Levodopa Challenge Test Predicts STN-DBS Outcomes in Various Parkinson's Disease Motor Subtypes: A More Accurate Judgment.

Background: The relationship between the levodopa challenge test (LDCT) and postoperative subthalamic nucleus-deep brain stimulation (STN-DBS) benefits is controversial in patients with Parkinson's disease (PD). We aim to evaluate the value of total levodopa response (TLR) and symptom levodopa response (SLR) in predicting postoperative improvement in different PD motor subtypes. Methods: Studies were split into a training set (147 patients) and a validation set (304 patients). We retrospectively collected data from 147 patients who received the Unified Parkinson's Disease Rating Scale- (UPDRS-) III and the Parkinson's Disease Questionnaire- (PDQ-) 39 evaluation. Patients were classified into tremor-dominant (TD), akinetic-rigid-dominant (AR), and mixed (MX) groups. Clinically important difference (CID) was employed to dichotomize DBS effects. For patients in each subtype group from the training set, we used the correlation and receiver operator characteristic (ROC) curve analyses to explore the strength of their relations. Areas under the curve (AUCs) were calculated and compared through the DeLong test. Results developed from the training set were applied into the validation set to predict postoperative improvement in different PD motor subtypes. Results: In the validation cohort, TLR significantly correlated with postoperative motor (p < 0.001) and quality of life (QOL) (p < 0.001) improvement in the MX group. The AUC between TLR and UPDRS-III (TU) is 0.800. The AUC between TLR and PDQ-39 (TP) is 0.770. An associated criterion in both TU and TP is around 50%. In the AR group, strong correlation was only found in SLR and PDQ-39 (SP) (p < 0.001). And the AUC of SP is significantly larger than that in TLR and PDQ-39 (TP) (p = 0.034). An associated criterion in SP is around 37%. No significant correlation was found in the TD group. Conclusions: We provide a more accurate judgment for LDCT. TLR strongly correlated with postoperative UPDRS-III and PDQ-39 improvement in MX patients. A TLR > 50% may indicate a higher possibility of clinically meaningful benefits from STN-DBS comparing to medication only. SLR can well predict QOL improvement in AR patients. Similarly, a SLR > 37% may indicate a higher possibility of clinically significant benefits from STN-DBS. LDCT provides limited information for TD patients.

Outcomes and Adverse Effects of Deep Brain Stimulation on the Ventral Intermediate Nucleus in Patients with Essential Tremor.

Objective: This study was aimed at identifying the potential outcome predictors, comparing the efficacy in patients with different tremor characteristics, and summarizing the adverse effect rates (AERs) of deep brain stimulation on the ventral intermediate nucleus (VIM-DBS) for essential tremor (ET). Methods: An extensive search of articles published to date in 2019 was conducted, and two main aspects were analyzed. Improvement was calculated as a percentage of change in any objective tremor rating scale (TRS) and analyzed by subgroup analyses of patients' tremor characteristics, laterality, and stimulation parameters. Furthermore, the AERs were analyzed as follows: the adverse effects (AEs) were classified as stimulation-related, surgical-related, or device-related effects. A simple regression analysis was used to identify the potential prognostic factors, and a two-sample mean-comparison test was used to verify the statistical significance of the subgroup analyses. Results: Forty-six articles involving 1714 patients were included in the meta-analysis. The pooled improvement in any objective TRS score was 61.3% (95% CI: 0.564-0.660) at the mean follow-up visit (20.0 ± 17.3 months). The midline and extremity symptoms showed consistent improvement (P = 0.440), and the results of the comparison of postural and kinetic tremor were the same (P = 0.219). In addition, the improvement in rest tremor was similar to that in action tremor (OR = 2.759, P = 0.120). In the simple regression analysis, the preoperative Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS) scores and follow-up time were negatively correlated with the percentage change in any objective TRS score (P < 0.05). The most common adverse event was dysarthria (10.5%), which is a stimulation-related AE (23.6%), while the rates of the surgical-related and device-related AEs were 6.4% and 11.5%, respectively. Conclusion: VIM-DBS is an efficient and safe surgical method in ET, and the efficacy was not affected by the body distribution of tremor, age at surgery, and disease duration. Lower preoperative FTM-TRS scores likely indicate greater improvement, and the effect of VIM-DBS declines over time.

Outcomes and Complications of Aggressive Resection Strategy for Pituitary Adenomas in Knosp Grade 4 With Transsphenoidal Endoscopy.

Surgery for pituitary adenomas (PAs) with cavernous sinus (CS) invasion in Knosp grade 4 is a great challenge and whether to adopt a conservative or aggressive surgical strategy is controversial. The aim of this study is to provide the outcomes and complications of an aggressive resection strategy for Knosp grade 4 PAs with transsphenoidal endoscopic surgery. Outcomes and complications were retrospectively analyzed in 102 patients with Knosp grade 4 PAs. Among them, primary PAs were seen in 60 patients and recurrent PAs were seen in 42 cases. Gross total resection (GTR) of the entire tumor was achieved in 72 cases (70.6%), subtotal tumor resection (STR) in 18 cases (17.6%), and partial tumor resection (PTR) in 12 cases (11.8%). Additionally, GTR of the tumor within the CS was achieved in 82 patients (80.4%), STR in 17 patients (16.7%), and PTR in 3 patients (2.9%). Statistical analyses showed that both recurrent tumors and firm consistency tumors were adverse factors for complete resection (P<0.05). Patients with GTR of the entire tumor were more likely to have favorable endocrine and visual outcomes than those with incomplete resection (P<0.05). Overall, the most common surgical complication was new cranial nerve palsy (n=7, 6.8%). The incidence of internal carotid artery (ICA) injury and postoperative cerebrospinal fluid (CSF) leakage was 2.0% (n=2) and 5.9% (n=6), respectively. Six patients (5.9%) experienced tumor recurrence postoperatively. For experienced neuroendoscopists, an aggressive tumor resection strategy via transsphenoidal endoscopic surgery may be an effective and safe option for Knosp grade 4 PAs.

[Surgical management of petroclival meningiomas invading into cavernous sinus].

OBJECTIVE: To analyze the clinical features, surgical strategy and management outcomes of petroclival meningioma invading into cavernous sinus. METHODS: Fifteen cases with petroclival meningioma invading into cavernous sinus were retrospectively analyzed. The presigmoidal approach was selected to remove tumors. The surgical strategy for tumor in cavernous sinus was partial resection combined with radiosurgery. Postoperative cranial nerve function and patient survival status were analyzed. RESULTS: The main symptoms of subtype of petroclival meningiomas were headache, abducens nerve palsy and trigeminal neuropathy. Gross total tumor removal was achieved in 13 cases and more than 90% resection in 2 cases. There was no operative death. Nine cases suffered from new postoperative cranial nerve deficits. After a follow-up of 6 - 59 months, complete improvement was achieved in oculomotor nerve deficits, much improvement in VII nerve deficit, but V and VI nerve function deficits improved slightly. The tumor progression-free survival rate was 86.7%. CONCLUSION: Rational surgical strategy to petroclival meningiomas invading into cavernous sinus should be suggested to reduce the operative morbidity and improve the survival quality of these patients.

Selection and Prognosis of Optic Canal Decompression for Traumatic Optic Neuropathy.

OBJECTIVE: To comprehensively compare the vision improvement rate in patients with traumatic optic neuropathy with different surgical timing and other different preoperative conditions. METHODS: PubMed, Embase, and MEDLINE Ovid were searched to identify studies. We performed subgroup analyses for differences in the surgical timing, surgical approach, optic canal fractures, state of consciousness after trauma, time of visual loss development, incision of the optic nerve sheath, and treatment methods. RESULTS: A total of 74 studies involving 6084 patients were included in the final analysis. In the groups of patients with early (≤3 days), middle (4-7 days), and late (>7 days) surgical interventions, 58.4%, 53.2%, and 45.4% demonstrated visual improvements, respectively. The results of the statistical analysis revealed that patients with early surgical intervention had a higher improvement rate than patients with late surgical intervention (P = 0.00953). The improvement rate was significantly lower for patients who presented with no light perception before surgery than for patients whose vision was better than no light perception (relative risk, 0.498; 95% confidence interval [CI], 0.443-0.561; P = 0.001) and lower for patients with immediate visual loss after trauma than for those with secondary visual loss (relative risk, 0.639; 95% CI, 0.498-0.819; P = 0.001). CONCLUSIONS: We recommend that patients seek medical treatment as soon as possible after traumatic optic nerve injury, and patients with secondary injuries can have a good recovery effect while still living with light perception or more. The option of treatment and whether to incise the optic nerve sheath still remains controversial.

Identification of gene co-expression modules and hub genes associated with the invasiveness of pituitary adenoma.

In pituitary adenoma (PA), invasiveness is the main cause of recurrence and poor prognosis. Thus, identifying specific biomarkers for diagnosis and effective treatment of invasive PAs is of great clinical significance. In this study, from the Gene Expression Omnibus database, we obtained and combined several microarrays of PA by the "sva" R package. Weighted gene co-expression network analysis was performed to construct a scale-free topology model and analyze the relationships between the modules and clinical traits. Our analysis results indicated that three key modules (dark turquoise, saddle brown, and steel blue) were associated with the invasiveness of PA. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and Gene Ontology analysis were performed for the functional annotation of the key modules. In addition, the hub genes in the three modules were identified and screened by differential expression analysis between normal samples and PA samples. Three upregulated differentially expressed genes (DGAT2, PIGZ, and DHRS2) were identified. The Fisher's exact test and receiver operating characteristic curve were used to validate the capability of these genes to distinguish invasive traits, and transcription factor interaction networks were used to further explore the underlying mechanisms of the three genes. Moreover, a lower expression level of DGAT2 in invasive PA tissue than in noninvasive PA tissue was validated by quantitative reverse transcription-polymerase chain reaction. In general, this study contributes to potential molecular biomarkers of invasive PAs and provides a broader perspective for diagnosis and new therapeutic targets for the invasive PAs.

Predictive factors of outcome in cervical dystonia following deep brain stimulation: an individual patient data meta-analysis.

BACKGROUND: Deep brain stimulation (DBS) therapy has been suggested to be a beneficial alternative in cervical dystonia (CD) for patients who failed nonsurgical treatments. This individual patient data meta-analysis compared the efficacy of DBS in the globus pallidus internus (GPi) versus subthalamic nucleus (STN) and identified possible predictive factors for CD. METHODS: Three electronic databases (PubMed, Embase and Web of Science) were searched for studies with no publication date restrictions. The primary outcomes were normalized by calculating the relative change in TWSTRS total scores and subscale scores at the last follow-up. Data were analyzed mainly using Pearson's correlation coefficients and a stepwise multivariate regression analysis. RESULTS: Thirteen studies (86 patients, 58 with GPi-DBS and 28 with STN-DBS) were eligible. Patients showed significant improvement in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) (52.5 ± 11.6 vs 21.9 ± 14.9, P < 0.001) scores at the last follow-up (22.0 ± 14.3 months), compared with scores at baseline, with a mean improvement of 56.6% (P < 0.001) (54.9% in severity, 63.2% in disability, 41.7% in pain). There was no significant difference in the improvement (%) of the total TWSTRS scores in 3 years for the GPI and STN groups (58.1 ± 22.6 vs 47.5 ± 39.2, P > 0.05). Age at surgery and age at symptom onset were negatively correlated with the relative changes in TWSTRS scores at the last follow-up, while there was a positive correlation with preoperative TWSTRS scores. On the stepwise multivariate regression, only the age at surgery remained significant in the best predictive model. CONCLUSIONS: GPi-DBS and STN-DBS both provided a common great improvement in the symptoms of CD patients in 3 years. Earlier age at surgery may probably indicate larger improvement. More randomized large-scale clinical trials are warranted in the future.

miR-137 functions as a tumor suppressor gene in pituitary adenoma by targeting AKT2.

Pituitary adenoma is a common intracranial tumor, but the underlying molecular carcinogenesis mechanisms remain unclear. Accumulative evidence has demonstrated that aberrant expression of microRNAs (miRNAs) is an important feature of cancer. The aim of the current study was to explore the role of miR-137 in pituitary tumor. The expression level of miR-137 in pituitary tumor tissues was measured by quantitative RT-PCR. Then the effects of miR-137 upregulation/downregulation on the proliferation and invasion as well as the potential molecular mechanisms were further investigated. Our results showed that the expression level of miR-137 was significantly reduced in pituitary tumor tissues compared to normal controls. Ectopic expression of miR-137 inhibited the proliferation and invasion of pituitary tumor cells, while miR-137 suppression promoted the proliferation and invasion capacity of cancer cells. Bioinformatic analysis of the downstream targets of miR-137 revealed that many enriched gene ontology functions and pathways were closely associated with carcinogenesis. Mechanically, AKT2 was demonstrated to be a direct downstream target of miR-137. The expression level of miR-137 was negatively correlated with AKT2 in pituitary tumor tissues. Taken together, miR-137 plays a tumor suppressive role in pituitary adenoma through regulating AKT2.

Is awake physiological confirmation necessary for DBS treatment of Parkinson's disease today? A comparison of intraoperative imaging, physiology, and physiology imaging-guided DBS in the past decade.

BACKGROUND: Deep brain stimulation (DBS) is a well-established surgical therapy for Parkinson's disease (PD). Intraoperative imaging (IMG), intraoperative physiology (PHY) and their combination (COMB) are the three mainstream DBS guidance methods. OBJECTIVE: To comprehensively compare the use of IMG-DBS, PHY-DBS and COMB-DBS in treating PD. METHODS: PubMed, Embase, the Cochrane Library and OpenGrey were searched to identify PD-DBS studies reporting guidance techniques published between January 1, 2010, and May 1, 2018. We quantitatively compared the therapeutic effects, surgical time, target error and complication risk and qualitatively compared the patient experience, cost and technical prospects. A meta-regression analysis was also performed. This study is registered with PROSPERO, number CRD42018105995. RESULTS: Fifty-nine cohorts were included in the main analysis. The three groups were equivalent in therapeutic effects and infection risks. IMG-DBS (p < 0.001) and COMB-DBS (p < 0.001) had a smaller target error than PHY-DBS. IMG-DBS had a shorter surgical time (p < 0.001 and p = 0.008, respectively) and a lower intracerebral hemorrhage (ICH) risk (p = 0.013 and p = 0.004, respectively) than PHY- and COMB-DBS. The use of intraoperative imaging and microelectrode recording correlated with a higher surgical accuracy (p = 0.018) and a higher risk of ICH (p = 0.049). CONCLUSIONS: The comparison of COMB-DBS and PHY-DBS showed intraoperative imaging's superiority (higher surgical accuracy), while the comparison of COMB-DBS and IMG-DBS showed physiological confirmation's inferiority (longer surgical time and higher ICH risk). Combined with previous evidence, the use of intraoperative neuroimaging techniques should become a future trend.

Long-noncoding RNA IFNG-AS1 exerts oncogenic properties by interacting with epithelial splicing regulatory protein 2 (ESRP2) in pituitary adenomas.

Despite the enormous development of medical technologies in recent decades, pituitary adenoma (PA) remains among the most refractory cancers in the world. Elucidating the molecular mechanisms underlying the pathology of PA is essential to identify new treatments for PA. In the present study, we found that IFNG-AS1 expression was significantly higher in PA tissues than in nontumor tissues via qRT-PCR and RNA fluorescence in situ hybridization (FISH). shRNA-mediated IFNG-AS1 knockdown in HP75 cells significantly inhibited tumor progression, and IFNG-AS1 overexpression remarkably promoted tumor progression. Epithelial splicing regulatory protein 2 (ESRP2) was demonstrated to be a target protein of IFNG-AS1 in PA; knocking down ESRP2 reversed the tumor-inhibitory effects of IFNG-AS1 knockdown, and overexpressing ESRP2 abolished the tumor-promoting effects of IFNG-AS1 overexpression in HP75 cells. In conclusion, our findings suggested that IFNG-AS1 may function as an oncogene in PA by interacting with ESRP2.

Persistent adverse effects following different targets and periods after bilateral deep brain stimulation in patients with Parkinson's disease.

BACKGROUND: Performed as one of the major treatments for advanced Parkinson's disease (PD), deep brain stimulation (DBS) surgery can induce adverse effects (AEs) on cognition, gait, mood, speech and swallowing, which are frequently reported and seriously affect the patient's daily life. OBJECTIVE: To comprehensively analysis the adverse effect rates (AERs) of cognition, mood, gait, speech and swallowing after bilateral DBS in patients with PD. METHOD: We performed a systematic search in PubMed, EMBASE and the Cochrane Library to collect all the articles reporting AEs after DBS in sufferers of PD. The cited articles were also manually searched. RESULTS: A total of 31 articles were quantitatively analyzed. Random-effects models were used to calculate the AERs and 95% confidence intervals. Of all patients, the pooled AER of the five types of events was 24.0%. Specifically, the risks of cognition, mood and speech disturbance were higher after subthalamic nucleus (STN) -DBS than after globus pallidus interna (GPi) -DBS: 25.1% versus 14.6%, 26.3% versus 22.2% and 29.0% versus 19.6%, respectively. However, the AER of dysphagia was slightly lower after STN-DBS: 8.6% versus 10.1%. The risk of gait disorders was similar between two target groups in sub-analysis of random control trials (RCTs): 38.3% in STN group and 37.3% in GPi group. In three follow-up intervals, short-term follow-up (STF), mid-term follow-up (MTF) and long-term follow-up (LTF), gait (17.6%~19.9%~28.0%), speech (7.8%~26.9%~31.5%) and mood (7.4%~24.9%~30.7%) disorders worsened progressively. While cognitive disturbance (22.5%~27.1%~16.7%) reached its highest rate at MTF. CONCLUSION: STN-DBS was 10% more likely to cause cognitive and speech disturbance than GPi-DBS, while STN-DBS had a lower risk of dysphagia. Two target groups had similar effects on gait. The pooled AER increased over time, while cognitive disturbance reached its highest rate at the 6- to 18-month follow-up. Additionally, speech and mood disturbance deteriorated rapidly from STF to MTF. Further investigation of the pathophysiology will help alleviate those AEs after DBS.

Extended endoscopic endonasal approach for recurrent or residual symptomatic craniopharyngiomas.

OBJECTIVES: Removal of recurrent or residual symptomatic craniopharyngiomas is more challenging than the primary surgery. The extended endoscopic endonasal (EEE) approach has been proposed an alternative surgical route for removal of various suprasellar tumors including craniopharyngiomas currently. In this study, we summarized the operative experience and described the feasibility and advantages of this technique in recurrent or residual symptomatic craniopharyngiomas. PATIENTS AND METHODS: A retrospective review of 15 patients (9 males and 6 females) whom underwent EEE approach between April 2012 and February 2017, were included in this study. The lesions included 8 purely suprasellar craniopharyngiomas (2 extraventricular, 6 intraextraventricular), 3 both intra- and suprasellar craniopharyngiomas, and 4 intrasellar craniopharyngiomas. The mean preoperative (that is, EEE approach) tumor volume was 10.54 cm3. The mean follow-up period was 23.1 months (range, 8-54). All patients were analyzed in terms of the treatment effect, complictions and follow-up results. RESULTS: Total removal of tumors was achieved in 12 patients (80.0%) and subtotal removal in 3 cases (20.0%). The pituitary stalks were identified in 11 patients during operations and secured in 8 patients. Postoperative visual acuity was improved in 10 cases, and normalization of the impairment was achieved in 3 patients. There were no significant differences between pre and postoperative endocrine function, except in one patient with normal preoperative pituitary hormone function who suffered postoperative hypopituitarism. Postoperative diabetes insipidus (DI) occurred in 14 patients including 6 patients who had long-term DI and others reporting transient postoperative DI. No cerebrospinal fluid (CSF) leak was identified. There were no deaths or major complications. Obesity developed in 2 patients, with no deaths and recurrent cases during follow-up period. CONCLUSION: The pure EEE approach is a safe, effective alternative for treatment of recurrent or residual symptomatic craniopharyngiomas owing to its advantages including wide-angle view, close observation and elimination of brain retraction. Larger studies with further follow-up is needed to assess the long-term efficacy of this minimal access approach.