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BACKGROUND: Serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are promising biomarkers that might be associated with clinical and radiological markers of multiple sclerosis (MS) severity. However, it is not known whether they can accurately identify patients at risk of disability progression in the medium and long term. OBJECTIVES: We wanted to determine the association between sNfL and sGFAP, Expanded Disability Status Scale score changes, and conversion to secondary progressive MS (SPMS) in a cohort of 133 patients with relapsing remitting MS. METHODS: Blood samples were collected at inclusion to measure SNfL and sGFAP by single molecule array and their prognostic value was assessed using a linear mixed model. RESULTS: In this cohort, 37 patients (27.8 % of 133) experienced disability progression and 12 patients (9.0 %) converted to SPMS during the follow-up (mean follow-up duration: 6.4 years). Only sNfL (p = 0.03) was associated with conversion to SPMS, and neither SNfL nor sGFAP was associated with disability progression. CONCLUSION: Serum NfL and GFAP do not seem to accurately predict MS outcome in the long term. More studies are needed to determine how serum biomarkers, associated with other clinical and MRI biomarkers, might be used to improve MS prognostication.
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The frequency of corticospinal tract (CST) T2/FLAIR hyperintensity in disorders with neuroglial antibodies is unclear. Herein, we retrospectively reviewed brain MRIs of 101 LGI1-antibody encephalitis patients, and observed CST hyperintensity in 30/101 (30%). It was mostly bilateral (93%), not associated with upper motor neuron signs/symptoms (7%), and frequently decreased over time (39%). In a systematic review including patients with other neuroglial antibodies, CST hyperintensity was reported in 110 with neuromyelitis optica (94%), myelin oligodendrocyte glycoprotein-associated disease (2%), Ma2-antibody (3%) and GAD65-antibody paraneoplastic neurological syndrome (1%). CST hyperintensity is not an infrequent finding in LGI1-Ab encephalitis and other disorders with neuroglial antibodies.
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Autoanticorpos , Encefalite , Peptídeos e Proteínas de Sinalização Intracelular , Tratos Piramidais , Humanos , Autoanticorpos/imunologia , Autoanticorpos/sangue , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Idoso , Adulto , Encefalite/imunologia , Encefalite/diagnóstico por imagem , Tratos Piramidais/diagnóstico por imagem , Tratos Piramidais/patologia , Tratos Piramidais/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Imageamento por Ressonância Magnética , Adulto Jovem , Neuroglia/patologia , Neuroglia/imunologia , Adolescente , Idoso de 80 Anos ou mais , Doenças do Sistema Nervoso Central/imunologia , Doenças do Sistema Nervoso Central/diagnóstico por imagemRESUMO
BACKGROUND: Transvenous embolization is a recent treatment strategy for cerebrospinal fluid-venous fistulas (CSFVF), which are associated with spontaneous intracranial hypotension (SIH). METHODS: Participants were selected from a prospective database on patients with CSFVF that received transvenous Onyx embolization. All patients underwent a brain magnetic resonance imaging (MRI) before and after embolization with MRI follow-up performed at least 3 months after treatment. Clinical and MRI results after treatment were described. RESULTS: Twenty-one consecutive patients (median age 63 years, IQR = 58-71; females: 15/21 = 71.5%) with 30 CSFVF were included. Most lesions were situated between T9 and L1 (19/30 = 63%), 70% were right-sided, and 38% of the patients had multiples fistulas. Embolization was successful in all cases. The mean MRI SIH score before and after treatment was 6 (±2.5) and 1.4 (±1.6), respectively (p < 0.0001). Twenty patients (90%) experienced improvement of their initial condition, of which 67% reported complete clinical recovery. The mean HIT-6 score decreased from 67 (±15) to 38 (±9) (p < 0.0001), the mean amount of monthly headache days from 23.5 (±10) and 3.2 (±6.6) (p < 0.0001), the visual assessment scale (VAS) for headache severity from 8 (±1.9) to 1.2 (±2) (p < 0.0001), and the mean VAS for perception quality of life improved from 2.6 (±2.5) to 8.6 (±1.8) (p < 0.0001). There were no major complications. The suspected rebound headache rate after treatment was 33%. CONCLUSION: Transvenous embolization of CSFVF allowed high rates of clinical improvement with no morbidity related to the treatment.
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BACKGROUND: Precise localization and understanding of the origin of cerebrospinal fluid (CSF) leak is crucial to allow targeted treatment. We report the technical feasibility and utility of dorsal-decubitus dynamic computed tomography (DDDCT) myelography to localize posteriorly located dural defects in patients with suspicion of posterolateral dural tears. METHODS: This study reports a series of four consecutive patients with posteriorly located SLEC and suspicion of posterolateral CSF leak who received DDDCT to localize the site of the leak. Patients were collected between October 2022 and October 2023. The technique of DDDCT and its efficacy to detect the site of CSF leak are reported. RESULTS: In all four patients (three females, one male, mean age 39 years), DDDCT myelography was technically successful and precisely demonstrated the site of the CSF leak. In one patient with both anterior and posterior SLEC, DDDCT allowed to exclude the presence of a posteriorly located leak, while a subsequent ventral decubitus dynamic CT myelography localized the leak. Leak sites were all thoracic, except for one that was cervical. Information obtained from the DDDCT myelography was considered useful to target the treatment of the leak. CONCLUSIONS: Based on our experience, DDDCT provided sufficient spatial and temporal resolution to pinpoint fast CSF leaks and it may be considered to localize posterolateral dural defects.
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BACKGROUND AND PURPOSE: In addition to combined central and peripheral demyelination, other immune diseases could involve both the central nervous system (CNS) and peripheral nervous system (PNS). METHODS: To identify immune-mediated diseases responsible for symptomatic combined central/peripheral nervous system involvement (ICCPs), we conducted a multicentric retrospective study and assessed clinical, electrophysiological, and radiological features of patients fulfilling our ICCP criteria. RESULTS: Thirty patients (20 males) were included and followed during a median of 79.5 months (interquartile range [IQR] = 43-145). The median age at onset was 51.5 years (IQR = 39-58). Patients were assigned to one of four groups: (i) monophasic disease with concomitant CNS/PNS involvement including anti-GQ1b syndrome (acute polyradiculoneuropathy + rhombencephalitis, n = 2), checkpoint inhibitor-related toxicities (acute polyradiculoneuropathy + encephalitis, n = 3), and anti-glial fibrillary acidic protein astrocytopathy (subacute polyradiculoneuropathy and meningoencephalomyelitis with linear gadolinium enhancements, n = 2); (ii) chronic course with concomitant CNS/PNS involvement including paraneoplastic syndromes (ganglionopathy/peripheral hyperexcitability + limbic encephalitis, n = 4); (iii) chronic course with sequential CNS/PNS involvement including POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome (polyradiculoneuropathy + strokes, n = 2), histiocytosis (polyradiculoneuropathy + lepto-/pachymeningitis, n = 1), and systemic vasculitis (multineuropathy + CNS vasculitis/pachymeningitis, n = 2); and (iv) chronic course with concomitant or sequential CNS/PNS involvement including combined central and peripheral demyelination (polyradiculoneuropathy + CNS demyelinating lesions, n = 10) and connective tissue diseases (ganglionopathy/radiculopathy/multineuropathy + limbic encephalitis/transverse myelitis/stroke, n = 4). CONCLUSIONS: We diagnosed nine ICCPs. The timing of central and peripheral manifestations and the disease course help determine the underlying immune disease. When antibody against neuroglial antigen is identified, CNS and PNS involvement is systematically concomitant, suggesting a common CNS/PNS antigen and a simultaneous disruption of blood-nerve and blood-brain barriers.
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Doenças Desmielinizantes , Doenças do Sistema Imunitário , Encefalite Límbica , Polirradiculoneuropatia , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Desmielinizantes/complicações , Doenças do Sistema Imunitário/complicações , Encefalite Límbica/complicações , Sistema Nervoso Periférico , Polirradiculoneuropatia/complicações , Estudos Retrospectivos , FemininoRESUMO
In this study, we aimed to determine the frequency and clinical impact of new ischemic lesions detected with diffusion-weighted-imaging-MRI (DWI-MRI) as well as the clinical outcomes after carotid artery stenting (CAS) using the simple flow blockage technique (SFB). This is a retrospective study with data extraction from a monocentric prospective clinical registry (from 2017 to 2019) of consecutive patients admitted for symptomatic cervical ICA stenosis or web. Herein, patients benefited from DWI-MRI before and within 48 h of CAS for symptomatic ICA stenosis or web. The primary endpoint was the frequency of new DWI-MRI ischemic lesions and the secondary (composite) endpoint was the rate of mortality, symptomatic stroke or acute coronary syndrome within 30 days of the procedure. All of the 82 CAS procedures were successfully performed. Among the 33 patients (40.2%) with new DWI-MRI ischemic lesions, 30 patients were asymptomatic (90.9%). Irregular carotid plaque surface with (n = 13, 44.8%) or without ulceration (n = 12, 60.0%) was associated with higher rates of new DWI-MRI lesions by comparison to patients with a regular plaque (n = 7, 25%) (p = 0.048) using the univariate analysis. Less than half of this CAS cohort using the SFB technique had new ischemic lesions detected with DWI-MRI. Among these patients, more than 90% were asymptomatic. Irregularity of the plaque seems to increase the risk of peri-procedural DWI-MRI lesions.
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BACKGROUND: Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating disorder. Given its variable prognosis, the identification of new prognostic biomarkers is needed. OBJECTIVES: The aims of our study were to assess the prognostic values of CSF ß-amyloid-42 (Aß42) and ß-amyloid-40 (Aß40) levels in MS patients. METHODS: Eighty-nine (55 RRMS, 34 PPMS) patients with a recent diagnosis and 27 controls were included in this single-centre retrospective study. Clinical, MRI and CSF data have been collected and were analysed to evaluate the potential value of CSF Aß42 and Aß40 levels as MS biomarkers. RESULTS: CSF Aß levels as well as Aß42/Aß40 ratio were identical in MS patients and controls. Although CSF Aß42 and Aß40 levels were higher in PPMS than in RRMS and in patients with higher EDSS, a multivariate analysis including age and EDSS demonstrated that only age of patients was associated with CSF amyloid levels. Additionally, 55 RRMS patients were followed for 3 years. We found no association between baseline amyloid levels and 3-year disability. CONCLUSION: Our data do not support an association between CSF amyloid levels and MS status and disease severity. We suggest that CSF amyloid levels are not a prognostic biomarker in recently diagnosed RRMS.
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Peptídeos beta-Amiloides , Esclerose Múltipla , Humanos , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Esclerose Múltipla/diagnóstico por imagem , Fragmentos de Peptídeos , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Leptomeningeal enhancement (LME) is a key feature of Susac syndrome (SuS) but is only occasionally depicted on post-contrast T1-weighted images (T1-WI). OBJECTIVE: As post-contrast fluid-attenuated inversion recovery (FLAIR) may be more sensitive, our aim was to assess LME in SuS on this sequence. METHODS: From 2010 to 2020, 20 patients with definite SuS diagnosis were retrospectively enrolled in this multicentre study. Two radiologists independently assessed the number of LME on post-contrast FLAIR and T1-WI acquisitions performed before any treatment. A chi-square test was used to compare both sequences and the interrater agreement was calculated. RESULTS: Thirty-five magnetic resonance imagings (MRIs) were performed before treatment, including 19 post-contrast FLAIR images in 17 patients and 25 post-contrast T1-WI in 19 patients. In terms of patients, LME was observed on all post-contrast FLAIR, contrary to post-contrast T1-WI (17/17 (100%) vs. 15/19 (79%), p < 0.05). In terms of sequences, LME was observed on all post-contrast FLAIR, contrary to post-contrast T1-WI (19/19 (100%) vs. 16/25 (64%), p < 0.005). LME was disseminated at both supratentorial (19/19) and infratentorial (18/19) levels on post-contrast FLAIR, contrary to post-contrast T1-WI (3/25 and 9/25, respectively). Interrater agreement was excellent for post-contrast FLAIR (κ = 0.95) but only moderate for post-contrast T1-WI (κ = 0.61). CONCLUSION: LME was always observed and easily visible on post-contrast FLAIR images prior to SuS treatment. In association with other MRI features, it is highly indicative of SuS.
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Síndrome de Susac , Meios de Contraste , Diagnóstico Precoce , Humanos , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Síndrome de Susac/diagnóstico por imagemRESUMO
MED1 (mediator subunit 1) co-amplifies with HER2, but its role in HER2-driven mammary tumorigenesis is still unknown. Here, we generate MED1 mammary-specific overexpression mice and cross them with mouse mammary tumor virus (MMTV)-HER2 mice. We observe significantly promoted onset, growth, metastasis, and multiplicity of HER2 tumors by MED1 overexpression. Further studies reveal critical roles for MED1 in epithelial-mesenchymal transition, cancer stem cell formation, and response to anti-HER2 therapy. Mechanistically, RNA sequencing (RNA-seq) transcriptome analyses and clinical sample correlation studies identify Jab1, a component of the COP9 signalosome complex, as the key direct target gene of MED1 contributing to these processes. Further studies reveal that Jab1 can also reciprocally regulate the stability and transcriptional activity of MED1. Together, our findings support a functional cooperation between these co-amplified genes in HER2+ mammary tumorigenesis and their potential usage as therapeutic targets for the treatment of HER2+ breast cancers.
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Neoplasias Mamárias Experimentais/patologia , Subunidade 1 do Complexo Mediador/metabolismo , Receptor ErbB-2/metabolismo , Animais , Antineoplásicos/uso terapêutico , Complexo do Signalossomo COP9/antagonistas & inibidores , Complexo do Signalossomo COP9/genética , Complexo do Signalossomo COP9/metabolismo , Movimento Celular , Transição Epitelial-Mesenquimal , Feminino , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Lapatinib/uso terapêutico , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/genética , Vírus do Tumor Mamário do Camundongo/genética , Subunidade 1 do Complexo Mediador/genética , Camundongos , Camundongos Nus , Metástase Neoplásica , Células-Tronco Neoplásicas/citologia , Células-Tronco Neoplásicas/metabolismo , Peptídeo Hidrolases/genética , Peptídeo Hidrolases/metabolismo , Fenótipo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ativação TranscricionalRESUMO
BACKGROUND: Symptomatic isolated carotid artery occlusions (ICAO) can lead to disability, recurrent stroke, and mortality, but natural history and best therapeutic management remain poorly known. The objective of this study was to describe our cohort of ICAO patients with an initial medical management. METHODS: We conducted a retrospective study including consecutive patients admitted to our Comprehensive Stroke Center for ICAO within 24 h after stroke onset between January 2016 and September 2018. Patients with immediate endovascular therapy (EVT) were excluded. Medical treatment was based on anticoagulation (delayed by 24 h if intravenous thrombolysis was performed). 'Rescue' EVT was considered if first-week neurological deterioration (FWND) occurred. RESULTS: Fifty-six patients were included, with a median National Institutes of Health Stroke Scale (NIHSS) of 3. Eleven patients (20%) had FWND during the first week, four benefited from rescue EVT. A mismatch volume > 40 cc on initial perfusion imaging and FLAIR vascular hyperintensities were associated with FWND (p = 0.007 and p = 0.009, respectively). Thirty-eight patients (69%) had a good outcome (modified Rankin Scale mRS 0-2) at 3 months, 36 (69%) had an excellent outcome (mRS 0-1). Seventeen patients (38%) had carotid patency on 3-month control imaging. Recurrences occurred in six (13%) of the survivors (mean follow-up: 13.6 months). CONCLUSION: Our results suggest that the prognosis of patients with acute ICAO was favorable with a medical strategy, albeit a substantial rate of FWND and recurrence. FWND was well predicted by a core-perfusion mismatch volume > 40 cc. Randomized controlled trials are necessary to assess the benefit of EVT in ICAO.
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Isquemia Encefálica , Procedimentos Endovasculares , Acidente Vascular Cerebral , Artéria Carótida Interna/diagnóstico por imagem , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Trombectomia , Resultado do TratamentoRESUMO
BACKGROUND: The advent of new, potent, disease-modifying therapies has dramatically changed the management of multiple sclerosis (MS). Along with these possibilities, it is crucial to better recognize patients who are at risk of first line treatment (FLT) failure and switch to highly effective therapies (HET). OBJECTIVES: To identify baseline prognostic factors associated with FLT failure in relapsing remitting MS (RR-MS) patients. METHODS: We included recently diagnosed RR-MS patients starting an FLT identified from 3 French MS centers databases. Baseline characteristics were included in a multivariable Cox analysis to identify the main factors associated with FLT failure. RESULTS: Eight hundred sixty-three patients were included. We observed an overall rate of treatment failure of 23.5%. The main baseline characteristics associated with treatment failure were age <26 years at treatment start (HR= 2.1, p<0.001), EDSS ≥2 (HR=2.1, p<0.001) and ≥2relapses in the previous year (HR=1.5, p=0.04). The association with the presence of gadolinium enhancement on MRI was not statistically significant. EDSS progression was only significantly associated with age at treatment start and treatment failure. CONCLUSION: Our series demonstrates that some clinical and imaging factors are associated with treatment failure, and should be considered when planning treatment strategy in patients with recently diagnosed RR-MS.
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Meios de Contraste , Esclerose Múltipla Recidivante-Remitente , Adulto , Estudos de Coortes , Gadolínio , Humanos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Falha de TratamentoRESUMO
Neurofilament light chain (NfL) has been demonstrated to correlate with multiple sclerosis disease severity as well as treatment response. Nevertheless, additional serum biomarkers are still needed to better differentiate disease activity from disease progression. The aim of our study was to assess serum glial fibrillary acid protein (s-GFAP) and neurofilament light chain (s-NfL) in a cohort of 129 multiple sclerosis (MS) patients. Eighteen primary progressive multiple sclerosis (PPMS) and 111 relapsing remitting MS (RRMS) were included. We showed that these 2 biomarkers were significantly correlated with each other (R = 0.72, p < 0.001). Moreover, both biomarkers were higher in PPMS than in RRMS even if multivariate analysis only confirmed this difference for s-GFAP (130.3 ± 72.8 pg/ml vs 83.4 ± 41.1 pg/ml, p = 0.008). Finally, s-GFAP was correlated with white matter lesion load and inversely correlated with WM and GM volume. Our results seem to confirm the added value of s-GFAP in the context of multiple sclerosis.
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Encéfalo/patologia , Proteína Glial Fibrilar Ácida/sangue , Imageamento por Ressonância Magnética , Esclerose Múltipla Crônica Progressiva/sangue , Esclerose Múltipla Recidivante-Remitente/sangue , Substância Branca/patologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/patologia , Esclerose Múltipla Recidivante-Remitente/patologia , Proteínas de Neurofilamentos/sangue , Índice de Gravidade de DoençaRESUMO
BACKGROUND AND PURPOSE: The best embolic protection strategy has not yet been established for carotid artery stenting (CAS). This article reports a new simplified approach using a balloon guide catheter inspired by stroke therapy, in patients harboring a symptomatic ICA atherosclerotic stenosis or web. In addition, the three angiographic patterns and clinical outcomes associated with this technique, called the simple flow blockage (SFB) technique are described. MATERIAL AND METHODS: This was a retrospective study with data extraction from a monocentric prospective clinical registry of consecutive patients admitted for symptomatic ICA stenosis or web. The primary study outcome (composite endpoint) was the rate of occurrence of death, symptomatic stroke or acute coronary syndrome within 30 days of the intervention. RESULTS: In this study 75 symptomatic patients with >50% carotid artery atherosclerotic stenosis or web were included. All procedures were successfully performed. The composite endpoint occurred in 3 patients (4.0%, 95% confidence interval, CI, 0.0-11.3): 1 had symptomatic ischemic stroke, 1 had reperfusion syndrome with symptomatic intracranial hemorrhage and 1 had acute coronary syndrome. After proximal balloon inflation three angiographic patterns were observed: complete contrast column stagnation in the ICA (38.7%), retrograde washout of the ICA from the intracranial circulation towards the external carotid artery (35.5%) and antegrade washout of contrast medium towards the intracranial circulation (25.8%). The median procedure length was 40â¯min. New asymptomatic ischemic lesions were observed in 22.5% on DWI-MRI. CONCLUSION: The SFB technique enables fast and safe procedures in CAS. A favorable angiographic pattern after proximal balloon inflation was observed in 74.2% of cases.
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Angiografia/métodos , Oclusão com Balão/métodos , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/terapia , Stents , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To describe the clinico-radiological features and long-term prognosis in patients with cerebral amyloid angiopathy-related inflammation (CAA-ri). METHODS: Twenty-eight CAA-ri patients were recruited retrospectively from 6 neurological centers. We recorded the clinico-radiological and biological data, at baseline and during follow-up. Baseline characteristics associated with relapse risk and prognosis were assessed. RESULTS: Five patients had pathologically confirmed CAA-ri whereas 23 had probable (n = 21) or possible (n = 2) CAA-ri. The mean age was 72 years; main clinical symptoms included confusion (54%), hemiparesis (36%), and aphasia (29%). Cerebral MRI disclosed a brain parenchymal lesion (89%), which was usually multifocal (82%) and bilateral (89%). It was associated with gadolinium enhancement (84%), small ischemic lesions (39%), cortical superficial siderosis (CSS; 50%), and a high number of microbleeds (mean 240 ± 277). An isolated leptomeningeal involvement was observed in 3 patients with pathological confirmation. Despite a favorable initial evolution after treatment, we observed a 42% risk of relapse, mostly within the first year (83%). After a mean follow-up of 2 years, 29% died and 25% had a marked disability. Disseminated CSS was associated with death. CONCLUSION: Despite an apparently favorable initial evolution, CAA-ri is characterized by a poor prognosis. Diagnostic criteria should consider patients with isolated leptomeningeal involvement.
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Angiopatia Amiloide Cerebral/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Encefalite/diagnóstico por imagem , Idoso , Angiopatia Amiloide Cerebral/complicações , Angiopatia Amiloide Cerebral/terapia , Encefalite/etiologia , Encefalite/terapia , Feminino , França , Humanos , Masculino , Valor Preditivo dos Testes , Recidiva , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Primary familial brain calcification (PFBC) is a rare neurological disease characterized by deposits of calcium phosphate in the basal ganglia and other regions of the brain. Pathogenic variants in the XPR1/SLC53A1 gene, which encodes the only known inorganic phosphate exporter, cause an autosomal dominant form of PFBC. These variants are typically located in the SPX N-terminal domain of the protein. Here, we characterize three XPR1 variants outside of SPX in three PFBC patients with an apparently sporadic presentation: c.1375C > T p.(R459C), c.1855A > G p.(N619D) and c.1886T > G p.(I629S), with the latter identified as the first XPR1/SLC53A1 de novo mutation to occur in a PFBC proband. When tested in an in vitro physiological complementation assay, the three XPR1 variants were impaired in phosphate export function, although they were normally expressed at the cell surface and could serve as functional receptors for retrovirus entry. Moreover, peripheral blood cells from the p.N619D patient could be assayed ex vivo and displayed significantly impaired phosphate export. Our results establish for the first time the clinical and molecular characteristics of XPR1 variants located outside the SPX domain and assert a direct link between these variants, deficient phosphate export, and PFBC. Moreover, we unveiled new structural features in XPR1 C-terminal domain that play a role in phosphate export and disease.
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Encefalopatias/patologia , Calcinose/patologia , Mutação , Hormônios Peptídicos/genética , Fosfatos/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Virais/genética , Encefalopatias/genética , Calcinose/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Linhagem , Domínios Proteicos , Receptor do Retrovírus Politrópico e XenotrópicoRESUMO
BACKGROUND: The diagnosis of atypical inflammatory demyelinating lesions can be difficult. Brain biopsy is often required to exclude neoplasms. Moreover, the relationship between these lesions and multiple sclerosis and NMOSD is not clear. OBJECTIVES: Our objectives were to describe radiological and pathological characteristics of patients with acute inflammatory demyelinating lesions. METHODS: We retrospectively identified patients with brain biopsy performed for diagnostic uncertainty revealing a demyelinating lesion. A complete clinical, biological, radiological and pathological analysis was performed. RESULTS: Twenty patients (15 with a single lesion) were included. MRI disclosed a wide range of lesions including infiltrative lesions (40%), ring-like lesion (15%) Baló-like lesion (15%) and acute haemorrhagic leukoencephalitis (20%). In spite of a marked heterogeneity, some findings were common: a peripheral B1000 hyperintense rim (70%), a slight oedema with mild mass effect (75%) and an open-rim peripheral enhancement (75%). Histopathology revealed that all cases featured macrophages distributed throughout, extensive demyelination, axonal preservation and absence of haemorrhagic changes. In the majority of cases, macrophages were the predominant inflammatory infiltrate and astrocytes were reactive and dystrophic. Aquaporin-4 staining was systematically preserved. After a mean follow-up of 5 years (1-12), 16/20 patients had a diagnosis of monophasic acute atypical inflammatory demyelinating lesion. One patient was diagnosed with MS and 3 with AQP4 negative NMOSD. DISCUSSION: Although imaging findings in patients with atypical inflammatory demyelinating lesions are heterogeneous, some common features such as peripheral DWI hyperintense rim with open-rim enhancement and absence of oedema argue in favour of a demyelinating lesion and should preclude a brain biopsy. In this context, AQP4 staining is systematically preserved and argues against an AQP4-positive NMOSD. Moreover, long-term follow-up is characterized by low recurrence rate.
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Aquaporina 4 , Doenças Desmielinizantes/diagnóstico por imagem , Doenças Desmielinizantes/epidemiologia , Imageamento por Ressonância Magnética , Doença Aguda , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/epidemiologia , Neuromielite Óptica/diagnóstico por imagem , Neuromielite Óptica/epidemiologia , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Few data are available regarding patients with very late-onset inflammatory demyelinating events. (VLO-IDE). OBJECTIVES: The aim of this study was to describe the clinical, biological, and radiological characteristics and aetiological diagnosis of very late first inflammatory demyelinating events of the central nervous system. METHODS: We conducted a national descriptive retrospective multicentre study on a case series of patients aged >70 years at the time of VLO-IDE. Patients were recruited from a national call on behalf of the 'Société Francophone de la Sclérose en Plaques' (French Multiple Sclerosis Society). RESULTS: Twenty-five patients were referred (F:M sex ratio 2.1:1). The most frequent clinical impairment was a spinal cord deficit (23/25), usually severe (disability score, median EDSS 4.5 [2-9.5]). Spinal cord lesions were usually extensive, spanning at least three segments (11/25), and large brain lesions were also observed (lesions >20â¯mm in 6/25). The final aetiological diagnoses comprised multiple sclerosis (9/25), neuromyelitis optica spectrum disorders (7/25), neurosystemic lupus erythematosus (2/25), transverse myelitis without aetiological diagnosis (6/25) and optic neuritis (1/25). CONCLUSIONS: This study highlights a particular phenotype of first clinical inflammatory demyelinating events in predominantly female patients aged >70 years who have severe motor impairment with common longitudinal extensive myelitis and large and common very active radiological inflammatory lesions. Neuromyelitis optica spectrum disorders seem overrepresented.
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Doenças do Sistema Nervoso Central/epidemiologia , Doenças Desmielinizantes/epidemiologia , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Doenças do Sistema Nervoso Central/diagnóstico , Doenças do Sistema Nervoso Central/terapia , Doenças Desmielinizantes/diagnóstico , Doenças Desmielinizantes/terapia , Feminino , Seguimentos , Humanos , Inflamação/diagnóstico , Inflamação/epidemiologia , Inflamação/terapia , Masculino , Estudos Retrospectivos , Medula Espinal/diagnóstico por imagemRESUMO
BACKGROUND: The recent 2017 modification have increased the sensitivity of McDonald criteria for MS. Nevertheless, some MS patients with atypical MRI findings have been identified, leading to prolonged delay to diagnosis and high costs to look for alternative diagnoses. OBJECTIVE: To describe a series of MS patients with atypical MRI presentation. MATERIAL AND METHODS: Patients with atypical MS were identified through a nationwide retrospective study. We established a five groups classification: tumefactive demyelinating lesion (TDL)-onset MS, acute disseminated encephalomyelitis (ADEM)-like MS, cavitary MS and leukodystrophy-like MS. All the patients meeting our radiological criteria for atypical MS were included. RESULTS: A total of 57 patients met the inclusion criteria. 7 cases were classified in the TDL-onset group, 10 in the ADEM-like group, 26 in the cavitary group and 14 in the leukodystrophy-like group. Overall risk of conversion to MS after an isolated TDL was around 30% at five years. Patients in the TDL-onset and ADEM-like groups globally presented an acute onset and a relapsing-remitting evolution. Conversely, patients in the cavitary and leukodystrophy- groups largely evolved with a progressive and severe course. CONCLUSION: A significant number of MS patients can have a striking atypical presentation and may be misdiagnosed. This preliminary analysis helps to refine the spectrum of atypical MS patients.