Inherited SCN1A missense mutation in a Dravet Syndrome family: Neuropathological correlation, family screening and implications for adult carriers.

INTRODUCTION: Neuropathological findings in Dravet Syndrome (DS) are scarce, especially in adult patients, and often do not have a genetic confirmation. Additionally, the missense SCN1A pathogenic variant found has only been described as de novo mutation in previous literature. METHODS: We describe the clinical and genetic findings of a family (including three sisters and his father), using Sanger sequencing in the three sisters and in postmortem brain tissue in the father. The present study also shows the neuropathological findings of the father. RESULTS: Despite the presence of long term drug resistant epilepsy, starting with febrile seizures between 6 and 12 months of age, and intellectual disability (ID), the three sisters were diagnosed with DS in adulthood, identifying a missense SCN1A pathogenic variant in exon 20, previously described as de novo -p.Gly1332Glu (c .3995 G>A). The oldest sister had the most severe phenotype, with severe ID and wheel chair dependency, passing away at 52. The other two sisters had a moderate phenotype, being at the present seizure free, but with significant comorbidities, such as crouch gait and parkinsonism. Several relatives from the paternal path (including the father) presented epilepsy, but without ID. The father was diagnosed with Alzheimer´s Disease (AD) at 60, and because he donated his brain, the same variant was confirmed in postmortem study. Neither the MRI nor the histopathology showed specific morphological changes for DS, consistent with previous studies. CONCLUSIONS: This work supports the need to review the clinical and genetic spectra of DS in adults with epilepsy and unknown ID. The clinical consequences of this syndrome seem to have a functional rather than a structural basis, supported by the absence of specific neuropathological findings.

[(123)I-MIBG myocardial scintigraphy in the diagnosis of Lewy body dementia]. / Gammagrafía miocárdica con I-MIBG en el diagnóstico de la demencia con cuerpos de Lewy.

INTRODUCTION: Lewy body dementia (LBD) is the second most common cause of neurodegenerative dementia after Alzheimer's disease (AD). A cardiac post-ganglionic sympathetic denervation has been described in this condition which can be quantified by MIBG (metaiodobenzylguanidine) myocardial scintigraphy. The aim of our work was to retrospectively evaluate cardiac MIBG uptake (expressed as the heart-to-mediastinum ratio at 4h (HMR) in patients with suspected LBD, and to examine its relationship with clinical and para-clinical data. MATERIAL AND METHODS: A total of 77 patients with clinical suspicion of LBD evaluated at our centre between September 2005 and June 2008 to whom a MIBG myocardial scintigraphy has been performed were retrospectively reviewed. International Consensus Criteria of LBD were applied to divide the sample into probable LBD, possible LBD and non-LBD. HMR values and their relationships with clinical and neuropsychological data were analysed. A subgroup of patients had FP-CIT (fluoropropyl-carbomethoxy-3ß-4-iodophenyltropane) SPECT as a part of the evaluation. RESULTS: Mean HMR values were significantly lower in probable LBD group than in possible LBD and non-LBD groups. Low HMR values were associated only with reduced FP-CIT uptake in the striatum, but not with any clinical or neuropsychological item. CONCLUSIONS: Low MIBG myocardial scintigraphy uptake is a robust measure in LBD, and it is not largely affected by medical conditions, or by the stage of the disease. In LBD reduced MIBG myocardial uptake is associated with nigrostriatal degeneration.

Gammagrafía miocárdica con 123I-MIBG en el diagnóstico de la demencia con cuerpos de Lewy / 123I-MIBG myocardial scintigraphy in the diagnosis of Lewy body dementia

Introducción: La demencia con cuerpos de Lewy (DCLw) es la segunda causa más frecuente de demencia degenerativa tras la demencia tipo Alzheimer (DTA). En esta entidad se ha descrito una denervación simpática cardíaca posganglionar, que puede cuantificarse mediante la gammagrafía miocárdica con MIBG (metayodobencilguanidina). El objetivo de nuestro trabajo fue evaluar retrospectivamente la captación miocárdica de MIBG, expresada cuantitativamente como el índice corazón/mediastino a las 4h (ICM) en pacientes con sospecha clínica de DCLw, y examinar su relación con los datos clínicos y paraclínicos. Pacientes y métodos:Se revisaron retrospectivamente datos de 77 pacientes con sospecha clínica de DCLw evaluados entre septiembre de 2005 y junio de 2008 en nuestro hospital a los que se les había realizado una gammagrafía miocárdica con MIBG. Se aplicaron los criterios internacionales de consenso para dividir la muestra en DCLw probable, DCLw posible y sin DCLw. Se analizaron el ICM en cada grupo y su relación con variables clínicas y neuropsicológicas. A un subgrupo de pacientes se le había realizado además un SPECT con FP-CIT (fluoropropil-carbometoxi-3β-4-yodofeniltropano) como parte de la evaluación. Resultados:Los valores medios de ICM fueron significativamente menores en el grupo de DCLw probable que en los grupos de DCLw posible y sin DCLw. Valores disminuidos de ICM solamente se asociaron a una captación disminuida en el estriado en el FP-CIT SPECT, pero no a ninguna variable clínica ni neuropsicológica. Conclusiones:La captación miocárdica reducida de MIBG es una medida robusta en la DCLw, y no se ve afectada por condiciones médicas o el estadio de la enfermedad. Una disminución en la captación miocárdica de MIBG se asocia a la degeneración nigroestriada en la DCLw (AU)

Introduction: Lewy body dementia (LBD) is the second most common cause of neurodegenerative dementia after Alzheimer's disease (AD). A cardiac post-ganglionic sympathetic denervation has been described in this condition which can be quantified by MIBG (metaiodobenzylguanidine) myocardial scintigraphy. The aim of our work was to retrospectively evaluate cardiac MIBG uptake (expressed as the heart-to-mediastinum ratio at 4h (HMR) in patients with suspected LBD, and to examine its relationship with clinical and para-clinical data. Material and methods: A total of 77 patients with clinical suspicion of LBD evaluated at our centre between September 2005 and June 2008 to whom a MIBG myocardial scintigraphy has been performed were retrospectively reviewed. International Consensus Criteria of LBD were applied to divide the sample into probable LBD, possible LBD and non-LBD. HMR values and their relationships with clinical and neuropsychological data were analysed. A subgroup of patients had FP-CIT (fluoropropyl-carbomethoxy-3β-4-iodophenyltropane) SPECT as a part of the evaluation.Results: Mean HMR values were significantly lower in probable LBD group than in possible LBD and non-LBD groups. Low HMR values were associated only with reduced FP-CIT uptake in the striatum, but not with any clinical or neuropsychological item.Conclusions: Low MIBG myocardial scintigraphy uptake is a robust measure in LBD, and it is not largely affected by medical conditions, or by the stage of the disease. In LBD reduced MIBG myocardial uptake is associated with nigrostriatal degeneration (AU)

Hemostatic markers of recanalization in patients with ischemic stroke treated with rt-PA.

OBJECTIVE: To determine whether pretreatment markers of coagulation and fibrinolysis are related to recanalization and functional outcome. METHODS: The authors included patients treated with IV rt-PA with occlusion on baseline transcranial Doppler (Thrombolysis in Brain Ischemia [TIBI] criteria) in whom recanalization within 6 hours was monitored. At baseline, the authors recorded data about demographics, vascular risk factors, the NIH Stroke Scale (NIHSS) score, early CT signs, etiology, blood glucose, and time to rt-PA. The authors also measured plasmatic markers of coagulation (fibrinogen, prothrombin fragments 1 + 2, Factor XIII, Factor VII) and fibrinolysis (alpha2-antiplasmin, Plasminogen Activator Inhibitor, Functional Thrombin Activatable Fibrinolysis Inhibitor [fTAFI]). A favorable outcome was defined as a modified Rankin score < 2 at 3 months. RESULTS: The authors studied 63 patients with a mean age of 67.3 +/- 12.5 years. The median NIHSS score was 16. Patients who recanalized had lower concentrations of alpha2-antiplasmin (87.5 +/- 18% vs 96.5 +/- 12.5%, p = 0.023) and fTAFI (91.7 +/- 26.7% vs 104.4 +/- 21%, p = 0.039). A multivariant logistic regression analysis showed that the level of alpha2-antiplasmin was the only predictive variable of recanalization (OR 0.95, 95% CI 0.91, 0.99, p = 0.038), while the NIHSS score was the only predictive variable of functional outcome (OR 0.81, 95% CI 0.72, 0.92, p = 0.001). CONCLUSION: Baseline levels of alpha2-antiplasmin were predictive of recanalization but were not related to the long-term outcome in patients treated with rt-PA within the first 3 hours.

Reasons for exclusion from thrombolytic therapy following acute ischemic stroke.

Despite evidence for the efficacy of thrombolytic therapy in acute ischemic stroke, only 1 to 7% of patients receive this therapy. The authors sought to determine the reasons for exclusion from tissue plasminogen activator (tPA) in an acute setting and found avoidable causes in 18% of patients. Improvements in intrahospital coordination would increase the number of patients who might benefit from tPA treatment at the authors' center.