Multiple-system atrophy

Fanciulli and Wenning's review (Jan. 15 issue) on multiple-system atrophy is comprehensive and up to date. In it, the authors state that the open-label administration of gabapentin could ameliorate cerebellar symptoms in single cases of this disease. However, the cited reference describes a noticeable improvement in gait in one patient who received a diagnosis of olivopontocerebellar atrophy (OPCA) after a single dose of 400 mg of gabapentin and alleviation of dysarthria and oscillopsia in another patient with OPCA during long-term therapy with gabapentin. These patients could not have received a diagnosis of multiple-system atrophy, since neither had features of autonomic dysfunction. In contrast, gabapentin was found to cause generalized weakness and to worsen gait and dysarthria in three patients with multiple-system atrophy, forcing withdrawal of the drug..

Competencia estadística del futuro profesorado de educación primaria: análisis de la repercusión del ABP en su adquisición

En este póster se presenta parte del trabajo de investigación que analiza cómo el futuro profesorado de Educación Primaria adquiere las competencias profesionales en cuanto al bloque curricular de Tratamiento de la información, azar y probabilidad (National Council of Teachers of Mathematics, 2000). Concretamente, se pretende medir la repercusión de la metodología docente basada en Aprendizaje Basado en Proyectos en la adquisición de las competencias relativas al conocimiento del contenido de Estadística, al conocimiento del currículo de Estadística de Educación Primaria, a su utilidad en la vida cotidiana y al uso de las nuevas tecnologías para el aprendizaje de la Estadística

Episodic Vestibulocerebellar Ataxia Associated with a CACNA1G Missense Variant

Episodic vestibulocerebellar ataxias are rare diseases, frequently linked to mutations in different ion channels. Our objective in this work was to describe a kindred with episodic vestibular dysfunction and ataxia, associated with a novel CACNA1G variant. Two individuals from successive generations developed episodes of transient dizziness, gait unsteadiness, a sensation of fall triggered by head movements, headache, and cheek numbness. These were suppressed by carbamazepine (CBZ) administration in the proband, although acetazolamide and topiramate worsened instability, and amitriptyline and flunarizine did not prevent headache spells. On examination, the horizontal head impulse test (HIT) yielded saccadic responses bilaterally and was accompanied by cerebellar signs. Two additional family members were asymptomatic, with normal neurological examinations. Reduced vestibulo-ocular reflex gain values, overt and covert saccades were shown by video-assisted HIT in affected subjects. Hearing acuity was normal. Whole-exome sequencing demonstrated the heterozygous CACNA1G missense variant c.6958G>T (p.Gly2320Cys) in symptomatic individuals. It was absent in 1 unaffected member (not tested in the other asymptomatic individual) and should be considered likely pathogenic. CACNA1G encodes for the pore-forming, a1G subunit of the T-type voltage-gated calcium channel (VGCC), in which currents are transient owing to fast inactivation, and tiny, due to small conductance. Mutations in CACNA1G cause generalized absence epilepsy and adult-onset, dominantly inherited, spinocerebellar ataxia type 42. In this kindred, the aforementioned CACNA1G variant segregated with disease, which was consistent with episodic vestibulocerebellar ataxia. CBZ proved successful in bout prevention and provided symptomatic benefit in the proband, probably as a result of interaction of this drug with VGCC. Further studies are needed to fully determine the vestibular and neurological manifestations of this form of episodic vestibulocerebellar ataxia. This novel disease variant could be designated episodic vestibulocerebellar ataxia type 10. © 2021 The Author(s). Published by S. Karger AG, Basel

Hsp70 Chaperones and Type I PRMTs Are Sequestered at Intranuclear Inclusions Caused by Polyalanine Expansions in PABPN1

Genomic instability at loci with tandem arrays of simple repeats is the cause for many neurological, neurodegenerative and neuromuscular diseases. When located in coding regions, disease-associated expansions of trinucleotide repeats are translated into homopolymeric amino acid stretches of glutamine or alanine. Polyalanine expansions in the poly(A)-binding protein nuclear 1 (PABPN1) gene causes oculopharyngeal muscular dystrophy (OPMD). To gain novel insight into the molecular pathophysiology of OPMD, we studied the interaction of cellular proteins with normal and expanded PABPN1. Pull-down assays show that heat shock proteins including Hsp70, and type I arginine methyl transferases (PRMT1 and PRMT3) associate preferentially with expanded PABPN1. Immunofluorescence microscopy further reveals accumulation of these proteins at intranuclear inclusions in muscle from OPMD patients. Recombinant PABPN1 with expanded polyalanine stretches binds Hsp70 with higher affinity, and data from molecular simulations suggest that expansions of the PABPN1 polyalanine tract result in transition from a disordered, flexible conformation to a stable helical secondary structure. Taken together, our results suggest that the pathological mutation in the PABPN1 gene alters the protein conformation and induces a preferential interaction with type I PRMTs and Hsp70 chaperones. This in turn causes sequestration in intranuclear inclusions, possibly leading to a progressive cellular defect in arginine methylation and chaperone activity

Ataxia de Marie: en recuerdo de un epónimo clásico caído en desuso

Introducción. Nikolaus Friedreich introdujo el término ataxia hereditaria para designar una nueva forma de ataxia hereditaria de inicio temprano, una entidad clinicopatológica que describió en una serie de estudios publicados entre 1863 y 1877. Este término fue pronto remplazado por el epónimo ataxia de Friedreich, dejando vacante el término ataxia hereditaria. En 1893, Pierre Marie propuso reintroducir el término ataxia hereditaria, añadiendo el calificativo ?cerebelosa?. Muchos autores, especialmente en el ámbito francófono, cambiaron este término por el epónimo ataxia de Marie. Objetivos. Aclaramos la nosología de la ataxia de Marie, y abordamos la cuestión de si está justificado el uso de este término. Desarrollo. Analizamos en detalle las descripciones originales de la ataxia de Friedreich y la ataxia de Marie. Friedreich realizó una descripción magistral de una enfermedad que posteriormente, y de pleno derecho, pasaría a conocerse por su apellido. Marie propuso otra entidad, basándose no en casos clínico-patológicos propios sino en cuatro estudios previamente descritos por otros autores. Las principales diferencias de la ataxia de Marie con respecto de la ataxia de Friedreich eran la mayor edad de inicio y la conservación de los reflejos tendinosos. Hacia 1893, dos estudios post mortem habían mostrado cambios predominantemente en el cerebelo, lo que llevó a Pierre Marie a acuñar el término ataxia cerebelosa hereditaria. Durante las cuatro décadas siguientes, otros ocho estudios mostraron que las lesiones más importantes se hallaban en la médula espinal, afectando a las columnas de Clarke, los tractos espinocerebelosos anteriores y, en menor medida, los tractos espinocerebelosos posteriores y las columnas dorsales. Sin ningún tipo de base, Marie y sus discípulos postularon que la degeneración del tracto espinocerebeloso anterior era un rasgo distintivo de la ataxia cerebelosa hereditaria. El concepto de ataxia de Marie recibió numerosas críticas. Conclusión. El uso del epónimo ataxia de Marie ya no está justificado

A new perspective on the submillimetre galaxy MM 18423+5938 at redshift 3.9296 from radio continuum imaging

The bright submillimetre (sub-mm) galaxy MM 18423+5938 at redshift 3.9296 has been predicted from mid-infrared and millimetre photometry to have an exceptionally large total infrared (IR) luminosity. We present new radio imaging at 1.4 GHz with the Westerbork Synthesis Radio Telescope that is used to determine a radio-derived total IR luminosity for MM 18423+5938 via the well established radio-far-infrared correlation. The flux density is found to be S_1.4 GHz = 217 +/- 37 \mu Jy, which corresponds to a rest-frame luminosity density of L_1.4 GHz = 2.32 +/- 0.40 x 10^25 / u W / Hz, where u is the magnification from a probable gravitational lens. The radio-derived total IR luminosity and star-formation rate are L_8-1000 \mu m = 5.6^+4.1_-2.4 x 10^13 / u L_sol and SFR = 9.4^+7.4_-4.9 x 10^3 / u M_sol / yr, respectively, which are ~9 times smaller than those previously reported. These differences are attributed to the IR spectral energy distribution of MM 18423+5938 being poorly constrained by the limited number of reliable photometric data that are currently available, and from a previous misidentification of the object at 70 \mu m. Using the radio derived total IR luminosity as a constraint, the temperature of the cold dust component is found to be T ~ 24^+7_-5 K for a dust emissivity of \beta = 1.5 +/- 0.5. The radio-derived properties of this galaxy are still large given the low excitation temperature implied by the CO emission lines and the temperature of the cold dust. Therefore, we conclude that MM 18423+5938 is probably gravitationally lensed.Comment: 5 pages, 2 figures, 1 table, accepted for publication in MNRAS Letter

Novel mutation of SACS gene in a Spanish family with autosomal recessive spastic ataxia

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an inherited neurodegenerative disorder characterized by early-onset, spastic ataxia and peripheral neuropathy. It was originally described in an inbred population of Quebec and later in some other countries. We report a new missense SACS mutation (7848C>T) in a Spanish family whose phenotype is similar to that of the previously described ARSACS patients. 7848C>T is the first SACS mutation reported in Spain confirming worldwide distribution of the disease. (c) 2005 Movement Disorder Society

Hollow Fiber Membranes of PCL and PCL/Graphene as Scaffolds with Potential to Develop In Vitro Blood—Brain Barrier Models

There is a huge interest in developing novel hollow fiber (HF) membranes able to modulate neural differentiation to produce in vitro blood–brain barrier (BBB) models for biomedical and pharmaceutical research, due to the low cell-inductive properties of the polymer HFs used in current BBB models. In this work, poly(ε-caprolactone) (PCL) and composite PCL/graphene (PCL/G) HF membranes were prepared by phase inversion and were characterized in terms of mechanical, electrical, morphological, chemical, and mass transport properties. The presence of graphene in PCL/G membranes enlarged the pore size and the water flux and presented significantly higher electrical conductivity than PCL HFs. A biocompatibility assay showed that PCL/G HFs significantly increased C6 cells adhesion and differentiation towards astrocytes, which may be attributed to their higher electrical conductivity in comparison to PCL HFs. On the other hand, PCL/G membranes produced a cytotoxic effect on the endothelial cell line HUVEC presumably related with a higher production of intracellular reactive oxygen species induced by the nanomaterial in this particular cell line. These results prove the potential of PCL HF membranes to grow endothelial cells and PCL/G HF membranes to differentiate astrocytes, the two characteristic cell types that could develop in vitro BBB models in future 3D co-culture systems.This research was funded by IDIVAL (INNVAL 17/20), MINECO/EIG-Concert Japan (X-MEM PCI2018-092929 project, International Joint Program 2018) and MINECO/Spain Feder (CTM-2016-75509-R project)

Very early Guillain-Barré syndrome: A clinical-electrophysiological and ultrasonographic study

Objectives: Using recent optimized electrodiagnostic criteria sets, we primarily aimed at verifying the accuracy of the initial electrophysiological test in very early Guillain-Barré syndrome (VEGBS), ?4 days of onset, compared with the results of serial electrophysiology. Our secondary objective was to correlate early electrophysiological results with sonographic nerve changes. Methods: This is a retrospective study based on consecutive VEGBS patients admitted to the hospital. Each patient had serial nerve conduction studies (NCS) in at least 4 nerves. Initial NCS were done within 4 days after onset, and serial ones from the second week onwards. Electrophysiological recordings of each case were re-evaluated, GBS subtype being established accordingly. Nerve ultrasonography was almost always performed within 2 weeks after onset. Results: Fifteen adult VEGBS patients were identified with a mean age of 57.8 years. At first NCS, VEGBS sub-typing was only possible in 3 (20%) cases that showed an axonal pattern, the remaining patterns being mixed (combining axonal and demyelinating features) in 6 (40%), equivocal in 5 (33.3%), and normal in 1 (6.7%). Upon serial NCS, 7 (46.7%) cases were categorized as acute demyelinating polyneuropathy, 7 (46.7%) as axonal GBS, and 1 (6.6%) as unclassified syndrome. Antiganglioside reactivity was detected in 5 out of the 7 axonal cases. Nerve US showed that lesions mainly involved the ventral rami of scanned cervical nerves. Conclusions: Serial electrophysiological evaluation is necessary for accurate VEGBS subtype classification. Ultrasonography helps delineate the topography of nerve changes. Significance: We provide new VEGBS pathophysiological insights into nerve conduction alterations within the first 4 days of the clinical course.Acknowledgement: This paper was supported by IDIVAL (ID APG/11) and CIBERNED. The authors are most grateful to Mrs Marta de la Fuente for secretarial assistance