Subthalamic Nucleus Deep Brain Stimulation in a Patient with Severe Axial Symptoms and Suboptimal Levodopa Responsive Parkinson's Disease.

AIM: Deep brain stimulation (DBS) is a well-established treatment option for improving function and quality of life (QoL) in carefully selected patients with Parkinson?s disease (PD). Patient selection is a crucial step that should be performed by an experienced multidisciplinary team according to the proposed inclusion and exclusion criteria to increase the QoL of patients. CASE REPORT: A 47-year-old bedridden woman with a 20-year history of PD presented with levodopa-unresponsive tremor and severe axial symptoms. Despite various antiparkinsonian medications, a suboptimal improvement was observed with the levodopa challenge test. After detailed evaluations, she underwent bilateral subthalamic nucleus DBS. During the 2-year follow-up, her axial symptoms improved significantly leading to a better QoL. CONCLUSION: Although levodopa-resistant axial symptoms are considered a relative contraindication to DBS surgery, this case report demonstrates that with an interdisciplinary approach and an accurate assessment of symptoms, even bedridden and latestage selected PD cases may benefit from DBS.

Electrode Fixation with Bone Cement or Stimloc® in Deep Brain Stimulation Surgery: A Comparative Study.

AIM: To examine the postoperative outcomes of electrode fixation using bone cement and Stimloc® in patients with Parkinson?s disease (PD) who underwent subthalamic nucleus (STN) deep brain stimulation (DBS). MATERIAL AND METHODS: Between 2016 and 2018, permanent electrode fixation was performed in 30 patients with PD, of which 15 received bone cement and the remaining 15 received Stimloc®. Data regarding preoperative Unified Parkinson?s Disease Rating Scale (UPDRS) III scores, levodopa equivalent daily dose (LEDD) values, surgery duration, and the fixation technique used were recorded. Brain computed tomography was performed for early postoperative evaluation of pneumocephalus and possible hematoma as well as for the determination of migration 1 year postoperatively. UPDRS III scores and LEDD values were re-evaluated 1 year postoperatively; surgery duration, clinical effectiveness, and complication rates were compared between the two fixation techniques. RESULTS: A statistically significant difference in application time was observed between the two techniques (bone cement: 21 min, Stimloc®: 6 min). After 1 year from surgery, 0.92- and 0.88-mm migrations were observed in the bone cement and Stimloc® groups, respectively. A significant correlation between migration and the pneumocephalus volume was observed in both groups. No differences were observed between the groups regarding infection, migration, pneumocephalus volume, wound erosion, and clinical outcomes. CONCLUSION: Stimloc® is preferred over bone cement for electrode fixation in DBS surgeries as it is associated with shorter application duration; this increases patient comfort and tolerance during awake surgery. Clinical efficacy and complication rates associated with both techniques are similar.

Multicenter Validation of Individual Preoperative Motor Outcome Prediction for Deep Brain Stimulation in Parkinson's Disease.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN DBS) is an established therapy for Parkinson's disease (PD) patients suffering from motor response fluctuations despite optimal medical treatment, or severe dopaminergic side effects. Despite careful clinical selection and surgical procedures, some patients do not benefit from STN DBS. Preoperative prediction models are suggested to better predict individual motor response after STN DBS. We validate a preregistered model, DBS-PREDICT, in an external multicenter validation cohort. METHODS: DBS-PREDICT considered eleven, solely preoperative, clinical characteristics and applied a logistic regression to differentiate between weak and strong motor responders. Weak motor response was defined as no clinically relevant improvement on the Unified Parkinson's Disease Rating Scale (UPDRS) II, III, or IV, 1 year after surgery, defined as, respectively, 3, 5, and 3 points or more. Lower UPDRS III and IV scores and higher age at disease onset contributed most to weak response predictions. Individual predictions were compared with actual clinical outcomes. RESULTS: 322 PD patients treated with STN DBS from 6 different centers were included. DBS-PREDICT differentiated between weak and strong motor responders with an area under the receiver operator curve of 0.76 and an accuracy up to 77%. CONCLUSION: Proving generalizability and feasibility of preoperative STN DBS outcome prediction in an external multicenter cohort is an important step in creating clinical impact in DBS with data-driven tools. Future prospective studies are required to overcome several inherent practical and statistical limitations of including clinical decision support systems in DBS care.

The Effect of Bitter Melon (Momordica charantia) Extract on the Uptake of 99mTc Labeled Paclitaxel: In Vitro Monitoring in Breast Cancer Cells.

BACKGROUND: Bitter Melon Extract (BME) is widely used for the treatment of various diseases worldwide due to its rich phytochemical and antioxidant content. The well-known anti-cancer drug Paclitaxel (PAC) plays a major role in the treatment of various cancer types such as ovarian, breast, and lung cancer. Technetium-99m (99mTc) radiolabeled paclitaxel is emerging as an imaging probe for breast cancer in vivo. 99mTc labeled compounds have been attracting more scientific attention since the achievement of earlier researches in Nuclear Medicine. People consume several types of diets of plant origin without knowing the interaction with radiolabeled compounds or radiopharmaceuticals. Objective: In the current study, we aimed to monitor the potential effects of the BME on the uptake of 99mTc labeled Paclitaxel (99mTc-PAC) against MCF-7 (ER+) and MDA-MB-231 (ER-) cell lines by using in vitro methods. METHODS: BME was obtained by the extraction of BM seeds by 80% ethanol. PAC was labeled with 99mTc by stannous chloride (SnCl2) as a reducing agent. Cytotoxicity and incorporation assays were performed on MCF-7 and MDA-MB-231 cells within the cell culture studies. RESULTS: The uptake value of 99mTc-PAC on MCF-7 cells at 240 minutes was 6.20% and BME treated 99mTc- PAC value was 17.39%. Conclusion: It is observed that BME treatment has a significant effect on the uptake of 99mTc-PAC on MCF-7 cells which is a known estrogen receptor-positive breast carcinoma cell line. It is concluded that this effect could be due to the estrogen receptor-dependent interaction of BME.

Microelectrode Recording for Deep Brain Stimulation of the Subthalamic Nucleus in Patients with Advanced Parkinson's Disease: Advantage or Loss of Time?

AIM: To investigate the effect of using microelectrode recording (MER) on the length of time required to carry out a deep brain stimulation (DBS) procedure of the subthalamic nucleus in patients with Parkinson's disease (PD). MATERIAL AND METHODS: The time required to include MER in the DBS operation was calculated for the first and second sides in 24 patients with PD. The number of microelectrodes used on each trajectory for the first and second sides, and the percentage of permanent electrodes implanted on each trajectory for the first and second sides, were quantified. RESULTS: The average times taken to use MER were 23.4 ± 6.2 minutes, 17.4 ± 6.5 minutes, and 41.2 ± 6.3 minutes for the first side, second side and total procedure, respectively. In 75% of patients, the permanent electrode was implanted at the planned target site for the first side, and in 61% of patients for the second side. CONCLUSION: MER extends the time required to carry out the DBS procedure. However, during surgery, it provides real-time information on the electrodes' neurophysiological locations and helps the surgical team choose an alternative target if the planned target does not produce satisfying results.

Inhibitory effect of sub-conjunctival tocilizumab on alkali burn induced corneal neovascularization in rats.

BACKGROUND: To evaluate the effects of sub-conjunctivally applied interleukin-6 receptor (IL-6R) antibody (tocilizumab) on alkali burn induced corneal neovascularization (CNV) in rats. METHODS: Alkali burn induced corneal neovascularization was created in 24 right eyes of 24 rats. The rats were then randomized into 2 groups. Group 1 received sub-conjunctival injection of 4 mg/0.2 ml tocilizumab and Group 2 received sub-conjunctival injection of 0.2 ml normal saline at the 5th day of alkali burn. The corneal surface area invaded with neovascular vessels were calculated on photographs. The rats were sacrificed and the corneas were excised at the15th day. The corneal specimens were stained with hemotoxylin-eosin to evaluate tissue morphology and with Willebrand factor (vWF) to evaluate microvascular structures immunohistochemically. Vascular endothelial growth factor (VEGF) expression was analyzed by ELISA. RESULTS: The percent area of CNV was 26.9% in Group 1 and 56.5% in Group 2 (p < 0.001). The histological evaluation showed that the corneal structures were not visibly altered by sub-conjuntival tocilizumab injection. Group 1 showed significantly lower corneal inflammation score than Group 2 (p < 0.001). The number of vessels stained with vWF were significantly higher in Group 2 than Group 1 (15.23 and 5.46, respectively; p < 0.001). ELISA analyses showed that corneal VEGF levels were significantly lower in Group 1 compared to Group 2 (p = 0.013) CONCLUSION: The present data demonstrated first time the beneficial effects of sub-conjunctival tocilizumab on decreasing CNV in alkali burn model of the rat cornea. Further studies are warranted to confirm these findings for the clinical application.

The protective effect of selenium in cisplatin-related retinotoxicity.

PURPOSE: The aim of this study is to evaluate the retinal toxicity of cisplatin and neuroprotective effect of selenium in cisplatin-related retinal toxicity. METHODS: Eighteen adult Wistar-Albino rats were divided into three groups. Group 1 (n = 6) received intraperitoneal (i.p.) injection of 2.5 ml physiologic saline for three days, group 2 (n = 6) received i.p. 16 mg/kg cisplatin for three days and group 3 (n = 6) received i.p. 16 mg/kg cisplatin for three days and 1.5 mg/kg twice daily selenium via gavage five days prior to cisplatin injection and for three days concomitantly with cisplatin injections. The total retinal thickness, outer nuclear layer (ONL), inner nuclear layer (INL) and inner plexiform layer (IPL) thicknesses were measured in hematoxylin/eosin and apoptotic index (AI) of ganglion cell layer (GCL) and INL was evaluated in TdT-mediated dUTP-biotin nick end labeling (TUNEL)-stained retina sections. RESULTS: Selenium statistically succeeded to reduce total retinal thickness in cisplatin-toxicated retinas: from 210.17 ± 23.40 to 173.55 ± 20.43, ONL: 49.79 ± 5.32 to 41.87 ± 6.30, INL: 33.72 ± 7.93 to 25.06 ± 5.73 and IPL: 53.61 ± 8.63 to 45.61 ± 6.92 µm in hematoxylin/eosin-stained retina sections. The AI was also reduced in INL (30.10 ± 12.02 to 19.48 ± 12.99) and in GCL (37.59 ± 17.70 to 33.15 ± 13.78). However, statistical significance was present in only AI values of INL. CONCLUSIONS: Selenium limited edema due to the toxicity and reduced the retinal thickness and showed neuroprotection in cisplatin-induced retinotoxicity.