Recent advances in corneal neovascularization imaging.

Corneal neovascularization (CoNV) is a vision-threatening ocular disease commonly secondary to infectious, inflammatory, and traumatic etiologies. Slit lamp photography, in vivo confocal microscopy, angiography, and optical coherence tomography angiography (OCTA) are the primary diagnostic tools utilized in clinical practice to evaluate the vasculature of the ocular surface. However, there is currently a dearth of comprehensive literature that reviews the advancements in imaging technology for CoNV administration. Initially designed for retinal vascular imaging, OCTA has now been expanded to the anterior segment and has shown promising potential for imaging the conjunctiva, cornea, and iris. This expansion allows for the quantitative monitoring of the structural and functional changes associated with CoNV. In this review, we emphasize the impact of algorithm optimization in anterior segment-optical coherence tomography angiography (AS-OCTA) on the diagnostic efficacy of CoNV. Through the analysis of existing literature, animal model assessments are further reported to investigate its pathological mechanism and exhibit remarkable therapeutic interventions. In conclusion, AS-OCTA holds broad prospects and extensive potential for clinical diagnostics and research applications in CoNV.

Genome Editing VEGFA Prevents Corneal Neovascularization In Vivo.

Corneal neovascularization (CNV) is a common clinical finding seen in a range of eye diseases. Current therapeutic approaches to treat corneal angiogenesis, in which vascular endothelial growth factor (VEGF) A plays a central role, can cause a variety of adverse side effects. The technology of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 can edit VEGFA gene to suppress its expression. CRISPR offers a novel opportunity to treat CNV. This study shows that depletion of VEGFA with a novel CRISPR/Cas9 system inhibits proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. Importantly, subconjunctival injection of this dual AAV-SpCas9/sgRNA-VEGFA system is demonstrated which blocks suture-induced expression of VEGFA, CD31, and α-smooth muscle actin as well as corneal neovascularization in mice. This study has established a strong foundation for the treatment of corneal neovascularization via a gene editing approach for the first time.

Multifunctional Hydrogel Eye Drops for Synergistic Treatment of Ocular Inflammatory Disease.

Uveitis is a complex ocular inflammatory disease with a multifactorial etiology that can result in blindness. Although corticosteroid eye drops are the primary treatment for anterior uveitis, their efficacy is limited by low bioavailability, adverse effects, and a narrow focus on inflammation. In this study, the multifunctional hydrogel eye drops (designated as DCFH) were developed by incorporating the anti-inflammatory agent dexamethasone (DSP) and reactive oxygen species (ROS) scavenger cerium-based metal-organic frameworks (Ce-MOFs) into thermosensitive triblock copolymer F127 for the synergistic treatment against uveitis. The resulting F127 eye drops offer a favorable alternative to ophthalmic solution due to its thermosensitivity, thixotropy, light transmittance, improved ocular bioavailability, and unexpected anti-inflammatory efficacy. Notably, the participation of nanoporous Ce-MOFs, functional drug carriers, not only reduces ROS level but also boosts the anti-inflammatory activity of DSP in vitro. Therapeutically, the multifunctional DCFH exhibits superior efficacy in treating endotoxin-induced uveitis by mitigating the ophthalmic inflammatory reaction, suppressing inflammatory cytokines (e.g., TNF-α, IL-6, and IL-17) and downregulating the expression of iNOS and NLPR3. This synergistic treatment provides a valuable and promising approach for the management of uveitis and other ocular inflammatory conditions.

Nanomedicine for the Detection and Treatment of Ocular Bacterial Infections.

Ocular bacterial infection is a prevalent cause of blindness worldwide, with substantial consequences for normal human life. Traditional treatments for ocular bacterial infections areless effective, necessitating the development of novel techniques to enable accurate diagnosis, precise drug delivery, and effective treatment alternatives. With the rapid advancement of nanoscience and biomedicine, increasing emphasis has been placed on multifunctional nanosystems to overcome the challenges posed by ocular bacterial infections. Given the advantages of nanotechnology in the biomedical industry, it can be utilized to diagnose ocular bacterial infections, administer medications, and treat them. In this review, the recent advancements in nanosystems for the detection and treatment of ocular bacterial infections are discussed; this includes the latest application scenarios of nanomaterials for ocular bacterial infections, in addition to the impact of their essential characteristics on bioavailability, tissue permeability, and inflammatory microenvironment. Through an in-depth investigation into the effect of sophisticated ocular barriers, antibacterial drug formulations, and ocular metabolism on drug delivery systems, this review highlights the challenges faced by ophthalmic medicine and encourages basic research and future clinical transformation based on ophthalmic antibacterial nanomedicine.

Nuclear Radiation Knowledge and Anxiety Levels among Residents around a Nuclear Power Plant in Liaoning Province, China.

ABSTRACT: Awareness of radiation-related knowledge (RRK) and nuclear energy-related knowledge (NERK) among residents around a nuclear power plant (NPP), as well as their concerns about a NPP, were investigated. A face-to-face survey was conducted among 1,775 residents within 30 km around the NPP in Liaoning Province, China. A single-item Likert scale, Spearman's/Pearson's correlation coefficients, Student's t-test, ANOVA, and multiple-linear regression analysis were employed. Awareness of RRK and NERK among residents around the NPP was 27.7% and 36.6%, respectively. The anxiety level of respondents was negatively corelated with the distance from their residence to the NPP and age. Also, 55.6% of respondents thought that the publicity about nuclear energy/NPPs was insufficient, and 82.7% of respondents wanted to know relevant information about NPPs. Awareness of RRK and NERK among residents around the NPP was relatively low, which was related to education, occupation, and income. The anxiety level among residents was related to distance and age. The public was eager to know about RRK and NERK. These findings indicate that the publicity and education of RRK and NERK among residents around the NPP should be strengthened.

[Enrichment and Ecological Risk Assessment of Available Phosphorus in Paddy Soil of Fujian Province Over Past 40 years].

The ecological risks such as water eutrophication caused by soil phosphorus loss have attracted extensive attention, and its dynamic changes and enrichment effects are the basis for formulating reasonable control measures. In this study, based on the paddy soils of 1.8×106 hm2 in Fujian province, the dynamic changes and ecological risks of available phosphorus in paddy soils over the past 40 years were analyzedusing a soil database of 1:50000. The soil database contained 1471, 215534, and 2895 paddy soil samples in different periods, respectively. The paddy soil samples were derived from the 1982 Second National Soil Census, the 2008 Ministry of Agriculture and Rural Areas Soil Testing and Formulated Fertilization Project and the 2018 Ministry of Agriculture, and the Rural Areas Arable Land Quality Monitoring Project, respectively. The results showed that from 1982 to 2018, the content of available phosphorus in paddy soils increased by 47 mg·kg-1, and the enriched area reached 1.65×106 hm2, accounting for 91% of the total paddy soils in Fujian province. From 1982 to 2008, the available phosphorus content of paddy soils in Fujian province increased by 28 mg·kg-1, with the enriched area reaching 1.47×106 hm2, accounting for 82% of the total paddy soils in Fujian province. From 2008 to 2018, the available phosphorus content of paddy soils in Fujian province increased by 19 mg·kg-1, with the enriched area reaching 1.22×106 hm2, accounting for 69% of the total paddy soils in Fujian province. Further ecological risk assessment showed that from 2008 to 2018, the area of paddy soil with ecological phosphorus enrichment risk in the province gradually increased, mainly distributed in percogenic paddy soils and hydromorphic paddy soils with a slope of less than 2°. In the future, effective phosphorus fertilizer management measures should be formulated for different types of paddy soil to prevent the occurrence of environmental problems such as water eutrophication.

Engineering Hibiscus-Like Riboflavin/ZIF-8 Microsphere Composites to Enhance Transepithelial Corneal Cross-Linking.

Riboflavin-5-phosphate (RF) is the most commonly used photosensitizer in corneal cross-linking (CXL), but its hydrophilicity and negative charge limit its penetration through the corneal epithelium into the stroma. To enhance the corneal permeability of RF and promote its efficacy in the treatment of keratoconus, novel hibiscus-like RF@ZIF-8 microsphere composites [6RF@ZIF-8 NF (nanoflake)] are prepared using ZIF-8 nanomaterials as carriers, which are characterized by their hydrophobicity, positive potential, biocompatibility, high loading capacities, and large surface areas. Both hematoxylin and eosin endothelial staining and TUNEL assays demonstrate excellent biocompatibility of 6RF@ZIF-8 NF. In in vivo studies, the 6RF@ZIF-8 NF displayed excellent corneal permeation, and outstanding transepithelial CXL (TE-CXL) efficacy, slightly better than the conventional CXL protocol. Furthermore, the special hibiscus-like structures of 6RF@ZIF-8 NF meant that it has better TE-CXL efficacy than that of 6RF@ZIF-8 NP (nanoparticles) due to the larger contact area with the epithelium and the shorter RF release passage. These results suggest that the 6RF@ZIF-8 NF are promising for transepithelial corneal cross-linking, avoiding the need for epithelial debridement.

Hydrogel eye drops as a non-invasive drug carrier for topical enhanced Adalimumab permeation and highly efficient uveitis treatment.

Uveitis is one of the most popular blind-causing eye diseases worldwide. Adalimumab (ADA) is used for the uveitis treatment through systemic or intravitreal injection at the expense of systemic side effects and increased medical risks. Although eye drops, a non-invasive topical treatment, could be a potential strategy to reduce side effects, it remains challenging to apply due to limited bioavailability mainly linked to poor retention time and permeation capacity for eye biological barriers. Here, we reported hydrogel eye drops composed of low-deacetylated chitosan and ß-glycerophosphate as an ADA carrier and tested its toxicity, tolerability, intraocular permeability, and efficacy of non-invasive treatment for uveitis. It's found the ADA-loaded hydrogel eye drops were more efficient than free ADA both in permeation rate and clinical efficacy for uveitis, Overall, this study provides a friendly non-invasive strategy to improve drug permeation rate and uveitis treatment efficacy, which may be valuable to clinically ophthalmic medication.

Globus Pallidus Internus (GPi) Deep Brain Stimulation for Parkinson's Disease: Expert Review and Commentary.

INTRODUCTION: The globus pallidus internus (GPi) region has evolved as a potential target for deep brain stimulation (DBS) in Parkinson's disease (PD). DBS of the GPi (GPi DBS) is an established, safe and effective method for addressing many of the motor symptoms associated with advanced PD. It is important that clinicians fully understand this target when considering GPi DBS for individual patients. METHODS: The literature on GPi DBS in PD has been comprehensively reviewed, including the anatomy, physiology and potential pitfalls that may be encountered during surgical targeting and post-operative management. Here, we review and address the implications of lead location on GPi DBS outcomes. Additionally, we provide a summary of randomized controlled clinical trials conducted on DBS in PD, together with expert commentary on potential applications of the GPi as target. Finally, we highlight future technologies that will likely impact GPi DBS, including closed-loop adaptive approaches (e.g. sensing-stimulating capabilities), advanced methods for image-based targeting and advances in DBS programming, including directional leads and pulse shaping. RESULTS: There are important disease characteristics and factors to consider prior to selecting the GPi as the DBS target of PD surgery. Prior to and during implantation of the leads it is critical to consider the neuroanatomy, which can be defined through the combination of image-based targeting and intraoperative microelectrode recording strategies. There is an increasing body of literature on GPi DBS in patients with PD suggesting both short- and long-term benefits. Understanding the GPi target can be useful in choosing between the subthalamic (STN), GPi and ventralis intermedius nucleus as lead locations to address the motor symptoms and complications of PD. CONCLUSION: GPi DBS can be effectively used in select cases of PD. As the ongoing DBS target debate continues (GPi vs. STN as DBS target), clinicians should keep in mind that GPi DBS has been shown to be an effective treatment strategy for a variety of symptoms, including bradykinesia, rigidity and tremor control. GPi DBS also has an important, direct anti-dyskinetic effect. GPi DBS is easier to program in the outpatient setting and will allow for more flexibility in medication adjustments (e.g. levodopa). Emerging technologies, including GPi closed-loop systems, advanced tractography-based targeting and enhanced programming strategies, will likely be future areas of GPi DBS expansion. We conclude that although the GPi as DBS target may not be appropriate for all PD patients, it has specific clinical advantages.

Microenvironment-Triggered Degradable Hydrogel for Imaging Diagnosis and Combined Treatment of Intraocular Choroidal Melanoma.

Human choroidal melanoma (HCM) is one of the most common primary intraocular tumors and easily provokes liver metastases owing to the lack of sensitive and noninvasive therapeutic methods. Concerning the imaging diagnostics and therapeutic predicaments for choroidal melanoma, we designed microenvironment-triggered degradable hydrogels (RENP-ICG@PNIPAM:Dox-FA) based on ultrasmall (<5 nm) rare-earth nanoparticles (RENPs) with enhanced NIR-II luminescence. The ultrasmall diameter can significantly enhance the NIR-II luminescence performance of RENPs. RENPs were encapsulated by a dual-response PNIPAM hydrogel, which could release drug by responding to heat energy and glutathione under the tumor microenvironment. The in vitro/in vivo NIR-II imaging detection and antitumor activity were also compared systematically after different treatment conditions on ocular choroidal melanoma-1 cells and tumor-bearing mice, respectively. Besides, the degradability of the hydrogel composites under physiological conditions could be conducive to enhance the photothermal-chemotherapeutic effect and alleviate long-term biological toxicity. Our work on the microenvironment-triggered hydrogels with enhanced NIR imaging and easy metabolism may provide a promising strategy for sensitive and noninvasive imaging and phototherapy in ocular tumors.

Reliability of a New Swept-Source Optical Coherence Tomography Biometer in Healthy Children, Adults, and Cataract Patients.

PURPOSE: To comprehensively assess the reliability of a new optical biometer (IOLMaster 700), based on swept-source optical coherence tomography (SS-OCT) and comparison with a standard biometer (IOLMaster 500), in healthy children, adults, and cataract patients. METHODS: A total of 301 eyes from 301 consecutive subjects were enrolled prospectively. Two experienced operators measured each eye three times consecutively with the IOLMaster 700. The axial length (AL), keratometry (K), anterior chamber depth (ACD), lens thickness (LT), central corneal thickness (CCT), and white-to-white (WTW) distance were recorded. Intraoperator repeatability and interoperator reproducibility of the IOLMaster 700 were analyzed using the test-retest (TRT), coefficients of variation (CoV), and intraclass correlation coefficients (ICCs). The agreement between the two devices was evaluated using the Bland-Altman method. RESULTS: The repeatability and reproducibility of the SS-OCT optical biometer were high for all ocular biometry parameters in all groups, except for the WTW in cataract patients (TRT, 0.27-0.44 mm; ICC, 0.86-0.95). The reproducibility of averaged measurements from three consecutive readings (TRT : AL = 0.02 mm, CCT = 5.41 µm, ACD = 0.03 mm, LT = 0.03 mm, Km = 0.17 D, and WTW = 0.22 mm) was higher than the reproducibility of single measurements (TRT : AL = 0.04 mm, CCT = 7.43 µm, ACD = 0.06 mm, LT = 0.05 mm, Km = 0.26 D, and WTW = 0.35 mm) in the three groups. The consistency in the data between the two biometers was high, with narrow 95% LoAs in the three groups. CONCLUSION: Repeatability and reproducibility of the new SS-OCT optical biometer were excellent and consistent with that of the standard biometer with respect to healthy children, healthy adults, and cataract patients.

Medications, Deep Brain Stimulation, and Other Factors Influencing Impulse Control Disorders in Parkinson's Disease.

Impulse control disorders (ICDs) in Parkinson's disease (PD) have a high cumulative incidence and negatively impact quality of life. ICDs are influenced by a complex interaction of multiple factors. Although it is now well-recognized that dopaminergic treatments and especially dopamine agonists underpin many ICDs, medications alone are not the sole cause. Susceptibility to ICD is increased in the setting of PD. While causality can be challenging to ascertain, a wide range of modifiable and non-modifiable risk factors have been linked to ICDs. Common characteristics of PD patients with ICDs have been consistently identified across many studies; for example, males with an early age of PD onset and dopamine agonist use have a higher risk of ICD. However, not all cases of ICDs in PD can be directly attributable to dopamine, and studies have concluded that additional factors such as genetics, smoking, and/or depression may be more predictive. Beyond dopamine, other ICD associations have been described but remain difficult to explain, including deep brain stimulation surgery, especially in the setting of a reduction in dopaminergic medication use. In this review, we will summarize the demographic, genetic, behavioral, and clinical contributions potentially influencing ICD onset in PD. These associations may inspire future preventative or therapeutic strategies.

Comprehensive Comparison of Axial Length Measurement With Three Swept-Source OCT-Based Biometers and Partial Coherence Interferometry.

PURPOSE: To compare axial length measurements (and failure rate) of three swept-source optical coherence tomography (SS-OCT)-based biometers: IOLMaster 700 (Carl Zeiss Meditec, Jena, Germany), OA-2000 (Tomey, Nagoya, Japan), and Argos (Movu Inc., Komaki, Japan) to those provided by a partial coherence interferometry (PCI)-based optical biometer (IOLMaster v5.4 [Carl Zeiss Meditec]). METHODS: A total of 119 patients (171 eyes) undergoing cataract surgery were enrolled. Axial length was measured with the four biometers in a random order. Chi-square analysis was used to determine whether statistically significant differences in success rates were found between biometers. Within-subject standard deviation (Sw), test-retest repeatability (TRT), coefficient of variation (CoV), and intraclass correlation coefficients (ICCs) were calculated to analyze the intraobserver repeatability. Bland-Altman plots were used for agreement assessment. RESULTS: Axial length measurements were successfully measured in 166 eyes (97.08%) with the IOLMaster 700, 166 eyes (97.08%) with the OA-2000, 170 eyes (99.42%) with the Argos, and 138 eyes (80.70%) with the IOLMaster v5.4. Chi-square analysis indicated a significant difference in the failure rate between PCI- and SS-OCT-based biometers (P < .001). Intraobserver repeatability for the IOLMaster 700, OA-2000, and Argos showed excellent repeatability with low TRT (0.03, 0.06, and 0.05 mm, respectively), low CoV (0.04%, 0.10%, 0.07%, respectively), and high ICC (1.000, 0.999, and 1.000, respectively). The Bland-Altman 95% limits of agreement were as narrow as 0.09 mm, indicating excellent agreement among the three SS-OCT biometers and the PCI biometer. CONCLUSIONS: The three SS-OCT biometers showed a significantly higher success rate for axial length measurement than the IOLMaster v5.4 in various lens opacities. These SS-OCT biometers are likely to become the gold standard for axial measurement. [J Refract Surg. 2019;35(2):115-120.].

High glucose induces the aging of mesenchymal stem cells via Akt/mTOR signaling.

It has previously been demonstrated that glucose is important in the process of stem cell aging. However, the mechanisms of cell senescence induced by high glucose (HG) remain to be elucidated. The preliminary study indicated that D­galactose induced mesenchymal stem cell (MSCs) aging. The present study demonstrated, following treatment with 11.0 or 22.0 mM HG for 14 days, that HG significantly promoted MSCs aging and the expression levels of phosphorylated (p-)phosphatidylinositol 3-kinase/protein kinase B (Akt) and p­mammalian target of rapamycin signaling (mTOR) in the HG groups were increased compared with the control group. However, following Akt inhibition with 1.0 or 10.0 nM MK­2206, which is an Akt­specific small molecule inhibitor, the senescence­cell value in the HG group was significantly decreased compared with the control group. These results indicated that HG induced MSCs senescence and this effect was primarily mediated via the Akt/mTOR signaling pathway.

Bilateral Lower Sternocleidomastoid Botulinum Toxin Injections to Address Refractory Anterocollis.

Anterocollis is a type of cervical dystonia characterized by simultaneous and repetitive antagonist muscles contractions, resulting in abnormal neck flexion. It was described with a frequency of 6.8% from 399 patients with diagnosis of cervical dystonia and usually coexists with torticollis and/or laterocollis, as mixed cervical dystonia patterns. Botulinum toxin is usually a practical and effective treatment for cervical dystonia. The target muscles to inject in anterocollis are usually sternocleidomastoid and scalene muscles. There is also a case report suggesting longus collis involvement. Nevertheless, the dosage of the medication in anterocollis is limited by frequent side effects of dysphagia. We described 2 cases of refractory anterocollis. They did not benefit from conventional bilateral upper portion of sternocleidomastoid muscle injections with OnabotulinumtoxinA, but notably improved their symptoms and clinical global impression after switching to injections into bilateral lower portion of sternocleidomastoid muscles, without significant side effects.

A Polysomnographic Study of Parkinson's Disease Sleep Architecture.

Sleep disturbance is a common nonmotor phenomenon in Parkinson's disease (PD) affecting patient's quality of life. In this study, we examined the association between clinical characteristics with sleep disorders and sleep architecture patterns in a PD cohort. Patients underwent a standardized polysomnography study (PSG) in their "on medication" state. We observed that male gender and disease duration were independently associated with obstructive sleep apnea (OSA). Only lower levodopa equivalent dose (LED) was associated with periodic limb movement disorders (PLMD). REM sleep behavior disorder (RBD) was more common among older patients, with higher MDS-UPDRS III scores, and LED. None of the investigated variables were associated with the awakenings/arousals (A/A). Sleep efficiency was predicted by amantadine usage and age, while sleep stage 1 was predicted by dopamine agonists and Hoehn & Yahr severity. The use of MAO-B inhibitors and MDS-UPDRS part III were predictors of sleep stages 2 and 3. Age was the only predictor of REM sleep stage and gender for total sleep time. We conclude that sleep disorders and architecture are poorly predictable by clinical PD characteristics and other disease related factors must also be contributing to these sleep disturbances.

Novel targets and stimulation paradigms for deep brain stimulation.

Deep brain stimulation (DBS) is an accepted therapy for appropriately selected patients with movement disorders and psychiatric disease. The recent advances in lead technology and the advent of novel stimulation parameters have spurred a number of improvements that will likely be implemented in the clinical setting. Although the mechanisms and biology of DBS remain poorly understood, the progress in our understanding of network level dysfunction has driven the introduction of a variety of new targets and approaches to the treatment of human disease. Here we summarize the recent advances in novel stimulation patterns and customized field shaping. We also review new targets, novel applications of DBS and the immediate and long-term horizon for this therapy.

Successful treatment of open jaw and jaw deviation dystonia with botulinum toxin using a simple intraoral approach.

Oromandibular dystonia (OMD) is a focal dystonia that involves the mouth, jaw, and/or tongue. It can be classified as idiopathic, tardive dystonia or secondary to other neurological disorders and subdivided into jaw opening, jaw closing, jaw deviation and lip pursing. The muscles involved in jaw opening dystonia are usually the digastrics and lateral pterygoids. It is known that the lateral pterygoids may be approached both internally and externally. The external approach is the most common; however neurologists experienced in treating patients with botulinum toxin can safely and with no extra cost perform the intraoral procedure. We report our experience in the treatment of jaw opening and jaw deviation dystonia using the intraoral injection approach. Eight patients were selected from the University of Florida with a clinical diagnosis of open jaw/jaw deviation dystonia. All of them were injected with onabotulinum toxin A using the internal approach and the clinical global impression scale was applied. The mean age of the patients was 67 (standard deviation [SD] 10.2) years, with a disease duration of 10.2 (SD 7.7) years and the mean distance they traveled to our institution was 448 km (278 miles). After treatment, six patients scored as very much improved in the clinical global impression scale and two patients scored as much improved. Only one patient reported an adverse event of nasal speech following one of the injections that improved after 4 weeks. Botulinum toxin injections for open jaw/jaw deviation dystonia can be safely performed with the intraoral approach without the need of special devices other than electromyography.

Atrophy and other potential factors affecting long term deep brain stimulation response: a case series.

OBJECTIVE: To describe three DBS cases which presented with new side effects or loss of benefit from stimulation after long-term follow-up and to discuss the potential contributing factors. METHODS: A University of Florida (UF) database (INFORM) search was performed, identifying three patients, two Parkinson's disease (PD) and one Essential Tremor (ET), with an unexpected change in long-term programming thresholds as compared to initial evaluation. Clinical follow-up, programming, imaging studies, and lead measurements were reviewed. The UF Institutional Review Board (IRB) approved this study. RESULTS: A substantial increase in the 3rd ventricular width (120%), Evans index (6%), ventricular index (5%), and cella media index (17%) was uncovered. A change in thresholds across lead contacts with a decrease in current densities as well as a relative lateral change of lead location was also observed. Hardware-related complications, lead migration, and impedance variability were not identified. CONCLUSIONS: Potential factors contributing to long-term side effects should be examined during a DBS troubleshooting assessment. Clinicians should be aware that in DBS therapy there is delivery of electricity to a changing brain, and atrophy may possibly affect DBS programming settings as part of long-term follow-up.

Intraoperative smile in a multiple sclerosis patient with medication-refractory tremor.

Deep brain stimulation has been utilized to improve disease symptoms in patients with Parkinson's disease, dystonia, essential tremor, and other neuropsychiatric syndromes such as depression and obsessive compulsive disorder. Deep brain stimulation has also been observed to improve tremor for select patients with multiple sclerosis. During intraoperative stimulation in these multiple sclerosis patients, researchers have observed a wide spectrum of motor and sensory phenomena, but no stimulation-induced emotional responses have been reported. We detailed intraoperative smiling associated with stimulation of the ventralis oralis anterior/ventralis oralis posterior border region of the left thalamus.  A single patient with medication-resistant multiple sclerosis tremor experienced smiling, laughing, and subjective euphoria during intraoperative stimulation of the left thalamus. Specifically, during intraoperative stimulation of the left thalamic ventralis oralis anterior border, the patient developed a contralateral smile which progressed to a bilateral smile and was accompanied by a feeling of subjective happiness. The smile habituated in approximately 60 seconds and it was reproducible on a repeat stimulation. The patient could subjectively feel the facial movement, and, at higher voltages, the movement was described as a pulling sensation. Stimulation of the anterior ventralis oralis anterior border of the left thalamus in an multiple sclerosis patient produced a unilateral smile that rapidly developed into a bilateral smile accompanied by euphoria. There were presumed capsular side effects at higher voltages. The exact mechanism by which stimulation of the thalamus produced a smile and mood elevation is unknown, but we speculate that the smile could be induced by stimulation of corticobulbar fibers arising from the caudal cingulate motor area connecting the contralateral facial nerve nucleus.