Emmanuelle Apartis

Hôpital Saint-Antoine (Hôpitaux Universitaires Est Parisien), Lutetia Parisorum, Île-de-France, France

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Publications (30)146.84 Total impact

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    ABSTRACT: To assess the clinical spectrum of ataxia-telangiectasia (A-T) in adults, with a focus on movement disorders.
    Neurology 08/2014; · 8.30 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. · 4.32 Impact Factor
  • Movement Disorders 02/2013; · 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.
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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 10/2012; · 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; · 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; · 3.58 Impact Factor
  • Revue Neurologique 04/2012; 168:A35–A36. · 0.51 Impact Factor
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    Movement Disorders 01/2012; 27(6):797-9. · 5.63 Impact Factor
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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. · 3.97 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. · 2.89 Impact Factor
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    Journal of Neurology 02/2011; 258(2):316-7. · 3.58 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 01/2011; 34(2):483-8. · 4.07 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. · 2.30 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.
    Biologie aujourd'hui. 01/2010; 204(4):295-300.
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    ABSTRACT: Our knowledge of the clinical, neurophysiological, and genetic aspects of myoclonus-dystonia (M-D) has improved markedly in the recent years. Basic research has provided new insights into the complex dysfunctions involved in the pathogenesis of M-D. On the basis of a comprehensive literature search, this review summarizes current knowledge on M-D, with a focus on recent findings. We also propose modified diagnostic criteria and recommendations for clinical management.
    Movement Disorders 01/2009; 24(4):479-89. · 5.63 Impact Factor
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    ABSTRACT: Atypical parkinsonism is extremely frequent in Guadeloupe and may have an environmental cause. One-half of the patients with this tauopathy have dopa-resistant parkinsonism, tremor, subcortical dementia and abnormal eye movements suggestive of progressive supranuclear palsy (PSP). They also have hallucinations, dysautonomia, which are not characteristic of PSP. Furthermore, the oculomotor abnormalities and the tremor, which is jerky, differ from what is observed in classical PSP patients. We therefore undertook an electrophysiological study to characterize these features in greater detail. Nine representative Guadeloupean PSP-like (Gd-PSP) patients were selected for electro-oculographic recordings of horizontal eye movements [visually guided saccades (VGS), antisaccades (AS) and smooth pursuit], clinical evaluation of vertical saccade velocity and electrophysiological analysis of abnormal limb movements [electromyographic polygraphy, EEG jerk-locked-back-averaging (JLBA) and long-loop C-reflex]. Vertical saccade velocity was reduced in five patients. The velocity of horizontal VGS was normal, although the latencies were increased and horizontal smooth pursuit (HSP) was mostly saccadic. The AS error rate was above 70% in most patients. Myoclonus was detected in 89% of the Gd-PSP patients. It was mainly small amplitude rest and action myoclonus in the upper limbs, characterized by short arrhythmic 24-76 ms bursts and was of cortical origin, as confirmed by JLBA in five patients. In conclusion, Gd-PSP patients have cortical myoclonus and cortical oculomotor impairments, but only minor signs of brainstem oculomotor dysfunction, suggesting that cortical dysfunction predominates over brainstem impairments. This electrophysiological study, added to previous clinical, neuropsychological and neuroradiological studies, has enriched the characterization of Guadeloupean atypical parkinsonism, which thus appears to be a new clinical entity.
    Brain 11/2008; 131(Pt 10):2701-9. · 10.23 Impact Factor
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    ABSTRACT: Myoclonus-dystonia is a movement disorder often associated with mutations in the maternally imprinted epsilon-sarcoglycan (SGCE) gene located on chromosome 7q21. Silver-Russell syndrome is a heterogeneous disorder characterized by prenatal and postnatal growth restriction and a characteristic facies, caused in some cases by maternal uniparental disomy of chromosome 7. To describe and investigate the combination of a typical myoclonus-dystonia syndrome and Silver-Russell syndrome. Clinical and neurophysiological examination as well as cytogenetic and molecular analyses. Movement disorder clinic. Patient A 36-year-old man with typical myoclonus-dystonia and Silver-Russell syndrome. Clinical description of the disease and its genetic cause. Cytogenetic analysis revealed mosaicism for a small chromosome 7 marker chromosome. Microsatellite analysis indicated loss of the paternal allele and maternal uniparental disomy of chromosome 7. In keeping with the maternal imprinting mechanism, no unmethylated allele of SGCE was detected after bisulfite treatment of the patient's DNA, and reverse transcription-polymerase chain reaction demonstrated loss of SGCE expression. Molecular analysis ruled out mutations in the SGCE gene. We identified a new genetic alteration-maternal chromosome 7 disomy-that can cause myoclonus-dystonia. This alteration results in repression of both alleles of the maternally imprinted SGCE gene and suggests SGCE loss of function as the disease mechanism.
    Archives of neurology 11/2008; 65(10):1380-5. · 7.58 Impact Factor
  • Movement Disorders 10/2008; 23(15):2256-7. · 5.63 Impact Factor
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    ABSTRACT: Glutaric aciduria type 1 (GA1) is an autosomal recessive neurometabolic disorder due to glutaryl CoA dehydrogenase deficiency. Comprehensive descriptions of GA1-associated movement disorders are rare. In order to refine the description of the motor phenotype, we prospectively studied 16 consecutive pediatric and adult GA1 patients, focusing on the movement disorders and their time course. In most patients, generalized dystonia, superimposed on baseline axial hypotonia, remained the predominant feature throughout the disease course. With aging, it tended to evolve from mobile to fixed dystonia and to be associated with akinetic-rigid parkinsonism. Prominent orofacial involvement was a consistent feature in GA1 patients with movement disorders, resulting in speech disorders with features of combined hyperkinetic dysarthria and speech apraxia. The types and outcome of movement disorders in this setting should be taken into consideration during rehabilitation and for patient selection and evaluation in therapeutic trials.
    Movement Disorders 10/2008; 23(16):2392-7. · 5.63 Impact Factor

Publication Stats

368 Citations
146.84 Total Impact Points

Institutions

  • 2010–2013
    • Hôpital Saint-Antoine (Hôpitaux Universitaires Est Parisien)
      Lutetia Parisorum, Île-de-France, France
    • Centre Hospitalier Universitaire Rouen
      Rouen, Upper Normandy, France
  • 2012
    • Charles University in Prague
      Praha, Praha, Czech Republic
  • 2006–2012
    • Assistance Publique – Hôpitaux de Paris
      • Department of Neurology
      Lutetia Parisorum, Île-de-France, France
  • 2008–2011
    • 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