The Newcastle Pediatric Mitochondrial Disease Scale: translation and cultural adaptation for use in Brazil / Escala Pediátrica de Doença Mitocondrial de Newcastle: tradução e adaptação cultural para uso no Brasil

ABSTRACT Objective The aim of this study was to translate and adapt the Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) to Portuguese for use in Brazil. Methods The scale was applied in 20 pediatric patients with mitochondrial disease, in three groups: myopathy (n = 4); Leigh syndrome (n = 8); and encephalomyopathy (n = 8). Scores were obtained for the various dimensions of the NPMDS, and comparisons were drawn between the groups. Results There was a statistically significant difference between the myopathy group and the Leigh syndrome group (p = 0.0085), as well as between the myopathy and encephalomyopathy groups (p = 0.01). Conclusions The translation of the NPMDS, and its adaptation to the socioeconomic and cultural conditions in Brazil, make the NPMDS score useful as an additional parameter in the evaluation and monitoring of pediatric patients with MD in Brazil.

RESUMO Objetivo O objetivo do presente estudo foi realizar a tradução e adaptação da escala NPMDS para a população brasileira. Métodos A escala foi aplicada em 20 crianças e adolescentes com doença mitocondrial (DM) divididos em três grupos: miopatia (n=4), síndrome de Leigh (n=8) e encefalomiopatia (n=8). Obteve-se os escores separados das dimensões da escala NPMDS, foram realizadas comparações entre os escores da NPMDS nos diferentes grupos. Conclusão A tradução da escala NPMDS e sua adequação as condições socioeconômicas e culturais de nossa população tornam este instrumento um parâmetro adicional na avaliação e acompanhamento de pacientes pediátricos com DM.

Relationship between work rate and oxygen uptake in mitochondrial myopathy during ramp-incremental exercise

We determined the response characteristics and functional correlates of the dynamic relationship between the rate (Δ) of oxygen consumption ( VO2) and the applied power output (work rate = WR) during ramp-incremental exercise in patients with mitochondrial myopathy (MM). Fourteen patients (7 males, age 35.4 ± 10.8 years) with biopsy-proven MM and 10 sedentary controls (6 males, age 29.0 ± 7.8 years) took a ramp-incremental cycle ergometer test for the determination of the VO2 on-exercise mean response time (MRT) and the gas exchange threshold (GET). The ΔVO2/ΔWR slope was calculated up to GET (S1), above GET (S2) and over the entire linear portion of the response (S T). Knee muscle endurance was measured by isokinetic dynamometry. As expected, peak VO2 and muscle performance were lower in patients than controls (P < 0.05). Patients had significantly lower ΔVO2/ΔWR than controls, especially the S2 component (6.8 ± 1.5 vs 10.3 ± 0.6 mL·min-1·W-1, respectively; P < 0.001). There were significant relationships between ΔVO2/ΔWR (S T) and muscle endurance, MRT-VO2, GET and peak VO2 in MM patients (P < 0.05). In fact, all patients with ΔVO2/ΔWR below 8 mL·min-1·W-1 had severely reduced peak VO2 values (<60 percent predicted). Moreover, patients with higher cardiopulmonary stresses during exercise (e.g., higher Δ ventilation/carbon dioxide output and Δ heart rate/ΔVO2) had lower ΔVO2/ΔWR (P < 0.05). In conclusion, a readily available, effort-independent index of aerobic dysfunction during dynamic exercise (ΔVO2/ΔWR) is typically reduced in patients with MM, being related to increased functional impairment and higher cardiopulmonary stress.

Implicaciones neuropsiquiátricas de las citopatías mitocondriales. A propósito de un caso / Neuropsychiatric implications of mitochondrial cytopathies. A case report

Las citopatías mitocondriales son enfermedades raras cuya fisiopatología común consiste en una disfunción del metabolismo energético mitocondrial. Comprometen especialmente a los tejidos muscular y cerebral debido a su alto metabolismo oxidativo, por lo que frecuentemente se les denomina «encefalomiopatías». Caso clínico. Mujer de 28 años, que a los 20 inicia un cuadro caracterizado por dificultad en la marcha y ptosis palpebral, diagnosticada de síndrome Kearns-Sayre. Es seguida ambulatoriamente tras presentar un episodio ansioso-depresivo. Método. Se realiza una exploración neuropsicológica con el fin de evaluar la situación cognitiva. Se administraron la Escala de Inteligencia de Wechler para Adultos (WAIS-III), el Test Barcelona Revisado y el Test de Clasificación de tarjetas de Wisconsin. Resultados. Los resultados revelan deterioro cognitivo a nivel general, que aparece invariablemente en todas las pruebas administradas. También se encuentran déficits específicos coherentes con los encontrados en estudios anteriores. Discusión. El interés del caso estriba en la creciente importancia de la exploración neuropsicológica en trastornos neurológicos que cursan con deterioro cognitivo y alteraciones psiquiátricas. Permite objetivar el grado de deterioro cognitivo global, así como dilucidar las funciones que de manera específica se encuentran afectadas. Ofrece un análisis detallado y ayuda a establecer una correlación entre los déficits y las áreas cerebrales implicadas, por lo que es un instrumento muy útil como complemento de las pruebas de neuroimagen. El perfil obtenido es de gran utilidad para elaborar programas de rehabilitación centrados en la estimulación y la recuperación de funciones alteradas. Se discute también su relación con los trastornos afectivos (AU)

Mitochondrial cytopathies are unusual diseases of which there are more than 50 variations. Their common pathophysiology involves a mitochondrial energy metabolism malfunction. Muscular and brain tissue are particularly affected due to their high oxidative metabolism, hence they are usually identified as «encephalomyopathies». Case report. A 28 year old woman, who, at the age of 20, presented with a gait disorder and drooping upper eye-lid, was diagnosed with Kearns-Sayre syndrome. After an anxious-depressive episode, she was followed up in the Outpatients of a Mental Health Centre with psychiatric and psychological treatment. Methods. Neuropsychological assessments were made to explore the cognitive state. We applied the Wechsler Adults Intelligence Scale (WAIS-III), the Revised Barcelona Test and the Wisconsin Card Sorting. Results. General cognitive impairment was found in all the tests administered. Specific cognitive impairments were also found which fitted in with those found in previous studies. Discussion. This case report emphasizes the increasing importance of neuropsychological assessment in neurological syndromes with cognitive impairments and psychiatric disturbances. It allows us to objectify the overall level of cognitive impairment and to establish a correlation between the deficits and the brain areas involved. The neuropsychological profile is very useful in future rehabilitation programs, focusing on stimulation and recovery of the affected cognitive areas. We discussed also her relationship with mood disorders (AU)

La disfunción mitocondrial en la fibromialgia y su implicación en la patogénesis de la enfermedad / Mitochondrial dysfunction in fibromyalgia and its implication in the pathogenesis of disease

La fibromialgia (FM) es un síndrome de dolor crónico generalizado de etiología desconocida. Recientes estudios han mostrado evidencias sobre el papel que podría tener el estrés oxidativo en la fisiopatología de la FM, pero aún no está claro si es la causa o el efecto de las anormalidades observadas en esta. Además, se desconoce la función de la mitocondria en la fisiopatología de la enfermedad, sin embargo, se han observado signos de alteración mitocondrial en esta. Se sabe que la mitocondria es una importante productora de especies reactivas de oxígeno, por lo que se la ha relacionado con el mecanismo patogénico de numerosas enfermedades, incluida la FM. A este respecto, se ha observado que los tratamientos con antioxidantes podrían ser beneficiosos para mejorar el funcionamiento mitocondrial. Por tanto, la disfunción mitocondrial abre un gran campo de investigación terapéutica, por lo que se debería empezar a considerar en la medicina clínica el abordaje de la FM mediante tratamiento con antioxidantes y fármacos relacionados con la biogénesis mitocondrial (AU)

Fibromyalgia (FM) is a chronic pain syndrome with unknown etiology. Recent studies have shown evidence demonstrating that oxidative stress may have a role in the pathophysiology of FM, however it is still not clear whether oxidative stress is the cause or the effect of the abnormalities documented in FM. Furthermore, it is also controversial the role of mitochondria in the pathophysiology of FM, however signs associated with mitochondrial dysfunction have been observed in FM. Mitochondria are also known to be strong producers of ROS, so have been related with the pathogenic mechanism of numerous diseases including FM. To this respect, it has been observed antioxidants therapies might be beneficial to improve the mitochondrial performance. Therefore, the dysfunction mitochondrial opens a great field of therapeutic research, for what it should start considering in the clinical medicine the boarding of the FM by means of therapy with antioxidant and drugs related to the mitochondrial biogenesis (AU)

La miopatía isquémica en la enfermedad arterial periférica / Ischaemic myopathy of peripheral arterial occlusive disease

Introducción. La mitocondria afectada por la isquemia provoca una miopatía y un aumento deradicales libres de oxígeno (RLO), que conduce a daño oxidativo y activación del proceso infl amatorio,ambos asociados al fenómeno isquemia-reperfusión.Objetivo. Estudiar la alteración mitocondrial del músculo estriado, provocada por la isquemia,y sus repercusiones en la enfermedad arterial periférica (EAP).Métodos. Estrategia de búsqueda avanzada en Pub-Med (http://www.ncbi.nlm.nih.gov/Pub-Med) y búsqueda manual de bibliografía.Desarrollo. Los principales trabajos consultados indican la existencia de una disfunción mitocondrialcaracterística con alteración de los complejos de la cadena respiratoria. Esto conducea un incremento de RLO que dañan el ADN mitocondrial, perpetuándose el círculo vicioso deempeoramiento de cadena respiratoria-daño oxidativo-alteración del ADN mitocondrial, al estarlos complejos CI, CIII y CIV codifi cados por el ADN mitocondrial lesionado.Conclusión. Se necesitan más trabajos para comprender la miopatía isquémica provocada porladisminución del fl ujo en la EAP(AU)

Introduction. Ischemic injury involves a mitochondrial dysfunction causing a typical miopathyand an increase of free radicals. It may lead to oxidative tissue injury and activation ofinfl ammatory response, both of them in relation to reperfusion ischemia injury.Aim. To study mitochondrial impairment in skeletal muscle as a consequence of ischemia andeffects of mitochondrial dysfunction in peripheral arterial disease (PAD).Methods. Advanced search strategy: PubMed (http://www.ncbi.nlm.nih.gov/PubMed) andmanual literature search. Results. The main studies reviewed indicate that there is a mitochondrial dysfunction havingspecial characteristics. Dysfunctions in the electron transport chain lead to increased productionof reactive oxygen species which cause damage to mitochondrial DNA, launching a vicious cycleof worsening electron transport chain disruption-oxidant production-further mitochondrialdeterioration since impaired complex are encoded by damaged mitochondrial DNA.Conclusion. Further work is required to understand ischemic miopathy as a consequence of adecreased blood fl ow in PAD(AU)

Teste de esforço cardiopulmonar na avaliaçäo de doenças musculares / Cardiopulmonary exercise testing for evaluation of muscle diseases

Objetivo: Analisar o teste de esforço cardiopulmonar (TECP) no diagnóstico de miopatias. Métodos: 27 pacientes com miopatia realizaram TECP (protocolo de bicicleta em rampa, máximo, interrompido por sintoma). Resultados: Pacientes distróficos e pacientes com mitocondriopatias mostraram diferenças significativas em relaçao aos controles para as variáveis potência do trabalho desenvolvido (watt) e pico do consumo de oxigênio (VO2máx). Pacientes com mitocondriopatias mostraram diminuiçao significativa do limiar anaeróbio em relaçao aos controles, além de elevaçao dos valores do quociente respiratório (QR) do pico do exercício em relaçao aos demais grupos. Conclusoes: TECP pode ser útil na avaliaçao evolutiva do grau de limitaçao física dos pacientes com miopatia. As variáveis potência do trabalho desenvolvido, VO2 máx, limiar anaeróbio e QR do pico do exercício podem sugerir o diagnóstico de miopatia e seus subtipos, excluindo quadros psicológicos.

Descargas repetitivas complejas en una miopatía mitocondrial / Complex repetitive discharges in a mitochondrial myopathy

Mujer de 54 años de edad estudiada por debilidad crónica, atrofia muscular y elevación de creatin Kinshasa en sangre. El EMG de musculatura proximal de miembros superiores e inferiores reveló se registraron numerosas descargas repetitivas de potenciales de unidad motora polifásicos con amplitudes y frecuencias de disparo constantes, estaban integradas por 6 potenciales de fibra simple con un “jitter” entre sus diferentes componentes inferior a 5 µseg. Que sepamos, no han sido descritas descargas repetitivas complejas de estas características en miopatías mitocondriales del hombre, aunque si han sido referidas en el perro

A 54 year old woman was studied in our lab because chronic weakness, limb-girdle muscular atrophy and increased blood CK level. Electromyography assessment of proximal muscles in arms and legs revealed complex repetitive discharges with a very low interpotential jitter lesser than 5 µseg, further indicating the absence of end plate activity in their causation. Then, they are thought to originate form spontaneous activity in a single muscle fiber which activates one or more adjacent muscle fibre ephaptically. Ephaptic transmission from fibre to fibre in skeletal muscle is ordinarily prevented by the absence of adjacent simultaneously depolarizing muscle fibres, because of the pseudorandom nature of the distribution of the motor unit. When this relation is disturbed by reorganization of the motor unit in neurogenic and, to a lesser extent, in cronic myopathic diseases, cross-firing of adjacent muscle fibres is more likely. In our knowledge, this is the first time that complex repetitive discharges have been found in a human mitochondrial myopathic although they have been yet reported in sheepdog littermates