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Effect of thalamic deep brain stimulation on swallowing in patients with essential tremor.


  • 影响因子:4.6560
  • DOI:10.1002/acn3.51099
  • 作者列表:"Lapa S","Claus I","Reitz SC","Quick-Weller J","Sauer S","Colbow S","Nasari C","Dziewas R","Kang JS","Baudrexel S","Warnecke T
  • 发表时间:2020-06-16

OBJECTIVE:Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) is a mainstay treatment for severe and drug-refractory essential tremor (ET). Although stimulation-induced dysarthria has been extensively described, possible impairment of swallowing has not been systematically investigated yet. METHODS:Twelve patients with ET and bilateral VIM-DBS with self-reported dysphagia after VIM-DBS were included. Swallowing function was assessed clinically and using by flexible endoscopic evaluation of swallowing in the stim-ON and in the stim-OFF condition. Presence, severity, and improvement of dysphagia were recorded. RESULTS:During stim-ON, the presence of dysphagia could be objectified in all patients, 42% showing mild, 42% moderate, and 16 % severe dysphagia. During stim-OFF, all patients experienced a statistically significant improvement of swallowing function. INTERPRETATION:VIM-DBS may have an impact on swallowing physiology in ET-patients. Further studies to elucidate the prevalence and underlying pathophysiological mechanisms are warranted.


目的: 腹侧中间核 (VIM) 深部脑刺激 (DBS) 是治疗严重和药物难治性特发性震颤 (ET) 的主要方法。虽然刺激诱导的构音障碍已被广泛描述,但吞咽可能的障碍尚未被系统研究。 方法: 纳入 12 例 VIM-DBS 术后自行报告吞咽困难的 ET 和双侧 VIM-DBS 患者。通过灵活的内镜评估 stim-ON 和 stim-OFF 条件下的吞咽功能进行临床和使用评估。记录吞咽困难的存在、严重程度和改善情况。 结果: 在 stim-ON 期间,所有患者均可客观化吞咽困难的存在,42% 显示轻度、 42% 中度和 16% 重度吞咽困难。在 stim-OFF 期间,所有患者吞咽功能均有统计学显著改善。 解读: VIM-DBS 可能对 ET 患者的吞咽生理有影响。需要进一步的研究来阐明患病率和潜在的病理生理机制。



作者列表:["Aimé P","Karuppagounder SS","Rao A","Chen Y","Burke RE","Ratan RR","Greene LA"]

METHODS::Identifying disease-causing pathways and drugs that target them in Parkinson's disease (PD) has remained challenging. We uncovered a PD-relevant pathway in which the stress-regulated heterodimeric transcription complex CHOP/ATF4 induces the neuron prodeath protein Trib3 that in turn depletes the neuronal survival protein Parkin. Here we sought to determine whether the drug adaptaquin, which inhibits ATF4-dependent transcription, could suppress Trib3 induction and neuronal death in cellular and animal models of PD. Neuronal PC12 cells and ventral midbrain dopaminergic neurons were assessed in vitro for survival, transcription factor levels and Trib3 or Parkin expression after exposure to 6-hydroxydopamine or 1-methyl-4-phenylpyridinium with or without adaptaquin co-treatment. 6-hydroxydopamine injection into the medial forebrain bundle was used to examine the effects of systemic adaptaquin on signaling, substantia nigra dopaminergic neuron survival and striatal projections as well as motor behavior. In both culture and animal models, adaptaquin suppressed elevation of ATF4 and/or CHOP and induction of Trib3 in response to 1-methyl-4-phenylpyridinium and/or 6-hydroxydopamine. In culture, adaptaquin preserved Parkin levels, provided neuroprotection and preserved morphology. In the mouse model, adaptaquin treatment enhanced survival of dopaminergic neurons and substantially protected their striatal projections. It also significantly enhanced retention of nigrostriatal function. These findings define a novel pharmacological approach involving the drug adaptaquin, a selective modulator of hypoxic adaptation, for suppressing Parkin loss and neurodegeneration in toxin models of PD. As adaptaquin possesses an oxyquinoline backbone with known safety in humans, these findings provide a firm rationale for advancing it towards clinical evaluation in PD.

翻译标题与摘要 下载文献
作者列表:["Sebastián-Serrano Á","Simón-García A","Belmonte-Alfaro A","Pose-Utrilla J","Santos-Galindo M","Del Puerto A","García-Guerra L","Hernández IH","Schiavo G","Campanero MR","Lucas JJ","Iglesias T"]

METHODS::Huntington's disease (HD) is an inherited progressive neurodegenerative disease characterized by brain atrophy particularly in the striatum that produces motor impairment, and cognitive and psychiatric disturbances. Multiple pathogenic mechanisms have been proposed including dysfunctions in neurotrophic support and calpain-overactivation, among others. Kinase D-interacting substrate of 220 kDa (Kidins220), also known as ankyrin repeat-rich membrane spanning (ARMS), is an essential mediator of neurotrophin signaling. In adult brain, Kidins220 presents two main isoforms that differ in their carboxy-terminal length and critical protein-protein interaction domains. These variants are generated through alternative terminal exon splicing of the conventional exon 32 (Kidins220-C32) and the recently identified exon 33 (Kidins220-C33). The lack of domains encoded by exon 32 involved in key neuronal functions, including those controlling neurotrophin pathways, pointed to Kidins220-C33 as a form detrimental for neurons. However, the functional role of Kidins220-C33 in neurodegeneration or other pathologies, including HD, has not been explored. In the present work, we discover an unexpected selective downregulation of Kidins220-C33, in the striatum of HD patients, as well as in the R6/1 HD mouse model starting at early symptomatic stages. These changes are C33-specific as Kidins220-C32 variant remains unchanged. We also find the early decrease in Kidins220-C33 levels takes place in neurons, suggesting an unanticipated neuroprotective role for this isoform. Finally, using ex vivo assays and primary neurons, we demonstrate that Kidins220-C33 is downregulated by mechanisms that depend on the activation of the protease calpain. Altogether, these results strongly suggest that calpain-mediated Kidins220-C33 proteolysis modulates onset and/or progression of HD.

翻译标题与摘要 下载文献
作者列表:["Mendes FR","Leclerc JL","Liu L","Kamat PK","Naziripour A","Hernandez D","Li C","Ahmad AS","Doré S"]

METHODS:BACKGROUND:Neuroinflammation has been recognized as an important factor in the pathogenesis of Alzheimer's disease (AD). One of the most recognized pathways in mediating neuroinflammation is the prostaglandin E2-EP1 receptor pathway. OBJECTIVE:Here, we examined the efficacy of the selective EP1 antagonist ONO-8713 in limiting amyloid-β (Aβ), lesion volumes, and behavioral indexes in AD mouse models after ischemic stroke. METHODS:Transgenic APP/PS1, 3xTgAD, and wildtype (WT) mice were subjected to permanent distal middle cerebral artery occlusion (pdMCAO) and sham surgeries. Functional outcomes, memory, anatomical outcomes, and Aβ concentrations were assessed 14 days after surgery. RESULTS:pdMCAO resulted in significant deterioration in functional and anatomical outcomes in the transgenic mice compared with the WT mice. No relevant differences were observed in the behavioral tests when comparing the ONO-8713 and vehicle-treated groups. Significantly lower cavitation (p = 0.0373) and percent tissue loss (p = 0.0247) were observed in APP/PS1 + ONO-8713 mice compared with the WT + ONO-8713 mice. However, the percent tissue injury was significantly higher in APP/PS1 + ONO-8713 mice compared with WT + ONO-8713 group (p = 0.0373). Percent tissue loss was also significantly lower in the 3xTgAD + ONO-8713 mice than in the WT + ONO-8713 mice (p = 0.0185). ONO-8713 treatment also attenuated cortical microgliosis in APP/PS1 mice as compared with the vehicle (p = 0.0079); however, no differences were observed in astrogliosis across the groups. Finally, APP/PS1 mice presented characteristic Aβ load in the cortex while 3xTgAD mice exhibited very low Aβ levels. CONCLUSION:In conclusion, under the experimental conditions, EP1 receptor antagonist ONO-8713 showed modest benefits on anatomical outcomes after stroke, mainly in APP/PS1 mice.