Clinical Aspects of the Differential Diagnosis of Parkinson’s Disease and Parkinsonism

Parkinsonism is a clinical syndrome presenting with bradykinesia, tremor, rigidity, and postural instability. Nonmotor symptoms have recently been included in the parkinsonian syndrome, which was traditionally associated with motor symptoms only. Various pathologically distinct and unrelated diseases have the same clinical manifestations as parkinsonism or parkinsonian syndrome. The etiologies of parkinsonism are classified as neurodegenerative diseases related to the accumulation of toxic protein molecules or diseases that are not neurodegenerative. The former class includes Parkinson’s disease (PD), multiple-system atrophy, progressive supranuclear palsy, and corticobasal degeneration. Over the past decade, clinical diagnostic criteria have been validated and updated to improve the accuracy of diagnosing these diseases. The latter class of disorders unrelated to neurodegenerative diseases are classified as secondary parkinsonism, and include drug-induced parkinsonism (DIP), vascular parkinsonism, and idiopathic normal-pressure hydrocephalus (iNPH). DIP and iNPH are regarded as reversible and treatable forms of parkinsonism. However, studies have suggested that the absence of protein accumulation in the nervous system as well as managing the underlying causes do not guarantee recovery. Here we review the differential diagnosis of PD and parkinsonism, mainly focusing on the clinical aspects. In addition, we describe recent updates to the clinical criteria of various disorders sharing clinical symptoms with parkinsonism.

Long-term Effects of Bilateral Subthalamic Deep Brain Stimulation on Postural Instability and Gait Difficulty in Patients with Parkinson’s Disease

The long-term effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on postural instability and gait difficulty (PIGD) in patients with Parkinson’s disease (PD) remain unclear. In this study, we aimed to evaluate the longterm effects of STN-DBS surgery on PIGD symptoms in patients with advanced-stage PD. Methods This study included 49 consecutively included patients with PD who underwent bilateral STN-DBS. The Unified Parkinson’s Disease Rating Scale (UPDRS) scores and subscores for PIGD were assessed at baseline and at 1, 3, and 5 years postoperatively. The PIGD subscore was divided into PIGD-motor and PIGD-activities of daily living (ADL) scores according to parts III and II of the UPDRS, respectively. Results The PIGD-motor and PIGD-ADL scores at the “medication-off” state improved at 3 and 5 years, respectively. Overall, the UPDRS III and II scores at “medication-off” improved at 5 years. The UPDRS IV score also significantly improved and the levodopa equivalent daily dosage decreased at all follow-ups. Finally, the PIGD-motor score at baseline was able to predict long-term improvement in the PIGD-motor score at the 5-year follow-up. Conclusion The STN-DBS has both short- and long-term effects on PIGD, as well as overall motor function, in patients with advanced PD. The degree of PIGD at the preoperative evaluation can be used to predict long-term outcomes after STN-DBS surgery.

A Patient with Spinocerebellar Ataxia 2 Presenting with Multiple System Atrophy

Spinocerebellar ataxia type-2 (SCA2) is an autosomal dominant cerebellar ataxia that occurs due to expanded CAG trinucleotide repeats in the ATXN2 gene. Clinical features of parkinsonism in SCA2 vary from phenotypes of levodopa-responsive parkinsonism to multiple system atrophy. We described a patient with SCA2 presenting typical clinical manifestations of multiple system atrophy-c type with levodopa responsive parkinsonism whose dopamine transporter (DAT) image showed atypically reduced DAT uptake in in the striatum.

Assisted Breathing with a Diaphragm Pacing System: A Systematic Review

Purpose@#Patients with respiratory failure associated with neurological dysfunction often require mechanical ventilator support, which poses increased economic burden and ventilator-associated complications. A diaphragm pacing system (DPS) is an implanted device that provides respiratory support for such patients. In this systematic review, we reviewed the literature to assess the safety and efficacy of DPS for patients with respiratory failure resulting from amyotrophic lateral sclerosis (ALS) or cervical spinal cord injuries. @*Materials and Methods@#The following databases were searched from July 10 to July 30, 2018: MEDLINE, EMBASE, Cochran library, KoreaMed, Research Information Sharing Service, Korean studies Information Service System, Korea Institute of Science and Technology Information, and Korean Medical database. The abstracts and full texts of the searched articles were reviewed by two reviewers. @*Results@#The search keywords generated 197 articles: two randomized controlled trials, two case-control studies, and one case report involving patients with ALS; one cohort study, one case-control study, and two case reports involving patients with cervical spine injury; and one case report involving patients with both conditions were included. The primary outcome was safety profile (complications and adverse event) and efficacy (overall survival and sleep improvement). Complications and adverse events were more common in patients with ALS and spinal cord injury receiving DPS than in controls. Efficacy outcomes were inconsistent across ALS studies. @*Conclusion@#Based on safety and efficacy results, we do not support using DPS to manage respiratory failure in patients with ALS or cervical spine injury.

Reversible Cerebral Vasoconstriction Syndrome Diagnosed by Visual Symptoms and Changes in Headache Patterns in a Patient with Chronic Migraine

No abstract available.

Hand Tremor Questionnaire: A Useful Screening Tool for Differentiating Patients with Hand Tremor between Parkinson's Disease and Essential Tremor

BACKGROUND AND PURPOSE: Hand tremor is one of the most frequent symptoms in movement disorders, and differential diagnoses for hand tremor include Parkinson's disease (PD) and essential tremor (ET). However, accurately differentiating between PD and ET in clinical practice remains challenging in patients presenting with hand tremor. We investigated whether a questionnaire-based survey could be useful as a screening tool in patients with hand tremor. METHODS: A questionnaire related to hand tremor consisting of 12 items was prospectively applied to patients with PD or ET in three movement-disorder clinics. Each question was analyzed, and a query-based scoring system was evaluated for differentiating hand tremors between PD and ET. RESULTS: This study enrolled 24 patients with PD and 25 patients with ET. Nine of the 12 questions differed significantly between PD and ET: 1 about resting tremor, 4 questions about action tremor, and 4 about asymmetry. A receiver operating characteristics curve analysis revealed that the 9-item questionnaire showed a good discrimination ability, with a sensitivity of 88% and a specificity of 84%. CONCLUSIONS: The developed Hand Tremor Questionnaire might be a good screening tool for hand tremors in patients with PD and ET.

A Novel Heterozygous ANO3 Mutation with Basal Ganglia Dysfunction in a Patient with Adult-Onset Isolated Segmental Dystonia

No abstract available.

Multifocal Myoclonus as a Manifestation of Acute Cerebral Infarction Recovered by Carotid Arterial Stenting

No abstract available.

Diagnostic Challenge of Diffusion Tensor Imaging in a Patient With Hemiplegia After Traumatic Brain Injury

A 51-year-old man showed hemiplegia on his right side after a traumatic brain injury (TBI). On initial brain computed tomography (CT) scan, an acute subdural hemorrhage in the right cerebral convexity and severe degrees of midline shifting and subfalcine herniation to the left side were evident. On follow-up brain magnetic resonance imaging (MRI), there were multiple microhemorrhages in the left parietal and occipital subcortical regions. To explain the occurrence of right hemiplegia after brain damage which dominantly on the right side of brain, we used diffusion tensor imaging (DTI) to reconstruct the corticospinal tract (CST), which showed nearly complete injury on the left CST. We also performed motor-evoked potentials, and stimulation of left motor cortex evoked no response on both sides of upper extremity. We report a case of patient with hemiplegia after TBI and elucidation of the case by DTI rather than CT and MRI.

Erratum to: The KMDS-NATION Study: Korean Movement Disorders Society Multicenter Assessment of Non-Motor Symptoms and Quality of Life in Parkinson's Disease NATION Study Group

The original version of this article contained wrong informations of some authors which should be changed.

The KMDS-NATION Study: Korean Movement Disorders Society Multicenter Assessment of Non-Motor Symptoms and Quality of Life in Parkinson's Disease NATION Study Group

BACKGROUND AND PURPOSE: Nonmotor symptoms (NMS) in Parkinson's disease (PD) have multisystem origins with heterogeneous manifestations that develop throughout the course of PD. NMS are increasingly recognized as having a significant impact on the health-related quality of life (HrQoL). We aimed to determine the NMS presentation according to PD status, and the associations of NMS with other clinical variables and the HrQoL of Korean PD patients. METHODS: We surveyed patients in 37 movement-disorders clinics throughout Korea. In total, 323 PD patients were recruited for assessment of disease severity and duration, NMS, HrQoL, and other clinical variables including demographics, cognition, sleep scale, fatigability, and symptoms. RESULTS: In total, 98.1% of enrolled PD subjects suffered from various kinds of NMS. The prevalence of NMS and scores in each NMS domain were significantly higher in the PD group, and the NMS worsened as the disease progressed. Among clinical variables, disease duration and depressive mood showed significant correlations with all NMS domains (p<0.001). NMS status impacted HrQoL in PD (rS=0.329, p<0.01), and the association patterns differed with the disease stage. CONCLUSIONS: The results of our survey suggest that NMS in PD are not simply isolated symptoms of degenerative disease, but rather exert significant influences throughout the disease course. A novel clinical approach focused on NMS to develop tailored management strategies is warranted to improve the HrQoL in PD patients.

Evaluation of the Effectiveness of the Heavy-Light Chain Quantitative Test

BACKGROUND: The heavy-light chain (HLC) quantitative test can identify and quantify the heavy and light chains of each immunoglobulin class. The purpose of this study was to evaluate the effectiveness of the HLC quantitative test. METHODS: To evaluate the effectiveness of the HLC quantitative test, a systemic review of the literature, using Ovid-MEDLINE, EMBASE, Cochrane library, and eight domestic databases including KoreaMed, was performed until October 10, 2013. We included five cohort studies and one diagnostic evaluation study in the final evaluation. Two reviewers independently assessed the quality of the included studies and extracted data from the studies. The quality of the studies was assessed according to the Scottish Intercollegiate Guidelines Network (SIGN) tool. RESULTS: A correlation between the HLC quantitative test and previous assays was evaluated in one study, which enrolled patients with increased monoclonal IgA. The correlation coefficient was reported as 0.94 in this study. The clinical significance of the quantitative HLC test to predict a prognosis was also reported in five cohort studies. The survival rate in patients with higher HLC ratio was significantly lower and the increased IgA kappa/lambda ratio or IgM kappa/lambda ratio was significantly correlated with higher survival rate in patients with monoclonal gammaglobulinemia. CONCLUSIONS: The HLC quantitative test is an effective test that can quantitatively measure the identified immunoglobulin type and predict the prognosis of patients with monoclonal gammopathy.

Diagnostic Effectiveness of PCR-based Tests Detecting BRAF Mutation for Treating Malignant Melanoma: A Systematic Review

BACKGROUND: We aimed to conduct a systematic review of previously published material to evaluate the diagnostic effectiveness of PCR-based tests in detecting BRAF mutation. METHODS: Eight Korean databases, including KoreaMed, Ovid-MEDLINE, and Ovid-EMBASE were used to identify relevant published studies. Nine studies describing usage of real-time PCR, dual-priming oligonucleotide (DPO)-multiplex real-time PCR and allele-specific PCR were included in the final assessment. Two reviewers screened all references independently for assessing the quality of the included articles and extracted data. RESULTS: The rate of detection of the BRAF mutations was lower in the Korean population (11.1-17.2%) than that in the Western population (36.7-82.2%). The diagnostic accuracy of the BRAF mutation tests was assessed on the basis of four previous reports, all of which employed real-time PCR on malignant melanoma. In fact, the diagnostic accuracy of real-time PCR was found to be higher than that of sequencing tests (pooled sensitivity, 0.96; pooled specificity, 0.83; and summary receiver operating characteristic area under the curve, 0.99). In addition, we found that there was no publication bias in meta-analysis. The concordance rate of the BRAF mutation tests compared with reference tests was 87.9-98.1%. CONCLUSIONS: Real-time PCR for the detection of the BRAF gene mutation is an effective technology for determining the appropriateness of treatment with BRAF kinase inhibitors in terminal stage cancer as well as metastatic and malignant melanoma.

Drug-Induced Parkinsonism

Drug-induced parkinsonism (DIP) is the second-most-common etiology of parkinsonism in the elderly after Parkinson's disease (PD). Many patients with DIP may be misdiagnosed with PD because the clinical features of these two conditions are indistinguishable. Moreover, neurological deficits in patients with DIP may be severe enough to affect daily activities and may persist for long periods of time after the cessation of drug taking. In addition to typical antipsychotics, DIP may be caused by gastrointestinal prokinetics, calcium channel blockers, atypical antipsychotics, and antiepileptic drugs. The clinical manifestations of DIP are classically described as bilateral and symmetric parkinsonism without tremor at rest. However, about half of DIP patients show asymmetrical parkinsonism and tremor at rest, making it difficult to differentiate DIP from PD. The pathophysiology of DIP is related to drug-induced changes in the basal ganglia motor circuit secondary to dopaminergic receptor blockade. Since these effects are limited to postsynaptic dopaminergic receptors, it is expected that presynaptic dopaminergic neurons in the striatum will be intact. Dopamine transporter (DAT) imaging is useful for diagnosing presynaptic parkinsonism. DAT uptake in the striatum is significantly decreased even in the early stage of PD, and this characteristic may help in differentiating PD from DIP. DIP may have a significant and longstanding effect on patients' daily lives, and so physicians should be cautious when prescribing dopaminergic receptor blockers and should monitor patients' neurological signs, especially for parkinsonism and other movement disorders.

Reversible Splenial Lesion in a Patient With Acute Alcohol Intoxication

No abstract available.

Resilience in Patients with Parkinson's Disease / 성인간호학회지

PURPOSE: The aim of this study was to investigate the level of resilience and related factors in patients with Parkinson's disease (PD) in Korea. METHODS: Data were obtained from 148 patients using the Resilience Scale (RS), Beck's Depression Inventory (BDI), and Spielberger's Anxiety Inventory (AI). RESULTS: The mean scores of the RS, BDI, and AI were 127.7+/-21.6, 12.9+/-9.3, and 41.9+/-11.1, respectively. The RS score was strongly correlated with the BDI score (r=-.531, p<.001) and the AI (r=-.572, p<.001). The resilience was significantly revealed by household income (F=4.002, p=.009) and presence of a hobby (t=-3.300, p=.001). In addition, resilience was significantly correlated with age of disease onset (r=.164, p=.046), years of living with PD (r=-.262, p=.001), and the length of treatment with levodopa (r=-.283, p<.001). From the stepwise multiple regression analysis, the most important factors related to the RS score were the AI score, household income, and length of treatment with levodopa. CONCLUSION: Understanding these factors is essential for developing effective interventions to improve resilience in patients with PD.

Characteristics of aac(6')-Ib-cr Gene in Extended-Spectrum beta-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Isolated from Chungnam Area / 대한진단검사의학회지

BACKGROUND: Concomitant quinolone resistance in extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae is a crucial problem in the clinical management of infections. In foreign countries, the fluoroquinolone acetylating aminoglycoside-(6)-N-acetyltransferase (aac[6']-Ib-cr) gene, a novel plasmid-mediated quinolone resistance determinant has been reported to occur in conjunction with qnr. We aim to investigate the prevalence and characteristics of concomitant aac(6')-Ib-cr and qnr expression in ESBL-producing Escherichia coli and Klebsiella pneumoniae in Korea. METHODS: Between December 2007 and April 2008, we collected 60 and 69 clonally unrelated non-repetitive clinical isolates of ESBL-producing E. coli and K. pneumoniae, respectively. We studied the expressions of 11 types of ESBL-encoding genes, 4 types of 16s rRNA methylase genes; rmtA, rmtB, rmtC and armA, 3 types of qnr genes; qnrA, qnrB, qnrS and aac(6')-Ib. The presence of aac(6')-Ib-cr variants was detected by sequencing. The involvement of integrons was studied using multiplex PCR and sequencing of gene-cassette arrays. Conjugation experiments were performed to confirm plasmid-mediated resistance and the relationships among coharbored genes. RESULTS: We observed a high prevalence of the cr variant (61.1%) of aac(6')-Ib, and the prevalence of this variant in qnr and aac(6')-Ib-coharboring isolates (67.4%) was higher than in qnr-negative isolates (51.7%). The high prevalence of the cr variant was significantly related to the high minimum inhibitory concentrations (MICs) of ciprofloxacin, tobramycin, and amikacin and indicated the statistically significant roles of qnrB, qnrS, rmtA, and rmtB in quinolone and aminoglycoside resistance. CONCLUSIONS: The aac(6')-Ib-cr variants were widespread and showed significant relation to the high-level quinolone and aminoglycoside resistance in ESBL-producing E. coli and K. pneumoniae.

The Effect of Bilateral Subthalamic Nucleus Stimulation in Parkinson's Disease: Experiences From 6 Month Follow-up in Sinchon Severance Hospital

BACKGROUND: Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) is known as an effective neurosurgical procedure for the treatment of advanced Parkinson disease (PD). Although short- and long-term effects of STN stimulation in PD are relatively well known, an interim analysis of its efficacy is essential for us to continue with this procedure in the future. We present the clinical outcome of 6 month follow-up in patients who were assessed in our hospital after bilateral STN stimulation. METHODS: Twenty-nine patients with PD treated with bilateral STN DBS were included in this study. The effect of STN DBS was assessed at 6 months after surgery, which included the followings; motor disability in 'DBS- off/on, medication-off/on' states, activity of daily living (ADL) in 'medication-off/on' states, levodopa-induced motor complication, daily levodopa and levodopa-equivalent dosage, neuropsychological assessment and quality of life. RESULTS: Nineteen patients completed the follow-up assessment. STN stimulation produced significant improvements in the motor disability score both during 'medication-off' and 'medication-on' states. The ADL score was improved only in 'medication-off' states. The amount of levodopa-induced dyskinesia and response fluctuation also significantly decreased. Scores of Korean version of Mini-mental status examination (K-MMSE), Korean version of Consortium to Establish a Registry for Alzheimer's Disease (CERAD-K) and Beck Depression Inventory (BDI) did not change. Daily levodopa and levodopa-equivalent dosages were significantly reduced. No serious side effect was encountered. CONCLUSIONS: Bilateral STN DBS is a relatively safe and beneficial treatment for PD patients with levodopa- induced motor complications. In order to obtain a better prognosis in the future, we should assess the long-term outcome and the clinical predictive factors of STN DBS.

Trinucleotide Repeats Number in SCA2, SCA3, and SCA17 in Early-Onset Parkinson's Disease

BACKGROUND: Abnormal expansion of trinucleotide repeats in genes causing spinocerebellar ataxias such as SCA2, SCA3, SCA8, or SCA17 was reported in sporadic or familial Parkinson's disease. Genetic factors play an important role especially in early-onset Parkinson's disease (EOPD). To investigate mutations of ATXN2, ATXN3, and TBP as a possible cause in Korean EOPD, we analyzed mutations in these genes. We also investgated the possibility that trinucleotide repeats numbers in these genes contribute to the development of EOPD. METHODS: Mutation analysis of ATXN2, ATXN3, and TBP was done in 153 EOPD defined as age-at-onset before 51. Distribution of CAG repeats numbers were compared between EOPD and age- and sex-matched controls. RESULTS: No patients with EOPD had CAG repeats numbers in ATXN2, ATXN3, and TBP in mutation range. There was no difference in the distribution of CAG repeats between EOPD and controls, although we found a trend that CAG repeats numbers in ATXN3 appear larger in EOPD than in controls. CONCLUSIONS: Mutations of genes causing SCA2, SCA3, or SCA17 may not be a common genetic cause in Korean EOPD.

Different Modulation of the Cortical Silent Period by Two Phases of Short Interval Intracortical Inhibition

PURPOSE: To investigate the influence of 2 phases of short interval intracortical inhibition (SICI) on the cortical silent period (SP). MATERIALS AND METHODS: Single- and paired-pulse transcranial magnetic stimulations (TMSs) at 1 and 2.5ms interstimulus intervals (ISIs) were applied to the left motor cortex in 12 healthy subjects while their right hand muscles were moderately activated. Conditioning stimulation intensity was 90% of the active motor threshold (AMT). Test stimulation intensities were 120, 140, 160, 180, 200, 220, 240, 260% of the AMT and at 100% of the maximal stimulator output, the order of which was arranged randomly. The rectified electromyography area of motor evoked potential (MEP) and duration of the SP were measured off-line using a computerized program. RESULTS: At high-test stimulation intensities, MEP areas were saturated in both single- and paired-pulse stimulations, except that saturated MEPs were smaller for the paired-pulse TMS at 1ms ISI than for the other conditions. As the test stimulation intensity increased, SP was progressively prolonged in both single- and paired-pulse stimulations but was shorter in paired-pulse than single-pulse TMS. Overall, the ratio of SP duration/MEP area was comparable between single- and paired-pulse TMS except for the paired-pulse TMS at 1 ms ISI with a test stimulation intensity at 140-180% of the AMT, in which the ratio was significantly higher than in the single pulse TMS. CONCLUSION: These results suggest that 2 phases of SICI modulate MEP saturation and SP duration differently and provide additional evidence supporting the view that 2 phases of SICI are mediated by different inhibitory mechanisms.