A J Lees

UCL Eastman Dental Institute, Londinium, England, United Kingdom

Are you A J Lees?

Claim your profile

Publications (503)4060.45 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To systematically review published literature to estimate the magnitude of association between premorbid constipation and later diagnosis of Parkinson's disease. Background: Constipation is a recognised non-motor feature of Parkinson's and has been reported to predate diagnosis in a number of observational studies. Methods: A systematic review and meta-analysis was carried out following the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) criteria. A literature search was undertaken in December 2014 using PubMed and the search terms 'Parkinson's disease' and 'constipation'. Articles were screened for suitability and reviewed against inclusion and exclusion criteria. Studies were included if they assessed constipation by means of a structured questionnaire or if constipation/drugs used to treat constipation were coded in patient medical records. Data were extracted using a standardised template and effect size estimates combined using a fixed-effects model. Heterogeneity was explored with the I(2) statistic. Results: 9 studies were included in the meta-analysis, with a combined sample size of 741 593 participants. Those with constipation had a pooled OR of 2.27 (95% CI 2.09 to 2.46) for developing subsequent Parkinson's disease compared with those without constipation. Weak evidence for heterogeneity was found (I(2)=18.9%, p=0.282). Restricting analysis to studies assessing constipation more than 10 years prior to Parkinson's disease gave a pooled OR of 2.13 (95% CI 1.78 to 2.56; I(2)=0.0%). Conclusions: This systematic review and meta-analysis demonstrates that people with constipation are at a higher risk of developing Parkinson's disease compared with those without and that constipation can predate Parkinson's diagnosis by over a decade.
    Journal of neurology, neurosurgery, and psychiatry 09/2015; DOI:10.1136/jnnp-2015-311680 · 6.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Atypical parkinsonism (AP) has a considerable impact on the lives not only of patients but also of their carers. The aim of this study was to develop an instrument for assessing the quality of life (QoL) of carers of patients with AP. A 40-item pool was generated from in-depth interviews with carers of patients with AP, a thorough review of the existing literature and consultation with movement disorder experts. Item refinement and reduction was performed using the results of pilot testing and a survey in 282 carers of multiple system atrophy (MSA) patients and 226 carers of progressive supranuclear palsy (PSP) patients. A validation study, with responses of 243 carers of MSA and 187 carers of PSP patients, was undertaken to evaluate the psychometric properties of the final 26-item scale. The validation study results suggest that the scale is unidimensional and has high internal consistency (Cronbach's α = 0.96). The correlations of scale scores with patients' health status and QoL measures, such as PDQ-39 summary score and EQ-5D index (Spearman's ρ = 0.56 and -0.31, respectively, P < 0.001), as well as carers' measures, such as Caregiver Burden Inventory (CBI) total and EQ-5D index (Spearman's ρ = 0.85 and -0.39, respectively, P < 0.001), document the convergent and concurrent validity of the scale. ANOVA results support the discriminant validity of the scale, as evidenced by its capacity to differentiate between carers with varying levels of self-reported health. The 26-item Parkinsonism Carers QoL (PQoL Carer) is a concise instrument with adequate psychometric qualities that can be used for clinical and research purposes.
    Quality of Life Research 08/2015; DOI:10.1007/s11136-015-1071-y · 2.49 Impact Factor
  • Source
  • Andrew Lees · Katrin Sikk · Pille Taba
    [Show abstract] [Hide abstract]
    ABSTRACT: The substituted amphetamines have had a checkered medical history intertwined with a sensational cultural history. Mankind's insatiable fascination with speed has led to widespread misuse sometimes with disastrous neurological and psychiatric consequences that may cause a permanent harm but their potential to enhance cognition should not be dismissed or forgotten. Further, smarter research could perhaps still lead to an expanded beneficial role for stimulant use in modern society. © 2015 Elsevier Inc. All rights reserved.
    International Review of Neurobiology 06/2015; 120:1-7. DOI:10.1016/bs.irn.2015.03.001 · 1.92 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Patients presenting with parkinsonian syndromes share many clinical features, which can make diagnosis difficult. This is important as atypical parkinsonian syndromes (APSs) such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and corticobasal syndrome (CBS) carry a poor prognosis, compared with patients with Parkinson's disease (PD). In addition, there is overlap between APS and dementia diseases, such as Alzheimer's disease (AD) and frontotemporal dementia (FTD). To use a panel of cerebrospinal fluid (CSF) biomarkers to differentiate patients with APS from PD and dementia. A prospective cohort of 160 patients and 30 control participants were recruited from a single specialist centre. Patients were clinically diagnosed according to current consensus criteria. CSF samples were obtained from patients with clinical diagnoses of PD (n=31), PSP (n=33), CBS (n=14), MSA (n=31), AD (n=26) and FTD (n=16). Healthy, elderly participants (n=30) were included as controls. Total τ (t-τ), phosphorylated τ (p-τ), β-amyloid 1-42 (Aβ42), neurofilament light chain (NFL), α-synuclein (α-syn), amyloid precursor protein soluble metabolites α and β (soluble amyloid precursor protein (sAPP)α, sAPPβ) and two neuroinflammatory markers (monocyte chemoattractant protein-1 and YKL-40) were measured in CSF. A reverse stepwise regression analysis and the false discovery rate procedure were used. CSF NFL (p<0.001), sAPPα (p<0.001) and a-syn (p=0.003) independently predicted diagnosis of PD versus APS. Together, these nine biomarkers could differentiate patients with PD from APS with an area under the curve of 0.95 and subtypes of APS from one another. There was good discriminatory power between parkinsonian groups, dementia disorders and healthy controls. A panel of nine CSF biomarkers was able to differentiate APS from patients with PD and dementia. This may have important clinical utility in improving diagnostic accuracy, allowing better prognostication and earlier access to potential disease-modifying therapies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Journal of Neurology Neurosurgery & Psychiatry 01/2015; DOI:10.1136/jnnp-2014-309562 · 6.81 Impact Factor
  • Source
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to assess the neuropsychological behavior of Parkinson's disease (PD) patients with addictive behaviors. Characteristically, these patients have younger onset of PD, higher novelty-seeking personality traits, jump to conclusions, and often make irrational choices. We assessed whether PD patients with and without addictive behaviors have deficits in a sequential sampling task, often called the secretary problem. In this task, participants needed to pick the best out of multiple offers. Critically, once participants rejected a deal, this option became unavailable. Thus, decisions needed to be balanced not to stop too soon or sample for too long and miss the best deal. We tested 13 PD patients with and 13 patients without addictive behaviors. Results were compared to healthy volunteers. We found that all patients declined fewer options before committing to a deal. There was, however, no difference between the two patient groups. Furthermore, there was no difference in overall choice rank between patients and controls. These results suggest that, compared to controls, PD patients gather less evidence before committing to an offer, but have no deficits in recognizing the best deal out of many options, regardless of whether or not they have addictive behaviors.
    12/2014; 1(4). DOI:10.1002/mdc3.12076
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: GTP cyclohydrolase 1, encoded by the GCH1 gene, is an essential enzyme for dopamine production in nigrostriatal cells. Loss-of-function mutations in GCH1 result in severe reduction of dopamine synthesis in nigrostriatal cells and are the most common cause of DOPA-responsive dystonia, a rare disease that classically presents in childhood with generalized dystonia and a dramatic long-lasting response to levodopa. We describe clinical, genetic and nigrostriatal dopaminergic imaging ([123I]N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl) tropane single photon computed tomography) findings of four unrelated pedigrees with DOPA-responsive dystonia in which pathogenic GCH1 variants were identified in family members with adult-onset parkinsonism. Dopamine transporter imaging was abnormal in all parkinsonian patients, indicating Parkinson's disease-like nigrostriatal dopaminergic denervation. We subsequently explored the possibility that pathogenic GCH1 variants could contribute to the risk of developing Parkinson's disease, even in the absence of a family history for DOPA-responsive dystonia. The frequency of GCH1 variants was evaluated in whole-exome sequencing data of 1318 cases with Parkinson's disease and 5935 control subjects. Combining cases and controls, we identified a total of 11 different heterozygous GCH1 variants, all at low frequency. This list includes four pathogenic variants previously associated with DOPA-responsive dystonia (Q110X, V204I, K224R and M230I) and seven of undetermined clinical relevance (Q110E, T112A, A120S, D134G, I154V, R198Q and G217V). The frequency of GCH1 variants was significantly higher (Fisher's exact test P-value 0.0001) in cases (10/1318 = 0.75%) than in controls (6/5935 = 0.1%; odds ratio 7.5; 95% confidence interval 2.4-25.3). Our results show that rare GCH1 variants are associated with an increased risk for Parkinson's disease. These findings expand the clinical and biological relevance of GTP cycloydrolase 1 deficiency, suggesting that it not only leads to biochemical striatal dopamine depletion and DOPA-responsive dystonia, but also predisposes to nigrostriatal cell loss. Further insight into GCH1-associated pathogenetic mechanisms will shed light on the role of dopamine metabolism in nigral degeneration and Parkinson's disease.
    Brain 09/2014; 137(9):2480-2492. DOI:10.1093/brain/awu179 · 9.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the study was to develop a culturally adapted translation of the 12-item smell identification test from Sniffin’ Sticks (SS-12) for the Estonian population in order to help diagnose Parkinson’s disease (PD). Methods A standard translation of the SS-12 was created and 150 healthy Estonians were questioned about the smells used as response options in the test. Unfamiliar smells were replaced by culturally familiar options. The adapted SS-12 was applied to 70 controls in all age groups, and thereafter to 50 PD patients and 50 age- and sex-matched controls. Results 14 response options from 48 used in the SS-12 were replaced with familiar smells in an adapted version, in which the mean rate of correct response was 87% (range 73 to 99) compared to 83% with the literal translation (range 50 to 98). In PD patients, the average adapted SS-12 score (5.4/12) was significantly lower than in controls (average score 8.9/12), p <0.0001. A multiple linear regression using the score in the SS-12 as the outcome measure showed that diagnosis and age independently influenced the result of the SS-12. A logistic regression using the SS12 and age as covariates showed that the SS12 (but not age) correctly classified 79.0% of subjects into the PD and control category, using a cut-off of <7 gave a sensitivity of 76% and specificity of 86% for the diagnosis of PD. Conclusions The developed SS-12 cultural adaption is appropriate for testing olfaction in Estonia for the purpose of PD diagnosis.
    Parkinsonism & Related Disorders 08/2014; 20(8). DOI:10.1016/j.parkreldis.2014.04.012 · 3.97 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Articles Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial Summary Background In preclinical studies, davunetide promoted microtubule stability and reduced tau phosphorylation. Because progressive supranuclear palsy (PSP) is linked to tau pathology, davunetide could be a treatment for PSP. We assessed the safety and effi cacy of davunetide in patients with PSP.
    The Lancet Neurology 07/2014; 13(7):676-685. DOI:10.1016/S1474-4422(14)70088-2 · 21.90 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Clinical and neuropathological similarities between dementia with Lewy bodies (DLB), Parkinson's and Alzheimer's diseases (PD and AD, respectively) suggest that these disorders may share etiology. To test this hypothesis, we have performed an association study of 54 genomic regions, previously implicated in PD or AD, in a large cohort of DLB cases and controls. The cohort comprised 788 DLB cases and 2624 controls. To minimize the issue of potential misdiagnosis, we have also performed the analysis including only neuropathologically proven DLB cases (667 cases). The results show that the APOE is a strong genetic risk factor for DLB, confirming previous findings, and that the SNCA and SCARB2 loci are also associated after a study-wise Bonferroni correction, although these have a different association profile than the associations reported for the same loci in PD. We have previously shown that the p.N370S variant in GBA is associated with DLB, which, together with the findings at the SCARB2 locus, suggests a role for lysosomal dysfunction in this disease. These results indicate that DLB has a unique genetic risk profile when compared with the two most common neurodegenerative diseases and that the lysosome may play an important role in the etiology of this disorder. We make all these data available.
    Human Molecular Genetics 06/2014; 23(23). DOI:10.1093/hmg/ddu334 · 6.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Problematic Internet Use (PIU) have been associated with impulse control disorders (ICD), and postulated to share characteristics of a behavioural addiction with both impulsive and compulsive features. However, Internet use has not been previously systematically studied in Parkinson’s disease. Aim We explore Internet use in PD patients with and without ICDs and matched healthy controls. We hypothesise that the PD-ICD patients will spend more time on the Internet, accessing websites related to their ICDs, compared with PD patients without ICDs and healthy volunteers. Methods Our study is the first to systematically explore problematic Internet use in patients with PD, with and without ICDs. Twenty-nine PD patients with ICDs, twenty PD patients without ICDs and nineteen healthy controls were recruited. All participants endorsed using the Internet for non-essential purposes. They underwent a semi-structured interview and completed questionnaires including the Yale-Brown Obsessive Compulsive Scale adapted for Internet use (Y-BOCS-Internet). Results PD-ICD patients scored significantly higher on the Y-BOCS-Internet than the PD-control and HV groups (PD-ICD: 13.69; PD-control: 5.42; HV: 4.70; p<0.0001). Compared to PD controls and HV groups, the PD-ICD group spent more time on the Internet (p=0.0001), described significantly more effort to resist Internet use (p=0.0002), thoughts about Internet use (p<0.0001) and its interference with their life functioning (p=0.0025). Discussion Our results suggest that PD patients with ICDs have a relative increased tendency towards excessive Internet use compared to those without ICDs and healthy controls. Clinicians should actively screen for excessive Internet use in patients with ICDs.
    Parkinsonism & Related Disorders 05/2014; 20(5). DOI:10.1016/j.parkreldis.2014.01.019 · 3.97 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mutations in the vacuolar protein sorting 35 homolog (VPS35) gene at the PARK17 locus, encoding a key component of the retromer complex, were recently identified as a new cause of late-onset, autosomal dominant Parkinson's disease (PD). Here we explore the pathogenic consequences of PD-associated mutations in VPS35 using a number of model systems. VPS35 exhibits a broad neuronal distribution throughout the rodent brain, including within the nigrostriatal dopaminergic pathway. In the human brain, VPS35 protein levels and distribution are similar in tissues from control and PD subjects, and VPS35 is not associated with Lewy body pathology. The common D620N missense mutation in VPS35 does not compromise its protein stability or localization to endosomal and lysosomal vesicles, or the vesicular sorting of the retromer cargo, sortilin, SorLA and cation-independent mannose 6-phosphate receptor, in rodent primary neurons or patient-derived human fibroblasts. In yeast we show that PD-linked VPS35 mutations are functional and can normally complement VPS35 null phenotypes suggesting that they do not result in a loss-of-function. In rat primary cortical cultures the overexpression of human VPS35 induces neuronal cell death and increases neuronal vulnerability to PD-relevant cellular stress. In a novel viral-mediated gene transfer rat model, the expression of D620N VPS35 induces the marked degeneration of substantia nigra dopaminergic neurons and axonal pathology, a cardinal pathological hallmark of PD. Collectively, these studies establish that dominant VPS35 mutations lead to neurodegeneration in PD consistent with a gain-of-function mechanism, and support a key role for VPS35 in the development of PD.
    Human Molecular Genetics 04/2014; 23(17). DOI:10.1093/hmg/ddu178 · 6.39 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It is believed that glycogen synthase kinase-3 (GSK-3) hyperphosphorylates tau protein in progressive supranuclear palsy (PSP). The Tau Restoration on PSP (TAUROS) study was a double-blind, placebo-controlled, randomized trial to assess the efficacy, safety, and tolerability of tideglusib, a GSK-3 inhibitor, as potential treatment for PSP. The study enrolled 146 PSP patients with mild-to-moderate disease who were randomized to receive once-daily 600 mg tideglusib, 800 mg tideglusib, or placebo (ratio, 2:2:1) administered orally over 52 weeks. The primary endpoint was the change from baseline to week 52 on the PSP rating scale. Secondary endpoints were safety and tolerability of tideglusib, changes in motor function (the Timed Up and Go Test), cognition (Dementia Rating Scale-2, Frontal Assessment Battery, verbal fluency), apathy (Starkstein scale), activities of daily living (Schwab and England scale; Unified Parkinson's Disease Rating Scale, part II), quality of life (EuroQol), and Global Clinical Assessment. Brain atrophy on magnetic resonance imaging and several biomarkers in plasma and cerebrospinal fluid also were examined. No significant differences were detected in the primary or secondary endpoints at week 52 between placebo and either dose of tideglusib. Tideglusib was safe, with the exception of some asymptomatic, transient, and reversible transaminase elevations (mainly alanine aminotransferase) in 9% of patients, and diarrhea in 13% of patients. Tideglusib was generally well tolerated but it did not show clinical efficacy in patients with mild-to-moderate PSP. © 2014 International Parkinson and Movement Disorder Society.
    Movement Disorders 04/2014; 29(4). DOI:10.1002/mds.25824 · 5.68 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Data from an open label randomised controlled trial have suggested possible advantages on both motor and non-motor measures in patients with Parkinson's disease following 12 months exposure to exenatide. Objective: Continued follow up of these same patients was performed to investigate whether these possible advantages persisted in the prolonged absence of this medication. Methods: All participants from an open label, randomised controlled trial of exenatide as a treatment for Parkinson's disease, were invited for a further follow up assessment at the UCL Institute of Neurology. This visit included all 20 individuals who had previously completed twelve months exposure to exenatide 10ug bd and the 24 individuals who had acted as randomised controls. Motor severity of PD was compared after overnight withdrawal of conventional PD medication using blinded video assessment of the MDS-UPDRS, together with several non-motor tests. This assessment was thus 24 months after their original baseline visit, i.e. 12 months after cessation of exenatide. Results: Compared to the control group of patients, patients previously exposed to exenatide had an advantage of 5.6 points (95% CI, 2.2-9.0; p = 0.002) using blinded video rating of the MDS-UPDRS part 3 motor subscale. There was also a difference of 5.3 points; (95% CI, 9.3-1.4; p = 0.006) between the 2 groups on the Mattis Dementia Rating scale. Conclusions: While these data must still not be interpreted as evidence of neuroprotection, they nevertheless provide strong encouragement for the further study of this drug as a potential disease modifying agent in Parkinson's disease.
    03/2014; 4(3). DOI:10.3233/JPD-140364
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Unlike most other cell types, neurons preferentially metabolize glucose via the pentose phosphate pathway (PPP) to maintain their antioxidant status. Inhibiting the PPP in neuronal cell models causes cell death. In rodents, inhibition of this pathway causes selective dopaminergic cell death leading to motor deficits resembling parkinsonism. Using postmortem human brain tissue, we characterized glucose metabolism via the PPP in sporadic Parkinson's disease (PD), Alzheimer's disease (AD), and controls. AD brains showed increased nicotinamide adenine dinucleotide phosphate (NADPH) production in areas affected by disease. In PD however, increased NADPH production was only seen in the affected areas of late-stage cases. Quantifying PPP NADPH-producing enzymes glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase by enzyme-linked immunosorbent assay, showed a reduction in the putamen of early-stage PD and interestingly in the cerebellum of early and late-stage PD. Importantly, there was no decrease in enzyme levels in the cortex, putamen, or cerebellum of AD. Our results suggest that down-regulation of PPP enzymes and a failure to increase antioxidant reserve is an early event in the pathogenesis of sporadic PD.
    Neurobiology of aging 11/2013; 35(5). DOI:10.1016/j.neurobiolaging.2013.11.001 · 5.01 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although Pisa syndrome and scoliosis are sometimes used interchangeably to describe a laterally flexed postural deviation in Parkinson's disease (PD), the imaging findings of Pisa syndrome in PD have not been previously studied in detail. Patients with Parkinson's disease and Pisa syndrome (lateral flexion >100 in the standing position) were examined clinically and underwent radiological assessment utilising standing radiograph and supine CT scan of the whole spine. Fifteen patients were included in this observational study. The mean age was 72 years, mean duration of Parkinson's disease 15 years and mean duration of lateral flexion deformity 6 years. All patients had scoliosis on standing radiographs, and 12 had scoliosis persisting in the supine position. Scoliotic curves improved by a mean of 44% when patients moved from standing to supine. Only one quarter of patients with structural scoliosis had evidence of bony fusion on the side of their lateral deviation rendering their deformity fixed. Pisa syndrome describes a patient who lists to the side whereas scoliosis is defined by spinal curvature and rotation and may not be associated with lateral flexion. The finding of 'structural scoliosis' in Pisa syndrome should not preclude intervening to improve posture as most patients had little or no evidence of structural bony changes even when the deformity had been present for a number of years.
    Journal of neurology, neurosurgery, and psychiatry 11/2013; 84(11):e2. DOI:10.1136/jnnp-2013-306573.152 · 6.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The Bradykinesia Akinesia Incoordination (BRAIN) test is an online computer keyboard-tapping task based on the alternate finger tap test. It has previously been used to measure upper limb motor function in Parkinson's disease (PD). Multiple Sclerosis (MS) is an autoimmune demyelinating disorder with a wide clinical spectrum, within which pyramidal motor impairment is encountered frequently. There is a need for simple objective measures of upper limb function in clinical studies of symptomatic and disease-modifying treatment in MS. We therefore set out to evaluate whether the BRAIN test would be a suitable objective test of upper limb motor impairment in MS patients. The BRAIN test records the following parameters: kinesia score (KS30), number of key taps in 30 seconds; akinesia time (AT30), mean dwell time on each key in milliseconds; dysmetria score (DS30), a weighted index using the number of incorrectly hit keys scored in a target fashion; and incoordination score (IS30), the variance of the time interval between keystrokes. The study was undertaken in 32 MS patients (5 primary progressive, 19 secondary progressive, and 8 relapsing-remitting). These data were compared to that from 53 PD patients and 86 non-neurological controls. Participants were recruited from outpatient departments at the Royal London Hospital and the National Hospital for Neurology and Neurosurgery. All participants submitted informed consent. Mean KS30 and median AT30, DS30 and IS30 were compared between groups using the unpaired t-test for parametric data and the Mann Whitney U test for non-parametric data. Furthermore, in MS patients, KS30 and AT30 were correlated against Expanded Disability Status Scale (EDSS), a validated method of quantifying disability, and 9-Hole Peg Test (9-HPT), a test of upper limb function in MS. Correlations were undertaken using Pearson's test and Spearman's rank test as necessary. Mean KS30 scores in PD and MS were similar (46.1 versus 45.7 taps respectively, p=0.88) and were significantly different when compared to controls (63.3 taps, p<0.0001). There was a significant difference between median AT30 in PD and MS (139.5 ms versus 108 ms, p=0.0014) but no difference between MS and controls (108 ms versus 97.5 ms, p=0.16). Median IS30 scores in PD and MS were different (21763 versus 9524 respectively, p=0.004), as were DS30 scores (1.05 versus 1.0 respectively, p=0.003). In MS patients, KS30 correlated strongly with EDSS (KS30 r=-0.59, p=0.0004) and 9-HPT (KS30 r=-0.57, p=0.0006). Other parameters did not show a significant correlation with EDSS and 9-HPT. The BRAIN test is a widely-available, objective test of upper limb motor function in neurological disease and can be use in the outpatient clinic, home and in clinical trials. Tapping speed is reduced in MS patients when compared to healthy controls and by a similar extent to that seen in PD. MS patients do not have prolonged dwell time when pressing keys, which is a feature of the PD patient group and perhaps extra-pyramidal slowing. This potential for the BRAIN test in differentiating pyramidal from extra-pyramidal motor dysfunction requires further study.
    Journal of neurology, neurosurgery, and psychiatry 11/2013; 84(11):e2. DOI:10.1136/jnnp-2013-306573.184 · 6.81 Impact Factor
  • Journal of the Neurological Sciences 10/2013; 333:e669-e670. DOI:10.1016/j.jns.2013.07.2316 · 2.47 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To compare the dopaminergic neuronal imaging features of different subtypes of genetic Parkinson's Disease. A retrospective study of genetic Parkinson's diseases cases in which DaTSCAN (123I-FP-CIT) had been performed. Specific non-displaceable binding was calculated for bilateral caudate and putamen for each case. The right:left asymmetry index and striatal asymmetry index was calculated. Scans were available from 37 cases of monogenetic Parkinson's disease (7 glucocerebrosidase (GBA) mutations, 8 alpha-synuclein, 3 LRRK2, 7 PINK1, 12 Parkin). The asymmetry of radioligand uptake for Parkinson's disease with GBA or LRRK2 mutations was greater than that for Parkinson's disease with alpha synuclein, PINK1 or Parkin mutations. The asymmetry of radioligand uptake in Parkinsons disease associated with GBA or LRRK2 mutations suggests that interactions with additional genetic or environmental factors may be associated with dopaminergic neuronal loss.
    PLoS ONE 07/2013; 8(7):e69190. DOI:10.1371/journal.pone.0069190 · 3.23 Impact Factor

Publication Stats

36k Citations
4,060.45 Total Impact Points


  • 2008–2015
    • UCL Eastman Dental Institute
      Londinium, England, United Kingdom
  • 1991–2014
    • University College London
      • • Institute of Neurology
      • • Department of Epidemiology and Public Health
      Londinium, England, United Kingdom
    • New South Wales Institute of Psychiatry
      Sydney, New South Wales, Australia
  • 2013
    • University of Campinas
      Conceição de Campinas, São Paulo, Brazil
    • Royal College of Physicians
      Londinium, England, United Kingdom
  • 2012
    • University of Sydney
      Sydney, New South Wales, Australia
  • 2001–2011
    • University of London
      • The School of Pharmacy
      Londinium, England, United Kingdom
    • MRC Clinical Sciences Centre
      London Borough of Harrow, England, United Kingdom
  • 2010
    • University of South Wales
      Понтиприте, Wales, United Kingdom
    • Bank of England
      Londinium, England, United Kingdom
  • 2009
    • National Institute on Aging
      • Laboratory of Neurogenetics (LNG)
      Baltimore, Maryland, United States
  • 1992–2008
    • London Research Institute
      Londinium, England, United Kingdom
  • 2007
    • WWF United Kingdom
      Londinium, England, United Kingdom
  • 2006
    • University of California, San Francisco
      San Francisco, California, United States
    • University of Bonn
      • Department of Neurobiology
      Bonn, North Rhine-Westphalia, Germany
  • 2000
    • Saint Mary's Hospital Center
      Montréal, Quebec, Canada
  • 1999
    • University Hospital Center Pointe-à-Pitre
      La Pointe à Pitre, Guadeloupe, Guadeloupe
  • 1995–1997
    • University College London Hospitals NHS Foundation Trust
      Londinium, England, United Kingdom
    • Ljubljana University Medical Centre
      Lubliano, Ljubljana, Slovenia
  • 1994
    • Freie Universität Berlin
      Berlín, Berlin, Germany
  • 1991–1994
    • Middlesex University, UK
      Londinium, England, United Kingdom
  • 1993
    • Repatriation General Hospital
      Tarndarnya, South Australia, Australia
  • 1990
    • King's College London
      Londinium, England, United Kingdom
  • 1989
    • St. Mark's Hospital
      Harrow i London, England, United Kingdom
    • Institute of Psychiatry, Kolkata
      Kolkata, West Bengal, India
  • 1985
    • The Whittington Hospital NHS Trust
      Londinium, England, United Kingdom