RESUMEN
Nucleotide-binding, leucine-rich repeat containing X1 (NLRX1) is a mitochondria-located innate immune sensor that inhibits major pro-inflammatory pathways such as type I interferon and nuclear factor-κB signaling. We generated a novel, spontaneous, and rapidly progressing mouse model of multiple sclerosis (MS) by crossing myelin-specific T-cell receptor (TCR) transgenic mice with Nlrx1-/- mice. About half of the resulting progeny developed spontaneous experimental autoimmune encephalomyelitis (spEAE), which was associated with severe demyelination and inflammation in the central nervous system (CNS). Using lymphocyte-deficient mice and a series of adoptive transfer experiments, we demonstrate that genetic susceptibility to EAE lies within the innate immune compartment. We show that NLRX1 inhibits the subclinical stages of microglial activation and prevents the generation of neurotoxic astrocytes that induce neuronal and oligodendrocyte death in vitro. Moreover, we discovered several mutations within NLRX1 that run in MS-affected families. In summary, our findings highlight the importance of NLRX1 in controlling the early stages of CNS inflammation and preventing the onset of spontaneous autoimmunity.
Asunto(s)
Encefalomielitis Autoinmune Experimental/etiología , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/fisiología , Adulto , Animales , Astrocitos/fisiología , Estudios de Casos y Controles , Sistema Nervioso Central/patología , Codón sin Sentido , Enfermedades Desmielinizantes , Encefalomielitis Autoinmune Experimental/patología , Femenino , Humanos , Inmunidad Innata , Masculino , Ratones Transgénicos , Persona de Mediana Edad , Mutación Missense , Adulto JovenRESUMEN
BACKGROUND: The SUNCT syndrome (short-unilateral neuralgiform headache with conjunctival injection and tearing) can be very disabling for affected patients and is often refractory to medical management. We report the first case of SUNCT with a successful response to stereotactic radiosurgery without any adverse effect. CASE: After failing optimal medical treatment, a 82-year old male patient suffering from SUNCT syndrome was treated with Gamma knife radiosurgery. The trigeminal nerve and sphenopalatine ganglion were targeted with a maximum dose of 80 Gy each. The patient had complete pain cessation 2 weeks after the treatment, and remains pain-free with no medication at the latest follow-up 39 months after radiosurgery. He did not have any side effect from the procedure. CONCLUSION: Gamma knife radiosurgery is an option for medically refractory SUNCT patients.
