Epidemiology of ataxia and hereditary spastic paraplegia in Spain: A cross-sectional study.

INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1933 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 938 patients were men (48.5%) and 995 were women (51.5%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

Epidemiology of ataxia and hereditary spastic paraplegia in Spain: a cross-sectional study. / Mapa epidemiológico transversal de las ataxias y paraparesias espásticas hereditarias en España.

INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1.809 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 920 patients were men (50.8%) and 889 were women (49.2%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

[Depressive symptoms and burden in family caregivers in Alzheimer's disease: a model of structural equations]. / Sintomas depresivos y sobrecarga en los familiares cuidadores en la enfermedad de Alzheimer: un modelo de ecuaciones estructurales.

INTRODUCTION: The care of patients with Alzheimer's disease increases the burden and depression of the main caregiver, although the relationship between the two is not clearly defined. AIMS: To explore the factors associated with depressive symptomatology and burden in the main caregiver and to apply a model of structural equations to identify the relationship between them. SUBJECTS AND METHODS: The sample consisted of 127 family caregivers of people with Alzheimer's disease, with a follow-up of 24 months. Multivariate regression analyses were performed to identify the characteristics of patients and caregivers associated with burden and depression of the main caregiver, and a model of structural equations was designed to analyse the relationship between the variables. RESULTS: In the model of structural equations, the burden had a direct effect on depression, both in the baseline assessment and at 24 months. The variables associated with burden were: schooling and the lower mental health of the main caregiver; and the behavioral alterations and the functional dependency of the patient. The lower cognitive level of the patient and the lower mental health of the main caregiver were associated with depression. The correlation between burden and depression increased from baseline to two years (r = 0.470 vs. r = 0.613). CONCLUSIONS: The deterioration of the patient and caregiver burden are risk factors for depression in the main caregiver. Interventions would be necessary to reduce the burden and prevent related depression.

TITLE: Sintomas depresivos y sobrecarga en los familiares cuidadores en la enfermedad de Alzheimer: un modelo de ecuaciones estructurales.Introduccion. El cuidado de los pacientes con enfermedad de Alzheimer incrementa la sobrecarga y la depresion del cuidador principal, aunque la relacion entre ambas no esta claramente definida. Objetivos. Explorar los factores asociados a la sintomatologia depresiva y la sobrecarga en el cuidador principal y aplicar un modelo de ecuaciones estructurales para identificar la relacion entre ellas. Sujetos y metodos. La muestra estuvo formada por 127 cuidadores familiares de personas con enfermedad de Alzheimer, con un seguimiento de 24 meses. Se realizaron analisis de regresion multivariante para identificar las caracteristicas de pacientes y cuidadores asociadas a la sobrecarga y la depresion del cuidador principal, y se diseño un modelo de ecuaciones estructurales para analizar la relacion entre las variables. Resultados. En el modelo de ecuaciones estructurales, la sobrecarga tuvo un efecto directo sobre la depresion, tanto en la evaluacion basal como a los 24 meses. Las variables asociadas a la sobrecarga fueron: la escolaridad y la menor salud mental del cuidador principal, y las alteraciones conductuales y la dependencia funcional del paciente. El menor nivel cognitivo del paciente y la menor salud mental del cuidador principal estuvieron asociados a la depresion. La correlacion entre sobrecarga y depresion aumento desde la evaluacion basal hasta los dos años (r = 0,47 frente a r = 0,613). Conclusiones. El deterioro del paciente y la sobrecarga son factores de riesgo para la depresion en el cuidador principal. Serian necesarias intervenciones para reducir la carga y poder prevenir la depresion relacionada.

Evidencia sobre el tratamiento de la enfermedad de alzheimer con inhibidores de la acetilcolinesterasa y/o memantina / No disponible

No disponible

Neurosarcoidosis: report of 30 cases and a literature survey.

INTRODUCTION: Neurosarcoidosis accounts for approximately 5% of cases of sarcoidosis. OBJECTIVE: To determine the frequency of Neurosarcoidosis in our setting and analyze the clinical-radiological findings and evolution of 30 patients consecutively diagnosed. METHODS: The medical records of patients with a diagnosis of Neurosarcoidosis were reviewed, and data regarding the clinical features, ancillary tests performed, treatment, and outcome were recorded. We revised the literature to summarize and discuss the previous clinical series of Neurosarcoidosis. RESULTS: It accounted for 6.7% of all cases of sarcoidosis. Seven patients had definite diagnosis and 23 had probable diagnosis. The mean age at onset of Neurosarcoidosis was 48.3 years and 66.7% of patients were women. Neurologic clinical features were the first manifestation of Neurosarcoidosis in 70% of cases. Cranial neuropathy was present in 17 patients and 14 of them had facial palsy. The central nervous system was affected in 10 patients and the peripheral nervous system in 5. Chest disease, the most common extraneurologic manifestation, was present in 20 patients. All patients were treated with corticosteroids, and all those with central nervous system involvement had poor outcome. CONCLUSION: Neurosarcoidosis requires a high degree of suspicion to establish the diagnosis. Central nervous system involvement is associated with a poor prognosis.

Encefalopatía de Wernicke en pacientes no alcohólicos: una serie de 8 casos / Wernicke's encephalopathy in non-alcoholic patients: a series of 8 cases

Introduction: Wernicke's encephalopathy (WE) is an underdiagnosed condition, usually associated with alcoholism, and has a worse prognosis if there is a delay in diagnosis. A series of 8 non-alcoholic patients with WE is presented and an assessment is made on whether a delay in diagnosis leads to a worse prognosis. Patients and methods:The clinical records of patients admitted to 2 university hospitals between 2004 and 2009 with the diagnosis of WE, excluding those with a history of alcoholism, were retrospectively reviewed. Results:The study included 4 men and 4 women aged 35-82 of whom 7 had a history of gastrointestinal pathology, and persistent vomiting was the precipitating factor in 7. Encephalopathy was the most frequent onset symptom (4). The classical triad was present in seven patients. Thiamine levels were low in 3/6 and normal in 3/6 cases. MRI was abnormal in seven patients, with high signal intensity in the diencephalon and mammillary bodies (7), periaqueductal grey matter (6), cortex (3) and cerebellum (1). Seven improved with thiamine. Sequelae were mild in 6, and severe in 2 after 6-12 months of follow-up. All patients with a diagnostic delay less than 18 days had mild sequelae.Conclusions: Non-alcoholic WE frequently occurs after gastrointestinal disturbances that could result in lower thiamine absorption. Whereas thiamine levels can be normal in many cases, in almost all cases the MRI shows signal alterations in typical locations. A delay in the diagnosis, and therefore, in treatment leads to a worse prognosis

Introducción: La encefalopatía de Wernicke (EW) es una entidad infradiagnosticada, generalmente asociada a alcoholismo, que tiene peor pronóstico si existe retraso diagnóstico. Se presenta una serie de 8 pacientes no alcohólicos con EW y se evalúa si el retraso en el diagnóstico implica un peor pronóstico. Pacientes y métodos:Revisión retrospectiva de las historias clínicas de pacientes ingresados en dos hospitales universitarios entre 2004 y 2009 con diagnóstico de EW, excluidos aquéllos con historia de alcoholismo.Resultados: Se incluyó a 4 varones y 4 mujeres, con edades comprendidas entre los 35 y los 82 años; 7 tenían antecedentes patológicos gastrointestinales y los vómitos persistentes fueron el desencadenante en 7 casos. La encefalopatía fue la forma de inicio más frecuente (4 casos). La tríada clásica llegó a estar presente en 7 pacientes. Los niveles de tiamina fueron bajos en 3/6 y normales en 3/6 pacientes. La RM fue patológica en 7 pacientes, con hiperintensidad en diencéfalo y cuerpos mamilares (7), sustancia gris periacueductal (6), corteza (3) y cerebelo (1). Siete pacientes mejoraron tras el tratamiento con tiamina. Las secuelas fueron leves en 5 casos y graves en 3 pacientes. Todos los pacientes con un retraso diagnóstico inferior a 18 días tuvieron secuelas leves.Conclusiones: En la EW no alcohólica son frecuentes los antecedentes gastrointestinales que podrían condicionar una menor absorción de tiamina. Mientras que los niveles de tiamina pueden ser normales en muchos casos, la RM casi siempre muestra alteración de señal en localizaciones típicas. El retraso en el diagnóstico y, por tanto, en el tratamiento podría implicar un peor pronóstico (AU)

[Wernicke's encephalopathy in non-alcoholic patients: a series of 8 cases]. / Encefalopatía de Wernicke en pacientes no alcohólicos: una serie de 8 casos.

INTRODUCTION: Wernicke's encephalopathy (WE) is an underdiagnosed condition, usually associated with alcoholism, and has a worse prognosis if there is a delay in diagnosis. A series of 8 non-alcoholic patients with WE is presented and an assessment is made on whether a delay in diagnosis leads to a worse prognosis. PATIENTS AND METHODS: The clinical records of patients admitted to 2 university hospitals between 2004 and 2009 with the diagnosis of WE, excluding those with a history of alcoholism, were retrospectively reviewed. RESULTS: The study included 4 men and 4 women aged 35-82 of whom 7 had a history of gastrointestinal pathology, and persistent vomiting was the precipitating factor in 7. Encephalopathy was the most frequent onset symptom (4). The classical triad was present in seven patients. Thiamine levels were low in 3/6 and normal in 3/6 cases. MRI was abnormal in seven patients, with high signal intensity in the diencephalon and mammillary bodies (7), periaqueductal grey matter (6), cortex (3) and cerebellum (1). Seven improved with thiamine. Sequelae were mild in 6, and severe in 2 after 6-12 months of follow-up. All patients with a diagnostic delay less than 18 days had mild sequelae. CONCLUSIONS: Non-alcoholic WE frequently occurs after gastrointestinal disturbances that could result in lower thiamine absorption. Whereas thiamine levels can be normal in many cases, in almost all cases the MRI shows signal alterations in typical locations. A delay in the diagnosis, and therefore, in treatment leads to a worse prognosis.

Familial Creutzfeldt-Jakob disease with E200K mutation presenting with neurosensorial hypoacusis.

Creutzfeldt-Jakob disease (CJD) is characterised by rapidly progressive dementia, myoclonus, ataxia, visual disturbances and motor dysfunction. Most of the cases are sporadic. Only 10% to 15% are familial, and the most frequent point mutation is E200K. A 53-year-old man presented with subacute progressive bilateral hypoacusis, with tinnitus in the left ear. During the following months, his hypoacusis worsened and he progressively developed bilateral stocking-type paresthaesia and gait instability. An audiometric examination showed bilateral neurosensorial hypoacusis and nerve conduction studies showed a mixed axonal polyneuropathy. A CT scan and MRI of the brain were normal and the electroencephalography (EEG) showed non-specific changes. He died of respiratory infection 10 months after onset of symptoms. Neuropathological examination showed neuronal loss, punctate, synaptic-like deposits of protease-resistant prionic protein (PrP(RES)) in the cerebral and cerebellar cortices and auditory nuclei. This is a rare case of sporadic CJD presenting with hearing loss.

Degeneración lobular frontotemporal: estudio descriptivo de 42 pacientes / Frontotemporal lobar degeneration: a descriptive study of 42 patients

Introducción. La degeneración lobular frontotemporal(DLFT) se considera la segunda causa de demencia presenil.A pesar del gran interés que ha generado en los últimosaños existen pocos estudios publicados en España.Métodos. Estudio descriptivo retrospectivo de 42 pacientescon DLFT evaluados en nuestra unidad durante elperíodo 1996-2006.Resultados. Treinta y un pacientes presentaban la variantefrontal de DLFT (DFT), ocho afasia progresiva no fluentey tres demencia semántica. La edad media de inicio fue 56años, el retraso diagnóstico 3,5 años y la supervivencia media6,8 años. El 35 % tenían historia familiar indicativa de demencia.En los pacientes con DFT la expresión clínica fue unacombinación de trastorno de conducta y personalidad juntocon alteración del lenguaje. La resonancia magnética mostróatrofia frontal y/o temporal en el 62% de los casos y la SPECThipoperfusión frontal y/o temporal en el 75%. En cuatro pacientes(dos de ellos hermanos) se detectó la mutación P301Lde tau y en otro la mutación A303AfsX57 de progranulina(PGRN). Se realizó necropsia a cinco pacientes, encontrándoseDLFT con inclusiones ubiquitina-inmunorreactivas (DLFT-U) yenfermedad de motoneurona en dos casos, DLFT-U con inclusionesintranucleares lanceoladas en el caso con mutación dePGRN y taupatía generalizada con predominio de isoformas4R en los otros dos, ambos con la mutación P301L.Conclusiones. Nuestros resultados son similares a losde las grandes series europeas. Debe sospecharse DLFT enpacientes preseniles con trastorno predominante y precozde la conducta y/o del lenguaje. La neuroimagen apoya eldiagnóstico en la mayoría de los casos. El gran impacto sociofamiliarde la DLFT, el inicio presenil, la alta frecuencia de antecedentesfamiliares de demencia y la posibilidad de realizarestudio y consejo genético realzan su importancia clínica (AU)

Introduction. Frontotemporal lobar degeneration (FTLD)is considered to be the second cause of presenile dementia.In spite of the great interest it has generated over the lastfew years, few studies have been published in our country.Methods. A descriptive retrospective study of 42 patientswith FTLD evaluated in our unit during the period1996-2006 was performed.Results. Thirty one patients presented with frontalvariant FTLD (FTD), eigth with non-fluent progressiveaphasia and three with semantic dementia. Mean age atonset was 56 years, diagnostic delay 3.5 years and meansurvival 6.8 years. 35% had a family history suggestiveof dementia. In patients with FTD the clinical expressionwas a combination of behavioral and personality disorderstogether with language impairment. Magnetic resonanceimaging showed frontal and/or temporal atrophy in62% of cases and SPECT showed frontal and/or temporalhypoperfusion in 75%. The P301L tau mutation was detectedin four patients (two of them siblings) and theA303AfsX57 progranulin mutation in one. Necropsy wasperformed in five patients, revealing FTLD with ubiquitininmunoreactiveinclusions (FTLD-U) and motor neuron diseasein two cases, FTLD-U with «cat’s-eye» shaped intranuclearinclusions in the case with the progranulinmutation and FTLD tauopathy with predominance of 4Rtau in the remaining two, both with the P301L mutation.Conclusions. Our results are similar to those of thegreat European series. FTLD must be suspected in presenilepatients with prominent behavioral and/or languagedisorders. Neuroimaging supports the diagnosis in themajority of cases. The huge sociofamiliar impact ofFTLD, presenile onset, high frequency of familial historyof dementia and possibility of genetic study and counse-69 ling highlight its clinical relevance (AU)

[Frontotemporal lobar degeneration: a descriptive study of 42 patients]. / Degeneración lobular frontotemporal: estudio descriptivo de 42 pacientes.

INTRODUCTION: Frontotemporal lobar degeneration (FTLD) is considered to be the second cause of presenile dementia. In spite of the great interest it has generated over the last few years, few studies have been published in our country. METHODS: A descriptive retrospective study of 42 patients with FTLD evaluated in our unit during the period 1996-2006 was performed. RESULTS: Thirty one patients presented with frontal variant FTLD (FTD), eigth with non-fluent progressive aphasia and three with semantic dementia. Mean age at onset was 56 years, diagnostic delay 3.5 years and mean survival 6.8 years. 35% had a family history suggestive of dementia. In patients with FTD the clinical expression was a combination of behavioral and personality disorders together with language impairment. Magnetic resonance imaging showed frontal and/or temporal atrophy in 62% of cases and SPECT showed frontal and/or temporal hypoperfusion in 75%. The P301L tau mutation was detected in four patients (two of them siblings) and the A303AfsX57 progranulin mutation in one. Necropsy was performed in five patients, revealing FTLD with ubiquitininmunoreactive inclusions (FTLD-U) and motor neuron disease in two cases, FTLD-U with <> shaped intranuclear inclusions in the case with the progranulin mutation and FTLD tauopathy with predominance of 4R tau in the remaining two, both with the P301L mutation. CONCLUSIONS: Our results are similar to those of the great European series. FTLD must be suspected in presenile patients with prominent behavioral and/or language disorders. Neuroimaging supports the diagnosis in the majority of cases. The huge sociofamiliar impact of FTLD, presenile onset, high frequency of familial history of dementia and possibility of genetic study and counseling highlight its clinical relevance.

Prevalence of dementia subtypes in El Prat de Llobregat, Catalonia, Spain: the PRATICON study.

BACKGROUND: Studies on dementia subtypes show a wide variation in the prevalence of Alzheimer's disease (AD) and vascular dementia (VD) worldwide. However, studies reporting on Lewy body dementia (LBD) and frontotemporal dementia (FTD) are sparse. AIMS: To describe the prevalence of dementia and subtypes. METHOD: A 34% sample of 5,150 subjects aged 70 years and over in El Prat de Llobregat (Barcelona) were screened by the Mini-Mental State Examination. When scoring <24, participants were assessed to establish a diagnosis. RESULTS: There were 165 subjects diagnosed with dementia (prevalence of 9.4%). Subtypes of dementia were: AD 69.1%, VD 12.7%, LBD 9.1%, FTD 3% and secondary dementia 1.8%. Prevalences were: AD 6.5%, VD 1.2%, LBD 0.9% and FTD 0.3%. CONCLUSIONS: AD and VD were the most common type of dementia. Prevalence of dementia, AD and FTD were similar to those reported, while prevalence of VD and LBD were lower.