Deep brain stimulation (DBS) has been increasingly used as a therapeutic approach for patients with advanced Parkinson’s disease (PD). This involves the stereotactic implantation of unilateral or bilateral deep brain electrodes followed by the subcutaneous placement of a pulse generator in the chest wall. As surgical methodologies have advanced, complications such as intracranial hemorrhage and infections have become less frequent. However, some complications persist. In this article, we describe an unprecedented case of allergic encephalitis following DBS in a patient diagnosed with advanced PD.

The patient, a 68-year-old man who denied a previous allergic reaction, with a long-standing 15-year history of PD, manifested a progressive deterioration of motor function over two years, despite rigorous pharmacological interventions. Due to pronounced motor fluctuations and intolerance to medications, the decision was made to pursue DBS, and the preoperative magnetic resonance imaging (MRI) evaluation of the brain was normal. In October 2018, he successfully underwent bilateral subthalamic nucleus electrode implantation, followed by implantation of a DBS pulse generator on the left chest wall three days later. The pulse generator was turned on one month after implantation. The system was an Activa PC DBS system (Medtronic, Taipei, Taiwan). However, repeated surgical interventions were required over the subsequent 5 months due to persistent inflammation at the pulse generator site, culminating in its removal. Histopathological evaluations revealed a chronic inflammatory response.

In October 2022, the patient demonstrated symptoms of progressive aphasia, impaired gait, and fluctuating levels of consciousness. A noncontrast cranial computed tomography scan revealed bilateral hypodensities accompanied by edematous changes proximal to the DBS electrodes. MRI revealed previous hemorrhagic events or possible abscess formation (Figure 1). Analysis of cerebrospinal fluid (CSF) from lumbar puncture revealed elevated protein concentrations, while glucose and LDH levels remained within normal ranges. Further panels for viral meningitis, cryptococcal antigens, and leukocyte count in the CSF were unremarkable. Furthermore, blood test indicators, such as erythrocyte sedimentation rate (17) and C-reactive protein (0.03 mg/dL), were also within normal limits. Given the precedent of a possible allergic event and potential infection, the decision was made to surgically remove the bilateral DBS electrodes in November 2022. The subsequent pathological evaluation revealed chronic inflammation with little eosinophil infiltration and little granulomatous change, suggesting an allergic etiology rather than an infectious source. The following IV steroid regimen was used: dexamethasone (5 mg every 8 hours to every 12 hours), which was subsequently altered to an oral form of 1 tablet every 12 hours, followed by a course of oral prednisolone (2 tablets twice daily), which was withdrawn within two weeks. In addition, PD medication regimens were also gradually added. After treatment, his neurological status improved, leading to outpatient transition. Subsequent MRI 5 months later revealed receding bilateral thalamic inflammation with residual minor lesions (Figure 1). The symptoms were almost resolved, and the patient returned to baseline activity without any evident neurologic problems.

The evolution of the neurosurgical apparatus has substantially improved clinical outcomes while simultaneously minimizing adverse events. However, DBS inherently poses risks, encapsulating both perioperative and postoperative complications that require rigorous supervision [1,2]. Standard complications arise from the integration of nonbiological materials, resulting primarily in infections at the pulse generator, the connector site, or the scalp. The surgical procedure also has hemorrhagic potential, with 5% of patients developing asymptomatic intracranial or intraventricular hemorrhages [2].

Although such complications are meticulously documented, certain adverse effects related to neuromodulation devices remain less recognized. Allergic reactions, commonly manifesting as localized pruritus and erythema, may be incited by constituents such as titanium, silicone, and polyurethanes [3]. In particular, Brown et al. [3] identified only one allergic presentation among 13 DBS recipients, located at the impulse generator site on the chest wall. However, the literature is devoid of reports of intracranial allergic reactions or encephalitis associated with DBS. Intriguingly, in the present case, the magnetic resonance findings revealed hyperintensities of T1 and T2 along the polyurethane-containing leads, which could elucidate this distinctive cerebral manifestation.

The pathogenesis of such allergic phenomena may involve host immunization against the introduced devices, thereby activating nonneuronal cells that are instrumental in maintaining the neural microenvironment. In our case, the coexisting material within these devices was polyurethane, which is known to be neurotoxic to animals after its breakdown and could induce a cytokine storm and persistent tissue inflammatory reactions [4-6].

The limitation of this presentation was that we did not complete the autoimmune encephalitis survey. Steroid treatments also have an impact on these populations.

In conclusion, the literature provides little information on brain tissue allergic responses to DBS, and the majority of evidence is extrapolated from animal models. This case accentuates the need to understand that allergic sensitivities can occur not only in peripheral tissues but also the central nervous system. Future studies are indispensable to further delineate this phenomenon, and increased vigilance may be necessary when other bodily regions exhibit allergic manifestations.

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