Managing Lafora body disease with vagal nerve stimulation

Mikati, Mohamad A.; Tabbara, Faysal

doi:10.1684/epd.2017.0892

Cited by 16 publications

(8 citation statements)

References 23 publications

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“…Besides AEDs, vagal nerve stimulation resulted in temporary cessation of generalized tonic-clonic seizures and status epilepticus in two single-case studies 103,104 . The ketogenic diet was also tried in a group of patients with relatively advanced disease but was shown to be ineffective 99 .…”

Section: Current Management Strategiesmentioning

confidence: 99%

Lafora disease — from pathogenesis to treatment strategies

et al. 2018

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Lafora disease is a severe, autosomal recessive, progressive myoclonus epilepsy. The disease usually manifests in previously healthy adolescents, and death commonly occurs within 10 years of symptom onset. Lafora disease is caused by loss-of-function mutations in EPM2A or NHLRC1, which encode laforin and malin, respectively. The absence of either protein results in poorly branched, hyperphosphorylated glycogen, which precipitates, aggregates and accumulates into Lafora bodies. Evidence from Lafora disease genetic mouse models indicates that these intracellular inclusions are a principal driver of neurodegeneration and neurological disease. The integration of current knowledge on the function of laforin-malin as an interacting complex suggests that laforin recruits malin to parts of glycogen molecules where overly long glucose chains are forming, so as to counteract further chain extension. In the absence of either laforin or malin function, long glucose chains in specific glycogen molecules extrude water, form double helices and drive precipitation of those molecules, which over time accumulate into Lafora bodies. In this article, we review the genetic, clinical, pathological and molecular aspects of Lafora disease. We also discuss traditional antiseizure treatments for this condition, as well as exciting therapeutic advances based on the downregulation of brain glycogen synthesis and disease gene replacement.

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Section: Current Management Strategiesmentioning

confidence: 99%

Lafora disease — from pathogenesis to treatment strategies

et al. 2018

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“…In conclusion, even if larger series are needed, VNS may be considered an effective adjunctive treatment in PMEs, acting on symptoms and improving patients' quality of life (QoL) [38][39][40][41][42].…”

Section: Vagus Nerve Stimulationmentioning

confidence: 99%

Emerging treatments for progressive myoclonus epilepsies

Riva

Guglielmo

Balagura

et al. 2020

Expert Review of Neurotherapeutics

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Introduction: Progressive myoclonus epilepsies (PMEs) are a group of neurodegenerative diseases, invariably leading to severe disability or fatal outcome in a few years or decades. Nowadays, PMEs treatment remains challenging with a significant burden of disability for patients. Pharmacotherapy is primarily used to treat seizures, which impact patients' quality of life. However, new approaches have emerged in the last few years, which try to curb the neurological deterioration of PMEs through a better knowledge of the pathogenetic process. This is a review on the newest therapeutic options for the treatment of PMEs.Areas covered: Experimental and clinical results on novel therapeutic approaches for the different forms of PME are reviewed and discussed. Special attention is primarily focused on the efficacy and tolerability outcomes, trying to infer the role novel approaches may have in the future. Expert opinion:The large heterogeneity of disease-causing mechanisms prevents researchers from identifying a single approach to treat PMEs. Understanding of pathophysiologic processes is leading the way to targeted therapies, which, through enzyme replacement or underlying gene defect correction have already proved to potentially strike on neurodegeneration.

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“…Se han descrito dos casos de pacientes en los que se ha producido una mejora de los síntomas mediante el implante de un estimulador del nervio vago [62,63]. El mecanismo por el cual esta técnica funciona no está claro, pero debe implicar alteraciones en la modulación de neurotransmisores de la irritabilidad cortical [62]. -Ácido 4-fenilbutírico (4-PBA, por sus siglas en inglés) y metformina.…”

Section: Manejo Y Tratamiento Multidisciplinar En La Enfermedad De Launclassified

Enfermedad de Lafora: revisión de la bibliografía

Desdentado

Espert

Sanz³

et al. 2019

RevNeurol

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Este trabajo no ha sido financiado por ninguna entidad. Conflictos de interésNo existen conflictos de interés Resumen.Introducción. La enfermedad de Lafora (LD) es una forma de epilepsia mioclónica progresiva de herencia autosómica recesiva, de inicio en la infancia tardía o en la adolescencia, y producida por mutaciones de pérdida de función en los genes EPM2A o EPM2B, los cuales codifican para las proteínas laforina y malina, respectivamente.Desarrollo. Los principales síntomas de la enfermedad, que empeoran progresivamente, son: mioclonías, crisis occipitales, crisis tónico-clónicas generalizadas, deterioro cognitivo, síntomas neuropsiquiátricos, y ataxia. El curso es progresivo y fatal. Patológicamente, la LD se caracteriza por la presencia de depósitos de poliglucosanos llamados cuerpos de Lafora (LBs, del inglés Lafora bodies) en el cerebro, hígado, músculo, y glándulas sudoríparas. El diagnóstico de LD se realiza mediante hallazgos clínicos, electrofisiológicos, histológicos y genéticos. Actualmente, no existe un tratamiento que erradique o prevenga el desarrollo de la enfermedad. Tradicionalmente, se utilizan fármacos antiepilépticos para el manejo de las mioclonías y las convulsiones, aunque aparecen resistencias a los mismos.Conclusiones. La LD es una enfermedad rara que, pese a su baja prevalencia, supone graves consecuencias para los pacientes y sus cuidadores. Así pues, resulta necesario continuar la investigación para clarificar los mecanismos subyacentes y desarrollar nuevos tratamientos paliativos y curativos de la enfermedad.

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Managing Lafora body disease with vagal nerve stimulation

Cited by 16 publications

References 23 publications

Lafora disease — from pathogenesis to treatment strategies

Lafora disease — from pathogenesis to treatment strategies

Emerging treatments for progressive myoclonus epilepsies

Enfermedad de Lafora: revisión de la bibliografía

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