The Risk of Venous Thromboembolism and Ischemic Stroke Stratified by VTE Risk Following Multiple Myeloma: A Korean Population-Based Cohort Study.

Background: Multiple myeloma (MM) is associated with high morbidity and mortality, with elevated rates of arterial thrombosis and venous thromboembolism (VTE) and ischemic stroke (IS). We aimed to estimate the incidence of VTE and IS categorized by the VTE risk grade among individuals with MM in Korea. Additionally, we explored the potential of the IMPEDE VTE score as a tool for assessing IS risk in patients with MM. Methods: This retrospective cohort study comprised 37,168 individuals aged ≥ 18 years newly diagnosed with MM between January 2008 and December 2021 using the representative claims database of the Korean population. The risk of the incidence of VTE and IS within 6 months after MM diagnosis was stratified based on high-risk (IMPEDE VTE score ≥ 8) and low-risk (<8) categories. The hazard ratios (HRs) were estimated using Cox proportional hazard models. Results: The VTE incidence was 120.4 per 1000 person-years and IS incidence was 149.3 per 1000 person-years. Statistically significant differences were observed in the cumulative incidence rates of VTE between groups with high and low VTE scores (p < 0.001) and between individuals aged ≤ 65 years (p < 0.001) and those with a Charlson comorbidity index (CCI) ≥ 3 compared to lower scores (p < 0.001). Additionally, the cumulative incidence rate of IS differed significantly across all groups (p < 0.001). The HR for the high-risk group in VTE and IS occurrence was 1.59 (95% CI, 1.26-2.00) and 3.47 (95% CI, 2.99-4.02), respectively. Conclusions: It is important to screen and manage high-risk groups for the early development of VTE or IS in patients with newly diagnosed MM.

Retrospective review of the toxicities and change in dosing patterns for pegaspargase in patients with acute lymphoblastic leukemia/lymphoma and T-cell lymphoma.

INTRODUCTION: Pegaspargase (PEG) is a key component of standard regimens for acute lymphoblastic leukemia/lymphoma (ALL) and extranodal natural killer/T-cell lymphoma (NKTCL). Emerging evidence suggests an opportunity to decrease incidence of PEG-associated toxicities with dose capping, but evidence is limited. This study aims to evaluate whether a significant difference in PEG-associated toxicities related to dosing strategy exists and to identify patient-specific or regimen-specific factors for PEG-related toxicity. METHODS: A retrospective analysis of PEG-associated toxicities was completed in adult patients with ALL or NKTCL who received PEG within Cancer and Leukemia Group B (CALGB) 10403 or modified dexamethasone, methotrexate, ifosfamide, L-asparaginase, etoposide (mSMILE) regimens at the UW Medical Center/Fred Hutchinson Cancer Center. PEG-associated toxicities that occurred through 8 weeks after PEG doses were noted. RESULTS: Twenty-eight patients received dose-capped PEG, and 29 received noncapped PEG. Fewer all-grade and grade 3/4 toxicities were observed in the dose-capped cohort. Grade 3/4 toxicities observed were hepatotoxicity, hyperglycemia, hypersensitivity, and hypertriglyceridemia. In addition, fewer grade 3/4 pancreatitis and thrombosis events occurred in the dose-capped cohort. Hypertriglyceridemia and hepatotoxicity were associated with the highest cumulative incidence proportions among all toxicities. CONCLUSION: Dose capping of PEG was associated with a similar or later median onset for most toxicities, a less heterogeneic toxicity profile, and a lower recurrence of most toxicities upon PEG rechallenge compared to the non-dose-capped cohort. Standardizing PEG dose capping in the CALGB 10403 and mSMILE regimens may translate to improved tolerance compared to a historical standard of no dose capping PEG.

Economic burden of opioid misuse focused on direct medical costs.

Background: Since their development, synthetic opioids have been used to control pain. With increased opioid use, problematic opioid prescription has also increased, resulting in a growing economic burden. However, there is a paucity of research studies on the economic burden of prescription opioid misuse in Asia, especially South Korea. Objectives: To estimate the incremental economic burden of prescription opioid misuse for the South Korean population. Methods: The National Health Insurance Service-National Sample Cohort database, covering 2% of the South Korean population between 2010 and 2015, was analyzed. Outpatients aged 18 or older who took one or more prescription opioids were selected. Based on their opioid prescription patterns, patients were classified into opioid misuse and non-misuse groups. The direct medical costs per person per year (PPPY) and the incremental economic burden of the opioid misuse group were explored using an exponential conditional model with a suitable distribution and log link function. All analyses were performed using SAS® Enterprise Guide version 9.4, and p < 0.05 was considered statistically significant. Results: The number of patients who had ≥1 opioid prescription was 345,020 including 84,648 (24.53%) in the opioid misuse group and 260,372 (75.47%) in the non-misuse group. The adjusted mean direct medical costs PPPY were estimated to be USD 401 for the opioid misuse group, which is 1.49 times significantly higher than that for the non-misuse group (p < 0.0001). The incremental economic burden of the opioid misuse group in the South Korean population was estimated to be approximately USD 0.52 billion for the period 2010-2015. Conclusion: Prescription opioid misuse was significantly associated with the increased economic burden. Along with proper policies for using opioids, it is necessary to monitor opioid prescription patterns to prevent opioid misuse and reduce the related economic burden.

Daunorubicin and Cytarabine Liposome in Newly Diagnosed Therapy-Related Acute Myeloid Leukemia (AML) or AML With Myelodysplasia-Related Changes.

OBJECTIVE: To evaluate the efficacy and safety of daunorubicin and cytarabine liposome in older adults with newly diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC). DATA SOURCE: A literature search of PubMed and MEDLINE (January 2017 to January 2018) was performed using the terms CPX-351, Vyxeos, daunorubicin and cytarabine liposome, and acute myeloid leukemia. STUDY SELECTION/DATA EXTRACTION: Phase I, II, and III clinical trials evaluating the efficacy and safety of daunorubicin and cytarabine liposome were reviewed with a specific focus on its use in older patients with newly diagnosed AML. All peer-reviewed articles with clinically relevant information were evaluated for inclusion. DATA SYNTHESIS: The phase II trial demonstrated that daunorubicin and cytarabine liposome improved response rates (RR), but there was no difference in event-free survival and overall survival in the overall patient population. However, clinical benefit was most pronounced in secondary AML with an increased RR and survival. The phase III trial illustrated that daunorubicin and cytarabine liposome improved survival and RR with tolerable toxicity compared with standard 7 plus 3 (daunorubicin and cytarabine) in patients 60 to 75 years of age with t-AML or AML-MRC. More patients proceeded to a stem cell transplant, and 30-day and 60-day mortality was lower with daunorubicin and cytarabine liposome. Grade 3 to 5 toxicities were similar between the 2 groups, except daunorubicin and cytarabine liposome had prolonged cytopenia and a higher risk of hemorrhage. CONCLUSIONS: Daunorubicin and cytarabine liposome improves RR and survival, with tolerable toxicity in older patients with t-AML or AML-MRC.

A comparison of toxicities in acute myeloid leukemia patients with and without renal impairment treated with decitabine.

Purpose There are limited data regarding the clinical use of decitabine for the treatment of acute myeloid leukemia in patients with a serum creatinine of 2 mg/dL or greater. Methods We retrospectively evaluated 111 patients with acute myeloid leukemia who had been treated with decitabine and compared the development of toxicities during cycle 1 in those with normal renal function (creatinine clearance greater than or equal to 60 mL/min) to those with renal dysfunction (creatinine clearance less than 60 mL/min). Results Notable differences in the incidence of grade ≥3 cardiotoxicity (33% of renal dysfunction patients vs. 16% of normal renal function patients, p = 0.042) and respiratory toxicity (40% of renal dysfunction patients vs. 14% of normal renal function patients, p = 0.0037) were observed. The majority of heart failure, myocardial infarction, and atrial fibrillation cases occurred in the renal dysfunction group. The odds of developing grade ≥3 cardiotoxicity did not differ significantly between patients with and without baseline cardiac comorbidities (OR 1.43, p = 0.43). Conclusions This study noted a higher incidence of grade ≥3 cardiac and respiratory toxicities in decitabine-treated acute myeloid leukemia patients with renal dysfunction compared to normal renal function. This may prompt closer monitoring, regardless of baseline cardiac comorbidities. Further evaluation of decitabine in patients with renal dysfunction is needed.

Midostaurin in Combination With Standard Chemotherapy for Treatment of Newly Diagnosed FMS-Like Tyrosine Kinase 3 (FLT3) Mutation-Positive Acute Myeloid Leukemia.

OBJECTIVE: To evaluate the efficacy and safety of midostaurin in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation in newly diagnosed FLT3-mutated acute myeloid leukemia (AML). DATA SOURCE: A literature search of PubMed and MEDLINE (September 2017) was performed using the terms midostaurin, PKC412, FLT3 gene, and acute myeloid leukemia. STUDY SELECTION/DATA EXTRACTION: Clinical trials evaluating the efficacy and safety of midostaurin in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation were reviewed for the treatment of newly diagnosed FLT3-mutated AML. All peer-reviewed articles with clinically relevant information were evaluated for inclusion. DATA SYNTHESIS: Midostaurin is a multikinase inhibitor also targeting FLT3 indicated for the treatment of newly diagnosed FLT3-mutated AML. A phase III trial illustrated that midostaurin in combination with standard chemotherapy improved event-free survival, disease-free survival, and overall survival in patients with newly diagnosed FLT3-mutation-positive AML compared with standard chemotherapy alone. However, midostaurin did not show a difference in the rate of patients who proceeded to receive an allogeneic stem cell transplant compared with placebo. There was no significant difference in toxicity between the midostaurin and placebo groups, except that more patients experienced grade 3 to 5 anemia and rash with midostaurin. CONCLUSIONS: Midostaurin in combination with standard induction and consolidation is safe and efficacious in newly diagnosed FLT3-mutated AML.

Inotuzumab Ozogamicin in Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia.

Despite initial complete remission rates of up to 90%, long-term, disease-free survival remains poor in patients with newly diagnosed acute lymphoblastic leukemia (ALL). Response to salvage chemotherapy is suboptimal; therefore, novel therapeutic agents are being investigated in order to improve outcomes in these patients. Inotuzumab ozogamicin is a CD22-directed antibody-drug conjugate recently approved by the US Food and Drug Administration for the treatment of adults with relapsed or refractory B-cell precursor ALL. Inotuzumab ozogamicin improves response rate, minimal residual disease negativity, and survival compared to standard chemotherapy in this population. In addition, it offers more opportunities to proceed to an allogeneic stem cell transplant in patients who otherwise may not be candidates.

Correlation of electrode position and clinical outcomes in globus pallidus stimulation for dystonia.

BACKGROUND: The correlation between the electrode location and the clinical outcome for internal globus pallidus (GPi) deep brain stimulation (DBS) has not been fully elucidated. OBJECTIVE: The aim of this study was to determine the discrepancies between the theoretical target planned by magnetic resonance imaging (MRI) and the actual electrode location in postoperative MRI, as well as to find the correlation between the final electrode locations and the clinical outcome after GPi DBS. METHODS: Thirty-six patients who underwent GPi DBS for dystonia were included in this retrospective study. The X coordinate was defined as the lateral distance from the midline, the Y coordinate as the anterior distance from the midcommissural point, and the Z coordinate as the inferior distance from the intercommissural line. RESULTS: All coordinates showed a significant difference between theoretical and actual values for all electrode locations (p < 0.05). In particular, greater differences were exhibited for Y than for the X and Z coordinates. There was no significant difference in the accuracy of the localization of the left-side versus the right-side electrode for any coordinates. The patients whose electrodes were located within or near the posteroventral GPi showed better clinical outcomes. CONCLUSIONS: The actual electrode location was slightly more posterior to the theoretically planned target. Electrodes concentrated near the posteroventral GPi tended to yield favorable outcomes.

Bilateral Deep Brain Stimulation of the Subthalamic Nucleus under Sedation with Propofol and Fentanyl.

Awakening during deep brain stimulation (DBS) surgery may be stressful to patients. The aim of the current study was to evaluate the effect on MER signals and their applicability to subthalmic nucleus (STN) DBS surgery for patients with Parkinson's disease (PD) under sedation with propofol and fentanyl. Sixteen consecutive patients with PD underwent STN-DBS surgery with propofol and fentanyl. Their MER signals were achieved during the surgery. To identify the microelectrodes positions, the preoperative MRI and postoperative CT were used. Clinical profiles were also collected at the baseline and at 6 months after surgery. All the signals were slightly attenuated and contained only bursting patterns, compared with our previous report. All electrodes were mostly located in the middle one third part of the STN on both sides of the brain in the fused images. Six months later, the patients were improved significantly in the medication-off state and they met with less dyskinesia and less off-duration. Our study revealed that the sedation with propofol and fentanyl was applicable to STN-DBS surgery. There were no significant problems in precise positioning of bilateral electrodes. The surgery also improved significantly clinical outcomes in 6-month follow-up.

Long-Term Clinical Outcome of Internal Globus Pallidus Deep Brain Stimulation for Dystonia.

BACKGROUND: GPi (Internal globus pallidus) DBS (deep brain stimulation) is recognized as a safe, reliable, reversible and adjustable treatment in patients with medically refractory dystonia. OBJECTIVES: This report describes the long-term clinical outcome of 36 patients implanted with GPi DBS at the Neurosurgery Department of Seoul National University Hospital. METHODS: Nine patients with a known genetic cause, 12 patients with acquired dystonia, and 15 patients with isolated dystonia without a known genetic cause were included. When categorized by phenomenology, 29 patients had generalized, 5 patients had segmental, and 2 patients had multifocal dystonia. Patients were assessed preoperatively and at defined follow-up examinations postoperatively, using the Burke-Fahn-Marsden dystonia rating scale (BFMDRS) for movement and functional disability assessment. The mean follow-up duration was 47 months (range, 12-84). RESULTS: The mean movement scores significantly decreased from 44.88 points preoperatively to 26.45 points at 60-month follow up (N = 19, P = 0.006). The mean disability score was also decreased over time, from 11.54 points preoperatively to 8.26 points at 60-month follow up, despite no statistical significance (N = 19, P = 0.073). When analyzed the movement and disability improvement rates at 12-month follow up point, no significant difference was noted according to etiology, disease duration, age at surgery, age of onset, and phenomenology. However, the patients with DYT-1 dystonia and isolated dystonia without a known genetic cause showed marked improvement. CONCLUSIONS: GPi DBS is a safe and efficient therapeutic method for treatment of dystonia patients to improve both movement and disability. However, this study has some limitations caused by the retrospective design with small sample size in a single-center.

Patients' reluctance to undergo deep brain stimulation for Parkinson's disease.

BACKGROUND: Many patients with advanced Parkinson's disease (PD) are reluctant to undergo the subthalamic nucleus deep brain stimulation (STN-DBS) when surgery is warranted. Reasons for this reluctance have not been examined. We undertook to establish the rate and causes of this reluctance for STN-DBS in patients with advanced PD. METHODS: A reluctant group was defined as patients who were hesitant to undergo DBS. Clinical information included age, onset age, disease duration, the Unified Parkinson Disease Rating Scale, Hoehn and Yahr stage and levodopa equivalent dose when they were evaluated with a view to consider surgery. RESULTS: We enrolled 186 patients who underwent STN-DBS. 84 patients (45%) belonged to the reluctant group. Between the reluctant and the non-reluctant, there were no differences in preoperative characteristics. Main reasons for hesitation were fear of complications (74%) and economic burden (50%). The main reasons that they finally underwent the DBS were confidence in the doctor's decision (80%) and encouragement from their family (36%). CONCLUSIONS: Building trust between patients and physicians is an important factor in guiding patients to undergo this treatment. To reduce the reluctance to undergo DBS at the appropriate time, we need to find effective ways of reducing their psychological and economic burden.

Influence of propofol and fentanyl on deep brain stimulation of the subthalamic nucleus.

We investigated the effect of propofol and fentanyl on microelectrode recording (MER) and its clinical applicability during subthalamic nucleus (STN) deep brain stimulation (DBS) surgery. We analyzed 8 patients with Parkinson's disease, underwent bilateral STN DBS with MER. Their left sides were done under awake and then their right sides were done with a continuous infusion of propofol and fentanyl under local anesthesia. The electrode position was evaluated by preoperative MRI and postoperative CT. The clinical outcomes were assessed at six months after surgery. We isolated single unit activities from the left and the right side MERs. There was no significant difference in the mean firing rate between the left side MERs (38.7 ± 16.8 spikes/sec, n=78) and the right side MERs (35.5 ± 17.2 spikes/sec, n=66). The bursting pattern of spikes was more frequently observed in the right STN than in the left STN. All the electrode positions were within the STNs on both sides and the off-time Unified Parkinson's Disease Rating Scale part III scores at six months after surgery decreased by 67% of the preoperative level. In this study, a continuous infusion of propofol and fentanyl did not significantly interfere with the MER signals from the STN. The results of this study suggest that propofol and fentanyl can be used for STN DBS in patients with advanced Parkinson's disease improving the overall experience of the patients.

The clinical impact of precise electrode positioning in STN DBS on three-year outcomes.

Few studies have analyzed the clinical impact of subthalamic nucleus (STN) deep brain stimulation (DBS) as a function of the positioning of the inserted electrode. We investigated retrospectively the three-year outcomes in Parkinson's disease (PD) patients following bilateral STN DBS in terms of the electrode positions. Forty-one advanced PD patients were followed up for over three years following bilateral STN DBS. Patients were evaluated with the Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr staging, Schwab and England Activities of Daily Living (ADL), and the Short Form-36 Health Survey (SF-36) before surgery and one, two, and three years after surgery. The patients were divided into two groups according to the electrode position based on the fused preoperative MRI and postoperative CT images: group I included patients who had both electrodes in the STN (n=30) while group II included patients who had one of the electrodes in the STN (n=11). The UPDRS, the Hoehn & Yahr staging, the Schwab and England ADL, and the SF-36 scores showed significant improvements with decreased l-dopa equivalent daily doses (LEDDs) in both groups as well as in the group as a whole for up to three years following bilateral STN DBS. However, the off-medication UPDRS total and motor (part III) scores significantly deteriorated with increased LEDDs for patients in group II three years after STN DBS compared to that of the group I patients. We conclude that more accurate electrode positioning in the STN leads to better long-term outcomes in advanced PD patients following DBS.

Crizotinib: a new treatment option for ALK-positive non-small cell lung cancer.

OBJECTIVE: To review the characteristics and clinical trial data of crizotinib in ALK-positive non-small cell lung cancer (NSCLC). DATA SOURCE: A literature search using PubMed/MEDLINE (up to December 2012) was performed using the terms crizotinib, ALK-positive, non-small cell lung cancer, and PF-02341066. STUDY SELECTION/DATA EXTRACTION: Phase 1, 2, and 3 trials evaluating the safety and efficacy of crizotinib in a cohort of patients with ALK rearrangements and advanced NSCLC were evaluated. All peer-reviewed articles with clinically relevant information were reviewed. DATA SYNTHESIS: ALK rearrangement results in an aberrant EML4-ALK fusion oncogene that constitutively activates ALK tyrosine kinase, resulting in inhibition of apoptosis and promotion of tumor cell proliferation. Approximately 3-5% of NSCLC exhibit this rearrangement. Crizotinib is an oral selective inhibitor of ALK and mesenchymal epithelial growth factor tyrosine kinases. Early phase trials with crizotinib showed improved response rates of 50-57% and extended duration of response of 6-10 months. Results of these studies led to accelerated Food and Drug Administration (FDA) approval of crizotinib. Further clinical trial results confirmed improvement in response rates, duration of response, as well as progression-free survival in ALK-positive patients with NSCLC receiving crizotinib. The drug undergoes hepatic metabolism by CYP3A4 and demonstrates autoinhibition of CY3A4, thus predisposing it to drug interactions. The most frequent toxicities with crizotinib include mild visual disturbances, nausea, vomiting, diarrhea, constipation, edema, and generally reversible, sometimes severe, elevations in aspartate aminotransferase and alanine aminotransferase. CONCLUSIONS: Crizotinib is a novel targeted anticancer agent that appears to be a favorable treatment option for patients with locally advanced or metastatic NSCLC that is ALK-positive as detected by an FDA-approved test.

Everolimus: a new treatment option for advanced pancreatic neuroendocrine tumors.

OBJECTIVE: To present the current clinical evidence on everolimus for use in pancreatic neuroendocrine tumors (pNET). DATA SOURCES: A literature search was performed using PubMed and MEDLINE (1946-March 2012). Search terms were everolimus, RAD001, mTOR inhibitor, and pancreatic neuroendocrine tumors. Abstracts from the American Society of Clinical Oncology 2000-2012 meetings and Food and Drug Administration (FDA) reviews were searched to obtain otherwise unpublished data. The national clinical trials registry was searched for current and future studies of everolimus in pNET. STUDY SELECTION AND DATA EXTRACTION: Clinical studies available in the English language describing the pharmacology, pharmacokinetics, clinical activity, and safety of everolimus in pNET were included. All peer-reviewed, clinically relevant publications were reviewed for inclusion. DATA SYNTHESIS: Everolimus is an oral mammalian target of rapamycin (mTOR) inhibitor approved by the FDA in May 2011 for the treatment of progressive, advanced pNET. Everolimus exerts its effect by inhibiting multiple downstream pathways of mTOR, which decreases cell proliferation, survival, and angiogenesis. Its pNET indication was based on the results of RADIANT-3, a Phase 3 trial demonstrating increased median progression-free survival (11 months) with everolimus 10 mg orally once daily compared to placebo (4.6 months). Everolimus was well tolerated in clinical trials. The most commonly reported adverse events included stomatitis, rash, diarrhea, fatigue, infections, nausea, and decreased appetite. Grade 3/4 events including anemia, thrombocytopenia, pneumonitis, and hyperglycemia occurred in approximately 5% of patients. CONCLUSIONS: Based on review of the available literature, everolimus is a safe and effective treatment option for patients with low- to intermediate-grade, unresectable or metastatic pNET that have progressed on prior therapies. Until results of head-to-head, randomized controlled trials are conducted to compare everolimus to other treatment options, it cannot be said whether everolimus is more efficacious or tolerable than other treatment options.

Romidepsin: a histone deacetylase inhibitor for refractory cutaneous T-cell lymphoma.

OBJECTIVE: To evaluate the efficacy and safety of romidepsin in refractory cutaneous T-cell lymphoma (CTCL). DATA SOURCES: An English-language literature search of PubMed and MEDLINE (Nov 2011-April 2012) was performed using the terms romidepsin, CTCL, and depsipeptide (FK228). The National Comprehensive Cancer Network guidelines, American Society of Clinical Oncology abstracts, American Society of Hematology abstracts, clinical trial registry, and prescribing information from the manufacturer were reviewed for additional information. STUDY SELECTION AND DATA EXTRACTION: Phase 1 and 2 trials evaluating the efficacy and safety of romidepsin were reviewed with a specific focus on its use in cutaneous T-cell lymphoma. All peer-reviewed articles with clinically relevant information were evaluated for inclusion. DATA SYNTHESIS: In advanced stage CTCL, single or combination chemotherapy regimen responses are variable and lack durability. Romidepsin is a histone deacetylase inhibitor approved for refractory cutaneous T-cell lymphoma. Romidepsin has shown an improvement in duration of response and pruritus over traditional therapy. In 2 independent Phase 2 trials, romidepsin showed an overall response rate of 34% and durable response of 13-15 months in patients with refractory CTCL. The most frequent toxicities of romidepsin include nausea, vomiting, fatigue, or myelosuppression. Clinically insignificant QT interval changes have been observed but did not correlate with a decrease in left ventricular ejection fraction, or elevated laboratory markers of myocardial damage. CONCLUSIONS: Romidepsin is an effective, durable, and well-tolerated single-agent therapy in patients with refractory CTCL and should be considered for formulary addition in this population.

Reprogramming guided by the fused images of MRI and CT in subthalamic nucleus stimulation in Parkinson disease.

OBJECTIVE: To evaluate the usefulness of the visual information about the location of the contacts in deep brain stimulation (DBS) programming, we compared the outcomes of subthalamic nucleus (STN) stimulation before and after reprogramming guided by the fused images of MRI and CT. METHODS: Of the 65 patients with Parkinson's disease, who underwent bilateral STN-DBS surgery between March 2005 and September 2006 and had been managed for at least 6 months with conventional programming which was only based on the physiological responses from the patients, 54 patients were reprogrammed based on the 3D anatomical location of the contacts revealed by the fused images of pre-operative MRI and post-operative CT scans taken at 6 months after surgery. A total 51 patients completed the evaluation after reprogramming. RESULTS: Reprogramming significantly improved the UPDRS part III scores during the on- and off-medication condition. The daily levodopa-equivalent dose was significantly reduced. Improvement in the UPDRS part III scores after reprogramming was greater in the patients with electrodes in the STN than the patients with electrodes off the STN. CONCLUSIONS: CT-MR fusion images helped to reprogram stimulation parameters with ease and confidence in a time-saving manner and resulted in further clinical improvement. This method could complement the conventional method of adjusting stimulation parameters after bilateral STN-DBS.

The effects of bilateral subthalamic nucleus deep brain stimulation (STN DBS) on cognition in Parkinson disease.

The effects of subthalamic nucleus (STN) stimulation on cognition and mood have not been well established. The authors estimated cognitive and mood effects of bilateral subthalamic nucleus deep brain stimulation (STN DBS) in patients with Parkinson's disease (PD) at 6 months and 1 year postoperatively. Forty-six patients were recruited from the Movement Disorder Center at Seoul National University Hospital. Neuropsychologic tests were performed three times, before, 6 months after, and 1 year after surgery. Mean patient age was 58 and mean education duration 8 years. Eighteen of the 46 patients were men. The instruments used for assessing cognitive functions were; the Mini-Mental Status Examination (MMSE), the Trail Making Test (TMT), the Korean Boston Naming Test (K-BNT), the Rey-Kim Memory Battery, the Grooved pegboard test, the Stroop test, a fluency test, the Wisconsin Card Sorting test (WCST), and the Beck depression inventory (BDI). Of these tests, the verbal memory test, the Stroop test, and the fluency test showed statistically significant changes. The verbal memory test using the Rey-Kim memory battery showed a decline in delayed recall and recognition at 6 months and 1 year postoperatively, whereas nonverbal memory showed no meaningful change. In terms of frontal lobe function tests, Stroop test and fluency test findings were found to be aggravated at 6 months and this continued at 1 year postoperatively. Previous studies have consistently reported a reduction in verbal fluency and improvements in self-reported symptoms of depression after STN DBS. However, in the present study, Beck depression inventory (B.D.I.) was not significantly changed. Other tests, namely, MMSE, TMT, K-BNT, Grooved pegboard test, and the WCST also failed to show significant changes. Of the baseline characteristics, age at onset, number of years in full-time education, and L-dopa equivalent dosage were found to be correlated with a postoperative decline in neuropsychological test results. The correlation of motor improvement and cognitive deterioration was not significant, which suggests that the stimulation effect is rather confined to the motor-related part in the STN. In conclusion, bilateral STN DBS in Parkinson's disease did not lead to a significant global deterioration in cognitive function. However, our findings suggest that it has minor detrimental long-term impacts on memory and frontal lobe function.

Chronic subthalamic deep brain stimulation improves pain in Parkinson disease.

BACKGROUND: Pain is a well recognized feature of Parkinson disease (PD). Like motor fluctuations, pain in PD may fluctuate as 'non-motor fluctuations'. Subthalamic deep brain stimulation (STN DBS) is an established treatment for motor fluctuations in PD. However, the effect of STN DBS on the pain in PD is only partially investigated. METHODS: PD patients who were considered for STN DBS were asked if they had pain. The severity of pain was scored in each body part. In patients with motor fluctuation, the pain in the 'on' and 'off ' state were recorded separately. Patients were evaluated preoperatively and 3 months after surgery. Some patients were followed for 6 months. RESULTS: Twenty-three of 29 patients had pain preoperatively. Of 24 with motor fluctuation, 21 had pain, and 18 had fluctuating pain. Pain improved in 20 out of 23 with preoperative pain at 3 months postoperatively. Of 18 with fluctuating pain, 12 reported a decrease in, and 5 complete disappearance of the 'off ' pain. Of 4 with nonfluctuating preoperative pain, 2 reported improvement. Pain was severe and functionally disabling in some. The STN DBS improved pain to a tolerable degree. In 7 of 29, new pain developed during the 3 month follow-up. Sixteen patients were followed for 6 months. All 11 patients who had improvement at 3 months continued to get benefit from STN DBS. Two additional patients who had no improvement at 3 months reported improvement at 6 months. CONCLUSIONS: Pain is frequent in PD and STN DBS improves pain, especially the 'off ' pain in PD.