Cystic Lesions as a Rare Complication of Deep Brain Stimulation

Abstract

DBS is a typically well‐tolerated operation for treatment of Parkinson's disease, dystonia, and essential tremor (ET). Complications related to the surgical procedure and implanted hardware may occur. More commonly reported complications include hemorrhage, seizure, confusion, and infection. In this article, we report on a rare, but important, complication of DBS surgery, a brain cyst formation at the tip of the implanted ventralis intermedius nucleus (VIM) DBS lead in 2 patients who underwent the procedure at 2 different centers. The indication for surgery was debilitating ET, and in both cases, there was development of a delayed‐onset neurological deficit associated with an internal capsule/thalamic cystic lesion formation located at the tip of the DBS lead. Case 1 presented within a few months post‐DBS, whereas case 2 had a 10‐mo delay to onset of symptoms. No clinical and radiological signs of infection were observed and both DBS systems were explanted with uneventful recovery.

DBS is an effective adjunctive therapy for selected patients with movement disorders, including Parkinson's disease (PD), dystonia, and essential tremor (ET). DBS surgery is considered reasonably safe; however, complications related to the surgical procedure and implanted hardware may occur. More commonly reported complications include hemorrhages, infarcts, seizures, confusion, and infections.1, 2 Complication rates vary in literature, and the overall risk has been considered minimal, especially in appropriately screened and selected patients.1, 2 Here, we present 2 cases of cyst formation at the tip of implanted DBS leads; 1 subacute presentation and 1 chronic presentation.

Patients and Methods

All of the DBS cases implanted at University of Texas Southwestern (UTSW) and at University of Florida (UF) between July 2002 and June 2014 were reviewed on the database, and 2 cases associated with formation of a cyst at the tip of the ventralis intermedius nucleus (VIM) DBS lead were identified. Case 1 was from UTSW, and case 2 from UF among 664 and 1027 lead implantations, respectively. Both cases were identified because the 2 patients developed new‐onset neurological deficits.

Results

Case 1

A 71‐yr‐old left‐handed man with a past medical history of diabetes, hypertension, and a 16‐yr history of ET was evaluated for DBS surgery. He was taking propranolol 160 mg 3 times a day (TID), primidone 250 mg TID, and gabapentin 300 mg TID. His tremors were refractory to medications and were interfering with daily activities. After a complete interdisciplinary DBS evaluation, he was considered an appropriate candidate for DBS surgery. He had bilateral VIM DBS implanted with intraoperative microelectrode recording (MER) assistance. Three simultaneous MER tracks were used on each brain hemisphere. No intraoperative complications were reported. An immediate postoperative CT scan revealed appropriate placement of the DBS leads with no acute abnormality. He developed mild dysarthria and gait imbalance the day after DBS surgery, but there was complete resolution of these 2 symptoms within 24 hr. He reported no new symptoms at his initial DBS programming visit, which occurred 3 weeks later, and the tremor had near complete suppression on stimulation. At postoperative week 6, he awoke with new‐onset dysarthria, left arm weakness, ataxia, and gait imbalance. On evaluation, he was afebrile and his cognition was intact. His laboratory workup, including complete blood count (CBC), C‐reactive protein, erythrocyte sedimentation rate, was normal. He had left hemibody weakness, left arm ataxia, and mild gait ataxia. He had no tremor in his left hand and a mild tremor in his right hand. A CT scan revealed a new hypodensity area in the right thalamocapsular region, with a mass effect impinging on the right lateral ventricle. The right thalamic stimulator was turned off; however, the tremor remained completely suppressed even in OFF stimulation. An MRI revealed a cystic lesion 18 × 16 mm, with a T1 hypointense and T2 hyperintense signal located at the right distal DBS lead tip. There was surrounding increased fluid‐attenuated inversion recovery (FLAIR) signal. There was no restricted diffusion or enhancement with gadolinium contrast (Fig. 1A–D). His symptoms gradually improved over several days. During a clinic visit 2 weeks later, he reported no worsening of symptoms, but continued to report difficulty with walking and weakness in his left foot. A repeat MRI revealed enlargement of the cyst, which increased in size to 22 × 28 mm with no restricted diffusion or enhancement after contrast administration (Fig. 1E,F). He underwent surgery to remove the right thalamic lead. A follow‐up MRI at 6 mo revealed a marked decrease in size of the cyst to 10 × 4 mm with resolution of the increased FLAIR signal (Fig. 1G,H). The patient is doing well without any complications after surgery. He has slight reoccurrence of left hand tremor, but continues to maintain hand functionality.

Figure 1.

Case 1. Brain FLAIR MRI image (A), T1 postcontrast (B), SWI (C), and diffusion‐weighted imaging with no restricted diffusion (D). MRI after 2 weeks and 6 mo showing enlargement (E and F) and involution of cyst (G and H), respectively.

Case 2

A 61‐yr‐old right‐handed man was evaluated for a 15‐yr history of bilateral medication refractory ET. He had a past history of anxiety, RLS, depression, hypertension, and coronary artery disease. He was taking primidone 100 mg TID, duloxetine 60 mg daily, aripiprazole 10 mg daily, pramipexole 0.25 mg daily, mirtazapine 30 mg nightly, and zolpidem 10 mg nightly. He reported initially his tremor was not severe and did not impair his ability to function, but over the past 10 yr the tremor increased in severity and became increasingly problematic. After a multidisciplinary DBS evaluation, he was recommended for DBS. He underwent an awake left VIM thalamic DBS implantation with intraoperative MER. A postoperative CT scan, fused with a preoperative MRI, confirmed the appropriate placement of the left VIM thalamic DBS lead (Fig. 2A–C). After a 10‐mo period of excellent right‐sided tremor suppression from DBS therapy, he developed a new‐onset dysarthria associated with a slowly progressive hemiparesis (leg worse than arm). His DBS site was clear with no signs of infection, and laboratory workup showed normal CBC and negative blood cultures. An MRI scan revealed a 21‐mm‐diameter benign‐appearing cyst in the left thalamus adjacent to the DBS lead (Fig. 2D). A trial of conservative management was undertaken with repeat imaging at 3 mo, but the patient reported a gradual progression of his dysarthria with stable hemiparesis. A follow‐up MRI scan revealed a slight increase in size of the cystic lesion in the left thalamus without associated edema or other radiological signs of infection (Fig. 2E–G). The size of the lesion on the latest MRI scan was 24 mm in diameter. The tremor was suppressed even with the DBS turned off. After discussing the risks, benefits, and alternatives, a left VIM thalamotomy was elected by the existing DBS lead, followed by aspiration of the cyst through a ventricular needle and explantation of the DBS lead. The procedure was carried out without complications, but an attempted thalamotomy was unsuccessful because of the presence of fluid in the cyst cavity adjacent to the proposed lesion, and therefore the thalamotomy was aborted. The explanted lead was not cultured because there was no pus or other sign of infection evident during the surgery. The patient was discharged with slight improvement of his symptoms and continued resolution of the tremor, presumably owing to a lesional effect. The patient was contacted several times, but he lost to follow‐up for unclear reasons.

Figure 2.

Case 2. Postoperative CT scan showing no complications (A–C). Ten months postoperative FLAIR MRI showing 21‐mm diameter left thalamic cyst (D). Thirteen months follow‐up contrast T1 (E), fast gray matter acquisition T1 inversion recovery (F), and diffusion‐weighted imaging (G) MRI showing cyst enlargement, without contrast enhancement, no restricted diffusion.

Discussion

These 2 cases demonstrate a rare, but potentially important, complication of DBS surgery. Interestingly, the initial clinical presentations suggested stroke or hemorrhage; however, imaging findings were consistent with structural cystic lesions. Based on the clinical presentation, in the first case it was initially thought that the patient may have possibly experienced a small undetected postoperative hemorrhage leading to formation of a hematoma and resultant edema, which led to evolution of neurological symptoms. The small undetected hemorrhage scenario would be unlikely given that immediate imaging after the surgery did not reveal a hemorrhage, though this could have been obscured by lead artifact. In the second case, there was immediate postoperative imaging 30 days after the procedure, and though there could have been a small resolved hemorrhage, this would have also been unlikely, given that the symptoms evolved many months after the DBS implantation. Early postoperative edema post‐DBS with or without hemorrhage resulting in a transient neurological deficit has, however, been reported, especially subsequent to a venous infarction.3 The imaging in both of our cases ruled out this possibility. Though in our first case there was a rim of low signal on susceptibility‐weighted imaging (SWI) images suggestive of blood products, remaining imaging sequences were not consistent with a hematoma. Additionally, the signal within the cystic cavity was consistent with the cerebrospinal fluid (CSF) signal on all sequences, and enlargement of the cyst on repeat imaging prompted surgical explantation of the lead. Interestingly, case 2 developed delayed neurological deficits after 10 mo of excellent tremor suppression. Given that the postoperative brain CT scan was obtained 1 mo postsurgery and was observed to be normal, this would imply a possible longer delay in development of the DBS‐related cystic cavity and, possibly, a different mechanism of action from case 1. Intracranial infection after DBS surgery was one of the possibilities; however, in both cases, there were no symptoms or signs to suggest infection. On imaging, there was an absence of contrast enhancement and restricted diffusion to suggest abscess formation, and also negative laboratory workup did not support infection as the etiology. Because the suspicion for infection was very low in both cases, DBS lead was not sent for culture. In the first case, resolution of cystic lesion after removal of lead, and the fact that the patient is doing clinically well without treatment with antibiotics, further supports that infection was unlikely. In the second case, the patient lost to follow‐up; but with negative imaging and laboratory workup, our suspicion for infection was low. The reasons for cyst formation in both cases remain speculative.

Ramirez‐Zamora et al. described 2 patients who presented with neurological deficits at 3 and 8 mo after DBS placement for ET and PD, respectively. Both patients developed noninfectious cysts at the tips of the DBS electrodes, and both required surgical removal because of worsening of symptoms. Both cysts resolved after removal of the DBS lead. These investigators suggested that the cause of cyst formation was tracked CSF during placement of the DBS lead or, alternatively, because of an autoimmune or inflammatory response to the DBS hardware.4, 5

Acute brain parenchymal reaction resulting from lead insertion has been suggested as a mechanism for rare findings of low‐attenuation signal around the DBS lead after surgery by Kim et al.6 They described 7 cases of transient increased low‐attenuation signals that circumferentially surrounded DBS electrodes. The signal extended into the subcortical white matter and was associated with unexpected and transient neurological symptoms during the immediate postoperative period. It was suggested that brain parenchymal reaction might be self‐limiting, which resolved in a few weeks, causing resolution of low‐attenuation signal. None of these cases were associated with cysts, and none had long delays before appearance of symptoms as in our case 2. It is possible, though unlikely, that an immunological tissue reaction from implanted lead, which failed to resolve spontaneously, led to cyst formation.

In summary, cyst formation is a potentially rare complication of DBS surgery. Combined, our 2 DBS centers have implanted approximately 1500 DBS leads, and these were the only 2 documented occurrences. Although, the mechanism and risk factors leading to development of cystic lesion remain unclear, clinicians should be aware that this complication may occur in an immediate or in a delayed fashion.

Author Roles

(1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique.

V.D.S.: 1C, 3A

A.R.B.: 1C, 3B

A.M.: 1C, 3B

S.M.: 1C, 3B

P.K.: 1A‐C, 3B

M.P.G.: 3B

K.D.F.: 3B

L.A.W.: 3B

S.C.: 1A, 1B, 3B

M.S.O.: 1A, 1B, 3B

Disclosures

Funding Sources and Conflicts of Interest: The authors report no sources of funding and no conflicts of interest.

Financial Disclosures for preceding 12 months: Dr. Chitnis serves as a consultant for Medtronic and Teva and is a speaker for Teva. Dr. Okun serves as a consultant for the National Parkinson Foundation (NPF) and has received research grants from National Institutes of Health (NIH), NPF, the Michael J. Fox Foundation/MJFF, the Parkinson Alliance, Smallwood Foundation, the Bachmann‐Strauss Foundation, the Tourette Syndrome Association, and the UF Foundation. Dr. Okun has previously received honoraria, but in the past >60 mo has received no support from industry. He has received royalties for publications with Demos, Manson, Amazon, Smashwords, Books4Patients, and Cambridge University Press. He Okun is an associate editor for New England Journal of Medicine Journal Watch Neurology. He has participated in continuing medical education (CME) and educational activities on movement disorders (in the last 36 mo) sponsored by PeerView, Prime, Quantia, Henry Stewart, and by Vanderbilt University. The institution and not Dr. Okun receives grants from Medtronic, AbbVie, and ANS/St. Jude, and the principal investigator (PI) has no financial interest in these grants. Dr. Okun has participated as a site PI and/or co‐investigator for several NIH‐, foundation‐, and industry‐sponsored trials over the years, but has not received honoraria. Dr. Foote has received research support from Medtronic, St. Jude, Boston Scientific, Neuropace, and Functional Neuromodulation. He has received fellowship support from Medtronic. He has received consulting fees from Neuropace for serving on their neurosurgery advisory board. He has received an honorarium from Medtronic for moderating a DBS expert practitioners forum.