RESUMEN
BACKGROUND: Cognitive difficulties experienced by people with multiple sclerosis (MS) impact on quality of life and daily functioning, from childcare and work to social and self-care activities. The Cognitive Occupation-Based programme for people with MS (COB-MS) was developed as a holistic, individualised cognitive rehabilitation intervention to address the wide-ranging symptoms and functional difficulties that present in MS, including the ability to maintain employment, social activities, home management and self-care. The aim of the research is to evaluate the feasibility and preliminary efficacy of COB-MS for people with MS. METHODS: Due to the impacts of COVID-19, trial activities that were planned for in-person delivery were completed remotely. One hundred and twenty people with MS will be assigned to participate in either the COB-MS programme or a treatment-as-usual, wait-list control group as part of this single-blind, cluster-randomised controlled feasibility and preliminary efficacy trial of the COB-MS programme. The COB-MS group will participate in an eight-session occupational-based cognitive rehabilitation programme over 9 weeks. The COB-MS intervention was planned for in-person delivery but was delivered online by occupational therapists to small groups of people with MS. The primary outcome measure is the Goal Attainment Scaling at 12 weeks. Participants will be assessed pre-intervention, post-intervention, 12 weeks post-intervention and 6 months post-intervention. Qualitative evaluations of participants' perspectives will also be examined as part of the feasibility study. Data, due to be collected in-person, was collected online or by post. The original study design, including the statistical analysis plan, remains unchanged despite the shift to a remote trial conduct. DISCUSSION: Results will provide recommendations for a future definitive trial of COB-MS, with respect to both feasibility and preliminary, clinical efficacy. TRIAL REGISTRATION: ISRCTN ISRCTN11462710 . Registered on 9 September 2019 and updated on 23 September 2020 to account for changes outlined here.
Asunto(s)
COVID-19 , Esclerosis Múltiple , Humanos , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/terapia , Estudios de Factibilidad , Calidad de Vida , Método Simple Ciego , Cognición , Ocupaciones , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
A 74-year-old farmer presented to the emergency department with a subacute history of progressive dyspnoea, wheeze and dysphonia. He was treated for an exacerbation of asthma with poor response to pharmacological therapy. Investigation of dysphonia via laryngoscopy identified a bilateral vocal cord palsy. Subsequently, the patient developed an episode of life-threatening stridor and hypercapnic respiratory failure requiring an emergency tracheostomy. Neurology input identified evidence of widespread muscle fasciculations on clinical examination. MRI of the brain and cervical spine were unremarkable. Electromyogram testing identified changes of acute denervation in several limbs consistent with a diagnosis of motor neuron disease (MND). Bilateral vocal cord palsy has been rarely reported in the literature as the heralding symptom resulting in the diagnosis of MND. In patients with a subacute onset of dysphonia, dyspnoea and stridor, MND should be a differential diagnosis.
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Enfermedad de la Neurona Motora , Parálisis de los Pliegues Vocales , Anciano , Vértebras Cervicales , Humanos , Laringoscopía , Masculino , Enfermedad de la Neurona Motora/complicaciones , Enfermedad de la Neurona Motora/diagnóstico , Ruidos Respiratorios/etiología , Parálisis de los Pliegues Vocales/diagnóstico , Parálisis de los Pliegues Vocales/etiología , Parálisis de los Pliegues Vocales/cirugíaRESUMEN
We report a case of severe amnestic syndrome following theophylline overdose. A woman in her early 30s was admitted to hospital where she developed status epilepticus following an intentional overdose of theophylline and lansoprazole. She developed a profound acidosis and required intubation in the intensive care unit. Following extubation the patient was noted to have a severe amnestic syndrome with poor short-term memory. A work-up to exclude infectious, autoimmune and paraneoplastic causes for encephalitis was undertaken. Cerebrospinal fluid analysis was normal and autoimmune encephalitis titres were negative. Initial MRI brain imaging demonstrated hyperintensities of the mesial temporal lobes bilaterally. Follow-up imaging at 4 months identified further interval reduction but persistent hippocampal hyperintensities. Theophylline toxicity with corresponding amnestic syndrome and hippocampal hyperintensities has been rarely reported. We believe this case with persistent abnormal Montreal Cognitive Assessment Score at 12 months correlates with persistent hippocampal abnormalities seen on imaging.
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Encefalitis , Enfermedad de Hashimoto , Femenino , Humanos , Imagen por Resonancia Magnética , Neuroimagen , TeofilinaRESUMEN
The cause of progressive disability in Primary Progressive Multiple Sclerosis (PPMS) is unknown. Pathogenic genes have been described in some MS cases that may contribute to progressive disability, independent of immune - mediated mechanisms (Jia et al., 2018). The autosomal dominant SPG4 (Spastin) mutation is the most common genotype in Hereditary Spastic Paraplegia (Solowska and Baas, 2015) and has been found in some patients with Relapsing Remitting Multiple Sclerosis (Mead et al., 2001, Yazici et al., 2013). Here, we describe the novel association of PPMS and the SPG4 (Spastin) mutation, in a patient with a family history of Hereditary Spastic Paraplegia, and discuss the therapeutic implications. While this single case report cannot discrimiate between simple co-occurence and the possibility of a pathogenic association, our report invites larger scale investigation.
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Esclerosis Múltiple Crónica Progresiva , Esclerosis Múltiple , Paraplejía Espástica Hereditaria , Adenosina Trifosfatasas/genética , Adenosina Trifosfatasas/metabolismo , Humanos , Esclerosis Múltiple Crónica Progresiva/complicaciones , Esclerosis Múltiple Crónica Progresiva/genética , Paraplejía Espástica Hereditaria/diagnóstico por imagen , Paraplejía Espástica Hereditaria/genética , Espastina/genéticaRESUMEN
Immune checkpoint inhibitors have transformed the treatment of advanced malignancy, while increasing the risk of immune-related adverse events. A 56-year-old woman who had received nivolumab for stage 4 renal cell carcinoma subsequently developed altered behaviour, memory deficits and worsening of previously stable epilepsy. MR scan of the brain showed bilateral FLAIR (fluid-attenuated inversion recovery) hyperintensity of the mesial temporal lobes, and there were anti-Ma2 antibodies in both serum and cerebrospinal fluid. She was treated with corticosteroids but developed further clinical relapses requiring immunoglobulin and rituximab. The immune-related adverse events relating to immune checkpoint inhibitors are an emerging challenge for the neurologist. Some cases are refractory and require serial immunosuppression.
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Antígenos de Neoplasias/metabolismo , Autoanticuerpos/metabolismo , Encefalitis/tratamiento farmacológico , Encefalitis/metabolismo , Enfermedad de Hashimoto/tratamiento farmacológico , Enfermedad de Hashimoto/metabolismo , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Proteínas del Tejido Nervioso/metabolismo , Autoanticuerpos/efectos de los fármacos , Encefalitis/diagnóstico por imagen , Femenino , Enfermedad de Hashimoto/diagnóstico por imagen , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Persona de Mediana EdadRESUMEN
BACKGROUND: Cognitive difficulties experienced by people with multiple sclerosis (MS) impact their quality of life and daily functioning, from childcare and work, to social and self-care activities. Despite the high prevalence of cognitive difficulties seen in MS, there is a lack of developed programmes that target cognition, while also supporting patients by helping them to function well in everyday life. The Cognitive Occupation-Based programme for people with MS (COB-MS) was developed as a holistic, individualised cognitive rehabilitation intervention. It addresses the wide-ranging symptoms and functional difficulties that present in MS, including the ability to maintain employment, social activities, home management and self-care. The aim of the current research is to evaluate the feasibility and preliminary efficacy of COB-MS for people with MS. The focus is on feasibility outcomes as well as functioning associated with cognitive difficulty and secondary outcomes related to cognition, fatigue and quality of life. METHODS: One hundred and twenty people with MS will be assigned to participate in either the COB-MS programme or a treatment as usual, wait-list control group as part of this single-blind, cluster-randomised controlled feasibility and preliminary efficacy trial of the COB-MS programme. The COB-MS group will participate in an eight-session occupational-based cognitive rehabilitation programme over 9 weeks. The primary outcome measure is the goal attainment scaling at 12 weeks. Participants will be assessed pre-intervention, post-intervention and at 12 weeks post-intervention and 6 months post-intervention. Qualitative evaluations of participants' perspectives will also be examined as part of the feasibility study. DISCUSSION: Results will provide recommendations for a future definitive trial of COB-MS, with respect to both feasibility and preliminary, clinical efficacy. In the event that results indicate efficacy, study findings will suggest that COB-MS requires consideration as a means of enhancing cognitive and daily functioning in people living with MS. TRIAL REGISTRATION: ISRCTN: ISRCTN11462710. Registered on 9 September 2019.
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Cognición , Terapia Cognitivo-Conductual/métodos , Esclerosis Múltiple/rehabilitación , Terapia Ocupacional/métodos , Actividades Cotidianas , Terapia Cognitivo-Conductual/economía , Análisis Costo-Beneficio , Estudios de Factibilidad , Humanos , Esclerosis Múltiple/economía , Esclerosis Múltiple/psicología , Terapia Ocupacional/economía , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Autocuidado , Método Simple Ciego , Resultado del TratamientoRESUMEN
PURPOSE OF REVIEW: This review will discuss the expanding clinical spectrum of paroxysmal movement disorders and therapeutic options in light of emerging genotypic heterogeneity in these conditions. RECENT FINDINGS: Paroxysmal movement disorders comprise a heterogeneous group of rare neurological conditions characterized by intermittent episodes of abnormal movement associated with various triggers. As the clinical and genotypic spectrum of these disorders evolves, so also has the range of therapeutic options. Triheptanoin has recently been shown to be a very promising alternative to the ketogenic diet in paroxysmal exercise-induced dyskinesia. Four-aminopyridine is now considered first-line symptomatic therapy for episodic ataxia type-2, with pre-clinical findings indicating cerebellar neuroprotection. SUMMARY: In light of the newly emerging therapies, careful clinical phenotyping is needed to ensure diagnostic precision and timely initiation of appropriate therapies.
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Corea/terapia , Corea/patología , Corea/fisiopatología , Discinesias , HumanosRESUMEN
Several factors are thought to contribute to inadequate seizure control in patients with juvenile myoclonic epilepsy (JME), including drug resistance, neuropsychiatric comorbidity, and poor lifestyle choices. Recent evidence supports the existence of frontal lobe microstructural deficits and behavioral changes that may contribute to poor seizure control in a minority of patients. Counseling patients on the importance of adequate sleep hygiene and alcohol restriction is an important part of the management strategy for patients with JME. However, information is lacking on how these lifestyle restrictions impact on patients with JME. We conducted a qualitative descriptive analysis of the social impact of JME on 12 patients, from their own perspective. We identified four prominent themes: the importance of alcohol use as a social "norm", how JME affected relationships, decision making (risk versus consequences), and knowledge imparting control. Given that these restrictions were interpreted by patients as social "curfews", we suggest that the term "Cinderella Syndrome" encapsulates the perceived imperative to be home before midnight. Our findings underscore the importance for clinicians to recognize that in counseling patients with JME about lifestyle adjustments, there may be a significant social consequence unique to this patient group.
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Consumo de Bebidas Alcohólicas/psicología , Relaciones Interpersonales , Estilo de Vida , Epilepsia Mioclónica Juvenil/psicología , Calidad de Vida , Convulsiones/psicología , Normas Sociales , Adolescente , Femenino , Humanos , Masculino , Investigación Cualitativa , Adulto JovenRESUMEN
BACKGROUND: The term "Clinically Isolated Syndrome" (CIS) was introduced to describe a first clinical neurologic episode suggestive of an inflammatory demyelinating CNS disorder. Thereafter, the risk of developing clinically definite multiple sclerosis ranges from 20% to 80%, depending on a number of prognostic factors. Although the concept of CIS has been an important component in improving our understanding of risk levels in Multiple Sclerosis and prognosis, communicating uncertainty in this context remains a challenge for both patients and their clinicians. We therefore wished to explore both the patients understanding of the concept of CIS and the subsequent impact of a diagnosis. We also explored the concept of CIS from the clinician's perspective. METHODS: The study uses a qualitative descriptive design involving both a semi-structured interview of patients with CIS as well as a short questionnaire sent to practising clinicians in the Republic of Ireland. Narrative data was coded onto themes. RESULTS: Thirty CIS patients were interviewed. The majority of patients understood the term "CIS" but not the link between CIS and MS. Two themes were identified: emotional reactions following CIS diagnosis; and terminology and communication. Confusion and anxiety among patients due to inconsistent communication of CIS was identified. Of the thirty-three clinicians surveyed, only thirty-nine per cent found the term "CIS" clinically useful. Eighteen per cent of clinicians diagnosed MS from the CIS case vignette provided. CONCLUSION: In the diagnosis of a first demyelinating event, use of the term "CIS" is confusing to patients and inconsistent among clinicians. We suggest that the term "CIS" be abandoned in favour of terminology that reflects both its pathogenesis and inherent risk of subsequent MS.
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Actitud del Personal de Salud , Enfermedades Desmielinizantes/diagnóstico , Enfermedades Desmielinizantes/psicología , Conocimientos, Actitudes y Práctica en Salud , Adulto , Ansiedad , Comprensión , Enfermedades Desmielinizantes/clasificación , Femenino , Comunicación en Salud , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Neurólogos/psicología , Enfermeras y Enfermeros/psicología , Investigación Cualitativa , Encuestas y Cuestionarios , Terminología como Asunto , Adulto JovenAsunto(s)
Toma de Decisiones Clínicas , Distonía/diagnóstico , Trastornos Neurológicos de la Marcha/diagnóstico , Trastornos Parkinsonianos/diagnóstico , Ubiquitina-Proteína Ligasas/genética , Adolescente , Distonía/etiología , Distonía/genética , Femenino , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/genética , Humanos , Trastornos Parkinsonianos/complicaciones , Trastornos Parkinsonianos/genéticaRESUMEN
Among Parkinson's disease (PD) symptoms, freezing of gait (FoG) is one of the most debilitating. To assess FoG, current clinical practice mostly employs repeated evaluations over weeks and months based on questionnaires, which may not accurately map the severity of this symptom. The use of a non-invasive system to monitor the activities of daily living (ADL) and the PD symptoms experienced by patients throughout the day could provide a more accurate and objective evaluation of FoG in order to better understand the evolution of the disease and allow for a more informed decision-making process in making adjustments to the patient's treatment plan. This paper presents a new algorithm to detect FoG with a machine learning approach based on Support Vector Machines (SVM) and a single tri-axial accelerometer worn at the waist. The method is evaluated through the acceleration signals in an outpatient setting gathered from 21 PD patients at their home and evaluated under two different conditions: first, a generic model is tested by using a leave-one-out approach and, second, a personalised model that also uses part of the dataset from each patient. Results show a significant improvement in the accuracy of the personalised model compared to the generic model, showing enhancement in the specificity and sensitivity geometric mean (GM) of 7.2%. Furthermore, the SVM approach adopted has been compared to the most comprehensive FoG detection method currently in use (referred to as MBFA in this paper). Results of our novel generic method provide an enhancement of 11.2% in the GM compared to the MBFA generic model and, in the case of the personalised model, a 10% of improvement with respect to the MBFA personalised model. Thus, our results show that a machine learning approach can be used to monitor FoG during the daily life of PD patients and, furthermore, personalised models for FoG detection can be used to improve monitoring accuracy.
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Acelerometría/métodos , Enfermedad de Parkinson/fisiopatología , Máquina de Vectores de Soporte , Caminata , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: After several years of treatment, patients with Parkinson's disease (PD) tend to have, as a side effect of the medication, dyskinesias. Close monitoring may benefit patients by enabling doctors to tailor a personalised medication regimen. Moreover, dyskinesia monitoring can help neurologists make more informed decisions in patient's care. OBJECTIVE: To design and validate an algorithm able to be embedded into a system that PD patients could wear during their activities of daily living with the purpose of registering the occurrence of dyskinesia in real conditions. MATERIALS AND METHODS: Data from an accelerometer positioned in the waist are collected at the patient's home and are annotated by experienced clinicians. Data collection is divided into two parts: a main database gathered from 92 patients used to partially train and to evaluate the algorithms based on a leave-one-out approach and, on the other hand, a second database from 10 patients which have been used to also train a part of the detection algorithm. RESULTS: Results show that, depending on the severity and location of dyskinesia, specificities and sensitivities higher than 90% are achieved using a leave-one-out methodology. Although mild dyskinesias presented on the limbs are detected with 95% specificity and 39% sensitivity, the most important types of dyskinesia (any strong dyskinesia and trunk mild dyskinesia) are assessed with 95% specificity and 93% sensitivity. CONCLUSION: The presented algorithmic method and wearable device have been successfully validated in monitoring the occurrence of strong dyskinesias and mild trunk dyskinesias during activities of daily living.
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Acelerometría/instrumentación , Antiparkinsonianos/uso terapéutico , Discinesias/diagnóstico , Levodopa/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Antiparkinsonianos/efectos adversos , Discinesias/etiología , Humanos , Levodopa/efectos adversos , Monitoreo Fisiológico , Enfermedad de Parkinson/complicaciones , Máquina de Vectores de SoporteRESUMEN
We describe a case of a 45-year-old man who presented with a transient syndrome consisting of headache with neurological deficits. Neuroimaging including brain angiography was normal. Cerebrospinal fluid (CSF) analysis revealed an elevated protein and lymphocytic pleocytosis. The diagnosis of a syndrome of Headache and Neurological Deficits with CSF Lymphocytosis (HaNDL) was made after excluding all the other possible causes for the patient's presentation. He made an excellent recovery following a short course of naproxen sodium.
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Encéfalo , Cefalea/diagnóstico , Linfocitos/metabolismo , Linfocitosis/diagnóstico , Migraña con Aura/diagnóstico , Enfermedades del Sistema Nervioso/diagnóstico , Angiografía , Antiinflamatorios no Esteroideos/uso terapéutico , Encéfalo/metabolismo , Encéfalo/patología , Proteínas del Líquido Cefalorraquídeo/metabolismo , Diagnóstico Diferencial , Cefalea/líquido cefalorraquídeo , Cefalea/tratamiento farmacológico , Cefalea/etiología , Humanos , Leucocitosis , Linfocitosis/líquido cefalorraquídeo , Linfocitosis/tratamiento farmacológico , Linfocitosis/etiología , Masculino , Persona de Mediana Edad , Migraña con Aura/líquido cefalorraquídeo , Migraña con Aura/tratamiento farmacológico , Migraña con Aura/etiología , Naproxeno/uso terapéutico , Enfermedades del Sistema Nervioso/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso/complicaciones , Neuroimagen , SíndromeRESUMEN
Topoisomerase II (TOP2) removes torsional stress from DNA and facilitates gene transcription by introducing transient DNA double-strand breaks (DSBs). Such DSBs are normally rejoined by TOP2 but on occasion can become abortive and remain unsealed. Here we identify homozygous mutations in the TDP2 gene encoding tyrosyl DNA phosphodiesterase-2, an enzyme that repairs 'abortive' TOP2-induced DSBs, in individuals with intellectual disability, seizures and ataxia. We show that cells from affected individuals are hypersensitive to TOP2-induced DSBs and that loss of TDP2 inhibits TOP2-dependent gene transcription in cultured human cells and in mouse post-mitotic neurons following abortive TOP2 activity. Notably, TDP2 is also required for normal levels of many gene transcripts in developing mouse brain, including numerous gene transcripts associated with neurological function and/or disease, and for normal interneuron density in mouse cerebellum. Collectively, these data implicate chromosome breakage by TOP2 as an endogenous threat to gene transcription and to normal neuronal development and maintenance.