The EGR2 gene is involved in axonal Charcot-Marie-Tooth disease.

BACKGROUND AND PURPOSE: A three-generation family affected by axonal Charcot-Marie-Tooth disease (CMT) was investigated with the aim of discovering genetic defects and to further characterize the phenotype. METHODS: The clinical, nerve conduction studies and muscle magnetic resonance images of the patients were reviewed. A whole exome sequencing was performed and the changes were investigated by genetic studies, in silico analysis and luciferase reporter assays. RESULTS: A novel c.1226G>A change (p.R409Q) in the EGR2 gene was identified. Patients presented with a typical, late-onset axonal CMT phenotype with variable severity that was confirmed in the ancillary tests. The in silico studies showed that the residue R409 is an evolutionary conserved amino acid. The p.R409Q mutation, which is predicted as probably damaging, would alter the conformation of the protein slightly and would cause a decrease of gene expression. CONCLUSIONS: This is the first report of an EGR2 mutation presenting as an axonal CMT phenotype with variable severity. This study broadens the phenotype of the EGR2-related neuropathies and suggests that the genetic testing of patients suffering from axonal CMT should include the EGR2 gene.

New insights into the pathophysiology of fasciculations in amyotrophic lateral sclerosis: An ultrasound study.

OBJECTIVE: To describe the fasciculation pattern in ALS and to analyse its clinical and pathophysiological significance. METHODS: Ultrasound of 19 muscles was performed in 44 patients with a recent diagnosis (<90 days) of ALS. The number of fasciculations was recorded in each muscle and the muscle thickness and strength were additionally measured in limb muscles. A subgroup of patients were electromyographically assessed. RESULTS: US was performed in 835 muscles and EMG was available in 263 muscles. US detected fasciculations more frequently than EMG. Fasciculations were widespread, especially in upper limbs onset patients and in the cervical region. Fasciculations' number inversely associated with ALSFR-R and body mass index (BMI) and directly with BMI loss and upper motor neuron (UMN) impairment. Our statistical model suggest that fasciculations increase with the initial lower motor neuron (LMN) degeneration, reach their peak when the muscle became mildly to moderately weak, decreasing afterwards with increasing muscle weakness and atrophy. CONCLUSIONS: Our study suggests that both UMN and LMN degeneration trigger fasciculations causing BMI loss. The degree of LMN impairment could account for differences in fasciculations' rates within and between muscles. SIGNIFICANCE: In ALS, fasciculations could explain the link between hyperexcitability and BMI loss.

[The vestibulocollic reflex: assessment and characteristics of vestibular-evoked myogenic potentials analysed by age groups]. / Reflejo vestibulocervical. Valoracion y caracteristicas de los potenciales vestibulares miogenicos evocados analizados por tramos de edad.

INTRODUCTION: Obtaining vestibular-evoked myogenic potentials (VEMP) by means of the vestibulocollic reflex is a readily available technique that provides an image of vestibular functioning and is useful for evaluating the pathologies that involve compromise of the anatomical pathway of the reflex. Although normal patterns do exist, responses vary at different ages. AIM: To obtain reference values of the vestibulocollic reflex according to different age groups. SUBJECTS AND METHODS: We studied 40 volunteers with no symptoms of auditory or vestibular compromise. Each ear was stimulated separately by a series of clicks (sounds lasting 0.1 s; 3 pps; intensities of 100 dB nHL and 85 dB nHL) and recordings were made in the sternocleidomastoid muscles by means of surface electrodes as patients who were lying on their backs contracted these muscles as they lifted their heads. We studied the latency of the initial p13-n23 positive-negative potential and the peak-to-peak amplitude. The existence of later n34-p44 potentials was evaluated. RESULTS: No statistically significant differences were found between genders or between the two ears. We did not find any differences between the latencies of the waves according to the intensity of the stimulus, but there is a relationship between the amplitude of the p13-n23 potential and the intensity of the stimulus. The latencies of the responses in children under 10 years of age differ from those of the other groups, but no differences were found among those over the age of 11. CONCLUSIONS: The VEMP display steady and easily identifiable latencies. We obtained different reference values for latency in children under the age of 10 and those over 11 years old. The amplitude decreases with the intensity of the stimulus.

[Electrodiagnosis in disorders of neuromuscular transmission]. / Electrodiagnóstico en los trastornos de transmisión neuromuscular.

INTRODUCTION: Electrophysiological studies are of recognized use in the confirmation of alterations of neuromuscular transmission in further determining their physiopathological characteristics, helping to differentiate them from other conditions with secondary effects on their function. DEVELOPMENT AND CONCLUSIONS: In our study we review the physiopathology of these disorders which compromise the safety factor of the neuromuscular junction, by presynaptic or postsynaptic alterations, and forms the basis of the results of electrophysiological studies. We describe the techniques currently most used: repetitive stimulation and single fibre electromyography complemented by conventional electromyography. Their application and findings in the commonest syndromes are discussed. Finally, their sensitivity, specificity and difficulties are considered.

Peripheral nerve hyperexcitability: a clinical and immunologic study of 38 patients.

OBJECTIVE: We studied a case series of peripheral nerve hyperexcitability (PNH) aiming to describe clinical characteristics, immunologic and cancer associations, antibodies against neuronal antigens (voltage-gated potassium channel antibodies [VGKC-Abs] and other), and muscle biopsy findings. METHODS: Patients presenting with clinical and electrophysiologic signs of PNH were selected. We studied clinical and electrophysiologic features; a panel of non-neuronal organ-specific antibodies, immunofluorescence on rat nervous tissues, and radioimmunoprecipitation for VGKC-Abs; and muscle biopsies. RESULTS: Thirty-eight patients were included. After the exclusion of 6 cases with axonopathy of known origin, patients were subdivided according to the presence of electrophysiologic findings of motor axonopathy and association with cancer: axonopathic-PNH (group A: 12 patients), isolated nonparaneoplastic PNH (group B: 16 patients), and isolated paraneoplastic PNH (3 with thymoma and myasthenia gravis, 1 with thyroid carcinoma). PNH clinical features were similar in groups A and B. We found an overall high prevalence of clinical autoimmunity (33% of group A and 63% of group B) and systemic non-neuronal autoantibodies (42% of group A and 75% of group B). However, VGKC-Abs were only positive in 2 patients of group B. Ten patients underwent muscle biopsy, which showed inflammatory changes in 2 cases and nonspecific myopathic features in 8. CONCLUSIONS: PNH is a heterogeneous disorder involving the peripheral nerves in patients with a high propensity for developing autoimmunity. Associated muscle diseases are frequent in the form of myositis, myasthenia gravis, or nonspecific myopathic pathologic findings. VGKC-Abs were uncommon in this series.

Reflejo vestibulocervical. Valoración y características de los potenciales vestibulares miogénicos evocados analizados por tramos de edad / The vestibulocollic reflex. assessment and characteristics of vestibular-evoked myogenic potentials analysed by age groups

Introducción. La obtención de potenciales vestibulares miogénicos evocados (PVME) mediante la realización del reflejo vestibulocervical es una técnica de fácil obtención que da una imagen de la función vestibular y es útil para valorar las patologías que impliquen afectación de la vía anatómica del reflejo. Aunque existen patrones normales, a distintas edades podemos encontrar variaciones en las respuestas. Objetivo. Obtener valores de referencia por tramos de edad del reflejo vestibulocervical. Sujetos y métodos. Estudiamos a 40 voluntarios sin síntomas de afectación auditiva o vestibular. Se estimula mediante clics (sonidos de 0,1 s de duración; 3 pps; intensidades de 100 dB nHL y 85 dB nHL), cada oído por separado, y se registra en los músculos esternocleidomastoideos mediante electrodos de superficie mientras el paciente los contrae al alzar la cabeza desde el decúbito supino. Hemos estudiado la latencia del potencial positivo-negativo inicial p13-n23 y la amplitud pico-pico. Se valora la existencia de potenciales más tardíos n34-p44. Resultados. No encontramos diferencias estadísticamente significativas entre géneros ni entre ambos oídos. No observamos diferencias entre latencias de las ondas en función de la intensidad del estímulo, y existe una relación entre la amplitud del potencial p13-n23 y la intensidad del estímulo. Las latencias de las respuestas en menores de 10 años difieren del resto de grupos, pero no existen diferencias en los mayores de 11 años. Conclusiones. Los PVME muestran unas latencias estables y fácilmente identificables. Obtenemos los valores de referencia de latencia diferentes para menores de 10 años y para los mayores de 11. La amplitud decrece en función de la intensidad del estímulo

Introduction. Obtaining vestibular-evoked myogenic potentials (VEMP) by means of the vestibulocollic reflex is a readily available technique that provides an image of vestibular functioning and is useful for evaluating the pathologies that involve compromise of the anatomical pathway of the reflex. Although normal patterns do exist, responses vary at different ages. Aim. To obtain reference values of the vestibulocollic reflex according to different age groups. Subjects and methods. We studied 40 volunteers with no symptoms of auditory or vestibular compromise. Each ear was stimulated separately by a series of clicks (sounds lasting 0.1 s; 3 pps; intensities of 100 dB nHL and 85 dB nHL) and recordings were made in the sternocleidomastoid muscles by means of surface electrodes as patients who were lying on their backs contracted these muscles as they lifted their heads. We studied the latency of the initial p13-n23 positive-negative potential and the peak-to-peak amplitude. The existence of later n34-p44 potentials was evaluated. Results. No statistically significant differences were found between genders or between the two ears. We did not find any differences between the latencies of the waves according to the intensity of the stimulus, but there is a relationship between the amplitude of the p13-n23 potential and the intensity of the stimulus. The latencies of the responses in children under 10 years of age differ from those of the other groups, but no differences were found among those over the age of 11. Conclusions. The VEMP display steady and easily identifiable latencies. We obtained different reference values for latency in children under the age of 10 and those over 11 years old. The amplitude decreases with the intensity of the stimulus

Electrodiagnóstico en los trastornos de transmisión neuromuscular / Electrodiagnosis in disorders of neuromuscular transmission

Introducción. Los estudios electrofisiológicos son de conocida utilidad en la confirmación de alteraciones de la transmisión neuromuscular, en la profundización de sus características fisiopatológicas, ayudando a su diferenciación con otros procesos que afectan secundariamente su función. Desarrollo y conclusiones. En nuestro trabajo, se revisa la fisiopatología de estos trastornos que van a converger en el compromiso del factor de seguridad de la unión neuromuscular, bien por alteración presináptica o postsináptica, y que serán la base de los resultados de los estudios electrofisiológicos. Se describen las técnicas más utilizadas en la actualidad: estimulación repetitiva y electromiografía de fibra simple complementadas con electromiografía convencional. Se comenta su aplicación y los hallazgos en los síndromes más frecuentes. Por último, se subraya su sensibilidad, especificidad y dificultades (AU)