Optimal timing for drug delivery into the hippocampus by focused ultrasound: A comparison of hydrophilic and lipophilic compounds.

Aims: Previous studies have reported that focused ultrasound (FUS) helps modulate the blood-brain barrier (BBB). These studies have generally used the paracellular pathway owing to tight junction proteins (TJPs) regulation. However, BBB transport pathways also include diffusion and transcytosis. Few studies have examined transcellular transport across endothelial cells. We supposed that increased BBB permeability caused by FUS may affect transcytosis. We investigated drug delivery through transcytosis and paracellular transport to the brain after BBB modulation using FUS. Main methods: FUS and microbubbles were applied to the hippocampus of rats, and were euthanized at 1, 4, 24, and 48 h after sonication. To investigate paracellular transport, we analyzed TJPs, including zona occludens-1 (ZO-1) and occludin. We also investigated caveola-mediated transcytosis by analyzing caveola formation and major facilitator superfamily domain-containing 2a (Mfsd2a) levels, which inhibit caveola vesicle formation. Key findings: One hour after FUS, ZO-1 and occludin expression was the lowest and gradually increased over time, returning to baseline 24 h after FUS treatment. Compared with that of TJPs, caveola formation started to increase 1 h after FUS treatment and peaked at 4 h after FUS treatment before returning to baseline by 48 h after FUS treatment. Decreased Mfsd2a levels were observed at 1 h and 4 h after FUS treatment, indicating increased caveola formation. Significance: FUS induces BBB permeability changes and regulates both paracellular transport and caveola-mediated transcytosis. However, a time difference was observed between these two mechanisms. Hence, when delivering drugs into the brain after FUS, the optimal drug administration timing should be determined by the mechanism by which each drug passes through the BBB.

Navigation Guided Biopsy Is as Effective as Frame-Based Stereotactic Biopsy.

BACKGROUND: Stereotactic biopsy is a standard procedure for brain biopsy. However, with advances in technology, navigation-guided brain biopsy has become a well-established alternative. Previous studies have shown that frameless stereotactic brain biopsy is as effective and safe as frame-based stereotactic brain biopsy is. In this study, the authors evaluate the diagnostic yield and complication rate of frameless intracranial biopsy. MATERIALS AND METHODS: We reviewed data from biopsy performed patients between March 2014 and April 2022. We retrospectively reviewed medical records, including imaging studies. Various intracerebral lesions were biopsied. Diagnostic yield and post-operative complications were compared with those of frame-based stereotactic biopsy. RESULTS: Forty-two frameless navigation-guided biopsy were performed, and the most common pathology was primary central nervous system lymphoma (35.7%), followed by glioblastoma (33.3%), and anaplastic astrocytomas (16.7%), respectively. The diagnostic yield was 100%. Post-operative intracerebral hematoma occurred in 2.4% of cases, but it was not symptomatic. Thirty patients underwent frame-based stereotactic biopsy, and the diagnostic yield was 96.7%. There was no difference in diagnostic rates between two methods (Fisher's exact test, p = 0.916). CONCLUSIONS: Frameless navigation-guided biopsy is as effective as frame-based stereotactic biopsy is, without causing further complications. We consider that frame-based stereotactic biopsy is no longer needed if frameless navigation-guided biopsy is used. A further study will be needed to generalize our results.

Long-lasting restoration of memory function and hippocampal synaptic plasticity by focused ultrasound in Alzheimer's disease.

BACKGROUND: Focused ultrasound (FUS) is a medical technology that non-invasively stimulates the brain and has been applied in thermal ablation, blood-brain barrier (BBB) opening, and neuromodulation. In recent years, numerous experiences and indications for the use of FUS in clinical and preclinical studies have rapidly expanded. Focused ultrasound-mediated BBB opening induces cognitive enhancement and neurogenesis; however, the underlying mechanisms have not been elucidated. METHODS: Here, we investigate the effects of FUS-mediated BBB opening on hippocampal long-term potentiation (LTP) and cognitive function in a 5xFAD mouse model of Alzheimer's disease (AD). We applied FUS with microbubble to the hippocampus and LTP was measured 6 weeks after BBB opening using FUS. Field recordings were made with a concentric bipolar electrode positioned in the CA1 region using an extracellular glass pipette filled with artificial cerebrospinal fluid. Morris water maze and Y-maze was performed to test cognitive function. RESULTS: Our results demonstrated that FUS-mediated BBB opening has a significant impact on increasing LTP at Schaffer collateral - CA1 synapses and rescues cognitive dysfunction and working memory. These effects persisted for up to 7 weeks post-treatment. Also, FUS-mediated BBB opening in the hippocampus increased PKA phosphorylation. CONCLUSION: Therefore, it could be a promising treatment for neurodegenerative diseases as it remarkably increases LTP, thereby improving working memory.

Endogenous Neural Stem Cell Activation after Low-Intensity Focused Ultrasound-Induced Blood-Brain Barrier Modulation.

Endogenous neural stem cells (eNSCs) in the adult brain, which have the potential to self-renew and differentiate into functional, tissue-appropriate cell types, have raised new expectations for neurological disease therapy. Low-intensity focused ultrasound (LIFUS)-induced blood-brain barrier modulation has been reported to promote neurogenesis. Although these studies have reported improved behavioral performance and enhanced expression of brain biomarkers after LIFUS, indicating increased neurogenesis, the precise mechanism remains unclear. In this study, we evaluated eNSC activation as a mechanism for neurogenesis after LIFUS-induced blood-brain barrier modulation. We evaluated the specific eNSC markers, Sox-2 and nestin, to confirm the activation of eNSCs. We also performed 3'-deoxy-3'[18F] fluoro-L-thymidine positron emission tomography ([18F] FLT-PET) to evaluate the activation of eNSCs. The expression of Sox-2 and nestin was significantly upregulated 1 week after LIFUS. After 1 week, the upregulated expression decreased sequentially; after 4 weeks, the upregulated expression returned to that of the control group. [18F] FLT-PET images also showed higher stem cell activity after 1 week. The results of this study indicated that LIFUS could activate eNSCs and induce adult neurogenesis. These results show that LIFUS may be useful as an effective treatment for patients with neurological damage or neurological disorders in clinical settings.

Supratotal Resection of Glioblastoma: Better Survival Outcome than Gross Total Resection.

OBJECTIVE: Supratotal resection (SupTR) of glioblastoma allows for a superior long-term disease control and increases overall survival. On the other hand, aggressive conventional approaches, including gross total resections (GTR), are limited by the impairment risk of adjacent eloquent areas, which may cause severe postoperative functional morbidity. This study aimed to analyze institutional cases with respect to the potential survival benefits of additional resection, including lobectomy, as a paradigm for SupTR in patients of glioblastoma. METHODS: Between 2014 and 2018, 15 patients with glioblastoma underwent SupTR (GTR and additional lobectomy) at the authors' institution. The postoperative Karnofsky performance score (KPS), progression-free survival (PFS), and overall survival (OS) were analyzed for the patients. RESULTS: Patients with SupTR showed significantly prolonged PFS and OS. The median PFS and OS values for the entire study group were 33.5 months (95% confidence intervals (CI): 18.5-57.3 months) and 49.1 months (95% CI: 24.7-86.6 months), respectively. Multivariate analysis revealed that the O6-DNA-methylguanine methyltransferase (MGMT) promoter methylation status was the only predictor for both superior PFS (p = 0.03, OR 5.7, 95% CI 1.0-49.8) and OS (p = 0.04, OR 6.5, 95% CI 1.1-40.2). There was no significant difference between the pre- and postoperative KPS scores. CONCLUSIONS: Our results suggest that SupTR with lobectomy allows for a superior PFS and OS without negatively affecting patient performance. However, due to the small number of patients, further studies that include more patients are needed.

Combined Effects of Focused Ultrasound and Photodynamic Treatment for Malignant Brain Tumors Using C6 Glioma Rat Model.

PURPOSE: Glioblastoma (GBM) is an intractable disease for which various treatments have been attempted, but with little effect. This study aimed to measure the effect of photodynamic therapy (PDT) and sonodynamic therapy (SDT), which are currently being used to treat brain tumors, as well as sono-photodynamic therapy (SPDT), which is the combination of these two. MATERIALS AND METHODS: Four groups of Sprague-Dawley rats were injected with C6 glioma cells in a cortical region and treated with PDT, SDT, and SPDT. Gd-MRI was monitored weekly and 18F-FDG-PET the day before and 1 week after the treatment. The acoustic power used during sonication was 5.5 W/cm² using a 0.5-MHz single-element transducer. The 633-nm laser was illuminated at 100 J/cm². Oxidative stress and apoptosis markers were evaluated 3 days after treatment using immunohistochemistry (IHC): 4-HNE, 8-OhdG, and Caspase-3. RESULTS: A decrease in tumor volume was observed in MRI imaging 12 days after the treatment in the PDT group (p<0.05), but the SDT group showed a slight increase compared to the 5-Ala group. The high expression rates of reactive oxygen species-related factors, such as 8-OhdG (p<0.001) and Caspase-3 (p<0.001), were observed in the SPDT group compared to other groups in IHC. CONCLUSION: Our findings show that light with sensitizers can inhibit GBM growth, but not ultrasound. Although SPDT did not show the combined effect in MRI, high oxidative stress was observed in IHC. Further studies are needed to investigate the safety parameters to apply ultrasound in GBM.

Comparison of Concordance between Chuna Manual Therapy Diagnostic Methods (Palpation, X-ray, Artificial Intelligence Program) in Lumbar Spine: An Exploratory, Cross-Sectional Clinical Study.

Before Chuna manual therapy (CMT), a manual therapy applied in Korean medicine, CMT spinal diagnosis using palpation or X-ray is performed. However, studies on the inter-rater concordance of CMT diagnostic methods, concordance among diagnostic methods, and standard CMT diagnostic methods are scarce. Moreover, no clinical studies have used artificial intelligence (AI) programs for X-ray image-based CMT diagnosis. Therefore, this study sought a feasible and standard CMT spinal diagnostic method and explored the clinical applicability of the CMT-AI program. One hundred participants were recruited, and the concordance within and among different diagnostic modalities was analyzed by dividing them into manual diagnosis (MD), X-ray image-based diagnosis (XRD) by experts and non-experts, and XRD using a CMT-AI program by non-experts. Regarding intra-group concordance, XRD by experts showed the highest concordance (used as a gold standard when comparing inter-group concordance), followed by XRD using the AI program, XRD by non-experts, and then MD. Comparing diagnostic results between the groups, concordance with the gold standard was the highest for XRD using the AI program, followed by XRD by non-experts, and MD. Therefore, XRD is a more reasonable CMT diagnostic method than MD. Furthermore, the clinical applicability of the CMT-AI program is high.

Comparison of concordance between chuna manual therapy diagnosis methods (palpation, X-ray, artificial intelligence program) in lumbar spine: An exploratory, cross-sectional, prospective observational study protocol.

INTRODUCTION: Chuna manual therapy (CMT) is a type of manual medicine practiced by Korean medical doctors in South Korea. Spinal diagnosis in CMT uses a system that applies manual diagnostic and X-ray tests to detect specific vertebral malpositions, based on the relative alignment across vertebral bodies. Recently, artificial intelligence (AI) programs have been developed to assist in the radiological diagnosis of CMT using X-ray images. Nevertheless, a few clinical studies have reported on the concordance between diagnosticians, diagnostics methodologies, and the use of AI programs for diagnosing CMT. At present, the evidence to support CMT diagnosis is insufficient. This study thus aims to overcome such limitations by collecting and comparing CMT diagnostic data from experts and non-experts through manual diagnosis, X-ray test, and images obtained using an AI program. The study aims to search for CMT diagnosis methods with more outstanding rationality and consistency and to explore the potential use of AI-based CMT diagnosis programs. METHODS/DESIGN: This study will be conducted as an exploratory, cross-sectional, prospective observational study that will recruit 100 non-specialist subjects. Each subject will submit a signed consent after the screening test and undergo L-spine standing AP & lateral X-ray imaging. Manual CMT diagnosis will be performed by 3 CMT experts according to the standard operation procedure (SOP). The X-ray images of the 100 subjects will subsequently be used to make the CMT radiological diagnoses according to the same SOP by the CMT expert group (n = 3) and CMT non-expert group (n = 3). Among the subjects, those in the non-expert group will receive another CMT radiological diagnosis with spinal data obtained using the AI program, approximately 1 month from after initial diagnosis.Based on the collected diagnostic data, within- and between-group concordance levels will be assessed for each diagnostic method. The verified level of concordance will be used to test the potential use of CMT diagnostic method and CMT AI programs with high levels of rationality and consistency. ETHICS AND DISSEMINATION: This trial has received complete ethical approval from the Wonkwang University Korean Medicine Hospital (IRB 2021-8). We intend to submit the results of the trial to a peer-reviewed journal and/or conferences. TRIAL REGISTRATION: https://cris.nih.go.kr/cris/search/detailSearch.do?search_lang=E&search_page=M&pageSize=10&page=undefined&seq=20613&status=5&seq_group=20613, Identifier: KCT0006707.

Factors Associated with Energy Efficiency of Focused Ultrasound Through the Skull: A Study of 3D-Printed Skull Phantoms and Its Comparison with Clinical Experiences.

While focused ultrasound (FUS) is non-invasive, the ultrasound energy is attenuated by the skull which results in differences in energy efficiency among patients. In this study, we investigated the effect of skull variables on the energy efficiency of FUS. The thickness and density of the skull and proportion of the trabecular bone were selected as factors that could affect ultrasound energy transmittance. Sixteen 3D-printed skull models were designed and fabricated to reflect the three factors. The energy of each phantom was measured using an ultrasonic sound field energy measurement system. The thickness and proportion of trabecular bone affected the attenuation of transmitted energy. There was no difference in the density of the trabecular bone. In clinical data, the trabecular bone ratio showed a significantly greater correlation with dose/delivered energy than that of thickness and the skull density ratio. Currently, for clinical non-thermal FUS, the data are not sufficient, but we believe that the results of this study will be helpful in selecting patients and appropriate parameters for FUS treatment.

Dural Injury in Unilateral Biportal Endoscopic Spinal Surgery.

STUDY DESIGN: Retrospective study. OBJECTIVES: Unilateral biportal endoscopic surgery (UBES) is a popular surgical method used to treat degenerative spinal diseases because of its merits, such as reduced tissue damage and outstanding visual capacity. However, dural injury is the most common complication of UBES with an incidence rate of 1.9% to 5.8%. The purpose of this study was to analyze the pattern of dural injury during UBES and to report the clinical course. METHODS: We retrospectively reviewed the medical and radiographic records of surgically treated patients who underwent UBES at a single institute between January 2018 and December 2019. RESULTS: Fifty-three patients, representing 67 segments, underwent UBES. Seven dural injuries occurred, and the incidence rate was 13.2%. Among 16 far lateral approaches, 2 dural injuries of the exiting roots occurred and were treated with fibrin sealant reinforcement. Among 51 median approaches, dural injury occurred at the thecal sac (n = 3) and traversing root (n = 2). A dural injury of the shoulder of the traversing root was treated with a fibrin sealant; however, a defect in the thecal sac required a revision for reconstruction. The other 2 thecal sac injuries were directly repaired via microscopic surgery. CONCLUSIONS: Dural injury during UBES can occur because of the various anatomical features of the meningo-vertebral ligaments. Direct repair of the central dural defect should be considered under microscopic vision. A linear tear in the lateral dura or root can be controlled with a simple patchy reinforcement under endoscopic vision.

Non-invasively enhanced intracranial transplantation of mesenchymal stem cells using focused ultrasound mediated by overexpression of cell-adhesion molecules.

Although there have been reports of promising results regarding the transplantation of mesenchymal stem cells (MSCs) for neurodegenerative diseases through the use of neuronal differentiation or control of the microenvironment, traditional surgical transplantation methods like parenchymal or intravenous injection have limitations such as secondary injuries in the brain, infection, and low survival rate of stem cells in the target site. Focused ultrasound (FUS) treatment is an emerging modality for the treatment of brain diseases, including neurodegenerative disorders. The various biological effects of FUS treatment have been investigated; therefore, the goal is now to improve the delivery efficiency and function of MSCs by capitalizing on the advantages of FUS. In this study, we demonstrated that FUS increases MSC transplantation into brain tissue by >2-fold, and that this finding might be related to the activation of intercellular adhesion molecule-1 in endothelial and subendothelial cells and vascular adhesion molecule-1 in endothelial cells.

Focused ultrasound-induced blood-brain barrier opening improves adult hippocampal neurogenesis and cognitive function in a cholinergic degeneration dementia rat model.

BACKGROUND: The persistence of adult hippocampal neurogenesis (AHN) is sharply decreased in Alzheimer's disease (AD). The neuropathologies of AD include the presence of amyloid-ß deposition in plaques, tau hyperphosphorylation in neurofibrillary tangles, and cholinergic system degeneration. The focused ultrasound (FUS)-mediated blood-brain barrier opening modulates tau hyperphosphorylation, the accumulation of amyloid-ß proteins, and increases in AHN. However, it remains unclear whether FUS can modulate AHN in cholinergic-deficient conditions. In this study, we investigated the effect of FUS on AHN in a cholinergic degeneration rat model of dementia. METHODS: Adult male Sprague-Dawley rats (n = 48; 200-250 g) were divided into control (phosphate-buffered saline injection), 192 IgG-saporin (SAP), and SAP+FUS groups; in the two latter groups, SAP was injected bilaterally into the lateral ventricle. We applied FUS to the bilateral hippocampus with microbubbles. Immunohistochemistry, enzyme-linked immunosorbent assay, immunoblotting, 5-bromo-2'-deoxyuridine labeling, an acetylcholinesterase assay, and the Morris water maze test were performed to assess choline acetyltransferase, acetylcholinesterase activity, brain-derived neurotrophic factor expression, neural proliferation, and spatial memory, respectively. Statistical significance of differences in between groups was calculated using one-way and two-way analyses of variance followed by Tukey's multiple comparison test to determine the individual and interactive effects of FUS on immunochemistry and behavioral analysis. P < 0.05 was considered significant. RESULTS: Cholinergic degeneration in rats significantly decreased the number of choline acetyltransferase neurons (P < 0.05) in the basal forebrain, as well as AHN and spatial memory function. Rats that underwent FUS-mediated brain-blood barrier opening exhibited significant increases in brain-derived neurotrophic factor (BDNF; P < 0.05), early growth response protein 1 (EGR1) (P < 0.01), AHN (P < 0.01), and acetylcholinesterase activity in the frontal cortex (P < 0.05) and hippocampus (P < 0.01) and crossing over (P < 0.01) the platform in the Morris water maze relative to the SAP group after sonication. CONCLUSIONS: FUS treatment increased AHN and improved spatial memory. This improvement was mediated by increased hippocampal BDNF and EGR1. FUS treatment may also restore AHN and protect against neurodegeneration, providing a potentially powerful therapeutic strategy for AD.

Four-year follow-up results of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor.

BACKGROUND: Following the emergence of magnetic resonance-guided focused ultrasound as a promising tool for movement disorder surgery, thalamotomy for essential tremor using this technique has become a useful tool based on its efficacy and lack of adverse effects. Here, we summarize the 4-year results of previous reports focusing on the durability of effectiveness of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor. METHODS: From October 2013 to August 2014, 15 patients with intractable essential tremor were enrolled. Twelve of them completed clinical assessment through 4 years of postoperative follow-up. Tremor severity, task performance, and disability were measured using the Clinical Rating Scale of Tremor. RESULTS: The mean age of the 12 patients was 61.7 ± 8.1 years. Maximally delivered energy was 15,552.4 ± 6574.1 joules. The mean number of sonications was 17.3 ± 1.6. The mean postoperative lesion volume was 82.6 ± 29.023 mm3 and in 1 year was a mean of 9.667 ± 8.573 mm3 . Four years postoperatively, improvement of the hand tremor score was 56%, that of the disability score was 63%, that of the postural score was 70%, and that of the action score was 63% compared with baseline; all improvements were significant and sustained over the 4-year period after thalamotomy. There was no permanent adverse effect throughout the 4-year follow-up period. CONCLUSIONS: Magnetic resonance-guided focused ultrasound thalamotomy exhibits sustained clinical efficacy 4 years after the treatment of intractable essential tremor. Adverse events are generally transient. A large cohort of patients who have undergone magnetic resonance-guided focused ultrasound thalamotomy with longer follow-up is needed to confirm our findings. © 2019 International Parkinson and Movement Disorder Society.

Focused ultrasound-mediated noninvasive blood-brain barrier modulation: preclinical examination of efficacy and safety in various sonication parameters.

OBJECTIVE The application of pharmacological therapeutics in neurological disorders is limited by the ability of these agents to penetrate the blood-brain barrier (BBB). Focused ultrasound (FUS) has recently gained attention for its potential application as a method for locally opening the BBB and thereby facilitating drug delivery into the brain parenchyma. However, this method still requires optimization to maximize its safety and efficacy for clinical use. In the present study, the authors examined several sonication parameters of FUS influencing BBB opening in small animals. METHODS Changes in BBB permeability were observed during transcranial sonication using low-intensity FUS in 20 adult male Sprague-Dawley rats. The authors examined the effects of FUS sonication with different sonication parameters, varying acoustic pressure, center frequency, burst duration, microbubble (MB) type, MB dose, pulse repetition frequency (PRF), and total exposure time. The focal region of BBB opening was identified by Evans blue dye. Additionally, H & E staining was used to identify blood vessel damage. RESULTS Acoustic pressure amplitude and burst duration were closely associated with enhancement of BBB opening efficiency, but these parameters were also highly correlated with tissue damage in the sonicated region. In contrast, MB types, MB dose, total exposure time, and PRF had an influence on BBB opening without conspicuous tissue damage after FUS sonication. CONCLUSIONS The study aimed to identify these influential conditions and provide safety and efficacy values for further studies. Future work based on the current results is anticipated to facilitate the implementation of FUS sonication for drug delivery in various CNS disease states in the near future.

Predictive factors of early distant brain failure after gamma knife radiosurgery alone in patients with brain metastases of non-small-cell lung cancer.

The objective of this study was to elucidate the predictive factors for early distant brain failure in patients with brain metastases of non-small-cell lung cancer (NSCLC) who were treated with gamma knife radiosurgery (GKRS) without previous whole-brain radiotherapy (WBRT) or surgery. We retrospectively reviewed clinical and imaging data of 459 patients with brain metastases of NSCLC who underwent GKRS from June 2008 to December 2013. The primary end-point was early distant brain failure, defined as the detection of newly developed metastatic lesions on magnetic resonance imaging (MRI) 3 months after GKRS. Factors such as tumor pathology subtype, concurrent systemic chemotherapy, epidermal growth factor receptor (EGFR) mutation status, use of EGFR tyrosine kinase inhibitors (TKIs), systemic disease status, presence of a metastatic lesion only in delayed MRI, and volume and number of metastases were analyzed. There were no statistically significant differences with respect to pathologic subtype, concurrent systemic chemotherapy, EGFR mutation, and early distant brain failure. Patients treated with EGFR-TKIs (p = 0.004), with a stable systemic disease status (p = 0.028) and 3 or fewer brain lesions (p = 0.000) experienced a significantly lower incidence of early distant brain failure. This study suggests that GKRS alone could be considered for patients treated with EGFR-TKIs who have a stable systemic disease status and 3 or fewer brain lesions. WBRT should be considered for other patients.

Bilateral globus pallidus interna deep-brain stimulation in a patient with myoclonus-dystonia: a case report.

OBJECTIVE: Myoclonus-dystonia is a movement disorder characterized by childhood onset of myoclonus and dystonia. We report a case of the epsilon-sarcoglycan mutation-negative myoclonus-dystonia patient who underwent bilateral globus pallidus interna deep-brain stimulation with subsequent improvement of both myoclonus and dystonia. CASE REPORT: A 37-year-old woman with myoclonic jerks and dystonia affecting predominantly the lower limbs was treated with chronic bilateral globus pallidus interna deep-brain stimulation. RESULTS: The movement subscore of the Burke-Fahns-Marsden Dystonia Rating Scale was 38 before surgery and improved to 7 after 3 years. The disability subscore of the Burke-Fahns-Marsden Dystonia Rating Scale improved from 7 to 2. The Unified Myoclonus Rating Scale also decreased significantly from 93 to 39. No hardware- or stimulation-related complications occurred during follow-up. CONCLUSION: This report suggests that patients with myoclonus-dystonia may significantly benefit from bilateral globus pallidus interna deep-brain stimulation. Larger studies of this patient population are needed to confirm the optimal target.

Initial clinical outcomes of minimally invasive lateral lumbar interbody fusion in degenerative lumbar disease: a preliminary report on the experience of a single institution with 30 cases.

OBJECTIVE: The object of this study was to evaluate the clinical and radiological outcomes of minimally invasive lateral lumbar interbody fusion. METHODS: This study included 30 patients who underwent minimally invasive lateral lumbar interbody fusion at our hospital between May 2011 and February 2012 for the following diagnoses: degenerative disc disease, adjacent-segment degeneration, degenerative spondylolisthesis and lumbar degenerative scoliosis. Pain assessment was reported from 0 to 10 using a subjective visual analog scale (VAS) upon admission and at every follow-up day. Lumbar X-rays were obtained in the standing position upon admission and the 1st and 5th postoperative day, and at every follow-up day after the operation. The heights of the intervertebral disc space and neural foramen were measured using an electronic caliper with the PACS software. The surgical outcome was assessed as excellent, good, fair or poor using the Odom scale at the last follow-up. RESULTS: The mean VAS for low back pain were 4.93±1.47 on admission and 2.01±1.35 at last follow-up, respectively, and for leg pain, the scores were 4.87±2.16 on admission and 1.58±1.52 at last follow-up. The mean height of intervertebral disc space increased by 34% (7.93±2.33 preoperatively, and 11.09±4.33 immediately after surgery, p<0.01). The mean height of neural foramen also increased by 6.4% without any statistical significance (19.17±2.84 preoperatively, and 20.49±4.50 immediately after the surgery). Minimally invasive lateral lumbar interbody fusion was successful in 27 patients (90%) at last follow-up. Surgical complications were reported as transient postoperative thigh sensory changes (5 patients, 16.7%), transient psoas muscle weakness (3 patients, 10%), cage migration (2 patients, 6.7%), lumbar plexus injury (1 patient, 3.3%), and pain aggravation (1 patient, 3.3%). CONCLUSION: The minimally invasive lateral lumbar interbody fusion is a safe and effective procedure for treating degenerative lumbar disease with good outcomes and moderate complications. Further follow-up is necessary to establish its safety and efficacy.