Emmanuelle Apartis

Pierre and Marie Curie University - Paris 6, Lutetia Parisorum, Île-de-France, France

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Publications (35)160.79 Total impact

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    ABSTRACT: Orthostatic tremor is a rare condition characterised by high-frequency tremor that appears on standing. Although the essential clinical features of orthostatic tremor are well established, little is known about the natural progression of the disorder. We report the long-term outcome based on the largest multicentre cohort of patients with orthostatic tremor. Clinical information of 68 patients with clinical and electrophysiological diagnosis of orthostatic tremor and a minimum follow-up of 5 years is presented. There was a clear female preponderance (76.5%) with a mean age of onset at 54 years. Median follow-up was 6 years (range 5-25). On diagnosis, 86.8% of patients presented with isolated orthostatic tremor and 13.2% had additional neurological features. At follow-up, seven patients who initially had isolated orthostatic tremor later developed further neurological signs. A total 79.4% of patients reported worsening of orthostatic tremor symptoms. These patients had significantly longer symptom duration than those without reported worsening (median 15.5 vs 10.5 years, respectively; p=0.005). There was no change in orthostatic tremor frequency over time. Structural imaging was largely unremarkable and dopaminergic neuroimaging (DaTSCAN) was normal in 18/19 cases. Pharmacological treatments were disappointing. Two patients were treated surgically and showed improvement. Orthostatic tremor is a progressive disorder with increased disability although tremor frequency is unchanged over time. In most cases, orthostatic tremor represents an isolated syndrome. Drug treatments are unsatisfactory but surgery may hold promise. 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 03/2015; DOI:10.1136/jnnp-2014-309942 · 5.58 Impact Factor
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    ABSTRACT: We propose a simple non-invasive novel method based on video/audio recordings to analyse soft palate abnormal movements and to study their changes in the frequency distribution under modifying tasks.
    02/2015; DOI:10.1002/mdc3.12128
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    ABSTRACT: Objective:To assess the clinical spectrum of ataxia-telangiectasia (A-T) in adults, with a focus on movement disorders.Methods:A total of 14 consecutive adults with A-T were included at 2 tertiary adult movement disorders centers and compared to 53 typical patients with A-T. Clinical evaluation, neurophysiologic and video-oculographic recording, imaging, laboratory investigations, and ATM analysis were performed.Results:In comparison with typical A-T cases, our patients demonstrated later mean age at onset (6.1 vs 2.5 years, p < 0.0001), later loss of walking ability (p = 0.003), and longer survival (p = 0.0039). The presenting feature was ataxia in 71% and dysarthria and dystonia in 14% each. All patients displayed movement disorders, among which dystonia and subcortical myoclonus were the most common (86%), followed by tremor (43%). Video-oculographic recordings revealed mostly dysmetric saccades and 46% of patients had normal latencies (i.e., no oculomotor apraxia) and velocities. The -fetoprotein (AFP) level was normal in 7%, chromosomal instability was found in 29% (vs 100% of typical patients, p = 0.0006), and immunoglobulin deficiency was found in 29% (vs 69%, p = 0.057). All patients exhibited 2 ATM mutations, including at least 1 missense mutation in 79% of them (vs 36%, p = 0.0067).Conclusion:There is great variability of phenotype and severity in A-T, including a wide spectrum of movement disorders. Karyotype and repeated AFP level assessments should be performed in adults with unexplained movement disorders as valuable clues towards the diagnosis. In case of a compatible phenotype, A-T should be considered even if age at onset is late and progression is slow.
    Neurology 08/2014; 83(12). DOI:10.1212/WNL.0000000000000794 · 8.30 Impact Factor
  • Revue Neurologique 04/2014; 170:A142-A143. DOI:10.1016/j.neurol.2014.01.381 · 0.60 Impact Factor
  • Revue Neurologique 04/2014; 170:A153. DOI:10.1016/j.neurol.2014.01.407 · 0.60 Impact Factor
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    ABSTRACT: Autosomal recessive cerebellar ataxia 2 (ARCA2) is a recently identified recessive ataxia due to ubiquinone deficiency and biallelic mutations in the ADCK3 gene. The phenotype of the twenty-one patients reported worldwide varies greatly. Thus, it is difficult to decide which ataxic patients are good candidates for ADCK3 screening without evidence of ubiquinone deficiency. We report here the clinical and molecular data of 10 newly diagnosed patients from seven families and update the disease history of four additional patients reported in previous articles to delineate the clinical spectrum of ARCA2 phenotype and to provide a guide to the molecular diagnosis. First signs occurred before adulthood in all 14 patients. Cerebellar atrophy appeared in all instances. The progressivity and severity of ataxia varied greatly, but no patients had the typical inexorable ataxic course that characterizes other childhood-onset recessive ataxias. The ataxia was frequently associated with other neurological signs. Importantly, stroke-like episodes contributed to significant deterioration of the neurological status in two patients. Ubidecarenone therapy markedly improved the movement disorders, including ataxia, in two other patients. The 7 novel ADCK3 mutations found in the 10 new patients were two missense and five truncating mutations. There was no apparent correlation between the genotype and the phenotype. Our series reveals that the clinical spectrum of ARCA2 encompasses a range of ataxic phenotypes. On one end, it may manifest as a pure ataxia with very slow progressivity and, on the other end, as a severe infantile encephalopathy with cerebellar atrophy. The phenotype of most patients, however, lies in between. It is characterized by a very slowly progressive or apparently stable ataxia associated with other signs of central nervous system involvement. We suggest undergoing the molecular analysis of ADCK3 in patients with this phenotype and in those with cerebellar atrophy and a stroke-like episode. The diagnosis of patients with a severe ARCA2 phenotype may also be performed on the basis of biological data, i.e. low ubiquinone level or functional evidence of ubiquinone deficiency. This diagnosis is crucial since the neurological status of some patients may be improved by ubiquinone therapy.
    Orphanet Journal of Rare Diseases 10/2013; 8(1):173. DOI:10.1186/1750-1172-8-173 · 3.96 Impact Factor
  • Movement Disorders 08/2013; 28(9). DOI:10.1002/mds.25340 · 5.63 Impact Factor
  • Emmanuelle Apartis
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    ABSTRACT: Neurophysiological tools are very helpful in characterizing various movement disorders, consequently guiding etiological research and therapy. Movement disorders recordings are currently underutilized in neurological practice in adults and could also be extended to the pediatric population. Surface polymyography (EMG) combined with accelerometry is commonly used for the analysis of many types of hyperkinetic movement disorders, mainly myoclonus, tremor, dystonia, and sometimes tics and chorea. To study myoclonus, techniques exploring cortical excitability, namely conventional EEG, EEG-jerk-locked-back-averaging (JLBA), somatosensory evoked potentials (SEP) and C-reflex studies, should necessarily complete the EMG analysis. Premovement potential recording and measures of the stimulus induced jerks latencies may help to differentiate psychogenic jerks from myoclonus. The field of clinical usefulness of movement disorders recordings is large. Main issues are: (1) to differentiate tremor from myoclonus, (2) to demonstrate and locate dystonic features, either isolated or associated to tremor and myoclonus, (3) to define the nature of a tremor, (4) to assess the psychogenic nature of a tremor or jerks, and (5) to define the neurophysiological generator of myoclonus in the central nervous system. Neurophysiological data allow us to clearly classify myoclonus as cortical, cortico-thalamic, and subcortical-resulting from lesions or dysfunctions of basal ganglia/reticular system-or spinal.
    Handbook of Clinical Neurology 01/2013; 111:87-92. DOI:10.1016/B978-0-444-52891-9.00008-7
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    ABSTRACT: BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is an inherited neurometabolic disorder. The main neurological manifestations of the disease are pyramidal syndrome, ataxia, peripheral neuropathy, cognitive impairment, epilepsy, and psychiatric disturbances. Myoclonic dystonia has been reported on in the setting of various neurometabolic diseases. Anecdotal reports describe movement disorders associated with CTX, but no dystonia with myoclonic events. METHODS: We collected clinical, biochemical, electrophysiological, neuroradiological, and genetic data of 6 patients with myoclonus and mild dystonia associated with CTX. From a systematic literature review, we analyzed 31 patients with movement disorders secondary to CTX. RESULTS: Our 6 patients presented distal myoclonus with mild dystonia of the upper limbs. Myoclonus was of subcortical origin, based on neurophysiological recordings, and differed from oromandibular myoclonus previously described in CTX patients. CONCLUSIONS: These results expand the phenotype of CTX and suggest that myoclonus and/or dystonia are underdiagnosed. In keeping with our findings, tremors previously observed in CTX patients might actually correspond to myoclonic events. We hypothesize that a dysfunction of the dentate nuclei-basal ganglia pathway may be involved. © 2012 Movement Disorder Society.
    Movement Disorders 12/2012; 27(14). DOI:10.1002/mds.25206 · 5.63 Impact Factor
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    ABSTRACT: OBJECTIVE: Fragile X-associated tremor ataxia syndrome (FXTAS) is defined by FMR1 premutation, cerebellar ataxia, intentional tremor, and middle cerebellar peduncle (MCP) hyperintensities. We delineate the clinical, neurophysiologic, and morphologic characteristics of FXTAS. METHODS: Clinical, morphologic (brain MRI, (123)I-ioflupane SPECT), and neurophysiologic (tremor recording, nerve conduction studies) study in 22 patients with FXTAS, including 4 women. RESULTS: A total of 43% of patients had no family history of fragile X syndrome (FXS), which contrasts with previous FXTAS series. A total of 86% of patients had tremor and 81% peripheral neuropathy. We identified 3 electroclinical tremor patterns: essential-like (35%), cerebellar (29%), and parkinsonian (12%). Two electrophysiologic patterns evocative of non-length-dependent (56%) and length-dependent sensory neuropathy (25%) were identified. Corpus callosum splenium (CCS) hyperintensity was as frequent (68%) as MCP hyperintensities (64%). Sixty percent of patients had parkinsonism and 47% abnormal (123)I-ioflupane SPECT. Unified Parkinson's Disease Rating Scale motor score was correlated to abnormal (123)I-ioflupane SPECT (p = 0.02) and to CGG repeat number (p = 0.0004). Scale for the assessment and rating of ataxia correlated with dentate nuclei hyperintensities (p = 0.03) and CCS hyperintensity was a marker of severe disease progression (p = 0.04). CONCLUSIONS: We recommend to include in the FXTAS testing guidelines both CCS hyperintensity and peripheral neuropathy and to consider them as new major radiologic and minor clinical criterion, respectively, for the diagnosis of FXTAS. FXTAS should also be considered in women or when tremor, MCP hyperintensities, or family history of FXS are lacking. Our study broadens the spectrum of tremor, peripheral neuropathy, and MRI abnormalities in FXTAS, hence revealing the need for revised criteria.
    Neurology 10/2012; DOI:10.1212/WNL.0b013e318271f7ff · 8.30 Impact Factor
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    ABSTRACT: Spinocerebellar ataxia type 3 (SCA3) can be present with a combination of cerebellar, neuropathic, pyramidal, or extrapyramidal symptoms. Tremor is a classical but not frequent manifestation of SCA3 and there is a lack of detailed knowledge regarding its origin. To study the clinical and electrophysiological characteristics of tremor in SCA3 patients, the authors conducted a case series of 72 SCA3 patients. Clinical characteristics of tremor and associated signs, response to treatments, follow-up, and genetic results were collected. Electrophysiological study including polymyographic recording was possible in 4/6 patients and DaTSCAN in 2/6. The authors also performed a systematic review of SCA3 cases with tremor (n = 36) reported previously in the literature. We identified two different tremor-types in 6/72 patients with SCA3 mutations, a "fast" (6.5-8 Hz) action, postural or tremor in orthostatism (initial symptom), which became slower over time with associated parkinsonism with a follow-up of 10 years and a "slow" rest, action and intention tremor (3-4 Hz) with distal and proximal component (including axial tremor in orthostatism). Total improvement of limbs and tremor in orthostatism was obtained with levodopa with occurrence of fluctuations/dyskinesia. Partial benefit was observed when additional signs were present (myoclunus/dystonia). The differences in tremor subtypes in SCA3 may be related to various combinations of mild to severe dysfunctions of the cerebello-thalamo-cortical loop and the nigro-striatal dopaminergic pathway.
    Journal of Neurology 05/2012; DOI:10.1007/s00415-012-6531-5 · 3.84 Impact Factor
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    Movement Disorders 05/2012; 27(6):797-9. DOI:10.1002/mds.24923 · 5.63 Impact Factor
  • Revue Neurologique 04/2012; 168:A35–A36. DOI:10.1016/j.neurol.2012.01.086 · 0.60 Impact Factor
  • Emmanuel Roze, Emmanuelle Apartis
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    ABSTRACT: Myoclonus-dystonia is an inherited syndrome with mainly dominant paternal inheritance. In this genetically heterogeneous syndrome, mutation or deletion of the epsilon sarcoglycan gene is found in about 40% of families. The typical phenotype consists of very brief, “lightning-like” myoclonic jerks, which may be either isolated or associated with mild to moderate dystonia and generally predominate in the upper body. Onset in the first or second decade is the rule. The pathogenic mechanism is likely to include dysfunction of the basal ganglia network. Pharmacological treatments are disappointing. Deep brain stimulation of the internal globus pallidus is an option in severe forms.
    Hyperkinetic Movement Disorders, 02/2012: pages 207-220; , ISBN: 9781444333527
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    ABSTRACT: Recent observations suggest that besides their role in the immune system, chemokines have important functions in the brain. There is a great line of evidence to suggest that chemokines are a unique class of neurotransmitters/neuromodulators, which regulate many biological aspects as diverse as neurodevelopment, neuroinflammation and synaptic transmission. In physiopathological conditions, many chemokines are synthesized in activated astrocytes and microglial cells, suggesting their involvement in brain defense mechanisms. However, when evoking chemokine functions in the nervous system, it is important to make a distinction between resting conditions and various pathological states including inflammatory diseases, autoimmune or neurodegenerative disorders in which chemokine functions have been extensively studied. We illustrate here the emergent concept of the neuromodulatory/neurotransmitter activities of neurochemokines and their potential role as a regulatory alarm system and as a group of messenger molecules for the crosstalk between neurons and cells from their surrounding microenvironment. In this deliberately challenging review, we provide novel hypotheses on the role of these subtle messenger molecules in brain functions leading to the evidence that previous dogmas concerning chemokines should be reconsidered.
    Journal of Neurochemistry 07/2011; 118(5):680-94. DOI:10.1111/j.1471-4159.2011.07371.x · 4.24 Impact Factor
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    ABSTRACT: Glucose transporter 1 deficiency syndrome (GLUT1-DS) is due to heterozygous mutation of the glucose transporter type 1 gene (GLUT1/SLC2A1). GLUT1-DS is characterized by movement disorders, including paroxysmal exercise-induced dystonia (PED), as well as seizures, mental retardation and hypoglycorrhachia. Tremor was recently shown to be part of the phenotype, but its clinical and electrophysiological features have not yet been described in detail, and GLUT1 tremor reports are rare. We describe two patients, a young woman and her mother, who were referred to us for tremor. We also systematically review published cases of GLUT1-DS with tremor (14 cases, including ours), focusing on clinical features. In most cases (10/14), the tremor, which involved the limbs and voice, fulfilled clinical criteria for dystonic tremor (DT), occurring in body areas affected by dystonia. Tremor was the only permanent symptom in 2 cases. Recordings, reported here for the first time, showed an irregular 6- to 8.5-Hz tremor compatible with DT in our two patients. These findings show that tremor, and particularly DT, may be a presenting symptom of GLUT1-DS. Patients who present with dystonic tremor, with or without mental retardation, seizures, movement disorders and/or a family history, should therefore be screened for GLUT1-DS.
    Journal of Inherited Metabolic Disease 04/2011; 34(2):483-8. DOI:10.1007/s10545-010-9264-6 · 4.14 Impact Factor
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    ABSTRACT: Cocaine-induced sensitization induces long-term neuroplastic changes in the striatum. Among these, extracellular signal-regulated kinase (ERK) is a fundamental component in striatal gene and epigenetic regulation and plays an important role in reward processes. As previous studies suggested that the chemokine CCL2 enhanced striatal dopamine release and as its cognate CCR2 receptor was located in brain structures implicated in cocaine reward, we tested the hypothesis that CCR2/CCL2 could be involved in cocaine-induced behavioral response. We used CCR2 knockout mice (CCR2(-/-)) and studied two crucial steps in cocaine sensitization: locomotor activity in sensitized mice and ERK activation in the striatum. We show that locomotor sensitization is significantly reduced in CCR2(-/-) mice as well as the dopamine transporter regulation and the cocaine-induced p-ERK striatal activation. Taken together, our results suggest that CCR2 receptor is involved in cocaine sensitization.
    Journal of Molecular Neuroscience 03/2011; 44(3):147-51. DOI:10.1007/s12031-011-9508-4 · 2.76 Impact Factor
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    Journal of Neurology 02/2011; 258(2):316-7. DOI:10.1007/s00415-010-5702-5 · 3.84 Impact Factor
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    ABSTRACT: Myoclonus dystonia (M-D) is a rare genetic movement disorder characterized by a combination of myoclonic jerks and dystonia. It is usually due to mutations in the SGCE gene. We report on a patient with a typical M-D syndrome, but also short stature, microcephaly, and mental retardation. Molecular analysis showed no mutations within the SGCE gene but a microdeletion encompassing the SGCE gene in chromosome region 7q21. Array-CGH analysis showed that the deletion spanned approximately 1.88 Mb. We suggest that M-D plus patients with mental retardation, microcephaly, dysmorphism, or short stature, all frequently associated disorders, should be screened for 7q21 microdeletion. By examining previously published cases of mental retardation associated with pure 7q21 deletions, we identified two distinct regions of respectively 455 and 496 kb that are critical for mental retardation and growth retardation. Among the genes located within these regions, LOC253012, also known as HEPACAM2, is a good candidate for both mental retardation and microcephaly.
    American Journal of Medical Genetics Part A 05/2010; 152A(5):1244-9. DOI:10.1002/ajmg.a.33369 · 2.05 Impact Factor
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    ABSTRACT: Previous neuroanatomical studies realized in our team allowed us to demonstrate the neuronal and glial expression of various chemokines and their receptors in central dopaminergic (DA) pathways. In the light of these original observations, we questioned the role of chemokines on the physiology of DA neuron and on the neurodegenerative process in the DA nigro-striatal pathway, which characterizes Parkinson's disease. We focused our attention on two particular chemokines, the Stromal cell-Derived Factor-1 (SDF-1/CXCL12) and the Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) and their cognate receptors CXCR4 and CCR2, as they are expressed constitutively in nearly all DA mesencephalic neurons. We demonstrated, by using in vivo and in vitro approaches, that SDF-1 and MCP-1 can modulate DA neurotransmission in the nigro-striatal pathway, modifying the electrophysiological state of the neuron and DA release, through their cognate receptors. These effects are produced through N-type high voltage-activated calcium currents for SDF-1 and potassium channels for MCP-1. We then discuss the possible implication of SDF-1 and its derivative SDF-1(5-67) in DA neurodegeneration.
    01/2010; 204(4):295-300. DOI:10.1051/jbio/2010023

Publication Stats

568 Citations
160.79 Total Impact Points

Institutions

  • 2008–2015
    • Pierre and Marie Curie University - Paris 6
      • • Institut de la Vision
      • • Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière
      Lutetia Parisorum, Île-de-France, France
  • 2011–2014
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      Lutetia Parisorum, Île-de-France, France
  • 2013
    • L'Institut du Cerveau et de la Moelle Épinière
      Lutetia Parisorum, Île-de-France, France
    • Hôpital Saint-Antoine (Hôpitaux Universitaires Est Parisien)
      Lutetia Parisorum, Île-de-France, France
  • 2012
    • Hôpital Foch
      Lutetia Parisorum, Île-de-France, France
  • 2006–2012
    • Assistance Publique – Hôpitaux de Paris
      • Department of Neurology
      Lutetia Parisorum, Île-de-France, France
  • 2010
    • Hôpital Armand-Trousseau (Hôpitaux Universitaires Est Parisien)
      Lutetia Parisorum, Île-de-France, France