Long-Term Outcomes of Bilateral Subthalamic Nucleus Deep Brain Stimulation for Patients With Parkinson's Disease: 10 Years and Beyond.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) represents an effective treatment for severe Parkinson's disease (PD), but little is known about the long-term benefit. OBJECTIVE: To investigate the survival rate and long-term outcome of DBS. METHODS: We investigated all 81 patients including 37 males and 44 females who underwent bilateral STN DBS from March 2005 to March 2008 at a single institution. The current survival status of the patients was investigated. Preoperative and postoperative follow-up assessments were analyzed. RESULTS: The mean age at the time of surgery was 62 (range 27-82) years, and the median clinical follow-up duration was 145 months. Thirty-five patients (43%) died during the follow-up period. The mean duration from DBS surgery to death was 110.46 ± 40.8 (range 0-155) months. The cumulative survival rate is as follows: 98.8 ± 1.2% (1 year), 95.1 ± 2.4% (5 years), and 79.0 ± 4.5% (10 years). Of the 81 patients, 33 (40%) were ambulatory up to more than 11 years. The Unified Parkinson's Disease Rating Scale (UPDRS) score was significantly improved until 5 years after surgery although it showed a tendency to increase again after 10 years. The patient group with both electrodes located within the STN showed a higher rate of survival and maintained ambulation. CONCLUSION: STN DBS is a safe and effective treatment for patients with advanced PD. This study based on the long-term follow-up of large patient populations can be used to elucidate the long-term fate of patients who underwent bilateral STN DBS for PD.

Patient-reported responses to medical treatment in primary dystonia.

In the absence of pathogenesis-targeted therapy in most types of primary dystonia, the current management strategy is largely symptomatic. Our aim was to comparatively evaluate the patients' perception of symptomatic benefits with the medical treatment of primary dystonia. We reviewed the medical records of 206 patients who received medical treatment upon diagnosis of primary dystonia. The patients were prescribed five different dystonia medications: clonazepam, trihexyphenidyl, nortriptyline, baclofen, and levodopa. Patients tried one type of medicine during each following week and whether each medication was beneficial was recorded in a binary fashion. Subgroups analysis was performed according to the body distribution, duration, ages at onset and treatment of dystonia. A total of 172 patients were included in the analysis. The majority (84%) had focal dystonia, most frequently cervical dystonia and blepharospasm. Clonazepam received the most favorable response (40%), followed by baclofen (20%) and trihexyphenidyl (20%). Patients with focal limb dystonia gave higher rate of positive responses to levodopa (24%) compared to other focal dystonia subgroups. Clonazepam, followed by baclofen and trihexyphenidyl is a useful pharmacologic option for primary dystonia. Levodopa can be considered for isolated limb dystonia.

Ghost radiance suppression using backward ray path analysis for a Risley prism scanner of an active laser ranging system.

The LAser raDAR (LADAR) system designed in this study shows a ghost pattern around the object image when operated. The system contains 4 wedge prisms, each with different rotational directions and speeds. Therefore, an efficient and thorough analysis method was established. Ray path analysis was performed, and categorized, for every instantaneous case sampled using a backward ray tracing method. The rays' flux and directions were accumulated according to their path histories. This backward ray tracing was performed repeatedly with different neutral density (ND) filter orientations, until no measurable ghost radiance remained in the field of regard (FOR): a tilt angle of 5°. The ND filter was replaced with a mechanical vignette. Subsequently, the ghost flux was 21% of the total accumulated point cloud, coinciding with the actual measurement of 19%. The final image has significantly improved resolution and shows no ghost reflections where they were previously.

Immunotherapy Targeting Neurodegenerative Proteinopathies: α-Synucleinopathies and Tauopathies.

α-Synuclein and tau deposition in the central nervous system is responsible for various parkinsonian syndromes, including Parkinson's disease, multiple system atrophy, dementia with Lewy bodies, progressive supranuclear palsy and corticobasal degeneration. Emerging evidence has suggested that pathologic α-synuclein and tau are transmitted from cell to cell and further accelerate the aggregation of pathologic proteins in neighboring cells. Furthermore, extracellular pathologic proteins have also been reported to provoke inflammatory responses that lead to neurodegeneration. Therefore, immunotherapies targeting extracellular α-synuclein and tau have been proposed as potential disease-modifying strategies. In this review, we summarize completed phase I trials and ongoing phase II trials of immunotherapies against α-synuclein and tau and further discuss concerns and hurdles to overcome in the future.

Submandibular gland is a suitable site for alpha synuclein pathology in Parkinson disease.

OBJECTIVE: To validate the role of α-synuclein (AS) pathology in submandibular gland (SMG) as a biomarker for Parkinson disease (PD). METHODS: We performed ultrasonography (USG) guided core needle biopsy of SMG in PD patients and procured SMG biopsy tissues or surgical excision specimens from non-PD patients as controls. Then, we compared AS deposition in the SMG tissues between the PD patients and the controls. We recruited 16 PD patients in this study. In each individual, two core needle biopsy tissues were obtained from the left submandibular gland under USG guidance. Fourteen sex and age-matched controls who did not have PD and dementia but received a core needle biopsy or surgical resection of the SMG due to SMG diseases were procured from the pathology archive. Biopsy tissues and surgical specimens were immuno-stained with serine 129 phosphorylated AS (pAS) antibody for microscopic examination. pAS deposition in neural structures such as ganglion cells and neurites was considered as positive. RESULTS: No serious complication occurred during and after the SMG biopsy. We found glandular parenchyma and neural structures in all biopsied SMG tissues from the patients and the controls. Nine out of 16 PD patients (56.2%) were positive for pAS staining, while none of the controls were positive (0%). CONCLUSIONS: SMG core needle biopsy can reliably and safely obtain sufficient glandular parenchyma and neural structures to evaluate the α-synuclein pathology. AS pathology in SMG has high specificity and good sensitivity as a biomarker for PD.

Intracranial plaque enhancement from high resolution vessel wall magnetic resonance imaging predicts stroke recurrence.

BACKGROUND: Intracranial atherosclerosis is associated with frequent stroke recurrence. High resolution vessel wall magnetic resonance imaging (HRMRI) can provide atheroma information related to its vulnerability. AIMS: We performed HRMRI in stroke patients with intracranial atherosclerosis to determine whether plaque characteristics from vessel wall imaging can predict future stroke recurrence. METHODS: Between July 2011 and June 2013, acute stroke patients with symptomatic intracranial atherosclerosis were prospectively enrolled and 3-tesla HRMRI was performed on the relevant artery. The plaque enhancement was visually determined from T1 post-gadolinium enhancement image. Stroke recurrence was monitored after index event and multivariate Cox proportional hazards model was constructed to identify factors related to future stroke recurrence. RESULTS: A total of 138 patients were included with a median follow-up of 18 months. There were 39 stroke recurrences. Plaque enhancement was detected in 108 patients (78.3%), and 37 of them experienced stroke recurrence. Among 30 stroke patients without plaque enhancement, two patients experienced stroke recurrence. Kaplan-Meier curves demonstrated a significant difference in event free survival between the patients with plaque enhancement and those patients without plaque enhancement (event rates at year 1: 30.3% vs. 6.8%, log-rank test, p = 0.004). Multivariate Cox-regression analysis showed that the plaque enhancement from HRMRI was independently associated with stroke recurrence (hazard ratio: 7.42, 95% confidence interval: 1.74-31.75, p = 0.007). CONCLUSION: Intracranial plaque enhancement from HRMRI is associated with stroke recurrence among the patients with symptomatic intracranial atherosclerosis.

Should genetic testing for SCAs be included in the diagnostic workup for MSA?

OBJECTIVE: To examine the prevalence of mutations in spinocerebellar ataxia (SCA) genes in patients who were clinically diagnosed with multiple system atrophy (MSA). METHODS: Genetic tests for SCA were performed in 302 of 528 patients who met the diagnostic criteria for MSA based on clinical features. Generally, when a patient had cerebellar symptoms or cerebellar atrophy on neuroimaging, genetic tests for SCA types 1, 2, 3, 6, 7, and 17, and dentatorubropallidoluysian atrophy were done, and when a patient had parkinsonism without cerebellar symptoms, genetic tests for SCA types 2, 3, and 17 were done. RESULTS: Mutations in SCA genes were found in 22 of the 302 patients (7.3%) with SCA17 comprising more than half of the mutation-positive cases. The age at disease onset in these 22 patients was not different compared with the 280 patients without mutations (55.9 ± 9.3 vs 59.2 ± 8.9, p = 0.102). All patients had urinary symptoms, and 10 patients also had orthostatic dizziness or orthostatic hypotension. A family history was reported in only 3 patients. Of note, dream enactment behavior suggesting REM sleep behavior disorder was reported in 9 of the 11 patients (81.8%) asked. CONCLUSIONS: The high proportion of patients with SCA mutations in this study indicates that genetic testing for SCA should be included for patients with MSA, especially for patients with cerebellar dysfunctions.

Risk factors associated with group B streptococcus resistant to clindamycin and erythromycin in pregnant korean women.

BACKGROUND: The prevalence of group B streptococcus (GBS) among pregnant women and neonates in the Republic of Korea has increased. In addition, rates of resistance to antibiotics recommended for pregnant women allergic to penicillin, such as clindamycin and erythromycin, have increased. The aim of this study was to evaluate subject characteristics associated with GBS resistance to clindamycin and erythromycin. MATERIALS AND METHODS: A total of 418 clinical isolates from pregnant women in Korea were screened for antibiotic resistance from January 2006 to December 2011. Sociodemographic information, medical and obstetric history, and details of events during the previous 2 weeks were recorded using a standardized questionnaire. RESULTS: The resistance rates were 39.5% for clindamycin and 23.0% for erythromycin. In multiple logistic regression analysis, the subject characteristic significantly associated with resistance to both antibiotics was a history of symptomatic sore throat in the 2 weeks before obtaining the specimen (erythromycin: odds ratio [OR]: 2.13, 95% confidence interval [CI]: 1.10 to 4.13; clindamycin: OR: 2.31, 95% CI: 1.21, 4.42). Premature rupture of membranes (PROM) had an association of borderline significance. CONCLUSIONS: In the urgent treatment of GBS-colonized pregnant women, the subject's history of previous sore throat and PROM should be considered when choosing appropriate antibiotics.

Risk factors for group B streptococcus colonization among pregnant women in Korea.

OBJECTIVES: To identify obstetric and maternal factors related to Group B Streptococcus (GBS) colonization in pregnant women in Korea. METHODS: The study was conducted between the years 2006-2008 in four hospitals, Cheil and Eulji hospital in Seoul, and Motae and Eulji hospital in Daejeon. We recruited 2,644 pregnant women between 35 to 37 weeks of gestation who had visited for antenatal care. Participants completed a questionnaire, and urine, vaginal and rectal specimens were obtained and cultured using selective broth media. After delivery, medical records were reviewed. RESULTS: GBS colonization was significantly associated with hospital, age group, education, frequency of pregnancy, and premature rupture of membranes (PROM, more than 18 hours). After adjustment for other variables, Cheil hospital (odds ratio [OR], 2.05; 95% confidence interval [CI], 1.20-3.52), and the first pregnancy (OR, 2.32; 95% CI, 1.12-4.81) remained significant. History of vaginitis showed marginal significance (OR, 1.50; 95% CI, 0.98-2.29). CONCLUSION: To prevent GBS infection of neonates, clinicians should be alert to the potentially higher risk of GBS colonization in pregnant women in their first pregnancy, and women with premature rupture of membranes (PROM) (18 hours+) or who have a history of vaginitis.

Changing molecular epidemiology of group B streptococcus in Korea.

The prevalence of group B streptococcus (GBS) among pregnant women and disease burdens in neonates and adults are increasing in Korea. Colonizing isolates, collected by screening pregnant women (n=196), and clinical isolates collected from clinical patients throughout Korea (n=234), were serotyped and screened for antibiotic resistance. Serotype III (29.8%) and V (27.7%) predominated, followed by Ia (17.0%). Antibiotic resistance was higher among clinical than colonizing isolates for erythromycin (35.1% and 26.9%; P=0.10) and for clindamycin (49.4% and 42.1%; P=0.17). erm(B) occurred in 91.9% of erythromycin resistant isolates, and 84.0% of isolates resistant to clindamycin. Only five isolates (4.2%) resistant to erythromycin were susceptible to clindamycin; by contrast, and unique to Korea, 34% of isolates resistant to clindamycin were erythromycin susceptible. Among these 60 erythromycin-susceptible & clindamycin-resistant isolates, 88% was serotype III, and lnu(B) was found in 89% of strains. Four fifths of the serotype V isolates were resistant to both erythromycin and clindamycin. Further characterization of the genetic assembly of these resistance conferring genes, erm(B) and lnu(B), will be useful to establish the clonal lineages of multiple resistance genes carrying strains.

A case of ovarian pregnancy after ipsilateral partial salpingectomy.

We present a case report of an ovarian pregnancy after ipsilateral partial salpingectomy. A 19-year-old woman was admitted with vaginal bleeding and right lower abdominal pain. She had a history of right partial salpingectomy caused by a tubal pregnancy. The pregnancy test result was positive, and a right adnexal mass was identified by ultrasonography. Laparoscopy revealed a right ovarian pregnancy. Thus the possibility of ipsilateral ectopic pregnancy should be considered even when the patient has a history of salpingectomy total or partial.

Characterization of mouthguard materials: thermal properties of commercialized products.

OBJECTIVES: Several mechanisms have been purported to describe how mouthguards protect the orofacial complex against injury. As the properties needed for these mechanisms to be effective are temperature and frequency dependent, the specific aim of this study was to provide a comprehensive thermal characterization of commercial mouthguard materials. METHODS: Five commercially representative thermoplastic mouthguard materials (Essix Resin, Erkoflex, Proform-regular, Proform-laminate, and Polyshok) were tested. Differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA) techniques were implemented to measure thermal transitions and mechanical properties. Measurements were conducted three times per sample. One-way ANOVA and one-sample t-tests were used to test for differences between commercial products on selected mean thermal property values. RESULTS: The DSC measurements indicated no differences between commercial materials for mean glass transition (p=0.053), onset melt (p=0.973), or peak melt (p=0.436) temperatures. Likewise, DMA measurements revealed no differences between commercial materials for the mean glass transition (p=0.093), storage modulus (p=0.257), or loss modulus (p=0.172) properties, respectively. The one-sample t-tests revealed that glass transition temperatures were different from intra-oral temperature (p<0.005) for all materials. SIGNIFICANCE: Commercialized mouthguard materials are sensitive to repetitive heating and cooling cycles, prolonged thermal treatment, and have glass transitions well below their end-use intra-oral temperature. As such, these materials are functioning as elastomers and not optimal mechanical damping materials. Dental clinicians, healthcare practitioners, or end-users should be aware that these materials are at best problematic with respect to this protective mechanism.

Characterization of mouthguard materials: physical and mechanical properties of commercialized products.

OBJECTIVES: Contemporary mouthguard materials need to perform consistently over a wide range of possible temperatures (-20 to 40 degrees C). Therefore the specific aim of this study was to characterize commercialized mouthguard materials' properties and investigate the effect of temperature on these properties. METHODS: Five commercially representative thermoplastic mouthguard materials (Essix Resin, Erkoflex, Proform-regular, Proform-laminate, and Polyshok) were tested. The durometer hardness, water absorption, tear strength, and impact attenuation of the mouthguard materials were measured according to ASTM D2240-05, D570-98 (2005), D624-00, and ASTM D6110-06f (modified) guidelines. Tests were conducted on five separate specimens at both room 23+/-2 degrees C and intra-oral 37+/-2 degrees C temperatures. Independent t-tests (alpha=0.05) were used to test for differences between room and intra-oral temperatures. RESULTS: Material hardness decreased (p<0.05) from room to intra-oral temperatures for all mouthguard materials. Water absorption increased (p<0.05) from room to intra-oral temperatures for all mouthguard materials. Tear strength decreased (p<0.05) from room to intra-oral temperatures for all mouthguard materials. Impact attenuation between room and intra-oral temperatures was different (p<0.05) for the Erkoflex, Proform-laminate, and Polyshok material respectfully. However, there was no difference between temperatures for the Essix Resin (p=.058) or Proform-regular (p=.275) materials. SIGNIFICANCE: Temperature measureably affects the physical and mechanical properties of mouthguard materials. It is particularly noteworthy that none of the commercialized products met current ANSI and SAI standards for impact attenuation.