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A man in his 30s was referred to neurology with right-sided paraesthesia, tremors, chest pain and lower urinary tract and erectile dysfunction. He had a medical history of left acetabular dysplasia, and subjective memory impairment, the latter being in the context of depression and chronic pain with opioid use. There was no notable family history. On examination, he had a spastic paraparesis. Imaging revealed atrophy of the thoracic spine. Lumbar puncture demonstrated a raised protein but other constituents were normal, including no presence of oligoclonal bands. Genetic testing revealed a novel heterozygous likely pathogenic SPAST variant c. 1643A>T p.(Asp548Val), confirming the diagnosis of hereditary spastic paraparesis. Symptomatic treatment with physiotherapy and antispasmodic therapy was initiated. This is the first study reporting a patient with this SPAST variant. Ensembl variant effect predictor was used, with the application of computational variant prediction tools providing support that the variant we have identified is likely deleterious and damaging. Our variant CADD score was high, indicating that our identified variant was a highly deleterious substitution.
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Paraparesia Espástica , Paraplejía Espástica Hereditaria , Humanos , Masculino , Pruebas Genéticas , Mutación , Paraparesia Espástica/genética , Linaje , Proteínas/genética , Paraplejía Espástica Hereditaria/genética , Espastina/genética , AdultoRESUMEN
BACKGROUND AND OBJECTIVES: Acute inflammatory CNS diseases include neuromyelitis optica spectrum disorders (NMOSDs) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Both MOGAD and acute disseminated encephalomyelitis (ADEM) have been reported after vaccination. Consequently, the mass SARS-CoV-2 vaccination program could result in increased rates of these conditions. We described the features of patients presenting with new acute CNS demyelination resembling NMOSDs or MOGAD within 8 weeks of SARS-CoV-2 vaccination. METHODS: The study included a prospective case series of patients referred to highly specialized NMOSD services in the UK from the introduction of SARS-CoV-2 vaccination program up to May 2022. Twenty-five patients presented with new optic neuritis (ON) and/or transverse myelitis (TM) ± other CNS inflammation within 8 weeks of vaccination with either AstraZeneca (ChAdOx1S) or Pfizer (BNT162b2) vaccines. Their clinical records and paraclinical investigations including MRI scans were reviewed. Serologic testing for antibodies to myelin oligodendrocyte glycoprotein (MOG) and aquaporin 4 (AQP4) was performed using live cell-based assays. Patients' outcomes were graded good, moderate, or poor based on the last clinical assessment. RESULTS: Of 25 patients identified (median age 38 years, 14 female), 12 (48%) had MOG antibodies (MOGIgG+), 2 (8%) had aquaporin 4 antibodies (AQP4IgG+), and 11 (44%) had neither. Twelve of 14 (86%) antibody-positive patients received the ChAdOx1S vaccine. MOGIgG+ patients presented most commonly with TM (10/12, 83%), frequently in combination with ADEM-like brain/brainstem lesions (6/12, 50%). Transverse myelitis was longitudinally extensive in 7 of the 10 patients. A peak in new MOGAD cases in Spring 2021 was attributable to postvaccine cases. Both AQP4IgG+ patients presented with brain lesions and TM. Four of 6 (67%) seronegative ChAdOx1S recipients experienced longitudinally extensive TM (LETM) compared with 1 of 5 (20%) of the BNT162b2 group, and facial nerve inflammation was reported only in ChAdOx1S recipients (2/5, 40%). Guillain-Barre syndrome was confirmed in 1 seronegative ChAdOx1S recipient and suspected in another. DISCUSSION: ChAdOx1S was associated with 12/14 antibody-positive cases, the majority MOGAD. MOGAD patients presented atypically, only 2 with isolated ON (1 after BNT162b2 vaccine) but with frequent ADEM-like brain lesions and LETM. Within the seronegative group, phenotypic differences were observed between ChAdOx1S and BNT162b2 recipients. These observations might support a causative role of the ChAdOx1S vaccine in inflammatory CNS disease and particularly MOGAD. Further study of this cohort could provide insights into vaccine-associated immunopathology.
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COVID-19 , Encefalomielitis Aguda Diseminada , Mielitis Transversa , Neuromielitis Óptica , Neuritis Óptica , Femenino , Humanos , Glicoproteína Mielina-Oligodendrócito , Acuaporina 4 , Mielitis Transversa/etiología , Vacunas contra la COVID-19/efectos adversos , SARS-CoV-2 , Vacuna BNT162 , COVID-19/prevención & control , Sistema Nervioso Central , Encefalomielitis Aguda Diseminada/etiología , Vacunación/efectos adversos , InflamaciónRESUMEN
BACKGROUND: Fatigue is common and disabling in multiple sclerosis (MS), yet its mechanisms are poorly understood. In particular, overlap in measures of fatigue and depression complicates interpretation. We applied a multivariate network approach to quantify relationships between fatigue and other variables in early MS. METHODS: Data were collected from patients with newly diagnosed immunotherapy-naïve relapsing-remitting MS at baseline and month 12 follow-up in FutureMS, a Scottish nationally representative cohort. Subjective fatigue was assessed by Fatigue Severity Scale. Detailed phenotyping included measures assessing each of physical disability, affective disorders, cognitive performance, sleep quality, and structural brain imaging. Network analysis was conducted to estimate partial correlations between variables. Baseline networks were compared between those with persistent and remitted fatigue at one-year follow up. RESULTS: Data from 322 participants at baseline, and 323 at month 12, were included. At baseline, 154 patients (47.8%) reported clinically significant fatigue. In the network analysis, fatigue severity showed strongest connections with depression, followed by Expanded Disability Status Scale. Conversely, fatigue severity was not linked to objective cognitive performance or brain imaging variables. Even after controlling for measurement of "tiredness" in our measure of depression, four specific depressive symptoms remained linked to fatigue. Results were consistent at baseline and month 12. Overall network strength was not significantly different between groups with persistent and remitted fatigue (4.89 vs 2.90, p = 0.11). CONCLUSIONS: Our findings support robust links between subjective fatigue and depression in early relapsing-remitting MS. Shared mechanisms between specific depressive symptoms and fatigue could be key targets of treatment and research in MS-related fatigue.
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Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Humanos , Esclerosis Múltiple Recurrente-Remitente/complicaciones , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/psicología , Esclerosis Múltiple/complicaciones , Depresión/etiología , Encéfalo/diagnóstico por imagen , Fatiga/psicologíaRESUMEN
BACKGROUND: In people with multiple sclerosis (PwMS), a complex interplay of neurological dysfunction, polypharmacy and psychological issues, contrive to impair their sexual and reproductive wellbeing. Realising an unmet need, the Tayside MS service in collaboration with a sexual health clinician (LJ), established a 'Pelvic Health Clinic' to improve quality of life for PwMS. OBJECTIVE: To explore clinician's perceptions of implementing an MS Pelvic Health service with a view to establishing future outcomes for health care professionals about the utility in such a service. METHOD: In this small-scale qualitative case study, we explored clinician's perceptions of such a clinic adjunct. Semi-structured interviews were conducted, transcribed, and thematically analysed in a reflexive manner. RESULTS: Five participants consented. Ten sub-themes emerged, which were organised into three main themes: service tensions, patient needs and practitioner feelings. CONCLUSION: Clinicians highly valued the new MS 'pelvic health clinic'. Knowing that there was a service available empowered clinicians to ask patients about sexual health needs. Specific referral criteria may help further develop the service and improve patient care. Staff welcome training and support in this area or the option to signpost onwards; either mechanism lends itself to enhancing MS patient needs.
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Tuberculosis is on the rise again. It brings with it potential for neurological involvement both as a direct infection and as a parainfectious process. Accordingly we report the development of neurological problems affecting a 48-year-old patient's vision and sensation while being treated for active tuberculosis. At its nadir her vision deteriorated to nil perception of light and she had a sensory level to T10. Neuromyelitis optica spectrum disorder was diagnosed. We discuss our management strategy with neuromodulation in the context of active tuberculosis infection.
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Neuromielitis Óptica/etiología , Neuromielitis Óptica/terapia , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/terapia , Diagnóstico Diferencial , Femenino , Glucocorticoides/uso terapéutico , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Neuromielitis Óptica/diagnóstico por imagen , Intercambio Plasmático , Prednisolona/uso terapéutico , Rituximab/uso terapéutico , Tuberculosis Pulmonar/diagnóstico por imagenRESUMEN
OBJECTIVE: Clinical outcomes in multiple sclerosis (MS) are highly variable. We aim to determine the long-term clinical outcomes in MS, and to identify early prognostic features of these outcomes. METHODS: One hundred thirty-two people presenting with a clinically isolated syndrome were prospectively recruited between 1984 and 1987, and followed up clinically and radiologically 1, 5, 10, 14, 20, and now 30 years later. All available notes and magnetic resonance imaging scans were reviewed, and MS was defined according to the 2010 McDonald criteria. RESULTS: Clinical outcome data were obtained in 120 participants at 30 years. Eighty were known to have developed MS by 30 years. Expanded Disability Status Scale (EDSS) scores were available in 107 participants, of whom 77 had MS; 32 (42%) remained fully ambulatory (EDSS scores ≤3.5), all of whom had relapsing-remitting MS (RRMS), 3 (4%) had RRMS and EDSS scores >3.5, 26 (34%) had secondary progressive MS (all had EDSS scores >3.5), and MS contributed to death in 16 (20%). Of those with MS, 11 received disease-modifying therapy. The strongest early predictors (within 5 years of presentation) of secondary progressive MS at 30 years were presence of baseline infratentorial lesions and deep white matter lesions at 1 year. INTERPRETATION: Thirty years after onset, in a largely untreated cohort, there was a divergence of MS outcomes; some people accrued substantial disability early on, whereas others ran a more favorable long-term course. These outcomes could, in part, be predicted by radiological findings from within 1 year of first presentation. ANN NEUROL 2020;87:63-74.
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Enfermedades Desmielinizantes/epidemiología , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple/patología , Adulto , Encéfalo/patología , Comorbilidad , Evaluación de la Discapacidad , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Esclerosis Múltiple/diagnóstico , Neuroimagen , Valor Predictivo de las Pruebas , Pronóstico , Factores de Tiempo , Reino Unido/epidemiología , Adulto JovenRESUMEN
AIMS: To explore the effect of latitude on incidence of multiple sclerosis (MS) in Scotland. METHODS: MS case data (2010-2015) was ascertained from the Scottish Multiple Sclerosis Register. Patient's postcode at diagnosis was linked to the Scottish Index of Multiple Deprivation (SIMD). Geographical data from SIMD was converted into latitude and longitude and patients were grouped by latitude band. A linear regression analysis was then performed. MS Cumulative Incidence was compared to population density calculated from SIMD. RESULTS: Latitude was associated with MS Incidence rate. Using a linear regression analysis (r2â¯=â¯0.22, pâ¯=â¯0.03), the data predicted an increase in the average MS Incidence of 1.31 cases/100,000 person years per increase in degree latitude. MS Cumulative Incidence rates rise with increasing northern latitude up until 59° north. CONCLUSIONS: We found an increasing incidence of MS with latitude without any relationship to population in Scotland. The reasons for this are likely to be multifactorial.
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Mapeo Geográfico , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/epidemiología , Adulto , Femenino , Humanos , Incidencia , Masculino , Factores de Riesgo , Escocia/epidemiologíaRESUMEN
We describe a 37-year-old woman who presented with progressive deafness, visual loss and ataxia. She latterly developed neuropsychiatric problems, including cognitive impairment, paranoid delusions and episodes of altered consciousness. She was found to be heterozygous for the Q212P mutation in the prion protein gene. She died over a decade after initial presentation and a diagnosis of prion disease was confirmed at postmortem.
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Enfermedad de Gerstmann-Straussler-Scheinker/diagnóstico , Proteínas Priónicas/genética , Adulto , Ataxia/etiología , Trastornos Sordoceguera/etiología , Diagnóstico Diferencial , Resultado Fatal , Femenino , Enfermedad de Gerstmann-Straussler-Scheinker/complicaciones , Enfermedad de Gerstmann-Straussler-Scheinker/genética , Humanos , MutaciónAsunto(s)
Leucoencefalopatía Multifocal Progresiva/diagnóstico , Leucoencefalopatía Multifocal Progresiva/patología , Imagen por Resonancia Magnética , Esclerosis Múltiple/patología , Natalizumab/efectos adversos , Natalizumab/uso terapéutico , Diagnóstico Diferencial , Femenino , Humanos , Factores Inmunológicos/efectos adversos , Factores Inmunológicos/uso terapéutico , Persona de Mediana Edad , Esclerosis Múltiple/tratamiento farmacológico , Natalizumab/administración & dosificaciónRESUMEN
Multiple sclerosis (MS) is a chronic disease with an inflammatory and neurodegenerative pathology. Axonal loss and neurodegeneration occurs early in the disease course and may lead to irreversible neurological impairment. Changes in brain volume, observed from the earliest stage of MS and proceeding throughout the disease course, may be an accurate measure of neurodegeneration and tissue damage. There are a number of magnetic resonance imaging-based methods for determining global or regional brain volume, including cross-sectional (e.g. brain parenchymal fraction) and longitudinal techniques (e.g. SIENA [Structural Image Evaluation using Normalization of Atrophy]). Although these methods are sensitive and reproducible, caution must be exercised when interpreting brain volume data, as numerous factors (e.g. pseudoatrophy) may have a confounding effect on measurements, especially in a disease with complex pathological substrates such as MS. Brain volume loss has been correlated with disability progression and cognitive impairment in MS, with the loss of grey matter volume more closely correlated with clinical measures than loss of white matter volume. Preventing brain volume loss may therefore have important clinical implications affecting treatment decisions, with several clinical trials now demonstrating an effect of disease-modifying treatments (DMTs) on reducing brain volume loss. In clinical practice, it may therefore be important to consider the potential impact of a therapy on reducing the rate of brain volume loss. This article reviews the measurement of brain volume in clinical trials and practice, the effect of DMTs on brain volume change across trials and the clinical relevance of brain volume loss in MS.
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Encéfalo/patología , Esclerosis Múltiple/patología , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/uso terapéutico , Atrofia , Ensayos Clínicos como Asunto , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/patología , Trastornos del Conocimiento/prevención & control , Estudios Transversales , Evaluación de la Discapacidad , Progresión de la Enfermedad , Humanos , Imagen por Resonancia Magnética , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/psicología , Tamaño de los Órganos , Sensibilidad y EspecificidadRESUMEN
A 19-year-old man presented 4 weeks after an electrical shock injury with gradual onset limb weakness, altered sensation in the peripheries and respiratory difficulty. There was immediate tingling of the fingers following the electrical injury that persisted. He subsequently had transient facial weakness responsive to oral steroids before the development of further limb symptoms. On admission the clinical picture and investigation findings, including neurophysiology, cerebrospinal fluid examination and MRI were consistent with a Guillain-Barre syndrome. He was managed with a course of intravenous immunoglobulin and extensive physiotherapy and occupational therapy. He made an initial modest improvement but worsened again over the subsequent 4-6 weeks. Further investigation identified no ongoing active disease and he is left with a significant residual deficit.
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Traumatismos por Electricidad/complicaciones , Síndrome de Guillain-Barré/etiología , Diagnóstico Diferencial , Disnea/etiología , Síndrome de Guillain-Barré/diagnóstico , Humanos , Masculino , Debilidad Muscular/etiología , Adulto JovenRESUMEN
As more investigations into factors affecting the quality of life of patients with multiple sclerosis (MS) are undertaken, it is becoming increasingly apparent that certain comorbidities and associated symptoms commonly found in these patients differ in incidence, pathophysiology and other factors compared with the general population. Many of these MS-related symptoms are frequently ignored in assessments of disease status and are often not considered to be associated with the disease. Research into how such comorbidities and symptoms can be diagnosed and treated within the MS population is lacking. This information gap adds further complexity to disease management and represents an unmet need in MS, particularly as early recognition and treatment of these conditions can improve patient outcomes. In this manuscript, we sought to review the literature on the comorbidities and symptoms of MS and to summarize the evidence for treatments that have been or may be used to alleviate them.
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Síndrome de Churg-Strauss/diagnóstico por imagen , Tos/etiología , Limitación de la Movilidad , Mononeuropatías/complicaciones , Síndrome de Churg-Strauss/complicaciones , Síndrome de Churg-Strauss/terapia , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana Edad , Mononeuropatías/diagnóstico , Mononeuropatías/terapia , RadiografíaRESUMEN
UNLABELLED: This study was designed to identify the indications for prescription of intravenous immunoglobulin (IVIg) in neurology and the cost effectiveness of this therapy. OBJECTIVES: IVIg is a relatively costly therapy and the annual budget spent on providing this therapy for various indications at Ninewells Hospital was close to £1.5 million. In today's economic times, a cost-benefit analysis of all therapies is prudent. This is of relevance to countries in the developing world as well where perhaps not everybody could afford such cost-intensive therapy. MATERIALS AND METHODS: We audited 2 time periods over 12 months each in 2004-2005 and 2008-2009 to look at the patterns of utilization of IVIg over these periods. We searched the literature for alternative and cost-effective therapies for the most common indications for use of IVIg. RESULTS: Fiscal costs on prescription of IVIg have rocketed up by almost 300% in this Neurology Department comparing data from 2004-2005 vs 2008-2009 and this is disproportionate to the increase in the annual admission rate (bed usage), partly because of the soaring costs of the drug available in the market and also because of the increased prescription of IVIg for numerous indications where clinical trials data are yet not so robust. CONCLUSION: We have looked at the cost of alternative therapies and offer some proposals that if implemented could potentially save £330,000 annually from the health budget at this NHS Trust. Perhaps similar models could evolve for better cost-effective utilization of IVIg in countries in the developing world where health budgeting is more acutely relevant.
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Paraneoplastic movement disorders are part of the spectrum of paraneoplastic syndromes caused by the production of onconeural antibodies such as anti-Hu by underlying tumours. These attack specific neurons depending on receptor aetiology. We report the case of a 53-year-old man who presented 8 years previously with symptoms of upper limb weakness, light headedness, dizziness and falls. His condition followed a progressive course. Two years after onset he had right-sided weakness, diplopia and generalised dystonia. Initial investigations identified a positive anti-Hu antibody, but an extensive search for a primary tumour was negative. A malignant fibrous histiocytoma in his right gluteal fold was subsequently identified. At this stage he was bed bound with severe ataxia, dystonia and spasticity. Following surgical excision and treatment with high dose steroids and pulse immunoglobulin, further progression was arrested and minor improvements occurred. He can now ambulate with bilateral assistance but remains severely disabled.
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Ataxia/etiología , Distonía/etiología , Histiocitoma Fibroso Maligno/complicaciones , Síndromes Paraneoplásicos del Sistema Nervioso/diagnóstico , Neoplasias de los Tejidos Blandos/complicaciones , Ataxia/diagnóstico , Nalgas , Diagnóstico Diferencial , Distonía/diagnóstico , Histiocitoma Fibroso Maligno/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Síndromes Paraneoplásicos del Sistema Nervioso/complicaciones , Síndromes Paraneoplásicos del Sistema Nervioso/etiología , Neoplasias de los Tejidos Blandos/diagnósticoRESUMEN
The significance of Chlamydia pneumoniae infection in patients with multiple sclerosis (MS) is unclear. We determined the frequency of serum C. pneumoniae-specific immune complexes in patients with MS, neurological (OND) and healthy controls in a blinded, cross-sectional study. C. pneumoniae immune complexes were detected in 24% (38/156) of MS patients, 16% (11/69) of OND and 15% (77/499) of healthy controls. The odds ratio for all MS patients was 3.95 (95% CI: 2.15 to 7.24; P < 0.0001) accounting for the covariates: sex, age, socio-economic status and area of residence. The odds ratio for recently diagnosed MS patients was 4.33 (95% CI: 1.76 to 10.64; P = 0.001). Systemic C. pneumoniae infection is more frequent in MS patients than the healthy population and occurs early in the course of the disease.
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Infecciones por Chlamydophila/complicaciones , Infecciones por Chlamydophila/inmunología , Chlamydophila pneumoniae/aislamiento & purificación , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/microbiología , Adulto , Anticuerpos Antibacterianos/sangre , Anticuerpos Monoclonales , Complejo Antígeno-Anticuerpo/sangre , Chlamydophila pneumoniae/inmunología , Estudios Transversales , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Persona de Mediana Edad , Sistema de Registros , Estudios RetrospectivosRESUMEN
Debate continues over the relative importance of genetic factors over infectious agents in the aetiology of multiple sclerosis (MS). Detection of clusters of MS in space and time in the Tayside region of Scotland, UK would provide valuable evidence for the movement of infectious agents into a genetically susceptible population. A spatial scan statistic was used to detect, locate and provide a robust statistical test of any clusters found, without prior knowledge of their location or size. This was applied to a population-based MS register for the Tayside region of Scotland from 1970 to 1997, allowing for age at symptom onset, gender, population density and social deprivation. There were a total of 772 cases during the study period; an annual incidence of 72 per 100000. The mean age of symptom onset was 35.7 (SD = 10.5) and 73.8% of cases were women. There was a general increase in cases over time probably reflecting gradually better detection and diagnosis. There was a peak around the mid-1990s and some evidence of periodicity. There was a highly significant temporal cluster between 1982 and 1995 (P = 0.002) for the whole region. Additionally, a significant spatial cluster for the time period 1993-1995 was found centred in the rural area south-west of Perth (P=0.016). Significant temporal and spatial-temporal clusters are consistent with exogenous factors contributing to the distribution of MS in Tayside, Scotland.