Publications by authors named "Antoine Guéguen"

25 Publications

  • Page 1 of 1

Comparison of Corticosteroid Tapering Regimens in Myasthenia Gravis: A Randomized Clinical Trial.

JAMA Neurol 2021 Feb 8. Epub 2021 Feb 8.

General Intensive Care Unit, APHP, Raymond Poincaré Hospital, University of Versailles Saint-Quentin en Yvelines, Garches, France.

Importance: The tapering of prednisone therapy in generalized myasthenia gravis (MG) presents a therapeutic dilemma; however, the recommended regimen has not yet been validated.

Objective: To compare the efficacy of the standard slow-tapering regimen of prednisone therapy with a rapid-tapering regimen.

Design: From June 1, 2009, to July 31, 2013, a multicenter, parallel, single-blind randomized trial was conducted to compare 2 regimens of prednisone tapering. Data analysis was conducted from February 18, 2019, to January 23, 2020. A total of 2291 adults with a confirmed diagnosis of moderate to severe generalized MG at 7 specialized centers in France were assessed for eligibility.

Interventions: The slow-tapering arm included a gradual increase of the prednisone dose to 1.5 mg/kg every other day and a slow decrease once minimal manifestation status of MG was attained. The rapid-tapering arm consisted of immediate high-dose daily administration of prednisone, 0.75 mg/kg, followed by an earlier and rapid decrease once improved MG status was attained. Azathioprine, up to a maximum dose of 3 mg/kg/d, was prescribed for all participants.

Main Outcomes And Measures: The primary outcome was attainment of minimal manifestation status of MG without prednisone at 12 months and without clinical relapse at 15 months. Intention-to-treat analysis was conducted.

Results: Of the 2291 patients assessed, 2086 did not fulfill the inclusion criteria, 87 declined to participate, and 1 patient registered after trial closure. A total of 117 patients (58 in the slow-tapering arm and 59 in the rapid-tapering arm) were selected for inclusion by MG specialists and were randomized. The population included 62 men (53%); median age was 65 years (interquartile range, 35-69 years). The proportion of patients having met the primary outcome was higher in the rapid- vs slow-tapering arm (23 [39%] vs 5 [9%]), with a risk ratio of 3.61 (95% CI, 1.64-7.97; P < .001) after adjusting for center and thymectomy. The rapid-tapering regimen allowed sparing of a mean of 1898 mg (95% CI, -3121 to -461 mg) of prednisone over 1 year (ie, 5.3 mg/d per patient, P = .03). The number of serious adverse events did not differ significantly between the slow- vs rapid-tapering group (13 [22%] vs 21 [36%], P = .15).

Conclusions And Relevance: In patients with moderate to severe generalized MG who require high-dose prednisone with azathioprine therapy, rapid tapering of prednisone appears to be feasible, well tolerated, and associated with a good outcome.

Trial Registration: ClinicalTrials.gov Identifier: NCT00987116.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaneurol.2020.5407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871208PMC
February 2021

SARS-CoV-2-associated encephalitis: arguments for a post-infectious mechanism.

Crit Care 2020 11 23;24(1):658. Epub 2020 Nov 23.

Neuro-Intensive Care Unit, Fondation Ophtalmologique Adolphe de Rothschild, 29 rue Manin, 75019, Paris, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13054-020-03389-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682681PMC
November 2020

Prognosis Factors and Outcomes of Neuro-ophthalmologic Sarcoidosis.

Ocul Immunol Inflamm 2020 Nov 9:1-8. Epub 2020 Nov 9.

Département de Médecine Interne et Immunologie Clinique, Sorbonne Université, Centre National De Référence Maladies Autoimmunes Systémiques Rares, Centre National De Référence Maladies Autoinflammatoires et Amylose Inflammatoire. INSERM UMRS 959, Immunologie-Immunopathologie-Immunotherapie, Groupe Hospitalier Pitié-Salpêtrière, AP-HP , Paris, France.

: Neuro-ophthalmologic manifestations are uncommon in sarcoidosis. We aim to assess the prognostic factors and outcome of neuro-ophthalmic sarcoidosis. : We conducted a multicenter retrospective study on patients with neuro-ophthalmic sarcoidosis. Response to therapy was based on visual acuity, visual field, and orbital MRI exam. Factors associated with remission and relapse were analyzed. : Thirty-five patients [median (IQR) age of 37 years (26.5-53), 63% of women] were included. The diagnosis of sarcoidosis was concomitant of neuro-ophthalmologic symptoms in 63% of cases. Optic neuritis was the most common manifestation. All patients received corticosteroids and 34% had immunosuppressants. At 6 months, 61% improved, 30% were stable, and 9% worsened. Twenty percent of patients had severe visual deficiency at the end of follow-up. Nonresponders patients had significantly worse visual acuity at baseline ( = 0.01). Relapses were less frequent in patients with retro-bulbar optic neuropathy ( = 0.03). : Prognosis of neuro-ophthalmic sarcoidosis is poor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09273948.2020.1834585DOI Listing
November 2020

Visual field loss and structure-function relationships in optic neuritis associated with myelin oligodendrocyte glycoprotein antibody.

Mult Scler 2020 Jul 7:1352458520937281. Epub 2020 Jul 7.

Department of Neurology, Hôpital Fondation Adolphe de Rothschild, Paris, France.

Background: A paradoxical discrepancy between severe peripapillary retinal nerve fiber layer (pRNFL) atrophy and good visual outcome had been reported in patients with myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG)-associated optic neuritis (ON). However, only visual acuity (VA) was assessed.

Objectives: To study visual field (VF) outcomes of patients with MOG-IgG-associated ON and evaluate the correlation between functional eye outcome and retinal structural changes assessed by optical coherence tomography.

Methods: The records of 32 patients with MOG-IgG-associated ON who underwent ophthalmological examination at least 12 months after ON onset were reviewed. Degree of VF disability was determined by mean deviation (MD).

Results: At final assessment (median, 35 months), 4.2% of 48 affected eyes (AE) had VA ⩽ 0.1, 40% had abnormal MD, and among AE with final VA ⩾ 1.0, 31% had mild to moderate damage. Thinning of the inner retinal layers was significantly correlated with MD impairment. Analysis demonstrated a threshold of pRNFL thickness (50 µm), below which MD was significantly worse (mean, -2.27 dB vs -17.72 dB;  = 0.0003). ON relapse was significantly associated with poor visual outcome assessed by MD.

Conclusion: Functional impairment measured with VF is not rare, and MD assessment better reflects actual structural damage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1352458520937281DOI Listing
July 2020

Clinical Characteristics and Outcomes in Patients With Coronavirus Disease 2019 and Multiple Sclerosis.

JAMA Neurol 2020 09;77(9):1079-1088

Service de Neurologie, Clinical Investigation Center Institut National de la Santé et de la Recherche Médicale 1434, Centre Hospitalier Universitaire de Strasbourg, Strasbourg, France.

Importance: Risk factors associated with the severity of coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (MS) are unknown. Disease-modifying therapies (DMTs) may modify the risk of developing a severe COVID-19 infection, beside identified risk factors such as age and comorbidities.

Objective: To describe the clinical characteristics and outcomes in patients with MS and COVID-19 and identify factors associated with COVID-19 severity.

Design, Setting, And Participants: The Covisep registry is a multicenter, retrospective, observational cohort study conducted in MS expert centers and general hospitals and with neurologists collaborating with MS expert centers and members of the Société Francophone de la Sclérose en Plaques. The study included patients with MS presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020, and May 21, 2020.

Exposures: COVID-19 diagnosed with a polymerase chain reaction test on a nasopharyngeal swab, thoracic computed tomography, or typical symptoms.

Main Outcomes And Measures: The main outcome was COVID-19 severity assessed on a 7-point ordinal scale (ranging from 1 [not hospitalized with no limitations on activities] to 7 [death]) with a cutoff at 3 (hospitalized and not requiring supplemental oxygen). We collected demographics, neurological history, Expanded Disability Severity Scale score (EDSS; ranging from 0 to 10, with cutoffs at 3 and 6), comorbidities, COVID-19 characteristics, and outcomes. Univariate and multivariate logistic regression models were used to estimate the association of collected variables with COVID-19 outcomes.

Results: A total of 347 patients (mean [SD] age, 44.6 [12.8] years, 249 women; mean [SD] disease duration, 13.5 [10.0] years) were analyzed. Seventy-three patients (21.0%) had a COVID-19 severity score of 3 or more, and 12 patients (3.5%) died of COVID-19. The median EDSS was 2.0 (range, 0-9.5), and 284 patients (81.8%) were receiving DMT. There was a higher proportion of patients with a COVID-19 severity score of 3 or more among patients with no DMT relative to patients receiving DMTs (46.0% vs 15.5%; P < .001). Multivariate logistic regression models determined that age (odds ratio per 10 years: 1.9 [95% CI, 1.4-2.5]), EDSS (OR for EDSS ≥6, 6.3 [95% CI. 2.8-14.4]), and obesity (OR, 3.0 [95% CI, 1.0-8.7]) were independent risk factors for a COVID-19 severity score of 3 or more (indicating hospitalization or higher severity). The EDSS was associated with the highest variability of COVID-19 severe outcome (R2, 0.2), followed by age (R2, 0.06) and obesity (R2, 0.01).

Conclusions And Relevance: In this registry-based cohort study of patients with MS, age, EDSS, and obesity were independent risk factors for severe COVID-19; there was no association found between DMTs exposure and COVID-19 severity. The identification of these risk factors should provide the rationale for an individual strategy regarding clinical management of patients with MS during the COVID-19 pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaneurol.2020.2581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320356PMC
September 2020

[Indications and follow-up for autologous hematopoietic stem cell transplantation in multiple sclerosis: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) in association with the Francophone Society of Multiple Sclerosis].

Bull Cancer 2019 Jan 5;106(1S):S92-S101. Epub 2018 Dec 5.

Hôpital Saint-Louis, centre de référence des maladies auto-immunes systémiques rares d'Île-de-France, filière FAI2R, IUH EA-3518, UF04, unité de médecine interne, maladies auto-immunes et pathologie vasculaire, 1, avenue Claude-Vellefaux, 75475 Paris, France. Electronic address:

The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organized the 8th allogeneic hematopoietic stem cell transplantation clinical practices harmonization workshop series in September 2017 in Lille, France. In this article we give the indications of autologous stem cell transplantation in multiple sclerosis as well as recommendations regarding post-transplant follow-up of patients under the hospice of the SFGM-TC and the Francophone Society of Multiple Sclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bulcan.2018.11.002DOI Listing
January 2019

A novel method of inducing endogenous pupil oscillations to detect patients with unilateral optic neuritis.

PLoS One 2018 22;13(8):e0201730. Epub 2018 Aug 22.

Institut de la Vision, UPMC, Inserm-CNRS, Paris, France.

Purpose: To use and test a new method of inducing endogenously generated pupillary oscillations (POs) in patients with unilateral optic neuritis (ON), to describe a signal analysis approach quantifying pupil activity and to evaluate the extent to which POs permit to discriminate patients from control participants.

Method: Pupil size was recorded with an eye-tracker and converted in real time to modulate the luminance of a stimulus (a 20° disk) presented in front of participants. With this biofeedback setting, an increasing pupil size transforms into a high luminance, entraining a pupil constriction that in turn decreases the stimulus luminance, and so on, resulting in endogenously generated POs. POs were recorded for 30 seconds in the affected eye, in the fellow eye and in binocular conditions with 22 patients having a history of unilateral ON within a period of 5 years, and with 22 control participants. Different signal analysis methods were used to quantify the power and frequency of POs.

Results: On average, pupil size oscillated at around 1 Hz. The amplitude of POs appears not to be a reliable marker of ON. In contrast, the frequency of POs was significantly lower, and was more variable over time, in the patients' affected eye, as compared to their fellow eye and to the binocular condition. No such differences were found in control participants. Receiver operating characteristic analyses based on the frequency and the variability of POs to classify patients and control participants gave an area under the curve of 0.82, a sensitivity of 82% (95%CI: 60%-95%) and a specificity of 77% (95%CI: 55%-92%).

Conclusions: The new method used to induce POs allowed characterizing the visual afferent pathway defect in ON patients with encouraging accuracy. The method was fast, easy to use, only requiring that participants look ahead, and allows testing many stimulus parameters (e.g. color, stimulus location, size, etc).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0201730PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104938PMC
February 2019

Remote brain microhaemorrhages may predict haematoma in glioma patients treated with radiation therapy.

Eur Radiol 2018 Oct 12;28(10):4324-4333. Epub 2018 Apr 12.

Department of Radiology, Fondation Ophtalmologique Adolphe de Rothschild, 25 rue Manin, 75019, Paris, France.

Objectives: To evaluate the prevalence of cerebral remote microhaemorrhages (RMH) and remote haematomas (RH) using magnetic resonance susceptibility-weighted imaging (SWI) among patients treated for gliomas during follow-up.

Methods: We conducted a retrospective single centre longitudinal study on 58 consecutive patients treated for gliomas from January 2009 through December 2010. Our institutional review board approved this study. We evaluated the presence and number of RMH and RH found outside the brain tumour on follow-up MR imaging. We performed univariate and bivariate analyses to identify predictors for RMH and RH and Kaplan-Meier survival analysis techniques.

Results: Twenty-five (43%) and four patients (7%) developed at least one RMH or RH, respectively, during follow-up. The risk was significantly higher for patients who received radiation therapy (49% and 8% versus 0%) (p = 0.02). The risk of developing RH was significantly higher in patients with at least one RMH and a high burden of RMH. The mean age of those presenting with at least one RMH or RH was significantly lower.

Conclusions: RMH were common in adult survivors of gliomas who received radiation therapy and may predict the onset of RH during follow-up, mainly in younger patients.

Key Points: • Brain RMH and RH are significantly more likely to occur after RT. • RMH occur in almost half of the patients treated with RT. • RMH and RH are significantly more frequent in younger patients. • RH occur only in patients with RMH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-018-5356-8DOI Listing
October 2018

Anti-MAG antibodies in 202 patients: clinicopathological and therapeutic features.

J Neurol Neurosurg Psychiatry 2018 05 25;89(5):499-505. Epub 2017 Oct 25.

Department of Neurology, University Hospital Saint-Etienne, Saint-Etienne, France.

Objective: To assess the clinicopathological and therapeutic features of patients with low (≥1000 to <10 000 Bühlmann Titre Units) (BTU), medium (10 000-70 000) or high (≥70 000) anti-myelin-associated glycoprotein (anti-MAG) antibody titres.

Methods: We retrospectively and prospectively analysed standardised report forms and medical records of 202 patients from 14 neuromuscular centres.

Results: Mean age at onset and mean time between symptom onset to last follow-up were respectively 62.6 years (25-91.4) and 8.4 years (0.3-33.3). Anti-MAG antibody titres at diagnosis were low, medium or high in 11%, 51% and 38% of patients. Patients presented with monoclonal gammopathy of undetermined significance in 68% of cases. About 17% of patients presented with 'atypical' clinical phenotype independently of anti-MAG titres, including acute or chronic sensorimotor polyradiculoneuropathies (12.4%), and asymmetric or multifocal neuropathy (3%). At the most severe disease stage, 22.4% of patients were significantly disabled. Seventy-eight per cent of patients received immunotherapies. Transient clinical worsening was observed in 12% of patients treated with rituximab (11/92). Stabilisation after rituximab treatment during the 7-12-month follow-up period was observed in 29% of patients. Clinical response to rituximab during the 6-month and/or 7-12-month follow-up period was observed in 31.5% of patients and correlated with anti-MAG titre ≥10 000 BTU.

Conclusion: Our study highlights the extended clinical spectrum of patients with anti-MAG neuropathy, which appears unrelated to antibody titre. Besides, it may also suggest beneficial use of rituximab in the early phase of anti-MAG neuropathy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jnnp-2017-316715DOI Listing
May 2018

Reply to "Axonal hyperexcitability due to Schwann cell involvement in chronic progressive external ophthalmoplegia".

Clin Neurophysiol 2017 10 31;128(10):2098. Epub 2017 Jul 31.

Fondation Ophtalmologique A. de Rothschild, Department of Neurology, 25 Rue Manin, Paris, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinph.2017.07.407DOI Listing
October 2017

Evaluation of French-language internet sites dealing with multiple sclerosis.

Mult Scler J Exp Transl Clin 2016 Jan-Dec;2:2055217316652419. Epub 2016 Jun 15.

Novartis Pharma S.A.S, Rueil-Malmaison, France.

Background: Information available on the internet has changed patient-neurologist relationships. Its evaluation for multiple sclerosis is only partial, regardless of the language used.

Objective: We aim to evaluate the content quality and ranking indexes of French-language sites dealing with multiple sclerosis.

Methods: Two French terms and three search engines were used to identify the sites whose ranking indexes were calculated according to their positions on each page designated by the search engines. Three evaluators used the DISCERN questionnaire to assess the content quality of the 25 selected sites. The sites were classified according to the mean of the evaluators' grades. Grading agreement between evaluators was calculated. Ranking indexes were computed as a rank/100.

Results: Content level was deemed mediocre, with poor referencing of the information provided. The naïve and two expert evaluators' grades differed. Content quality disparity was found within the different website categories, except for institutional sites. No correlation was found between content quality and ranking index.

Conclusion: The information available was heterogeneous. Physicians should guide patients in their internet searches for information so that they can benefit from good-quality input which is potentially able to improve their management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2055217316652419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433325PMC
June 2016

Erratum to: Plasma exchange response in 34 patients with severe optic neuritis.

J Neurol 2017 07;264(7):1547

Service de Neurologie, Fondation Ophtalmologique Adolphe de Rothschild, 25 Rue Manin, 75019, Paris, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00415-017-8534-8DOI Listing
July 2017

Nerve excitability changes related to muscle weakness in chronic progressive external ophthalmoplegia.

Clin Neurophysiol 2017 07 26;128(7):1258-1263. Epub 2017 Apr 26.

Institute of Neurology, University College London, London, United Kingdom. Electronic address:

Objective: To explore potential spreading to peripheral nerves of the mitochondrial dysfunction in chronic progressive external ophthalmoplegia (CPEO) by assessing axonal excitability.

Methods: CPEO patients (n=13) with large size deletion of mitochondrial DNA and matching healthy controls (n=22) were included in a case-control study. Muscle strength was quantified using MRC sum-score and used to define two groups of patients: CPEO-weak and CPEO-normal (normal strength). Nerve excitability properties of median motor axons were assessed with the TROND protocol and changes interpreted with the aid of a model.

Results: Alterations of nerve excitability strongly correlated with scores of muscle strength. CPEO-weak displayed abnormal nerve excitability compared to CPEO-normal and healthy controls, with increased superexcitability and responses to hyperpolarizing current. Modeling indicated that the CPEO-weak recordings were best explained by an increase in the 'Barrett-Barrett' conductance across the myelin sheath.

Conclusion: CPEO patients with skeletal weakness presented sub-clinical nerve excitability changes, which were not consistent with axonal membrane depolarization, but suggested Schwann cell involvement.

Significance: This study provides new insights into the spreading of large size deletion of mitochondrial DNA to Schwann cells in CPEO patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinph.2017.04.013DOI Listing
July 2017

Plasma exchange response in 34 patients with severe optic neuritis.

J Neurol 2016 May 10;263(5):883-887. Epub 2016 Mar 10.

Service de Neurologie, Fondation Ophtalmologique Adolphe de Rothschild, 25 Rue Manin, 75019, Paris, France.

Optic neuritis could lead to severe visual impairment despite corticosteroids. Our aim was to evaluate the rate of visual improvement in patients treated with plasma exchange (PLEX) for severe steroid unresponsive optic neuritis and to identify predictive factors of outcome. Thirty-four patients (41 optic nerves damaged) with remaining visual acuity of 0.1 or less despite steroid pulse therapy were treated with PLEX from September 2010 to May 2015. Demographic and clinical neuro-ophthalmic findings, and spectral domain-optical coherence tomography data before PLEX treatment were analyzed. The mean symptom duration before PLEX was 34.6 days (median 28 days; range 6-92 days). After PLEX, the median final visual acuity was 0.8 and in 56 % of cases, final acuity was 0.5 or better. Past history of ipsilateral optic neuritis was associated significantly with poor outcome defined as final acuity less than 0.5. No significant difference in the visual outcome after PLEX was found between multiple sclerosis and neuromyelitis optica. In conclusion, this observational study showed that PLEX as second-line therapy led to a functionally important visual recovery in more than half patients with severe optic neuritis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00415-016-8073-8DOI Listing
May 2016

[New treatments and strategy in multiple sclerosis]

Rev Prat 2016 01;66(1):44-50

Service de neurologie, Fondation ophtalmologique Adolphe-de-Rothschild, Paris, France.

New treatments and strategy in multiple sclerosis. Currently, ten drugs are approved for the relapsing-remitting form of multiple sclerosis (MS). Since 2007, 4 new disease-modifying therapies (DMT) have been approved and several DMT will soon be commercialized including new galenic forms of self-injectable DMTs (pegylated interferon beta 1a and glatiramer acetate). Although these self-injectable DMT have moderate efficacy they have proved to be safe on long term and able to delay disability progression and the entry in the secondary progressive phase of the disease. Some of the new DMT have similar efficacy to the first DMT, other are more efficient but carry the risk of serious adverse events. We report the efficacy and safety of these new drugs in reference to their pivotal study. The current therapeutic strategy is sequential: a first DMT is initiated, then in case of intolerance or failure an other DMT with a different mode of action or second line DMT is proposed. Others strategies may be proposed according to the patient's evolution such as an induction by an aggressive immunotherapy followed by a maintenance with a first line DMT. Whatever the strategy used the most important goal is to reach a shared decison between the patient and his or her neurologist which guarantee the best adherence to DMTs.
View Article and Find Full Text PDF

Download full-text PDF

Source
January 2016

Does HIV Infection Alter Parkinson Disease?

J Acquir Immune Defic Syndr 2015 Oct;70(2):129-36

*Service de Neurologie, Fondation Adolphe de Rothschild, Paris, France; †Service des Maladies Infectieuses et Tropicales, AP-HP, Hôpital Tenon, Paris, France; ‡Service des Maladies Infectieuses et Tropicales, AP-HP, Hôpital Saint Louis, Paris, France; §Service des Maladies Infectieuses et Tropicales, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France; ‖INSERM, IAME, UMR 1137, Paris, France; ¶Unité James Parkinson, Service de Neurologie, Fondation Adolphe de Rothschild, Paris, France; #Service des Maladies Infectieuses et Tropicales, AP-HP, Hôpital Saint Antoine, Paris, France; **Université Pierre et Marie Curie, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), UMRS 975, Equipe "Alzheimer's and Prion Diseases," Paris, France; ††Département d'Ophtalmologie, Fondation Adolphe de Rothschild, Paris, France; and ‡‡Service d'Ophtalmologie, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France.

Objective: To describe the clinical features, treatment(s), and outcomes of 15 HIV-infected patients with idiopathic Parkinson disease (PD) and sustained virus suppression and immunologic reconstitution, from a reference cohort of 9847 persons living with HIV (PLH).

Methods: This retrospective, single-center matched case-control 1:2 study included PLH-PD patients evaluated over a 12-year period (2002-2013) with mean follow-up of 6.5 years. PD clinical features and dopamine replacement therapy (DRT) were compared, and biologically relevant HIV data were assessed.

Results: PD prevalence in PLH was similar to that of the general population. At onset, clinical presentations and therapeutic management were similar for both groups. Rapidly effective DRT was well tolerated without combined antiretroviral therapy interactions or virus escape. At the end of the follow-up, compared with HIV-negative PD, PLH had a significantly lower median Unified Parkinson's Disease Rating Scale motor score (4 vs 14; P < 0.001), median Hoehn and Yahr stage (1 vs 2; P = 0.0005), and median Handipark scale score (2 vs 3; P = 0.0036) under the same daily DRT. One PLH underwent highly successful deep brain stimulation of the subthalamic nucleus.

Conclusions: HIV-associated PD is similar to idiopathic PD with some features suggesting an HIV-induced functional adaptation of dopaminergic neurons that might counterbalance the PD-induced neuronal loss. Concurrent HIV infection does not compromise the outcome of idiopathic PD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAI.0000000000000677DOI Listing
October 2015

First Ischemic Stroke in Sickle-Cell Disease: Are There Any Adult Specificities?

Stroke 2015 Aug 14;46(8):2315-7. Epub 2015 Jul 14.

From the Department of Neurology Hôpital Sainte-Anne, Université Paris-Descartes, INSERM 894, DHU Neurovasc-Paris Sorbonne, Paris, France (D.C.); Pediatrics, Referral Center for Sickle Cell Disease, Centre Hospitalier Intercommunal, Créteil, France (F.B.); Fondation Ophtalmologique A. de Rothschild, Paris, France (A.G.); Service de Neurologie, Hôpital Henri-Mondor, UPEC, Créteil, France (H.H.); Department of Neurology Sickle cell referral center, médecine interne, Hôpital Henri-Mondor, UPEC, Créteil, France (A.H, F.G., P.B.); and INSERM U955, team 2, Laboratoire d'Excellence Grex, Créteil, France (A.H, F.G., P.B.).

Background And Purpose: There is little evidence about characteristics of ischemic stroke (IS) occurring in adults with sickle-cell disease (SCD). The objective of this study was to assess characteristics of first-ever IS in adults with SCD and to assess whether they differ from those occurring in child patients with SCD.

Methods: Adult and child individuals with SCD who had a first-ever IS were identified from cohorts of patients followed up in an adult and a child sickle cell referral center. Mechanisms of IS were determined by consensus meeting from all available explorations using the following predefined classification: Vasculopathy, cardioembolism, other defined cause, and undetermined. Treatment and stroke recurrences were recorded from prospective follow-up performed in the referral centers.

Results: Twenty-nine adults and 26 children had a first-ever IS; mean age (SD) was 7.1 (4.3) and 32.3 (11.6), respectively. With regard to IS mechanism, vasculopathy was less often the cause of IS in adults (12/29, 41%) than in children (24/26, 92%; P<0.001). Other causes of IS in adults were cardioembolism in 7, antiphospholipid syndrome in 1, toxic (cocaine) in 1, and undetermined in 8. Adults with SCD had a higher risk of recurrent stroke (23.1% [7.0-39.2] at 5 years) compared with children (1 recurrence only; P log rank=0.046) despite exchange-blood transfusion in patients with vasculopathy.

Conclusions: First-ever IS occurring in adults with SCD has specificities that justify further studies conducted in adults with SCD to improve understanding and management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.115.010153DOI Listing
August 2015

Abnormal inflammatory activity returns after natalizumab cessation in multiple sclerosis.

J Neurol Neurosurg Psychiatry 2014 Sep 29;85(9):1038-40. Epub 2014 May 29.

Department of Neurology, Fondation Ophtalmologique A. de Rothschild, Paris, France.

Objective: To characterise recurrence of multiple sclerosis (MS) inflammatory activity during the year following natalizumab (NTZ) cessation.

Methods: Thirty-two patients with MS were included in a monocentric cohort study. Data were collected prospectively during and after NTZ, with serial clinical and MRI evaluations. The first relapse occurring after interrupting NTZ was the primary outcome measure. The numbers of gadolinium-enhancing lesions before, during and after NTZ treatment, were compared.

Results: During the year following NTZ cessation, the cumulative probability of relapses was estimated at 52.9% and an unusually high MRI inflammation was noticed. It was defined by a number of gadolinium-enhancing lesions >5 and exceeding the gadolinium lesions existing before NTZ initiation. Rebound of MS activity after NTZ cessation was characterised by association of relapses and unusual MRI inflammation. Cumulative probability of rebound was estimated at 39% and mostly occurring between 3 months and 9months after interrupting NTZ. Risk of rebound appears related with a higher annualised relapse rate and a lower Expanded Disability Status Scale score before NTZ initiation. Rebound was associated with severe recurring relapses in 9% of the patients.

Conclusions: This study identifies rebound after NTZ cessation as an association of relapses and high MRI activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jnnp-2014-307591DOI Listing
September 2014

Sickle-cell disease stroke throughout life: a retrospective study in an adult referral center.

Am J Hematol 2014 Mar;89(3):267-72

Strokes are one of the most severe complications of sickle-cell disease. Most studies have been restricted to children with sickle-cell disease. To better understand the characteristics and follow-up of strokes occurring from childhood to adulthood, we undertook a retrospective cohort study of 69 stroke patients among the 2,875 patients consulting at the French Adult Sickle-Cell Disease Referral Center. Between 1970 and 2008, they had experienced 104 strokes: 80 ischemic, 22 hemorrhagic, and 2 intracranial sinus thromboses. Coma and/or fatal outcomes underscored the severity of strokes in sickle-cell disease patients.Hemorrhagic strokes occurred mostly in adults and carried a higher risk of death than ischemic stroke. The mechanisms underlying sickle-cell disease associated strokes were reevaluated and etiologies were determined for first stroke and recurrences, in childhood and adulthood. Sickle-cell disease vasculopathy concerned only SS patients and remains their most frequent stroke etiology. Cardioembolism, vaso-occlusive crisis and triggering factors were other etiologies identified in adults. Recurrences occurred in 19 SS patients only after a first ischemic stroke. SC patients' strokes occurred in adulthood and were associated with cardiovascular risk factors. Our findings provide novel information about cerebrovascular pathologies throughout the lives of sickle-cell disease patients and suggest the need for different diagnostic and therapeutic management approaches in those different settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajh.23625DOI Listing
March 2014

Peripheral nerve hyperexcitability with preterminal nerve and neuromuscular junction remodeling is a hallmark of Schwartz-Jampel syndrome.

Neuromuscul Disord 2013 Dec 4;23(12):998-1009. Epub 2013 Sep 4.

Inserm, U975, Centre de recherche de l'Institut du Cerveau et de la Moelle Épinière (CRICM), Groupe hospitalier Pitié-Salpêtrière, Paris, France; Université Pierre et Marie Curie Paris 6, UMRS975, Paris, France; CNRS, UMR7225, Paris, France; Ecole Pratique des Hautes Etudes, Paris, France.

Schwartz-Jampel syndrome (SJS) is a recessive disorder with muscle hyperactivity that results from hypomorphic mutations in the perlecan gene, a basement membrane proteoglycan. Analyses done on a mouse model have suggested that SJS is a congenital form of distal peripheral nerve hyperexcitability resulting from synaptic acetylcholinesterase deficiency, nerve terminal instability with preterminal amyelination, and subtle peripheral nerve changes. We investigated one adult patient with SJS to study this statement in humans. Perlecan deficiency due to hypomorphic mutations was observed in the patient biological samples. Electroneuromyography showed normal nerve conduction, neuromuscular transmission, and compound nerve action potentials while multiple measures of peripheral nerve excitability along the nerve trunk did not detect changes. Needle electromyography detected complex repetitive discharges without any evidence for neuromuscular transmission failure. The study of muscle biopsies containing neuromuscular junctions showed well-formed post-synaptic element, synaptic acetylcholinesterase deficiency, denervation of synaptic gutters with reinnervation by terminal sprouting, and long nonmyelinated preterminal nerve segments. These data support the notion of peripheral nerve hyperexcitability in SJS, which would originate distally from synergistic actions of peripheral nerve and neuromuscular junction changes as a result of perlecan deficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nmd.2013.07.005DOI Listing
December 2013

Encephalitis and CSF increased level of interferon-α in Kikuchi-Fujimoto disease.

BMJ Case Rep 2012 Aug 27;2012. Epub 2012 Aug 27.

Neurology Department, Fondation Ophtalmologique Adolphe de Rothschild, Paris, France.

Neurological manifestations have been reported in Kikuchi-Fujimoto disease (KFD). Characteristics of brain lesions are not defined. In addition, no biological indexes are known to help clinicians along the diagnosis process. The authors describe encephalitis associated with KFD. Brain MRI, positron emission tomography (PET) scan and a large biological assessment including interferon α (INF-α) level measurement in cerebrospinal fluid (CSF) were performed. A 39-year-old man with chronic headaches developed diplopia, slow ideation and behavioural disturbances. MRI showed brain lesions particularly in the pontine region and internal temporal lobes with enhancement of the perivacular space and the walls of the lateral ventricle. The IFN-α level was increased in the CSF without viral infection. Cervical and mediastinal adenitis were evident as a hypermetabolic focus on a PET scan, and biopsy confirmed the diagnosis of KFD. The encephalitis spontaneously remitted. The authors characterised brain lesions especially related to KFD in association with increased of IFN-α level in the CSF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bcr.01.2012.5579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3433502PMC
August 2012

[Gliomatosis cerebri: a biopsy and autopsy case report].

Ann Pathol 2010 Feb 25;30(1):25-9. Epub 2009 Nov 25.

Service d'anatomie et de cytologie pathologiques, hôpital Lariboisière, AP-HP, université Paris 7, 2 rue Ambroise-Paré, Paris cedex 10, France.

Gliomatosis cerebri is a rare glial neoplasm, characterized by diffuse brain infiltration with relative preservation of the underlying cytoarchitecture. Its clinical and radiologic features are not specific and its antemortem diagnosis is difficult. We report a case of gliomatosis cerebri in a 68-year-old woman presenting with gait disturbances and episodic seizures. MRI showed bilateral white matter hypersignal intensities on Flair sequences and brain biopsy revealed a poorly cellular proliferation of neoplasic glial cells strongly expressing OLIG-2, Ki-67 and occasionally GFAP, without alpha-internexin expression. The patient status worsened rapidly and she died 2 months after the initial symptoms. Postmortem brain examination confirmed gliomatosis cerebri and revealed a focal glioblastoma in the frontal cortex, with nuclear p53 expression in the highest malignant areas. Gliomatosis cerebri should be included in the differential diagnostic of diffuse brain lesions. Antemortem diagnosis, although difficult, can be assessed by IRM and careful biopsy examination. Progression to glioblastoma has been seldom reported, enhancing the controversy about the etiopathogenesis of this rare tumour.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.annpat.2009.10.020DOI Listing
February 2010

Nerve excitability changes after intravenous immunoglobulin infusions in multifocal motor neuropathy and chronic inflammatory demyelinating neuropathy.

J Neurol Sci 2010 May 10;292(1-2):63-71. Epub 2010 Mar 10.

Service de Physiologie, Explorations Fonctionnelles, Hôpital Henri Mondor, Assistance Publique, Hôpitaux de Paris, Créteil, France.

Intravenous immunoglobulin (IVIg) infusions may provide clinical benefits in multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating polyneuropathy (CIDP). The short delay in the clinical response to IVIg therapy is not consistent with a process of remyelination or axonal regeneration. We assessed whether or not the efficacy of IVIg infusions in MMN and CIDP could reflect changes in axonal membrane properties and nerve excitability. Ulnar motor nerve excitability was studied before and after three to five consecutive days of IVIg infusions (0.4 g/kg/day) in 10 patients with MMN, 10 patients with CIDP, and 10 neurological controls (CTRLs). Excitability recovery cycle, stimulus-response and strength-duration properties were investigated. The recovery cycle parameters (absolute and relative refractory period durations, refractoriness and supernormality) were similar in all groups and did not change after IVIg infusions. At baseline, patients with CIDP, but not with MMN, showed a reduced strength-duration time constant (chronaxie) and increased rheobase when compared to CTRLs. After IVIg infusions, strength-duration time constant remained stable in CTRLs, but decreased in patients with MMN or CIDP. Rheobase increased in the three groups after treatment. The decreased strength-duration time constant after IVIg infusions in patients with MMN or CIDP could reflect a reduction of persistent Na(+) current, able to limit intraaxonal Na(+) accumulation and then to produce neuroprotective effects. However, this could also reflect compensatory mechanisms that did not directly underlie the therapeutic effect. Whatever the underlying process, this result revealed that IVIgs were able to produce early nerve excitability changes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jns.2010.02.002DOI Listing
May 2010