RESUMO
Objective: This study tested the hypothesis that a neuroprotective combined therapy based on epidermal growth factor (EGF) and growth hormone-releasing hexapeptide (GHRP6) could be safe for acute ischemic stroke patients, admitting up to 30% of serious adverse events (SAE) with proven causality. Methods: A multi-centric, randomized, open-label, controlled, phase I-II clinical trial with parallel groups was conducted (July 2017 to January 2018). Patients aged 18-80 years with a computed tomography-confirmed ischemic stroke and less than 12 h from the onset of symptoms were randomly assigned to the study groups I (75 µg rEGF + 3.5 mg GHRP6 i.v., n=10), II (75 µg rEGF + 5 mg GHRP6 i.v., n=10), or III (standard care control, n=16). Combined therapy was given BID for 7 days. The primary endpoint was safety over 6 months. Secondary endpoints included neurological (NIHSS) and functional [Barthel index and modified Rankin scale (mRS)] outcomes. Results: The study population had a mean age of 66 ± 11 years, with 21 men (58.3%), a baseline median NIHSS score of 9 (95% CI: 8-11), and a mean time to treatment of 7.3 ± 2.8 h. Analyses were conducted on an intention-to-treat basis. SAEs were reported in 9 of 16 (56.2%) patients in the control group, 3 of 10 (30%) patients in Group I (odds ratio (OR): 0.33; 95% CI: 0.06-1.78), and 2 of 10 (20%) patients in Group II (OR: 0.19; 95% CI: 0.03-1.22); only two events in one patient in Group I were attributed to the intervention treatment. Compliance with the study hypothesis was greater than 0.90 in each group. Patients treated with EGF + GHRP6 had a favorable neurological and functional evolution at both 90 and 180 days, as evidenced by the inferential analysis of NIHSS, Barthel, and mRS and by their moderate to strong effect size. At 6 months, proportion analysis evidenced a higher survival rate for patients treated with the combined therapy. Ancillary analysis including merged treated groups and utility-weighted mRS also showed a benefit of this combined therapy. Conclusion: EGF + GHRP6 therapy was safe. The functional benefits of treatment in this study supported a Phase III study. Clinical Trial Registration: RPCEC00000214 of the Cuban Public Registry of Clinical Trials, Unique identifier: IG/CIGB-845I/IC/1601.
RESUMO
Se presenta una secuencia de imágenes tomográficas cerebrales no contrastadas de calcinosis, identificada en un paciente masculino de 66 años con disartria, dislalia e historia de deterioro cognitivo progresivo, así como manifestaciones neuropsiquiátricas de depresión, delirio y psicosis de curso crónico con más de tres meses de evolución.El examen evidenció imágenes hiperdensas bilaterales sobre los ganglios de la base y la sustancia blanca cerebral y cerebelosa, compatibles con calcio (figura 1). En el panel A se observan calcificaciones periventriculares en ambos hemisferios cerebrales, en el panel B calcificaciones multifocales en ganglios basales y las interfases de sustancia gris y sustancia blanca de ambos hemisferios y en el panel C calcificaciones múltiples focales en región del puente y hemisferios cerebrales.Se planteó como diagnóstico el síndrome de Fahr, enfermedad poco frecuente dada su escasa prevalencia (cinco casos por 10 000 habitantes), cuyo patrón de herencia es autosómico dominante. Dado al pronóstico desfavorable de la enfermedad, se incrementaron las manifestaciones y el deterioro neurológico, lo que llevó al paciente hacia la discapidad, la postración y la muerte(AU)