[Innovations in Combined Surgery of Endoscopic Transsphenoidal Surgery and Craniotomy].

Combined endoscopic transsphenoidal surgery and craniotomy may be useful for tumors extending into the suprasellar region or ventricles and for tumors extending simultaneously into the nasal sinuses and intracranial space. This method allows two surgeons to share the surgical field while compensating for each other's blind spots and allows for safe tumor removal by separating the normal structure from the tumor and protecting the normal structure. Simultaneous combined endoscopic transsphenoidal surgery and craniotomy require a lot of equipment; however, by devising the layout of the equipment in the operating room, the staff involved in the surgery can perform their roles more effectively. However, this method results in extensive dural and cranial defects, and prevention of cerebrospinal fluid leakage and perioperative surgical site infection is essential. Skull base reconstruction using autologous tissues and medical materials at appropriate locations can reduce the risk of postoperative cerebrospinal fluid leakage and surgical site infection. Furthermore, multilayered reconstruction using restorative medical materials eliminates the need for autologous tissue, is minimally invasive, shortens the operative time, reduces postoperative stress, and shortens the length of hospital stay. A combination of endoscopic transsphenoidal surgery and craniotomy will contribute to the improvement of the safety of highly difficult tumorectomies under a reliable skull base reconstruction method.

Potent bystander effect and tumor tropism in suicide gene therapy using stem cells from human exfoliated deciduous teeth.

Herpes simplex virus thymidine kinase (HSVTK)/ganciclovir (GCV) suicide gene therapy has a long history of treating malignant gliomas. Recently, stem cells from human exfoliated deciduous teeth (SHED), which are collected from deciduous teeth and have excellent harvestability, ethical aspects, and self-renewal, have been attracting attention mainly in the field of gene therapy. In the present study, we assessed SHED as a novel cellular vehicle for suicide gene therapy in malignant gliomas, as we have previously demonstrated with various cell types. SHED was transduced with the HSVTK gene (SHEDTK). In vitro experiments showed a significant bystander effect between SHEDTK and glioma cell lines in coculture. Furthermore, apoptotic changes caused by caspase 3/7 activation were simultaneously observed in SHEDTK and glioma cells. Mice implanted with a mixture of U87 and SHEDTK and treated with intraperitoneal GCV survived for longer than 100 days. Additionally, tumors in treatment model mice were significantly reduced in size during the treatment period. SHEDTK implanted at the contralateral hemisphere migrated toward the tumor crossing the corpus callosum. These results suggested that SHEDTK-based suicide gene therapy has potent tumor tropism and a bystander-killing effect, potentially offering a new promising therapeutic modality for malignant gliomas.

Surgical management of skull base meningiomas and vestibular schwannomas.

PURPOSE OF REVIEW: The aim of this study is to discuss surgical management of meningiomas and schwannomas of skull base. RECENT FINDINGS: Meningiomas and schwannomas are typically benign neoplasm with a good prognosis after surgery. Patients should be treated individually related to several features: size and localization of tumor and its proximity with deep critical neurovascular structures, neurological status, age and comorbidity. Also, the widespread use of neuroimaging and the progressive and constant aging of the populations inevitably result in the increase of detection rate of incidental (asymptomatic) neoplasm.Nowadays, there are still controversies about the correct management strategy. SUMMARY: Surgery represents the gold standard treatment, with the objective of gross total resection; however, it is not always feasible due to localization, encasement of neuro-vascular structure, invasion of cranial nerve and brain parenchyma. Stereotactic radiosurgery and radiation therapy are important to achieve a satisfactory functional outcome and tumor control in case of residue or recurrence. A multidisciplinary approach is pivotal.

Efficacy of HSV-TK/GCV system suicide gene therapy using SHED expressing modified HSV-TK against lung cancer brain metastases.

Lung cancer is one of the most common cancers, and the number of patients with intracranial metastases is increasing. Previously, we developed an enzyme prodrug suicide gene therapy based on the herpes simplex virus thymidine kinase (HSV-TK)/ganciclovir (GCV) system using various mesenchymal stem cells to induce apoptosis in malignant gliomas through bystander killing effects. Here, we describe stem cells from human exfoliated deciduous teeth (SHED) as gene vehicles of the TK/GCV system against a brain metastasis model of non-small cell lung cancer (NSCLC). We introduced the A168H mutant TK (TKA168H) into SHED to establish the therapeutic cells because of the latent toxicity of wild type. SHED expressing TKA168H (SHED-TK) exhibited chemotaxis to the conditioned medium of NSCLC and migrated toward implanted NSCLC in vivo. SHED-TK demonstrated a strong bystander effect in vitro and in vivo and completely eradicated H1299 NSCLC in the brain. SHED-TK cells implanted intratumorally followed by GCV administration significantly suppressed the growth of H1299 and improved survival time. These results indicate that the TKA168H variant is suitable for establishing therapeutic cells and that intratumoral injection of SHED-TK followed by GCV administration may be a useful strategy for therapeutic approaches.

Largest neurosurgical social media group and its impact on communication and research.

BACKGROUND: The use of social media to communicate and disseminate knowledge has increased exponentially, especially in the field of neurosurgery. 'Neurosurgery cocktail' (NC) was developed by a group of young neurosurgeons as a means of sharing didactic materials and clinical experiences via social media. It connects 35.000 neurosurgeons worldwide on multiple platforms, primarily Facebook and Twitter. Given the rising utilization of social media in neurosurgery, the popularity of NC has also increased since its inception. In this study, the authors surveyed the social media analytics of NC for both Facebook and Twitter. Besides, we reviewed the literature on the use of social media in neurosurgery. METHODS: Facebook and Twitter metrics were extracted through each respective platform's analytics tools from December 2020 (earliest available date for data analysis) through January 2021. A literature search was conducted using PubMed (MEDLINE) and Scopus databases. RESULTS: On Facebook, as of January 2021, the group had a total of 25.590 members (87.6% male), most commonly (29%) between 35 and 44 years of age with over 100 countries were represented. As of January 2021, they had amassed 6457 followers on Twitter. During the last 28 d between December 2020 and January 2021, the account published 65 tweets that garnered a total of 196,900 impressions. Twelve articles were identified in our literature review on the use of social media within the neurosurgical community. CONCLUSIONS: NC is one of the most widely utilized neurosurgical social media resources available. Sharing knowledge has been broadened thanks to the recent social media evolution, and NC has become a leading player in disseminating neurosurgical knowledge.

Migration Capacity of Stem Cells from Human Exfoliated Deciduous Teeth Towards Glioma.

BACKGROUND: Stem cells from human exfoliated deciduous teeth (SHED) are a mesenchymal stem cell type and have recently attracted attention for their high proliferative rate, multipotency, and immunosuppressive properties. However, SHED have not yet been investigated for anticancer properties. We therefore investigated whether SHED can be used as a treatment modality, particularly for anti-glioma therapy. METHODS: In vitro, we examined the mobility of SHED and their ability to migrate towards glioma-conditioned medium and specific growth factors secreted by malignant gliomas. In vivo, we transplanted SHED into the left hemisphere of nude mice that had been previously implanted with human malignant glioma U87 cells into the right hemisphere. We assessed whether SHED had tumorigenic potential. RESULTS: SHED exhibited strong migration ability towards malignant glioma in both in vitro and in vivo assays. In vitro, SHED migrated towards glioma-conditioned medium and specific growth factors such as stem cell factor, platelet-derived growth factor BB, C-X-C motif chemokine ligand 12, and vascular endothelial growth factor. SHED were accumulated around tumor cells in the contralateral hemisphere 1 week after transplantation. Moreover, SHED remained in the brains of nude mice 150 days after transplantation. Finally, we verified that SHED had no malignant transformation or engraftment of SHED in the mouse brain. CONCLUSIONS: Our findings indicate that SHED can potentially be applied to track malignant glioma.

A novel technique for fence-post tube placement in glioma using the robot-guided frameless neuronavigation technique under exoscope surgery: patient series.

BACKGROUND: Robotic technology is increasingly used in neurosurgery. The authors reported a new technique for fence-post tube placement using robot-guided frameless stereotaxic technology with neuronavigation in patients with glioma. OBSERVATIONS: Surgery was performed using the StealthStation S8 linked to the Stealth Autoguide cranial robotic guidance platform and a high-resolution three-dimensional (3D) surgical microscope. A surgical plan was created to determine the removal area using fence-post tube placement at the tumor and normal brain tissue boundary. Using this surgical plan, the robotic system allowed quick and accurate fence-post tube positioning, automatic alignment of the needle insertion and measurement positions in the brain, and quick and accurate puncture needle insertion into the brain tumor. Use of a ventricular drainage tube for the outer needle cylinder allowed placement of the puncture needle in a single operation. Furthermore, use of a high-resolution 3D exoscope allowed the surgeon to simultaneously view the surgical field image and the navigation screen with minimal line-of-sight movement, which improved operative safety. The position memory function of the 3D exoscope allowed easy switching between the exoscope and the microscope and optimal field of view adjustment. LESSONS: Fence-post tube placement using robot-guided frameless stereotaxic technology, neuronavigation, and an exoscope allows precise glioma resection.

Ectopic Relapse of Anti-neutrophil Cytoplasmic Antibody-associated Pituitary Vasculitis with No Elevation of Anti-neutrophil Cytoplasmic Antibodies after Renal Remission.

The relationship between anti-neutrophil cytoplasmic antibody (ANCA) titer levels and relapse risk in patients with ANCA-associated vasculitis (AAV) following clinical remission remains controversial. We herein report a case showing ectopic relapse of AAV in the pituitary with no ANCA elevation after renal remission. Magnetic resonance imaging revealed an enlarged pituitary gland. A pituitary biopsy showed geographic necrosis with multinucleated giant cells. We diagnosed this case as relapse of AAV in the pituitary. One month after rituximab therapy, the pituitary gland volume had decreased. The intensification of therapy due to the possibility of vasculitis relapse may facilitate better control of AAV.

Development of a novel gripping test for the evaluation of the finger fine motor ability in MPTP-treated monkeys.

Assessing the finger fine motor ability is extremely important. However, conventional behavioral tests in monkeys are complicated and costly. We attempted to develop a new task to assess the precise finger grip in Parkinson's disease monkeys based on the principles of objectification, multipurpose, and simplification. This study involved seven adult male cynomolgus monkeys. A gripping test based on the previous food reaching test was developed. Parallel experiments of food reaching test and gripping test affected by the treatments of levodopa and deep brain stimulation of the subthalamic nucleus were performed to verify the utility of the gripping test. We found that gross motor ability (measured by food reaching test) could be significantly improved by both the subthalamic nucleus and levodopa administration, which reproduced the results of our previous study. The finger fine motor ability (measured by the gripping test) could be significantly improved by levodopa administration, but not by the subthalamic nucleus. Our results verified the utility and reliability of the gripping test, which is a simple, convenient, and objective task for evaluating the finger fine motor skill in Parkinson's disease monkeys. Mechanisms of the efficacy of deep brain stimulation on fine motor ability require further investigation.

Nicotine does not affect stem cell properties requisite for suicide gene therapy against glioma.

OBJECTIVE:: Glioblastoma is one of the most lethal tumors in adult central nervous system with a median survival of a year and half and effective therapeutic strategy is urgently needed. For that reason, stem cell-based suicide gene therapies have attracted much interest because of potent tumor tropism of stem cells and bystander effect. In this current clinical situation, stem cells are promising delivery tool of suicide genes for glioma therapy. Since habitual cigarette smoking still prevails worldwide, we investigated the effect of nicotine on stem cell tropism toward glioma and gap junctional intercellular communication (GJIC) function between glioma and stem cells, both of which are important for suicide gene therapies. Methods: Mouse induced pluripotent stem cell-derived neural stem cells (iPS-NSCs) and human dental pulp mesenchymal stem cells (DPSCs) were used. The effect of nicotine on tumor tropism to glioma-conditioned medium (CM) at a non-cytotoxic concentration was assessed with Matrigel invasion assay. Nicotine effect on GJIC was assessed with the scrape loading/dye transfer (SL/DT) assay for co-culture of glioma and stem cells and the parachute assay among glioma cells using high-content analysis. Results: Tumor tropism of iPS-NSCs toward GL261-CM and DPSCs toward U251-CM was not affected by nicotine (0.1 and 1 µM). Nicotine at the concentrations equivalent to habitual smoking (1 µM) did not affect GJIC of iPS-NSC/GL261 and DPSC/U251 and GJIC among each glioma cells. Conclusions: The study demonstrated that non-cytotoxic concentrations of nicotine did not significantly change the stem cell properties requisite for stem cell-based suicide gene therapy.

Acute and chronic hemorrhage from radiation-induced cavernous malformation associated with late-delayed radiation necrosis in long surviving glioma patients: A case report.

Although radiation therapy is a standard treatment strategy for patients with glioma, its delayed complications are not clearly understood. Radiation-induced cavernous malformation (RICM) is one of the complications in the delayed phase following radiation therapy, which usually occurs in children. Herein we present three cases of RICM with radiation necrosis in long surviving adult glioma patients, 2 with oligoastrocytoma and one with anaplastic ependymoma. Two of three patients had received an obvious overdose of radiation by additional stereotactic radiation therapy. Repeated episodes of either acute or chronic hemorrhages from RICM worsened the neurological symptoms in all cases. The interval between the last irradiation and the occurrence of symptoms was 45-173 months. The presence of hypointense rim on FLAIR or T2* on magnetic resonance imaging, which resembles the appearance of sporadic cavernous malformations, could be helpful in differentiating RICM from tumor recurrence. Surgical resection was effective in alleviating the symptoms. Microscopically, RICM is a vascular lesion with vulnerable vessels, which are observed in the center of the radiation necrosis. Repeated hemorrhages from these vessels cause either gradual or sudden worsening of neurological symptoms. Therefore, radiation overdose, which results in radiation injury, should be avoided in low grade glioma patients, who could potentially survive for a long period.

Cosmetic and Neuroprotective Placement of Custom-Made Ultra-High-Molecular-Weight Polyethylene Cranial Plate (SKULPIO) in Single-Step Surgery: Technical Note and Case Report.

BACKGROUND: Cranioplasty is a common procedure in neurosurgery. However, cosmetic and neuroprotective reconstructions are necessary after cranioplasty. Treatment of patients with a meningioma with bone infiltration requires removal of the tumor-infiltrated bone and subsequent cranioplasty. We report an efficient technique for cosmetic and neuroprotective reconstructions using a custom-made ultra-high-molecular-weight polyethylene cranial plate (SKULPIO, Kyocera Medical, Kyoto, Japan) in a single-step surgery involving tumor removal and skull reconstruction. METHODS: We present 2 illustrative cases of a 49-year-old female with a right frontal convexity meningioma and 69-year-old male with a bilateral parasagittal atypical meningioma, both involving extensive skull invasion. We preoperatively planned craniotomy size to facilitate the removal of the tumor-infiltrated skull bone using the patients' 3-dimensional cranial models followed by the construction of a custom-made cranial plate. After tumor removal, we drilled out the outer table and the diploe of the cranial edge until the custom-made bone plate accurately fit the bone defect. Finally, the cranial plate was fixed using titanium plates and screws. RESULTS: Postoperative magnetic resonance imaging for each case revealed total meningioma removal and an aesthetically reconstructed skull. Using this technique, precise adjustment of the cranial edge to the plate contributes to a gapless and aesthetic reconstruction. Furthermore, the intact inner table of the skull firmly supports the custom-made bone plate. CONCLUSIONS: This technique involving the placement of a custom-made cranial plate during a single-step surgery was found to be efficient for cosmetic and neuroprotective reconstructions.

Unexpectedly Smaller Artifacts of 3.0-T Magnetic Resonance Imaging than 1.5 T: Recommendation of 3.0-T Scanners for Patients with Magnet-Resistant Adjustable Ventriculoperitoneal Shunt Devices.

BACKGROUND: Magnetic resonance imaging (MRI) artifacts of adjustable shunt devices are thought to be similar to metal clip artifacts, in that they are larger with higher field strength scanners. We have published several reports about the artifacts of new MRI-resistant adjustable shunt devices, and we found a case in which a 3.0-T scanner showed smaller artifacts than the 1.5-T scanner. We aimed to clarify whether this claim is true or not. METHODS: Under permission of our institutional Ethical Committee, 2 volunteers underwent imaging studies using 3.0-T and 1.5-T scanners from GE, Siemens, and Philips. Four MRI-resistant adjustable shunt devices-proGAV2.0 (Miethke), Codman Certas Plus (Johnson & Johnson), Polaris (Sophysa), and Strata MR valve (Medtronic)-were fixed on the left temporal scalp. Routine MRI images, including T1-and T2-weighted imaging, fluid-attenuated inversion recovery, diffusion-weighted imaging (DWI), and magnetic resonance angiography (MRA), were obtained. We also compared artifacts between a 3.0-T scanner and a-1.5 T scanner in 4 patients. RESULTS: The 3.0 T-scanners showed smaller artifacts than the 1.5-T scanners on DWI and MRA images for all shunt devices and scanners. In the other sequences, the results depended on the MRI scanner manufacturer; however, the GE 3.0-T scanner showed smaller artifacts in every sequence. This was also true in the 4 clinical cases. CONCLUSIONS: A 3.0-T scanner is recommended over a 1.5-T scanner for patients with MRI-resistant adjustable shunt devices in the diagnosis of acute ischemic condition or when using GE scanners.

Fluid-Blood Level and Hematoma Expansion in a Cerebral Amyloid Angiopathy-Associated Intracerebral Hematoma.

BACKGROUND Cerebral amyloid angiopathy (CAA) results from progressive deposition of amyloid-ß in the walls of cortical and leptomeningeal vessels, leading to CAA-associated intracerebral hemorrhage (ICH). Hematoma expansion is a common early complication of spontaneous ICH, and is a strong independent predictor of poor outcome. However, there are limited reports of hematoma expansion related to CAA-associated ICH. Herein, we describe a novel case of hematoma expansion with a fluid-blood level in the cystic cavity of CAA-associated ICH. CASE REPORT A 76-year-old male was initially diagnosed with probable CAA according to the modified Boston criteria, and presented with lobar ICH in the left frontal lobe 4 months later. Admission computed tomography scans showed an ICH including a high-density hematoma within a cystic cavity, revealing a clearly lower-density fluid component. Serial computed tomography scans showed no evidence of an expansion of the high-density clot, but obvious expansion of the fluid component containing a fluid-blood level. We recognized a bleeding site with no enhancement on preoperative magnetic resonance imaging. Left frontal craniotomy revealed a liquefied hematoma, which was removed by suction. We subsequently evacuated the blood clot extending into the left frontal sulcus, and confirmed and cauterized the bleeding site, leading to successful hemostasis. CONCLUSIONS We report a CAA-associated ICH case showing hematoma expansion with a fluid-blood level. Intraparenchymal fluid-blood level suggests extravasation of blood into pre-existing cystic cavities because of hematoma liquefaction. Thus, fluid-blood levels are an important finding of hematoma expansion in acute CAA-associated ICH, and early treatment should be considered.

Can the Latest Computerized Technologies Revolutionize Conventional Assessment Tools and Therapies for a Neurological Disease? The Example of Parkinson's Disease.

Dramatic breakthroughs in the treatment and assessment of neurological diseases are lacking. We believe that conventional methods have several limitations. Computerized technologies, including virtual reality, augmented reality, and robot assistant systems, are advancing at a rapid pace. In this study, we used Parkinson's disease (PD) as an example to elucidate how the latest computerized technologies can improve the diagnosis and treatment of neurological diseases. Dopaminergic medication and deep brain stimulation remain the most effective interventions for treating PD. Subjective scales, such as the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr stage, are still the most widely used assessments. Wearable sensors, virtual reality, augmented reality, and robot assistant systems are increasingly being used for evaluation of patients with PD. The use of such computerized technologies can result in safe, objective, real-time behavioral assessments. Our experiences and understanding of PD have led us to believe that such technologies can provide real-time assessment, which will revolutionize the traditional assessment and treatment of PD. New technologies are desired that can revolutionize PD treatment and facilitate real-time adjustment of treatment based on motor fluctuations, such as telediagnosis systems and "smart treatment systems." The use of these technologies will substantially improve both the assessment and the treatment of neurological diseases before next-generation treatments, such as stem cell and genetic therapy, and next-generation assessments, can be clinically practiced, although the current level of artificial intelligence cannot replace the role of clinicians.

Deep Brain Stimulation for Intractable Obsessive-compulsive Disorder: The International and Japanese Situation/Scenario.

Deep brain stimulation (DBS) is used to treat symptoms by modulating the cortico-striato-thalamo-cortical (CSTC) loop in the central nervous system (CNS), and attempts to research loop circuit disorders have been globally initiated among the intractable neurological and psychiatric disorders. DBS treatment has been evaluated for all these newly found CNS loop circuit disorders. In 2011, neurosurgical treatments for psychiatric disorders were renamed from "psychosurgery" to "neurosurgery for psychiatric disorders (NPD)" by the World Society for Stereotactic and Functional Neurosurgery (WSSFN). Moreover, in 2014, "Consensus on guidelines for stereotactic neurosurgery for psychiatric disorders" was published by the WSSFN to address the differences in correspondence of stereotactic NPD. Globally, two multicenter prospective randomized control trials regarding DBS of the subcallosal cingulated gyrus and ventral anterior internal capsule/ventral striatum for intractable depression have been terminated after futility analysis. However, DBS for intractable obsessive-compulsive disorder (OCD), unlike for intractable depression, is showing steady development. In Japan, NPDs have not been performed since 1975 following the adoption of "Resolution of total denial for psychosurgery" by the Japanese Society of Psychiatry and Neurology. Nevertheless, a trend to adopt new neuro-modulation techniques for psychiatric disorders, including DBS, are emerging. We have created a clinical research protocol for the use of DBS in intractable OCD, which has been approved by the ethical committee of Hamamatsu University School of Medicine, with the hope of commencing DBS treatment for intractable OCD patients in the near future.

Current behavioral assessments of movement disorders in children.

Pediatric movement disorders (PMDs) are common and have recently received increasing attention. As these disorders have special clinical features, the selection of appropriate behavioral assessment tools that can clearly distinguish movement disorders from other diseases (eg, epilepsy and neuromuscular disorders) is crucial for achieving an accurate diagnosis and treatment. However, few studies have focused on behavioral assessments in children. The present report attempts to provide a critical review of the available subjective and objective assessment tests for common PMDs. We believe that the principles of objectification, multi-purpose use, and simplification are also applicable to the selection and development of satisfactory pediatric behavioral assessment tools. We expect that the development of wearable sensors, virtual reality, and augmented reality will lead to the establishment of more reliable and simple tests. In addition, more rigorous randomized controlled trials that have been specifically designed to evaluate behavioral testing in children are also expected in the future.

Setting pressure can change the size and shape of MRI artifacts caused by adjustable shunt valves: a study of the 4 newest models.

OBJECTIVE: Adjustable shunt valves that have been developed for the management of hydrocephalus all rely on intrinsically magnetic components, and artifacts with these valves on MRI are thus inevitable. The authors have previously reported that the shapes of shunt artifacts differ under different valve pressures with the proGAV 2.0 valve. In the present study the authors compared the size and shape of artifacts at different pressure settings with 4 new-model shunt valves. METHODS: The authors attached 4 new models of MRI-resistant shunt valve to the temporal scalp of a healthy volunteer: the proGAV 2.0; Codman Certas Plus; Polaris; and Strata MR. They set 3 different scales of pressures for each valve, depending on magnet orientation to the body axis. Artifacts were evaluated and compared among all valves on a 3.0-T GE scanner and 2 valves were also evaluated on a Philips scanner and a Siemens scanner. In-plane artifact sizes were evaluated as the maximum distance of the artifact from the expected scalp. RESULTS: The sizes and shapes of artifacts changed depending on valve pressure for all valves on the 3 different MRI scanners. Artifacts were less prominent on spin echo sequences than on gradient echo sequences. For diffusion-weighted imaging and time-of-flight MR angiography, the authors matched image numbers within the same sequence and compared appearances of artifacts. For all valves, the number of images affected by artifacts and the image number showing the largest artifact differed among valve settings. CONCLUSIONS: Artifacts of all adjustable shunt valves showed gross changes corresponding to pressure setting. Not only the maximum distance of artifacts but also the shape changed significantly. The authors suggest that changing pressure settings offers one of the easiest ways to minimize artifacts on MRI.

Effect of Subthalamic Deep Brain Stimulation on Upper Limb Dexterity in Patients with Parkinson Disease.

OBJECTIVE: The efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on dexterity remains controversial despite its recognition as an effective strategy for Parkinson disease. The present study investigated the efficacy of STN-DBS for ameliorating bradykinesia and dexterity compared with dopaminergic medications. METHODS: Part III of the Unified Parkinson's Disease Rating Scale was used for the evaluation of bradykinesia, whereas the Purdue Pegboard Test and the Box and Block test were selected for dexterity. RESULTS: Our findings indicate that bradykinesia is significantly improved with both DBS and dopaminergic medication, whereas dexterity is improved only with DBS. Dopaminergic medication did not show a satisfactory efficacy on dexterity, and there was little synergistic effect of dopaminergic medication and STN-DBS for improving dexterity associated with Parkinson disease. CONCLUSIONS: Our results suggest that DBS is potentially more effective than dopaminergic medications for improving dexterity. The disparities in efficacy for bradykinesia and dexterity between DBS and dopaminergic medication hint at the potential mechanisms of STN-DBS. We speculate that DBS follows at least 2 different mechanisms for improving parkinsonian symptoms: 1) the dopaminergic system, primarily for the improvement of bradykinesia and 2) the nondopaminergic system, for the improvement of dexterity. This hypothesis requires further verification and investigation.