ImportanceAn increased risk of Parkinson disease (PD) has been associated with exposure to the solvent trichloroethylene (TCE), but data are limited. Millions of people in the US and worldwide are exposed to TCE in air, food, and water.ObjectiveTo test whether the risk of PD is higher in veterans who served at Marine Corps Base Camp Lejeune, whose water supply was contaminated with TCE and other volatile organic compounds (VOCs), compared with veterans who did not serve on that base.Design, Setting, and ParticipantsThis population-based cohort study examined the risk for PD among all Marines and Navy personnel who resided at Camp Lejeune, North Carolina (contaminated water) (n = 172 128), or Camp Pendleton, California (uncontaminated water) (n = 168 361), for at least 3 months between 1975 and 1985, with follow-up from January 1, 1997, until February 17, 2021. Veterans Health Administration and Medicare databases were searched for International Classification of Diseases diagnostic codes for PD or other forms of parkinsonism and related medications and for diagnostic codes indicative of prodromal disease. Parkinson disease diagnoses were confirmed by medical record review.ExposuresWater supplies at Camp Lejeune were contaminated with several VOCs. Levels were highest for TCE, with monthly median values greater than 70-fold the permissible amount.Main Outcome and MeasuresRisk of PD in former residents of Camp Lejeune relative to residents of Camp Pendleton. In those without PD or another form of parkinsonism, the risk of being diagnosed with features of prodromal PD were assessed individually and cumulatively using likelihood ratio tests.ResultsHealth data were available for 158 122 veterans (46.4%). Demographic characteristics were similar between Camp Lejeune (5.3% women, 94.7% men; mean [SD] attained age of 59.64 [4.43] years; 29.7% Black, 6.0% Hispanic, 67.6% White; and 2.7% other race and ethnicity) and Camp Pendleton (3.8% women, 96.2% men; mean [SD] age, 59.80 [4.62] years; 23.4% Black, 9.4% Hispanic, 71.1% White, and 5.5% other race and ethnicity). A total of 430 veterans had PD, with 279 from Camp Lejeune (prevalence, 0.33%) and 151 from Camp Pendleton (prevalence, 0.21%). In multivariable models, Camp Lejeune veterans had a 70% higher risk of PD (odds ratio, 1.70; 95% CI, 1.39-2.07; P < .001). No excess risk was found for other forms of neurodegenerative parkinsonism. Camp Lejeune veterans also had a significantly increased risk of prodromal PD diagnoses, including tremor, anxiety, and erectile dysfunction, and higher cumulative prodromal risk scores.Conclusions and RelevanceThe study’s findings suggest that the risk of PD is higher in persons exposed to TCE and other VOCs in water 4 decades ago. Millions worldwide have been and continue to be exposed to this ubiquitous environmental contaminant.

Bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective and proven treatment option for patients with advanced Parkinson’s disease (PD). Long-term outcomes (>5 years) have demonstrated sustained improvement in objective motor symptoms; however, few studies have evaluated patient-centered outcomes other than quality of life (QOL). A locally developed DBS-patient-centered outcomes questionnaire was administered to PD patients >5 years post-DBS. All questions were scored on a ten-point scale, whereby 0 represented the most ‘positive’ answer and 10 the most ‘negative’ answer. Pre-operative scales were repeated at the time of survey. Fifty-two patients (mean 8.2 ± 2.6 years post-DBS) were included. Satisfaction was high with median score (range) of 1/10 (0–8) at the time of survey. Patients endorsed having made the correct decision by undergoing DBS, with a score of 0 (0–10), would choose to have DBS again, with a score of 0 (0–10), and would recommend DBS to others, with a score of 0 (0–10). Pre-operative expectation target was set at a high level with a score of 2 (0–10). Parkinson’s Disease QOL (PDQ-39) Questionnaire Summary Index (SI) scores were, mean (SD), 2.1 (18.2) above baseline (p = 0.44). Those with worsening in PDQ-39-SI scores had less satisfaction with DBS (rs = 0.57, p ≤ 0.0001). This is the first study to assess long-term patient satisfaction with STN DBS. We are currently collecting data prospectively to confirm the results of these preliminary findings.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders, but it is often diagnosed after the majority of dopaminergic cells are already damaged. It is critical to develop biomarkers to identify the disease as early as possible for early intervention. PD patients appear to have an altered pupillary response consistent with an abnormality in photoreceptive retinal ganglion cells. Tracking the pupil size manually is a tedious process and offline automated systems can be prone to errors that may require intervention; for this reason in this work we describe a system for pupil size estimation with a user interface to allow rapid adjustment of parameters and extraction of pupil parameters of interest for the present study. We implemented a user-friendly system designed for clinicians to automate the process of tracking the pupil diameter to measure the post-illumination pupillary response (PIPR), permit manual corrections when needed, and continue automation after correction. Tracking was automated using a Kalman filter estimating the pupil center and diameter over time. The resulting system was tested on a PD classification task in which PD subjects are known to have similar responses for two wavelengths of light. The pupillary response is measured in the contralateral eye to two different light stimuli (470 and 610 nm) for 19 PD and 10 control subjects. The measured Net PIPR indicating different responsiveness to the wavelengths was 0.13 mm for PD subjects and 0.61 mm for control subjects, demonstrating a highly significant difference (p < 0.001). Net PIPR has the potential to be a biomarker for PD, suggesting further study to determine clinical validity.

We previously demonstrated that several dopamine (DA) neurotoxins produced punctate areas of FITC-labeled albumin (FITC-LA) leakage in the substantia nigra and striatum suggesting blood brain barrier (BBB) dysfunction. Further, this leakage was co-localized with αvβ3 integrin up-regulation, a marker for angiogenesis. This suggested that the FITC-LA leakage might have been a result of angiogenesis. To assess the possible role of angiogenesis in DA neuron loss, we treated mice with 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) and on the following day treated with cyRGDfV, a cyclic peptide that binds to integrin αvβ3 and prevents angiogenesis. Post-treatment for three days (b.i.d.) with cyRGDfV blocked the MPTP-induced upregulation of integrin β3 immunoreactivity (a marker for angiogenesis), leakage of FITC-LA into brain parenchyma (a marker for BBB disruption) as well as the down regulation of Zona Occludin-1 (ZO-1; a marker for tight junction integrity). In addition, cyRGDfV also completely prevented tyrosine hydroxylase immunoreactive cell loss (a marker for DA neurons) and markedly attenuated the up-regulation of activated microglia (Iba1 cell counts and morphology). These data suggest that cyRGDfV, and perhaps other anti-angiogenic drugs, are neuroprotective following acute MPTP treatment and may suggest that compensatory angiogenesis and BBB dysfunction may contribute to inflammation and DA neuron loss.