RESUMEN
BACKGROUND AND PURPOSE: Individuals with GBA (glucocerebrosidase) mutations are at increased risk of Parkinson's disease (PD). It is still debated, however, whether this increased risk results from impaired glucocerebrosidase activity leading to substrate accumulation. Comparing the presence of prodromal PD marker in GBA mutation carriers and patients with Gaucher disease (GD) (in which substrate accumulation is extensive) can assist in clarifying this issue. METHODS: In this cross-sectional study, we compared the hyperechogenic area of the substantia nigra, a prodromal PD marker, in large cohorts of GBA mutation carriers (n = 71) and patients with GD (n = 145). Our control populations were healthy, non-carriers (n = 49) and patients with GBA -related PD (n = 11). Substrate accumulation was assessed from dry blood spot levels of glucosylsphingosine. RESULTS: Our findings indicate no contribution of substrate accumulation, as the area of hyperechogenicity is similarly enlarged relative to healthy controls in both GBA mutation carriers and patients with GD. Moreover, this similarity between GBA carriers and patients with GD persists when comparing only carriers of the N370S (c.1226A>G) mutation (n = 38) with untreated patients with GD who were homozygotes for the same mutation (n = 47). In addition, measurements of hyperechogenic area did not correlate with levels of glucosylsphingosine in the untreated patients with GD. CONCLUSION: The presence of a marker of prodromal PD (substantia nigra hyperechogenicity) is independent of substrate accumulation in a population with mutated GBA . Although further longitudinal studies are needed to determine the precise predictive value of this marker for GBA -related PD, our findings raise doubts regarding the contribution of substance reduction strategies to PD prevention.
Asunto(s)
Enfermedad de Gaucher/diagnóstico por imagen , Glucosilceramidasa/genética , Enfermedad de Parkinson/diagnóstico por imagen , Sustancia Negra/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores , Estudios Transversales , Femenino , Enfermedad de Gaucher/genética , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Mutación , Enfermedad de Parkinson/genética , Síntomas Prodrómicos , Psicosina/análogos & derivados , UltrasonografíaRESUMEN
BACKGROUND AND PURPOSE: MMRT may be beneficial in a subset of patients with large hemispheric stroke who cannot be treated with systemic thrombolysis. Because most previous studies only included relatively young patients, the outcome of very old patients given MMRT remains unknown. MATERIALS AND METHODS: Consecutive patients with large hemispheric stroke treated with MMRT and admitted to intensive care were included. We compared neurologic and functional outcomes between patients younger and older than 80 years. RESULTS: We included 14 patients older than 80 years and compared them with 66 patients who were younger than 80. Cerebrovascular risk factor profile, admission NIHSS scores, stroke etiology and pathogenesis, and procedure-related variables did not differ between the groups except for a higher prevalence of smoking in younger patients. Excellent target vessel recanalization (Thrombolysis in Myocardial Infarction score of 3) and good outcome at 90 days (modified Rankin Score ≤ 2) were more common in younger patients (45% versus 14%, P = .047, and 41% versus 0%, P = .008, respectively). In contrast, mortality rates were higher in octogenarians (43% versus 17%, respectively). CONCLUSIONS: In this study, very old patients had higher chances of mortality and a very low probability of achieving functional independence even after MMRT. Further prospective studies are needed to examine the futility of MMRT in the very old.