Electrophysiological and functional signs of Guillain-Barré syndrome predicted by a multiscale neuromuscular computational model.

Objective.The diagnosis of nerve disorders in humans has relied heavily on the measurement of electrical signals from nerves or muscles in response to electrical stimuli applied at appropriate locations on the body surface. The present study investigated the demyelinating subtype of Guillain-Barré syndrome using multiscale computational model simulations to verify how demyelination of peripheral axons may affect plantar flexion torque as well as the ongoing electromyogram (EMG) during voluntary isometric or isotonic contractions.Approach.Changes in axonal conduction velocities, mimicking those found in patients with the disease at different stages, were imposed on a multiscale computational neuromusculoskeletal model to simulate subjects performing unipodal plantar flexion force and position tasks.Main results.The simulated results indicated changes in the torque signal during the early phase of the disease while performing isotonic tasks, as well as in torque variability after partial conduction block while performing both isometric and isotonic tasks. Our results also indicated changes in the root mean square values and in the power spectrum of the soleus EMG signal as well as changes in the synchronization index computed from the firing times of the active motor units. All these quantitative changes in functional indicators suggest that the adoption of such additional measurements, such as torques and ongoing EMG, could be used with advantage in the diagnosis and be relevant in providing extra information for the neurologist about the level of the disease.Significance.Our findings enrich the knowledge of the possible ways demyelination affects force generation and position control during plantarflexion. Moreover, this work extends computational neuroscience to computational neurology and shows the potential of biologically compatible neuromuscular computational models in providing relevant quantitative signs that may be useful for diagnosis in the clinic, complementing the tools traditionally used in neurological electrodiagnosis.

Eficacia de la movilización de células madre en pacientes con Polineuropatía Desmielinizante Inflamatoria Crónica refractaria / Efficacy of mobilization of stem cells in patients with Refractory Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Introducción: La polineuropatía desmielinizante inflamatoria crónica (CIDP) es una enfermedad desmielinizante e inflamatoria de mediación autoinmune. El tratamiento convencional es basado en la inmunomodulación e inmunosupresión. El uso de células madre es una terapia novedosa en los trastornos autoinmune, siendo incluida como terapia. Objetivo: Determinar la eficacia de la movilización de células madre mediante la aplicación del factor estimulador de colonias granulocíticas (F-ECG) en pacientes con CIDP que han recibido otras líneas de tratamiento. Material y Métodos: Se realizó un estudio aleatorizado, doble ciego sobre una cohorte de 45 pacientes con CIDP, donde se administró el (F-ECG) en 25 pacientes y 20 continuaron con el tratamiento habitual, tratados anteriormente con otras variantes terapéuticas por más de tres años, sin respuesta satisfactoria. Resultados: Predominio de los hombres para 64,4 por ciento, la Diabetes Mellitus tuvo mayor asociación y la medicación más usada fueron los esteroides. Los síntomas y signos clínicos mejoraron significativamente tras el tratamiento. Los valores de la puntuación del TCSS al mes y 3 meses después del tratamiento disminuyeron significativamente; pero este decremento no se mantuvo al final del estudio. La velocidad de conducción y el potencial de acción de los nervios sensoriales y motores mejoraron considerablemente después del tratamiento. Conclusiones: La efectividad de la aplicación del (F-ECG) para la mejoría de los síntomas clínicos y resultados de estudios neurofisiológicos evolutivamente son mayores que otras variantes terapéuticas en los primeros meses, con buena seguridad y tolerabilidad, por lo que se puede incluir en la terapéutica convencional para la CIDP(AU)

Introduction: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune demyelinating disease. Conventional treatment is based on immunomodulation and immunosuppression. The use of stem cells is a novel therapy in autoimmune disorders, so it is included as therapy. Objective: To determine the efficacy of mobilization of stem cells by applying granulocyte colony-stimulating factor (G-CSF) in patients with CIDP who have followed other lines of treatment. Material and Methods: A randomized, double-blind study was carried out on a cohort of 45 patients with CIDP. G-CSF was administered to 25 patients and 20 of them continued with the usual treatment. These patients were previously treated with other therapeutic variants for more than three years without satisfactory response. Results: There was a prevalence of men (64.4 percent), Diabetes Mellitus had a greater association, and the most used medications were steroids. Clinical symptoms and signs improved significantly after treatment. TCSS scores significantly decreased at one and three months after treatment, but this decrease was not maintained at the end of the study. The conduction velocity and action potential of sensory and motor nerves improved considerably after treatment. Conclusions: The effectiveness of the use of G-CSF shows an improvement of clinical symptoms. The results of neurophysiological studies have a better course than other therapeutic variants during the first months, with good safety and tolerability, so it can be included in the conventional therapy for the CIDP(AU)

Clinical characteristics and plasma exchange response in Guillain-Barré patients / Características clínicas y respuesta al recambio plasmático terapéutico en los pacientes con síndrome de Guillain Barré

El objetivo del estudio fue describir las características clínicas, la respuesta al tratamiento y posibles factores asociados de los pacientes con síndrome de Guillain Barré en el Instituto Nacional de Ciencias Neurológicas. Se realizó un estudio descriptivo sobre egresos hospitalarios durante el periodo 2017-2019. La respuesta al tratamiento se evaluó mediante la escala de discapacidad de Hughes. De los 31 pacientes el 61,3% eran varones, y la edad promedio fue de 50 años. Al ingreso, el 87,1% de pacientes se encontraban en el grado 3 o 4 de la escala de Hughes, la mayoría con compromiso axonal, el cual estuvo asociado a discapacidad. Solo 22 pacientes recibieron recambio plasmático; luego de seis meses el 90,9% disminuyó al menos en un grado en la escala de Hughes y el 42,8% quedaron sin discapacidad. En conclusión, se encontró un predominio del sexo masculino y del compromiso axonal, este último asociado a discapacidad.

Características clínicas y respuesta al recambio plasmático terapéutico en los pacientes con síndrome de Guillain Barré / Clinical characteristics and plasma exchange response in Guillain-Barré patients

RESUMEN El objetivo del estudio fue describir las características clínicas, la respuesta al tratamiento y posibles factores asociados de los pacientes con síndrome de Guillain Barré en el Instituto Nacional de Ciencias Neurológicas. Se realizó un estudio descriptivo sobre egresos hospitalarios durante el periodo 2017-2019. La respuesta al tratamiento se evaluó mediante la escala de discapacidad de Hughes. De los 31 pacientes el 61,3% eran varones, y la edad promedio fue de 50 años. Al ingreso, el 87,1% de pacientes se encontraban en el grado 3 o 4 de la escala de Hughes, la mayoría con compromiso axonal, el cual estuvo asociado a discapacidad. Solo 22 pacientes recibieron recambio plasmático; luego de seis meses el 90,9% disminuyó al menos en un grado en la escala de Hughes y el 42,8% quedaron sin discapacidad. En conclusión, se encontró un predominio del sexo masculino y del compromiso axonal, este último asociado a discapacidad.

ABSTRACT The objective of the study was to describe the clinical characteristics, treatment response and possible associated factors of patients with Guillain-Barré syndrome at the National Institute of Neurological Sciences. A descriptive study on hospital discharges was conducted during the period 2017-2019. Treatment response was evaluated based on Hughes' disability scale. From 31 patients 61.3% were males and the mean age was 50 years. At admission, 87.1% of patients were on grade 3 or 4 of Hughes scale, most of them with axonal compromise which was associated to disability. Only 22 patients received plasma exchange; 6 months thereafter, 90.9% of patients decreased by at least one degree in Hughes scale and 42.8% were left without disability. In conclusion, a male and axonal subtype predominance was found, been the latter associated to disability.

Características clínicas y respuesta al recambio plasmático terapéutico en los pacientes con síndrome de Guillain Barré / Clinical characteristics and plasma exchange response in Guillain-Barré patients

RESUMEN El objetivo del estudio fue describir las características clínicas, la respuesta al tratamiento y posibles factores asociados de los pacientes con síndrome de Guillain Barré en el Instituto Nacional de Ciencias Neurológicas. Se realizó un estudio descriptivo sobre egresos hospitalarios durante el periodo 2017-2019. La respuesta al tratamiento se evaluó mediante la escala de discapacidad de Hughes. De los 31 pacientes el 61,3% eran varones, y la edad promedio fue de 50 años. Al ingreso, el 87,1% de pacientes se encontraban en el grado 3 o 4 de la escala de Hughes, la mayoría con compromiso axonal, el cual estuvo asociado a discapacidad. Solo 22 pacientes recibieron recambio plasmático; luego de seis meses el 90,9% disminuyó al menos en un grado en la escala de Hughes y el 42,8% quedaron sin discapacidad. En conclusión, se encontró un predominio del sexo masculino y del compromiso axonal, este último asociado a discapacidad.

ABSTRACT The objective of the study was to describe the clinical characteristics, treatment response and possible associated factors of patients with Guillain-Barré syndrome at the National Institute of Neurological Sciences. A descriptive study on hospital discharges was conducted during the period 2017-2019. Treatment response was evaluated based on Hughes' disability scale. From 31 patients 61.3% were males and the mean age was 50 years. At admission, 87.1% of patients were on grade 3 or 4 of Hughes scale, most of them with axonal compromise which was associated to disability. Only 22 patients received plasma exchange; 6 months thereafter, 90.9% of patients decreased by at least one degree in Hughes scale and 42.8% were left without disability. In conclusion, a male and axonal subtype predominance was found, been the latter associated to disability.

Morphometric analysis of nerve fibers in neural leprosy.

BACKGROUND: The present study assesses the contributions of axonal degeneration and demyelination in leprosy nerve damage. New clinical strategies can emerge from an in-depth understanding of the pathogenesis of neural leprosy (NL). METHODS: Morphometric analysis of myelinated nerve fibers was performed on 44 nerve biopsy samples collected from leprosy patients. Measures of density, diameter distribution, g-ratios, and the counting of axonal ovoids on the myelinated fibers were taken and compared to those in the control group. RESULTS: The proportion of small myelinated fibers increased in the leprosy group while large fiber frequency decreased. Indicative of axonal atrophy, the g-ratio was lower in the leprosy group. The frequency of axonal ovoids was identical to that found in the non-leprosy neuropathies. CONCLUSIONS: Axonal atrophy, Wallerian degeneration, and demyelination coexist in NL. Axonal degeneration predominates over demyelination in the chronic course of the disease; however, this may change during leprosy reactive episodes. This study regards demyelination and axon degeneration as concurrent mechanisms of damage to nerve fibers in leprosy. It also calls into question the view that demyelination is the primary and predominant mechanism in the complex pathogeny of NL.

Connexin and Pannexin-Based Channels in Oligodendrocytes: Implications in Brain Health and Disease.

Oligodendrocytes are the myelin forming cells in the central nervous system (CNS). In addition to this main physiological function, these cells play key roles by providing energy substrates to neurons as well as information required to sustain proper synaptic transmission and plasticity at the CNS. The latter requires a fine coordinated intercellular communication with neurons and other glial cell types, including astrocytes. In mammals, tissue synchronization is mainly mediated by connexins and pannexins, two protein families that underpin the communication among neighboring cells through the formation of different plasma membrane channels. At one end, gap junction channels (GJCs; which are exclusively formed by connexins in vertebrates) connect the cytoplasm of contacting cells allowing electrical and metabolic coupling. At the other end, hemichannels and pannexons (which are formed by connexins and pannexins, respectively) communicate the intra- and extracellular compartments, serving as diffusion pathways of ions and small molecules. Here, we briefly review the current knowledge about the expression and function of hemichannels, pannexons and GJCs in oligodendrocytes, as well as the evidence regarding the possible role of these channels in metabolic and synaptic functions at the CNS. In particular, we focus on oligodendrocyte-astrocyte coupling during axon metabolic support and its implications in brain health and disease.

Inflammatory demyelinating neuropathy heralding accelerated chediak-higashi syndrome.

INTRODUCTION: Chediak-Higashi syndrome (CHS) is a very rare autosomal recessive disorder (gene CHS1/LYST) characterized by partial albinism, recurrent infections, and easy bruising. Survivors develop a constellation of slowly progressive neurological manifestations. METHODS: We describe clinical, laboratory, electrophysiological, and genetic findings of a patient who developed an immune-mediated demyelinating neuropathy as the main clinical feature of CHS. RESULTS: The patient presented with subacute flaccid paraparesis, absent reflexes, and reduced vibration sense. Protein and immunoglobulins (Igs) were elevated in the cerebrospinal fluid. Electrodiagnostic tests indicated an acquired chronic demyelinating polyneuropathy. Intravenous Ig and immunosuppressant treatment resulted in neurological improvement. The patient later developed organomegaly and pancytopenia. Bone-marrow smear revealed giant azurophilic granules pathognomonic for CHS. Two novel mutations in the LYST gene were identified through whole exome sequencing [c.7786C>T and c.9106 + 1G>T]. CONCLUSIONS: This case expands the clinical phenotype of CHS and highlights inflammatory demyelinating neuropathy as a manifestation of the disease. Muscle Nerve 55: 756-760, 2017.