BACKGROUND AND PURPOSE: Individualized drug testing for tumors using a strategy analogous to antibiotic tests for infectious diseases would be highly desirable for personalized and individualized cancer care. METHODS: Primary cultures containing tumor and nontumor stromal cells were utilized in a novel strategy to test drug responses with respect to both efficacy and specificity. The strategy tested in this pilot study was implemented using four primary cultures derived from plexiform neurofibromas. Responses to two cytotoxic drugs (nilotinib and imatinib) were measured by following dose-dependent changes in the proportions of tumor and nontumor cells, determined by staining them with cell-type-specific antibodies. The viability of the cultured cells and the cytotoxic effect of the drugs were also measured using proliferation and cytotoxicity assays. RESULTS: The total number of cells decreased after the drug treatment, in accordance with the observed reduction in proliferation and increased cytotoxic effect upon incubation with the two anticancer drugs. The proportions of Schwann cells and fibroblasts changed dose-dependently, although the patterns of change varied between the tumor samples (from different sources) and between the two drugs. The highly variable in vitro drug responses probably reflect the large variations in the responses of tumors to therapies between individual patients in vivo. CONCLUSIONS: These preliminary results suggest that the concept of assessing in vitro drug responses using primary cultures is feasible, but demands the extensive further development of an application for preclinical drug selection and drug discovery.
Antibodies ; Cells, Cultured ; Communicable Diseases ; Drug Discovery ; Fibroblasts ; Humans ; Precision Medicine ; Neurofibroma, Plexiform* ; Pilot Projects ; Schwann Cells ; Sensitivity and Specificity ; Stromal Cells

BACKGROUND AND PURPOSE: The aim of this study was to determine the efficacy and tolerability of granulocyte colony-stimulating factor (G-CSF) in subjects with amyotrophic lateral sclerosis (ALS). METHODS: Forty subjects with ALS were randomly assigned to two groups, which received either subcutaneous G-CSF (5 microg/kg/q12h) or placebo for 5 days. The subjects were then followed up for 3 months using the ALS Functional Rating Scale-Revised (ALSFRS-R), manual muscle testing, ALS Assessment Questionnaire-40, and nerve conduction studies. CD34+/CD133+ cell count and monocyte chemoattractant protein-1 (MCP-1) levels were evaluated at baseline. RESULTS: The rate of disease progression did not differ significantly between the two groups. The reduction in ALSFRS-R scores was greater in female subjects in the G-CSF group than in their counterparts in the placebo group. There was a trend toward a positive correlation between baseline CSF MCP-1 levels and the change in ALSFRS-R scores in both groups (Spearman's rho=0.370, p=0.070). CONCLUSIONS: With the protocol implemented in this study, G-CSF is not a promising option for the treatment of ALS. Furthermore, it may accelerate disease progression in females.
Amyotrophic Lateral Sclerosis* ; Cell Count ; Chemokine CCL2 ; Disease Progression ; Female ; Granulocyte Colony-Stimulating Factor* ; Humans ; Neural Conduction

BACKGROUND AND PURPOSE: The aim of this study was to determine the face and criterion validity, stability reliability, and internal consistency of the Persian version of the Impact on Participation and Autonomy (IPA-p) scale among Iranian people with multiple sclerosis (MS). METHODS: Trained experts interviewed 364 MS patients and their relatives to assess the criterion validity, stability reliability, and internal consistency of the IPA-p scale. Ten specialists from different disciplines were also recruited to assess its face validity. A consent form was completed by the patients and their relatives. Internal consistency reliability was measured using Cronbach's alpha and stability reliability was assessed using interclass correlation coefficients (ICCs). The test-retest method was used to detect the reliability of the questioner. The study subjects completed the IPA-p scale on two occasions separated by an interval of 30-45 days. Study checklists were also used to assess the face validity, stability reliability, and internal consistency of the IPA-p scale. RESULTS: About 50% of the respondents reported their perceived overall participation to be "good" or "very good" and 60% of the specialists rated the ability of the IPA-p scale to measure what it was designed for as "excellent." Spearman correlation coefficients were >0.8 for all but one IPA-p domain. Cronbach's alpha between the mean IPA-p scale scores achieved on two separate occasions ranged from 0.858 to 0.913. The highest and lowest internal consistencies belonged to the "social relationships" and "education and learning" domains, respectively. The test-retest ICCs for the nine domains were between 0.789 and 0.919, and all were significant at p<0.001. CONCLUSIONS: The IPA-p questionnaire can be considered a valid and reliable instrument for assessing self-reported participation among Iranian MS patients.
Checklist ; Consent Forms ; Surveys and Questionnaires ; Humans ; Multiple Sclerosis* ; Quality of Life ; Specialization

BACKGROUND AND PURPOSE: Carotid artery stenting (CAS) is emerging as an alternative to carotid endarterectomy for the treatment of carotid artery stenosis (CS), but the effect of CAS on the cognitive function of patients with severe CS has not been fully investigated. The aim of this study was to use comprehensive neuropsychological tests to determine the effect of CAS on cognitive function from baseline to 3 months postprocedure in patients with severe CS. METHODS: Thirty-one patients due to undergo CAS due to high-grade CS (> or =70%) and 11 control subjects who were diagnosed with CS, but who did not undergo CAS, and who visited the clinic or emergency room between February 2009 and February 2012 were recruited consecutively at baseline (i.e., pre-CAS). Follow-up neuropsychological evaluations after 3 months were completed by 23 of the 31 patients who underwent CAS, and by 10 of the 11 control subjects. The primary cognitive outcome was assessed using a neuropsychological test containing subcategories designed to test general cognitive function, attention, visuospatial function, language and related functions, memory, and frontal lobe/executive function. RESULTS: Of the 23 patients undergoing CAS who completed the 3-month follow-up tests, 12 had asymptomatic CS. During the 3-month follow-up period, the patients who underwent CAS and those with asymptomatic CS achieved similar results to the control group on all cognitive tests. However, symptomatic CS patients (n=11) who underwent CAS exhibited improvements in visuospatial function (p=0.046) and total Seoul Neuropsychological Screening Battery-Dementia Version scores (p=0.010) in comparison with both the asymptomatic CS patients and the control group. CONCLUSIONS: The findings of this study suggest that CAS has a positive effect on cognitive function in patients with symptomatic CS over a 3-month follow-up period. A long-term, multicenter, prospective case-control study would be helpful to predict quality of life and prognoses for patients undergoing CAS.
Carotid Arteries* ; Carotid Stenosis* ; Case-Control Studies ; Cognition ; Constriction, Pathologic ; Emergency Service, Hospital ; Endarterectomy, Carotid ; Follow-Up Studies ; Humans ; Mass Screening ; Memory ; Neuropsychological Tests ; Prognosis ; Prospective Studies* ; Quality of Life ; Seoul ; Stents*

BACKGROUND AND PURPOSE: Recent advances in information technology have created opportunities for advances in the management of stroke. The objective of this study was to test the feasibility of using a smartphone software application (app) for the management of vascular risk factors in patients with stroke. METHODS: This prospective clinical trial developed a smartphone app, the 'Korea University Health Monitoring System for Stroke: KUHMS2,' for use by patients with stroke. During a 6-month follow-up period, its feasibility was assessed by measuring the changes in their vascular risk-factor profiles and the number of days per patient with data registration into the app. The effect of the app on the achievement rate of risk-factor targets was assessed by classifying subjects into compliant and noncompliant groups. RESULTS: At the end of the trial, data on 48 patients were analyzed. The number of days on which data were registered into the app was 60.42+/-50.17 (mean+/-standard deviation). Among predefined vascular risk factors, the target achievement rate for blood pressure and glycated hemoglobin (HbA1c) improved significantly from baseline to the final measurement. The serial changes in achievement rates for risk-factor targets did not differ between the compliant and noncompliant groups. CONCLUSIONS: Many challenges must be overcome before mobile apps can be used for patients with stroke. Nevertheless, the app tested in this study induced a shift in the risk profiles in a favorable direction among the included stroke patients.
Blood Pressure ; Delivery of Health Care ; Follow-Up Studies ; Hemoglobin A, Glycosylated ; Humans ; Mobile Applications* ; Prospective Studies ; Risk Factors* ; Stroke ; Smartphone

Cerebrospinal fluid (CSF) can provide vital informative about pathological processes occurring in the brain. In particular, the CSF concentrations of Abeta42, tTau, and pTau181 are useful for the early diagnosis of Alzheimer's disease (AD). However, many studies have demonstrated that confounding factors related to the preanalytical processing of CSF can seriously influence measurements of these AD biomarkers. It is therefore important to develop a standardized protocol for the acquisition and handling of CSF, particularly with regard to the types of tube used for collection and storage, the proper aliquot volume, blood contamination, and the number of tube transfers and freeze-thaw cycles, because these aspects of the procedure have been shown to affect AD biomarker measurements. A survey of the impact of several individual preanalytical procedures on the measurement of AD biomarkers in CSF was conducted for this review article, and the implications of the differences among them are discussed. Furthermore, following a review of the procedures used in Korean and international biomarker laboratories, a consensus was reached among a cooperative Korean multicenter research group regarding a standardized protocol for the analysis of AD biomarkers in CSF. All efforts were made to be stringent regarding the controversial issues associated with this protocol, thus minimizing the confounding influence of various factors on current investigations using established AD biomarkers and on future studies using novel biomarkers of AD and other neurodegenerative disorders.
Alzheimer Disease* ; Biomarkers* ; Blood Volume ; Brain ; Cerebrospinal Fluid* ; Consensus* ; Early Diagnosis ; Korea ; Neurodegenerative Diseases ; Pathologic Processes

Tourette syndrome is a childhood-onset disorder characterized by a combination of motor and vocal tics, often associated with psychiatric comorbidities including attention deficit and hyperactivity disorder and obsessive-compulsive disorder. Despite an onset early in life, half of patients may present symptoms in adulthood, with variable degrees of severity. In select cases, the syndrome may lead to significant physical and social impairment, and a worrisome risk for self injury. Evolving research has provided evidence supporting the idea that the pathophysiology of Tourette syndrome is directly related to a disrupted circuit involving the cortex and subcortical structures, including the basal ganglia, nucleus accumbens, and the amygdala. There has also been a notion that a dysfunctional group of neurons in the putamen contributes to an abnormal facilitation of competing motor responses in basal ganglia structures ultimately underpinning the generation of tics. Surgical therapies for Tourette syndrome have been reserved for a small group of patients not responding to behavioral and pharmacological therapies, and these therapies have been directed at modulating the underlying pathophysiology. Lesion therapy as well as deep brain stimulation has been observed to suppress tics in at least some of these cases. In this article, we will review the clinical aspects of Tourette syndrome, as well as the evolution of surgical approaches and we will discuss the evidence and clinical responses to deep brain stimulation in various brain targets. We will also discuss ongoing research and future directions as well as approaches for open, scheduled and closed loop feedback-driven electrical stimulation for the treatment of Tourette syndrome.
Amygdala ; Basal Ganglia ; Brain* ; Comorbidity ; Deep Brain Stimulation* ; Electric Stimulation ; Humans ; Neurons ; Nucleus Accumbens ; Obsessive-Compulsive Disorder ; Putamen ; Tics* ; Tourette Syndrome*

Ultrasound of cranial nerves is a novel subdomain of neuromuscular ultrasound (NMUS) which may provide additional value in the assessment of cranial nerves in different neuromuscular disorders. Whilst NMUS of peripheral nerves has been studied, NMUS of cranial nerves is considered in its initial stage of research, thus, there is a need to summarize the research results achieved to date. Detailed scanning protocols, which assist in mastery of the techniques, are briefly mentioned in the few reference textbooks available in the field. This review article focuses on ultrasound scanning techniques of the 4 accessible cranial nerves: optic, facial, vagus and spinal accessory nerves. The relevant literatures and potential future applications are discussed.
Accessory Nerve ; Cranial Nerves* ; Peripheral Nerves ; Ultrasonography*

BACKGROUND AND PURPOSE: The detection of alpha-synuclein in the body fluids of patients with synucleinopathy has yielded promising but inconclusive results, in part because of conformational changes of alpha-synuclein in response to environmental conditions. The aim of this study was to determine the feasibility of using alpha-synuclein as a biological marker for Parkinson's disease (PD). METHODS: Twenty-three drug-naive patients with PD (age 62.4+/-12.7 years, mean+/-SD; 11 males) and 29 age- and sex-matched neurologic control subjects (age 60.1+/-16.2 years; 16 males) were recruited. The levels of oligomeric and total alpha-synuclein in the cerebrospinal fluid (CSF) and plasma were measured using two simultaneous enzyme-linked immunosorbent assays. RESULTS: The level of alpha-synuclein oligomer in the CSF of PD patients was significantly higher in PD patients than in neurological controls, but other findings (plasma alpha-synuclein oligomer and total alpha-synuclein in CSF and plasma) did not differ significantly between the two groups. When the control subjects were divided into a symptomatic control group (11 patients who complained of parkinsonian symptoms and were diagnosed with hydrocephalus and drug-induced or vascular parkinsonism) and a neurologic control group (10 normal subjects and 8 patients with diabetic ophthalmoplegia), the level of alpha-synuclein oligomer in the CSF was still significantly higher in PD patients than in both of the control subgroups. CONCLUSIONS: These findings provide further evidence for a pathogenic role of the alpha-synuclein oligomer and suggest that CSF levels of alpha-synuclein oligomer can be a reliable marker for PD.
alpha-Synuclein ; Biomarkers ; Body Fluids ; Enzyme-Linked Immunosorbent Assay ; Humans ; Hydrocephalus ; Parkinson Disease ; Plasma

BACKGROUND AND PURPOSE: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited microangiopathy caused by mutations in the Notch3 gene. Although previous studies have shown an association between lacunar infarction and cognitive impairment, the relationship between MRI parameters and cognition remains unclear. In this study we investigated the influence of MRI parameters on cognitive impairment in CADASIL. METHODS: We applied a prospective protocol to 40 patients. MRI analysis included the normalized volume of white-matter hyperintensities (nWMHs), number of lacunes, and number of cerebral microbleeds. Cognition was assessed with the aid of psychometric tests [Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognition (ADAS-cog), Trail-Making Test, and Stroop interference (Stroop IF)]. RESULTS: A multivariate regression analysis revealed that the total number of lacunes influenced the performance in the MMSE, ADAS-cog, and Stroop IF, while nWMHs had a strong univariate association with ADAS-cog and Stroop IF scores. However, this association disappeared in the multivariate analysis. CONCLUSIONS: These findings demonstrate that the number of lacunes is the main predictive factor of cognitive impairment in CADASIL.
Alzheimer Disease ; CADASIL ; Cognition ; Humans ; Leukoencephalopathies ; Prospective Studies ; Psychometrics ; Stroke, Lacunar