Two Ethnic Clusters with Huntington Disease in Israel: The Case of Mountain Jews and Karaites.

BACKGROUND: Worldwide prevalence estimates of Huntington disease (HD) vary widely, with no reliable information regarding the Jewish population in Israel. METHODS: This specialized tertiary single-center cross-sectional study assessed clinical, cognitive, and demographic characteristics of 84 HD patients who were treated at the Movement Disorder Unit of the Tel Aviv Medical Center, Israel. RESULTS: Our cohort was composed of one-third Ashkenazi Jews, 27% Mountain Jews (Caucasus Jews), 18% Sephardi Jews, and 21% Karaites, with both Mountain Jews and Karaites over-represented compared to their relevant proportion in the population of the state of Israel, which is less than 1%. No between-group differences were detected regarding the number of CAG (cytosine-adenine-guanine) repeats, age at onset, disease duration, years from symptom onset to diagnosis, gender, years of education, Unified Huntington Disease Rating Scale scores, or the Montreal Cognitive Assessment scores. CONCLUSION: We detected clustering of HD among the population treated at our Medical Center, which has the only specialized HD clinic in the country, with a high percentage of HD among 2 relatively small subpopulations of Jews: Mountain Jews and Karaites.

Levodopa-carbidopa intestinal gel for advanced Parkinson's disease: Impact of LRRK2 and GBA1 mutations.

BACKGROUND: Advanced Parkinson's disease (PD) can be treated with Levodopa-Carbidopa Intestinal Gel (LCIG). OBJECTIVE: To compare descriptive data of LCIG treatment in GBA1-PD and LRRK2-PD. METHODS: This multicenter retrospective study compared clinical data obtained from electronic medical records of PD patients treated with LCIG. Patients were grouped based on their genetic status. RESULTS: Fifty-two iPD, 15 LRRK2-PD and 23 GBA1-PD were included in this study. No difference in daily dose of LCIG or levodopa equivalent daily dose were detected. GBA1-PD had significantly shorter disease duration at LCIG initiation (p = 0.01) and experienced more hallucinations (p = 0.03) compared with LRRK2-PD and iPD. LRRK2-PD and iPD had significantly longer duration of LCIG treatment compared with GBA1-PD (p < 0.01). CONCLUSION: Overall, LCIG treatment was well tolerated in LRRK2-PD and GBA1-PD. GBA1-PD required LCIG earlier in their course of their disease and had higher frequencies of hallucinations during treatment, attesting to a more severe disease course.

Reduced mind wandering in patients with Parkinson's disease.

BACKGROUND: Mind Wandering (MW) refers to the process of disengaging from the immediate external environment and participating in internally driven mentation. This process has been suggested to be supported by a distributed set of brain regions, collectively referred to as the Default Mode Network (DMN). Recently, reduced recruitment and connectivity of the DMN has been described in Parkinson's disease (PD) patients compared to healthy controls. We thus aimed to explore whether PD patients with normal cognitive test scores show differential MW capabilities compared to healthy controls. METHODS: Thirty PD patients and thirty age-matched controls, all with a Montreal cognitive assessment (MoCA) score of 26 or above, performed a novel yet validated thought-sampling paradigm used to assess the frequency and extent of MW irrespective of cognitive load in which participants were asked to observe a series of geometric shapes and describe their thoughts after watching them. Shapes were presented one at a time for varying durations across nine trials. RESULTS: PD patients showed significantly less MW compared to the control. ANCOVA revealed a significant interaction indicating that the difference in MW scores was driven by trials with short stimulus presentation times. CONCLUSIONS: These findings provide evidence for decreased MW in PD patients. We propose that this is due to difficulties in performing MW within short time frames.

Pharmacokinetics of etilevodopa compared to levodopa in patients with Parkinson's disease: an open-label, randomized, crossover study.

"Dose failures" and "delayed on" phenomena following an intake of levodopa dose in patients with Parkinson's disease (PD) with motor fluctuations may be caused by stagnation of poorly soluble levodopa in the atonic stomach. Etilevodopa is a unique, highly soluble prodrug of levodopa. When ingested, etilevodopa is more readily dissolved in the stomach than levodopa. It passes unchanged through the stomach to the duodenum, where it is rapidly hydrolyzed by local esterases and rapidly absorbed as levodopa. To compare the pharmacokinetics of three different modes of etilevodopa/carbidopa administration with standard levodopa/carbidopa tablets in fluctuating PD patients, 29 patients with PD and response fluctuations were enrolled in an open-label, randomized, four-way crossover study of single doses of 4 treatments: swallowed etilevodopa/carbidopa tablets, etilevodopa/carbidopa tablets dissolved in water, etilevodopa oral solution with carbidopa tablets, and standard levodopa/carbidopa tablets. To measure the maximal concentration (Cmax), time to Cmax (tmax), and area under the curve (AUC) of plasma levodopa, etilevodopa, and carbidopa, blood samples were drawn before drug administration and at intervals up to 240 minutes thereafter. Plasma levodopa tmax was significantly shorter with all three modes of administration of etilevodopa (mean of about 30 minutes) than with levodopa treatment (mean of 54 minutes). During the first 45 minutes after drug ingestion, plasma levodopa AUC was significantly greater after etilevodopa administration than after levodopa administration. Levodopa AUC for 0 to 1 hour and 0 to 2 hours were also significantly greater following administration of etilevodopa/carbidopa swallowed tablets than following administration of levodopa/carbidopa tablets. Mean levodopa Cmax was in the range 2.3 to 2.7 microg/mL for all treatments. Levodopa Cmax was significantly greater following treatment with etilevodopa swallowed tablets than with levodopa tablets. Etilevodopa/carbidopa was well tolerated, with a safety profile comparable to that of levodopa/carbidopa. The shorter levodopa tmax observed with etilevodopa potentially translates to a shorter time to "on". Clinical trials with etilevodopa/carbidopa tablets should be carried out in PD patients with response fluctuations such as "delayed on" and "dose failures".