Multiple system atrophy: Clinical, evolutive and histopathological characteristics of a series of cases / Atrofia multisistémica: características clínicas, anatomopatológicas y evolución de una serie de casos

Background and objective: Multiple system atrophy is a rare and fatal neurodegenerative disorder, characterized by autonomic dysfunction in association with either parkinsonism or cerebellar signs. The pathologic hallmark is the presence of alpha-synuclein aggregates in oligodendrocytes, forming glial cytoplasmic inclusions. Clinically, it may be difficult to distinguish form other parkinsonisms or ataxias, particularly in the early stages of the disease. In this case series we aim to describe in detail the features of MSA patients. Material and methods: Unified MSA Rating Scale (UMSARS) score, structural and functional imaging and cardiovascular autonomic testing, are summarized since early stages of the disease. Results: UMSARS proved to be useful to perform a follow-up being longitudinal examination essential to stratify risk of poor outcome. Neuropathological diagnosis showed an overlap between parkinsonian and cerebellar subtypes, with some peculiarities that could help to distinguish from other subtypes. Conclusion: A better description of MSA features with standardized test confirmed by means of neuropathological studies could help to increase sensitivity.(AU)

Antecedentes y objetivo: La atrofia multisistémica es un trastorno neurodegenerativo raro y letal que se caracteriza por una disfunción autonómica en asociación con parkinsonismo o signos cerebelosos. La marca anatomopatológica es la presencia de agregados de α-sinucleína en los oligodendrocitos, que forman inclusiones citoplasmáticas gliales. Desde un punto de vista clínico, puede ser difícil de distinguir de otros parkinsonismos o ataxias, particularmente en las primeras etapas de la enfermedad. En esta serie de casos, nuestro objetivo es describir en detalle las características de los pacientes con atrofia multisistémica. Material y métodos: Se resumen los datos objetidos de la puntuación de la Escala de calificación unificada de la atrofia multisistémica (UMSARS), imágenes estructurales y funcionales y las pruebas autonómicas cardiovasculares realizadas desde las primeras etapas de la enfermedad. Resultados: La escala UMSAR demostró ser útil para hacer un seguimiento: el examen longitudinal esencial fue para estratificar el riesgo de peor evolución. El diagnóstico neuropatológico mostró un solapamiento entre los subtipos parkinsoniano y cerebeloso, con algunas peculiaridades que podrían ayudar a distinguir los subtipos. Conclusión: Una mejor descripción de las características de la atrofia multisistémica en casos confirmados mediante neuropatología podría ayudar a aumentar la sensibilidad del diagnóstico.(AU)

Multiple system atrophy: Clinical, evolutive and histopathological characteristics of a series of cases.

BACKGROUND AND OBJECTIVE: Multiple system atrophy is a rare and fatal neurodegenerative disorder, characterized by autonomic dysfunction in association with either parkinsonism or cerebellar signs. The pathologic hallmark is the presence of alpha-synuclein aggregates in oligodendrocytes, forming glial cytoplasmic inclusions. Clinically, it may be difficult to distinguish form other parkinsonisms or ataxias, particularly in the early stages of the disease. In this case series we aim to describe in detail the features of MSA patients. MATERIAL AND METHODS: Unified MSA Rating Scale (UMSARS) score, structural and functional imaging and cardiovascular autonomic testing, are summarized since early stages of the disease. RESULTS: UMSARS proved to be useful to perform a follow-up being longitudinal examination essential to stratify risk of poor outcome. Neuropathological diagnosis showed an overlap between parkinsonian and cerebellar subtypes, with some peculiarities that could help to distinguish from other subtypes. CONCLUSION: A better description of MSA features with standardized test confirmed by means of neuropathological studies could help to increase sensitivity.

Multiple system atrophy: Clinical, evolutive and histopathological characteristics of a series of cases.

BACKGROUND AND OBJECTIVE: Multiple system atrophy is a rare and fatal neurodegenerative disorder, characterized by autonomic dysfunction in association with either parkinsonism or cerebellar signs. The pathologic hallmark is the presence of alpha-synuclein aggregates in oligodendrocytes, forming glial cytoplasmic inclusions. Clinically, it may be difficult to distinguish form other parkinsonisms or ataxias, particularly in the early stages of the disease. In this case series we aim to describe in detail the features of MSA patients. MATERIAL AND METHODS: Unified MSA Rating Scale (UMSARS) score, structural and functional imaging and cardiovascular autonomic testing, are summarized since early stages of the disease. RESULTS: UMSARS proved to be useful to perform a follow-up being longitudinal examination essential to stratify risk of poor outcome. Neuropathological diagnosis showed an overlap between parkinsonian and cerebellar subtypes, with some peculiarities that could help to distinguish from other subtypes. CONCLUSION: A better description of MSA features with standardized test confirmed by means of neuropathological studies could help to increase sensitivity.

Bilateral facial nerve palsy associated with COVID-19 and Epstein-Barr virus co-infection.

COVID-19 can occasionally be associated with cranial nerve involvement, but facial palsy, particularly if bilateral, is exceptional. We here report a patient who presented with severe bilateral facial palsy and evidence of SARS-CoV-2 infection preceded by upper respiratory symptoms. He also had serological evidence of coinfection with Epstein-Barr virus, which could have also played a role in his neurological manifestations. PCR in the cerebrospinal fluid was negative for both EBV and SARS-CoV-2, which suggests an indirect, immune-mediated mechanism rather than direct, viral-induced damage. The patient was treated with prednisone 60 mg/24h with a tapering schedule and had a favorable outcome, with an almost complete recovery in 3 weeks. SARS-CoV-2 adds to the list of infectious agents causative of bilateral facial palsy. Coinfection with SARS-CoV-2 is not rare and should be considered in the differential diagnosis.

Brain aging and Parkinson's disease: New therapeutic approaches using drug delivery systems.

The etiology and pathogenesis of Parkinson's disease (PD) is unknown, aging being the strongest risk factor for brain degeneration. Understanding PD pathogenesis and how aging increases the risk of disease would aid the development of therapies able to slow or prevent the progression of this neurodegenerative disorder. In this review we provide an overview of the most promising therapeutic targets and strategies to delay the loss of dopaminergic neurons observed both in PD and aging. Among them, handling alpha-synuclein toxicity, enhancing proteasome and lysosome clearance, ameliorating mitochondrial disruptions and modifying the glial environment are so far the most promising candidates. These new and conventional drugs may present problems related to their labile nature and to the difficulties in reaching the brain. Thus, we highlight the latest types of drug delivery system (DDS)-based strategies for PD treatment, including DDS for local and systemic drug delivery. Finally, the ongoing challenges for the discovery of new targets and the opportunities for DDS-based therapies to improve and efficacious PD therapy will be discussed.

[Neuropsychological profile of frontotemporal lobar degeneration]. / Perfil neuropsicológico de la degeneración lobar frontotemporal.

Frontotemporal lobar degeneration encompasses three different syndromes, with clinical and pathologic commonalities, making diagnosis difficult in early stages. Three subtypes are recognized: frontotemporal dementia and its three variants, corticobasal syndrome and supranuclear palsy syndrome. The objective of this study is to review the neuropsychological features of each syndrome in order to differentiate amongst subtypes as well as from other forms of dementia. We review multiple studies from the literature, highlighting the main clinical features, neuropathology and changes in brain imaging of each syndrome. Subsequently, we describe the neuropsychological profile compared to other dementias, and how it progresses over time. Although there is an overlap amongst the different subtypes of frontotemporal lobar degeneration, neuropsychological profiles can help identify subtypes and discriminate frontotemporal lobar degeneration from other forms of dementia.

Structural and functional neuroimaging in human prion diseases.

INTRODUCTION: Prion diseases are neurodegenerative disorders resulting from the accumulation of a misfolded isoform of the cellular prion protein (PrPc). They can occur as acquired, sporadic, or hereditary forms. Although prion diseases show a wide range of phenotypic variations, pathological features and clinical evolution, they are all characterised by a common unfavourable course and a fatal outcome. REVIEW SUMMARY: Some variants, such as kuru, have practically disappeared, while others, for example the variant Creutzfeldt-Jakob (vCJD) or those attributable to iatrogenic causes, are still in force and pose a challenge to current medicine. There are no definitive pre-mortem diagnostic tests, except for vCJD, where a tonsil biopsy detects 100% of the cases. For this reason, diagnostic criteria dependent on statistical probability have had to be created. These require complementary examinations, such as an electroencephalogram (EEG) or the detection of 14-3-3 protein in cerebrospinal fluid (CSF). Only the pulvinar sign in magnetic resonance imaging (MRI) has been included as a vCJD diagnostic criterion. The present review discusses neuroimaging findings for each type of prion disease in patients with a definitive histopathological diagnosis. CONCLUSIONS: The aim is to define the usefulness of these complementary examinations as a tool for the diagnosis of this family of neurodegenerative diseases.

[Video-EEG monitoring and simultaneous ECG for the differential diagnosis of transient consciousness disorders. A case report]. / Monitorización con vídeo-EEG y ECG simultáneo para el diagnóstico diferencial de trastornos de conciencia transitorios. A propósito de un caso.

We present the case of a 36 year-old woman, with history of transient consciousness disorders with vegetative state, interpreted as epileptic crises and treated with valproate for two years. After nine asymptomatic years, they reappeared associated with migraine, vomiting and some generalized convulsions. Electroencephalogram and cerebral magnetic resonance turned out normal, and treatment with zonisamide was started, without beneficial results. Later cardiological studies objectified a blockage of the left branch that coincided with dizziness. The study was completed with Video-EGG monitoring, where there was an episode that showed temporary right epileptiform activity, with a diagnosis established of focal epilepsy of unknown cause. At present, she remains asymptomatic with oxycarbazepine.

«Tiempo es cerebro», ¿solo en la fase aguda del ictus? / "Time is brain": only in the acute phase of stroke?

Introducción y objetivo: El ictus representa en España la primera causa de muerte por entidades específicas en mujeres, la primera causa de invalidez en los adultos y supone un enorme coste tanto humano como económico. En los últimos años se han producido avances importantes tanto en el tratamiento de la fase aguda como en el proceso neurorrehabilitador; sin embargo, continúa sin quedar claro cuál es el momento óptimo en el que debe iniciarse la neurorrehabilitación después de un ictus y cuáles son las consecuencias de retrasar este inicio. El objetivo de este estudio es comprobar el efecto que supone cada día de retraso en el inicio de la neurorrehabilitación en la recuperación funcional y su influencia en la tasa de institucionalización al alta.Métodos: Estudio retrospectivo en el que se incluyeron los pacientes ingresados entre abril de 2005 y septiembre de 2008, en la Unidad de Neurorrehabilitación de Ictus (UNRHI) del Hospital Parkwood (Universidad de Western Ontario, Canadá). Se obtuvo la edad, la puntuación FIM al ingreso y al alta, los días entre la aparición del ictus y el ingreso en la Unidad de Neurorrehabilitación y el destino al alta.Resultados: Después de ajustar por edad y FIM al ingreso, se encontró una asociación estadísticamente significativa entre la mejoría funcional de los pacientes (ganancia de FIM) y el retraso por cada día en comenzar la rehabilitación. Existe una correlación estadísticamente significativa entre el retraso en iniciar esta terapia y el grado de institucionalización al alta. Conclusiones: Por cada día que se retrase el inicio del tratamiento neurorrehabilitador empeora el pronóstico funcional de los pacientes al alta. Este retraso se relaciona también con una mayor tasa de institucionalización al alta (AU)

Introduction and objective: In Spain, stroke is the leading cause of death in women as well as the leading cause of disability in adults. This translates into a huge human and economic cost. In recent years there have been significant advances both in the treatment of acute stroke and in the neuro-rehabilitation process; however, it is still unclear when the best time is to initiate neurorehabilitation and what the consequences of delaying treatment are. To test the effect of a single day delay in the onset of neurorehabilitation on functional improvement achieved, and the influence of that delay in the rate of institutionalisation at discharge.Methods: A retrospective study of patients admitted to Parkwood Hospital's Stroke Neurorehabilitation Unit (UNRHI) (University of Western Ontario, Canada) between April 2005 and September 2008 was performed. We recorded age, Functional Independence Measurement (FIM) score at admission and discharge, the number of days between the onset of stroke and admission to the Neurorehabilitation Unit and discharge destination. Results: After adjustment for age and admission FIM, we found a significant association between patient functional improvement (FIM gain) and delay in starting rehabilitation. We also observed a significant correlation between delay in initiating therapy and the level of institutionalisation at discharge. Conclusions: A single day delay in starting neurorehabilitation affects the functional prognosis of patients at discharge. This delay is also associated with increased rates of institutionalisation at discharge (AU)

Monitorización con vídeo-EEG y ECG simultáneo para el diagnóstico diferencial de trastornos de conciencia transitorios. A propósito de un caso / Video-EEG monitoring and simultaneous ECG for the differential diagnosis of transient consciousness disorders. A case report

Se presenta el caso de una mujer de 36 años, con antecedentes de trastornos de conciencia transitorios con cortejo vegetativo en la adolescencia, interpretados como crisis epilépticas y tratados con ácido valproico durante dos años. Tras permanecer nueve años asintomática, reaparecieron asociados a migraña, vómitos y alguna convulsión generalizada. El electroencefalograma y la resonancia magnética cerebral resultaron normales e inició tratamiento con zonisamida, sin beneficio. Estudios cardiológicos posteriores objetivaron bloqueo de rama izquierda, que coincidía con mareo. Se completó el estudio mediante monitorización con vídeo-EEG, donde tuvo un episodio que evidenció actividad epileptiforme temporal derecha, estableciéndose el diagnóstico de epilepsia focal de causa desconocida. Actualmente, permanece asintomática con oxcarbacepina. La anamnesis es fundamental para diferenciar trastornos de conciencia transitorios, especialmente síncopes y crisis epilépticas, pero no siempre es suficiente. La monitorización con vídeo-EEG y registro simultáneo de electrocardiograma resulta muy útil para distinguirlos(AU)

We present the case of a 36 year-old woman, with history of transient consciousness disorders with vegetative state, interpreted as epileptic seizures and treated with valproic acid for two years. After nine asymptomatic years, they reappeared associated with migraine, vomiting and some generalized convulsions. Electroencephalogram and cerebral magnetic resonance turned out normal, and treatment with zonisamide was started, without beneficial results. Later cardiological studies objectified a blockage of the left branch that coincided with dizziness. The study was completed with Video-EEG monitoring, where there was an episode that showed right temporal epileptiform activity, with a diagnosis established of focal epilepsy of unknown etiology. At present, she remains asymptomatic with oxycarbazepine(AU)

["Time is brain": only in the acute phase of stroke?]. / «Tiempo es cerebro¼, ¿solo en la fase aguda del ictus?

INTRODUCTION AND OBJECTIVE: In Spain, stroke is the leading cause of death in women as well as the leading cause of disability in adults. This translates into a huge human and economic cost. In recent years there have been significant advances both in the treatment of acute stroke and in the neuro-rehabilitation process; however, it is still unclear when the best time is to initiate neurorehabilitation and what the consequences of delaying treatment are. To test the effect of a single day delay in the onset of neurorehabilitation on functional improvement achieved, and the influence of that delay in the rate of institutionalisation at discharge. METHODS: A retrospective study of patients admitted to Parkwood Hospital's Stroke Neurorehabilitation Unit (UNRHI) (University of Western Ontario, Canada) between April 2005 and September 2008 was performed. We recorded age, Functional Independence Measurement (FIM) score at admission and discharge, the number of days between the onset of stroke and admission to the Neurorehabilitation Unit and discharge destination. RESULTS: After adjustment for age and admission FIM, we found a significant association between patient functional improvement (FIM gain) and delay in starting rehabilitation. We also observed a significant correlation between delay in initiating therapy and the level of institutionalisation at discharge. CONCLUSIONS: A single day delay in starting neurorehabilitation affects the functional prognosis of patients at discharge. This delay is also associated with increased rates of institutionalisation at discharge.