Stewart A Factor

Emory University, Atlanta, Georgia, United States

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Publications (221)1283.07 Total impact

  • Kevin Michael Biglan · Ira Shoulson · Karl Kieburtz · David Oakes · Elise Kayson · M Aileen Shinaman · Hongwei Zhao · Megan Romer · Anne Young · Steven Hersch · [...] · Alicia Brocht · Arthur Watts · Shirley Eberly · Christine Weaver · Tatiana Foroud · James Gusella · Marcy MacDonald · Richard Myers · Stanley Fahn · Clifford Shults ·
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    ABSTRACT: Importance: Identifying measures that are associated with the cytosine-adenine-guanine (CAG) expansion in individuals before diagnosis of Huntington disease (HD) has implications for designing clinical trials. Objective: To identify the earliest features associated with the motor diagnosis of HD in the Prospective Huntington at Risk Observational Study (PHAROS). Design, setting, and participants: A prospective, multicenter, longitudinal cohort study was conducted at 43 US and Canadian Huntington Study Group research sites from July 9, 1999, through December 17, 2009. Participants included 983 unaffected adults at risk for HD who had chosen to remain unaware of their mutation status. Baseline comparability between CAG expansion (≥37 repeats) and nonexpansion (<37 repeats) groups was assessed. All participants and investigators were blinded to individual CAG analysis. A repeated-measures analysis adjusting for age and sex was used to assess the divergence of the linear trend between the expanded and nonexpanded groups. Data were analyzed from April 27, 2010, to September 3, 2013. Exposure: Huntington disease mutation status in individuals with CAG expansion vs without CAG expansion. Main outcomes and measures: Unified Huntington's Disease Rating Scale motor (score range, 0-124; higher scores indicate greater impairment), cognitive (symbol digits modality is the total number of correct responses in 90 seconds; lower scores indicate greater impairment), behavioral (score range, 0-176; higher scores indicate greater behavioral symptoms), and functional (Total Functional Capacity score range, 0-13; lower scores indicate reduced functional ability) domains were assessed at baseline and every 9 months up to a maximum of 10 years. Results: Among the 983 research participants at risk for HD in the longitudinal cohort, 345 (35.1%) carried the CAG expansion and 638 (64.9%) did not. The mean (SD) duration of follow-up was 5.8 (3.0) years. At baseline, participants with expansions had more impaired motor (3.0 [4.2] vs 1.9 [2.8]; P < .001), cognitive (P < .05 for all measures except Verbal Fluency, P = .52), and behavioral domain scores (9.4 [11.4] vs 6.5 [8.5]; P < .001) but not significantly different measures of functional capacity (12.9 [0.3] vs 13.0 [0.2]; P = .23). With findings reported as mean slope (95% CI), in the longitudinal analyses, participants with CAG expansions showed significant worsening in motor (0.84 [0.73 to 0.95] vs 0.03 [-0.05 to 0.11]), cognitive (-0.54 [-0.67 to -0.40] vs 0.22 [0.12 to 0.32]), and functional (-0.08 [-0.09 to -0.06] vs -0.01 [-0.02 to 0]) measures compared with those without expansion (P < .001 for all); behavioral domain scores did not diverge significantly between groups. Conclusions and relevance: Using these prospectively accrued clinical data, relatively large treatment effects would be required to mount a randomized, placebo-controlled clinical trial involving premanifest HD individuals who carry the CAG expansion.
    11/2015; DOI:10.1001/jamaneurol.2015.2736

  • International Psychogeriatric Association; 10/2015
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    ABSTRACT: Objective: To identify the causal gene in a multi-incident U.S. kindred with Parkinson's disease (PD). Methods: We characterized a family with a classical PD phenotype in which 7 individuals (5 males and 2 females) were affected with a mean age at onset of 46.1 years (range, 29-57 years). We performed whole exome sequencing on 4 affected and 1 unaffected family members. Sanger-sequencing was then used to verify and genotype all candidate variants in the remainder of the pedigree. Cultured cells transfected with wild-type or mutant constructs were used to characterize proteins of interest. Results: We identified a missense mutation (c.574G > A; p.G192R) in the RAB39B gene that closely segregated with disease and exhibited X-linked dominant inheritance with reduced penetrance in females. The mutation occurred in a highly conserved amino acid residue and was not observed among 87,725 X chromosomes in the Exome Aggregation Consortium dataset. Sequencing of the RAB39B coding region in 587 familial PD cases yielded two additional mutations (c.428C > G [p.A143G] and c.624_626delGAG [p.R209del]) that were predicted to be deleterious in silico but occurred in families that were not sufficiently informative to assess segregation with disease. Experiments in PC12 and SK-N-BE(2)C cells demonstrated that p.G192R resulted in mislocalization of the mutant protein, possibly by altering the structure of the hypervariable C-terminal domain which mediates intracellular targeting. Conclusions: Our findings implicate RAB39B, an essential regulator of vesicular-trafficking, in clinically typical PD. Further characterization of normal and aberrant RAB39B function might elucidate important mechanisms underlying neurodegeneration in PD and related disorders.
    Molecular Neurodegeneration 09/2015; 10(1):50. DOI:10.1186/s13024-015-0045-4 · 6.56 Impact Factor
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    ABSTRACT: Background Tardive dyskinesia is a persistent movement disorder induced by chronic neuroleptic exposure. NBI-98854 is a novel, highly selective, vesicular monoamine transporter 2 inhibitor. We present results of a randomized, 6-week, double-blind, placebo-controlled, dose-titration study evaluating the safety, tolerability, and efficacy of NBI-98854 for the treatment of tardive dyskinesia.Methods Male and female adult subjects with moderate or severe tardive dyskinesia were included. NBI-98854 or placebo was given once per day starting at 25 mg and then escalated by 25 mg to a maximum of 75 mg based on dyskinesia and tolerability assessment. The primary efficacy endpoint was the change in Abnormal Involuntary Movement Scale from baseline at week 6 scored by blinded, central video raters. The secondary endpoint was the Clinical Global Impression of Change—Tardive Dyskinesia score assessed by the blinded investigator.ResultsTwo hundred five potential subjects were screened, and 102 were randomized; 76% of NBI-98854 subjects and 80% of placebo subjects reached the maximum allowed dose. Abnormal Involuntary Movement Scale scores for NBI-98854 compared with placebo were significantly reduced (p = 0.0005). Active drug was also superior on the Clinical Global Impression of Change—Tardive Dyskinesia (p < 0.0001). Treatment-emergent adverse event rates were 49% in the NBI-98854 and 33% in the placebo subjects. The most common adverse events (active vs. placebo) were fatigue and headache (9.8% vs. 4.1%) and constipation and urinary tract infection (3.9% vs. 6.1%). No clinically relevant changes in safety assessments were noted.ConclusionNBI-98854 significantly improved tardive dyskinesia and was well tolerated in patients. These results support the phase 3 clinical trials of NBI-98854 now underway. © 2015 International Parkinson and Movement Disorder Society
    Movement Disorders 09/2015; 30(12). DOI:10.1002/mds.26330 · 5.68 Impact Factor
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    ABSTRACT: Loss-of-function mutations in the GBA gene are associated with more severe cognitive impairment in PD, but the nature of these deficits is not well understood and whether common GBA polymorphisms influence cognitive performance in PD is not yet known. We screened the GBA coding region for mutations and the E326K polymorphism in 1,369 PD patients enrolled at eight sites from the PD Cognitive Genetics Consortium. Participants underwent assessments of learning and memory (Hopkins Verbal Learning Test-Revised), working memory/executive function (Letter-Number Sequencing Test and Trail Making Test A and B), language processing (semantic and phonemic verbal fluency), visuospatial abilities (Benton Judgment of Line Orientation), and global cognitive function (MoCA). We used linear regression to test for association between genotype and cognitive performance with adjustment for important covariates and accounted for multiple testing using Bonferroni's corrections. Mutation carriers (n = 60; 4.4%) and E326K carriers (n = 65; 4.7%) had a higher prevalence of dementia (mutations, odds ratio = 5.1; P = 9.7 × 10(-6) ; E326K, odds ratio = 6.4; P = 5.7 × 10(-7) ) and lower performance on Letter-Number Sequencing (mutations, corrected P[Pc ] = 9.0 × 10(-4) ; E326K, Pc = 0.036), Trail Making B-A (mutations, Pc = 0.018; E326K, Pc = 0.018), and Benton Judgment of Line Orientation (mutations, Pc = 0.0045; E326K, Pc = 0.0013). Both GBA mutations and E326K are associated with a distinct cognitive profile characterized by greater impairment in working memory/executive function and visuospatial abilities in PD patients. The discovery that E326K negatively impacts cognitive performance approximately doubles the proportion of PD patients we now recognize are at risk for more severe GBA-related cognitive deficits. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.
    Movement Disorders 08/2015; DOI:10.1002/mds.26359 · 5.68 Impact Factor
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    ABSTRACT: This study reports the baseline characteristics of diffusion tensor imaging data in Parkinson's disease (PD) patients and healthy control subjects from the Parkinson's Progression Markers Initiative. The main goals were to replicate previous findings of abnormal diffusion imaging values from the substantia nigra. in a large multicenter cohort and determine whether nigral diffusion alterations are associated with dopamine deficits. Two hundred twenty subjects (PD = 153; control = 67) from 10 imaging sites were included. All subjects had a full neurological exam, a ((123) I)ioflupane dopamine transporter (DAT) single-photon emission computer tomography scan, and diffusion tensor imaging. Fractional anisotropy as well as radial and axial diffusivity was computed within multiple regions across the substantia nigra. A repeated-measures analysis of variance found a marginally nonsignificant interaction between regional fractional anisotropy of the substantia nigra and disease status (P = 0.08), conflicting with an earlier study. However, a linear mixed model that included control regions in addition to the nigral regions revealed a significant interaction between regions and disease status (P = 0.002), implying a characteristic distribution of reduced fractional anisotropy across the substantia nigra in PD. Reduced fractional anisotropy in PD was also associated with diminished DAT binding ratios. Both axial and radial diffusivity were also abnormal in PD. Although routine nigral measurements of fractional anisotropy are clinically not helpful, the findings in this study suggest that more-sophisticated diffusion imaging protocols should be used when exploring the clinical utility of this imaging modality. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.
    Movement Disorders 08/2015; DOI:10.1002/mds.26325 · 5.68 Impact Factor
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    ABSTRACT: A 12-month double-blind sham-surgery-controlled trial assessing adeno-associated virus type 2 (AAV2)-neurturin injected into the putamen bilaterally failed to meet its primary endpoint, but showed positive results for the primary endpoint in the subgroup of subjects followed for 18 months and for several secondary endpoints. Analysis of postmortem tissue suggested impaired axonal transport of neurturin from putamen to substantia nigra. In the present study, we tested the safety and efficacy of AAV2-neurturin delivered to putamen and substantia nigra. We performed a 15- to 24-month, multicenter, double-blind trial in patients with advanced Parkinson disease (PD) who were randomly assigned to receive bilateral AAV2-neurturin injected bilaterally into the substantia nigra (2.0 × 10(11) vector genomes) and putamen (1.0 × 10(12) vector genomes) or sham surgery. The primary endpoint was change from baseline to final visit performed at the time the last enrolled subject completed the 15-month evaluation in the motor subscore of the Unified Parkinson's Disease Rating Scale in the practically defined off state. Fifty-one patients were enrolled in the trial. There was no significant difference between groups in the primary endpoint (change from baseline: AAV2-neurturin, -7.0 ± 9.92; sham, -5.2 ± 10.01; p = 0.515) or in most secondary endpoints. Two subjects had cerebral hemorrhages with transient symptoms. No clinically meaningful adverse events were attributed to AAV2-neurturin. AAV2-neurturin delivery to the putamen and substantia nigra bilaterally in PD was not superior to sham surgery. The procedure was well tolerated, and there were no clinically significant adverse events related to AAV2-neurturin. Ann Neurol 2015. © 2015 American Neurological Association.
    Annals of Neurology 06/2015; 78(2). DOI:10.1002/ana.24436 · 9.98 Impact Factor
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    ABSTRACT: Objective Ocular palatal tremor (OPT) typically develops after a breach in the Guillian-Mollaret triangle. We herein describe a variant of this syndrome in which dystonia is also present, hence called, here, ocular palatal tremor plus dystonia.Methods We assessed eye-head movements and dystonia in 6 patients with ocular palatal plus dystonia.ResultsAmong 6 patients with OPT, 2 had focal dystonia, 3 had multifocal dystonia, and 1 had generalized dystonia. The dystonia affected the upper extremities and neck in 4 patients, the lower extremities in 3, and the face in 2. Three of four cervical dystonia patients had head tremor. Two patients also had speech involvement. Lack of correlation between eye and head oscillations suggested that head oscillations were not compensatory or secondary to the eye oscillations and vice versa.Conclusions We describe a novel variant of OPT with dystonia. We speculate that in such a variant, the dystonia possibly could be a result of abnormal cerebellar outflow in patients with a breach in the Guillain-Mollaret triangle.
    06/2015; DOI:10.1002/mdc3.12193
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    ABSTRACT: Research suggests an association between global cognition and postural instability/gait disturbance (PIGD) in Parkinson disease (PD), but the relationship between specific cognitive domains and PIGD symptoms is not clear. This study examined the association of cognition (global and specific cognitive domains) with PIGD symptoms in a large, well-characterized sample of individuals with PD. Cognitive function was measured with a detailed neuropsychological assessment, including global cognition, executive function, memory, visuospatial function, and language. PIGD symptoms were measured using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III, Motor Examination subscale. Multiple linear regression analyses were performed to assess the relationship between cognition and PIGD symptoms with models adjusting for age, sex, education, enrollment site, disease duration, and motor symptom severity. The analysis included 783 participants, with mean (standard deviation) age of 67.3 (9.7) years and median (interquartile range) MDS-UPDRS Motor Subscale score of 26 (17, 35). Deficits in global cognition, executive function, memory, and phonemic fluency were associated with more severe PIGD symptoms. Deficits in executive function were associated with impairments in gait, freezing, and postural stability, while visuospatial impairments were associated only with more severe freezing, and poorer memory function was associated only with greater postural instability. While impairments in global cognition and aspects of executive functioning were associated with more severe PIGD symptoms, specific cognitive domains were differentially related to distinct PIGD components, suggesting the presence of multiple neural pathways contributing to associations between cognition and PIGD symptoms in persons with PD. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Parkinsonism & Related Disorders 04/2015; 21(7). DOI:10.1016/j.parkreldis.2015.04.002 · 3.97 Impact Factor
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    ABSTRACT: Increasing evidence suggests that genetic factors play a role in the variability associated with cognitive performance in Parkinson's disease (PD). Mutations in the LRRK2 gene are the most common cause of monogenic PD; however, the cognitive profile of LRRK2-related PD is not well-characterized. A cohort of 1,447 PD patients enrolled in the PD Cognitive Genetics Consortium was screened for LRRK2 mutations and completed detailed cognitive testing. Associations between mutation carrier status and cognitive test scores were assessed using linear regression models. LRRK2 mutation carriers (n = 29) demonstrated better performance on the Mini Mental State Examination (P = 0.03) and the Letter-Number Sequencing Test (P = 0.005). A smaller proportion of LRRK2 carriers were demented (P = 0.03). Our cross-sectional study demonstrates better performance on certain cognitive tests, as well as lower rates of dementia in LRRK2-related PD. Future longitudinal studies are needed to determine whether LRRK2 mutation carriers exhibit slower cognitive decline. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.
    Movement Disorders 02/2015; 30(5). DOI:10.1002/mds.26161 · 5.68 Impact Factor
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    ABSTRACT: Background: Sleep disturbance and cognitive impairment are correlated in non-diseased populations, but their association in Parkinson's disease (PD) is uncertain. Prior studies employing measures of cognition and actigraphically-measured sleep have produced conflicting findings. Objective: In this descriptive study, we correlated measurements of sleep in PD patients derived from the gold-standard measurement, in-lab polysomnography, with an extensive battery of cognitive measures. We hypothesized that poorer sleep would be related to relatively more impaired cognition. Methods: Idiopathic PD patients (n = 34) completed a cognitive battery encompassing three broad domains (executive function, immediate memory and delayed memory), and underwent PSG for two nights. Scores for each domain from individual cognitive measures were converted to z-scores and then averaged to produce a composite score. We used second night PSG data and quantified measures of sleep architecture, sleep continuity, sleep apnea and nocturnal movement (periodic leg movements, PLMS). Results: Lower executive function was associated with higher PLMS after controlling for chronological age, mini-mental state examination scores, and UPDRS motor subscale scores. These results were independent from psychomotor speed. There was a marginally significant positive correlation between the proportion of time spent in REM and immediate recall ability. Measures of sleep continuity and sleep apnea were unrelated to cognition in these patients. Conclusions: PLMS, known to be a frequent feature of PSG-measured sleep in PD, may be an important correlate of impaired executive function in PD. Whether treating this disorder of sleep results in improvement in cognition remains to be determined.
    Journal of Parkinson's Disease 01/2015; 5(1). DOI:10.3233/JPD-140475 · 1.91 Impact Factor
  • H.A. Jinnah · Stewart A. Factor ·
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    ABSTRACT: The dystonias are a group of disorders characterized by excessive involuntary muscle contractions leading to abnormal postures and/or repetitive movements. A careful assessment of the clinical manifestations is helpful for identifying syndromic patterns that focus diagnostic testing on potential causes. If a cause is identified, specific etiology-based treatments may be available. In most cases, a specific cause cannot be identified, and treatments are based on symptoms. Treatment options include counseling, education, oral medications, botulinum toxin injections, and several surgical procedures. A substantial reduction in symptoms and improved quality of life is achieved in most patients by combining these options. Copyright © 2015 Elsevier Inc. All rights reserved.
    Neurologic Clinics 11/2014; 33(1). DOI:10.1016/j.ncl.2014.09.002 · 1.40 Impact Factor
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    ABSTRACT: Several case reports and small series have indicated that tardive dystonia is responsive to globus pallidus deep brain stimulation. Whether different subtypes or distributions of tardive dystonia are associated with different outcomes remains unknown.Methods We assessed the outcomes and temporal profile of improvement of eight tardive dystonia patients who underwent globus pallidus deep brain stimulation over the past six years through record review. Due to the retrospective nature of this study, it was not blinded or placebo controlled.ResultsConsistent with previous studies, deep brain stimulation improved the overall the Burke-Fahn-Marsden motor scores by 85.1±13.5%. The distributions with best responses in descending order were upper face, lower face, larynx/pharynx, limbs, trunk, and neck. Patients with prominent cervical dystonia demonstrated improvement in the Toronto Western Spasmodic Torticollis Rating Scale but improvements took several months. In four patients the effects of deep brain stimulation on improvement in Burke Fahn Marsden score was rapid, while in four cases there was partial rapid response of neck and trunk dystonia followed by was gradual resolution of residual symptoms over 48 months.Conclusion Our retrospective analysis shows excellent resolution of tardive dystonia after globus pallidus deep brain stimulation. We found instantaneous response, except with neck and trunk dystonia where partial recovery was followed by further resolution at slower rate. Such outcome is encouraging for using deep brain stimulation in treatment of tardive dystonia.
    Parkinsonism & Related Disorders 11/2014; 21(2). DOI:10.1016/j.parkreldis.2014.11.013 · 3.97 Impact Factor
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    PLoS Genetics 11/2014; 10(11):e1004774. DOI:10.1371/journal.pgen.1004774 · 7.53 Impact Factor
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    ABSTRACT: Background: Hallucinations and delusions that complicate Parkinson's disease (PD) could lead to nursing home placement and are linked to increased mortality. Cognitive impairments are typically associated with the presence of hallucinations but there are no data regarding whether such a relationship exists with delusions. Objective: We hypothesized that hallucinations would be associated with executive and visuospatial disturbance. An exploratory examination of cognitive correlates of delusions was also completed to address the question of whether they differ from hallucinations. Methods: 144 PD subjects completed a neuropsychological battery to assess cognition and the SAPS to examine psychosis. Correlational analyses assessed associations between hallucinations and delusions with cognitive domains. Results: 48 subjects (33%) reported psychotic symptoms: 25 (17%) experienced hallucinations without delusions, 23 (16%) had symptoms dominated by delusions. Severity and/or number of hallucination subtypes were significantly correlated with lower scores in language, memory, attention, executive functioning, and visuospatial ability. Correlations with delusions were non-significant. Tests of differences in the size of the correlations between groups revealed a significant relationship between language and visuospatial performance with hallucinations. Conclusions: Cognitive correlates of hallucinations and delusions appear to be different in PD, suggesting distinct pathogenic mechanisms and possibly anatomical substrates. Hence, delusions may not share the same associations with dementia as hallucinations. Since this is a new finding, further studies will be needed to confirm our results.
    Journal of the Neurological Sciences 10/2014; 347(1-2). DOI:10.1016/j.jns.2014.10.033 · 2.47 Impact Factor
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    Deepti Zutshi · Leslie J Cloud · Stewart A Factor ·
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    ABSTRACT: Background Several studies have examined reversibility of tardive syndromes (TS), primarily in psychotic patients who are maintained on dopamine receptor blocking drugs. The results have varied widely. However, few have assessed remission rates after discontinuing the offending agents. This study evaluated reversibility of TS in patients who permanently withdrew the causative agent(s). We also examined for any possible clinical predictors of reversibility. Methods A retrospective cohort of 108 TS patients was studied. Most of the patients were not psychotic; most patients were being treated either for a mood disorder with atypical antipsychotics or for a gastrointestinal disturbance with metoclopramide. Patients were stratified on the basis of reversibility, and statistical tests were used for subgroup comparisons of relevant clinical variables. Logistic regression was undertaken to identify clinical variables predictive of reversibility. Results Only 13% of the cohort experienced reversibility of the TS, 2% without medical intervention. When stratified by reversibility, there were no significant differences in any study variables between subgroups. None of the study variables predicted reversibility in the logistic regression. Discussion Our study demonstrated a low remission rate for TS in a cohort of psychiatric and non-psychiatric patients seen in a movement disorder clinic after the offending agents were completely withdrawn. Such a finding has significant prognostic implications. It is possible that limitations of the retrospective design may have resulted in an underestimation. There is a clear need for prospective, multicenter, clinical trials in populations that can be safely withdrawn from dopamine receptor blocking agents so that true remission rates can be measured.
    10/2014; 4:266. DOI:10.7916/D8MS3R8C

  • Neurology 10/2014; 83(15):1388-9. DOI:10.1212/01.wnl.0000455698.16732.0a · 8.29 Impact Factor
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    ABSTRACT: Background Freezing of gait (FOG) is major concern for Parkinson’s disease (PD) patients because it is a leading cause of falls and is associated with poor quality of life. The pathophysiology is unknown but it is hypothesized that it relates to cognitive abnormalities; particularly executive and visuospatial dysfunction. However, prior results have been discrepant. Pharmacologic subtypes of FOG include those that are responsive and unresponsive to levodopa. Objective To determine whether executive and visuospatial dysfunction are associated specifically with the levodopa unresponsive subtype of FOG. Methods 135 PD subjects completed a single assessment included FOG questionnaire, UPDRS motor scale, comprehensive cognitive battery and measure of hallucinations. Analyses compared unresponsive (n=16), responsive (n=20) and no FOG (n=99) subtypes. Results The unresponsive subtype had a significantly older age of onset of PD than the responsive group (p=.03) and had worse motor scores (p=.003) than the no FOG group. Longer disease duration was associated with the responsive group compared to the no FOG group (p=.002). The unresponsive FOG group had significantly poorer visuospatial ability (p=.001) and executive functioning (p=.02) than both the no and responsive FOG subgroups. These latter groups were not significantly different. The responsive FOG group was associated with the presence of hallucinations. Conclusion Aside from pharmacological differences, unresponsive FOG is associated with executive and visuospatial dysfunction implicating frontostriatal pathways while responsive FOG is associated with hallucinations suggesting involvement of posterior cortical regions. Further study and treatment of FOG should include appropriate subtype classification.
    Parkinsonism & Related Disorders 09/2014; 20(12). DOI:10.1016/j.parkreldis.2014.09.023 · 3.97 Impact Factor
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    ABSTRACT: Introduction Generalized dystonia, both primary and secondary forms, and axial dystonias such as tardive dystonia, and idiopathic cervical dystonia are responsive to globus pallidus interna (GPi) DBS. There is a paucity of investigations probing the impact of DBS on adult-onset axial dystonia. We assessed the efficacy of GPi DBS in four patients with rare adult-onset axial dystonia. Methods Primary outcome measure was improvement in the motor component of the Burke-Fahn-Marsden (BFM) rating scale. Secondary outcome measures were quality of life as determined by the SF-36 questionnaire, time to achieve best possible benefit and DBS parameters that accounted for the best response. In patients with prominent concomitant cervical dystonia we also used the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Results GPi DBS improved BFM scores by 87.63 ± 11.46%. Improvement in total severity scale of TWSTRS was 71.5 ± 12.7%. Quality of life also remarkably improved as evidenced by 109.38 ± 82.97 and 7.05 ± 21.48% percent change in psychometrically-based physical component summary (PCS), and a mental component summary (MCS) score respectively. Conclusions GPi DBS is a very effective treatment for adult-onset axial dystonia. Considering its refractoriness to medical therapy and significant impact on quality of life DBS should be considered for this disorder.
    Parkinsonism & Related Disorders 09/2014; 20(11). DOI:10.1016/j.parkreldis.2014.09.005 · 3.97 Impact Factor
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    ABSTRACT: Importance Cognitive impairment is a common and disabling problem in Parkinson disease (PD) that is not well understood and is difficult to treat. Identification of genetic variants that influence the rate of cognitive decline or pattern of early cognitive deficits in PD might provide a clearer understanding of the etiopathogenesis of this important nonmotor feature.Objective To determine whether common variation in the APOE, MAPT, and SNCA genes is associated with cognitive performance in patients with PD.Design, Setting, and Participants We studied 1079 PD patients from 6 academic centers in the United States who underwent assessments of memory (Hopkins Verbal Learning Test–Revised [HVLT-R]), attention and executive function (Letter-Number Sequencing Test and Trail Making Test), language processing (semantic and phonemic verbal fluency tests), visuospatial skills (Benton Judgment of Line Orientation test), and global cognitive function (Montreal Cognitive Assessment). Participants underwent genotyping for the APOE ε2/ε3/ε4 alleles, MAPT H1/H2 haplotypes, and SNCA rs356219. We used linear regression to test for association between genotype and baseline cognitive performance with adjustment for age, sex, years of education, disease duration, and site. We used a Bonferroni correction to adjust for the 9 comparisons that were performed for each gene.Main Outcomes and Measures Nine variables derived from 7 psychometric tests.Results The APOE ε4 allele was associated with lower performance on the HVLT-R Total Recall (P = 6.7 × 10−6; corrected P [Pc] = 6.0 × 10−5), Delayed Recall (P = .001; Pc = .009), and Recognition Discrimination Index (P = .004; Pc = .04); a semantic verbal fluency test (P = .002; Pc = .02); the Letter-Number Sequencing Test (P = 1 × 10−5; Pc = 9 × 10−5); and Trail Making Test B minus Trail Making Test A (P = .002; Pc = .02). In a subset of 645 patients without dementia, the APOE ε4 allele was associated with lower scores on the HVLT-R Total Recall (P = .005; Pc = .045) and the semantic verbal fluency (P = .005; Pc = .045) measures. Variants of MAPT and SNCA were not associated with scores on any tests.Conclusions and Relevance Our data indicate that the APOE ε4 allele is an important predictor of cognitive function in PD across multiple domains. Among PD patients without dementia, the APOE ε4 allele was only associated with lower performance on word list learning and semantic verbal fluency, a pattern more typical of the cognitive deficits seen in early Alzheimer disease than PD.
    JAMA Neurology 09/2014; 71(11). DOI:10.1001/jamaneurol.2014.1455 · 7.42 Impact Factor

Publication Stats

7k Citations
1,283.07 Total Impact Points


  • 2006-2015
    • Emory University
      • Department of Neurology
      Atlanta, Georgia, United States
  • 2014
    • Wayne State University
      • Department of Neurology
      Detroit, Michigan, United States
    • Zoo Atlanta
      Atlanta, Georgia, United States
  • 2007-2008
    • University of Washington Seattle
      • • Department of Environmental and Occupational Health Sciences
      • • International Clinical Research Center (ICRC)
      Seattle, WA, United States
  • 2005-2008
    • Albany Stratton VA Medical Center
      Albany, New York, United States
  • 1989-2006
    • Albany Medical College
      • Department of Neurology
      Albany, New York, United States
  • 1999-2005
    • Parkinson's and Movement Disorders Center Of Maryland
      Maryland, United States
  • 2004
    • University of Florida
      • Department of Medicine
      Gainesville, FL, United States
  • 2001
    • University of Texas Southwestern Medical Center
      • Division of Neuro-oncology
      Dallas, TX, United States
  • 1989-2001
    • University of Miami Miller School of Medicine
      • Department of Neurology
      Miami, Florida, United States
  • 2000
    • Memorial Hospital of Rhode Island
      Pawtucket, Rhode Island, United States
  • 1987-2000
    • University of Miami
      • Department of Neurology
      كورال غيبلز، فلوريدا, Florida, United States