Search

Background: Inflammation is an integral part of neurodegeneration including in Parkinson’s disease (PD). Ashkenazi Jews have high rates of genetic PD with divergent phenotypes among GBA-PD and LRRK2-PD. The role of inflammation in the prodromal phase of PD and the association with disease phenotype has yet to be elucidated. Objective: To assess central and peripheral cytokines among PD patients with mutations in the LRRK2 and GBA genes and among non-manifesting carriers (NMC) of these mutations in order to determine the role of inflammation in genetic PD. Methods: The following cytokines were assessed from peripheral blood and cerebrospinal fluid (CSF): TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10 and INF- γ. A comprehensive intake including general medical conditions, use of anti-inflammatory treatments, motor and cognitive assessments and additional laboratory measures were recorded, enabling the construction of the MDS probable prodromal score. Results: Data from 362 participants was collected: 31 idiopathic PD (iPD), 30 LRRK2-PD, 77 GBA-PD, 3 homozygote GBA-PD, 3 GBA-LRRK2-PD, 67 LRRK2-NMC, 105 GBA-NMC, 14 LRRK2-GBA-NMC, and 32 healthy controls. No between-group differences in peripheral or CSF cytokines were detected. No correlation between disease characteristics or risk for prodromal PD could be associated with any inflammatory measure. Conclusion: In this study, we could not detect any evidence on dysregulated immune response among GBA and LRRK2 PD patients and non-manifesting mutation carriers.

The phenotype of Parkinson’s disease (PD) is variable with mutations in genes such as LRRK2 and GBA explaining part of this heterogeneity. Additional genetic and environmental factors contribute to disease variability. To assess the association between biochemical markers, PD severity and probability score for prodromal PD, among GBA and LRRK2 mutation carriers. Levels of uric acid, vitamin D, C-reactive protein, microalbumin/creatinine ratio (ACR), white blood count (WBC), hemoglobin, platelets, neutrophil/lymphocyte ratio and estimated glomerular filtration rate (eGFR) were assessed from patients with PD and non-manifesting carriers (NMC) of mutations in GBA and LRRK2, together with disease related questionnaires enabling the construction of the MDS prodromal probability score. A total of 241 patients with PD: 105 idiopathic PD (iPD), 49 LRRK2-PD and 87 GBA-PD and 412 non-manifesting subjects; 74 LRRK2-NMC, 118 GBA-NMC and 220 non-manifesting non-carriers (NMNC), participated in this study. No significant differences in biochemical measures were detected among patients with PD or non-manifesting carriers. Among GBA-PD patients, worse motor performance was associated with ACR (B = 4.68, 95% CI (1.779–7.559); p = 0.002). The probability score for prodromal PD among all non-manifesting participants was associated with eGFR; NMNC (B = − 0.531 95% CI (− 0.879 to − 0.182); p

Autonomic involvement, including cardiac denervation, may precede the motor symptoms of Parkinson’s disease by several years. L-3,4-dihydroxy-6-[18F] fluoro-phenylalanine is a positron emitter and a true analog of L-dopa, used in clinical practice to assess striatal dopaminergic integrity. The present study aimed to assess the feasibility of evaluating cardiac sympathetic denervation in Parkinson’s disease patients using L-3,4-dihydroxy-6-[18F] fluoro-phenylalanine positron emission tomography/computed tomography. Patients referred for an L-3,4-dihydroxy-6-[18F] fluoro-phenylalanine positron emission tomography/computed-tomography between July 2015 and May 2017 to evaluate striatal presynaptic dopaminergic integrity underwent a heart positron emission tomography scan following a brain positron emission tomography scan. L-3,4-dihydroxy-6-[18F] fluoro-phenylalanine uptake in the left ventricle was quantified using CarimasT⁢M software and compared between patients with and without Parkinson’s disease. The area under the receiver operating characteristic curve was used to evaluate the ability of the left ventricular mean standardized uptake value to discriminate between patients with Parkinson’s disease and those with other extrapyramidal syndromes. Seventy-six patients were included, of whom 52 were diagnosed with Parkinson’s disease. The mean L-3,4-dihydroxy-6-[18F] fluoro-phenylalanine left ventricular mean standardized uptake value was lower in the Parkinson’s disease patients compared to the non- Parkinson’s disease patients (1.08 ± 0.21 vs. 1.24 ± 0.32, P = 0.015). The left ventricular mean standardized uptake value was able to discriminate between Parkinson’s disease and non- Parkinson’s disease patients (the area under the receiver operating characteristic curve = 0.641, P = 0.049). In conclusion, quantification of cardiac L-3,4-dihydroxy-6-[18F] fluoro-phenylalanine uptake may be able to differentiate between patients with and without Parkinson’s disease. Validation of this finding in more substantial, prospective trials are warranted.

BACKGROUND The phenotype of Parkinson's disease (PD) is milder among patients with LRRK2-PD and more severe among patients with GBA-PD; however, whether an additive phenotypical effect occurs among dual-mutation carriers requires validation. OBJECTIVE The objective of this study was to explore the phenotypic expression of patients with PD who carry mutations in both genes compared with a single-mutation presentation. METHODS Patients with PD were genotyped for the G2019S-LRRK2 mutation and 9 mutations in the GBA gene. Subjects were classified into 5 groups: idiopathic PD, mild GBA-PD, severe GBA-PD, LRRK2-PD, and LRRK2+GBA-PD. Clinical symptoms were evaluated using performance-based measures. RESULTS A total of 1090 patients with idiopathic PD, 155 patients with LRRK2-PD, 155 patients with mild GBA-PD, 56 patients with severe GBA-PD, and 27 patients with LRRK2+GBA-PD participated in this study. The patients with LRRK2-PD and LRRK2+GBA-PD exhibited lower scores on total Unified Parkinson's Disease Rating Scale (P

Background: Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of disorders best known for causing inherited forms of peripheral neuropathy. History of CMT disease is not considered relevant in patients presenting with acute central neurologic manifestations of acute stroke. The case described here should alert clinicians to the possibility of transient stroke-like episodes in young patients suffering from CMTX1, X‐linked variant of CMT. Case description: A 21-year-old man presented to our emergency department with acute onset dysarthria, right facial weakness and right hemiparesis, which started 2 hours before his admission. He was treated with intravenous thrombolysis with a suspected diagnosis of acute ischemic stroke with full resolution of symptoms. The following day he experienced another stroke-like episode of acute onset of dysarthria and left facial weakness that resolved within 3 hours. The patient underwent stroke in the young work-up which was normal. MRI of the brain showed symmetric, non-enhancing areas of restricted diffusion in the corona radiata bilaterally and corpus callosum, also demonstrated on T2/fluid-attenuated inversion recovery (FLAIR) sequences. Clinical and familial investigations resulted in diagnosing CMTX1, X‐linked variant of CMT. Discussion: This case illustrates that CMTX1 disease can have central nervous system (CNS) manifestations that could mimic stroke-like neurological deficits with pathological MRI findings. The prognosis of the CNS phenotype of CMTX1 is usually good, with spontaneous resolution without

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.

Background Mutations in the GBA gene, which encodes the lysosomal enzyme glucocerebrosidase (GCase), are risk factors for Parkinson's disease (PD). Objective To explore the association between GCase activity, PD phenotype, and probability for prodromal PD among carriers of mutations in the GBA and LRRK2 genes. Methods Participants were genotyped for the G2019S-LRRK2 and nine GBA mutations common in Ashkenazi Jews. Performance-based measures enabling the calculation of the Movement Disorder Society (MDS) prodromal probability score were collected. Results One hundred and seventy PD patients (102 GBA-PD, 38 LRRK2-PD, and 30 idiopathic PD) and 221 non-manifesting carriers (NMC) (129 GBA-NMC, 45 LRRK2-NMC, 15 GBA-LRRK2-NMC, and 32 healthy controls) participated in this study. GCase activity was lower among GBA-PD (3.15 ± 0.85 μmol/L/h), GBA-NMC (3.23 ± 0.91 μmol/L/h), and GBA-LRRK2-NMC (3.20 ± 0.93 μmol/L/h) compared to the other groups of participants, with no correlation to clinical phenotype. Conclusions Low GCase activity does not explain the clinical phenotype or risk for prodromal PD in this cohort. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The phenotype of Parkinson's disease (PD) is variable with mutations in genes such as LRRK2 and GBA explaining part of this heterogeneity. Additional genetic and environmental factors contribute to disease variability.To assess the association between biochemical markers, PD severity and probability score for prodromal PD, among GBA and LRRK2 mutation carriers.Levels of uric acid, vitamin D, C-reactive protein, microalbumin/creatinine ratio (ACR), white blood count (WBC), hemoglobin, platelets, neutrophil/lymphocyte ratio and estimated glomerular filtration rate (eGFR) were assessed from patients with PD and non-manifesting carriers (NMC) of mutations in GBA and LRRK2, together with disease related questionnaires enabling the construction of the MDS prodromal probability score.A total of 241 patients with PD: 105 idiopathic PD (iPD), 49 LRRK2-PD and 87 GBA-PD and 412 non-manifesting subjects; 74 LRRK2-NMC, 118 GBA-NMC and 220 non-manifesting non-carriers (NMNC), participated in this study. No significant differences in biochemical measures were detected among patients with PD or non-manifesting carriers. Among GBA-PD patients, worse motor performance was associated with ACR (B = 4.68, 95% CI (1.779-7.559); p = 0.002). The probability score for prodromal PD among all non-manifesting participants was associated with eGFR; NMNC (B = - 0.531 95% CI (- 0.879 to - 0.182); p 0.001, LRRK2-NMC (B = - 1.014 95% CI (- 1.663 to - 0.366); p 0.001) and GBA-NMC (B = - 0.686 95% CI (1.300 to - 0.071); p = 0.029).Sub-clinical renal impairment is associated with increased likelihood for prodromal PD regardless of genetic status. While the mechanism behind this finding needs further elucidation, it suggests that kidney function might play a role in PD pathogenesis.

Background: Cerebrospinal fluid (CSF) is essential for the medical workup of patients with neurological conditions and for disease-modifying clinical trials. Post- lumbar puncture (LP) headache is influenced by both operator and patient-related factors, including needle type and gauge, age, and gender. Objectives: We aimed to assess whether CSF volume measured based on pre-procedural brain MRI is associated with the risk of developing a post-LP headache. Methods: In total, n = 117 participants (n = 58 Parkinson's disease patients, and n = 59 healthy controls) underwent an LP and CSF collection. Of those, n = 89 underwent MRI scans prior to the LP procedure acquiring high-resolution 3D magnetization-prepared rapid gradient echo (MP-RAGE) T1-weighted images using a 3 T MR scanner. Clinical and behavioral assessments were performed for all participants, and CSF was assessed for content. The T1-weighted images were segmented producing gray matter, white matter, and CSF probability maps. Results: Thirteen participants (11.1%) experienced post-LP headache. They were younger (p = .033) and had lower CSF volumes (p = .040) compared to participants that did not develop a post LP headache. Conclusions: The results of this pilot study suggest that low CSF volumes might increase the risk for the occurrence of post-LP adverse events and should be taken into consideration when planning LP's.

In order toevaluate the influence of the metabolic syndrome (MS) (obesity, hypertension, elevated triglycerides, reduced levels of HDL cholesterol and glucose impairment) on the phenotype of LRRK2 and GBA Parkinson’s disease (PD), and on the prevalence of prodromal features among individuals at risk, we collected, laboratory test results, blood pressure, demographic, cognitive, motor, olfactory and affective information enabling the assessment of each component of MS and the construction of the MDS prodromal probability score. The number of metabolic components and their levels were compared between participants who were separated based on disease state and genetic status. One hundred and four idiopathic PD, 40 LRRK2-PD, 70 GBA-PD, 196 healthy non-carriers, 55 LRRK2-NMC and 97 GBA-NMC participated in this study. PD groups and non manifesting carriers (NMC) did not differ in the number of metabolic components (p = 0.101, p = 0.685, respectively). LRRK2-PD had higher levels of triglycerides (p = 0.015) and higher rates of prediabetes (p = 0.004), while LRRK2-NMC had higher triglyceride levels (p = 0.014). NMC with probability rates for prodromal PD above 50% had higher frequencies of hypertriglyceridemia and prediabetes (p LRRK2 carriers, MS does not seem to influence GBA and LRRK2-PD phenotype.

BackgroundHuntington’s disease (HD) is a neurodegenerative disease characterized by increasing dysphagia as the disease progresses. Specific characteristics of the HD dysphagia are not well defined.ObjectiveTo characterize the swallowing disturbances of HD patients, to evaluate the feasibility of Fiberoptic Endoscopic Evaluation of Swallowing (FEES) in assessing dysphagia in HD patients, and to discern the relation between FEES findings and patients’ self-report on dysphagia symptoms and swallowing related quality of life (SWAL-QOL).MethodA retrospective case series in a tertiary referral center. All recruited HD patients underwent Bed Side Swallowing Evaluation (BSE), FEES, the Unified Huntington’s Disease Rating Scale (UHDRS), and the Montreal Cognitive Assessment (MoCA). All completed the Swallowing Disturbances Questionnaire (SDQ) and the SWAL-QOL questionnaire.ResultsFourteen HD patients were recruited. All were able to complete the FEES study. The FEES demonstrated delayed swallowing reflex, solid food residues, and pre/post swallowing spillage in most patients (50%, 53.5%, 83.3%, and 87.5%, respectively). The mean SDQ score was 13.2. Significant correlations were found between the SWAL-QOL fear of eating score; the SDQ oral, pharyngeal, and total scores; and the FEES parameters of pureed and solid food bolus flow time. Significant correlations were also found between the total UHDRS score, the volitional cough score, and the SWAL-QOL disease burden score.ConclusionHD patients exhibit prominent unique oropharyngeal dysphagia features that may serve as a marker of disease progression. The FEES and the SDQ are valuable tools for detecting these features in HD patients with swallowing disturbance.

Sleep disturbances and nocturnal hypokinesia are common in Parkinson's disease (PD). Recent work using wearable technologies showed fewer nocturnal movements in PD when compared with controls. However, it is unclear how these manifest across the disease spectrum.We assessed the prevalence of sleep disturbances and nocturnal hypokinesia in early and advanced PD and their relation to nonmotor symptoms and dopaminergic medication.A total of 305 patients with PD with diverse disease severity (Hoehn and Yahr [HY] stage 1 = 47, HY stage 2 = 181, HY stage 3 = 77) and 205 healthy controls continuously wore a tri-axial accelerometer on the lower back for at least 2 days. Lying, turning, and upright -time at night were extracted from the acceleration signals. Percent upright time and nighttime walking were classified as sleep interruptions. The number, velocity, time, side, and degree of rotations in bed were used to evaluate nocturnal movements.Nocturnal lying time was similar among all groups (healthy controls, 7.5 ± 1.2 hours; HY stage 1, 7.3 ± 0.9 hours; HY stage 2, 7.2 ± 1.3 hours; HY stage 3, 7.4 ± 1.6 hours; P = 0.501). However, patients with advanced PD had more upright periods, whereas the number and velocity of their turns were reduced (P ≤ 0.021). Recently diagnosed patients (1 year from diagnosis) were similar to controls in the number of nocturnal turns (P = 0.148), but showed longer turning time (P = 0.001) and reduced turn magnitude (P = 0.002). Reduced nocturnal movements were associated with increased PD motor severity and worse dysautonomia and cognition and with dopaminergic medication.Using wearable sensors for continuous monitoring of movement at night may offer an unbiased measure of disease severity that could enhance optimal nighttime dopaminergic treatment and utilization of turning strategies. © 2020 International Parkinson and Movement Disorder Society.

The effect of repeated intravenous amantadine (IVAM) in advanced Parkinsonism has not been studied in depth.To report the experience of our medical center with repeated IVAM infusions in patients with advanced Parkinsonism.Thirty patients with advanced Parkinsonism of various etiologies were enrolled in an open-label retrospective study. All patients were treated with IVAM infusions in a neurological daycare center. Treatment was initiated with a loading dose of 200/400 mg per day for 5 days followed by a once-daily maintenance dose of 200/400 mg every 1 to 3 weeks. Patients and their caregivers participated in a structured interview and independently completed a clinical global impression of changes scale questionnaire on various motor and non-motor symptoms.Patient mean age was 73.3 ± 9.7 years, average disease duration was 6.2 ± 5.7 years, and mean Hoehn and Yahr score was 3.2 ± 0.84. Mean duration of the IVAM treatment was 15.1 ± 11.6 months. An improvement in general function was reported by 91% of the patients and 89% of the caregivers. Most of the patients reported improvement in tremor and rigidity, as well as in gait stability, freezing of gait, and reduced falls. The treatment was safe with few side effects.Our data suggest that repeated IVAM infusions could be an effective treatment against various motor symptoms and for improvement of mobility in patients with advanced Parkinsonism. Further randomized clinical trials with a larger sample size using objective measures are warranted to validate our results.

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.

Background: Sleep interruptions and nocturnal hypokinesia are common in Parkinson's disease (PD). Pilot work using wearable technologies showed fewer nocturnal movements in patients with advanced PD compared to controls. However, the prevalence of these impairments in early stage of the disease and the influence of non-motor symptoms, and dopaminergic medication are unknown. Methods: This study evaluated wearable sensor data collected in 305 patients with PD at different Hohen and Yahr disease stages (HY HY H&Y3=77) and 205 healthy controls (HC). Subjects wore a tri-axial accelerometer continuously (24/7) on the lower back for at least 2 days. Percent upright-time and nighttime walking were defined based on the vertical axis of the acceleration signal and were classified as sleep interruptions. The number, velocity, time, side, and degree of rotations in bed during the night evaluated nocturnal movements. Findings: Nocturnal lying-time was similar between PD and controls (p=0.501), however, the number of turns and the turn velocity significantly decreased (p

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.

LRRK2 mutations are present in 1% of all sporadic Parkinson's disease (PD) cases and 5% of all familial PD cases. Several mutations in the LRRK2 gene are associated with PD, the most common of which is the Gly2019Ser mutation. In the following review, we summarize the demographics and motor and non-motor symptoms of LRRK2 carriers with PD, as well as symptoms in non-manifesting carriers. The clinical features of LRRK2-associated PD are often indistinguishable from those of idiopathic PD on an individual basis. However, LRRK2 PD patients are likely to have less non-motor symptoms compared to idiopathic PD patients, including less olfactory and cognitive impairment. LRRK2-associated PD patients are less likely to report REM sleep behavior disorder (RBD) than noncarriers. In addition, it is possible that carriers are more prone to cancer than noncarriers with PD, but larger studies are required to confirm this observation. Development of more sensitive biomarkers to identify mutation carriers at risk of developing PD, as well as biomarkers of disease progression among LRRK2 carriers with PD, is required. Such biomarkers would help evaluate interventions, which may prevent PD among non-manifesting carriers, or slow down disease progression among carriers with PD.

LRRK2 mutations are present in 1% of all sporadic Parkinson's disease (PD) cases and 5% of all familial PD cases. Several mutations in the LRRK2 gene are associated with PD, the most common of which is the Gly2019Ser mutation. In the following review, we summarize the demographics and motor and non-motor symptoms of LRRK2 carriers with PD, as well as symptoms in non-manifesting carriers. The clinical features of LRRK2-associated PD are often indistinguishable from those of idiopathic PD on an individual basis. However, LRRK2 PD patients are likely to have less non-motor symptoms compared to idiopathic PD patients, including less olfactory and cognitive impairment. LRRK2-associated PD patients are less likely to report REM sleep behavior disorder (RBD) than noncarriers. In addition, it is possible that carriers are more prone to cancer than noncarriers with PD, but larger studies are required to confirm this observation. Development of more sensitive biomarkers to identify mutation carriers at risk of developing PD, as well as biomarkers of disease progression among LRRK2 carriers with PD, is required. Such biomarkers would help evaluate interventions, which may prevent PD among non-manifesting carriers, or slow down disease progression among carriers with PD.

Bone morphogenic proteins (BMPs) signaling blockade induce neurogenesis and oligodendrogenesis. Differential screening-selected gene aberrative in neuroblastoma (DAN) is a glycoprotein that antagonizes BMPs. We found that DAN levels were higher in CSF compared to serum in all participants. CSF-DAN levels were elevated in RR-and progresssive MS patients compared to controls. Moreover, serum-DAN levels were reduced in those patients, but elevated in IFN-β1a treated patients. The main source of DAN is apparently CNS- resident cells. The enhanced levels of CSF-DAN in MS patients suggest a tendency to induce neurogenesis/oligodendrogenesis in the patients CNS. Our results suggest an unreported mode of action of IFN-β1a.

The aim of this study was to estimate the prevalence and assess the clinical correlates of intention tremor in the legs in essential tremor (ET) patients. The cerebellar features of ET are of growing interest to clinical neurologists. Arm tremor has an intentional component in many ET patients. Intention tremor in the legs, however, has never been systematically evaluated. One hundred twenty-eight ET patients were enrolled in a clinical-epidemiological study at Columbia University (New York, NY). A videotaped neurological examination included 10 toe-to-target movements with each foot. Videotapes were independently reviewed by two movement disorder neurologists who noted the presence versus absence of intentional leg tremor. Two patients underwent quantitative computerized tremor analysis to study the physiological characteristics of the tremor. Thirty-five patients (27.3%) had intentional leg tremor; in 21, tremor was unilateral and in 14 it was bilateral. The 35 patients with intentional leg tremor did not differ from the remaining 93 in their clinical characteristics. Analyses comparing the 14 patients with bilateral intentional leg tremor to the 93 with no intentional leg tremor showed trends toward longer disease duration and more-severe intentional arm tremor in the former. Tremor analysis showed a 3-fold increase in average tremor amplitude from movement onset to the point just before touching the target. Our data suggest that intentional leg tremor, another cerebellar feature, is common in ET patients. The tremor may be associated with longer disease duration and more-severe intentional arm tremor, but these preliminary trends need to be assessed in larger study samples.

Levodopa (LD) is the most effective treatment for Parkinson's disease (PD). However, chronic use of LD commonly results in the development of motor complications, including wearing off and dyskinesia. The presumption that the short serum half-life of LD is associated with the development of motor complications has raised the need to develop treatments with increased durations of stable LD concentrations.We conducted a PubMed search for IPX066 articles and also reviewed abstracts from meetings that included this topic. IPX066 is a newly developed formulation of extended release carbidopa-LD (CD-LD) with a one to four ratio of CD to LD, that was approved by the FDA in January 2015 for the treatment of PD, post-encephalitic parkinsonism, and parkinsonism that may follow carbon monoxide or manganese intoxication. It will be marketed by the trade name Rytary®. A Phase III clinical trial showed that IPX066 is efficacious in improving motor symptoms in early PD patients. In advanced PD patients with motor fluctuations, IPX066 reduced off time and increased on time without troublesome dyskinesia compared to CD-LD immediate release and CD-LD with entacapone. IPX066 had an acceptable safety profile. Adverse events of IPX066 from the different trials are presented.IPX066 will probably have a role in the treatment of advanced PD with motor fluctuations. IPX066 could also be used initially when LD therapy is prescribed, but the question of whether this usage could reduce or prevent the development of motor complications is yet to be answered.

Making an accurate diagnosis of Parkinson’s disease (PD) is critical for patient counseling and therapeutic management. The diagnosis of PD remains primarily clinical and is based on nonspecific findings on examination. Magnetic resonance imaging and nuclear imaging of the brain can assist in making timely diagnoses and managing treatment appropriately. These tests should not be used routinely, but only in a selected subgroup of patients where the diagnosis of PD is not clear