Clinical and neuroimaging characteristics of 14 patients with prionopathy: a descriptive study.

INTRODUCTION: Prionopathy is the cause of 62% of the rapidly progressive dementias (RPD) in which a definitive diagnosis is reached. The variability of symptoms and signs exhibited by the patients, as well as its different presentation, sometimes makes an early diagnosis difficult. METHODS: Patients withdiagnosis of definite or probable prionopathy during the period 1999-2012 at our hospital were retrospectively reviewed.The clinical features and the results of the complementary tests (14-3-3 protein, EEG, MRI, FDG-PET, and genetic analysis) were evaluated in order to identify some factors that may enable an earlier diagnosis to be made. RESULTS: A total of 14 patients are described: 6 with definite sporadic Creutzfeldt-Jakob (sCJD) disease, 3 with probable sCJD, 4 with fatal familial insomnia, and 1 with the new variant. The median age at diagnosis was 54 years old. The mean survival was 9.5 months. Mood disorder was the most common feature, followed by instability and cognitive impairment. 14-3-3 protein content in the cerebrospinal fluid was positive in 7 of 11 patients, and the EEG showed typical signs in 2 of 12 patients. Neuroimaging (FDG-PET, MRI) studies suggested the diagnosis in 13 of the 14 patients included. CONCLUSIONS: Most patients presenting with RPD suffer from a prion disease. In our series the most useful complementary tests were MRI and FDG-PET, being positive in 13 of the 14 patients studied.

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.

Seizure prophylaxis in meningiomas: a systematic review and meta-analysis.

INTRODUCTION: No formal indication currently exists for seizure prophylaxis in neurosurgical oncology patients. Neither have specific recommendations been made on the use of antiepileptic drugs (AED) in seizure-free patients with meningiomas scheduled for surgery. AEDs are generally prescribed on a discretionary basis, taking into consideration a range of clinical and radiological risk factors. We present a systematic review and meta-analysis exploring the effectiveness of antiepileptic prophylaxis in patients with meningioma and no history of seizures. METHODS: We performed a systematic review of the PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase, and clinicaltrials.gov databases. Of a total of 4368 studies initially identified, 12 were selected for extraction of data and qualitative analysis. Based on the clinical data presented, we were only able to include 6 studies in the meta-analysis. We performed heterogeneity studies, calculated a combined odds ratio, evaluated publication bias, and conducted a sensitivity analysis. RESULTS: AED prophylaxis in patients with meningioma and no history of seizures did not significantly reduce the incidence of post-operative seizures in comparison to controls (Mantel-Haenszel combined odds ratio, random effects model: 1.26 [95% confidence interval, 0.60-2.78]; 2041 patients). However, we are unable to establish a robust recommendation against this treatment due to the lack of prospective studies, the presence of selection bias in the studies reviewed, the likelihood of underestimation of seizure frequency during follow-up, and the strong influence of one study on the overall effect. CONCLUSIONS: Despite the limitations of this review, the results of the meta-analysis do not support the routine use of seizure prophylaxis in patients with meningioma and no history of seizures.

["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.

Seizure prophylaxis in meningiomas: A systematic review and meta-analysis. / Profilaxis antiepiléptica en meningiomas: revisión sistemática y metaanálisis.

INTRODUCTION: No formal indication currently exists for seizure prophylaxis in neurosurgical oncology patients. Neither have specific recommendations been made on the use of antiepileptic drugs (AED) in seizure-free patients with meningiomas scheduled for surgery. AEDs are generally prescribed on a discretionary basis, taking into consideration a range of clinical and radiological risk factors. We present a systematic review and meta-analysis exploring the effectiveness of antiepileptic prophylaxis in patients with meningioma and no history of seizures. METHODS: We performed a systematic review of the PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase, and clinicaltrials.gov databases. Of a total of 4368 studies initially identified, 12 were selected for extraction of data and qualitative analysis. Based on the clinical data presented, we were only able to include 6 studies in the meta-analysis. We performed heterogeneity studies, calculated a combined odds ratio, evaluated publication bias, and conducted a sensitivity analysis. RESULTS: AED prophylaxis in patients with meningioma and no history of seizures did not significantly reduce the incidence of post-operative seizures in comparison to controls (Mantel-Haenszel combined odds ratio, random effects model: 1.26 [95% confidence interval, 0.60-2.78]; 2041 patients). However, we are unable to establish a robust recommendation against this treatment due to the lack of prospective studies, the presence of selection bias in the studies reviewed, the likelihood of underestimation of seizure frequency during follow-up, and the strong influence of one study on the overall effect. CONCLUSIONS: Despite the limitations of this review, the results of the meta-analysis do not support the routine use of seizure prophylaxis in patients with meningioma and no history of seizures.

Globular glial tauopathy caused by MAPT P301T mutation: clinical and neuropathological findings.

OBJECTIVE: To describe the clinical, biochemical, and neuropathological findings of an autosomal dominant globular glial tauopathy caused by the P301T mutation at the MAPT gene. METHODS: Five patients from two unrelated pedigrees underwent clinical evaluation. Genetic analysis, brain pathological examination, and biochemical analysis of tau were performed. RESULTS: The patients studied were 3 men and 2 women with a mean age at onset of 52.2 years and mean disease duration of 5.2 years. Three patients presented a corticobasal syndrome, one patient an asymmetric pyramidal syndrome compatible with primary lateral sclerosis, and one patient a frontotemporal dementia. In both pedigrees (4 patients) Sanger sequencing showed the p.P301T mutation in exon 10 of the MAPT gene. Neuropathological findings consisted of atrophy of frontal and temporal lobes with marked spongiosis and astrogliosis, and abundant phosphorylated tau protein deposits in the frontal and temporal cortex, limbic area, basal ganglia, and brain stem. The most striking finding was the presence of oligodendroglial 4R phospho-tau globular positive inclusions in the white matter and cortex. Globose-type neurofibrillary neuronal tangles, and in particular astrocytic globular inclusions and coarse tufts, were present in the grey matter. Biochemical analysis of sarkosyl-insoluble fractions revealed two tau bands of 64 and 68 kDa and case-dependent bands of lower molecular weight. CONCLUSION: This is the first pathological and biochemical study of the MAPT p.P301T mutation showing variable clinical manifestation and neuropathological phenotype of globular glial tauopathy not only among different families but also within families.

Profilaxis antiepiléptica en meningiomas: revisión sistemática y metaanálisis / Seizure prophylaxis in meningiomas: A systematic review and meta-analysis

Introducción: En la actualidad, no existe una indicación formal de profilaxis anticomicial en neurocirugía oncológica. Tampoco existen recomendaciones específicas sobre el uso de fármacos antiepilépticos (FAE) en pacientes portadores de meningiomas y libres de crisis que van a ser intervenidos. En general, se prescriben FAE de forma discrecional, teniendo en cuenta diversos factores de riesgo clínico-radiológicos. Presentamos una revisión sistemática y metaanálisis sobre la efectividad de la profilaxis anticomicial en meningiomas sin historia previa de crisis. Métodos: Se realizó una búsqueda sistemática en las bases de datos PubMed/MEDLINE, Cochrane Central Register of Controlled trials, Embase y clinicaltrials.gov. De los 4.368 estudios inicialmente identificados, finalmente se incluyeron 12 para la extracción de datos y análisis cualitativo. Los datos clínicos permitieron incluir únicamente 6 estudios en el metaanálisis. Se realizaron estudios de heterogeneidad, cálculo de OR combinada, evaluación del sesgo de publicación y análisis de sensibilidad. Resultados: La profilaxis con FAE en meningiomas sin crisis previas no redujo de forma significativa la incidencia de crisis postoperatorias respecto a los controles (OR combinada de Mantle-Haenszel, efectos aleatorios, de 1,26, IC del 95%, 0,60-2,78, sobre 2.041 pacientes). Sin embargo, la ausencia de estudios prospectivos, la presencia de sesgo de selección en los estudios, una probable infraestimación del número de crisis durante el seguimiento y la influencia marcada de un estudio sobre el efecto global impiden establecer una recomendación sólida en contra de la profilaxis anticomicial. Conclusiones: Dentro de las limitaciones de esta revisión, los resultados del metaanálisis no apoyan el uso rutinario de la profilaxis antiepiléptica en pacientes con meningiomas sin historia previa de crisis.(AU)

Introduction: No formal indication currently exists for seizure prophylaxis in neurosurgical oncology patients. Neither have specific recommendations been made on the use of antiepileptic drugs (AED) in seizure-free patients with meningiomas scheduled for surgery. AEDs are generally prescribed on a discretionary basis, taking into consideration a range of clinical and radiological risk factors. We present a systematic review and meta-analysis exploring the effectiveness of antiepileptic prophylaxis in patients with meningioma and no history of seizures. Methods: We performed a systematic review of the PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase, and clinicaltrials.gov databases. Of a total of 4368 studies initially identified, 12 were selected for extraction of data and qualitative analysis. Based on the clinical data presented, we were only able to include 6 studies in the meta-analysis. We performed heterogeneity studies, calculated a combined odds ratio, evaluated publication bias, and conducted a sensitivity analysis. Results: AED prophylaxis in patients with meningioma and no history of seizures did not significantly reduce the incidence of post-operative seizures in comparison to controls (Mantel-Haenszel combined odds ratio, random effects model: 1.26 [95% confidence interval, 0.60-2.78]; 2041 patients). However, we are unable to establish a robust recommendation against this treatment due to the lack of prospective studies, the presence of selection bias in the studies reviewed, the likelihood of underestimation of seizure frequency during follow-up, and the strong influence of one study on the overall effect. Conclusions: Despite the limitations of this review, the results of the meta-analysis do not support the routine use of seizure prophylaxis in patients with meningioma and no history of seizures.(AU)

Fused in Sarcoma (FUS) gene mutations are not a frequent cause of essential tremor in Europeans.

FUS/TLS (denoting fused in sarcoma/translocated in liposarcoma [MIM 137070]) codifies an RNA binding protein. Mutations in this gene cause amyotrophic lateral sclerosis (ALS; MIM 608030). Essential tremor (ET [MIM 190300]) is the most frequent movement disorder. Despite its strong familiar aggregation, recently a whole exome sequencing study has identified FUS mutations as a cause of familial ET. To determine whether mutations in FUS are also common in other populations, we sequenced FUS gene in 178 unrelated Spanish subjects with ET. We detected only an intronic single-pair nucleotide deletion (c.1293-37delC), which was predicted to affect mRNA splicing. However, leukocyte mRNA analysis showed no changes in FUS expression. In conclusion, coding or splicing FUS mutations are not a frequent cause of ET in the Spanish population.

Descripción de una serie de pacientes con diagnóstico de enfermedad priónica / Clinical and neuroimaging characteristics of 14 patients with prionopathy: A descriptive study

Introducción: Las prionopatías representan hasta el 62% de los casos de demencia rápidamente progresiva (DRP) en los que se alcanza un diagnóstico definitivo. La variabilidad de los síntomas y signos iniciales y las diferencias en su evolución dificultan el diagnóstico precoz. Métodos: Estudio retrospectivo en el que se incluye a pacientes con prionopatía probable o definitiva, que acudieron a la consulta de Neurología de nuestro centro durante el periodo 1999-2012. Se describen las características clínicas y los resultados de las exploraciones complementarias (proteína 14-3-3, EEG, RM, PET-FDG y análisis genético), con la finalidad de identificar qué marcadores permiten un diagnóstico precoz. Resultados: Se describe a 14 pacientes: 6 con enfermedad de Creutzfeldt-Jakob esporádica (ECJe) definitiva, 3 con ECJe probable, 4 con insomnio familiar fatal y uno con la nueva variante de la enfermedad de Creutzfeldt-Jakob. La mediana de edad al diagnóstico fue de 54 años y la mediana de supervivencia de 9,5 meses. El trastorno del ánimo fue el síntoma inicial más frecuente, seguido de inestabilidad de la marcha y deterioro cognitivo. La proteína 14-3-3 fue positiva en el líquido cefalorraquídeo en 7 de 11 pacientes y el EEG mostró signos típicos en 2 de 12 pacientes explorados. El estudio de neuroimagen mostró alteraciones en 13 de los 14 pacientes. Conclusiones: Además de la DRP, el trastorno conductual y de la marcha son síntomas iniciales frecuentes en las prionopatías. En nuestra serie, las pruebas complementarias más útiles para apoyar el diagnóstico fueron la RM y la PET-FDG

Introduction: Prionopathy is the cause of 62% of the rapidly progressive dementias (RPD) in which a definitive diagnosis is reached. The variability of symptoms and signs exhibited by the patients, as well as its different presentation, sometimes makes an early diagnosis difficult. Methods: Patients withdiagnosis of definite or probable prionopathy during the period 1999-2012 at our hospital were retrospectively reviewed.The clinical features and the results of the complementary tests (14-3-3 protein, EEG, MRI, FDG-PET, and genetic analysis) were evaluated in order to identify some factors that may enable an earlier diagnosis to be made. Results: A total of 14 patients are described: 6 with definite sporadic Creutzfeldt-Jakob (sCJD) disease, 3 with probable sCJD, 4 with fatal familial insomnia, and 1 with the new variant. The median age at diagnosis was 54 years old. The mean survival was 9.5 months. Mood disorder was the most common feature, followed by instability and cognitive impairment. 14-3-3 protein content in the cerebrospinal fluid was positive in 7 of 11 patients, and the EEG showed typical signs in 2 of 12 patients. Neuroimaging (FDG-PET, MRI) studies suggested the diagnosis in 13 of the 14 patients included. Conclusions: Most patients presenting with RPD suffer from a prion disease. In our series the most useful complementary tests were MRI and FDG-PET, being positive in 13 of the 14 patients studied

Neuroimagen estructural y funcional en las enfermedades priónicas humanas / Structural and functional neuroimaging in human prion diseases

Introducción: Las prionopatías son un conjunto de enfermedades neurodegenerativas producidas por el acúmulo de una isoforma anormal de la proteína priónica celular (PrPc). Se clasifican en adquiridas, hereditarias y esporádicas. Aunque son muchas las características clí- nicas, evolutivas y anatomopatológicas que las diferencian, todas ellas tienen en común un curso desfavorable y un pronóstico fatal. Desarrollo: Si bien algunos tipos como el kuru, prácticamente han desaparecido, otras formas como la variante de la enfermedad de Creutzfeldt-Jakob (vECJ) o la iatrogénica siguen vigentes y suponen un reto en la medicina actual. El diagnóstico de certeza se realiza postmortem, salvo en el caso de la vECJ en la que la biopsia amigdalar puede detectar el 100% de los casos. Ello ha supuesto que se definan criterios diagnósticos en función de una probabilidad estadística, que precisa la realización de exámenes complementarios tales como el estudio electroencefalográ- fico y la detección de la proteína 14-3-3 en el líquido cefalorraquídeo (LCR). Solamente la vECJ ha llegado a incluir en los criterios diagnósticos de la OMS el «signo del pulvinar» en resonancia magnética cerebral(RM). En este artículo se revisan los hallazgos de neuroimagen que han sido descritos para cada tipo de prionopatía en pacientes con un diagnóstico de certeza. Conclusiones: La finalidad es definir la utilidad de estas pruebas complementarias como una herramienta de apoyo para el diagnóstico de este conjunto de enfermedades neurodegenerativas (AU)

Introduction: Prion diseases are neurodegenerative disorders resulting from the accumulation of a misfolded isoform ofthe 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) orthe 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 presentreview 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 (AU)

«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)