Chromatographic and Spectrometric Evaluation of Extractables and Leachables from Polyurethane-Insulated Deep Brain Stimulation Probes

Deep brain stimulation involves several neurological conditions in which implantable leads deliver electrical impulses to specific brain regions. Although biocompatibility testing is necessary for regulatory approval, leachables (chemical compounds that migrate from medical devices into the surrounding brain tissue or medium) have not yet been identified. This has inspired a study which has inspired a study investigating extractables (chemical compounds that migrate from manufacturing components, container closure systems, or medical devices when exposed to an appropriate solvent under exaggerated or harsh conditions) and leachables from polyurethane (PU)-insulated DBS probes, shedding light on their safety in clinical contexts. Analyses were performed via gas and liquid chromatography (GC and LC, respectively) coupled with mass spectrometry (MS) and via inductively coupled plasma (ICP). A paper based on the study was published in Scientific Reports.¹

DBS is a breakthrough surgery that helps treat conditions like severe Parkinson's disease, tremors, and dystonia. It works by placing tiny, flexible wires deep inside the brain that send controlled electrical pulses to help calm and regulate brain activity.² While clinical effectiveness has been demonstrated to enhance the quality of life of patients,^3-5 there are a variety of side effects which may occur, including dysarthria, gait disorders and behavioral disorders.⁶ The implanted wire (or electrode) associated with DBS has a few electrical contact points at its tip. To make sure it is completely safe for the human body, it goes through strict testing before being approved for use. Made from durable metals and special plastics, these wires are designed to stay securely inside the brain for the patient's entire life.⁷ For this reason, the authors of the paper state,¹ “the study of leachables from DBS probes should be of upmost importance in evaluating their safety, particularly the biocompatibility of these medical devices.”

The researchers placed two types of PUs, polyether (PEU) and polycarbonate urethane (PCU), in contact with a brain phantom for 180 days at 37 °C. An extraction was then performed using acetone and n-hexane on parts that were or were not in contact with the phantom to establish extractable profiles and to estimate leachable migration in the phantom. In addition to the chromatography and spectrometry analyses performed, surface characterization was performed before and after contact to explain the differences in leachable migration between both PEU and PCU.¹

The researchers identified extractables and potential leachables from PEU and PCU implantable DBS probes by comparing the extractable profiles before and after contact with a brain phantom. The extraction and quantification of 4,4’-MDI, a suspected carcinogenic chemical, revealed a remarkable decrease in both polymers after 180 days of contact, but was more important in the PEU than in the PCU. Signals consistent with the presence and possible redistribution of aluminum containing additives within the polymers were also observed.¹

“While EDS revealed a higher relative aluminum signal at the surface of PCU after contact,” write the authors of the paper,¹ “this observation suggests a distinct surface exposure or redistribution profile of inorganic additives compared to the polymer matrix. Bulk extractable analysis by inductively coupled plasma optical emission spectroscopy (ICP-OES) suggested a more pronounced aluminum loss in PEU, which may be consistent with its higher susceptibility to degradation compared with PCU. These results need to be strengthened by analyzing leachables directly in the brain phantom to confirm those results.”¹

The researchers believe that future studies combining direct simulant analysis with targeted methods addressing transformation pathways and release kinetics are necessary before any toxicological extrapolation can be made.¹

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References

1. Bouattour, Y.; Pinguet, J.; Bourgogne, D. et al. Screening for Compounds Released from Deep Brain Stimulation Probes by Contact with a Brain Simulant. Sci Rep. 2026.DOI: 10.1038/s41598-026-46292-5
2. 2.Benabid, A. L.; Pollak, P.; Louveau, A. et al. Combined (Thalamotomy and Stimulation) Stereotactic Surgery of the VIM Thalamic Nucleus for Bilateral Parkinson Disease. Appl Neurophysiol. 1987, 50 (1-6), 344-346. DOI: 10.1159/000100803
3. Koller, W. C.; Lyons, K. E.; Wilkinson, S. B. et al. Efficacy of Unilateral Deep Brain Stimulation of the VIM Nucleus of the Thalamus for Essential Head Tremor. Mov. Disord. Off. J. Mov. Disord. Soc. 1999, 14, 847–850. DOI: 10.1002/1531-8257(199909)14:5<847::aid-mds1021>3.0.co;2-g
4. Ondo, W.; Jankovic, J.; Schwartz, K. et al. Unilateral Thalamic Deep Brain Stimulation for Refractory Essential Tremor and Parkinson’s Disease Tremor. Neurology 1998, 51, 1063–1069. DOI: 10.1212/wnl.51.4.1063
5. Rehncrona, S. et al. Long-Term Efficacy of Thalamic Deep Brain Stimulation for Tremor: Double-Blind Assessments. Mov. Disord. Off. J. Mov. Disord. Soc. 2003, 18, 163–170. DOI: 10.1002/mds.10309
6. Zarzycki, M. Z.; Domitrz, I. Stimulation-Induced Side Effects After Deep Brain Stimulation – A Systematic Review. Acta Neuropsychiatr.2020, 32, 57–64. DOI: 10.1017/neu.2019.35
7. Chapelle, F. et al. Early Deformation of Deep Brain Stimulation Electrodes Following Surgical Implantation: Intracranial, Brain, and Electrode Mechanics. Front. Bioeng. Biotechnol. 2021, 9, 422. DOI: 10.3389/fbioe.2021.657875