Parkinson's disease with hyposmia and dysautonomia: does it represent a distinct subtype?

BACKGROUND AND PURPOSE: Olfactory dysfunction or dysautonomia is one of the earliest prodromal nonmotor symptoms of Parkinson's disease (PD). We aimed to investigate whether PD patients with dysautonomia and hyposmia at the de novo stage present different prognoses regarding PD dementia (PDD) conversion, motor complication development, and change in levodopa-equivalent doses (LED). METHODS: In this retrograde cohort study, we included 105 patients with newly diagnosed PD patients who underwent cross-cultural smell identification test (CC-SIT), autonomic function tests (AFT), and dopamine transporter (DAT) scan at the de novo stage. PD patients were divided into Hyposmia + /Dysautonomia + (H + /D +) and Hyposmia - /Dysautonomia - (H - /D -) groups depending on the result of AFT and CC-SIT. Baseline clinical, cognitive, imaging characteristics, longitudinal risks of PDD development and motor complication occurrence, and longitudinal LED changes were compared between the two groups. RESULTS: When compared with the H - /D - group, the H + /D + group showed lower standardized uptake value ratios in all subregions, lower asymmetry index, and steeper ventral - dorsal gradient in the DAT scan. The H + /D + group exhibited poorer performance in frontal/executive function and a higher risk of PDD development. The risk of motor complications including levodopa-induced dyskinesia, wearing off, and freezing of gait, was comparable between the two groups. The analysis of longitudinal changes in LED using a linear mixed model showed that the increase of LED in the H + /D + group was more rapid. CONCLUSIONS: Our results suggest that PD patients with dysautonomia and hyposmia at the de novo stage show a higher risk of PD dementia conversion and rapid progression of motor symptoms.

Distribution of Neurofilament in Peeled Internal Limiting Membrane.

BACKGROUND AND OBJECTIVE: The aim was to study the distribution of neurofilament in peeled internal limiting membrane (ILM). PATIENTS AND METHODS: Prospective case study. Vitrectomy and ILM peeling were performed in patients with epiretinal membrane and macular hole. ILM flap specimens were obtained as one disc area size from five locations. Immunofluorescent staining was performed with an antineurofilament heavy antibody. Using a confocal microscope, retinal cell debris density was studied using the ImageJ program. RESULTS: Percent of stained neurofilament was 1.58 ± 1.14% in total (2.45 ± 1.37% in extranasal, 1.97 ± 0.75% in extratemporal, 1.93 ± 1.26% in juxta-nasal, 0.89 ± 0.69% in fovea, and 0.63 ± 0.46% in juxtatemporal). The Kruskal-Wallis test revealed significant differences among groups (P < 0.05). Bonferroni post hoc analysis only confirmed significant difference between juxtatemporal and extranasal groups (P < 0.05). CONCLUSIONS: In peeled ILM flap, neurofilaments are rarely detected in the juxtatemporal area. However, they are frequently detected in the extranasal area. [Ophthalmic Surg Lasers Imaging Retina 2023;54:643-648.].

A Nonrandomized Phase 2 Trial of EG-Mirotin, a Novel, First-in-Class, Subcutaneously Deliverable Peptide Drug for Nonproliferative Diabetic Retinopathy.

Background and objectives: EG-Mirotin (active ingredient EGT022) targets nonproliferative diabetic retinopathy (NPDR), the early stage of retinopathy. EG-Mirotin reverses capillary damage before NPDR progresses to an irreversible stage. EG-Mirotin safety and efficacy were investigated in patients with type 1 or type 2 diabetes mellitus and moderate to severe NPDR. Methods: In this open-label, single-arm, single-center, exploratory phase II study, 10 patients (20 eyes) received EG-Mirotin once a day (3 mg/1.5 mL sterile saline) for 5 days and were evaluated for ischemic index changes and safety. End of study was approximately 8 ± 1 weeks (57 ± 7 days) after the first drug administration. Results: EG-Mirotin injections were well tolerated, with no dose-limiting adverse events, serious adverse events, or deaths. Four treatment-emergent adverse events (TEAEs) unrelated to the investigational drug were observed in 2 out of 10 participants (20%) who had received the investigational drug. The overall average percent change in ischemic index at each evaluation point compared with baseline was statistically significant (Greenhouse-Geisser F = 9.456, p = 0.004 for the main effect of time), and a larger change was observed when the baseline ischemic index value was high (Greenhouse-Geisser F = 10.946, p = 0.002 for time × group interaction). Conclusions: The EG-Mirotin regimen established in this study was shown to be feasible and safe and was associated with a trend toward potential improvement in diabetes-induced ischemia and retinal capillary leakage.