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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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Implantable loop recorders (ILRs) are a central tool in the evaluation of unexplained syncope. These devices record and store electrocardiograms, both automatically and on patient-dependent activation. Therefore, obtaining optimal diagnostic results relies on a patient's comprehension and collaboration., Objectives: To evaluate the effect of ethnic background and mother-tongue language on the diagnostic yield (DY) of ILRs., Methods: Patients at two medical centers in Israel, who had ILRs as part of syncope workup were included. Inclusion criteria were age over 18 years and an ILR for at least one year (or less if the cause of syncope was detected). Patient demographics, ethnic background, and previous medical history were recorded. All findings from ILR recordings, activation mode (manual vs. automatic), and treatment decisions (none, ablation, device implantation) were collected., Results: The study comprised 94 patients, 62 Jews (i.e., ethnic majority) and 32 non-Jews (i.e., ethnic minority). While baseline demographic characteristics, medical history, and drug therapy were similar in both groups, Jewish patients were significantly older at the time of device implantation: 64.3 ± 16.0 years of age vs. 50.6 ± 16.9, respectively; (P < 0.001). Arrhythmias recorded in both groups as well as treatment decisions and device activation mode were similar. Total follow-up time from device implantation was longer in the non-Jewish vs. the Jewish group (17.5 ± 12.2 vs. 24.0 ± 12.4 months, respectively; P < 0.017)., Conclusions: The DY of ILR implanted for unexplained syncope did not seem to be influenced by patient's mother-tongue language or ethnicity.

Background: The Unified Dyskinesia Rating Scale (UDysRS) is a well-established tool for producing comprehensive assessments of severity and disability associated with dyskinesia in patients with Parkinson's disease (PD). The scale was originally developed in English, and a broad international effort has been undertaken to develop and validate versions in additional languages. Our aim was to validate the Hebrew version of the UDysRS., Methods: We translated the UDysRS into Hebrew, back-translated it into English, and carried out cognitive pretesting. We then administered the scale to non-demented native Hebrew-speaking patients who fulfilled the Brain Bank diagnostic criteria for probable PD (n = 250). Data were compared to the Reference Standard data used for validating UDysRS translations., Results: The different portions of the Hebrew UDysRS showed high internal consistency (α ≥ 0.92). A confirmatory factor analysis in which we compared the Hebrew UDysRS to the Reference Standard version produced a comparative fit index (CFI) of 0.98, exceeding the threshold criterion of CFI > 0.9 indicating factor validity. A secondary exploratory factor analysis provided further support to the consistency between the factor structures of the Hebrew and Reference Standard versions of the UDysRS., Conclusion: The UDysRS Hebrew version shows strong clinimetric properties and fulfills the criteria for designation as an official International Parkinson and Movement Disorder Society-approved translation for use in clinical and research settings., (© 2020 S. Karger AG, Basel.)

Background: The Movement Disorders Society (MDS) published the English new Unified Parkinson's Disease Rating Scale (MDS-UPDRS) as the official benchmark scale for Parkinson's disease (PD) in 2008. We aimed to validate the Hebrew version of the MDS-UPDRS, explore its dimensionality and compare it to the original English one., Methods: The MDS-UPDRS questionnaire was translated to Hebrew and was tested on 389 patients with PD, treated at the Movement Disorders Unit at Tel-Aviv Medical Center. The MDS-UPDRS is made up of four sections. The higher the score, the worst the clinical situation of the patient is. Confirmatory and explanatory factor analysis were applied to determine if the factor structure of the English version could be confirmed in the Hebrew version., Results: The Hebrew version of the MDS-UPDRS showed satisfactory clinimetric properties. The internal consistency of the Hebrew-version was satisfactory, with Cronbach's alpha values 0.79, 0.90, 0.93, 0.80, for parts 1 to 4 respectively. In the confirmatory factor analysis, all four parts had high (greater than 0.90) comparative fit index (CFI) in comparison to the original English MDS-UPDRS with high factor structure (0.96, 0.99, 0.94, 1.00, respectively), thus confirming the pre-specified English factor structure. Explanatory factor analysis yielded that the Hebrew responses differed from the English one within an acceptable range: in isolated item differences in factor structure and in the findings of few items having cross loading on multiple factors., Conclusions: The Hebrew version of the MDS-UPDRS meets the requirements to be designated as the Official Hebrew Version of the MDS-UPDRS., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The use of medical cannabis (MC) is controversial. Support for its benefits is based on small clinical series., Objective: The aim of this study was to report the results of a standardized interview study that retrospectively assessed the effects of MC on symptoms of Parkinson disease (PD) and its adverse effects in patients treated for at least 3 months., Methods: The survey used telephone interviews using a structured questionnaire based on subjective global impressions of change for various parkinsonian symptoms and yes/no questions on adverse effects., Results: Forty-seven nondemented patients with PD (40 men) participated. Their mean age was 64.2 ± 10.8 years, mean disease duration was 10.8 ± 8.3 years, median Hoehn and Yahr (H&Y) was stage III. The duration of MC use was 19.1 ± 17.0 months, and the mean daily dose was 0.9 ± 0.5 g. The delivery of MC was mainly by smoking cigarettes (38 cases, 80.9%). Effect size (r) improvement for falls was 0.89, 0.73 for pain relief, 0.64 for depression, 0.64 for tremor, 0.62 for muscle stiffness, and 0.60 for sleep. The most frequently reported adverse effects from MC were cough (34.9%) in those who used MC by smoking and confusion and hallucinations (reported by 17% each) causing 5 patients (10.6%) to stop treatment., Conclusions: Medical cannabis was found to improve symptoms of PD in the initial stages of treatment and did not cause major adverse effects in this pilot, 2-center, retrospective survey. The extent of use and the reported effects lend support to further development of safer and more effective drugs derived from Cannabis sativa.

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., (Copyright © 2017. Published by Elsevier Ltd.)

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., (© 2017 S. Karger AG, Basel.)

Alterations of impulse control that have recently been associated with Parkinson's disease (PD) are serious behavioural disturbances with significant impact on PD patients and their families.A total of 193 consecutive PD patients with no history of psychiatric illness and 190 age/gender-matched healthy controls were queried on the presence of new onset heightened interest or drive for gambling, shopping, eating or sexual activity (GSES). Clinical data were retrieved from medical charts and interviews. logistic regressions models assessed risk factors for these specific troublesome behaviours. New or heightened interests or drives for GSES behaviours were reported by 27 patients (14% vs 0% for controls). Younger age at PD motor symptoms onset (OR = 0.99, p = 0.0172), male gender (OR = 1.10, p = 0.0576) and longer duration of treatment with dopamine agonists (DAs)(OR = 1.18, >/=6 years versus never treated, p = 0.0459) contributed additively to the risk of developing one or more of these behavioural features. New onset heightened interests or drives for GSES are not rare behavioural disturbances among patients with PD. Age, gender and duration of treatment with DAs have an independent and additive effect on the risk to develop such behavioural changes. Patients should be informed about potential treatment-associated behavioural changes.

Objective: To compare the safety and efficacy of quetiapine versus clozapine for the treatment of psychosis in patients with Parkinson's disease (PD)., Methods: Twenty-seven patients with PD and recent-onset psychosis were randomly allocated to 2 arms of 22 weeks' treatment with quetiapine or clozapine after 2 weeks of adjustment of antiparkinsonian medications. Assessment was done by a blinded neuropsychologist using the Clinical Global Impression of Change (CGIC) questionnaire and the Neuropsychiatric Inventory (NPI). Mixed-effect models were used to compare CGIC and Neuropsychological Inventory scores over time between the 2 groups., Results: Both drugs were equally effective based on the CGIC. Clozapine had a trend over quetiapine in controlling the frequency of hallucinations (P = 0.097) and a significant advantage in reducing delusions (P = 0.011). However, one patient in the clozapine arm developed leukopenia. None of the drugs worsened parkinsonism., Conclusions: Clozapine and quetiapine are effective atypical neuroleptics for the treatment of psychotic symptoms in PD. Clozapine had greater efficacy in reducing hallucinations and delusions frequency, but its use is associated with an increased risk of leukopenia.

The purpose of this study was to assess whether rivastigmine, a cholinergic agent, affects tremor features when given to improve cognition in demented Parkinson's disease (PD) patients. Demented PD patients (n = 26; Mini-Mental State Examination score, 13-25; age, 75.2 +/- 4.9 yr) were given rivastigmine (mean dose, 8.0 mg/day) for 12 weeks. They underwent tremor assessment before and during treatment. Global Tremor Score (GTS) was based on eight items specific to tremor in the Unified Parkinson's Disease Rating Scale. Tremor amplitude was also measured using accelerometers during the ON state in both hands in 19 patients. Drug therapy for other PD symptoms was unchanged. The mean group baseline GTS was 1.2 +/- 1.6 points, increasing to 1.6 +/- 2.4 points after treatment (mean increase, 0.4 +/- 1.2 points; P > 0.05). The GTS increased by 3.2 +/- 1.9 points (range, 1-5) in 7 patients (26.9%) and decreased by 1 +/- 0 points in 3 patients (11.5%). Accelerometric assessment showed a significant increase of the average tremor amplitude in the right hand (0.08 +/- 0.03 xg at baseline; 0.12 +/- 0.02 xg at Week 12 of treatment, P = 0.02). Left-hand tremor amplitude did not change. Rivastigmine caused only slight worsening of tremor in demented PD patients, while improving cognition.

"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".

Germ line mutations in three genes have been detected in patients with familial Alzheimer's disease (FAD) and sporadic, early onset disease: amyloid precursor protein (APP), presenilin 1 (PS-1), and presenilin 2 (PS-2). The relative proportions in which mutations in these genes occur among AD patients in Israel has not been evaluated. To that end, we screened 52 Jewish-Israeli patients with AD: 22 with sporadic, early-onset disease (below 65 years), and 30 with FAD. Mutation screen employed denaturing gradient gel electrophoresis (DGGE) of exon-specific PCRs and restriction enzyme digest. Five patients from three different families displayed mutations within the PS-1 gene: three patients of one family showed a mis-sense mutation in codon 120 (Glu 120Lys), and two other unrelated patients showed an identical mis-sense mutation in codon 318 (Glu318Gly). No patient showed an abnormal migration on DGGE (for APP) or mutant restriction digest pattern (for PS-2) genes. These data may indicate the existence of another familial Alzheimer disease (FAD) gene locus in the Israeli Jewish population.

This study examined the prevalence of post-traumatic stress disorder (PTSD) in a sample of 100 Israeli myocardial infarction (MI) patients. Chronic PTSD was diagnosed in 16% of these patients and acute (PTSD) in 9%. The appearance of PTSD following MI was found to be related to the following variables: ethnic background; prior traumatic experiences, including prior MI; and anticipation of disability following MI. Objective measures of MI severity were not related to propensity to develop PTSD. The presence of PTSD correlated with self reports of dysfunction in these MI patients and may account for the majority of failures in rehabilitation.

In 1913, Guggenheim identified L-DOPA in the seedlings, pods, and beans of the broad bean, Vicia faba (VF). Since then, anecdotal cases of symptomatic improvement after VF consumption have been described in patients with PD. In the present study, five healthy volunteers and six PD patients (mean age, 63.5 years; mean disease duration, 13 years; stage III, Hoehn-Yahr scale) ate 250 g cooked VF after 12 hours off medication. Blood samples for L-DOPA measurements (by HPLC-ED) were obtained before eating VF and every 30 minutes, for 4 hours. During this period, a substantial clinical improvement was noted and three patients also showed severe dyskinesias. High plasma L-DOPA values were also measured (Cmax 0.66 to 1.20 micrograms/ml; AUC 1.82 to 4.12 micrograms/ml/H). In addition, their clinical performance and plasma L-DOPA levels were compared to those found after 125 mg L-DOPA + 12.5 mg carbidopa ingested on another day. These data show that VF ingestion produces a substantial increase in L-DOPA plasma levels, which correlates with a substantial improvement in motor performance. Our findings may have implications for the treatment of PD, especially in patients with mild symptoms.