Baseline Characteristics of Fabry Disease "Amenable" Migalastat Patients in Argentinian Cohort.

Fabry disease (FD) is a multisystem lysosomal storage disorder induced by genetic variants in the alpha-galactosidase A (αGalA) gene. Some FD patients have GLA variants with a reduction in overall αGalA enzymatic activity due to mutated proteins with reduced stability, caused by protein misfolding and premature degradation, but the αGalA catalytic activity remains conserved ("amenable" genetic variants). To correct this misfolding and to prevent premature degradation, migalastat, a small iminosugar molecule was developed. We report the clinical characteristics of FD "amenable" cohort patients from Argentina, prior to starting treatment with migalastat. Seventeen Fabry adult patients were recruited from 13 Argentinian Centers; 8 males (47.1%) and 9 females (52.9%) were included. All genotypes included were missense-type "amenables" mutations. Some classic FD typical early manifestations were more frequent in patients with "classic" versus "late-onset" FD phenotype (pain, p=0.002; cornea verticillata, p=0.019). There was a statistically significant difference in estimated glomerular filtration rate in the "classic" versus "late-onset" phenotype (p=0.026) but no difference between genders (p=0.695). Left ventricular mass was similar between genders (p=0.145) and phenotypes (p=0.303). Cardiovascular risk factors were present among "late-onset" females (obesity 50% and smoke 25%). In patients who started "de novo" migalastat, the main indications were (i) heart disease, (ii) kidney damage, and (iii) pain, while in "switched from prior enzyme replacement therapy" patients, the most frequent indication was "patient decision;" this coincides with publications by other authors.

Potenciales evocados miogénicos vestibulares con clicks y estímulos galvánicos / Vestibular evoked myogenic potentials with clicks and galvaric stimulation

El análisis del reflejo vestíbulo-cólico, que consiste en la activación de los vestibulares primarios, aporta una una valiosa información sobre la fisiología vestibular y es una herramienta útil para la evaluación de pacientes con alteraciones vestibulares. El objetivo de este trabajo es determinar las respuestas vestíbulo-cólicas mediante los estímulos con clicks de alta intensidad y mediante estímulos eléctricos transmastoideos (estimulación galvánica), establecer los valores de referencia y evaluar los parámetros según la edad. Se evaluaron a 20 personas sanas asintomáticas: en cada uno de ellos se evaluó la respuesta vestíbulo-cólica ante la estimulación con clicks, donde se registró una respuesta bifásica p13-n23 y ante la estimulación galvánica, donde se obtuvo una respuesta positivo-negativa p1-n1. Se utilizaron dos electrodos de registro, uno activo, ubicado en el tercio superior del músculo esternocleidomastoideo y otro de referencia ubicado en la unión esternoclavicular ipsilateral. Se analizaron las latencias, las amplitudes de los componentes y los índices de asimetría de amplitudes;las medianas de las latencias de los componentes p13 y n23 fueron significativamente menores que las de los componentes p1-n1; las amplitudes, tras la estimulación galvánica fueron menores que las obtenidas con clicks. Asimismo, se halló una correlación negativa entre la amplitud de la respuestas y la edad de los sujetos. El índice de asimetría de amplitudes fue similar en ambos paradigmas. El empleo de ambos tipos de estímulo es complementario para el estudio de la fisiología vestibular

The assessment of the vestibulocollic reflex consists of the activation of primary vestibular afferents; it also provides valuable information about vestibular physiology, and thus, can be used as a diagnostic tool in vestibular disorders. The aim of this research work is to evaluate this vestibule-collic response by using high intensity auditory as well as galvanic stimuli in order to provide normal referente values and search a correlation between each parameter and the age of individuals. Twenty healthy individuals of both sexes were subjetct to an assessment and after high intensity clicks a p13-n23 a response was obtained; furthermore, after galvanic stimuli a p1-n1 response was obtained. Two surface electrodes (active and reference) were used to read the responses obtained. Latency and amplitudes of p13-n23 and p1-n1 responses and asymmetry indexes were analyzed. Median latencies of p13-n23 responses were shorter than those of p1-n1 responses; and amplitudes of p1-n1 were smaller than those of p13-n23. It was observed a negative correlation between amplitudes of responses and age of the subjets. Asymmetry indexes were similar in both paradigms. The assessment of the vestibulo-collic reflex by using both clicks and galvanic stimulation gives valuable information about vestibular physiology

[The impairment of A-delta fibers in median nerve compression at the wrist, using the cutaneous silent period]. / Alteración de las fibras finas A-delta por entrampamiento del nervio mediano en la muñeca utilizando el período silente cutáneo.

Carpal tunnel síndrome (CTS) is an entrapment neuropathy of the median nerve at the wrist, that leads to pain, paresthesia and painful dysesthesia. The electrophysiological diagnosis is based upon nerve conduction studies which evaluate thick nerve fibers. Our hypothesis is that there is an additional dysfunction of small fibers in CTS, which correlates with the degree of severity of the neuropathy. A retrospective study of 69 hands that belonged to 47 patients of both sexes (mean age 53.8, years, range 22-87) was performed, and, as a control group, 21 hands which corresponded to the asymptomatic side of those patients were evaluated. Motor and sensory conduction studies, as well as F-waves were performed to classify the neuropathy according to the degree of severity. Cutaneous silent period (CSP) was elicited in all hands. Mean onset latencies and durations of CSP were evaluated. Mean onset latencies were significantly prolonged in neuropathic hands (84.3 ± 16.3 msec) compared to asymptomatic hands (74.8 ± 11.6 msec) (p < 0.05). Mean latencies of the CSP were even prolonged (p < 0.05) in hands affected by a more severe neuropathy. In the 3 hands with most severe neuropathy, a CSP could not be elicited. In CTS an impairment of A-delta fibers was recorded through the CSP. The more severe the neuropathy is, the more impairment of A-delta fibers can be found. CSP may be assessed as a complement of motor and sensory nerve conduction studies in this neuropathy.

Alteración de las fibras finas A-delta por entrampamiento del nervio mediano en la muñeca utilizando el período silente cutáneo / The impairment of A-delta fibers in median nerve compression at the wrist, using the cutaneous silent period

El síndrome del túnel carpiano (STC) es una neuropatía por entrampamiento a nivel de la muñeca que cursa con dolor, parestesias y disestesias dolorosas. El diagnóstico electrofisiológico se basa en el estudio de la neuroconducción de las fibras gruesas. Nuestra hipótesis consiste en la existencia del compromiso de las fibras nerviosas finas y que este compromiso se correlaciona con el grado de gravedad. Se evaluaron retrospectivamente 69 manos correspondientes a 47 pacientes, varones y mujeres (edad media 53.8, rango 22-87 años) y como grupo contro, 21 manos correspondientes a los lados asintomáticos de estos casos. Se realizaron estudios de neuroconducción motora, sensitiva y ondas F para clasificar a las manos según el grado de gravedad. Se realizó el período silente cutáneo (PSC) en todas las manos. Se evaluaron latencias medias y duraciones medias del PSC. Las latencias medias se hallaron significativamente prolongadas en las manos con neuropatía (84.3 ± 16.3 mseg) con respecto a las manos sin neuropatía (74.8 ± 11.6 mseg), p < 0.05. Las latencias medias se hallaron más prolongadas en las manos con neuropatía de mayor gravedad (p < 0.05). En los 3 pacientes con neuropatía grado más grave no se halló el PSC. Se demostró el compromiso de las fibras finas A-delta en los pacientes con STC, con mayor compromiso a mayor severidad. El PSC puede usarse como complemento de los estudios de neuroconducción motora y sensitiva.

Carpal tunnel síndrome (CTS) is an entrapment neuropathy of the median nerve at the wrist, that leads to pain, paresthesia and painful dysesthesia. The electrophysiological diagnosis is based upon nerve conduction studies which evaluate thick nerve fibers. Our hypothesis is that there is an additional dysfunction of small fibers in CTS, which correlates with the degree of severity of the neuropathy. A retrospective study of 69 hands that belonged to 47 patients of both sexes (mean age 53.8, years, range 22-87) was performed, and, as a control group, 21 hands which corresponded to the asymptomatic side of those patients were evaluated. Motor and sensory conduction studies, as well as F-waves were performed to classify the neuropathy according to the degree of severity. Cutaneous silent period (CSP) was elicited in all hands. Mean onset latencies and durations of CSP were evaluated. Mean onset latencies were significantly prolonged in neuropathic hands (84.3 ± 16.3 msec) compared to asymptomatic hands (74.8 ± 11.6 msec) (p < 0.05). Mean latencies of the CSP were even prolonged (p < 0.05) in hands affected by a more severe neuropathy. In the 3 hands with most severe neuropathy, a CSP could not be elicited. In CTS an impairment of A-delta fibers was recorded through the CSP. The more severe the neuropathy is, the more impairment of A-delta fibers can be found. CSP may be assessed as a complement of motor and sensory nerve conduction studies in this neuropathy.