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1.  Endovascular Therapy for Ischemic Stroke 
The utility of intravenous tissue plasminogen activator (IV t-PA) in improving the clinical outcomes after acute ischemic stroke has been well demonstrated in past clinical trials. Though multiple initial small series of endovascular stroke therapy had shown good outcomes as compared to IV t-PA, a similar beneficial effect had not been translated in multiple randomized clinical trials of endovascular stroke therapy. Over the same time, there have been parallel advances in imaging technology and better understanding and utility of the imaging in therapy of acute stroke. In this review, we will discuss the evolution of endovascular stroke therapy followed by a discussion of the key factors that have to be considered during endovascular stroke therapy and directions for future endovascular stroke trials.
doi:10.3988/jcn.2015.11.1.1
PMCID: PMC4302170  PMID: 25628731
endovascular therapy; stroke; mechanical thrombectomy
6.  Cognitive Function in Childhood Epilepsy: Importance of Attention Deficit Hyperactivity Disorder 
Background and Purpose
To determine how cognitive function is related to epilepsy classification and comorbid attention deficit hyperactivity disorder (ADHD) in children with newly diagnosed epilepsy of genetic or unknown etiology.
Methods
The medical records of children aged 6-16 years with newly diagnosed epilepsy of genetic or unknown etiology were reviewed retrospectively. The Korean Education Development Institute-Wechsler Intelligence Scale for Children and the Comprehensive Attention Test were used to evaluate intelligence and attention/executive function, respectively.
Results
The data of a total of 149 children, 103 with focal seizures and 46 with generalized seizures, were reviewed. The prevalence of ADHD was 49.2% (59 out of 120 examined patients), and ADHD patients exhibited significantly worse auditory selective attention, flanker test results, and spatial working memory. Patients with generalized seizures exhibited significantly worse auditory selective and sustained attention than patients with focal seizures. In patients with generalized seizures, sustained attention, flanker test findings, and spatial working memory were found to be affected by ADHD, and auditory selective and sustained attention were significantly worse in patients with benign childhood epilepsy with centrotemporal spikes and ADHD than in their counterparts without ADHD.
Conclusions
Cognitive processes are affected by seizure type and comorbid ADHD. Proper characterization of these neuropsychiatric impairments may allow earlier intervention during the disease course.
doi:10.3988/jcn.2015.11.1.20
PMCID: PMC4302175  PMID: 25628733
cognition; attention; working memory; epilepsy; attention deficit hyperactivity disorder
7.  Efficacy of and Patient Compliance with a Ketogenic Diet in Adults with Intractable Epilepsy: A Meta-Analysis 
Background and Purpose
Despite the successful use of a ketogenic diet in pediatric epilepsy, its application in adults has been limited. The aim of this meta-analysis was to summarize the findings of relevant published studies in order to identify the efficacy of and compliance with a ketogenic diet and its main subtypes (i.e., classic ketogenic diet and modified Atkins diet) in adults with intractable epilepsy, and to provide useful information for clinical practice.
Methods
Electronic searches of PubMed, EMBASE, Google Scholar, and the ISI Web of Science were conducted to identify studies of the efficacy of and patient compliance with a ketogenic diet in adults with intractable epilepsy; the included studies were reviewed. Meta-analyses were performed using STATA to determine combined efficacy rates and combined rates of compliance with the ketogenic diet and its main subtypes.
Results
In total, 12 studies qualified for inclusion, and data from 270 patients were evaluated.The results of the meta-analysis revealed combined efficacy rates of all types of ketogenic diet, a classical ketogenic diet, and a modified Atkins diet were 42%, 52%, and 34%, respectively; the corresponding combined compliance rates were 45%, 38%, and 56%.
Conclusions
The results indicate that a ketogenic diet is a promising complementary therapy in adult intractable epilepsy, and that while a classical ketogenic diet may be more effective, adult patients are likely to be less compliant with it than with a modified Atkins diet.
doi:10.3988/jcn.2015.11.1.26
PMCID: PMC4302176  PMID: 25628734
ketogenic diet; adult; intractable epilepsy; efficacy; compliance
8.  Suicidality and Its Risk Factors in Korean People with Epilepsy: A MEPSY Study 
Background and Purpose
People with epilepsy (PWE) are more likely to experience suicidality, with suicidal ideation and attempts, than people without epilepsy (PWoE). The aims of the present study were to determine 1) the characteristics of suicidality in Korean PWE, 2) whether PWE with suicidality receive psychiatric intervention, and 3) the risk factors for suicidality.
Methods
Patients who consecutively visited epilepsy clinics at secondary- and tertiary-care hospitals were recruited (n=684), along with age- and sex-matched PWoE (n=229). The presence of current major depressive disorder (MDD), generalized anxiety disorder (GAD), and/or suicidality was established using the Mini International Neuropsychiatric Interview-Plus Version 5.0.0. The Korean version of the Liverpool Adverse Events Profile (K-LAEP) was applied to detect adverse effects of antiepileptic drugs (AEDs).
Results
Suicidality was present in 208 (30.4%) of the 684 PWE. The rate of suicidality was 4.6 times higher among PWE than PWoE, and 108 (15.7%) PWE had suicidal ideation and had attempted suicide. Among those who had attempted suicide, 40.7% had made at least two attempts. The most common method of suicide attempt was drug overdose (34.9%). Unfortunately, of the 208 PWE with suicidality, 136 (65.4%) did not receive psychiatric intervention. The risk factors for suicidality were MDD [odds ratio (OR)=6.448, 95% confidence interval (CI)=3.739-11.120, p<0.001], GAD (OR=3.561, 95% CI=1.966-6.452, p<0.001), item scores of 3 or 4 on the K-LAEP (OR=2.688, 95% CI=1.647-4.387, p<0.001), and a history of febrile convulsion (OR= 2.188, 95% CI=1.318-3.632, p=0.002).
Conclusions
Suicidality is more prevalent in PWE than in PWoE. Clinicians should monitor psychiatric disorders and the adverse effects of AEDs in PWE in an attempt to reduce the incidence of suicidal ideation or suicide attempts in this patient population.
doi:10.3988/jcn.2015.11.1.32
PMCID: PMC4302177  PMID: 25628735
suicide; epilepsy; depression; anxiety; adverse effect; risk factor
9.  Whole-Brain Diffusion-Tensor Changes in Parkinsonian Patients with Impulse Control Disorders 
Background and Purpose
The aim of this study was to determine the changes in diffusion-tensor images associated with medication-related impulse control disorder (ICD) in Parkinson's disease (PD) patients undergoing chronic dopamine-replacement therapy.
Methods
Nineteen PD patients, comprising 10 with ICD (PD-ICD) and 9 without ICD (PD-nonICD), and 18 age-matched healthy controls (HCs) with no cognitive or other psychiatric disorders were analyzed. All subjects underwent 3-T magnetic resonance diffusion-tensor imaging. For all PD patients, clinical data on PD duration, antiparkinsonian medication dosages, Unified Parkinson's Disease Rating Scale and Mini-Mental State Examination were collected. Whole-brain voxel-based measures of fractional anisotropy (FA) and mean diffusivity (MD) were analyzed.
Results
In comparison with HCs, the PD-nonICD subjects had low FA at the bilateral orbitofrontal areas. While the PD-ICD subjects exhibited no such difference, their FA was significantly elevated at the anterior corpus callosum. Analysis of FA between the two PD groups revealed that FA in the anterior corpus callosum, right internal capsule posterior limbs, right posterior cingulum, and right thalamic radiations were significantly higher (corrected p<0.05) in the PD-ICD than in the PD-nonICD patients. MD did not differ between the PD-ICD and PD-nonICD groups in any brain regions.
Conclusions
The PD-ICD patients appear to have relatively preserved white-matter integrity in the regions involved in reward-related behaviors compared to PD-nonICD patients. Further investigation is required to determine whether the difference in FA between PD-ICD and PD-nonICD patients reflects microstructural differences in the pathological progression of PD or is secondary to ICD.
doi:10.3988/jcn.2015.11.1.42
PMCID: PMC4302178  PMID: 25628736
impulse control disorders; Parkinson's disease; diffusion-tensor imaging
10.  Improved Serum Leptin and Ghrelin Following Bariatric Surgery Predict Better Postoperative Cognitive Function 
Background and Purpose
Bariatric surgery is associated with improved cognitive function, but the mechanisms underlying these gains remain poorly understood. Disturbed leptin and ghrelin systems are common in obese individuals and are associated with impaired cognitive function in other samples. Bariatric surgery has been shown to improve serum leptin and ghrelin levels, and these changes may underlie postoperative cognitive improvements.
Methods
Eighty-four patients completed a computerized cognitive test battery prior to bariatric surgery and at 12 months postoperatively. Participants also submitted to an 8-hour fasting blood draw to quantify serum leptin and ghrelin concentrations at these same time points.
Results
Baseline cognitive impairments and disturbed leptin and ghrelin levels improved at the 12-month follow-up compared to presurgery. Higher leptin levels were associated with worse attention/executive function at baseline; no such findings emerged for ghrelin. Regression analyses controlling for baseline factors and demographic characteristics showed that both decreased leptin and increased ghrelin following surgery was associated with better attention/executive function at the 12-month follow-up. These effects diminished after controlling for the postoperative change in body mass index (BMI); however, BMI change did not predict 12-month cognitive function.
Conclusions
Improvements in leptin and ghrelin levels following bariatric surgery appear to contribute to postoperative cognitive benefits. These gains may involve multiple mechanisms, such as reduced inflammation and improved glycemic control. Future studies that employ neuroimaging are needed to clarify the underlying mechanisms and determine whether the effects of bariatric surgery on leptin and ghrelin levels can attenuate adverse brain changes and/or risk of dementia in severely obese individuals.
doi:10.3988/jcn.2015.11.1.48
PMCID: PMC4302179  PMID: 25628737
obesity; bariatric surgery; cognitive function; leptin; ghrelin
11.  Low-Molecular-Weight Heparin or Dual Antiplatelet Therapy Is More Effective Than Aspirin Alone in Preventing Early Neurological Deterioration and Improving the 6-Month Outcome in Ischemic Stroke Patients 
Background and Purpose
Dual antiplatelet therapy (DAT) with clopidogrel and aspirin has been shown to confer greater protection against early neurological deterioration (END) and early recurrent ischemic stroke (ERIS) than aspirin alone in patients who have experienced an acute ischemic stroke. However, few studies have compared the effects of anticoagulation therapy with low-molecular-weight heparin (LMWH), DAT, and aspirin.
Methods
Patients with acute ischemic stroke (n=1,467) were randomized to therapy groups receiving aspirin (200 mg daily for 14 days, followed by 100 mg daily for 6 months), DAT (200 mg of aspirin and 75 mg of clopidogrel daily for 14 days, then 100 mg of aspirin daily for 6 months), or LMWH (4,000 antifactor Xa IU of enoxaparin in 0.4 mL subcutaneously twice daily for 14 days, followed by 100 mg of aspirin daily for 6 months). The effects of these treatment strategies on the incidence of END, ERIS, and deep-vein thrombosis (DVT) were observed for 10-14 days after treatment, and their impacts on a good outcome were evaluated at 6 months.
Results
The DAT and LMWH were associated with a more significant reduction of END and ERIS within 14 days compared with aspirin-alone therapy. In addition, LMWH was associated with a significantly lower incidence of DVT within 14 days. At 6 months, DAT or LMWH improved the outcome among patients aged >70 years and those with symptomatic stenosis in the posterior circulation or basilar artery compared with aspirin.
Conclusions
LMWH or DAT may be more effective than aspirin alone for reducing the incidence of END and ERIS within 14 days, and is associated with improved outcomes in elderly patients and those with stenosis in the posterior circulation or basilar artery at 6 months poststroke.
doi:10.3988/jcn.2015.11.1.57
PMCID: PMC4302180  PMID: 25628738
acute ischemic stroke; low-molecular-weight heparin; dual antiplatelet therapy; outcomes; early neurological deterioration
12.  The Effects of Galantamine Treatment on Attention and Its Relationship with Cognition and Activities of Daily Living in Patients with Mild to Moderate Alzheimer's Disease 
Background and Purpose
The positive effects of galantamine on cognition and activities of daily living (ADL) in Alzheimer's disease (AD) are thought to be mediated via improvements in attention. The purpose of this study was to determine the effect of galantamine on attention in AD patients using a computerized attention test and to elucidate the relationship between improvements in attention and change in cognition and ADL.
Methods
In this multicenter, open-label, prospective study, patients with mild to moderate AD received galantamine and then submitted to computerized attention tests, the Alzheimer's Disease Assessment Scale-cognitive subscale, and instrumental ADL (IADL) at baseline, 4 weeks, and 12 weeks. The differences in reaction time on computerized tests were explored relative to the changes in cognition and IADL.
Results
After 12 weeks of taking the trial medication there was a significant reduction from baseline levels in the choice reaction time (baseline, 5,216±3,650 sec; 12 weeks, 4,139±2,920 sec; p<0.01) and the simple reaction time (baseline, 1,089±782 sec; 12 weeks, 908±606 sec; p<0.01). Correlation analyses of changes in choice or simple reaction times relative to cognition and ADL measures yielded no significant associations. The improvement in attention observed at 4 weeks of galantamine treatment was not associated with any significant changes in outcome measures at the end of trial.
Conclusions
This study found no significant association between the improvement in attention after treatment with galantamine and changes in cognition and ADL in patients with mild to moderate AD, despite the significant improvement in attention over the course of the treatment.
doi:10.3988/jcn.2015.11.1.66
PMCID: PMC4302181  PMID: 25628739
Alzheimer's disease; galantamine; attention; computerized test
13.  A Low Baseline Glomerular Filtration Rate Predicts Poor Clinical Outcome at 3 Months after Acute Ischemic Stroke 
Background and Purpose
Chronic kidney disease (CKD) is an established risk factor for numerous cardiovascular diseases including stroke. The relationship between the baseline estimated glomerular filtration rate (eGFR) and clinical 3-month outcomes in patients with acute ischemic stroke were evaluated in this study.
Methods
This was a prospective cohort study involving a hospital-based stroke registry; 1373 patients with acute ischemic stroke were enrolled. Patients were divided into the following four groups according their eGFR (calculated using the CKD Epidemiology Collaboration equations): ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2. The primary endpoint of poor functional outcome was defined as 3-month death or dependency (modified Rankin Scale score ≥3); secondary endpoints were neurological deterioration (increase in National Institutes of Health Stroke Severity score of ≥4 at discharge compared to baseline) during hospitalization and in-hospital mortality.
Results
The overall eGFR was 84.5±20.8 mL/min/1.73 m2 (mean±SD). The distribution of baseline renal impairment was as follows: 1,218, 82, 40, and 33 patients had eGFRs of ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2, respectively. At 3 months after the stroke, 476 (34.7%) patients exhibited poor functional outcome. Furthermore, a poor functional outcome occurred more frequently with increasingly advanced stages of CKD (rates of 31.9%, 53.7%, 55.0%, and 63.6% for CKD stages 1/2, 3a, 3b, and 4/5, respectively; p<0.001). Multivariate analysis revealed that a baseline eGFR of <30 mL/min/1.73m2 increased the risk of a poor functional outcome by 2.37-fold (p=0.047). In addition, baseline renal dysfunction was closely associated with neurological deterioration during hospitalization and with in-hospital mortality.
Conclusions
A low baseline eGFR was strongly predictive of both poor functional outcome at 3 months after ischemic stroke and neurological deterioration/mortality during hospitalization.
doi:10.3988/jcn.2015.11.1.73
PMCID: PMC4302182  PMID: 25628740
chronic kidney disease; functional outcome; mortality; stroke
14.  Low-Density-Lipoprotein Particle Size Predicts a Poor Outcome in Patients with Atherothrombotic Stroke 
Background and Purpose
Low-density lipoprotein (LDL) particle size is considered to be one of the more important cardiovascular risk factors, and small LDL particles are known to have atherogenic potential. The aim of this study was to determine whether LDL particle size is associated with stroke severity and functional outcome in patients with atherothrombotic stroke.
Methods
Between January 2009 and May 2011, 248 patients with first-episode cerebral infarction who were admitted to our hospital within 7 days after symptom onset were prospectively enrolled. LDL particle size was measured using the nondenaturing polyacrylamide gradient gel electrophoresis assay. Stroke severity was assessed by applying the National Institutes of Health Stroke Scale (NIHSS) at admission. Functional outcome was investigated at 3 months after the index stroke using the modified Rankin Scale (mRS), and poor functional outcome was defined as an mRS score of ≥3.
Results
The LDL particle size in the 248 patients was 25.9±0.9 nm (mean±SD). LDL particle size was inversely correlated with the degree of cerebral artery stenosis (p=0.010). Multinomial multivariate logistic analysis revealed that after adjustment for age, sex, and variables with p<0.1 in univariate analysis, LDL particle size was independently and inversely associated with stroke severity (NIHSS score ≥5; reference, NIHSS score 0-2; odds ratio=0.38, p=0.028) and poor functional outcome (odds ratio=0.44, p=0.038).
Conclusions
The results of this study demonstrate that small LDL particles are independently correlated with stroke outcomes. LDL particle size is thus a potential biomarker for the prognosis of atherothrombotic stroke.
doi:10.3988/jcn.2015.11.1.80
PMCID: PMC4302183  PMID: 25628741
low-density-lipoprotein particle size; lipoprotein; stroke severity; stroke outcome; atherosclerosis
15.  Paraneoplastic Limbic Encephalitis in a Male with Squamous Cell Carcinoma of the Lung 
Background
Paraneoplastic limbic encephalitis (PLE) is a rare syndrome characterized by memory impairment, symptoms of hypothalamic dysfunction, and seizures. It commonly precedes the diagnosis of cancer. Small-cell lung cancer is the neoplasm that is most frequently reported as the etiology underlying PLE.
Case Report
This report describes a male patient who presented with neurologic symptoms consistent with anterograde amnesia, apathy, and disorientation. MRI revealed diffuse hyperintensities located predominantly in the medial bitemporal lobes, basal ganglia, frontal lobes, and leptomeninges on fluid attenuated inversion recovery images, suggesting PLE. Study of the primary tumor revealed squamous cell carcinoma of the lung. The patient was treated with neoadjuvant chemotherapy followed by surgery and adjuvant chemoradiotherapy, which resulted in his neurologic symptoms gradually improving.
Conclusions
PLE might be a rare debut of squamous cell carcinoma of the lung. Treatment of the primary tumor may improve the neurologic symptoms.
doi:10.3988/jcn.2015.11.1.87
PMCID: PMC4302184  PMID: 25628742
lung cancer; squamous cell carcinoma; paraneoplastic syndrome; limbic encephalitis
16.  Oral Disease-Modifying Therapies for Multiple Sclerosis 
Classical multiple sclerosis (MS) treatments using first-line injectable drugs, although widely applied, remain a major concern in terms of therapeutic adherence and efficacy. New oral drugs recently approved for MS treatment represent significant advances in therapy. The oral route of administration clearly promotes patient satisfaction and increases therapeutic compliance. However, these drugs may also have safety and tolerability issues, and a thorough analysis of the risks and benefits is required. Three oral drugs have been approved by regulatory agencies for MS treatment: fingolimod, teriflunomide, and dimethyl fumarate. This article reviews the mechanisms of action, safety, and efficacy of these drugs and two other drugs that have yielded positive results in phase III trials: cladribine and laquinimod.
doi:10.3988/jcn.2015.11.1.9
PMCID: PMC4302185  PMID: 25628732
multiple sclerosis; oral drug; clinical trial; treatment
17.  Novel Compound Heterozygous Nonsense PRX Mutations in a Korean Dejerine-Sottas Neuropathy Family 
Background
Mutations in the gene encoding periaxin (PRX) are known to cause autosomal recessive Dejerine-Sottas neuropathy (DSN) or Charcot-Marie-Tooth disease type 4F. However, there have been no reports describing Korean patients with these mutations.
Case Report
We examined a Korean DSN patient with an early-onset, slowly progressive, demyelinating neuropathy with prominent sensory involvement. Whole-exome sequencing and subsequent capillary sequencing revealed novel compound heterozygous nonsense mutations (p.R392X and p.R679X) in PRX. One mutation was transmitted from each of the patient's parents. No unaffected family member had both mutations, and the mutations were not found in healthy controls.
Conclusions
We believe that these novel compound heterozygous nonsense mutations are the underlying cause of DSN. The clinical, electrophysiologic, and pathologic phenotypes in this family were similar to those described previously for patients with PRX mutations. We have identified the first PRX mutation in a Korean patient with DSN.
doi:10.3988/jcn.2015.11.1.92
PMCID: PMC4302186  PMID: 25628743
Dejerine-Sottas neuropathy; Charcot-Marie-Tooth disease; periaxin; whole-exome sequencing; peripheral nerve
18.  Mild Clinical Features and Histopathologically Atypical Cores in Two Korean Families with Central Core Disease Harboring RYR1 Mutations at the C-Terminal Region 
Background
Central core disease (CCD) is a congenital myopathy characterized by distinctive cores in muscle fibers. Mutations in the gene encoding ryanodine receptor 1 (RYR1) have been identified in most CCD patients.
Case Report
Two unrelated patients presented with slowly progressive or nonprogressive proximal muscle weakness since childhood. Their family history revealed some members with the same clinical problem. Histological analysis of muscle biopsy samples revealed numerous peripheral cores in the muscle fibers. RYR1 sequence analysis disclosed a novel mutation in exon 101 (c.14590T>C) and confirmed a previously reported mutation in exon 102 (c.14678G>A).
Conclusions
We report herein two families with CCD in whom missense mutations at the C-terminal of RYR1 were identified. Although it has been accepted that such mutations are usually associated with a severe clinical phenotype and clearly demarcated central cores, our patients exhibited a mild clinical phenotype without facial muscle involvement and skeletal deformities, and atypical cores in their muscle biopsy specimens.
doi:10.3988/jcn.2015.11.1.97
PMCID: PMC4302187  PMID: 25628744
central core disease; ryanodine receptor 1; RYR1; core myopathy
19.  Hyperhomocysteinemia and Neurologic Disorders: a Review 
Homocysteine (Hcy) is a sulfur-containing amino acid that is generated during methionine metabolism. It has a physiologic role in DNA metabolism via methylation, a process governed by the presentation of folate, and vitamins B6 and B12. Physiologic Hcy levels are determined primarily by dietary intake and vitamin status. Elevated plasma levels of Hcy (eHcy) can be caused by deficiency of either vitamin B12 or folate, or a combination thereof. Certain genetic factors also cause eHcy, such as C667T substitution of the gene encoding methylenetetrahydrofolate reductase. eHcy has been observed in several medical conditions, such as cardiovascular disorders, atherosclerosis, myocardial infarction, stroke, minimal cognitive impairment, dementia, Parkinson's disease, multiple sclerosis, epilepsy, and eclampsia. There is evidence from laboratory and clinical studies that Hcy, and especially eHcy, exerts direct toxic effects on both the vascular and nervous systems. This article provides a review of the current literature on the possible roles of eHcy relevant to various neurologic disorders.
doi:10.3988/jcn.2014.10.4.281
PMCID: PMC4198708  PMID: 25324876
hyperhomocysteinemia; neurologic disorders; pregnancy
20.  Cardiotoxicity of Mitoxantrone Treatment in a German Cohort of 639 Multiple Sclerosis Patients 
Background and Purpose
The aim of this study was to elucidate the role of therapy-related cardiotoxicity in multiple sclerosis (MS) patients treated with mitoxantrone and to identify potential predictors for individual risk assessment.
Methods
Within a multicenter retrospective cohort design, cardiac side effects attributed to mitoxantrone were analyzed in 639 MS patients at 2 MS centers in Germany. Demographic, disease, treatment, and follow-up data were collected from hospital records. Patients regularly received cardiac monitoring during the treatment phase.
Results
None of the patients developed symptomatic congestive heart failure. However, the frequency of patients experiencing cardiac dysfunction of milder forms after mitoxantrone therapy was 4.1% (26 patients) among all patients. Analyses of the risk for cardiotoxicity revealed that cumulative dose exposure was the only statistically relevant risk factor associated with cardiac dysfunction.
Conclusions
The number of patients developing subclinical cardiac dysfunction below the maximum recommended cumulative dose is higher than was initially assumed. Interestingly, a subgroup of patients was identified who experienced cardiac dysfunction shortly after initiation of mitoxantrone and who received a low cumulative dose. Therefore, each administration of mitoxantrone should include monitoring of cardiac function to enhance the treatment safety for patients and to allow for early detection of any side effects, especially in potential high-risk subgroups (as determined genetically).
doi:10.3988/jcn.2014.10.4.289
PMCID: PMC4198709  PMID: 25324877
multiple sclerosis; mitoxantrone; cardiotoxicity; dose dependency
21.  Contingent Negative Variation Is Associated with Cognitive Dysfunction and Secondary Progressive Disease Course in Multiple Sclerosis 
Background and Purpose
The relationship between contingent negative variation (CNV), which is an event-related potential, and cognition in multiple sclerosis (MS) has not been examined previously. The primary objective of the present study was thus to determine the association between CNV and cognition in a sample of MS patients.
Methods
The subjects of this study comprised 66 MS patients [50 with relapsing-remitting MS (RRMS) and 16 with secondary progressive MS (SPMS)] and 40 matched healthy volunteers. A neuropsychological battery was administered to all of the subjects; CNV recordings were made from the Cz, Fz, and Pz electrodes, and the amplitude and area under the curve (AUC) were measured at each electrode.
Results
RRMS patients exhibited CNVs with lower amplitudes and smaller AUCs than the controls at Pz. SPMS patients exhibited CNVs with lower amplitudes and smaller AUCs than the controls, and CNVs with a smaller amplitude than the RRMS patients at both Cz and Pz. After correcting for multiple comparisons, a lower CNV amplitude at Pz was significantly associated with worse performance on measures of speed of information processing, verbal fluency, verbal learning, and verbal recall.
Conclusions
CNV may serve as a marker for disease progression and cognitive dysfunction in MS. Further studies with larger samples and wider electrode coverage are required to fully assess the value of CNV in these areas.
doi:10.3988/jcn.2014.10.4.296
PMCID: PMC4198710  PMID: 25324878
relapsing-remitting multiple sclerosis; secondary progressive multiple sclerosis; contingent negative variation cognitive dysfunction; event-related potentials; neuropsychological test
22.  Sleep Disturbances and Predictive Factors in Caregivers of Patients with Mild Cognitive Impairment and Dementia 
Background and Purpose
We examined the characteristics of sleep disturbances and sleep patterns in the caregivers of patients with amnestic mild cognitive impairment (aMCI) and dementia.
Methods
We prospectively studied 132 patients (60 with aMCI and 72 with dementia) and their caregivers, and 52 noncaregiver controls. All caregivers and controls completed several sleep questionnaires, including the Pittsburgh Sleep Quality Index (PSQI). The patients were administered neuropsychological tests and the neuropsychiatric inventory to evaluate their behavioral and neuropsychiatric symptoms of dementia (BPSD).
Results
The PSQI global score was 6.25±3.88 (mean±SD) for the dementia caregivers and 5.47±3.53 for the aMCI caregivers. The Insomnia Severity Index (ISI) and short form of the Geriatric Depression Scale (GDS-S) predicted higher PSQI global scores in aMCI caregivers, and higher scores for the ISI, Epworth Sleepiness Scale (ESS), and GDS-S in dementia caregivers. BPSD, including not only agitation, depression, and appetite change in dementia patients, but also depression, apathy, and disinhibition in aMCI patients, was related to impaired sleep quality of caregivers, but nighttime behavior was not. Age and gender were not risk factors for disturbed sleep quality.
Conclusions
Dementia and aMCI caregivers exhibit impaired quality of sleep versus non-caregivers. ISI, GDS-S, and ESS scores are strong indicators of poor sleep in dementia caregivers. In addition, some BPSD and parts of the neuropsychological tests may be predictive factors of sleep disturbance in dementia caregivers.
doi:10.3988/jcn.2014.10.4.304
PMCID: PMC4198711  PMID: 25324879
sleep disturbance; caregiver; Alzheimer's disease; vascular dementia; mild cognitive impairment
23.  Dysautonomia in Narcolepsy: Evidence by Questionnaire Assessment 
Background and Purpose
Excessive daytime sleepiness and sudden sleep attacks are the main features of narcolepsy, but rapid-eye-movement sleep behavior disorder (RBD), hyposmia, and depression can also occur. The latter symptoms are nonmotor features in idiopathic Parkinson's disease (IPD). In the present study, IPD-proven diagnostic tools were tested to determine whether they are also applicable in the assessment of narcolepsy.
Methods
This was a case-control study comparing 15 patients with narcolepsy (PN) and 15 control subjects (CS) using the Scales for Outcomes in Parkinson's Autonomic Test (SCOPA-AUT), Parkinson's Disease Nonmotor Symptoms (PDNMS), University of Pennsylvania Smell Test, Farnsworth-Munsell 100 Hue test, Beck Depression Inventory, and the RBD screening questionnaire.
Results
Both the PN and CS exhibited mild hyposmia and no deficits in visual tests. Frequent dysautonomia in all domains except sexuality was found for the PN. The total SCOPA-AUT score was higher for the PN (18.47±10.08, mean±SD) than for the CS (4.40±3.09), as was the PDNMS score (10.53±4.78 and 1.80±2.31, respectively). RBD was present in 87% of the PN and 0% of the CS. The PN were more depressed than the CS. The differences between the PN and CS for all of these variables were statistically significant (all p<0.05).
Conclusions
The results of this study provide evidence for the presence of dysautonomia and confirm the comorbidities of depression and RBD in narcolepsy patients. The spectrum, which is comparable to the nonmotor complex in IPD, suggests wide-ranging, clinically detectable dysfunction beyond the narcoleptic core syndrome.
doi:10.3988/jcn.2014.10.4.314
PMCID: PMC4198712  PMID: 25324880
autonomic failure; multisystem disorder; narcolepsy; Parkinson's disease
24.  Evaluation of Temperament and Character Features as Risk Factors for Depressive Symptoms in Patients with Restless Legs Syndrome 
Background and Purpose
Restless legs syndrome (RLS) is a common sleep-related movement disorder that is frequently associated with psychological disturbances. Personality traits are of considerable importance with respect to coping with chronic illness and disease vulnerability. This study assessed the temperament and character traits of RLS patients using an approach that involves the psychobiological model of personality.
Methods
The personality features of 65 newly diagnosed and untreated RLS patients with no neurological or psychiatric diseases and 109 healthy controls were determined using the Temperament and Character Inventory and compared using covariance analyses. The International RLS Study Group Severity Scale was used to assess the severity of the RLS symptoms, and the Beck Depression Inventory was used to assess the presence and severity of depressive symptoms.
Results
RLS patients scored significantly higher than healthy controls on the temperament dimension of harm avoidance (HA, p=0.02) and significantly lower on self-directedness (SD, p=0.001). No significant difference was observed in terms of the temperament dimension of novelty seeking (p=0.435). HA scores were significantly correlated with the BDI score but not with the RLS severity or duration.
Conclusions
High HA and low SD scores are the main characterizing personality features of RLS patients. These personality dimensions may be among the factors predisposing patients to development of the depressive symptoms that are frequently associated with RLS.
doi:10.3988/jcn.2014.10.4.320
PMCID: PMC4198713  PMID: 25324881
restless legs syndrome; Temperament and Character Inventory; personality; harm avoidance; serotonin; dopamine
25.  Process Improvement to Enhance Existing Stroke Team Activity Toward More Timely Thrombolytic Treatment 
Background and Purpose
Process improvement (PI) is an approach for enhancing the existing quality improvement process by making changes while keeping the existing process. We have shown that implementation of a stroke code program using a computerized physician order entry system is effective in reducing the in-hospital time delay to thrombolysis in acute stroke patients. We investigated whether implementation of this PI could further reduce the time delays by continuous improvement of the existing process.
Methods
After determining a key indicator [time interval from emergency department (ED) arrival to intravenous (IV) thrombolysis] and conducting data analysis, the target time from ED arrival to IV thrombolysis in acute stroke patients was set at 40 min. The key indicator was monitored continuously at a weekly stroke conference. The possible reasons for the delay were determined in cases for which IV thrombolysis was not administered within the target time and, where possible, the problems were corrected. The time intervals from ED arrival to the various evaluation steps and treatment before and after implementation of the PI were compared.
Results
The median time interval from ED arrival to IV thrombolysis in acute stroke patients was significantly reduced after implementation of the PI (from 63.5 to 45 min, p=0.001). The variation in the time interval was also reduced. A reduction in the evaluation time intervals was achieved after the PI [from 23 to 17 min for computed tomography scanning (p=0.003) and from 35 to 29 min for complete blood counts (p=0.006)].
Conclusions
PI is effective for continuous improvement of the existing process by reducing the time delays between ED arrival and IV thrombolysis in acute stroke patients.
doi:10.3988/jcn.2014.10.4.328
PMCID: PMC4198714  PMID: 25324882
stroke; thrombolysis; quality improvement; emergency medical services; stroke teams; code stroke

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