Publications (22)78.15 Total impact
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Article: Effects of asymmetric dopamine depletion on sensitivity to rewarding and aversive stimuli in Parkinson's disease.
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ABSTRACT: The onset and progression of Parkinson's disease (PD) motor symptoms is generally asymmetric, reflecting differential extent of nigral pathology and resulting dopamine depletion in each of the hemispheres. Given the role of dopamine in processing rewarding and aversive events, and considering findings associating asymmetric neural activity with differential sensitivity to positive and negative stimuli, the current study examined the possibility that dopamine asymmetry in PD is related to differential approach and avoidance tendencies. An original task assessing and comparing sensitivity to positive and negative probabilistic feedback was administered to 29 right-handed participants with idiopathic PD, 16 with predominant right-side and 13 with predominant left-side motor symptoms, to compare the two groups. As dopamine replacement therapy (DRT) has shown different effects on reward and punishment processing, all participants were assessed in both off- and on-medication states. As predicted, when off medication, participants with relatively greater dopamine deficit in the left hemisphere minimized losses better than they increased gains, while those with a greater right hemisphere deficit showed a trend toward the opposite pattern. Medication reversed the relationship between gain and loss sensitivity in the left-hemisphere PD group, but not in the right-hemisphere group. Particularly in the left-hemisphere PD group, findings support the possibility that subcortical dopaminergic asymmetry is reflected in behaviorally-expressed approach and avoidance tendencies. Furthermore, the effects of DRT on approach and avoidance appear to interact with asymmetry, shedding light on previous conclusions regarding the role of dopamine in reinforcement processing.Neuropsychologia 02/2013; · 3.64 Impact Factor -
Article: Snord 3A: A Molecular Marker and Modulator of Prion Disease Progression.
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ABSTRACT: Since preventive treatments for prion disease require early identification of subjects at risk, we searched for surrogate peripheral markers characterizing the asymptomatic phases of such conditions. To this effect, we subjected blood mRNA from E200K PrP CJD patients and corresponding family members to global arrays and found that the expression of Snord3A, a non-coding RNA transcript, was elevated several times in CJD patients as compared to controls, while asymptomatic carriers presented intermediate Snord3A levels. In the brains of TgMHu2ME199K mice, a mouse model mimicking for E200K CJD, Snord 3A levels were elevated in an age and disease severity dependent manner, as was the case for brains of these mice in which disease was exacerbated by copper administration. Snord3A expression was also elevated in scrapie infected mice, but not in PrP(0/0) mice, indicating that while the expression levels of this transcript may reflect diverse prion etiologies, they are not related to the loss of PrP(C)'s function. Elevation of Snord3A was consistent with the activation of ATF6, representing one of the arms of the unfolded protein response system. Indeed, SnoRNAs were associated with reduced resistance to oxidative stress, and with ER stress in general, factors playing a significant role in this and other neurodegenerative conditions. We hypothesize that in addition to its function as a disease marker, Snord3A may play an important role in the mechanism of prion disease manifestation and progression.PLoS ONE 01/2013; 8(1):e54433. · 4.09 Impact Factor -
Article: Dyskinesias in patients with Parkinson's disease: Effect of the leucine-rich repeat kinase 2 (LRRK2) G2019S mutation.
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ABSTRACT: BACKGROUND: While Parkinson's disease (PD) phenotype in leucine-rich repeat kinase 2 gene (LRRK2)-associated and sporadic PD seems similar, there is paucity of data on the possible effect of mutations in LRRK2 on response to and complications of dopaminergic therapy. OBJECTIVE: To assess the impact of the LRRK2 Gly2019Ser (G2019S) carrier status on the time to the onset of levodopa-induced dyskinesias (LID). METHODS: Consecutive PD patients treated with levodopa were genotyped for the LRRK2 G2019S mutation. The relationship between mutation carrier status and the time to LID onset was explored after matching carriers to non-carriers for age at PD onset, gender, and time from PD diagnosis to levodopa initiation, using Kaplan-Meier curves and the Cox proportional hazards model, using LID onset as an end-point. RESULTS: Overall, 349 Israeli PD patients [222 Ashkenazi-Jewish (AJ), 60.5% males, mean age at diagnosis: 60.6 ± 13.2 years] participated in the study. Of these, 33 patients (9.5%, 30 AJ) carried the LRRK2 G2019S mutation. The prevalence of LID was non-significantly higher among carriers (22/33, 66.7%) than non-carriers (168/316, 53.2%, p = 0.15). The mean duration of therapy from levodopa initiation to the development of LID or last follow-up (in cases who were LID-free) was 5.1 ± 5.4 years for carriers and 4.4 ± 4.0 years in non-carriers (p = 0.47) and the survival curves in carriers and matched non-carriers were not significantly different (Cox proportional hazards test and log-rank test; p = 0.79). CONCLUSIONS: The LRRK2 G2019S mutation status has no discernable effect on the prevalence of LID or on LID latency in Israeli levodopa-treated PD patients.Parkinsonism & Related Disorders 06/2012; · 3.80 Impact Factor -
Article: The frontal assessment battery as a tool for evaluation of frontal lobe dysfunction in patients with Parkinson disease.
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ABSTRACT: Frontal-type cognitive deficits are common in patients with Parkinson disease (PD). The Frontal Assessment Battery (FAB) was developed to assess frontal lobe functions. However, many studies found that it also correlated with a variety of other general neuropsychological tests. To evaluate whether the FAB has an added value over the Mini-Mental State Examination (MMSE) and other bedside neuropsychological tests in reflecting cognitive deficits in patients with PD. Seventy-two consecutive patients with PD underwent cognitive assessment including the FAB, the MMSE, and a variety of other neuropsychological tests. Correlations were examined using the Spearman's r. Highly significant correlations were found between the total FAB score and tests of attention, executive functions, and memory. To evaluate the contribution of the FAB beyond that of the MMSE, partial correlation was used. Analyses revealed that the FAB still correlated with most of the tests. Dividing the patients according to the median MMSE score revealed that the high correlation between the FAB and the MMSE was preserved in the low MMSE group, while in the high MMSE group the correlation was relatively low. In the high MMSE group, the FAB correlated with 11 tests compared to the MMSE that correlated with one (P < .001), while in the low MMSE group the number of correlations was 13 versus 7, respectively (P = .05). In our sample of patients with PD, the FAB correlated with dysfunction in a variety of cognitive domains including attention, memory, and executive functions. The FAB has an added value over the MMSE, particularly among nondemented patients, an advantage that can be used in clinical practice.Journal of Geriatric Psychiatry and Neurology 06/2012; 25(2):71-7. · 3.07 Impact Factor -
Article: Immunology, Autoimmunity, and Autoantibodies in Parkinson’s Disease
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ABSTRACT: Recent revelations of immune alterations in Parkinson’s disease have led to the convergence that an autoimmune mechanism may play a role in the etiopathogenesis of this neurodegenerative disease. In the current study, 77 Parkinson’s disease patients and 77 matched healthy controls were analyzed for the presence of seven autoantibodies previously found to be associated with central nervous system manifestations namely: antineuronal-cells, anti-brain lysate, anti-dsDNA, anti-phosphatidylserine, anti-cardiolipin, anti-serotonin, and anti-melanocytes antibodies. Patients underwent systematic assessments of demographics, clinical, and biochemical manifestations. Three autoantibodies were found to be more prevalent among Parkinson’s disease patients (antineuronal cells10.3% vs. 1.3%, p = 0.017; anti-brain lysate 9.1% vs. 1.3%, p = 0.032; anti-dsDNA 10.3% vs. 2.6%, p = 0.049). Clinical manifestations of Parkinson’s disease, particularly dyskinesia and depression, were found to be associated with the presence of these autoantibodies. KeywordsParkinson’s disease–Autoimmune–Autoantibodies–Dyskinesia–DepressionClinical Reviews in Allergy & Immunology 04/2012; 42(2):164-171. · 3.68 Impact Factor -
Article: The leucine rich repeat kinase 2 (LRRK2) G2019S substitution mutation
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ABSTRACT: Background A single missense mutation (G2019S) in the leucine rich repeat kinase 2 (LRRK2) gene has been reported to be prevalent among Ashkenazi Jewish patients with Parkinson disease (PD). An association between malignant melanoma (MM) and PD was also recently reported. The nature of this association is still elusive. Objective To evaluate the rate of the G2019S* LRKK2 mutation among ethnically diverse, Jewish PD patients, MM patients, and Ashkenazi, Iraqi and Moroccan healthy controls. Patients and methods Overall, 242 Jewish PD patients (155 Ashkenazim and 7 of mixed origin) and 169 Jewish MM patients (142 Ashkenazim) were genotyped for the G2019S mutation. In addition, 900 healthy ethnic Jewish controls (300 Ashkenazim, 300 Moroccans and 300 Iraqis) were similarly analyzed. Genotyping was performed using PCR amplification followed by restriction digest and gel electrophoresis. Statistical analysis was done using the Chi square test. Results Overall 19/242 (7.9 %) of the PD patients (16/155 of Ashkenazim, 10.3 %; 3/87 of non-Ashkenazim, 3.4 %) harbored the G2019S LRKK2 mutation. The age at diagnosis of PD in mutation carriers was 60.6 ± 10.9 years compared with an age at diagnosis of 61.1 ± 13.4 years in non-carriers (p = 0.87). Nine of 38 familial Ashkenazi PD patients (23.68 %) carried the mutation, as did 2/169 MM patients (1.2 %; 2/142, 1.4 % of the Ashkenazim). A single mutation carrier of Ashkenazi origin was detected among 900 controls (0.3 % of the Ashkenazi controls). Conclusion The G2019S*LRKK2 mutation is significantly more prevalent in Ashkenazi PD patients than in controls (p = 1 × 10–6), it is less commonly detected in non-Ashkenazi affected individuals, and its contribution to MM predisposition in Jewish individuals needs to be explored further.Journal of Neurology 04/2012; 256(3):483-487. · 3.47 Impact Factor -
Article: Characterization of movement disorders in patients with familial Creutzfeldt-Jakob disease carrying the E200K mutation.
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ABSTRACT: While myoclonus and ataxia are considered common in patients with familial Creutzfeld-Jakob disease (fCJD), other movement disorders are less prevalent. Objectives: To systemically evaluate the frequency of extrapyramidal signs and movement disorders in patients with fCJD. A detailed neurological examination, with special emphasis on movement disorders and extrapyramidal signs, was conducted in 43 consecutive symptomatic CJD patients (26 males and 17 females; mean age 58.7 +/- 8.9 yrs, range 43-77 years) carrying the E200K mutation in the PRNPgene. Limb or gait ataxia was noted in 38 patients (88%) (37 patients, 86%, had ataxia at presentation). Myoclonus was evident in 25/43 patients (58%) (21 patients, 49%, at presentation). In 95% of the patients (41/43) (37/43, 86% at presentation) at least one extrapyramidal sign throughout the disease course was noted, the most prevalent being rigidity (28/43, 65% of the patients; and 22/43, 51% at presentation), followed by the glabellar sign (24/43, 56% of the patients; and 22/43, 51% at presentation), bradykinesia (19/43, 44%; and 15/43, 35% at presentation), dystonia (15/43, 35%; 12/43, 28% at presentation) and tremor (13/43, 30%; 12/43, 28% at presentation). In this unique population of fCJD patients, myoclonus was less prevalent than previously reported while other extrapyramidal signs were common and occurred at a relatively early stage of the disease. The high prevalence of movement disorders can be added to other phenomena characteristic of this familial disorder among Libyan lews. Whether this is attributable to the E200K mutation itself or to some other mechanism has still to be elucidated.The Israel Medical Association journal: IMAJ 03/2012; 14(3):162-5. · 1.02 Impact Factor -
Article: The EEG in E200K familial CJD: relation to MRI patterns.
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ABSTRACT: The aim of the study was to examine the relationship between EEG abnormalities and the pattern of MRI changes in familial Creutzfeldt-Jakob Disease (fCJD) patients with E200K mutation. As part of a controlled, prospective study, 13 E200K fCJD patients underwent comprehensive evaluations, with EEG and an extensive MRI protocol that included one of the most prion-disease sensitive sequences, diffusion-weighted imaging (DWI). The relationship between EEG abnormalities and the pattern of DWI hyperintensities was examined. EEG demonstrated the classical CJD finding of PSWC (periodic sharp wave complexes) in five patients (38%) while in eight patients (62%) the EEG showed only slow activity. Six patients showed the typical cortical changes on MRI, and in five of them (83%) concordance between the MRI and the EEG was found. Five patients had isolated basal ganglia involvement per MRI, and in two of them (40%) concordance between the MRI and the EEG laterality was found. In the remaining two patients MRI did not show any changes suggesting CJD and EEG showed focal slow activity. The EEG of our E200K fCJD patients appears similar to that of the largest prion disease patient group, sporadic CJD (sCJD). EEG abnormalities in E200K fCJD appear to correlate mainly with cortical pathology, as revealed by DWI, rather than basal ganglia pathology. The observation that PSWC abnormalities reflect cortical rather than basal ganglia pathology is significant with respect to theories of the origins of EEG abnormalities in prion disease.Journal of Neurology 08/2011; 259(3):491-6. · 3.47 Impact Factor -
Article: Gender effect on time to levodopa-induced dyskinesias.
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ABSTRACT: Levodopa-induced dyskinesias (LID) are commonly observed during long-term treatment of patients with Parkinson's disease (PD). The impact of non-pharmacological factors on the latency to LID appearance is not known. The aim of the paper was to identify factors associated with time to appearance of LID. Consecutive PD patients treated with levodopa (n = 155) were included in this historical prospective analysis and LID and non-LID groups were compared. The relationship between possible risk factors and the time of LID onset was explored using the Kaplan-Meier method and the Cox multivariate regression model, controlling for the confounding effects of gender, age of disease onset, time to initiation of levodopa treatment, and history of smoking. Patients with LID (57.4%) were significantly younger at disease onset and had a slightly longer latency from diagnosis to levodopa treatment than those without; disease duration and age had no effect on LID appearance. Female gender was associated with a shorter time to LID and the median time to LID was 6 years for males and 4 years for females (p = 0.004). In the multivariate survival analysis a younger age of onset of PD and a longer time from diagnosis to levodopa treatment initiation were also associated with a shorter time to LID appearance (p = 0.030 and 0.036, respectively). Female gender is associated with a significantly shorter latency to LID appearance. Younger age at PD diagnosis and a longer time until starting levodopa are associated with both higher likelihood to develop LID, and a shorter latency until LID were observed.Journal of Neurology 05/2011; 258(11):2048-53. · 3.47 Impact Factor -
Article: Phenotype of the 202 adenine deletion in the parkin gene: 40 years of follow-up.
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ABSTRACT: We describe the four decades follow-up of 14 parkin patients belonging to two large eight-generation-long in-bred Muslim-Arab kindreds. All patients had a single base-pair of adenine deletion at nucleotide 202 of exon 2 (202A) of the parkin gene (all homozygous, one heterozygous). Parkinson's disease onset age was 17-68 years. Special features were intractable axial symptoms (low back pain, scoliosis, camptocormia, antecollis), postural tremor, and preserved cognition. The 202A deletion of the parkin gene causes early-onset Parkinson's disease with marked levodopa/STN-DBS-resistant axial features. Postural tremor and preserved cognition, even after 40 years of disease, were also evident.Movement Disorders 03/2011; 26(4):719-22. · 4.51 Impact Factor -
Article: Tau and 14-3-3 of genetic and sporadic Creutzfeldt-Jakob disease patients in Israel.
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ABSTRACT: One of the largest clusters of genetic Creutzfeldt-Jakob disease (gCJD) is found among Jews of Libyan origin in Israel and is linked to the E200K mutation in PRNP (gCJDE200K). The aim of this study was to compare the levels of cerebrospinal fluid (CSF) biomarkers, Tau and 14-3-3 proteins, between gCJDE200K patients, sporadic CJD (sCJD) patients and non-CJD controls in Israel between the years 1996-2006. The levels of Tau and 14-3-3 proteins in CSF were measured by ELISA and immunoblotting, respectively. CSF Tau levels were similar in gCJDE200K and sCJD, both were significantly higher than in controls [1,107 ± 470 pg/ml [33/46 (72%)] of the cases >1,000 pg/ml, 1,280 ± 580 pg/ml [25/30 (83.3%)], and 354 ± 338 pg/ml [17/243 (6.9%)], respectively, p < 0.001]. 14-3-3 was detected in CSF of 41/53 (77%) of each gCJDE200K and sCJD patients tested, but only in 70/417 (16.8%) of controls (p < 0.001). An inverse correlation was found between disease duration and Tau levels in both gCJDE200K and sCJD (r = -0.464 and r = -0.284). No difference was found in Tau or 14-3-3 between the various codon 129 genotypes. We conclude that CSF biomarkers, Tau and 14-3-3, may be used in the diagnosis in both patients' populations, presenting a similar sensitivity yet Tau assay having higher specificity.Journal of Neurology 02/2011; 258(2):255-62. · 3.47 Impact Factor -
Article: Genomic duplications mediate overexpression of lamin B1 in adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms.
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ABSTRACT: Adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms features micturition urgency, constipation, erectile dysfunction, and orthostatic hypotension, usually followed by pyramidal signs and ataxia. Peripheral nerve conduction is normal. The disease is often mistaken for multiple sclerosis in the initial phase. There is a characteristic pattern of white matter changes in the brain and spinal cord on magnetic resonance imaging (MRI), mild atrophy of the brain, and a more marked atrophy of the spinal cord. ADLD is associated with duplications of the lamin B1 (LMNB1) gene but the mechanism by which the rearrangement conveys the phenotype is not fully defined. We analyzed four unrelated families segregating ADLD with autonomic symptoms for duplications of the LMNB1 gene. A single nucleotide polymorphism (SNP) array analysis revealed novel duplications spanning the entire LMNB1 gene in probands from each of the four families. We then analyzed the expression of lamin B1 in peripheral leukocytes by Western blot analysis in five patients from two available families. The protein levels of lamin B1 were found significantly increased. These results indicate that the ADLD phenotype associated with LMNB1 duplications is mediated by increased levels of the lamin B1 protein. Furthermore, we show that a molecular diagnosis for ADLD with autonomic symptoms can be obtained by a direct analysis of lamin B1 in peripheral leukocytes.Neurogenetics 02/2011; 12(1):65-72. · 3.35 Impact Factor -
Article: Pruritus in familial Creutzfeldt-Jakob disease: a common symptom associated with central nervous system pathology.
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ABSTRACT: Pruritus, a common feature of animal prion diseases such as scrapie, is rarely reported in humans with Creutzfeldt-Jakob disease (CJD), and its anatomical background is not well defined. The present study was undertaken to carry out a methodical prospective search for the prevalence of pruritus in CJD patients and investigate its anatomical substrate by MRI. The study group included consecutive familial and sporadic CJD patients carrying the E200K PRNP mutation followed up in a longitudinal prospective study between the years 2005 and 2008. Pruritus was prospectively screened for and diffusion-weighted imaging (DWI) was used to correlate brain diffusion abnormalities with pruritus in CJD patients. Pruritus was present in 6/31 (19.35%) patients with familial disease (fCJD) and in none of the patients with sporadic disease (sCJD). Pruritus was a presenting symptom in one patient and evolved during the course of the disease in the other five patients. The pruritus was generalized in three patients, regional in two and localized in one patient. It was transient in one patient and continued throughout the disease in five patients. DWI showed that pruritus was significantly associated with reduced diffusion in the several areas known to be affected by CJD, but most significantly in the midbrain periaqueductal grey matter. Pruritus is relatively common in patients with familial CJD carrying the E200K mutation. Our findings point to a central origin that involves damage to the inhibitory gating mechanism for itch in the periaqueductal grey matter.Journal of Neurology 01/2011; 258(1):89-95. · 3.47 Impact Factor -
Article: Immunology, autoimmunity, and autoantibodies in Parkinson's disease.
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ABSTRACT: Recent revelations of immune alterations in Parkinson's disease have led to the convergence that an autoimmune mechanism may play a role in the etiopathogenesis of this neurodegenerative disease. In the current study, 77 Parkinson's disease patients and 77 matched healthy controls were analyzed for the presence of seven autoantibodies previously found to be associated with central nervous system manifestations namely: antineuronal-cells, anti-brain lysate, anti-dsDNA, anti-phosphatidylserine, anti-cardiolipin, anti-serotonin, and anti-melanocytes antibodies. Patients underwent systematic assessments of demographics, clinical, and biochemical manifestations. Three autoantibodies were found to be more prevalent among Parkinson's disease patients (antineuronal cells10.3% vs. 1.3%, p = 0.017; anti-brain lysate 9.1% vs. 1.3%, p = 0.032; anti-dsDNA 10.3% vs. 2.6%, p = 0.049). Clinical manifestations of Parkinson's disease, particularly dyskinesia and depression, were found to be associated with the presence of these autoantibodies.Clinical Reviews in Allergy & Immunology 01/2011; 42(2):164-71. · 3.68 Impact Factor -
Article: Is C-reactive protein level a marker of advanced motor and neuropsychiatric complications in Parkinson's disease?
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ABSTRACT: C-reactive protein (CRP) is a plasma protein involved in inflammation. While its levels have been associated with stroke, cognitive impairment and depression, the association with clinical characteristics of Parkinson's disease (PD) is unknown. A total of 73 consecutive patients with PD (46 males, age 68.8 ± 11.5 years) were evaluated regarding motor as well as cognitive and psychiatric features of PD. Plasma CRP levels were determined and tests for associations with disease parameters were performed. The average level of CRP was 3.9 ± 4.1 μmol/L, and 45.2% of the patients (n = 33) had a level above 3.0 μmol/L. Patients in the high CRP group tended to be older (71.4 ± 9.2 vs. 66.7 ± 12.9 years; p = 0.08) and coronary artery disease (CAD) was more common (36 vs. 10%, p < 0.05) in the high CRP group, but no differences were found between the groups regarding gender, disease duration, levodopa dose, motor scores or most of the neuropsychiatric complications such as severity of depression, psychosis, dementia, cognitive decline or frontal lobe dysfunction. Reported depression (at present or in the past) was more common in the high CRP group (54.5 vs. 25%, p = 0.01). CRP levels in patients with PD are associated with a higher prevalence of CAD, but are not associated with PD duration or severity, or with neuropsychiatric complications other than reported depression.Acta Neurovegetativa 12/2010; 118(4):539-43. · 2.73 Impact Factor -
Article: Putaminal volume and diffusion in early familial Creutzfeldt-Jakob disease.
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ABSTRACT: The putamen is centrally implicated in the pathophysiology of Creutzfeldt-Jakob Disease (CJD). To our knowledge, its volume has never been measured in this disease. We investigated whether gross putaminal atrophy can be detected by MRI in early stages, when the diffusion is already reduced. Twelve familial CJD patients with the E200K mutation and 22 healthy controls underwent structural and diffusion MRI scans. The putamen was identified in anatomical scans by two methods: manual tracing by a blinded investigator, and automatic parcellation by a computerized segmentation procedure (FSL FIRST). For each method, volume and mean Apparent Diffusion Coefficient (ADC) were calculated. ADC was significantly lower in CJD patients (697+/-64 microm(2)/s vs. 750+/-31 microm(2)/s, p<0.005), as expected, but the volume was not reduced. The computerized FIRST delineation yielded comparable ADC values to the manual method, but computerized volumes were smaller than manual tracing values. We conclude that significant diffusion reduction in the putamen can be detected by delineating the structure manually or with a computerized algorithm. Our findings confirm and extend previous voxel-based and observational studies. Putaminal volume was not reduced in our early-stage patients, thus confirming that diffusion abnormalities precede detectible atrophy in this structure.Journal of the neurological sciences 10/2009; 288(1-2):129-34. · 2.32 Impact Factor -
Article: The leucine rich repeat kinase 2 (LRRK2) G2019S substitution mutation. Association with Parkinson disease, malignant melanoma and prevalence in ethnic groups in Israel.
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ABSTRACT: A single missense mutation (G2019S) in the leucine rich repeat kinase 2 (LRRK2) gene has been reported to be prevalent among Ashkenazi Jewish patients with Parkinson disease (PD). An association between malignant melanoma (MM) and PD was also recently reported. The nature of this association is still elusive. To evaluate the rate of the G2019S(*) LRKK2 mutation among ethnically diverse, Jewish PD patients, MM patients, and Ashkenazi, Iraqi and Moroccan healthy controls. Overall, 242 Jewish PD patients (155 Ashkenazim and 7 of mixed origin) and 169 Jewish MM patients (142 Ashkenazim) were genotyped for the G2019S mutation. In addition, 900 healthy ethnic Jewish controls (300 Ashkenazim, 300 Moroccans and 300 Iraqis) were similarly analyzed. Genotyping was performed using PCR amplification followed by restriction digest and gel electrophoresis. Statistical analysis was done using the Chi square test. Overall 19/242 (7.9 %) of the PD patients (16/155 of Ashkenazim, 10.3 %; 3/87 of non-Ashkenazim, 3.4 %) harbored the G2019S LRKK2 mutation. The age at diagnosis of PD in mutation carriers was 60.6 +/- 10.9 years compared with an age at diagnosis of 61.1 +/- 13.4 years in non-carriers (p = 0.87). Nine of 38 familial Ashkenazi PD patients (23.68 %) carried the mutation, as did 2/169 MM patients (1.2 %; 2/142, 1.4 % of the Ashkenazim). A single mutation carrier of Ashkenazi origin was detected among 900 controls (0.3 % of the Ashkenazi controls). The G2019S*LRKK2 mutation is significantly more prevalent in Ashkenazi PD patients than in controls (p = 1 x 10(-6)), it is less commonly detected in non-Ashkenazi affected individuals, and its contribution to MM predisposition in Jewish individuals needs to be explored further.Journal of Neurology 04/2009; 256(3):483-7. · 3.47 Impact Factor -
Article: Thalamo-striatal diffusion reductions precede disease onset in prion mutation carriers.
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ABSTRACT: Human prion diseases present substantial scientific and public health challenges. They are unique in being sporadic, infectious and inherited, and their pathogen is distinct from all other pathogens in lacking nucleic acids. Despite progress in understanding the molecular structure of prions, their initial cerebral pathophysiology and the loci of cerebral injury are poorly understood. As part of a large prospective study, we analysed early diffusion MRI scans of 14 patients with the E200K genetic form of Creutzfeldt-Jakob Disease, 20 healthy carriers of this mutation that causes the disease and 20 controls without the mutation from the same families. Cerebral diffusion was quantified by the Apparent Diffusion Coefficient, and analysed by voxel-wise statistical parametric mapping technique. Compared to the mutation-negative controls, diffusion was significantly reduced in a thalamic-striatal network, comprising the putamen and mediodorsal, ventrolateral and pulvinar thalamic nuclei, in both the patients and the healthy mutation carriers. With disease onset, these diffusion reductions intensified, but did not spread to other areas. The caudate nucleus was reduced only after symptomatic onset. These findings indicate that cerebral diffusion reductions can be detected early in the course of Creutzfeldt-Jakob Disease, and years before symptomatic onset in mutation carriers, in a distinct subcortical network. We suggest that this network is centrally involved in the pathogenesis of Creutzfeldt-Jakob Disease, and its anatomical connections are sufficient to account for the common symptoms of this disease. Further, we suggest that the abnormalities in healthy mutation-carrying subjects may reflect the accumulation of abnormal prion protein and/or associated vacuolation at this time, temporally close to disease onset.Brain 04/2009; 132(Pt 10):2680-7. · 9.46 Impact Factor -
Article: Association of preoperative symptom profile with psychiatric symptoms following subthalamic nucleus stimulation in patients with Parkinson's disease.
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ABSTRACT: In order to evaluate the severity of behavioral complications after deep brain stimulation of the subthalamic nucleus (STN-DBS) for Parkinson's disease and to explore possible predictive factors, the authors evaluated 22 patients for pre- and postoperative symptoms using a neurobehavioral battery. Compared to the time before STN-DBS, several behavioral symptoms had worsened in terms of prevalence and severity and appeared de novo in other patients. Apathy, anxiety, and suicidal ideation increased significantly, while depressive symptoms appeared stable. Compared with patients who improved, patients who had deteriorated behaviorally had similar prevalence and severity of preoperative behavioral symptoms but significantly shorter disease duration.The Journal of neuropsychiatry and clinical neurosciences 01/2009; 21(4):398-405. · 2.34 Impact Factor -
Article: Deep brain stimulation of the internal globus pallidus for refractory tardive dystonia.
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ABSTRACT: We report a rapid, dramatic and sustained improvement following bilateral pallidal stimulation in two patients affected by intractable generalized tardive dystonia. Both patients had a chronic psychiatric disorder and developed chronic disabling generalized dystonic symptoms persisting despite prolonged withdrawal of neuroleptics and all available symptomatic treatment. The clinical benefit in both patients persisted throughout all the follow up period of 13 and 7 months. The favorable and prolonged response in our two patients suggests that deep brain stimulation may be an effective treatment for medically refractory tardive dystonia.Parkinsonism & Related Disorders 01/2008; 13(8):541-4. · 3.80 Impact Factor
Top co-authors
Top Journals
Institutions
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2012
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State of Israel Ministry of Health
Tel Aviv, Tel Aviv, Israel
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2007–2012
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Tel Aviv University
- Department of Neurology
Tel Aviv, Tel Aviv, Israel -
Sheba Medical Center
Ramat Gan, Tel Aviv, Israel
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2009
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Mount Sinai School of Medicine
- Department of Psychiatry
Manhattan, NY, USA
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