Bi-allelic mutations in EGR2 cause autosomal recessive demyelinating neuropathy by disrupting the EGR2-NAB complex.

BACKGROUND AND PURPOSE: Mutations in the early growth response 2 gene (EGR2) cause demyelinating, but also axonal, neuropathies differing in severity and age of onset. Except for one family, all reported cases have autosomal dominant inheritance and mutations are localized within the three zinc finger (ZNF) DNA-binding domain. The aim of this study was to provide a clinical and molecular analysis of a novel recessive mutation in EGR2. METHODS: Clinical and electrophysiological assessments of three affected patients, from a consanguineous family, were performed. Genetic analyses of EGR2 were carried out by Sanger sequencing. Functional effects of clinical recessive mutations were assessed using a mammalian two-hybrid assay. RESULTS: A novel missense mutation (c.791C>T; p.P264L) in the homozygous state was detected outside the ZNF domains of the EGR2 gene. Three affected siblings presented with distal demyelinating polyneuropathy with severe sensory loss, progressive thoracolumbar scoliosis and trigeminal neuralgia. Respiratory compromise and cranial nerve dysfunction were also found. Our data indicate that the p.P264L mutation prevents interaction of EGR2 transcription factor with NAB corepressors, suggesting that a disruption of the NAB-EGR2 protein interactions can result in dramatic neuropathy. CONCLUSION: Mutations in, or next to, the R1 domain of EGR2 should be considered with extreme caution for genetic counseling, since these could cause a severe neuropathy with an autosomal recessive manner of transmission.

Clinical spectrum of BICD2 mutations.

BACKGROUND AND PURPOSE: Mutations in the BICD2 gene cause autosomal dominant lower extremity-predominant spinal muscular atrophy 2A (SMALED2A), a condition that is associated with a specific pattern of thigh and calf muscle involvement when studied by magnetic resonance imaging (MRI). Patients may present minor clinical sensory impairment, but objective sensory involvement has yet to be demonstrated. METHODS: We collected clinical data from 11 patients from five different families carrying mutations in BICD2. Genetic diagnosis was achieved using gene panel testing and skin biopsies were taken from two patients to study the epidermal nerve fiber density. RESULTS: In the studied patients, three new pathogenic mutations were detected as well as the already defined pathogenic p.Ser107Leu mutation. The most frequent clinical picture was characterized by lower-limb weakness in combination with foot deformities. One patient manifested clinical and electrophysiological sensory impairment, and the epidermal nerve fiber density study of another patient revealed the existence of a small-fiber neuropathy. Muscle MRI showed a common pattern of fat deposition including selective involvement of gluteus medius and minimus at the pelvic level, the anterior compartment of the thigh and the posterior compartment of the calf, with only mild or no involvement of the intrinsic foot muscles. CONCLUSIONS: We report three new pathogenic mutations in the BICD2 gene. Muscle MRI confirms the existence of a selective pattern of thigh and leg muscle involvement in SMALED2A, providing additional information regarding pelvic and foot muscles. Moreover, our results raise the possibility of sensory involvement in the disease.

[Effectiveness of a tablet telerehabilitation application in patients with distal radius fracture]. / Efectividad de una aplicación de telerrehabilitación para tableta en pacientes con fractura de extremo distal del radio.

INTRODUCTION: To assess whether, in patients with distal radius fracture feedback-guided exercises performed on a tablet touchscreen reduce healthcare usage and improve clinical recovery, more than the conventional home exercise program prescribed on paper. MATERIAL AND METHODS: A multicentre, parallel, two-group, pragmatic, controlled trial with assessor blinding and intention-to-treat analysis. Forty-six patients with distal radius fracture were recruited in Andalusian Public Health System. Participants in the experimental and control groups received the same in-patient physiotherapy sessions. Experimental group received a home exercise program using the ReHand tablet application and control group received an evidence-based home exercise program on paper. The primary outcome was the number of physiotherapy sessions tallied from hospitals data management system. Secondary outcomes included: the face-to-face rehabilitation consultations with a physiatrist, and clinical outcomes such as functional ability, grip strength, dexterity, pain intensity and range of motion. RESULTS: The experimental group required fewer physiotherapy sessions (MD: -16.94; 95%CI: -32.5 to -1.38) and rehabilitation consultations (MD: -1.7; 95%CI: -3.39 to -0.02) compared to the control group. CONCLUSIONS: In patients with distal radius fracture, prescribing feedback-guided exercises performed on a tablet touchscreen provided by ReHand reduced number of physiotherapy sessions and rehabilitation consultations.

[Validation of the Spanish version of the Charcot-Marie-Tooth disease Pediatric Scale (CMTPedS)]. / Validación de la versión española de la Charcot-Marie-Tooth Disease Pediatric Scale (CMTPedS).

INTRODUCTION AND AIMS: The Charcot-Marie-Tooth Pediatric Scale (CMTPedS) is a validated and change-sensitive tool for assessing the severity of neuropathy in children and adolescents between 3 and 20 years of age. The aim of this article is to translate and validate a Spanish version of the CMTPedS in order to disseminate its use in Spanish-speaking countries. MATERIALS AND METHODS: The process used to translate the CMTPedS into Spanish was the reverse parallel translation method based on the principles of good practice for translation and the cultural adaptation process of the Food and Drug Administration Guidelines. A direct translation of the original source of the CMTPedS into Spanish was performed first and reviewed by experts in Charcot-Marie-Tooth (CMT) disease trained in the use of the CMTPedS tool. The Spanish version was then translated back into English by a linguist specialised in translation. RESULTS: The preliminary Spanish version of the CMTPedS was evaluated in 18 children with CMT aged 6-20 years (mean: 13.27). The scale was well tolerated and easy for children to understand and easy for clinicians to apply. None of the patients had any difficulty completing the scale. CONCLUSIONS: The Spanish version of the CMTPedS can be used for monitoring and conducting clinical trials in the Spanish population and in Spanish-speaking countries.

TITLE: Validación de la versión española de la Charcot-Marie-Tooth Disease Pediatric Scale (CMTPedS).Introducción y objetivos. La Charcot-Marie-Tooth Pediatric Scale (CMTPedS) es una herramienta validada y sensible al cambio para evaluar la gravedad de la neuropatía en niños y adolescentes entre 3 y 20 años. El objetivo de este artículo es traducir y validar una versión española de la CMTPedS para difundir su utilización en países de habla hispana. Material y métodos. El proceso para la traducción al español de la CMTPedS ha sido el método de traducción paralela invertida basado en los principios de buena práctica para la traducción y el proceso de adaptación cultural de las Food and Drug Administration Guidelines. Se realizó primero una traducción directa de la fuente original de la CMTPedS al español que fue revisada por expertos en la enfermedad de Charcot-Marie-Tooth (CMT) formados en la utilización de la herramienta CMTPedS. La versión española fue traducida de nuevo al inglés por un lingüista especialista de la traducción. Resultados. La versión preliminar en español de la CMTPedS se evaluó en 18 niños con CMT entre 6 y 20 años (media: 13,27). La escala fue bien tolerada y fácil de comprender en los niños y fácil de aplicar para los clínicos. Ningún paciente tuvo dificultad en completar la escala. Conclusiones. La versión española de la CMTPedS se puede utilizar para el seguimiento y la realización de ensayos clínicos en población española y países de habla hispana.

[Non-invasive mechanical ventilation with a facial interface during sedation for a percutaneous endoscopic gastrostomy in a patient with amyotrophic lateral sclerosis]. / Ventilación mecánica no invasiva con interfase facial durante la sedación para una gastrostomía endoscópica percutánea en un paciente con esclerosis lateral amiotrófica.

Amyotrophic lateral sclerosis is a chronic neurodegenerative disease of the central nervous system which affects the motor neurons and produces a progressive muscle weakness, leading to atrophy and muscle paralysis, and ultimately death. Performing a percutaneous endoscopic gastrostomy with sedation in patients with amyotrophic lateral sclerosis can be a challenge for the anesthesiologist. The case is presented of a 76-year-old patient who suffered from advanced stage amyotrophic lateral sclerosis, ASA III, in which a percutaneous endoscopic gastrostomy was performed with deep sedation, for which non-invasive ventilation was used as a respiratory support to prevent hypoventilation and postoperative respiratory complications.

[Effect of insulin on germination and ionic exchange in Raphanus sativus (author's transl)]. / Efectos de la insulina sobre la germinación e intercambio iónico del Raphanus sativus.

Hypoglycemic sulfamide BZ-55 activates or inhibits germination of Raphanus sativus, depending upon the dosis. Since this drug acts upon the glycemia by increasing the secretion and action of insulin, the influence of this hormone on germination and ionic changes (Na+-K+) between seeds and culture medium, were studied. Seeds were incubated during 72 h with different concentrations of insulin in 10 ml deionized water or in 10 ml 18 mM K+ (KCl) solutions at 37 degrees C in vapor saturated atmosphere. A solution of 0.125 IU insulin/ml in water increases the germination to 110% whereas 0.175 IU insulin/ml inhibits it to 40% against controls. Further increases in insulin concentration always inhibit germination. Similar results have been obtained with K+ containing media. Germination rate changes in a small concentration range suggest that insulin might affect an enzymatic activity in the seed.

[Effect of alloxan in pancreatectomized rats (author's transl)]. / Contribución al estudio de la aloxana en ratas pancreoprivas.

Sensitivty to alloxan of pancreatectomized rats is studied injecting on the seventh day after surgical resection with different dose of monohydrated alloxan. Totally pancreatectomized rats develop a strong diabetes just the same as the control group, but the former present higher glycemias and longer survival.