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BACKGROUND: Risk factors for aquaporin-4 (AQP4+) antibody neuromyelitis optica spectrum disorder (NMOSD) are not well-established. OBJECTIVE: To investigate demographic and environmental factors associated with NMOSD using a validated questionnaire and case-control design. METHODS: We enrolled patients with AQP4 + NMOSD through six Canadian Multiple Sclerosis Clinics. Participants completed the validated Environmental Risk Factors in Multiple Sclerosis Study (EnvIMS) questionnaire. Their responses were compared to those of 956 unaffected controls from the Canadian arm of EnvIMS. We calculated odds ratios (ORs) for the association between each variable and NMOSD using logistic regression and Firth's procedure for rare events. RESULTS: In 122 participants (87.7% female) with NMOSD, odds of NMOSD in East Asian and Black participants were ⩾8 times that observed in White participants. Birthplace outside Canada was associated with an increased risk of NMOSD (OR = 5.5, 95% confidence interval (CI) = 3.6-8.3) as were concomitant autoimmune diseases (OR = 2.7, 95% CI = 1.4-5.0). No association was observed with reproductive history or age at menarche. CONCLUSION: In this case-control study, risk of NMOSD in East Asian and Black versus White individuals was greater than that observed in many previous studies. Despite the preponderance of affected women, we did not observe any association with hormonal factors such as reproductive history or age at menarche.
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Esclerosis Múltiple , Neuromielitis Óptica , Humanos , Femenino , Masculino , Estudios de Casos y Controles , Canadá/epidemiología , Acuaporina 4 , Esclerosis Múltiple/complicaciones , Demografía , AutoanticuerposRESUMEN
PURPOSE OF REVIEW: Neuromyelitis optica spectrum disorder (NMOSD) is a rare but highly disabling disease of the central nervous system. Unlike multiple sclerosis, disability in NMOSD occurs secondary to relapses that, not uncommonly, lead to blindness, paralysis, and death. Recently, newer, targeted immunotherapies have been trialed and are now in the treatment arsenal. We have endeavoured to evaluate the current state of NMOSD therapeutics. RECENT FINDINGS: This review provides a pragmatic evaluation of recent clinical trials and post-marketing data for rituximab, inebilizumab, satralizumab, eculizumab, and ravalizumab, contrasted to older agents. We also review contemporary issues such as treatment in the context of SARS-CoV2 infection and pregnancy. There has been a dramatic shift in NMOSD morbidity and mortality with earlier and improved disease recognition, diagnostic accuracy, and the advent of more effective, targeted therapies. Choosing a maintenance therapy remains nuanced depending on patient factors and accessibility. With over 100 putative agents in trials, disease-free survival is now a realistic goal for NMOSD patients.
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COVID-19 , Neuromielitis Óptica , Humanos , Neuromielitis Óptica/diagnóstico , Neuromielitis Óptica/tratamiento farmacológico , ARN Viral/uso terapéutico , COVID-19/complicaciones , SARS-CoV-2 , Inmunoterapia , Acuaporina 4RESUMEN
BACKGROUND: Accurate anti-aquaporin-4 (AQP4) and anti-myelin oligodendrocyte glycoprotein (MOG) autoantibody assays are needed to effectively diagnose neuromyelitis optica spectrum disorder and MOG antibody-associated disease. A proportion of patients at our centre have been tested for anti-AQP4 and anti-MOG autoantibodies locally, followed by an outsourced test as part of real-world practice. Outsourced testing is costly and of unproven utility. We conducted a quality improvement project to determine the value of outsourced testing for anti-AQP4 and anti-MOG autoantibodies. METHODS: All patients seen by Calgary neurological services who underwent cell-based testing for anti-AQP4 and/or anti-MOG autoantibodies at both MitogenDx (Calgary, AB) and Mayo Clinic Laboratories (Rochester, MN, USA) between 2016 and 2020 were identified from a provincial database. The interlaboratory concordance was calculated by pairing within-subject results collected no more than 365 days apart. Retrospective chart review was done for subjects with discordant results to determine features associated with discordance and use of outsourced testing. RESULTS: Fifty-seven anti-AQP4 and 46 anti-MOG test pairs from January 2016 to July 2020 were analyzed. Concordant tests pairs comprised 54/57 (94.7%, 95%CI 88.9-100.0%) anti-AQP4 and 41/46 (89.1%, 95%CI 80.1-98.1%) anti-MOG results. Discordant anti-AQP4 pairs included two local weak positives (negative when outsourced) and one local negative (positive when outsourced). Discordant anti-MOG pairs were all due to local weak positives (negative when outsourced). CONCLUSION: Interlaboratory discordant results for cell-based testing of anti-AQP4 autoantibodies were rare. Local anti-MOG weak positive results were associated with discordance, highlighting the need for cautious interpretation based on the clinical context. Our findings may reduce redundant outsourced testing.
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BACKGROUND: Choosing Wisely Canada (CWC) is a national branch of a global campaign advocating for fewer unnecessary tests and for optimizing patient care. Professional societies representing physicians, pharmacists, and nurses participate by generating lists of recommendations meant to reduce patient harm and resource mismanagement in healthcare. The Canadian Neurological Society (CNS) plays an important role in advocating for quality patient care demonstrated by deriving specific recommendations. This process is described. METHOD: The CNS Choosing Wisely task force adapted 10 recommendations for Canadian neurology practice. These were approved by the CNS board, and subsequently ranked by CNS members. RESULTS: Ten recommendations were brought forward and ranked in a survey completed by CNS members. Survey ranking is presented. The top five recommendations were selected and optimized, resulting in seven key recommendations. CONCLUSION: The recommendations set forth by the CNS will help with resource stewardship and patient safety in the delivery of neurological care by healthcare providers in Canada.
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Neurología , Médicos , Canadá , Atención a la Salud , Humanos , Sociedades MédicasRESUMEN
In this topical review, we discuss the history of the area postrema syndrome, with special attention given to early studies aimed at identifying the area postrema and its function, possible early cases of the syndrome and its current relevance in neuroimmunology and demyelinating diseases. In 1896, Retzius named a structure in the posterior medulla oblongata as the area postrema. The work of Borison in the middle of the 20th century led to the elucidation of its function as a "vomiting center." The historical medical literature is filled with excellent examples that could be described as "area postrema syndrome." While severe and bilateral optic neuritis and transverse myelitis still constitute the classic components of neuromyelitis optica spectrum disorder (NMOSD), intractable vomiting and hiccups due to area postrema involvement is now recognized as essentially pathognomonic, indeed a shiny pearl in neuroimmunology and demyelinating diseases.
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Área Postrema/fisiopatología , Hipo/fisiopatología , Náusea/fisiopatología , Neuromielitis Óptica/fisiopatología , Vómitos/fisiopatología , Hipo/etiología , Hipo/historia , Historia del Siglo XIX , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Náusea/etiología , Náusea/historia , Neuromielitis Óptica/complicaciones , Neuromielitis Óptica/historia , Síndrome , Vómitos/etiología , Vómitos/historiaRESUMEN
BACKGROUND: Multiple sclerosis (MS) is the most common nontraumatic neurological disorder of young adults, and roughly 85% of patients present with the relapsing form of the disease. Over the past 2 decades, the treatment arsenal for relapsing MS has expanded and evolved from mildly effective and relatively benign injectable agents to potent cell-depleting monoclonal agents. The latter have the potential to achieve disease remission coupled with risk of moderate to severe adverse events with which all MS care providers will need to acquaint themselves. METHODS: This review is based on a detailed assessment of MS pivotal trials, extension studies, and expert reviews of the agents discussed. RESULTS/CONCLUSIONS: The following review should aid those practitioners directly and indirectly involved in the care of MS patients in understanding the benefits and risks associated with the medications they prescribe.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Inmunosupresores/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Humanos , RecurrenciaRESUMEN
BACKGROUND: Vitamin D sufficiency is associated with better inflammatory outcomes in multiple sclerosis (MS). We hypothesize that it is also associated with better long-term neurodegenerative measures. OBJECTIVES: To show that vitamin D sufficient patients (25-hydroxy vitamin D (25(OH)D) > 80 nmol/L) have better optical coherence tomography (OCT) neuroaxonal measures of ganglion cell layer (GCL) and retinal nerve fiber layer (RNFL) thickness after optic neuritis. METHODS: In this prospective cohort study, acute optic neuritis patients underwent OCT and serum 25(OH)D assessments at baseline and at month 6, with comparisons between vitamin D sufficient and insufficient patients, and men and women. Potential confounding variables were evaluated. RESULTS: Of 49 enrolled, 36 had complete, analyzable data. At baseline, vitamin D insufficiency was associated with greater RNFL thickness (134.3 vs. 95.2 µm; p = 0.003) in affected eyes. At month 6, insufficient patients had greater GCL thinning (GCL inter-eye difference: 14.2 vs. 4.0 µm, p = 0.008). Men had greater RNFL and GCL thinning than women (GCL: 61.2 vs. 69.6 µm, p = 0.036). CONCLUSION: Acutely, in optic neuritis, RNFL thickness is increased with vitamin D insufficiency. Chronically, neuronal, and possibly axonal loss are associated with vitamin D insufficiency and male gender, suggesting vitamin D and female gender may confer neuroprotection in optic neuritis, and possibly, central nervous system (CNS) inflammatory disease.
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Fibras Nerviosas/efectos de los fármacos , Nervio Óptico/efectos de los fármacos , Neuritis Óptica/tratamiento farmacológico , Neuritis Óptica/metabolismo , Vitamina D/farmacología , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/complicaciones , Nervio Óptico/fisiopatología , Neuritis Óptica/etiología , Estudios Prospectivos , Retina/fisiopatología , Células Ganglionares de la Retina/efectos de los fármacos , Células Ganglionares de la Retina/patología , Tomografía de Coherencia Óptica/métodos , Vitamina D/metabolismo , Adulto JovenRESUMEN
Severe longitudinally extensive transverse myelitis (LETM) can cause quadriplegia, marked sensory dysfunction, and respiratory failure. Some patients are unresponsive to conventional immune therapy. We report two cases of severe immune-mediated LETM requiring intensive care admission that failed to respond to high-dose corticosteroids, plasma exchange, intravenous immunoglobulin, and rituximab. Disease cessation and significant recovery was achieved after cyclophosphamide induction. In patients with severe acute immune-mediated LETM who fail to respond to corticosteroids and plasma exchange, cyclophosphamide induction should be considered. This agent and regimen provides a robust immunosuppressive response and can be induced rapidly. Cyclophosphamide effects and supportive evidence are discussed.
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Ciclofosfamida/uso terapéutico , Inmunosupresores/uso terapéutico , Mielitis Transversa/tratamiento farmacológico , Neuromielitis Óptica/tratamiento farmacológico , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Mielitis Transversa/diagnóstico , Mielitis Transversa/patología , Neuromielitis Óptica/diagnóstico , Neuromielitis Óptica/patología , Columna Vertebral/patología , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Pituitary tumors are one of the most common types of intracranial neoplasms, and can cause progressive visual loss. An ongoing challenge in the management of patients with pituitary tumors is the cost, availability, and reliability of current magnetic resonance imaging (MRI) techniques to capture clinically significant incremental tumor growth. The purpose of this study was to evaluate the various MRI-based structural analyses and to explore the relationship between measures of structure and function in the afferent visual pathway of patients with pituitary tumors. METHODS: We performed a critical review of literature on MRI-based structural analyses of pituitary adenomas using PubMed, Embase, Cochrane Library, and Google Scholar. In addition, preoperative structural characteristics of the optic apparatus, optic nerve compression, and optic chiasm elevation identified as important in the literature review, were examined in 18 of our patients from October 2010 to January 2014. RESULTS: In our review of literature, a total of 443 citations were obtained from our search strategy and review of bibliographies. Eight of these studies met inclusion/exclusion criteria and were retrieved for critical review. Of the 8 included studies, only 2 studies examined the relationship between MRI-based structural measurements and postoperative visual recovery. In our small case-series, MRI analysis of chiasm elevation, severity of optic nerve compression, chiasm position, height of chiasm, tumor height, and tumor volume failed to differentiate patients with postoperative visual dysfunction vs those with visual recovery (P > 0.05). CONCLUSIONS: Although MRI-based structural analysis is an important and useful tool for managing patients with pituitary tumors, there are limited objective measures shown to be predictive of postoperative visual recovery.
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Imagen por Resonancia Magnética/estadística & datos numéricos , Quiasma Óptico/patología , Enfermedades del Nervio Óptico/diagnóstico , Neoplasias Hipofisarias/complicaciones , Constricción Patológica , Humanos , Enfermedades del Nervio Óptico/etiología , Neoplasias Hipofisarias/diagnósticoRESUMEN
BACKGROUND: In this prospective case series, we aimed to characterise the temporal evolution of functional and structural measures in the afferent visual pathway of patients with acute optic neuritis (ON). METHODS: Fifty patients with ON were followed over 12 months. Testing with spectral-domain optical coherence tomography, Early Treatment Diabetic Retinopathy Study logarithm of the minimum angle of resolution (LogMAR) visual acuity and Humphrey perimetry central 30-2 threshold (SITA strategy) was performed at baseline, 3, 6 and 12 months after symptom onset. The main outcome measure was mean peripapillary retinal nerve fibre layer (RNFL) thickness in ON eyes. Secondary outcomes included mean ganglion cell layer (GCL) thickness, LogMAR visual acuity, and Humphrey perimetry measured visual field mean deviation (VFMD). Survival analyses were performed to Kaplan-Meier curves and variables in the models were tested using the log-rank test. RESULTS: Over 12 months, RNFL and GCL values progressively declined in ON eyes, and intereye differences were significantly different across all time points. When functional recovery was defined as a VFMD better than -5.00 dB in ON eyes, the mean recovery time for the entire cohort was 3 months (survival was 48%, SE=0.09, 95% CI 0.30 to 0.64). There were significant differences in cumulative recovery when comparisons were made between genders: 3 months after symptom onset there was a higher percentage cumulative recovery for female (75%) versus male (25%) patients. CONCLUSIONS: Structural and functional measures evolve over time in patients with ON. There may be sex-specific differences in recovery after an acute ON event.
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Neuritis Óptica/patología , Enfermedad Aguda , Adulto , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Neuritis Óptica/fisiopatología , Estudios Prospectivos , Recuperación de la Función , Retina/patología , Análisis de Supervivencia , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Pruebas de Visión , Agudeza VisualRESUMEN
BACKGROUND: There is a role for brief assessment instruments in detection and management of major depression in MS. However, candidate scales have rarely been validated against a validated diagnostic interview. In this study, we evaluated the performance of several candidate scales: Patient Health Questionnaire (PHQ)-9, PHQ-2, Center for Epidemiologic Studies Depression rating scale (CES-D), and Hospital Anxiety and Depression Scale (HADS-D) in relation to the Structured Clinical Interview for DSM-IV (SCID). METHODS: The sample was an unselected series of 152 patients attending a multiple sclerosis (MS) clinic. Participants completed the scales during a clinic visit or returned them by mail. The SCID was administered by telephone within two weeks. The diagnosis of major depressive episode, according to the SCID, was used as a reference standard. Receiver-operator curves (ROC) were fitted and indices of measurement accuracy were calculated. RESULTS: All of the scales performed well, each having an area under the ROC > 90%. For example, the PHQ-9 had 95% sensitivity and 88.3% specificity when scored with a cut-point of 11. This cut-point achieved a 56% positive predictive value for major depression. CONCLUSIONS: While all of the scales performed well in terms of their sensitivity and specificity, the availability of the PHQ-9 in the public domain and its brevity may enhance the feasibility of its use.
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Trastorno Depresivo Mayor/etiología , Trastorno Depresivo Mayor/psicología , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/psicología , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Edad de Inicio , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/tratamiento farmacológico , Valor Predictivo de las Pruebas , Curva ROC , Recurrencia , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
BACKGROUND: The role of vitamin D as both a risk factor and a disease modifier in multiple sclerosis (MS) has a storied history with ongoing accumulation of supportive convergent evidence from animal data, clinical studies and trials, and biomarkers of disease. EVIDENCE ACQUISITION: A detailed review of the published literature ranging from in vivo immune studies to human clinical studies of epidemiology, physiology, immunology, clinical, and radiological markers was undertaken. RESULTS: There is compelling evidence that vitamin D is not only a risk factor for central nervous system (CNS) demyelinating disease (namely MS) but also seems to modify both the inflammatory and neurodegenerative elements of the disease, with large-scale treatment trials underway. The authors also address questions of interest that remain unanswered. CONCLUSIONS: Vitamin D is an important contributor and modifiable risk factor in CNS demyelinating disease. Further work will determine whether it is also neuroprotective and if such benefits will apply to other inflammatory and degenerative neurological diseases.
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Enfermedades del Sistema Nervioso Central/metabolismo , Enfermedades Desmielinizantes/metabolismo , Esclerosis Múltiple/metabolismo , Vitamina D/metabolismo , Enfermedades del Sistema Nervioso Central/complicaciones , Enfermedades Desmielinizantes/complicaciones , HumanosRESUMEN
BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an idiopathic central nervous system (CNS) demyelinating disease gaining recognition with wider availability of cell-based assay (CBA) testing and recently published diagnostic criteria. However, uncertainty remains regarding the interpretation of antibody titers, particularly cerebrospinal fluid (CSF) MOG antibody titers. METHODS: All MOG IgG CBA results performed by the provincial MitogenDx laboratory in Alberta from July 2017 to July 2023 were retrieved. Chart review was performed in patients with both serum and CSF testing and ≥ 1 positive MOG antibody result. Demographics, antibody titers, clinical and imaging features, treatment, and diagnosis were analyzed based on serum/CSF status. RESULTS: Among 4494 MOG CBA assays, there were 413 CSF samples in 402 patients, and 268 patients had at least one associated serum sample. Mean time between CSF and serum testing was 20.9 days (range 0-870 days), most with testing within 30 days. Five of the 268 patients had serum positive/CSF positive MOG antibodies, 4 with acute disseminated encephalomyelitis and 1 with longitudinally extensive transverse myelitis. Twenty-three patients had serum positive/CSF negative MOG and 13/23 with optic neuritis. CSF MOG antibody positive patients were younger, and more likely to remain MOG seropositive versus CSF negative patients. No seronegative patient had MOG antibodies in CSF. CONCLUSIONS: In province-wide testing, CSF MOG antibodies were rare, only in MOG seropositive patients and none with optic neuritis. Our study does not support a clear role for CSF MOG antibody testing in the majority of patients, although further study is required.
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Autoanticuerpos , Glicoproteína Mielina-Oligodendrócito , Humanos , Glicoproteína Mielina-Oligodendrócito/inmunología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Autoanticuerpos/líquido cefalorraquídeo , Autoanticuerpos/sangre , Anciano , Adolescente , Adulto Joven , Niño , Anciano de 80 o más Años , Preescolar , Enfermedades Autoinmunes Desmielinizantes SNC/líquido cefalorraquídeo , Enfermedades Autoinmunes Desmielinizantes SNC/inmunología , Enfermedades Autoinmunes Desmielinizantes SNC/diagnóstico , Enfermedades Autoinmunes Desmielinizantes SNC/sangre , Encefalomielitis Aguda Diseminada/diagnóstico , Encefalomielitis Aguda Diseminada/líquido cefalorraquídeo , Encefalomielitis Aguda Diseminada/inmunología , Encefalomielitis Aguda Diseminada/sangre , Estudios Retrospectivos , Neuritis Óptica/líquido cefalorraquídeo , Neuritis Óptica/inmunología , Neuritis Óptica/diagnóstico , Neuritis Óptica/sangreRESUMEN
BACKGROUND: This is an updated Cochrane review of the previous version published (Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD006921. DOI: 10.1002/14651858.CD006921.pub2).Multiple sclerosis (MS), a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS), is characterized by recurrent relapses of CNS inflammation ranging from mild to severely disabling. Relapses have long been treated with steroids to reduce inflammation and hasten recovery. However, the commonly used intravenous methylprednisolone (IVMP) requires repeated infusions with the added costs of homecare or hospitalization, and may interfere with daily responsibilities. Oral steroids have been used in place of intravenous steroids, with lower direct and indirect costs. OBJECTIVES: The primary objective was to compare efficacy of oral versus intravenous steroids in promoting disability recovery in MS relapses <= six weeks. Secondary objectives included subsequent relapse rate, disability, ambulation, hospitalization, immunological markers, radiological markers, and quality of life. SEARCH METHODS: A literature search was performed using Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group's Trials Register (January 2012), abstracts from meetings of the American Academy of Neurology (2008-2012), the European Federation of Neurological Sciences (2008-2012), the European Committee for Treatment and Research in Multiple Sclerosis and American Committee for Treatment and Research in Multiple Sclerosis (2008-2012) handsearching. No language restrictions were applied. SELECTION CRITERIA: Randomized or quasi-randomized trials comparing oral versus intravenous steroids for acute relapses (<= six weeks) in patients with clinically definite MSover age 16 were eligible. DATA COLLECTION AND ANALYSIS: Three review authors (JB, PO and MH) participated in the independent assessment of all published articles as potentially relevant to the review. Any disagreement was resolved by discussion among review authors.We contacted study authors for additional information.Methodological quality was assessed by the same three review authors. Relevant data were extracted, and effect size was reported as mean difference (MD), mean difference (MD), odds ratio (OR) and absolute risk difference (ARD). MAIN RESULTS: With this current update, a total of five eligible studies (215 patients) were identified. Only one outcome, the proportion of patients with Expanded Disability Status Scale (EDSS) improvement at four weeks, was common to three trials, while two trials examined magnetic resonance imaging (MRI) outcomes. The results of this review shows there is no significant difference in relapse recovery at week four (MD -0.22, 95% confidence interval (95% CI), 0.71 to 0.26, P = 0.20) nor differences in magnetic resonance imaging (MRI) gadolinium enhancement activity based on oral versus intravenous steroid treatment. However, only two of the five studies employed more current and rigorous methodological techniques, so these results must be taken with some caution. The Oral Megadose Corticosteroid Therapy of Acute Exacerbations of Multiple Sclerosis (OMEGA) trial and the "Efficacy and Safety of Methylprednisolone Per os Versus IV for the Treatment of Multiple Sclerosis (MS) Relapses" (COPOUSEP) trial, designed to address such limitations, are currently underway. AUTHORS' CONCLUSIONS: The analysis of the five included trials comparing intravenous versus oral steroid therapy for MS relapses do not demonstrate any significant differences in clinical (benefits and adverse events), radiological or pharmacological outcomes. Based on the evidence, oral steroid therapy may be a practical and effective alternative to intravenous steroid therapy in the treatment of MS relapses.
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Glucocorticoides/administración & dosificación , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Administración Oral , Antiinflamatorios/administración & dosificación , Humanos , Inyecciones Intravenosas , Metilprednisolona/administración & dosificación , Prednisona/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , RecurrenciaRESUMEN
Despite convergent evidence that upwards of 50% of patients with MS transition from a relapsing to progressive phase within 20 years of disease onset, and the recent acknowledgement of the commonality of progression independent of relapses, there remains no consensus regarding the nature and timing of a discussion about the possibility of a secondary progressive phase with relapsing-remitting MS patients. Some neurologists prefer to conduct this at the inaugural visit to provide more information about disease behaviour and potential planning that might entail, while others may defer any discussion about this phase, as there is no clear consensus for it and it can be a sensitive topic, with concern that too early a discussion could worsen anxiety and discourage or delay decisions regarding disease modifying treatments. Furthermore, it is unknown at onset which patients will transition to a progressive phenotype. This review and opinion paper will outline some of the opportunities and challenges associated with such a disclosure, and attempt to provide a balanced, patient-centred approach to address this delicate topic.