Directional Deep Brain Stimulation-A Step in the Right Direction? A Systematic Review of the Clinical and Therapeutic Efficacy of Directional Deep Brain Stimulation in Parkinson Disease.

BACKGROUND: The use of directional deep brain stimulation (dDBS) electrodes for the treatment of movement disorders such as Parkinson disease (PD) has become relatively widespread. However, the efficacy of dDBS relative to its omnidirectional deep brain stimulation (oDBS) counterpart is not well characterized. This systematic review aims to synthesize the literature comparing clinical and therapeutic outcomes of dDBS relative to oDBS in patients with PD. METHODS: A systematic literature search for studies with comparative clinical outcome data between dDBS and oDBS was performed across the PubMed, Ovid MEDLINE, and Web of Science databases. Data including therapeutic window (TW) and surrogate measures and the Unified Parkinson's Disease Rating Scale score were collected and summarized across multiple time periods. RESULTS: Ten studies met the eligibility criteria. Three of these studies evaluated motor performance in the form of Unified Parkinson's Disease Rating Scale III, with none finding differences between dDBS and oDBS. Two studies assessed quality-of-life measures with neither finding differences between dDBS and oDBS. TW or a surrogate measure was assessed in 6 studies; 5 studies found an increase or strong trend toward increase in dDBS relative to oDBS. CONCLUSIONS: The current evidence, although limited by bias, does suggest that dDBS in the treatment of PD yields improvements in motor symptoms and quality of life that are comparable to oDBS; TW and surrogate measures are consistently improved in patients with PD under a directional configuration relative to omnidirectional.

Cyanocobalamin prevents cardiomyopathy in type 1 diabetes by modulating oxidative stress and DNMT-SOCS1/3-IGF-1 signaling.

Patients with long-standing diabetes have a high risk for cardiac complications that is exacerbated by increased reactive oxygen species (ROS) production. We found that feeding cyanocobalamin (B12), a scavenger of superoxide, not only prevented but reversed signs of cardiomyopathy in type 1 diabetic Elmo1H/H Ins2Akita/+ mice. ROS reductions in plasma and hearts were comparable to those in mice treated with other antioxidants, N-acetyl-L-cysteine or tempol, but B12 produced better cardioprotective effects. Diabetes markedly decreased plasma insulin-like growth factor (IGF)-1 levels, while B12, but not N-acetyl-L-cysteine nor tempol, restored them. B12 activated hepatic IGF-1 production via normalization of S-adenosylmethionine levels, DNA methyltransferase (DNMT)-1/3a/3b mRNA, and DNA methylation of promoters for suppressor of cytokine signaling (SOCS)-1/3. Reductions of cardiac IGF-1 mRNA and phosphorylated IGF-1 receptors were also restored. Thus, B12 is a promising option for preventing diabetic cardiomyopathy via ROS reduction and IGF-1 retrieval through DNMT-SOCS1/3 signaling.