A boy with biallelic frameshift variants in TTC5 and brain malformation resembling tubulinopathies.

Brain malformations have heterogeneous genetic backgrounds. Tubulinopathies are a wide range of brain malformations caused by variants in tubulin and microtubules-associated genes. Recently biallelic variants in TTC5, also known as stress responsive activator of p300, have been reported in 11 patients from seven families with developmental delay, intellectual disability, and brain malformations. Here, we report compound heterozygous frameshift variants in TTC5 in a Japanese boy who showed severe psychomotor developmental delay and pseudobulbar palsy with growth failure. Brain magnetic resonance imaging showed a simplified gyral pattern and undetectable anterior limb of the internal capsule, suggesting tubulinopathies. Immunoblotting using lymphoblastoid cells derived from the patient showed undetectable TTC5 protein. Ttc5 silencing by RNA interference in Neuro2a cells reduced Tubulin ß3 protein level and caused abnormal cell cycle. Our report suggests a possible link between TTC5-related brain malformation and tubulinopathies.

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.

Scalp Nerve Block Alleviates Headaches Associated With Sonication During Transcranial Magnetic Resonance-Guided Focused Ultrasound.

BACKGROUND AND OBJECTIVES: In magnetic resonance-guided focused ultrasound (MRgFUS) procedures, headache is a frequent symptom and cause of treatment discontinuation. Herein, we assessed the efficacy of scalp nerve block (SNB) for alleviating headache during MRgFUS procedures. METHODS: The effect of SNB on intraprocedural headache was examined by retrospectively comparing 2 patient cohorts at a single institution. During the study period from April 2020 to February 2022, an SNB protocol for all patients with a skull density ratio ≤0.55 was instituted on October 6, 2021. The number of patients with a skull density ratio ≤0.55 was 34 before the protocol and 36 afterward. Headache intensity was evaluated using a numerical rating scale (NRS) after each sonication. To evaluate the effect of SNB on headache intensity, multiple regression analysis was performed per patient and per sonication. In the per-patient analysis, the effect of SNB was evaluated using the maximum NRS, mean NRS, and NRS at the first ultrasound exposure that reached 52.5°C. In the per-sonication analysis, the effect of SNB was evaluated not only for the entire sonication but also for sonications classified into ≤9999 J, 10 000 to 29 999 J, and ≥30 000 J energy doses. RESULTS: With SNB, headache alleviation was observed in the NRS after the first sonication that reached 52.5°C in each patient (ß = -2.40, 95% CI -4.05 to -0.758, P = .00499), in the NRS when all sonications were evaluated (ß = -0.647, 95% CI -1.19 to -0.106, P = .0201), and in the NRS when all sonications were classified into 10 000 to 29 999 J (ß = -1.83, 95% CI -3.17 to -0.485, P = .00889). CONCLUSION: SNB significantly reduced headache intensity during MRgFUS, especially that caused by sonication with a moderate-energy dose. These findings suggest that scalp nerves play a role in headache mechanisms during MRgFUS.

Effects of ghrelin on the intracellular calcium concentration in rat aorta vascular smooth muscle cells.

BACKGROUND/AIMS: Ghrelin has been regarded as a cardioprotective factor with complicated mechanisms. Whether ghrelin is vasodilative or vasoconstrictive in nature is controversial, and the effects of ghrelin on intracellular calcium concentration are still unclear. To explore the mechanisms involved in the vasoactive regulation of ghrelin at the cellular level, we investigated the effects of ghrelin on calcium concentrations in rat aorta vascular smooth muscle cells (VSMCs). METHODS: We obtained VSMCs via cell culture and stained the cells with Furo-2 AM. Western blotting was used to verify growth hormone secretagogue receptor (GHS-R1a) expression in VSMCs. The intracellular calcium variations affected by ghrelin and the interactions of ghrelin with angiotensin II (AngII), Sq22536, and potassium chloride (KCl) were observed using a calcium imaging and analysis system. RESULTS: Western blotting revealed good GHS-R1a expression in VSMCs. The most prominent finding in the present study was that ghrelin inhibited the AngII-induced increase in the calcium concentration. This inhibition was reversed by the adenylate cyclase inhibitor Sq22536 and the GHS-R1a antagonist (D-Lys(3))- GHRP-6. This finding revealed the potential vasodilative effects of ghrelin at the cellular level. We did not observe any effects of ghrelin on intracellular calcium concentrations in resting VSMCs or the increase of calcium concentration induced by KCl. CONCLUSION: Ghrelin inhibited the increase in the intracellular calcium concentration of rat aorta VSMCs induced by AngII, which may depend on the activation of the cAMP/PKA pathway.

Erythema and Induration of Bacillus Calmette-Guérin Scar Associated With Multisystem Inflammatory Syndrome in Children in Japan: A Case Report.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare febrile disorder with multisystem organ involvement temporally associated with coronavirus 2019 infection (COVID-19) and frequently exhibits features mimicking Kawasaki disease (KD), another febrile disorder in children. The pathogenesis and the full clinical spectrum of MIS-C is poorly understood: It is still unclear whether MIS-C and KD are different syndromes or represent a common spectrum. The erythema and induration of Bacillus Calmette-Guérin (BCG) scar is one of the characteristic findings of KD, and is useful for the diagnosis in countries where BCG vaccination is mandated in infancy. Furthermore, such findings in BCG scar were also reported after SARS-CoV-2 vaccination, which may be related to molecular mimicry. However, there are no reports of changes at the BCG scar in MIS-C cases. Here, we report a case of MIS-C in a 3-year-old Hispanic boy in Japan, with erythema and induration at the BCG scar. The patient received BCG vaccination at 16 months of age in Japan. Four weeks before the onset, he had positive polymerase chain reaction (PCR) results for SARS-CoV-2 following household outbreak, although he was asymptomatic. He presented with fever and gastrointestinal symptoms, followed by the appearance of all six principal findings of complete KD. He exhibited congestive heart failure, following intravenous immunoglobulin (IVIG) therapy. He was diagnosed with MIS-C based on characteristic mucocutaneous and gastrointestinal symptoms, decreased cardiac function, and coagulopathy, in addition to laboratory data consistent with MIS-C. The BCG finding was present from the early stage of the disease. The patient was refractory to two doses of IVIGs, and the third IVIG plus prednisolone resulted in defervescence and improvement in heart failure. No coronary involvement was observed. This is the first case of erythema and induration at the BCG scar associated with MIS-C accompanied by KD features, which may give clinical and mechanistic insights in the understanding of the disease. Since the full spectrum of MIS-C is still evolving and both of them are syndromes with overlapped clinical features, further studies are warranted for deep phenotyping of MIS-C with KD features relative to KD in countries with mandatory BCG programs in infancy.

A supramolecular approach on using poly(fluorenylstyrene)-block-poly(2-vinylpyridine):PCBM composite thin films for non-volatile memory device applications.

Supramolecular composite thin films of poly[4-(9,9-dihexylfloren-2-yl)styrene]-block-poly(2-vinylpyridine) (P(St-Fl)-b-P2VP):[6,6]-phenyl-C(61)-butyric acid methyl ester (PCBM) were prepared for write-once-read-many times (WORM) non-volatile memory devices. The optical absorption and photoluminescence results indicated the formation of charge transfer complexation between the P2VP block and PCBM, which led to the varied PCBM aggregated size and memory characteristics. The ITO/PCBM:(P(St-Fl)-b-P2VP)/Al device exhibited the WORM characteristic with low threshold voltage (-1.6 to -3.2 V) and high ON/OFF ratio (10(3) to 10(5)) by tuning the PCBM content. The switching behavior could be explained by the charge injection dominated thermionic emission in the OFF state and field-induced charge transfer in the ON state. The present study provides a novel approach system for tuning polymer memory device characteristics through the supramolecular materials approach.

Increased anteroventral striatal dopamine transporter and motor recovery after subthalamic deep brain stimulation in Parkinson's disease.

OBJECTIVE: Subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease is effective; however, its mechanism is unclear. To investigate the degree of neuronal terminal survival after STN-DBS, the authors examined the striatal dopamine transporter levels before and after treatment in association with clinical improvement using PET with [11C]2ß-carbomethoxy-3ß-(4-fluorophenyl)tropane ([11C]CFT). METHODS: Ten patients with Parkinson's disease who had undergone bilateral STN-DBS were scanned twice with [11C]CFT PET just before and 1 year after surgery. Correlation analysis was conducted between [11C]CFT binding and off-period Unified Parkinson's Disease Rating Scale (UPDRS) scores assessed preoperatively and postoperatively. RESULTS: [11C]CFT uptake reduced significantly in the posterodorsal putamen contralateral to the parkinsonism-dominant side after 1 year; however, an increase was noted in the contralateral anteroventral putamen and ipsilateral ventral caudate postoperatively (p < 0.05). The percentage increase in [11C]CFT binding was inversely correlated with the preoperative binding level in the bilateral anteroventral putamen, ipsilateral ventral caudate, contralateral anterodorsal putamen, contralateral posteroventral putamen, and contralateral nucleus accumbens. The percentage reduction in UPDRS-II score was significantly correlated with the percentage increase in [11C]CFT binding in the ipsilateral anteroventral putamen (p < 0.05). The percentage reduction in UPDRS-III score was significantly correlated with the percentage increase in [11C]CFT binding in the ipsilateral anteroventral putamen, ventral caudate, and nucleus accumbens (p < 0.05). CONCLUSIONS: STN-DBS increases dopamine transporter levels in the anteroventral striatum, which is correlated with the motor recovery and possibly suggests the neuromodulatory effect of STN-DBS on dopaminergic terminals in Parkinson's disease patients. A preoperative level of anterior striatal dopamine transporter may predict reserve capacity of STN-DBS on motor recovery.

Combining living anionic polymerization with branching reactions in an iterative fashion to design branched polymers.

This paper reviews the precise synthesis of many-armed and multi-compositional star-branched polymers, exact graft (co)polymers, and structurally well-defined dendrimer-like star-branched polymers, which are synthetically difficult, by a commonly-featured iterative methodology combining living anionic polymerization with branched reactions to design branched polymers. The methodology basically involves only two synthetic steps; (a) preparation of a polymeric building block corresponding to each branched polymer and (b) connection of the resulting building unit to another unit. The synthetic steps were repeated in a stepwise fashion several times to successively synthesize a series of well-defined target branched polymers.

An influenza virus replicon system in yeast identified Tat-SF1 as a stimulatory host factor for viral RNA synthesis.

Influenza viruses infect vertebrates, including mammals and birds. Influenza virus reverse-genetics systems facilitate the study of the structure and function of viral factors. In contrast, less is known about host factors involved in the replication process. Here, we developed a replication and transcription system of the negative-strand RNA genome of the influenza virus in Saccharomyces cerevisiae, which depends on viral RNAs, viral RNA polymerases, and nucleoprotein (NP). Disruption of SUB2 encoding an orthologue of human RAF-2p48/UAP56, a previously identified viral RNA synthesis stimulatory host factor, resulted in reduction of the viral RNA synthesis rate. Using a genome-wide set of yeast single-gene deletion strains, we found several host factor candidates affecting viral RNA synthesis. We found that among them, Tat-SF1, a mammalian homologue of yeast CUS2, was a stimulatory host factor in influenza virus RNA synthesis. Tat-SF1 interacted with free NP, but not with NP associated with RNA, and facilitated formation of RNA-NP complexes. These results suggest that Tat-SF1 may function as a molecular chaperone for NP, as does RAF-2p48/UAP56. This system has proven useful for further studies on the mechanism of influenza virus genome replication and transcription.

Application of Deep Brain Stimulation for Treatment-resistant Obsessive Compulsive Disorder: Current Status and Future Perspectives in Japan.

As in many Western countries, deep brain stimulation (DBS) is already being used daily in Japan to clinically treat neurological diseases such as Parkinson's disease, essential tremor, and dystonia. Additionally, in both Europe and the United States, numerous case reports as well as multicenter randomized controlled trials have examined its use for treatment-refractory mental illnesses such as obsessive compulsive disorder (OCD) and major depressive disorder. Based on a number of the reports, the European Union (EU) and the USA Food and Drug Administration (FDA) granted limited approval of DBS for treatment-resistant OCD in 2009. Furthermore, a systematic review and meta-analysis in 2015 showed that DBS therapy for patients with treatment-resistant OCD had efficacy and was safe. Unlike the EU and the USA, DBS is not used to treat OCD or other psychiatric disorders in Japan, even though people with treatment-resistant OCD and their physicians and families urgently need additional treatments. This situation results from the "Resolution of total denial for psychosurgery," which the Japanese Society of Psychiatry and Neurology adopted in 1975. We believe that the appropriateness of using DBS for treating psychiatric disorders including OCD should be considered after thorough discussion and consideration based on accurate and objective understanding. Currently, the field of psychiatry in Japan seems to lack scientific consideration as well as scientific understanding in this area. Under these circumstances, we hope that this review article will help psychiatrists and other relevant parties in Japan to gain an accurate and scientific understanding of DBS.

A randomized controlled trial of 5 daily sessions and continuous trial of 4 weekly sessions of repetitive transcranial magnetic stimulation for neuropathic pain.

We conducted a multicenter, randomized, patient- and assessor-blinded, sham-controlled trial to investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) in patients with neuropathic pain (NP). Patients were randomly assigned to receive 5 daily sessions of active or sham rTMS of M1 corresponding to the part of the body experiencing the worst pain (500 pulses per session at 5 Hz). Responders were invited to enroll in an open-label continuous trial involving 4 weekly sessions of active rTMS. The primary outcome was a mean decrease in a visual analogue scale of pain intensity (scaled 0-100 mm) measured daily during the daily sessions in an intention-to-treat population. Secondary outcomes were other pain scores, quality-of-life measures, and depression score. One hundred forty-four patients were assigned to the active or sham stimulation groups. The primary outcome, mean visual analogue scale decreases, was not significantly different (P = 0.58) between the active stimulation group (mean, 8.0) and the sham group (9.2) during the daily sessions. The secondary outcomes were not significantly different between 2 groups. The patients enrolled in the continuous weekly rTMS achieved more pain relief in the active stimulation group compared with the sham (P < 0.01). No serious adverse events were observed. Five daily sessions of rTMS with stimulus conditions used in this trial were ineffective in short-term pain relief in the whole study population with various NP. Long-term administration to the responders should be investigated for the clinical use of rTMS on NP in the future trials.

Improvement of radiation-induced healing delay by etanercept treatment in rat arteries.

Surgical treatment often causes difficulty in the irradiated field because of delayed wound healing, which is mainly due to vascular dysfunction. To overcome this difficulty, we attempted to accelerate the recovery from clamp injury in irradiated superficial epigastric arteries of rats as a model. Etanercept, a soluble receptor of tumor necrosis factor-alpha, was administered four times to rats with irradiated arteries before and after clamp injury. Loss of endothelial cells and necrosis of the media in the irradiated arteries continued for more than 1 week after the injury; however, in the rats treated with etanercept, the endothelial cells recovered in the intima, and alpha-smooth muscle actin-positive smooth muscle cells recovered in the injured and irradiated arteries. After clamp injury of common carotid arteries that had previously been irradiated, the blood flow in these arteries was visualized by magnetic resonance (MR) angiography. The time-of-flight signal was weakened in the injured and irradiated arteries. This time-of-flight signal was recovered by the etanercept treatment. These findings suggest that etanercept improves the radiation-impaired healing of arteries in rats.

Comparison of microsomal prostaglandin E synthase-1 deletion and COX-2 inhibition in acute cardiac ischemia in mice.

The aim of the present study was to compare the effects of genetic mPGES-1 loss and COX-2 inhibition on myocardial damage after coronary occlusion. mPGES-1(-/-) mice and their wild-type littermates were injected with vehicle or COX-2 inhibitor (celecoxib), and 30min later the left coronary artery was surgically occluded. At 24h, myocardial infarct (MI) volume was measured histologically. Post-MI survival was reduced in WT mice receiving celecoxib (12/20) compared with vehicle-treated controls (12/12) or the loss of mPGES-1 (13/13) together with increased phosphokinase (CPK) and cardiac troponin-I release. Endogenous mPGES-1 expression was unchanged by ischemia in WT mice and absent in mPGES-1(-/-) hearts. COX-2 expression was markedly increased at 24h after MI in WT hearts; this upregulation was largely attenuated in mPGES-1(-/-) mice. We conclude that loss of mPGES-1 prevents the upregulation of COX-2 after myocardial infarct, and in contrast to inhibition of COX-2, does not increase ischemic myocardial damage.

An Application of Photoactivatable Substrate for the Evaluation of Epithelial-mesenchymal Transition Inhibitors.

Epithelial-mesenchymal transition (EMT), phenotypic changes in cell adhesion and migration, is involved in cancer invasion and metastasis, hence becoming a target for anti-cancer drugs. In this study, we report a method for the evaluation of EMT inhibitors by using a photoactivatable gold substrate, which changes from non-cell-adhesive to cell-adhesive in response to light. The method is based on the geometrical confinement of cell clusters and the subsequent migration induction by controlled photoirradiation of the substrate. As a proof-of-concept experiment, a known EMT inhibitor was successfully evaluated in terms of the changes in cluster area or leader cell appearance, in response to biochemically and mechanically induced EMT. Furthermore, an application of the present method for microbial secondary metabolites identified nanaomycin H as an EMT inhibitor, potentially killing EMTed cells in disseminated conditions. These results demonstrate the potential of the present method for screening new EMT inhibitors.

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.

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.

Improvement of the breaking strength of wound by combined treatment with recombinant human G-CSF, recombinant human M-CSF, and a TGF-beta1 receptor kinase inhibitor in rat skin.

Effective doses of ionizing radiation during preoperative radiotherapy occasionally cause wound complications after subsequent surgery. The authors attempted to accelerate radiation-impaired wound healing in animal models. Recombinant human granulocyte colony-stimulating factor (rhG-CSF), recombinant human macrophage colony-stimulating factor (rhM-CSF), and an inhibitor of transforming growth factor (TGF)-beta1 receptor kinase, SB431542, were injected s.c. into a full-thickness incisional wound site in the dorsal skin of rats after local irradiation of X-ray (30 Gy). Wound healing of irradiated skin was assessed using the breaking strength of the wound and histological analyses. The impaired wound healing in irradiated skin was found to be associated with impaired mobilization of bone marrow-derived cells and enhanced expression of TGF-beta1 mRNA. The breaking strength of the wound in the irradiated skin was approximately one-eighth of that in the non-irradiated skin; however, following combined treatment with the above three compounds the breaking strength increased to approximately one-half of that in the non-irradiated skin. Histological analysis of the wounded skin revealed an increase in formation of collagen fibers and the panniculus carnosus following the combined treatment. Moreover, the increased breaking strength was associated with an increase in a subpopulation of fibrocytes (collagen I/ED1 double positive cells). These findings suggested that a combined treatment with rhG-CSF, rhM-CSF, and SB431542 is promising as a means of improving radiation-impaired wound healing.

Complex macromolecular chimeras.

By combining two living polymerizations, anionic and ring opening (ROP), the following novel multiblock multicomponent linear and miktoarm star (micro-star) polymer/polypeptide hybrids (macromolecular chimeras) were synthesized: Linear, PBLL-b-PBLG-b-PS-b-PBLG-b-PBLL; 3micro-stars, (PS)2(PBLG or PBLL), (PS)(PI)(PBLG or PBLL); 4micro-stars, (PS)2[P(alpha-MeS)](PBLG or PBLL), (PS)2(PBLG or PBLL)2 [PS, polystyrene; PI, polyisoprene; P(alpha-MeS), poly(alpha-methylstyrene); PBLG, poly(gamma-benzyl-L-glutamate); and PBLL, poly(-tert-butyloxycarbonyl-L-lysine)]. The procedure involves (a) the synthesis of end- or in-chain amino-functionalized polymers, by anionic polymerization high vacuum techniques and appropriate linking chemistry and (b) the use of the amino groups for the ROP of alpha-amino acid carboxyanhydrides (NCAs). Molecular characterization revealed the high molecular weight and compositional homogeneity of the macromolecular chimeras prepared. The success of the synthesis was based mainly on the high vacuum techniques used for the ROP of NCAs, ensuring the avoidance of unwanted polymerization mechanisms and termination reactions.

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.