Relationship between Hearing Loss and Dementia Differs According to the Underlying Mechanism

Background@#and Purpose The associations between hearing loss (HL) and the mechanisms underlying cognitive impairment (CI) remain unclear. We evaluated the effects of clinical factors, vascular magnetic resonance imaging (MRI) markers, and CI mechanisms on HL. @*Methods@#In total, 112 patients with CI (59% demented) and subjective HL prospectively underwent MRI, amyloid positron-emission tomography (PET), hearing evaluations, and neuropsychological tests including a language comprehension test. Patients were categorized into pure-Alzheimer’s disease-related CI (ADCI), pure-Lewy-body disease-related CI (LBCI), mixed-ADCI/LBCI, and non-ADCI/LBCI groups based on clinical features and PET biomarkers. @*Results@#The risk of peripheral HL [defined as a pure-tone average (PTA) threshold >40 dB] was higher in the pure-LBCI group than in the pure-ADCI and mixed-ADCI/LBCI groups, and lower in the presence of ADCI. The non-ADCI/LBCI group had the most-severe vascular MRI markers and showed a higher risk of peripheral HL than did the pure-ADCI and mixed-ADCI/LBCI groups. While the pure-LBCI group had a higher risk of comprehension dysfunction than the pure-ADCI group regardless of the PTA and the score on the Korean version of the Mini Mental State Examination (K-MMSE), those in the pure-LBCI group even with a better K-MMSE score had a risk of comprehension dysfunction comparable to that in the mixed-ADCI/LBCI group due to a worse PTA. @*Conclusions@#Peripheral HL could be associated with the absence of significant β-amyloid deposition in patients with CI and characteristic of the pure-LBCI and non-ADCI/LBCI groups.

Relationship between Hearing Loss and Dementia Differs According to the Underlying Mechanism

Background@#and Purpose The associations between hearing loss (HL) and the mechanisms underlying cognitive impairment (CI) remain unclear. We evaluated the effects of clinical factors, vascular magnetic resonance imaging (MRI) markers, and CI mechanisms on HL. @*Methods@#In total, 112 patients with CI (59% demented) and subjective HL prospectively underwent MRI, amyloid positron-emission tomography (PET), hearing evaluations, and neuropsychological tests including a language comprehension test. Patients were categorized into pure-Alzheimer’s disease-related CI (ADCI), pure-Lewy-body disease-related CI (LBCI), mixed-ADCI/LBCI, and non-ADCI/LBCI groups based on clinical features and PET biomarkers. @*Results@#The risk of peripheral HL [defined as a pure-tone average (PTA) threshold >40 dB] was higher in the pure-LBCI group than in the pure-ADCI and mixed-ADCI/LBCI groups, and lower in the presence of ADCI. The non-ADCI/LBCI group had the most-severe vascular MRI markers and showed a higher risk of peripheral HL than did the pure-ADCI and mixed-ADCI/LBCI groups. While the pure-LBCI group had a higher risk of comprehension dysfunction than the pure-ADCI group regardless of the PTA and the score on the Korean version of the Mini Mental State Examination (K-MMSE), those in the pure-LBCI group even with a better K-MMSE score had a risk of comprehension dysfunction comparable to that in the mixed-ADCI/LBCI group due to a worse PTA. @*Conclusions@#Peripheral HL could be associated with the absence of significant β-amyloid deposition in patients with CI and characteristic of the pure-LBCI and non-ADCI/LBCI groups.

Effectiveness of Exercise on the Sequence Effect in Parkinson’s Disease

Objective@#To determine the benefits of motor training on the sequence effect (SE), an essential component of bradykinesia in Parkinson’s disease (PD). @*Methods@#Seven patients with de novo PD participated in this study. The patients performed regular pentagon drawing tests and exercises during four visits. The first two visits occurred before the start of medication, and the last two visits occurred at least six months after the start of medication. We assessed the severity of bradykinesia and SE at each visit and compared the results before and after exercise in both the de novo and treatment conditions. @*Results@#In the de novo condition, the severity of bradykinesia significantly improved after motor training (p = 0.018), but it did not resolve and only showed a trend of improvement after treatment (p = 0.068). The severity of the SE decreased significantly in the drug-naïve condition (p = 0.028) but not after medication (p = 0.273). @*Conclusion@#Our study suggests that regular motor training may be beneficial for the SE in PD.

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

No abstract available.

Sleepiness and Depression in Parkinson's Disease Patients Treated with Ropinirole and Levodopa

OBJECTIVE: We aimed to investigate the effect of ropinirole on excessive daytime sleepiness (EDS) and depression in Parkinson’s disease (PD) with a large population. METHODS: We conducted a cross-sectional observational study at nine hospitals in Korea between April 24, 2013, and April 22, 2015. We analyzed the demographic and clinical features, other medical history, history of antiparkinsonian medication within 6 months, Hoehn and Yahr stage (HY stage), Unified Parkinson’s Disease Rating Scale (UPDRS) part II and III, Epworth Sleepiness Scale (ESS), and 30-item Geriatric Depression Scale (GDS-30). RESULTS: Four-hundred-thirteen patients with PD (mean age: 65.2 ± 9.0 years; men: 227 patients) were analyzed. Multivariate logistic regression analysis showed that age at examination, UPDRS II, and GDS-30 were independent risk factors for EDS and that sex, UPDRS II, and ESS were independent risk factors for depression. CONCLUSION: Our large group study did not find any significant associations of ropinirole with EDS and depression in Korean PD patients.

The Prevalence and Incidence of Parkinson's Disease in South Korea: A 10-Year Nationwide Population: Based Study

BACKGROUND: The prevalence and incidence of Parkinson's disease (PD) are important for supporting the better comprehension of disease aspects and helping public health planning. Our aim is to evaluate the prevalence and incidence in South Korea between 2004 and 2013. METHODS: This retrospective, nationwide, longitudinal population-based study used National Health Insurance Service-National Sample Cohort Database to define patients with PD from 2004 to 2013 based on having Korean Classification of Diseases code G20, which were assigned by neurologists, and being prescribed PD medication. Annual prevalence and incidence were calculated. RESULTS: The prevalence of PD per 100,000 of population was 41.4 in 2004 and 142.5 in 2013, and there was 13.2% yearly increase over the 10 years. However, the incidence of PD per 100,000 of population increased steadily from 20.2 in 2004 to 53.1 in 2013. The prevalence and incidence were higher in women than in men. CONCLUSIONS: Our data show that there was an increasing trend in the prevalence and incidence of PD from 2004 to 2013, particularly in 70 years and older.

Factors Related to Outcomes of Subthalamic Deep Brain Stimulation in Parkinson's Disease

OBJECTIVE: Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective treatment of choice for patients with advanced idiopathic Parkinson's disease (PD) who have motor complication with medication. The objectives of this study are to analyze long-term follow-up data of STN DBS cases and to identify the factors related to outcomes. METHODS: Fifty-two PD patients who underwent STN DBS were followed-up for more than 3 years. The Unified Parkinsons Disease Rating Scale (UPDRS) and other clinical profiles were assessed preoperatively and during follow-up. A linear regression model was used to analyze whether factors predict the results of STN DBS. We divided the study individuals into subgroups according to several factors and compared subgroups. RESULTS: Preoperative activity of daily living (ADL) and the magnitude of preoperative levodopa response were shown to predict the improvement in UPDRS part II without medication, and preoperative ADL and levodopa equivalent dose (LED) were shown to predict the improvement in UPDRS part II with medication. In UPDRS part III with medication, the magnitude of preoperative levodopa response was a predicting factor. CONCLUSION: The intensity of preoperative levodopa response was a strong factor for motor outcome. And preoperative ADL and LED were strong factors for ADL improvement. More vigorous studies should be conducted to elucidate how levodopa-induced motor complications are ameliorated after STN DBS.

The Role of Subcortical Regions in Speech Production

BACKGROUND: Speech production requires accurate coordination of the speech musculature, and is dependent upon cooperation among cortical and subcortical structures. Multiple subcortical structures, including the basal ganglia, thalamus, and cerebellum, are involved in several parallel and segregated cortical-subcortical-cerebellum circuits. These circuits serve critical functions in integrating neural networks that modulate speech motor behaviors. Previous studies on speech disorders linked to subcortical lesions have been limited to perceptual evaluations of speech in patients with lesions. However, more recent studies using neuroimaging have confirmed the results of the lesion studies and provided further evidence of the important contributions of the subcortical structures to speech motor control. METHODS: We reviewed recent research literature on both behavioral and functional neuroimaging to reveal the role of subcortical structures in speech production. A review of this topic was conducted by searching the literature and electronic databases. RESULTS: Based on numerous articles, we found that the basal ganglia, thalamus, and cerebellum make different contributions to the modulation of speech-related variables. The cerebellum is the structure that is most strongly associated with speech rate, complexity, and timing. CONCLUSIONS: We conclude that the subcortical structures may play critical functions in speech production. The function of each structure involves the stimulation of cortical regions through the neural circuits and neurotransmitters. Thus, the function of the subcortical structures should be understood within the paradigm of neural networks.

Camptocormia Due to Selective Paraspinal Muscle Atrophy

No abstract available.

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.

Impaired Tactile Spatial Discrimination in Parkinson's disease

BACKGROUND: The basal ganglia plays a major role in regulating motor, cognitive and emotional functions. In addition, it has been proposed that the functions of the basal ganglia is also related to control of sensory discrimination and sensorimotor integration. One possible way to test this hypothesis would be to investigate sensory functions in patients with various diseases affecting basal ganglia functions. Since idiopathic Parkinson's disease (IPD) is caused by selective impairment of basal ganglia functions, it could be a good model for this purpose. METHODS: We measured the grating resolution threshold (GRT) using the JVP (Johnson-Van Boven-Phillips) dome in 52 patients with IPD and 25 age-matched healthy controls. Statistical analysis employed unpaired t-test, paired t-test and simple regression analysis. P-values less than 0.05 were considered as significant. RESULTS: Patients showed significantly higher GRT than controls (3.07 +/- 0.74 vs 2.03 +/- 0.80; p<0.05). In patients, the mean GRT was not different between symptomatically dominant and non-dominant hands (3.10 +/- 0.95 vs 2.93 +/- 0.82). In the patients with hemiparkinsonism, GRT was also significantly higher in asymptomatic hands compared with controls (3.00 +/- 0.71 vs 2.03 +/- 0.80; p<0.05). The severity of sensory dysfunction in patients was not correlated with symptom duration or to symptom severity, measured by the modified Columbia rating scale (MCRS). CONCLUSIONS: The present results demonstrate that spatial discrimination is impaired in IPD, suggesting the basal ganglia plays a role in sensory regulation.

A Case of HIV Infection with Progressive Cerebellar Dysfunction as Initial Manifestation / 감염과화학요법

Human immunodeficiency virus (HIV) is known to affect the nervous system at all levels. Neurological complications of HIV occur at all stage of HIV infection, but cerebellar degeneration associated with HIV infection in the absence of cognitive impairment is exceedingly rare. We report a case of HIV infection, in which cerebellar degeneration was the first clinical manifestation. The brain MRI showed marked isolated cerebellar atrophy with severe cerebellar degeneration, but the patient did not have cognitive dysfunction. She was diagnosed as cerebellar form of progressive multifocal leukoencephalopathy with HIV infection. HIV infection should be considered in the diagnosis of any patient with cerebellar dysfunction of unclear origin.

A Case of HIV Infection with Progressive Cerebellar Dysfunction as Initial Manifestation / 감염과화학요법

Human immunodeficiency virus (HIV) is known to affect the nervous system at all levels. Neurological complications of HIV occur at all stage of HIV infection, but cerebellar degeneration associated with HIV infection in the absence of cognitive impairment is exceedingly rare. We report a case of HIV infection, in which cerebellar degeneration was the first clinical manifestation. The brain MRI showed marked isolated cerebellar atrophy with severe cerebellar degeneration, but the patient did not have cognitive dysfunction. She was diagnosed as cerebellar form of progressive multifocal leukoencephalopathy with HIV infection. HIV infection should be considered in the diagnosis of any patient with cerebellar dysfunction of unclear origin.

Complications of Diagnostic Intra-arterial Cerebral Angiography in Ischemic Cerebrovascular Diseases

BACKGROUND: Intra-arterial cerebral angiography, which is a prerequisite for carotid endarterectomy and angioplasty, carries some risks but provides the best visualization of the cerebral vasculatures. We attempted to examine the inci-dence of complications associated with cerebral angiography in patients with ischemic stroke. METHODS: We retrospec-tively reviewed the medical records of patients with ischemic stroke or transient ischemic attack (TIA) who underwent the digital subtraction cerebral angiography. Four hundred nineteen procedures were performed between October 1994 and August 1999. The systemic, local, and neurologic complications were evaluated. The neurologic complications were defined as occurrences of any new focal neurologic deficits or progressions of the preexisting neurologic deficits during or within 24 hours after the procedure. RESULTS: There were 5 systemic (1.2%), 17 local (4.1%), and 10 neuro-logic (2.4%) complications. The neurologic complications were reversible within 7 days in 6 (1.4%) and were persistent after 7 days in 4 (1.0%). Six out of 10 patients with neurologic complications had previous stroke or TIA. The angio-graphic studies revealed the stenosis or obstruction of the relevant arteries in 7 patients. CONCLUSIONS: Cerebral angiog-raphy in patients with ischemic stroke was associated with 1.4 % reversible and 1.0% persistent neurologic complica-tions, all of which developed after the angiographic procedure. The history of previous stroke or TIA and the presence of severe stenosis or occlusion of the symptomatic arteries may carry a high risk of neurologic complications. (J Korean Neurol Assoc 19(4):354~358, 2001)

Dihydroergocryptine in the Treatment of Parkinson's Disease / 대한정신약물학회지

OBJECTIVE: This study was performed to investigate the safety and clinical efficacy of Dihydroergocryptine (DHE) in Parkinson's disease. METHOD: Study subjects were 30 patients with idiopathic Parkinson's disease. DHE was administered orally for 3 months. Parkinsonian severity was assessed by UPDRS, UPDRS-motor score, modified Columbia Rating Scale and the number of finger tapping in both hands for 20 seconds. Patients were asked to report any side-effects related to DHE. Various laboratory tests as well as EKG were performed to exclude possible side-effects. RESULTS: Eight patients were dropped out during the first month of DHE treatment. Although about half of the patients experienced dizziness, indigestion and nausea, most of them were mild and transient. Laboratory tests showed mild and reversible increase in liver enzyme level in 4 patients. Three-month DHE therapy significantly reduced parkinsonian severity that 32%, 44%, 52% reduction of UPDRS, UPDRS-motor and MCRS was observed respectively. CONCLUSION: These results suggest that DHE is a safe and effective dopamine agonist and can be used in treatment of Parkinson's disease.

Temporal Bone Magnetic Resonance Imaging Study in Hemifacial Spasm

BACKGROUND: Hemifacial spasm (HS) has been attributed frequently to vascular compression of facial nerve root exit zone from brainstem. A recent brain CT scan study showed that patients with HS had narrower posterior fossa than normal controls. However, cause relationship between narrowed posterior fossa and vascular tortuosity is unknown. METHODS: In 25 patients with HS and 29 controls, using temporal bone MRI, we measured petrous angle (PA) and pons diameter index (PDI) to define correlation between severity of posterior fossa narrowing and compression to brainstem. We compared severity of narrowing of posterior fossa between patients with and without tortuous arteries in posterior fossa. We also compared degree of narrowing of posterior fossa and clinical severity of HS. RESULTS: The mean (+/-standard deviation) of PA of 24 patients with HS (115.5 +/-6.0 degree) was significantly smaller than that of controls ( 118.6 +/- 4.8 degree). The mean (+/-standard deviation) of PDI of patients with HS (82.5 +/-4.7%) was significantly greater than that of controls (77.3 +/-3.7%). However, there was no correlation between PA and PDI in patients with HS. There was no correlation between degree of narrowing of posterior fossa and clinical severity of HS. CONCLUSIONS: Patients with HS have narrower posterior fossa as compared with controls. However, narrow posterior fossa does not seem to be a single important factor causing deformity of brainstem or tortuous arteries in posterior fossa.

D3 and D5 Dopamine Receptor mRNA Expression in Peripheral Blood Mononuclear Cells from Patients with Parkinson's Disease

BACKGROUND: Among 5 subfamilies of dopamine receptors (DAR), D3 and D5 DAR are expressed on peripheral blood mononuclear cells (PBMC). Recently, those DARs have been reported to change in Parkinson's disease (PD). METHODS: We measured the DAR mRNA expression in PBMC from 15 PD patients who had never taken antiparkinson medication, and 16 age-matched healthy people by reverse transcription and quantitative competitive polymerase chain reaction. The beta-actin mRNA expression was also measured to evaluate the relative expression of DAR mRNA. RESULTS: The D3 and D5 DAR mRNA expression was not different between patients and controls. In patients, no significant cor-relation was found between DAR mRNA expression in PBMC and clinical variables such as severity and duration of symptoms, and patients' age. CONCLUSIONS: We confirmed the presence of D3 and D5 DAR in PBMC. However, their mRNA expressions were not influenced by the disease process of PD.

The Mechanism of Striatal Damage in Mice after Intraperitoneal Injection of 3-nitropropionic Acid

BACKGROUND: A newly-found mitochondrial toxin, 3-nitropropionic acid (3-NP), has been proved to induce apoptosis in the striatum. Although striatal lesions produced by 3-NP could develop through an excitotoxic mechanism, the exact relationship between apoptosis induction and excitotoxicity after 3-NP treatment is still not clear. We investigated the role of excitotoxicity and oxidative stress on apoptosis induction within the striatum following intra-peritoneal injection of 3-NP. METHODS: 3-NP was injected for 5 days intra-peritoneally in three month-old mice. One day after the last injection, animals were decapitated. To confirm the presence of apoptosis, we performed in-situ detection of DNA fragmentation by using TUNEL technique and agarose gel elctrophoresis after DNA extraction from striatum. To examine the effect of frontal cortex removal on 3-NP-indeced apoptosis, we removed left frontal cortex by aspiration. For excitotoxicity, NMDA-receptor antagonist-MK 801, non-NMDA antagonist-NBQX, and saline were injected intraperitoneally before 3-NP treatment To detect superoxide, we administered hydroethidium (HEt: 200 ul; 1mg/ml) into the jugular vein 2 days after 3-NP, and the density of oxidized HEt in samples were examined under flouscent microscope. We performed caspase staining to test immunoreactivity of caspase 3 in samples. RESULTS: The TUNEL positive cells were not observed in the striatum ipsilateral to the frontal cortex-removed side, but found in the contralateral striatum. Superoxide radicals measured by using HEt and caspase immunoreactivity were also significantly weaker in the striatum ipsilateral to the frontal cortex-removed side than the contralateral striatum. TUNEL staining revealed less apoptotic changes in the striatum of MK801-treated group than NBQX-or saline-treated groups. DNA laddering on agarose gel electrophoresis was observed in the striatum of NBQX- or saline-treated mice, but not found in MK 801-treated group. CONCLUSION: We demonstrated that removal of the corticostriatal glutamate pathway reduced superoxide production as well as apoptosis induced by 3-NP and NMDA receptor antogonist, but not non-NMDA antagonist, prevented 3-NP-induced apoptosis in the striatum. These results suggest that NMDA-mediated glutamatergic excitotokicity plays an important role in 3-NP related striatal damage.