Diagnostic validity of the Alzheimer's disease functional assessment and change scale in mild cognitive impairment and mild to moderate Alzheimer's disease.

BACKGROUND: The Alzheimer's Disease Functional Assessment and Change Scale (ADFACS) is a functional assessment instrument widely used in clinical research. AIMS: To test the diagnostic and concurrent validity of the Spanish version of this scale and to describe the functional deficit pattern for mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia. METHODS: The ADFACS, the Interview for Deterioration in Daily Living Activities in Dementia (IDDD), and the Mini Mental State Examination (MMSE) were administered to 146 control subjects (CS) and 165 patients (67 MCI and 98 AD). Nonparametric tests were used to compare the diagnostic groups. Cronbach's α and correlations with the MMSE and the IDDD were calculated. Sensitivity, specificity and predictive values were studied. RESULTS: The ADFACS had a high internal consistency (α = 0.95). Three cutoff points of 1, 4, and 17 were provided to separate CS and MCI patients, MCI and mild AD patients, and mild AD and moderate AD patients, respectively. The ADFACS strongly correlated with functional (IDDD, 0.927) and cognitive (MMSE, 0.747) measures. A similar pattern of dysfunction, but in different grades, was found for the MCI and AD groups. CONCLUSION: The ADFACS is a reliable, valid, and sensitive instrument to assess functional abilities; it is useful in dementia assessment for elderly populations.

Evaluación de la conveniencia del cambio de vía de administración de rivastigmina en pacientes con enfermedad de Alzheimer / Evaluation of the convenience of changing the rivastigmine administration route in patients with Alzheimer disease

Introducción: Los parches transdérmicos de rivastigmina para el tratamiento de la enfermedad de Alzheimer presentan posibles beneficios respecto a las cápsulas por su absorción sostenida a través de la piel, buena tolerabilidad local y reducción de problemas gastrointestinales. Objetivo: Evaluar la tolerabilidad gastrointestinal y cutánea y la necesidad de titulación para obtener dosis óptimas de rivastigmina transdérmica en pacientes con Alzheimer previamente tratados oralmente. Pacientes y métodos: Se llevó a cabo un estudio multicéntrico, aleatorizado y abierto que incluyó a 142 pacientes con Alzheimer de leve a moderado y previamente tratados con rivastigmina oral (6-12 mg/día). La muestra fue aleatorizada a: continuar con tratamiento oral durante 3 meses (n = 49); cambio al parche sin titulación (9,5 mg/día durante 3 meses, n = 47) o cambio al parche con titulación (4,6 mg/día por 1 mes seguido de 9,5 mg/día por 2 meses, n = 43). Resultados: La incidencia de efectos adversos gastrointestinales fue del 6,1% en el grupo tratado oralmente y del 4,2% en el grupo tratado con parche sin titulación (p = 0,908). La tolerabilidad cutánea fue buena (n = 15, 16,7%), sin observarse acontecimientos adversos graves. El tratamiento con parche fue considerado muy fácil de utilizar por el 72% de pacientes en comparación con el 30% con tratamiento oral (p = 0,0005). El 60% se mostraron satisfechos con el parche, mientras que únicamente un 14% se declaró satisfecho con las cápsulas (p < 0,0001). Conclusiones: Los parches de rivastigmina presentan un perfil de tolerabilidad similar a las cápsulas y se asocian con una mayor satisfacción de los pacientes (AU)

Introduction: Rivastigmine transdermal patches for the treatment of Alzheimer’s disease (AD) have potential benefits compared to capsules because of their sustained absorption through the skin, good local tolerability and reduction of gastrointestinal problems. Purpose: To assess gastrointestinal and skin tolerability and the need for optimal dose titration of rivastigmine transdermal patches in Alzheimer’s disease patients previously treated with oral rivastigmine. Patients and methods: A multicenter, randomized, open-label study including patients with mild to moderate AD (DSM-IV) previously treated with rivastigmine capsules (6-12 mg/day) was conducted. Patients were randomized to: continue with capsules for 3 months (n = 49) or switch to rivastigmine patch without titration (9.5 mg/day for 3 months; n = 48), or switch to rivastigmine patch with titration (4.6 mg/day for 1 month followed by 9.5 mg/day for 2 months, n = 43). Results: Incidence of gastrointestinal adverse events was 6.1% in the group treated orally and 4.2% in the group treated with non-titrated patches (P = .908). Skin tolerability was good (n = 15, 16.7%) without any serious adverse events registered. Patch treatment was considered very easy to use by 72% of patients compared with 30% in the group with oral treatment (P = .0005). 60% of patients were satisfied with the patch, while only 14% were satisfied with capsules (P < .0001). Conclusions: Rivastigmine patches have a tolerability profile similar to that shown by capsules, but are associated with greater patient satisfaction (AU)

Evaluation of the convenience of changing the rivastigmine administration route in patients with Alzheimer disease.

INTRODUCTION: Rivastigmine transdermal patches for the treatment of Alzheimer's disease (AD) have potential benefits compared to capsules because of their sustained absorption through the skin, good local tolerability and reduction of gastrointestinal problems. PURPOSE: To assess gastrointestinal and skin tolerability and the need for optimal dose titration of rivastigmine transdermal patches in Alzheimer's disease patients previously treated with oral rivastigmine. PATIENTS AND METHODS: A multicenter, randomized, open-label study including patients with mild to moderate AD (DSM-IV) previously treated with rivastigmine capsules (6-12 mg/day) was conducted. Patients were randomized to: continue with capsules for 3 months (n=49) or switch to rivastigmine patch without titration (9.5mg/day for 3 months; n=48), or switch to rivastigmine patch with titration (4.6 mg/day for 1 month followed by 9.5mg/day for 2 months, n=43). RESULTS: Incidence of gastrointestinal adverse events was 6.1% in the group treated orally and 4.2% in the group treated with non-titrated patches (P=.908). Skin tolerability was good (n=15, 16.7%) without any serious adverse events registered. Patch treatment was considered very easy to use by 72% of patients compared with 30% in the group with oral treatment (P=.0005). 60% of patients were satisfied with the patch, while only 14% were satisfied with capsules (P<.0001). CONCLUSIONS: Rivastigmine patches have a tolerability profile similar to that shown by capsules, but are associated with greater patient satisfaction.

Síndrome de Weber de origen isquémico / Weber´s síndrome of ischemic origin

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[Transient ischemic attack]. / Accidente isquémico transitorio.

During recent years a new definition for transient ischemic attack (TIA) has been proposed. This has been based on the advances in neuroimaging techniques and because it has been observed that most TIA last only a few minutes. Brain damage must be ruled out and TIA duration can be no longer than one hour. TIA increases the chance of stroke or vascular episodes, above all during the first days and of other vascular diseases such as ischemic heart disease. It is a prevalent condition which must be considered as an emergency even though the patient is usually asymptomatic. For the initial evaluation, routine blood test, electrocardiogram, chest X-ray, brain computed tomography and extra and intracranial ultrasonography study must be performed. Treatment is based on the control of risk factors and antithrombotic therapy.

Accidente isquémico transitorio / Transient ischemic attack

En los últimos años, al evidenciarse que la mayoría de los accidentes isquémicos transitorios (AIT) duran pocos minutos y favorecido por el desarrollo de técnicas de neuroimagen, se ha propuesto una nueva definición para esta patología que es la vigente en la actualidad. Limita la duración del episodio a un máximo de una hora y exige descartar la presencia de una lesión cerebral. El AIT aumenta el riesgo de sufrir ictus, sobre todo los primeros días, y otras patologías vasculares como la cardiopatía isquémica. Es una patología prevalente que debe considerarse una urgencia médica y no como un proceso benigno, a pesar de que al examinar al paciente suele estar asintomático. En su evaluación inicial debe realizarse un estudio básico que incluye analítica, radiografía de tórax, electrocardiograma, neuroimagen y ultrasonografía de arterias cervicales e intracraneales. El tratamiento se basa en controlar los factores de riesgo vascular y terapia antitrombótica (AU)

During recent years a new definition for transient ischemic attack (TIA) has been proposed. This has been based on the advances in neuroimaging techniques and because it has been observed that most TIA last only a few minutes. Brain damage must be ruled out and TIA duration can be no longer than one hour. TIA increases the chance of stroke or vascular episodes, above all during the first days and of other vascular diseases such as ischemic heart disease. It is a prevalent condition which must be considered as an emergency even though the patient is usually asymptomatic. For the initial evaluation, routine blood test, electrocardiogram, chest X-ray, brain computed tomography and extra and intracranial ultrasonography study must be performed. Treatment is based on the control of risk factors and antithrombotic therapy (AU)

Medicamentos transdérmicos en neurología / Transdermal drugs in neurology

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[Anticonvulsant hypersensitivity syndrome with severe repercussions in the skin and kidneys due to carbamazepine]. / Síndrome de hipersensibilidad por antiepilépticos con repercusión cutánea y renal grave por carbamacepina.

INTRODUCTION: Anticonvulsant hypersensitivity syndrome (AHS) is characterised by fever, skin rashes and involvement of the internal organs. Owing to the low frequency with which it appears and its high clinical heterogeneity, it is not always suspected. Moreover, the symptoms often overlap with those of a vasculitis or of an infection. The most commonly associated antiepileptic drugs (AED) are the aromatic agents. We report the case of a female patient who developed AHS with several different AED and presented an especially severe kidney and skin disorder due to carbamazepine (CBZ). CASE REPORT: We describe the case of a 26-year-old woman who, after being diagnosed as suffering from secondarily generalised partial seizures, began treatment with 200 mg/12 hours CBZ. A few weeks later, she developed itchy skins lesions compatible with exanthematic pustulosis, together with acute kidney failure requiring haemodialysis. A biopsy study of the kidney revealed immunoallergic tubulointerstitial nephropathy, which is a lesion that has only very occasionally been reported in relation to CBZ therapy. The patient also presented a moderate rise in the level of transaminases and leukocytosis with eosinophilia. She was discharged from hospital without AED but suffered new seizures and was treated with phenytoin and, later, with valproic acid, both as monotherapy. With these drugs she developed AHS consisting in fever, rashes, eosinophilia and subclinical hepatitis. In epicutaneous tests with anticonvulsants, the three AED presented a positive reading, as well as others. The patient was treated with tiagabine, and there were no further hypersensitivity phenomena and a good control of seizures was achieved. CONCLUSIONS: AHS is an infrequent, but potentially serious, clinical entity and must therefore be suspected in patients taking AED who develop fever, rashes or disorders affecting the internal organs.

Síndrome de hipersensibilidad por antiepilépticos con repercusión cutánea y renal grave por carbamacepina / Anticonvulsant hypersensitivity syndrome with severe repercussions in the skin and kidneys due to carbamazepine

Introducción. El síndrome de hipersensibilidad por antiepilépticos (SHA) se caracteriza por fiebre, exantema y afectación visceral. Su baja frecuencia, junto con su gran heterogeneidad clínica, hace que no siempre se sospeche. Además, los síntomas se superponen frecuentemente a una vasculitis o a un cuadro infeccioso. Los fármacos antiepilépticos (FAE) asociados con mayor frecuencia son los aromáticos. Presentamos una paciente que desarrolló un SHA con varios FAE, en la cual fue especialmente grave la afectación renal y cutánea por carbamacepina (CBZ). Caso clínico. Se trata de una mujer de 26 años quien, tras el diagnóstico de crisis parcial secundariamente generalizada, comenzó un tratamiento con 200 mg de CBZ cada 12 horas. Pocas semanas más tarde, desarrolló lesiones cutáneas pruriginosas compatibles con pustulosis exantemática, junto con fallo renal agudo por el que precisó hemodiálisis. La biopsia renal mostró nefropatía tubulointersticial inmunoalérgica. Esta lesión se ha descrito en escasas ocasiones en relación con el tratamiento con CBZ. Presentaba una ligera elevación de las transaminasas y leucocitosis con eosinofilia. Se le dio de alta sin FAE, pero sufrió nuevas crisis, por lo que se trató con fenitoína y, posteriormente, ácido valproico, ambos en monoterapia; desarrolló con dichos fármacos un SHA consistente en fiebre, exantema, eosinofilia y hepatitis subclínica. En las pruebas epicutáneas con antiepilépticos, presentaron una lectura positiva los tres FAE, además de otros. Se trató con tiagabina, con la que no se presentaron nuevos fenómenos de hipersensibilidad y permitió un buen control de las crisis. Conclusión. El SHA es una entidad infrecuente, pero potencialmente grave, por lo que es imprescindible sospecharlo en pacientes con FAE que desarrollen fiebre, exantema y/o afectación visceral (AU)

Introduction. Anticonvulsant hypersensitivity syndrome (AHS) is characterised by fever, skin rashes and involvement of the internal organs. Owing to the low frequency with which it appears and its high clinical heterogeneity, it is not always suspected. Moreover, the symptoms often overlap with those of a vasculitis or of an infection. The most commonly associated antiepileptic drugs (AED) are the aromatic agents. We report the case of a female patient who developed AHS with several different AED and presented an especially severe kidney and skin disorder due to carbamazepine (CBZ). Case report. We describe the case of a 26-year-old woman who, after being diagnosed as suffering from secondarily generalised partial seizures, began treatment with 200 mg/12 hours CBZ. A few weeks later, she developed itchy skins lesions compatible with exanthematic pustulosis, together with acute kidney failure requiring haemodialysis. A biopsy study of the kidney revealed immunoallergic tubulointerstitial nephropathy, which is a lesion that has only very occasionally been reported in relation to CBZ therapy. The patient also presented a moderate rise in the level of transaminases and leukocytosis with eosinophilia. She was discharged from hospital without AED but suffered new seizures and was treated with phenytoin and, later, with valproic acid, both as monotherapy. With these drugs she developed AHS consisting in fever, rashes, eosinophilia and subclinical hepatitis. In epicutaneous tests with anticonvulsants, the three AED presented a positive reading, as well as others. The patient was treated with tiagabine, and there were no further hypersensitivity phenomena and a good control of seizures was achieved. Conclusions. AHS is an infrequent, but potentially serious, clinical entity and must therefore be suspected in patients taking AED who develop fever, rashes or disorders affecting the internal organs (AU)

[Correlation between reaction time and bradykinesia in Huntington's disease]. / Correlación entre el tiempo de reacción y la bradicinesia en la enfermedad de Huntington.

BACKGROUND: Bradykinesia is the clinical feature of Huntington's disease most closely related to functional discapacity and stage, probably as a consequence of spreading of neuronal injury. The aim of the present article is to verify whether a choice reaction time could be considered an estimate measurement of clinical bradykinesia, and its possible relationships with other evolutive parameters such as functional discapacity, clinical stage and prefrontal executive dysfunction. METHODS: Fifteen patients were studied (9 in advanced stage and 6 initials), equal number of controls and 3 asymptomatic gene carriers. We used clinical bradykinesia and functional capacity scales, an extensive prefrontal battery and a computerized paradigm of reaction time. RESULTS: Clinical bradykinesia and reaction time are closely related. The associations between reaction time with those parameters indicatives of prefrontal dysfunction, functional discapacity and clinical stage are closer and more significatives than those that could be established with clinical bradykinesia. CONCLUSIONS: Reaction time is an objective measurement of global motor slowness that allow us assigning each subject to a specific stage, and avoid possible errors derived from interobserver bias in clinical scales.

Correlación entre el tiempo de reacción y la bradicinesia en la enfermedad de Huntington / Correlation between reaction time and bradykinesia in Huntington's disease

FUNDAMENTO: La bradicinesia es el rasgo clínico de la enfermedad de Huntington más estrechamente asociado con la discapacidad funcional y el estadio evolutivo, probablemente como consecuencia de la extensión del daño neuronaI. El objetivo del presente artículo es comprobar si el tiempo de reacción de elección puede ser considerado una medida estimativa de la bradicinesia clínica, y su posible relación con otros parámetros evolutivos, como la discapacidad funcional, el estadio clínico y la disfunción ejecutiva prefrontal. MÉTODOS: Se ha estudiado a 15 pacientes (nueve en estudio avanzado y seis iniciales), el mismo número de controles y 3 sujetos presintomáticos. Para ello se han empleado escalas clínicas de bradicinesia y de capacidad funcional, una extensa batería prefrontal y un paradigma computarizado de tiempo de reacción. RESULTADOS: La bradicinesia clínica y el tiempo de reacción guardan una alta correlación. Las asociaciones del tiempo de reacción con los parámetros indicativos de la disfunción prefrontal, la discapacidad funcional y el estadio clínico son más estrechas y significativas que las que se pueden establecer con la bradicinesia clínica. CONCLUSIONES: El tiempo de reacción constituye una medida objetiva de la lentitud motora global que permite asignar un sujeto a un determinado estadio evolutivo, y corregir los posibles errores derivados de los sesgos del observador en las escalas clínicas (AU)

BACKGROUND: Bradykinesia is the clinical feature of Huntington's disease most closely related to functional discapacity and stage, probably as a consequence of spreading of neuronal injury. The aim of the present article is to verify whether a choice reaction time could be considered an estimate measurement of clinical bradykinesia, and its possible relationships with other evolutive parameters such as functional discapacity, clinical stage and prefrontal executive dysfunction. METHODS: Fifteen patients were studied (9 in advanced stage and 6 initials), equal number of controls and 3 asymptomatic gene carriers. We used clinical bradykinesia and functional capacity scales, an extensive prefrontal battery and a computerized paradigm of reaction time. RESULTS: Clinical bradykinesia and reaction time are closely related. The associations between reaction time with those parameters indicatives of prefrontal dysfunction, functional discapacity and clinical stage are closer and more significatives than those that could be established with clinical bradykinesia. CONCLUSIONS: Reaction time is an objective measurement of global motor slowness that allow us assigning each subject to a specific stage, and avoid possible errors derived from interobserver bias in clinical scales (AU)

Amnesia topográfica progresiva primaria: ¿una nueva entidad? / Primary progressive topographical amnesia: a new entity?

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[The treatment of myasthenia gravis by video thoracoscopic thymectomy. The technic and the initial results]. / Tratamiento de la miastenia grave mediante timectomía videotoracoscópica. Técnica y resultados iniciales.

The primary role of thymectomy for the treatment of myasthenia gravis is currently undisputed. Traditionally, the approach of choice has been sternotomy, although a transcervical route has also been advocated because of its lower rate of associated morbidity. Our department performed thymectomy using a video-assisted thoracoscopic technique in 7 patients (2 men and 5 women) between March 1993 and October 1995. The patients' mean age was 43.4 years (range 20 to 66 years). Complications were few, consisting of 2 cases of pneumothorax due to contralateral opening of the pleura, resolved by pleural drainage. No deaths occurred. Clinical results over periods of observation ranging from 14 to 44 months were excellent in 2 cases of complete remission; good in 3 patients with considerable reduction in drug requirements; and fair in 2 patients who continued to need the same doses of medication throughout the 14 months after thymectomy. The technique we propose is less aggressive than mid-sternotomy, offering incontrovertible advantages and leading to faster. No patient required assisted ventilation for longer than 4 hours and the maximum time spent in the intensive care unit was 24 hours. We therefore suggest that thymectomy to treat myasthenia gravis be performed by thoracoscopy.

[Sensitivity and efficiency of intrathecal IgG secretion in multiple sclerosis. Comparison of several indices and formulas using pre-established values of specificity]. / Sensibilidad y eficiencia de la secreción intratecal de IgG en la esclerosis múltiple. Comparación de los distintos índices y fórmulas utilizando valores de especificidad predeterminados.

To furnish greater specificity in the analysis of cerebrospinal fluid from patients suspected of having multiple sclerosis, we studied the sensitivity and efficiency of indices and formulas used to calculate intrathecal IgG synthesis in a group of 49 patients with clinically defined multiple sclerosis, using cutoff values based on preestablished levels of specificity (75 and 90%), and compared the findings to those for a control group of patients with other neurological diseases. The best results were obtained with the indices and formulas based on computer models of brain-blood barrier function set forth most recently, namely Reiber's formula and Ohman's index, which had the highest specificity with the least loss of sensitivity.

Memory and learning disturbances in multiple sclerosis. MRI lesions and neuropsychological correlation.

Thirty-five patients with definite multiple sclerosis (MS) were studied. They underwent neuropsychological testing and magnetic resonance imaging (MRI). The MRI findings at different brain areas levels were compared with the neuropsychological findings. A quantitative system was used to measure MRI-MS lesions. In this series, a positive correlation was established between memory and learning disturbances measured by Battery 144, and the lesions measured by MRI (total, hemispheric and, particularly, periventricular lesions). MRI can detect MS lesions, and this study shows that a correlation between MRI and neuropsychological findings is possible if quantitative methods are used to distinguish different MS involvement areas in relation to neuropsychological tasks. These findings suggest that hemispheric lesions in MS produce cognitive disturbances and MRI could be a useful tool in predicting memory and learning impairment.