Publications by authors named "Eavan McGovern"

29 Publications

  • Page 1 of 1

Long-term effect of apomorphine infusion in advanced Parkinson's disease: a real-life study.

NPJ Parkinsons Dis 2021 Jun 11;7(1):50. Epub 2021 Jun 11.

Neurology Department, Pitié-Salpêtrière Hospital, AP-HP, Paris, France.

Long-term effects of continuous subcutaneous apomorphine infusion (CSAI) on health-related quality of life (HRQoL) and predictors of CSAI discontinuation are poorly known. Data from consecutive advanced Parkinson's disease patients treated in routine care were retrospectively collected over 24 months after CSAI initiation, with a focus on the 39-item Parkinson's disease questionnaire (PDQ-39). We determined predictors of CSAI discontinuation and HRQoL improvement using multiple regression analysis. Of the 110 subjects evaluated over a 2-year period, 35% discontinued CSAI. Of those who continued treatment, HRQoL remained stable with a sustained reduction in motor fluctuations. The observed effect on dyskinesias was mild and transient. Of note, patients with preexisting impulse control disorders showed an overall good tolerability. PDQ-39 was the only baseline predictor of HRQoL improvement after 2 years of treatment. The presence of dyskinesias, poorer psychological status, shorter disease duration, male sex, and worse OFF state were predictors of discontinuation. Best candidates for CSAI are patients with: (i) poor baseline HRQoL and (ii) marked motor fluctuations.
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http://dx.doi.org/10.1038/s41531-021-00194-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196159PMC
June 2021

NeuroQ: A neurophobia screening tool assesses how roleplay challenges neurophobia.

J Neurol Sci 2021 Feb 20;421:117320. Epub 2021 Jan 20.

AP-HP, Hôpital Pitié-Salpêtrière, Département de Neurologie, Paris, France; Sorbonne Université, France; INSERM U1127, CNRS 7225, Institut du Cerveau, Paris, France.

Background: Neurophobia is a chronic disease of medical students and junior doctors. Early detection is needed to facilitate prevention and management as this fear can negatively impact patient care.

Methods: We conducted a two-part mono-centric study at the faculty of Medicine, Sorbonne University, in Paris. Part one: a cross-sectional study to validate a newly constructed neurophobia scale, NeuroQ. Part two: a prospective longitudinal study to assess the impact of The Move on student neurophobia using NeuroQ. A population-based sample of second-year medical students of the 2019 and 2020 class of the Faculty of Medicine of Sorbonne University were invited to participate.

Results: NeuroQ incorporates the main themes of the neurophobia definition and demonstrates uni-dimensionality. Three hundred and ninety-five medical students participated in the study (mean age was 20.0 years, SD: 2.1 years) assessing the effect of The Move teaching on neurophobia. Two hundred and eighty-eight (72.9%) students were female. After the Move teaching the mean NeuroQ score was significantly lower compared to the baseline NeuroQ score (mean [SD] variation, -1.1 [2.6], p < 0.001). There was a 22.3% relative reduction in the number of neurophobic students after The Move teaching.

Conclusion: Our results highlight the utility of NeuroQ in assessing (i) baseline neurophobia and (ii) the impact of pre-clinical educational interventions on neurophobia. Furthermore, we have shown the importance of pre-clinical educational interventions, such as The Move, in tackling neurophobia.
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http://dx.doi.org/10.1016/j.jns.2021.117320DOI Listing
February 2021

Multiparametric in vivo analyses of the brain and spine identify structural and metabolic biomarkers in men with adrenomyeloneuropathy.

Neuroimage Clin 2021 19;29:102566. Epub 2021 Jan 19.

INSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013 Paris, France; AP-HP, Pitié-Salpêtrière University Hospital, Department of Genetics, Paris, France; University Pierre and Marie Curie, Neurometabolic Research Group, Paris, France. Electronic address:

Objective: Progressive myelopathy causes severe handicap in men with adrenomyeloneuropathy (AMN), an X-linked disorder due to ABCD1 pathogenic variants. At present, treatments are symptomatic but disease-modifying therapies are under evaluation. Given the small effect size of clinical scales in AMN, biomarkers with higher effect size are needed. Here we used high-resolution magnetic resonance techniques to identify non-invasive in vivo biomarkers of the brain and spine with high effect sizes.

Methods: We performed a multiparametric imaging and spectroscopy study in 23 male patients with AMN (age: 44 ± 11) and 23 male controls (age: 43 ± 11) of similar age and body-mass index. We combined (i) macrostructural analyses of the spine, using cross-sectional area (CSA) and magnetization transfer ratio (MTR), (ii) microstructural analyses of the spine and the brain, using diffusion tensor and the newly developed fixel-based analysis, and (iii) advanced metabolic analyses of the spine using metabolite cycling coupled to a semi-LASER sequences.

Results: Macrostructural alterations (decrease in CSA and MTR) were observed in patients at all spinal cord levels studied (C1-T2 for CSA and C1-C5 for MTR) (p < 0.001). Microstructural alterations were observed in the spine and brain on diffusion tensor and fixel-based metrics though the latter showed higher effect sizes. Metabolic alterations were observed in patients as a decreased total N-acetylaspartate/myo-inositol ratio (p < 0.001). Overall, MTR showed the highest effect size.

Conclusion: This cross-sectional study supports the use of multiparametric techniques that elucidate the structural, microstructural and metabolic alterations in AMN. These outcome measures should be tested longitudinally and in clinical trials.
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http://dx.doi.org/10.1016/j.nicl.2021.102566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847955PMC
June 2021

Transitional Care for Young People with Neurological Disorders: A Scoping Review with A Focus on Patients with Movement Disorders.

Mov Disord 2021 06 17;36(6):1316-1324. Epub 2020 Nov 17.

Department of Neurology, Salpêtrière Hospital, Sorbonne University and Assistance Publique - Hôpitaux de Paris, Paris, France.

Childhood-onset movement disorders represent a heterogenous group of conditions. Given the complexity of these disorders, the transition of care from pediatric to adult medicine is an important consideration. We performed a scoping review of the literature on transitional care in chronic neurological disease, exploring key transitional issues and proposed transitional care models. Our aim was to describe the current knowledge and gaps about the transition process of young adults with chronic neurological disorders, paying special attention to childhood onset movement disorders. A total of 64 articles were included in the qualitative synthesis; 56 articles reported on transitional care issues, and 8 articles reported on transitional care models. Only 2 articles included patients with movement disorders. The following 4 main transitional issues were identified following synthesis of the available literature: (1) inadequate preparation for the transition process, (2) inappropriate and inconsistent transition practices, (3) inadequate adult services, and (4) heightened emotional response surrounding transition. Of the reported transitional care models, multidisciplinary ambulatory care was the most common approach. In studies evaluating patient-related outcomes, positive health, educational, and vocational outcomes were found. The available literature provides insights on issues that can arise during transition that should be addressed to improve patient and caregiver comfort and satisfaction with care. Further research is needed to evaluate how transitional care programs affect outcomes and their cost effectiveness. More studies are required to determine the needs and outcomes specific to patients with childhood onset movement disorders. © 2020 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28381DOI Listing
June 2021

Dissociation in reactive and proactive inhibitory control in Myoclonus dystonia.

Sci Rep 2020 08 18;10(1):13933. Epub 2020 Aug 18.

Sorbonne University, 75005, Paris, France.

Myoclonus-dystonia (MD) is a syndrome characterized by myoclonus of subcortical origin and dystonia, frequently associated with psychiatric comorbidities. The motor and psychiatric phenotypes of this syndrome likely result from cortico-striato-thamalo-cerebellar-cortical pathway dysfunction. We hypothesized that reactive and proactive inhibitory control may be altered in these patients. Using the Stop Signal Task, we assessed reactive and proactive inhibitory control in MD patients with (n = 12) and without (n = 21) deep brain stimulation of the globus pallidus interna and compared their performance to matched healthy controls (n = 24). Reactive inhibition was considered as the ability to stop an already initiated action and measured using the stop signal reaction time. Proactive inhibition was assessed through the influence of several consecutive GO or STOP trials on decreased response time or inhibitory process facilitation. The proactive inhibition was solely impaired in unoperated MD patients. Patients with deep brain stimulation showed impairment in reactive inhibition, independent of presence of obsessive-compulsive disorders. This impairment in reactive inhibitory control correlated with intrinsic severity of myoclonus (i.e. pre-operative score). The results point to a dissociation in reactive and proactive inhibitory control in MD patients with and without deep brain stimulation of the globus pallidus interna.
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http://dx.doi.org/10.1038/s41598-020-70926-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434767PMC
August 2020

Subcortical Myoclonus and Associated Dystonia in 22q11.2 Deletion Syndrome.

Tremor Other Hyperkinet Mov (N Y) 2019 24;10. Epub 2020 Jan 24.

Neurology Unit, Avicenne University Hospital, Hôpitaux Universitaires de Paris-Seine Saint Denis, Bobigny, FR.

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http://dx.doi.org/10.7916/tohm.v0.729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982424PMC
January 2020

Slowed Luminance Reaction Times in Cervical Dystonia: Disordered Superior Colliculus Processing.

Mov Disord 2020 05 26;35(5):877-880. Epub 2020 Jan 26.

Department of Neurology, St. Vincent's University Hospital, Dublin, Ireland.

Background: Abnormal temporal discrimination in cervical dystonia is hypothesized to be attributable to disrupted processing in the superior colliculus. The fast, luminance-based, retinotectal pathway, projects to the superior colliculus; chromatic stimuli responses, by the retino-geniculo-calcarine pathway, are up to 30 ms longer.

Objectives: We sought to interrogate visual processing and reaction times in patients with cervical dystonia compared with healthy controls. We hypothesized that cervical dystonia patients would have impaired reaction times to luminance based stimuli accessing the retino-tectal pathway in comparison to healthy control participants.

Methods: In 20 cervical dystonia and 20 age-matched control participants, we compared reaction times to two flashing visual stimuli: (1) a chromatic annulus and (2) a luminant, noncolored annulus. Participants pressed a joystick control when they perceived the annulus flashing.

Results: Reaction times in control participants were 20 ms significantly faster in the luminant condition than the chromatic (P = 0.017). Patients with cervical dystonia had no reaction time advantage in response to the luminant stimulus.

Conclusion: Cervical dystonia patients (compared to control participants) demonstrated no reduction in their reaction time to luminant stimuli, processed through the retinotectal pathway. This finding is consistent with superior colliculus dysfunction in cervical dystonia. © 2020 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.27975DOI Listing
May 2020

Characterizing Brain Network Topology in Cervical Dystonia Patients and Unaffected Relatives via Graph Theory.

Annu Int Conf IEEE Eng Med Biol Soc 2019 Jul;2019:1694-1697

Cervical Dystonia (CD) is a neurological movement disorder characterized by intermittent muscle contractions in the head and neck. The pathophysiology and neural networks underpinning this condition are incompletely understood. There is increasing evidence that isolated focal dystonias are due to network-wide functional alterations. An abnormal temporal discrimination threshold (TDT) is believed to be a mediational endophenotype due to its prevalence in unaffected first-degree relatives as well as patients. However the neural correlates linking abnormal TDT and CD remain poorly understood. Probing changes in large-scale network topology via graph theory with resting state fMRI data from relatives and patients may provide further insight into the pathophysiology of CD. In this study, resting state fMRI data were acquired and analyzed from 16 CD patients with abnormal TDT, 32 unaffected first degree relatives (16 with normal TDT and 16 with abnormal TDT) and 16 healthy controls. Graph theory metrics demonstrating network topology were extracted. The results indicate large-scale functional reorganization of networks in relatives (with abnormal TDT) along with a manifestation of topological aberrations similar to patients.
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http://dx.doi.org/10.1109/EMBC.2019.8856624DOI Listing
July 2019

Visual sensory processing is altered in myoclonus dystonia.

Mov Disord 2020 01 30;35(1):151-160. Epub 2019 Sep 30.

Sorbonne Université, Paris, France; Inserm U1127, CNRS UMR 7225, UM 75, ICM, Paris, France.

Background: Abnormal sensory processing, including temporal discrimination threshold, has been described in various dystonic syndromes.

Objective: To investigate visual sensory processing in DYT-SGCE and identify its structural correlates.

Methods: DYT-SGCE patients without DBS (DYT-SGCE-non-DBS) and with DBS (DYT-SGCE-DBS) were compared to healthy volunteers in three tasks: a temporal discrimination threshold, a movement orientation discrimination, and movement speed discrimination. Response times attributed to accumulation of sensory visual information were computationally modelized, with μ parameter indicating sensory mean growth rate. We also identified the structural correlates of behavioral performance for temporal discrimination threshold.

Results: Twenty-four DYT-SGCE-non-DBS, 13 DYT-SGCE-DBS, and 25 healthy volunteers were included in the study. In DYT-SGCE-DBS, the discrimination threshold was higher in the temporal discrimination threshold (P = 0.024), with no difference among the groups in other tasks. The sensory mean growth rate (μ) was lower in DYT-SGCE in all three tasks (P < 0.01), reflecting a slower rate of sensory accumulation for the visual information in these patients independent of DBS. Structural imaging analysis showed a thicker left primary visual cortex (P = 0.001) in DYT-SGCE-non-DBS compared to healthy volunteers, which also correlated with lower μ in temporal discrimination threshold (P = 0.029). In DYT-SGCE-non-DBS, myoclonus severity also correlated with a lower μ in the temporal discrimination threshold task (P = 0.048) and with thicker V1 on the left (P = 0.022).

Conclusion: In DYT-SGCE, we showed an alteration of the visual sensory processing in the temporal discrimination threshold that correlated with myoclonus severity and structural changes in the primary visual cortex. © 2019 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.27857DOI Listing
January 2020

Sleep in -Related Dyskinesia: Prolonged Awakenings Caused by Abnormal Movements.

J Clin Sleep Med 2019 07 15;15(7):1021-1029. Epub 2019 Jul 15.

Sleep Disorders (Department "R3S"), Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.

Study Objectives: mutations cause early-onset hyperkinetic movement disorders comprising diurnal and nocturnal paroxysmal dyskinesia, and patient-reported sleep fragmentation. We aimed to characterize all movements occurring during sleep and in the transition from sleep to awakening, to ascertain if there is a primary sleep disorder, or if the sleep disturbance is rather a consequence of the dyskinesia.

Methods: Using video polysomnography, we evaluated the nocturnal motor events and abnormal movements in 7 patients with -related dyskinesia and compared their sleep measures with those of 14 age- and sex-matched healthy controls.

Results: We observed an increased occurrence of abnormal movements during wake periods compared to sleep in patients with -related dyskinesia. While asleep, abnormal movements occurred more frequently during stage N2 and REM sleep, in contrast with stage N3 sleep. Abnormal movements were also more frequent during morning awakenings compared to wake periods before falling asleep. The pattern of the nocturnal abnormal movements mirrored those observed during waking hours. Compared to controls, patients with -related dyskinesia had lower sleep efficiencies due to prolonged awakenings secondary to the abnormal movements, but no other differences in sleep measures. Notably, sleep onset latency was short and devoid of violent abnormal movements.

Conclusions: In this series of patients with -related dyskinesia, nocturnal paroxysmal dyskinesia were not associated with drowsiness or delayed sleep onset, but emerged during nighttime awakenings with subsequent delayed sleep, whereas sleep architecture was normal.
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http://dx.doi.org/10.5664/jcsm.7886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6622513PMC
July 2019

Caffeine and the Dyskinesia Related to Mutations in the ADCY5 Gene.

Ann Intern Med 2019 09 11;171(6):439. Epub 2019 Jun 11.

Assistance Publique - Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Inserm U 1127, CNRS UMR 7225, Sorbonne University, UPMC Univ Paris 06 UMR S 1127, Paris, France (A.M., E.M., E.R.).

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http://dx.doi.org/10.7326/L19-0038DOI Listing
September 2019

Long-term outcome in neuroZika: When biological diagnosis matters.

Neurology 2019 05 26;92(21):e2406-e2420. Epub 2019 Apr 26.

From the Service de Neurologie (A.L., Q.L.), Service de Radiologie (P.P.), Laboratoire de Microbiologie Clinique et Environnementale (C.H., S.B.), and Service de Réanimation (G.T.), Centre Hospitalier Universitaire de la Guadeloupe, Institut Pasteur de Guadeloupe (S.B.), Faculté de Médecine (A.L., Q.L., R.C., G.T., S.B., A.C.), Equipe d'accueil 4537 (F.N., R.C., A.C.), Université des Antilles; Faculté de Médecine de Sorbonne Université (A.L., E.H., E.R.), Institut National de la Santé et de la Recherche Médicale, U 1127, CNRS, Unité Mixte de Recherche 7225, Institut du Cerveau et de la Moelle Épinière, ICM, Paris; Service de Réanimation (J.-L.F., A.-C.S., R.V.), Service de Neurologie (A.S.), Service de Maladies Infectieuses et Tropicales (A.C., B.R.), and Laboratoire de Virologie (R.C., F.N.), Centre Hospitalier Universitaire de la Martinique (A.C.); Inserm CIC 1424 (B.T., A.C.), Centre d'Investigation Clinique Antilles Guyane; Emerging Diseases Epidemiology Unit (Y.M.), Institut Pasteur; Département de Neurologie (E.M., E.R.), AP-HP, Hôpital de la Pitié-Salpêtrière; and Institut Pasteur, Perception and Memory Unit (P.-M.L., F.L.), Centre National de la Recherche Scientifique, Unité Mixte de Recherche 3571, Paris, France.

Objective: To characterize the full spectrum, relative frequency, and prognosis of the neurologic manifestations in Zika virus (ZIKV) postnatal infection.

Methods: We conducted an observational study in consecutive ZIKV-infected patients presenting with neurologic manifestations during the French West Indies 2016 outbreak.

Results: Eighty-seven patients, including 6 children, were enrolled. Ninety-five percent of all cases required hospitalization. Guillain-Barré syndrome was the most frequent manifestation (46.0%) followed by encephalitis or encephalomyelitis (20.7%), isolated single or multiple cranial nerve palsies (9.2%), other peripheral manifestations (6.9%), and stroke (1.1%). Fourteen patients (16.1%), including one child, developed a mixed disorder involving both the central and peripheral nervous system. Mechanical ventilation was required in 21 cases, all of whom had ZIKV RNA in at least one biological fluid. Two adult patients died due to neuroZika. Clinical follow-up (median 14 months; interquartile range, 13-17 months) was available for 76 patients. Residual disability (modified Rankin Scale score ≥2) was identified in 19 (25.0%) patients; in 6 cases (7.9%), disability was severe (modified Rankin Scale score ≥4). Among patients with ZIKV RNA detected in one biological fluid, the risk of residual disability or death was higher (odds ratio 9.19; confidence interval 1.12-75.22; = 0.039).

Conclusions: NeuroZika spectrum represents a heterogeneous group of clinical neurologic manifestations. During an outbreak, clinicians should consider neuroZika in patients presenting with cranial nerve palsies and a mixed neurologic disorder. Long-term sequelae are frequent in NeuroZika. ZIKV reverse-transcription PCR status at admission can inform prognosis and should therefore be taken into consideration in the management of hospitalized patients
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http://dx.doi.org/10.1212/WNL.0000000000007536DOI Listing
May 2019

Neural Correlates of Abnormal Temporal Discrimination in Unaffected Relatives of Cervical Dystonia Patients.

Front Integr Neurosci 2019 12;13. Epub 2019 Mar 12.

Trinity Centre for Bioengineering, Trinity College Dublin, University of Dublin, Dublin, Ireland.

An abnormal temporal discrimination threshold in cervical dystonia (CD) is considered to be a mediational endophenotype; in unaffected relatives it is hypothesized to indicate non-manifesting gene carriage. The pathogenesis underlying this condition remains unknown. Investigation of the neural networks involved in disordered temporal discrimination may highlight its pathomechanisms. To examine resting state brain function in unaffected relatives of CD patients with normal and abnormal temporal discrimination. We hypothesized that the endophenotype, an abnormal temporal discrimination, would manifest as altered connectivity in relatives in regions associated with CD, thereby illuminating the neural substrates of the link between temporal discrimination and CD. Rs-fMRI data was analyzed from two sex- and age-matched cohorts: 16 unaffected relatives of CD patients with normal temporal discrimination and 16 with abnormal temporal discrimination. Regional and whole brain functional connectivity measures were extracted via Independent Component Analysis (ICA), Regional Homogeneity (ReHo), and Amplitude of Low Frequency (ALFF) analyses. Our ICA analysis revealed increased connectivity within both the executive control and cerebellar networks and decreased connectivity within the sensorimotor network in relatives with abnormal temporal discrimination when compared to relatives with normal temporal discrimination. The ReHo and ALFF analyses complimented these results and demonstrated connectivity differences in areas corresponding to motor planning, movement coordination, visual information processing, and eye movements in unaffected relatives with abnormal temporal discrimination. Disordered connectivity in unaffected relatives with abnormal temporal discrimination illuminates neural substrates underlying endophenotype expression and supports the hypothesis that genetically determined aberrant connectivity, when later coupled with unknown environmental triggers, may lead to disease penetrance.
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http://dx.doi.org/10.3389/fnint.2019.00008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423170PMC
March 2019

Miming neurological syndromes improves medical student's long-term retention and delayed recall of neurology.

J Neurol Sci 2018 08 7;391:143-148. Epub 2018 Jun 7.

Faculty of Medicine of Sorbonne University, University Pierre-et-Marie-Curie (UPMC), 91, boulevard de l'Hôpital, 75013 Paris, France; Department of Internal Medicine, Hôpital Tenon, AP-HP, 4, rue de la Chine, 75020 Paris, France.

Basic examination and diagnostic skills in neurology are important for every graduating medical student. However, a majority of medical students consider neurology as complex and difficult to master. We evaluate the impact a learner-friendly, innovative simulation-based training programme has on long-term retention and delayed recall of neurological semiology amongst third-year medical students from the University Pierre et Marie Curie in Paris, France. The 2013 class received standard teaching in neurological semiology. The 2015 class who received the same standard teaching in neurological semiology were also invited to voluntarily participate in The Move, a mime-based role-play training programme of neurological semiology. During the Move, students were trained to simulate a patient with a neurological syndrome or the physician examining the patient. Students were evaluated with an assessment thirty months after their neurological rotation, including 15 questions to evaluate long-term retention of neurological semiology, and 10 to test background knowledge in general semiology. The semiology test was performed by 366/377 students from the 2013 class (standard education group) and by 272/391 students from the 2015 class, among which 186 participated in The Move (The Move group) and 86 did not (standard education group). The mean neurological semiology score was higher in the 2015 class compared to the 2013 class (p = 0.007) and remained so after adjustment for the general semiology performance (p = 0.003). The adjusted mean neurological semiology score was 1.21/15 points higher [95% CI 0.66, 1.75] in The Move group compared to the standard education group, corresponding to a 14% better ranking. The Move programme improves medical student's long-term retention and delayed recall of neurological semiology. This learner-friendly interactive teaching may in turn enhance clinical proficiency of future physicians in neurological semiology.
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http://dx.doi.org/10.1016/j.jns.2018.06.003DOI Listing
August 2018

The expanding spectrum of paroxysmal movement disorders: update from clinical features to therapeutics.

Curr Opin Neurol 2018 08;31(4):491-497

Department of Neurology, University Hospital Galway.

Purpose Of Review: This review will discuss the expanding clinical spectrum of paroxysmal movement disorders and therapeutic options in light of emerging genotypic heterogeneity in these conditions.

Recent Findings: Paroxysmal movement disorders comprise a heterogeneous group of rare neurological conditions characterized by intermittent episodes of abnormal movement associated with various triggers. As the clinical and genotypic spectrum of these disorders evolves, so also has the range of therapeutic options. Triheptanoin has recently been shown to be a very promising alternative to the ketogenic diet in paroxysmal exercise-induced dyskinesia. Four-aminopyridine is now considered first-line symptomatic therapy for episodic ataxia type-2, with pre-clinical findings indicating cerebellar neuroprotection.

Summary: In light of the newly emerging therapies, careful clinical phenotyping is needed to ensure diagnostic precision and timely initiation of appropriate therapies.
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http://dx.doi.org/10.1097/WCO.0000000000000576DOI Listing
August 2018

Further evidence for a distinctive atypical degenerative parkinsonism in the Caribbean: A new cluster in the French West Indian Island of Martinique.

J Neurol Sci 2018 05 6;388:214-219. Epub 2018 Feb 6.

Institut National de la Santé et de la Recherche Médicale, U 1127, CNRS, Unité Mixte de Recherche (UMR) 7225, Université de la Sorbonne, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France; AP-HP, Hôpital de la Pitié-Salpêtrière, Département de Neurologie, Paris F-75013, France.

Background: A high prevalence of an atypical levodopa-resistant parkinsonism has been reported in the Caribbean island of Guadeloupe. These seminal observations have not been replicated or extended to neighbouring populations who share genetic and environmental characteristics.

Methods: To further characterise this atypical parkinsonism we prospectively investigated 305 consecutive patients with neurodegenerative parkinsonism in a community-based population from Guadeloupe and Martinique, a neighbouring French Caribbean island where the population has similar environmental and genetic backgrounds. The aims of this study were to confirm the frequency of atypical parkinsonism within this cohort and to precisely define its clinical phenotype.

Results: A high frequency (66%) of atypical parkinsonism was identified in both Guadeloupe and Martinique. The clinical phenotype consisted of a levodopa-resistant parkinsonism with postural instability (72%), early dementia (58%), dysautonomia (58%), rapid-eye-movement sleep behavioural disorder (53%), hallucinations (43%), and supranuclear gaze palsy (29%). A low educational level was identified as a major risk factor for developing atypical parkinsonism (p < .001).

Conclusion: Our findings support the existence of a distinctive atypical parkinsonism - Caribbean Parkinsonism - within the French Caribbean Islands. This could either correspond to a single entity or reflect a propensity for developing more widespread and rapidly progressive lesions in Caribbean patients with parkinsonism. In both cases, genetic susceptibility and/or environmental exposure may be involved.
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http://dx.doi.org/10.1016/j.jns.2018.02.019DOI Listing
May 2018

Measurement & Analysis of the Temporal Discrimination Threshold Applied to Cervical Dystonia.

J Vis Exp 2018 01 27(131). Epub 2018 Jan 27.

School of Engineering, Trinity College Dublin, The University of Dublin; School of Medicine Trinity College Dublin, The University of Dublin.

The temporal discrimination threshold (TDT) is the shortest time interval at which an observer can discriminate two sequential stimuli as being asynchronous (typically 30-50 ms). It has been shown to be abnormal (prolonged) in neurological disorders, including cervical dystonia, a phenotype of adult onset idiopathic isolated focal dystonia. The TDT is a quantitative measure of the ability to perceive rapid changes in the environment and is considered indicative of the behavior of the visual neurons in the superior colliculus, a key node in covert attentional orienting. This article sets out methods for measuring the TDT (including two hardware options and two modes of stimuli presentation). We also explore two approaches of data analysis and TDT calculation. The application of the assessment of temporal discrimination to the understanding of the pathogenesis of cervical dystonia and adult onset idiopathic isolated focal dystonia is also discussed.
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http://dx.doi.org/10.3791/56310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908707PMC
January 2018

Health-Related Quality of Life Is Severely Affected in Primary Orthostatic Tremor.

Front Neurol 2017 15;8:747. Epub 2018 Jan 15.

Département de Neurologie, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.

Background: Primary orthostatic tremor (POT) is a movement disorder characterized by unsteadiness upon standing still due to a tremor affecting the legs. It is a gradually progressive condition with limited treatment options. Impairments in health-related quality of life (HQoL) seem to far exceed the physical disability associated with the condition.

Methods: A multi-center, mixed-methodology study was undertaken to investigate 40 consecutive patients presenting with POT to four movement disorder centers in France. HQoL was investigated using eight quantitative scales and a qualitative study which employed semi-structured interviews. Qualitative data were analyzed with a combination of grounded-theory approach.

Results: Our results confirm that HQoL in POT is severely affected. Fear of falling was identified as the main predictor of HQoL. The qualitative arm of our study explored our initial results in greater depth and uncovered themes not identified by the quantitative approach.

Conclusion: Our results illustrate the huge potential of mixed methodology in identifying issues influencing HQoL in POT. Our work paves the way for enhanced patient care and improved HQoL in POT and is paradigmatic of this modern approach for investigating HQoL issues in chronic neurological disorders.
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http://dx.doi.org/10.3389/fneur.2017.00747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5775514PMC
January 2018

Temporal Discrimination: Mechanisms and Relevance to Adult-Onset Dystonia.

Front Neurol 2017 28;8:625. Epub 2017 Nov 28.

Department of Neurology, St Vincent's University Hospital Dublin, Dublin, Ireland.

Temporal discrimination is the ability to determine that two sequential sensory stimuli are separated in time. For any individual, the temporal discrimination threshold (TDT) is the minimum interval at which paired sequential stimuli are perceived as being asynchronous; this can be assessed, with high test-retest and inter-rater reliability, using a simple psychophysical test. Temporal discrimination is disordered in a number of basal ganglia diseases including adult-onset dystonia, of which the two most common phenotypes are cervical dystonia and blepharospasm. The causes of adult-onset focal dystonia are unknown; genetic, epigenetic, and environmental factors are relevant. Abnormal TDTs in adult-onset dystonia are associated with structural and neurophysiological changes considered to reflect defective inhibitory interneuronal processing within a network which includes the superior colliculus, basal ganglia, and primary somatosensory cortex. It is hypothesized that abnormal temporal discrimination is a mediational endophenotype and, when present in unaffected relatives of patients with adult-onset dystonia, indicates non-manifesting gene carriage. Using the mediational endophenotype concept, etiological factors in adult-onset dystonia may be examined including (i) the role of environmental exposures in disease penetrance and expression; (ii) sexual dimorphism in sex ratios at age of onset; (iii) the pathogenesis of non-motor symptoms of adult-onset dystonia; and (iv) subcortical mechanisms in disease pathogenesis.
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http://dx.doi.org/10.3389/fneur.2017.00625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5712317PMC
November 2017

Application of virtual reality head mounted display for investigation of movement: a novel effect of orientation of attention.

J Neural Eng 2016 10 12;13(5):056006. Epub 2016 Aug 12.

School of Engineering, Trinity College, Dublin, Ireland.

Objective: To date human kinematics research has relied on video processing, motion capture and magnetic search coil data acquisition techniques. However, the use of head mounted display virtual reality systems, as a novel research tool, could facilitate novel studies into human movement and movement disorders. These systems have the unique ability of presenting immersive 3D stimulus while also allowing participants to make ecologically valid movement-based responses.

Approach: We employed one such system (Oculus Rift DK2) in this study to present visual stimulus and acquire head-turn data from a cohort of 40 healthy adults. Participants were asked to complete head movements towards eccentrically located visual targets following valid and invalid cues. Such tasks are commonly employed for investigating the effects orientation of attention and are known as Posner cueing paradigms. Electrooculography was also recorded for a subset of 18 participants.

Main Results: A delay was observed in onset of head movement and saccade onset during invalid trials, both at the group and single participant level. We found that participants initiated head turns 57.4 ms earlier during valid trials. A strong relationship between saccade onset and head movement onset was also observed during valid trials.

Significance: This work represents the first time that the Posner cueing effect has been observed in onset of head movement in humans. The results presented here highlight the role of head-mounted display systems as a novel and practical research tool for investigations of normal and abnormal movement patterns.
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http://dx.doi.org/10.1088/1741-2560/13/5/056006DOI Listing
October 2016

Exploring the unknown: electrophysiological and behavioural measures of visuospatial learning.

Eur J Neurosci 2016 05 16;43(9):1128-36. Epub 2016 Mar 16.

Trinity Centre for Bioengineering, Trinity College Dublin, 152-160 Pearse St, Dublin 2, Ireland.

Visuospatial memory describes our ability to temporarily store and manipulate visual and spatial information and is employed for a wide variety of complex cognitive tasks. Here, a visuospatial learning task requiring fine motor control is employed to investigate visuospatial learning in a group of typically developing adults. Electrophysiological and behavioural data are collected during a target location task under two experimental conditions: Target Learning and Target Cued. Movement times (MTs) are employed as a behavioural metric of performance, while dynamic P3b amplitudes and power in the alpha band (approximately 10 Hz) are explored as electrophysiological metrics during visuospatial learning. Results demonstrate that task performance, as measured by MT, is highly correlated with P3b amplitude and alpha power at a consecutive trial level (trials 1-30). The current set of results, in conjunction with the existing literature, suggests that changes in P3b amplitude and alpha power could correspond to different aspects of the learning process. Here it is hypothesized that changes in P3b correspond to a diminishing inter-stimulus interval and reduced stimulus relevance, while the corresponding changes in alpha power represent an automation of response as habituation occurs in participants. The novel analysis presented in the current study demonstrates how gradual electrophysiological changes can be tracked during the visuospatial learning process under the current paradigm.
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http://dx.doi.org/10.1111/ejn.13195DOI Listing
May 2016

Age-Related Sexual Dimorphism in Temporal Discrimination and in Adult-Onset Dystonia Suggests GABAergic Mechanisms.

Front Neurol 2015 14;6:258. Epub 2015 Dec 14.

Department of Neurology, St. Vincent's University Hospital , Dublin , Ireland ; School of Medicine and Medical Sciences, University College Dublin , Dublin , Ireland.

Background: Adult-onset isolated focal dystonia (AOIFD) presenting in early adult life is more frequent in men, whereas in middle age it is female predominant. Temporal discrimination, an endophenotype of adult-onset idiopathic isolated focal dystonia, shows evidence of sexual dimorphism in healthy participants.

Objectives: We assessed the distinctive features of age-related sexual dimorphism of (i) sex ratios in dystonia phenotypes and (ii) sexual dimorphism in temporal discrimination in unaffected relatives of cervical dystonia patients.

Methods: We performed (i) a meta-regression analysis of the proportion of men in published cohorts of phenotypes of adult-onset dystonia in relation to their mean age of onset and (ii) an analysis of temporal discrimination thresholds in 220 unaffected first-degree relatives (125 women) of cervical dystonia patients.

Results: In 53 studies of dystonia phenotypes, the proportion of men showed a highly significant negative association with mean age of onset (p < 0.0001, pseudo-R (2) = 59.6%), with increasing female predominance from 40 years of age. Age of onset and phenotype together explained 92.8% of the variance in proportion of men. Temporal discrimination in relatives under the age of 35 years is faster in women than men but the age-related rate of deterioration in women is twice that of men; after 45 years of age, men have faster temporal discrimination than women.

Conclusion: Temporal discrimination in unaffected relatives of cervical dystonia patients and sex ratios in adult-onset dystonia phenotypes show similar patterns of age-related sexual dimorphism. Such age-related sexual dimorphism in temporal discrimination and adult-onset focal dystonia may reflect common underlying mechanisms. Cerebral GABA levels have been reported to show similar age-related sexual dimorphism in healthy participants and may be the mechanism underlying the observed age-related sexual dimorphism in temporal discrimination and the sex ratios in AOIFD.
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http://dx.doi.org/10.3389/fneur.2015.00258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677337PMC
December 2015

Young Women do it Better: Sexual Dimorphism in Temporal Discrimination.

Front Neurol 2015 9;6:160. Epub 2015 Jul 9.

Trinity Centre for Bioengineering, Trinity College Dublin , Dublin , Ireland ; School of Engineering, Trinity College Dublin , Dublin , Ireland ; School of Medicine, Trinity College Dublin , Dublin , Ireland.

The temporal discrimination threshold (TDT) is the shortest time interval at which two sensory stimuli presented sequentially are detected as asynchronous by the observer. TDTs are known to increase with age. Having previously observed shorter thresholds in young women than in men, in this work we sought to systematically examine the effect of sex and age on temporal discrimination. The aims of this study were to examine, in a large group of men and women aged 20-65 years, the distribution of TDTs with an analysis of the individual participant's responses, assessing the "point of subjective equality" and the "just noticeable difference" (JND). These respectively assess sensitivity and accuracy of an individual's response. In 175 participants (88 women) aged 20-65 years, temporal discrimination was faster in women than in men under the age of 40 years by a mean of approximately 13 ms. However, age-related decline in temporal discrimination was three times faster in women so that, in the age group of 40-65 years, the female superiority was reversed. The point of subjective equality showed a similar advantage in younger women and more marked age-related decline in women than men, as the TDT. JND values declined equally in both sexes, showing no sexual dimorphism. This observed sexual dimorphism in temporal discrimination is important for both (a) future clinical research assessing disordered mid-brain covert attention in basal-ganglia disorders, and (b) understanding the biology of this sexual dimorphism which may be genetic or hormonal.
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http://dx.doi.org/10.3389/fneur.2015.00160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497309PMC
July 2015

Sun exposure is an environmental factor for the development of blepharospasm.

J Neurol Neurosurg Psychiatry 2016 Apr 22;87(4):420-4. Epub 2015 Apr 22.

Department of Neurology, St. Vincent's University Hospital, Dublin, Ireland School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.

Background: Adult-onset isolated focal dystonia may present with various phenotypes including blepharospasm and cervical dystonia. Although inherited in an autosomal dominant manner with a markedly reduced penetrance, environmental factors are considered important in disease penetrance and expression. We observed a marked variation by latitude in the reports of the frequency of patients with blepharospasm relative to those with cervical dystonia; we hypothesised that sun exposure is an environmental risk factor for the development of blepharospasm in genetically susceptible individuals.

Methods: From published clinic cohorts and epidemiological reports, the ratio of the number of cases of blepharospasm to cervical dystonia (phenotype case ratio) at each study site was analysed with regard to latitude and measures of annual insolation. Meta-regression analyses of the phenotype case ratio to these environmental factors were performed.

Results: The phenotype case ratio in 15 eligible study sites over 41° of latitude demonstrated a statistically significant inverse association with latitude (p=0.0004, R(2)=53.5%). There were significant positive associations between the phenotype case ratio and quarter-one (January-March) insolation (p=0.0005, R(2)=53%) and average annual insolation (p=0.003, R(2)=40%).

Conclusion: The increase in the blepharospasm: cervical dystonia case ratio with decreasing latitude and increasing insolation suggests that sunlight exposure is an environmental risk factor for the development of blepharospasm (rather than cervical dystonia) in individuals genetically susceptible to adult-onset dystonia.
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http://dx.doi.org/10.1136/jnnp-2014-310266DOI Listing
April 2016

Tremor severity is a poor predictor of social disability in patients with essential tremor.

Parkinsonism Relat Disord 2014 Nov 16;20(11):1311-2. Epub 2014 Sep 16.

School of Medicine, National University of Ireland Galway, Galway, Ireland; Department of Neurology, Galway University Hospital, Galway, Ireland. Electronic address:

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http://dx.doi.org/10.1016/j.parkreldis.2014.09.006DOI Listing
November 2014
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