Hospital and Medical Center Muntinlupa City, Philippines
,
Cid Czarina Diesta
1   Movement Disorders Clinic, MakatiMed Institute of Neurological, Neurosurgical and Behavioral Sciences (M.I.N.D.S.), Makati City, Philippines
3   Asian Brain Institute, Asian Hospital and Medical Center Muntinlupa City, Philippines
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Abstract

Deep brain stimulation of subthalamic nucleus (STN-DBS) is recognized as the gold standard for symptomatic treatment of advanced Parkinson's disease (PD). However, despite adherence to screening protocol, perioperative neuropsychiatric complications are increasingly being recognized. The rapid development of psychiatric symptoms within less than 24 hours is rare, and acute episodes occurring during surgery are uncommon. We present a 57-year-old female patient diagnosed with PD, with good premorbid personality. However, mild depression was detected on neuropsychological assessment. After thorough deliberation and family meeting, patient was cleared to undergo STN-DBS as the expected benefits outweighed the potential risks. Intraoperatively, during microstimulation of the left STN, patient developed sudden onset of aggressive behavior. The behavioral change lessened when the DBS lead location was adjusted to a more lateral location. The psychiatric symptoms were then controlled with quetiapine until the behavioral changes had resolved after 7 days. No recurrence was noted during follow-up consults.This case report confirms the importance of fundamental knowledge and understanding of the neuroanatomical structures affected in DBS of the STN, and their clinical implications. A thorough preoperative psychiatric evaluation is essential for comprehensive management and allows anticipation of possible adverse events.


 

Keywords

Parkinson's disease - deep brain stimulation - subthalamic nucleus - psychiatric complication

Background

Deep brain stimulation (DBS) of subthalamic nucleus (STN) has revolutionized Parkinson's disease (PD) management. It has been recognized as a gold standard for treatment of advanced PD.[1] [2] This procedure allows the reduction of levodopa dose, ameliorates side effects associated with levodopa use, and improves motor and nonmotor symptoms of PD.[1] DBS lead implantation is a safe surgical procedure with surgery-related complications that are usually mild and reversible.[3]

However, postoperative neuropsychiatric complications after STN-DBS implantation are being reported. These can include a broad range of manifestations, such as mood disorders, impulsive behaviors, apathy, and cognitive dysfunction.[4] The most recently published systematic review of selected studies over the past 10 years revealed that depression was the most common psychiatric disorder after STN-DBS.[5] The stimulation of the limbic STN and the propagation of electricity to adjacent structures during DBS has been acknowledged as a likely cause of these unintended behavioral outcomes.[6] [7]

Majority of papers in the literature state that these psychiatric complications were noted several days, weeks, and even months after DBS. Acute development (< 24 hours) of psychiatric symptoms is rare, and intraoperative acute episodes are very uncommon.[8] Hence, we report a case of an acute intraoperative aggressive behavior of an adult female during STN-DBS for PD.


 

Case Description

Clinical History and Examination Findings

A 57-year-old, right-handed, Filipino female housewife was admitted for scheduled DBS of bilateral STN. This was 11 years after her initial PD diagnosis. She first presented with gait difficulties, followed by softening of voice, slowness of movements, and mild tremor and stiffness of all limbs. Levodopa-induced choreiform dyskinesias initially appeared on the 6th year of illness. Patient had no history of psychiatric illness, nor intake of any psychiatric medications and illicit drug use. There was no family history of epilepsy, psychiatric disorders, and movement/neurodegenerative disorders.

The patient is described as pleasant, cooperative, and invested in her medical encounters, with no inappropriate behavior noted. Her relatives characterized her as strong-willed, and her personality has remained relatively stable. However, she experiences anger during misunderstandings about her medication intake and occasional crying spells during the wearing off of levodopa. Her daughter manages her medications due to a tendency to exceed the prescribed dose. The patient has a history of physical and emotional trauma from a difficult marital relationship, which occasionally leads to tears when discussing family conflicts and her condition's challenges.

A presurgical neuropsychological evaluation revealed mild levels of depression based on the Hamilton Depression (HAM-D) scale. However, no antidepressive medication was warranted at this point. In addition, no signs of dementia were detected, albeit mild impairments in visuo-perception, memory, word finding ability, and executive functioning.

By the time of surgery, she had extremity and body bradykinesia, rigidity (lower more than upper extremities), postural instability, persistent right truncal flexion, and painful choreoballistic dyskinesias. Her Unified Parkinson's Disease Rating Scale (UPDRS) Part III motor score was 40. Hoehn and Yahr score was 4. Montreal Cognitive Assessment (MoCA) score was normal at 27. Prior to DBS, medication regimen included levodopa/carbidopa (1,200 mg/day), biperiden, amantadine, and melatonin.


 

DBS Procedure and Intraoperative Aggressive Behavior

Patient was cleared to undergo DBS despite the findings of mild depression on HAM-D.

Considering her substantial disability, the potential benefits of DBS outweighed the possible risks. STN was selected as the DBS target to improve her motor symptoms and to allow substantial reduction of her medication dosage. A meeting was arranged to align the expectations of both the patient and her family.

Conscious sedation was done during the insertion of six in-bone fiducials for NexFrame (Medtronic Inc.,) registration. Preoperative magnetic resonance imaging was obtained and overlapped with a stereotactic computed tomography (CT) scan for registration. Bilateral implantation of STN-targeted DBS used initial coordinates chosen using a standard anterior commissure-posterior commissure–based coordinates, and coordinates relative to the borders of the red nucleus. Two guide cannulas were passed on each side ([Fig. 1A–D]).

Zoom
Fig. 1 Coregistration of coronal (A), sagittal (B), and axial (C) reconstruction from preoperative magnetic resonance imaging (MRI) with computed tomography (CT) scan and automatic identification of right (yellow line) and left (green line) deep brain stimulation (DBS) leads, revealing the final location of DBS implants. Theoretical anatomic reference is superimposed on the axial cut (D). Final planned coordinates were [x, y, z]: [+110.0, +87.6, +129.5 mm] on the left and [+86.0, +87.9, +129.3] on the right, relative to mid commissural point and the anterior commissure-posterior commissure (AC-PC) plane.

On the left, STN-like cellular activity was recorded from 4.5 mm above to 3.5 mm below the target, with modulation of firing rates with passive joint movement of the upper and lower extremity. Macrostimulation through a DBS electrode placed with its distal contact at 4.5 mm below target improved rigidity. On the right, STN activity spanned 4.5 mm above to 4 mm below target, with modulation with passive movement of the right upper extremity. On this side also, the DBS lead was placed with distal contact 4.5 mm below target, with rigidity improvement during stimulation.

Microstimulation of the left STN at 3.5 to 4.5 V triggered an unexpected change in behavior. The patient suddenly became angry and agitated, raising her voice while crying and verbally lashing out at the movement neurologists assessing her during surgery. She refused to follow commands and needed to be restrained as she attempted to break free. The patient tightly squeezed the hands of the examiners and displayed a tense facial expression throughout the episode, which lasted approximately 15 to 20 minutes. Her aggressive behavior was disproportionate to any apparent stressors present at that time. Despite her agitation, she remained alert and answered the examiners' questions correctly. Her pupils were equally round and responsive to light, and there were no seizure-like movements observed. Due to the aggressive episode and limitations within the surgical environment, further clinical examination could not be conducted. Verbal consent was obtained from the relatives prior to continuing the procedure.

The DBS lead placement in the left STN was adjusted to a more lateral position. Repeated stimulation led to a reduced level of behavioral changes. No further worsening of aggressive behavior was observed during placement of lead in the right STN. There was optimal control of all parkinsonian features in each contact bilaterally. The quadripolar DBS electrodes (Activa RC 37612; Medtronic Inc., Minneapolis, Minnesota, United States) were then connected to an implantable pulse generator (Activa PC; Medtronic).


 

Postoperative Recurrence of Behavioral Changes

After awakening from anesthesia, the patient was talkative and irritable. Cranial CT scan confirmed proper lead placement ([Fig. 2A–C]) with some pneumocephalus noted ([Fig. 2D]). Blood test results were unremarkable. On the first postoperative day, she was aggressive toward the medical staff, was disoriented, and accused her daughters of theft. Quetiapine treatment started at 12.5 mg was ineffective until the dosage was raised to 50 mg, which led to improvement. All psychiatric symptoms resolved by day 7, and the patient was discharged from the hospital.

Zoom
Fig. 2 Computed tomography scan displaying the implanted permanent lead in the bilateral subthalamic nucleus (STN) (arrows) on coronal (A), sagittal (B), and transverse (C) sections. Image D shows the pneumocephalus over the bifrontal lobes.

 

 

Initial DBS Programming

At home and during the initial programming at 1 month, the patient experienced no recurrence of behavioral changes. Stimulation began at contact 9 in the right STN and contact 1 in the left STN, yielding the best motor outcomes. The stimulation amplitudes were set to 0.5 mA for the right electrode and 1.5 mA for the left, with pulse width of 60 usec and frequency of 140 Hz. Continuous bilateral stimulation improved parkinsonian motor disability, although the levodopa equivalent daily dose remained similar. The patient showed no behavioral changes during stimulation adjustments. Throughout follow-up visits at the Movement Disorders Clinic and at home, there were no aggressive behaviors, and her psychiatric evaluation was normal. Quetiapine was gradually reduced and eventually discontinued.


 

Discussion

We present the case of an adult female living with PD for 11 years who experienced a sudden onset of anger and aggressive behavior during DBS of the bilateral STN. The behavioral changes persisted postoperatively until resolving after 7 days.

The rapid development of psychiatric symptoms within less than 24 hours is rare, and acute episodes occurring during surgery are uncommon.[8] Few cases have been reported to develop depressive and psychotic symptoms soon after initiation of DBS stimulation.[9] [10] Acute intraoperative aggressive behavior during STN stimulation procedure, just like in our case, has also been described in case reports,[11] [12] and also explored in larger studies.[13] [14]

The STN has become a target for DBS in PD to modulate its firing patterns and improve clinical manifestations. It is a compact structure with a biconvex lens shape located between the thalamus and midbrain, ventral to the zona incerta and adjacent to the substantia nigra.[15] STN has shown to have dorsolateral sensorimotor, medial limbic, and ventromedial (or central) cognitive–associative regions, forming the so-called tripartite model of STN.[16] [17] The behavioral and cognitive changes are thought to be caused by unintended stimulation of the limbic SNT, which has connections to emotion-regulating regions such as the orbitofrontal cortex, anterior cingulate cortex, and amygdala.[18]

Studies confirmed the anatomical basis for psychiatric manifestations, which were found to be more frequent or severe when electrodes were positioned more medially or anteriorly in the STN.[19] [20] [21] This observation was also applicable to our patient, where aggressive behavior improved after the left STN lead was repositioned more laterally.

Previous reports have attributed the following factors as responsible to the onset of mood changes: (1) microlesional effects during neurosurgery[22]; (2) amplitude (voltage) of stimulation[23]; (3) position of the active electrode contact within the STN[24]; and (4) current spread to passing fibers and/or neighboring structures responsible for limbic manifestations.[12]

In our patient's situation, the aggressive behavior might be related to the positioning of the lead and stimulation of the limbic STN, as evidenced by the clinical improvement following the lead's repositioning. Meanwhile, the persistence of behavioral changes for 2 weeks after DBS was possibly due to lesioning effect or perilesional edema.


 

Conclusion

This case report emphasizes the significance of understanding the neuroanatomy of DBS targets and their clinical implications. Prompt adjustments to address potential neuropsychiatric complications can significantly impact DBS outcomes. A thorough preoperative psychiatric evaluation is essential for comprehensive management. The DBS team should communicate goals and expectations clearly with patients and their families, considering that psychiatric manifestations are possible complications and may arise from multiple factors.


 

 

Conflict of Interest

None declared.

Authors' Contributions

P.C. contributed to the conception, organization, and execution of the research project and drafted the first version of the manuscript. J.N.O. participated in the conception, organization, and execution of the research project and critically reviewed the manuscript. R.T., A.P., C.C.B., and R.H. contributed to the critical review of the manuscript. J.Q.O. was involved in the conception, organization, and execution of the research project and critically reviewed the manuscript. C.C.D. contributed to the conception, organization, and execution of the research project and also reviewed the manuscript critically.


Ethical Approval

This case report was conducted in accordance with ethical standards and was approved by the Institutional Review Board of Makati Medical Center (MMCIRB2025–05–77-EXEMPTED). Patient consent was obtained for publication of this case report.



Address for correspondence

Cid Czarina Diesta, MD
Movement Disorders Clinic, MakatiMed Institute of Neurological, Neurosurgical and Behavioral Sciences (M.I.N.D.S.)
Makati City
Philippines   

Publication History

Article published online:
25 September 2025

© 2025. Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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Zoom
Fig. 1 Coregistration of coronal (A), sagittal (B), and axial (C) reconstruction from preoperative magnetic resonance imaging (MRI) with computed tomography (CT) scan and automatic identification of right (yellow line) and left (green line) deep brain stimulation (DBS) leads, revealing the final location of DBS implants. Theoretical anatomic reference is superimposed on the axial cut (D). Final planned coordinates were [x, y, z]: [+110.0, +87.6, +129.5 mm] on the left and [+86.0, +87.9, +129.3] on the right, relative to mid commissural point and the anterior commissure-posterior commissure (AC-PC) plane.
Zoom
Fig. 2 Computed tomography scan displaying the implanted permanent lead in the bilateral subthalamic nucleus (STN) (arrows) on coronal (A), sagittal (B), and transverse (C) sections. Image D shows the pneumocephalus over the bifrontal lobes.