RESUMEN
Amyotrophic lateral sclerosis (ALS) is an aggressive neurodegenerative disorder that selectively attacks motor neurons in the brain and spinal cord. Despite important advances in the knowledge of the etiology and progression of the disease, there are still no solid grounds in which a clinician could make an early objective and reliable diagnosis from which patients could benefit. Diagnosis is difficult and basically made by clinical rating scales (ALSRs and El Escorial). The possible finding of biomarkers to aid in the early diagnosis and rate of disease progression could serve for future innovative therapeutic approaches. Recently, it has been suggested that ALS has an important immune component that could represent either the cause or the consequence of the disease. In this report, we analyzed 19 different cytokines and growth factors in the cerebrospinal fluid of 77 ALS patients and 13 controls by decision tree and PanelomiX program. Results showed an increase of Adipsin, MIP-1b, and IL-6, associated with a decrease of IL-8 thresholds, related with ALS patients. This biomarker panel analysis could represent an important aid for diagnosis of ALS alongside the clinical and neurophysiological criteria.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/líquido cefalorraquídeo , Esclerosis Amiotrófica Lateral/líquido cefalorraquídeo , Factor D del Complemento/líquido cefalorraquídeo , Interleucina-8/líquido cefalorraquídeo , Adulto , Biomarcadores/líquido cefalorraquídeo , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Amyotrophic lateral sclerosis (ALS) is described as a neurodegenerative disorder. However, neuroinflammation and chemokine expression are prominent pathological finding at sites of injury. Adipsin and adiponectin are molecules that are implicated in the pathogenesis of neurodegenerative and neuroimmune disorders. Adipsin and adiponectin concentrations were determined in the CSF of ALS patients and controls and the relationship of these chemokines with clinical severity and disease duration in ALS was determined. Seventy-seven ALS patients (mean age 49.5 ± 10.4 years) (mean body mass index 23.5 ± 4.5) were included. Twenty patients had bulbar, 53 spinal, and four bulbospinal onset ALS. Median adipsin CSF level was 12,650.94 pg/ml in ALS patients and 3290.98 pg/ml in controls (p < 0.001). Median adiponectin CSF level was 4608 pg/ml in ALS patients and 3453 pg/ml in controls (p = 0.1). No differences were observed in disease duration, progression rate or disease severity. There was a significant positive correlation between adipsin and adiponectin concentrations (r = 0.379, p = 0.01). No correlation with age, body mass index or ALFRS-R score was found. Adipsin was significantly elevated in CSF, suggesting that this chemokine might have a role in ALS pathogenesis. Adiponectin showed a trend towards higher concentrations, but failed to reach statistical significance. Due to the clinical heterogeneity in our cohort, these chemokines do not appear to be associated with disease duration or severity.
Asunto(s)
Adiponectina/líquido cefalorraquídeo , Esclerosis Amiotrófica Lateral/líquido cefalorraquídeo , Factor D del Complemento/líquido cefalorraquídeo , Adulto , Anciano , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: Adipokines, especially leptin and adiponectin, have gained increasing importance in pathophysiology of various neurological diseases including epilepsy. There are experimental data suggesting a role for leptin in the genesis of seizures and neuroprotection related to seizures. However there are no clinical studies on the effects of epileptic seizures on adipokines. METHODS: We measured cerebrospinal fluid (CSF) and plasma levels of leptin, adiponectin and adipsin after provoked or unprovoked primary or secondarily generalized tonic-clonic seizures in 13 female patients and seven controls. The samples were taken within 24h after the seizure onset. RESULTS: Leptin plasma levels correlated negatively with the time to sample withdrawal, i.e. the longer the time interval between the seizure and the sample the lower the leptin levels in the patients. Interestingly, plasma adiponectin levels were significantly increased after the seizure episode. CONCLUSION: This study provides further evidence that there are seizure-induced acute changes in adipokine metabolism. Leptin concentrations seem to decrease during the first 24h after the seizure whereas adiponectin levels increase. The meaning of this response is far from clear, but it might be an endogenous attempt to prevent harmful effects of epileptic seizures in the central nervous system.
Asunto(s)
Adiponectina/metabolismo , Factor D del Complemento/metabolismo , Epilepsia Tónico-Clónica/metabolismo , Leptina/metabolismo , Adiponectina/sangre , Adiponectina/líquido cefalorraquídeo , Adolescente , Adulto , Anciano , Factor D del Complemento/líquido cefalorraquídeo , Epilepsia Tónico-Clónica/sangre , Epilepsia Tónico-Clónica/líquido cefalorraquídeo , Femenino , Humanos , Leptina/sangre , Leptina/líquido cefalorraquídeo , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: The aim of this study was to investigate the levels of three adipocytokines: leptin, adiponectin and adipsin, in serum and cerebrospinal fluid (CSF) of twins discordant for multiple sclerosis (MS). Adipose tissue is an important component connecting immune system and several tissues and organs including CNS. Fat cells produce adipocytokines, which seem to have a role in various autoimmune disorders including MS. METHODS: Plasma samples were collected from twelve twins and CSF samples from four twins discordant for MS. The concentrations of interleukine (IL)-6, adiponectin, adipsin and leptin in plasma and CSF samples were determined by enzyme immuno assay. RESULTS: A significant difference was seen in the adipocytokine levels in CSF samples. Twins with MS had higher concentrations of adiponectin (P = 0.039) and adipsin (P = 0.039), than their asymptomatic co-twins. CONCLUSION: As adiponectin and adipsin levels in CSF did not correlate with their levels in plasma, it seems that there could be a secondary intrathecal synthesis of these adipocytokines in MS.