RESUMEN
BACKGROUND: Inflammation triggers secondary neurodegeneration in multiple sclerosis (MS). OBJECTIVES: It is unclear whether classical anti-inflammatory cytokines have the potential to interfere with synaptic transmission and neuronal survival in MS. METHODS: Correlation analyses between cerebrospinal fluid (CSF) contents of anti-inflammatory cytokines and molecular, imaging, clinical, and neurophysiological measures of neuronal alterations were performed. RESULTS: Our data suggest that interleukin-13 (IL-13) plays a neuroprotective role in MS brains. We found, in fact, that the levels of IL-13 in the CSF of MS patients were correlated with the contents of amyloid-ß(1-42). Correlations were also found between IL-13 and imaging indexes of axonal and neuronal integrity, such as the retinal nerve fibre layer thickness and the macular volume evaluated by optical coherence tomography. Furthermore, the levels of IL-13 were related to better performance in the low-contrast acuity test and Multiple Sclerosis Functional Composite scoring. Finally, by means of transcranial magnetic stimulation, we have shown that GABAA-mediated cortical inhibition was more pronounced in patients with high IL-13 levels in the CSF, as expected for a neuroprotective, anti-excitotoxic effect. CONCLUSIONS: The present correlation study provides some evidence for the involvement of IL-13 in the modulation of neuronal integrity and synaptic function in patients with MS.
Asunto(s)
Interleucina-13/líquido cefalorraquídeo , Corteza Motora/inmunología , Esclerosis Múltiple Recurrente-Remitente/inmunología , Degeneración Nerviosa/inmunología , Neuronas/inmunología , Adulto , Péptidos beta-Amiloides/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Sensibilidad de Contraste , Evaluación de la Discapacidad , Potenciales Evocados Motores , Femenino , Humanos , Italia , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Corteza Motora/patología , Corteza Motora/fisiopatología , Esclerosis Múltiple Recurrente-Remitente/líquido cefalorraquídeo , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Esclerosis Múltiple Recurrente-Remitente/patología , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Degeneración Nerviosa/líquido cefalorraquídeo , Degeneración Nerviosa/patología , Degeneración Nerviosa/fisiopatología , Degeneración Nerviosa/prevención & control , Neuronas/patología , Fragmentos de Péptidos/líquido cefalorraquídeo , Transmisión Sináptica , Tomografía de Coherencia Óptica , Estimulación Magnética Transcraneal , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Spasticity is a common disorder and a major cause of long-term disability in patients with multiple sclerosis (MS). Our aim was to evaluate whether a recently developed repetitive transcranial magnetic stimulation protocol, the intermittent theta burst stimulation (iTBS) is effective in modulating lower limb spasticity in MS patients. METHODS: Twenty MS patients were pseudorandomized to undergo a 2-week daily sessions of real or sham iTBS protocol. The H/M amplitude ratio of the Soleus H reflex, a reliable neurophysiological index of spinal excitability and the Modified Ashworth Scale (MAS) for spasticity were evaluated by blinded raters before and after the stimulation protocols. RESULTS: Patients receiving real iTBS showed a significant reduction of H/M amplitude ratio and MAS scores 1 week after the stimulation and persisting up to 2 weeks after the end of stimulation protocol. There were no significant effects for sham stimulation. CONCLUSIONS: These results show that iTBS, a safe, non-invasive, well-tolerated and feasible protocol, is a promising tool for the treatment of spasticity in MS.