Sleep Related Problems as a Nonmotor Symptom of Dentatorubropallidoluysian Atrophy

Dentatorubropallidoluysian atrophy (DRPLA) is a neurodegenerative disease caused by an expansion of a cytosine-adenine-guanine (CAG) repeat encoding a polyglutamine tract in the atrophin-1 protein. Unlike other CAG repeat diseases, sleep related problems have not been reported in patients with DRPLA. There was a 65-year-old man and his family with DRPLA. They suffered from seizure, gait disturbance, and cognitive decline. The patients commonly showed dream enacting sleep disorder, insomnia. The results from overnight polysomnography showed rapid eye movement (REM) without atonia in patients with DRPLA. The man died 2 years after diagnosis and was subjected for brain autopsy. We report REM sleep behavior disorders in patients with DRPLA confirmed with polysomnography with pathological description of the patient.

Individual Therapeutic Singing Program for Vocal Quality and Depression in Parkinson's Disease

OBJECTIVE: Patients with Parkinson's disease (PD) frequently experience depression associated with voice problems. Singing involves the use of similar muscles and the neural networks associated with vocal function and emotional response. The purpose of this study is to enhance vocal quality and depressive symptoms of patients with PD using individual singing program. METHODS: The Individual Therapeutic Singing Program for PD (ITSP-PD) was conducted by a certified music therapist. In total, nine PD patients with a subjective voice problem or depression participated in 6 sessions over 2 weeks. We measured the Maximum Phonation Time (MPT) via the Praat test, the Voice Handicap Index (VHI), the Voice-Related Quality of Life (V-RQOL) and the Geriatric Depression Scale (GDS). RESULTS: In total, 8 out of 9 patients completed all the sessions; 6 out of 8 patients participated in the follow-up test after 6 months. A statistically significant change in MPT (p = 0.011) was observed between the pre- and post-tests. The VHI (p = 0.035) and the GDS (p = 0.018) were significantly lower in the post-test. In the pre-, post-, and follow-up tests, the MPT (p = 0.030), V-RQOL (p = 0.008), and GDS (p = 0.009) were significantly changed. CONCLUSION: The ITSP-PD based on neurological singing therapy for PD showed therapeutic possibility for vocal function and depression in patients with PD. Our findings suggest the need for a randomized study to examine the continuing positive effects of the ITSP-PD over a longer period of time.

Unilateral Ptosis with Bilateral Incomplete Ophthalmoplegia as the Initial Presentation in Metastatic Cancer / 이화의대지

Orbital metastases are rare and predominantly unilateral occurrences. Bilateral metastases affecting the extraocular muscles are extremely rare. A few case reports of bilateral metastases to extraocular muscles described binocular diplopia with conspicuous bilateral external ophthalmoplegia as an initial symptom. We report a case in which unilateral ptosis was an initial symptom and bilateral incomplete ophthalmoplegia was found on initial neurologic examination in invasive ductal carcinoma of the breast. The patient had hormone receptor-positive breast cancer, and so was treated by hormonal therapies and closely monitored. The presence of a secondary orbital lesion presents many difficulties of differential diagnosis and treatment. A thorough neurologic examination to detect ocular manifestations is most important for localization and broad differential diagnosis including mechanical orbital metastatic lesion.

Effect of Individual and District-level Socioeconomic Disparities on Cognitive Decline in Community-dwelling Elderly in Seoul

This study was to investigate the effects of individual and district-level socioeconomic status (SES) on the development of cognitive impairment among the elderly. A 3-year retrospective observational analysis (2010–2013) was conducted which included 136,217 community-dwelling healthy elderly who participated in the Seoul Dementia Management Project. Cognitive impairment was defined as 1.5 standard deviations below the norms on the Mini-mental status examination. In the individual lower SES group, the cumulative incidence rate (CIR) of cognitive impairment was 8.7% (95% confidence interval [CI], 8.64–8.70), whereas the CIR in the individual higher SES group was 4.1% (95% CI, 4.08–4.10). The CIR for lower district-level SES was 4.7% (95% CI, 4.52–4.86), while that in the higher district-level SES was 4.3% (95% CI, 4.06–4.44). There were no additive or synergistic effects between individual and district-level SES. From this study, the individual SES contributed 1.9 times greater to the development of cognitive impairment than the district-level SES, which suggests that individual SES disparities could be considered as one of the important factors in public health related to cognitive impairment in the elderly.

Impact of Vascular Risk Factors, Axial Medial Temporal Atrophy, White Matter Hyperintensity on Cognitive Outcome in Alzheimer's Diseases

BACKGROUND: There is epidemiologic evidence to support vascular disease as a possible cause of Alzheimer's dementia (AD). The primary aim of this study was to determine the prevalence of vascular risk factors (vRFs) with respect to various clinical measures, such as axial-rated medial temporal lobe atrophy (MTA), ischemic white-matter changes, and cognition. The secondary aim was to determine the most significant clinical measure associated with cognitive outcome. METHODS: The study subjects comprised 198 probable AD and 38 subjective memory impairment-no cognitive impairment controls (SMI-NCI), for whom medical data including history vRF-related blood tests, clinical dementia evaluation, cognitive assessment, and brain MRI, were available. The grading of white-matter hyperintensities (WMHs) was achieved using Fazekas' method. MTA was graded by two neurologists independently based on axial T1-weighted MRI images. The prevalence of risk factors for Koreans aged > or =65 years was reviewed for comparison. RESULTS: All vRFs except smoking were more severe in the AD group than in both the SMI-NCI group and Koreans aged > or =65 years, but the high prevalence of vRFs had no impact on WMH lesions, axial MTA, or cognitive outcome. Both white-matter changes and MTA were significantly worse in AD than in SMI-NCI (p<0.001). The degree of MTA was negatively correlated with WMH grade (p<0.001), but the severity of clinical dementia was correlated only with increased axial MTA in AD (Instrumental Activities of Daily Living and Clinical Dementia Rating scores, p<0.001; Clinical Dementia Rating-Sum of Boxes score, p<0.005). CONCLUSIONS: WMHs and axial MTA were significantly more severe in the AD group than in the SMI-NCI subjects. The findings of this study indicate that worsening of cognitive dysfunction in AD appears to be driven by MTA, which is evident even in axial MTA visual grading, irrespective of WMH severity and the presence of vRFs.

Predictive Factors for Decline in Activities of Daily Living in Alzheimer's Disease Dementia with More than 2 Follow-up

BACKGROUND: Impairment in activities of daily living (ADL) is a major problem in Alzheimer's disease (AD), and is related to increased caregiver burden.The present study evaluated whether there are any components of initial dementia evaluation that could predict ADL decline in years follow-up. METHODS: The 32 subjects underwent more than two consecutive neuropsychological evaluation and maintained anti-dementia medication from the Ewha Dementia Cohort. The first clinical, neuropsychological test results, medial temporal atrophy rating and white matter ratings were correlated with the final ADL scores. The subjects were further divided into ADL-preserved and declined groups for the comparison depending on final ADL scores. RESULTS: The annual decline of the Korean Mini-mental status examination (K-MMSE) score was 1.5+/-1.2 and of the Seoul-instrumental ADL score was 6.1+/-4.6. The Factors correlated with the ADL at baseline were the clinical dementia rating, K-MMSE, memory function score and the total neuropsychological test score, left medial temporal lobe atrophy rating, and the neuropsychiatric total score. Only the neuropsychological component including total test, frontal and visuospatial function scores were statistically different between the two groups in the baseline evaluation. CONCLUSIONS: The result of our preliminary study emphasize the other study results that the initial cognitive and dementia status are the strong predictive factors not only for the initial ADL dysfunction but also for the ADL decline in years followed-up dementia cohort.

Painful Ophthalmoplegia as a Presenting Sign of Internal Carotid Artery Occlusion

No abstract available.

Painful Ophthalmoplegia as a Presenting Sign of Internal Carotid Artery Occlusion

No abstract available.

Comparison between Clinical Disabilities and Electrophysiological Values in Charcot-Marie-Tooth 1A Patients with PMP22 Duplication

BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease (CMT) type 1A (CMT1A) is the demyelinating form of CMT that is significantly associated with PMP22 duplication. Some studies have found that the disease-related disabilities of these patients are correlated with their compound muscle action potentials (CMAPs), while others have suggested that they are related to the nerve conduction velocities. In the present study, we investigated the correlations between the disease-related disabilities and the electrophysiological values in a large cohort of Korean CMT1A patients. METHODS: We analyzed 167 CMT1A patients of Korean origin with PMP22 duplication using clinical and electrophysiological assessments, including the CMT neuropathy score and the functional disability scale. RESULTS: Clinical motor disabilities were significantly correlated with the CMAPs but not the motor nerve conduction velocities (MNCVs). Moreover, the observed sensory impairments matched the corresponding reductions in the sensory nerve action potentials (SNAPs) but not with slowing of the sensory nerve conduction velocities (SNCVs). In addition, CMAPs were strongly correlated with the disease duration but not with the age at onset. The terminal latency index did not differ between CMT1A patients and healthy controls. CONCLUSIONS: In CMT1A patients, disease-related disabilities such as muscle wasting and sensory impairment were strongly correlated with CMAPs and SNAPs but not with the MNCVs or SNCVs. Therefore, we suggest that the clinical disabilities of CMT patients are determined by the extent of axonal dysfunction.

Erratum: Comparison between Clinical Disabilities and Electrophysiological Values in Charcot-Marie-Tooth 1A Patients with PMP22 Duplication

The publisher wishes to apologize for incorrectly displaying the author (Seok Beom Gwon) name. We correct his name from Seok Beom Gwon to Seok Beom Kwon.

Distal Hereditary Motor Neuropathy Type V (dHMN-V) With N88S Mutation in BSCL2 Gene

Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) gene is known to be associated with different clinical phenotypes; Silver syndrome, Charcot-Marie-Tooth type 2 with a dominant hand involvement and distal hereditary motor neuropathy type V (dHMN-V). Up to now, only two heterozygous mutations (N88S and S90L) in BSCL2 have been reported. We identified a N88S BSCL2 mutation in a dHMN-V family with a spastic gait by whole-exome sequencing. To our knowledge, this is the first report of a N88S BSCL2 mutation in Korean patient.

No correlation between COMT genotype and entacapone benefi ts in Parkinson’s disease

Catechol-O-methyltransferase (COMT) inhibitors are used to increase the bioavailability of therapeutic L-dopa. We examined the effi cacy of entacapone in Parkinson’s disease patients who had daily “off” duration of ≤2 hours, and carried different COMT polymorphisms. A total of 168 PD patients were recruited from 19 centers. Subjects were administered with 100–200 mg of entacapone in combination with each dose of L-dopa for 2 months. The clinical effi cacy was evaluated based on the activities of daily living (ADL), score on the Unifi ed Parkinson’s Disease Rating Scale (UPDRS), Hoehn and Yahr (H&Y) stage, and Clinical Global Impression (CGI). COMT polymorphisms were genotyped. 3-O-methyldopa (3-OMD) levels were measured before and after the administration of entacapone. Entacapone administration produced signifi cant improvements in the total daily “on” duration, ADL, UPDRS score, and H&Y stage. Nineteen patients (11.3%) had the low-activity COMT genotype, 68 patients (40.5%) had the intermediate-activity COMT genotype, and 81patients (48.2%) had the high-activity COMT genotype. The effi cacy, and adverse effects of entacapone therapy did not differ between the three groups. There was a signifi cant reduction in 3-OMD, but this did not differ among the three genotypes. Entacapone provided an increased “on” duration and improved motor function in all COMT genotypes.

Cerebral Adrenomyeloneuropathy with Trp77-Leu82del Mutation in ABCD1 Gene

Cerebral adrenomyeloneuropathy is a subtype of X-linked adrenoleukodystrophy with a mutation of ABCD1; however, there have been no reported cases of cerebral adrenomyeloneuropathy with myelopathy. Here we report a 20-year-old male cerebral adrenomyeloneuropathy patient with myelopathy harboring a deletion mutation of c.225-242 (Trp77-Leu82del) from exon 1 of ABCD1. His spinal cord MRI revealed high signal intensities in the cervical spinal cord. Electrophysiological and histopathologic studies revealed mixed axonal and demyelinating neuropathy.

Parasomnia Overlap Disorder Associated With Pontine Glioblastoma

Parasomnia overlap disorder is characterized by coexisting rapid eye movement (REM) sleep behavior disorder and non-REM parasomnia. We report herein an 8-year-old boy with REM sleep behavior disorder, sleep talking, and confusional arousal. Polysomnography revealed REM sleep without atonia, and arousal disorder. Neurological examination revealed bilateral ptosis, lateral gaze palsy, facial palsy, vertical nystagmus, and dysmetria. A pontine glioblastoma was found on brain magnetic resonance imaging, which could have been responsible for his neurologic deficit and sleep problem.

Peri-ictal Heart Rate Changes in Patients With Localization-Related Epilepsy

BACKGROUND: Epileptic seizures can be associated with changes in autonomic functions. This study evaluated heart rate (HR) changes at the transition from the preictal to the ictal state in patients with epileptic seizures, and investigated whether peri-ictal HR changes can help to predict electroencephalography (EEG) seizures prior to their onset. METHODS: We retrospectively studied 94 seizures in 33 patients who underwent video-EEG monitoring with scalp EEG and electrocardiography. The existence and initial timing of HR changes relative to the onset of EEG seizures were determined by analyzing consecutive RR-interval changes in 10-minute recordings. We evaluated the correlation between the peri-ictal HR changes and the type of localization-related epilepsy. RESULTS: Peri-ictal HR changes were documented in 70.2% (66/94) of all seizures, of which 62 were tachycardia (66.0%) and 4 were bradycardia (4.3%). Peri-ictal tachycardia occurred significantly with seizures as an ictal manifestation, more often in seizures with a right hemispheric onset than in those with a left hemispheric onset (77.4% vs. 50%, p=0.016). Peri-ictal HR changes were observed much earlier in seizures of mesial temporal lobe epilepsy (TLE) than in those of extratemporal lobe epilepsy (-54.4 s vs. -6.7 s, p<0.001). CONCLUSIONS: Peri-ictal HR changes were observed in 70.2% of seizures, 94% of which were tachycardia. These changes could be helpful in predicting seizure onset, especially in mesial TLE.

Predictive Factors of Neurologic Outcome in Patients With Hypoxic-Ischemic Encephalopathy After Cardiopulmonary Resuscitation

BACKGROUND: Cardiopulmonary resuscitation (CPR) can lead to various neurologic outcomes in patients with hypoxicischemic encephalopathy (HIE). This study investigated the usefulness of clinical markers and electroencephalography (EEG) in predicting the neurologic prognosis of HIE after CPR. METHODS: We reviewed the clinical findings of 51 patients with HIE, including the medical history, the duration from the onset of symptoms to the recovery of spontaneous circulation, Glasgow Coma Scale (GCS) and Full Outline of Unresponsiveness (FOUR) scores, and presence of seizure or status epilepticus. Patients were divided into three outcomes groups: death, persistent vegetative state, and recovering alertness and awareness. Digital EEG and visual and quantitative analyses were performed in each patient. For quantitative EEG (qEEG) analysis, we defined and compared the distance in the spatial band-power patterns and phase coherence patterns between healthy normal subjects and each patient. RESULTS: Patients with HIE showed a high mortality rate (54.9%, 28/51), and their neurologic prognosis was significantly related to the initial GCS and FOUR scores. In the qEEG analysis, patients' groups showed a prominent delta frequency band, and the healthy normal group presented a marked alpha predominance. As the severity decreased, the similarity in the spatial band-power pattern and functional connectivity pattern between normal subjects and patients increased. CONCLUSIONS: Low initial GCS and FOUR scores could be predictive of a poor neurologic prognosis in patients with HIE, and qEEG analysis might be a useful predictor of their neurologic outcomes.

Is Obstructive Sleep Apnea a Risk Factor of Subclinical White Matter Damages?

BACKGROUND: Obstructive sleep apnea (OSA) has been reported to increase risk of ischemic stroke. This study was performed to investigate the prevalence and relationship of subclinical white matter damages (SD) in patients with OSA. METHODS: All subjects (n = 54) had brain MRI and nocturnal polysomnogram (PSG). SD are defined by nonsymptomatic lacunar infarcts > 3 mm or periventricular white matter changes (PVWC). We analyzed the difference between OSA patients with and without SD (SD and non-SD groups), and also with and without PVWC. Using apnea-hypopnea index (AHI), we classified OSA into mild (515). RESULTS: SD group (n = 31) showed significantly increased apnea-hypopnea index (AHI), apnea index (AI) and oxygen desaturation index (ODI) compared to non-SD (n = 23). Among the 37 patients without lacunar infarctions, 14 showed PVWC while the other 23 did not have any lesions. Compared to non-SD group, SD group showed increased AHI and ODI, and decreased lowest SaO2 (p < 0.05). Similarly, AHI and ODI were higher and the lowest SaO2 was lower in patients with PVWC than without PVWC (p < 0.05). Moderate to severe OSA group showed more frequent subclinical or periventricular white matter changes than mild group (p < 0.05). CONCLUSIONS: Severity of OSA showed a positive correlation with the occurrence of subclinical white matter damages. OSA may cause subclinical white matter damages.

Dissociated Automatic-Voluntary Lower Cranial Nerve Palsies and Anarthria After Left Corona Radiata Infarction: Foix-Chavany-Marie Sydrome

Foix-Chavany-Marie Syndrome (FCMS) is characterized by anarthria and bilateral facio-pharyngo-glosso-masticatory paralysis with an automatic-voluntary dissociation, which usually develops in bilateral opercular lesions. We present a case of FCMS caused by unilateral subcortical lesion. A 54-year-old man was admitted due to acute right hemiparesis with anarthria. He had voluntary facial paresis but automatic-involuntary facial movements were preserved. MRI showed an acute left corona radiata infarction and PET revealed decreased glucose metabolism in left basal ganglia and fronto-parietal lobe.

Multiplex Analysis of Cytokines in the Serum and Cerebrospinal Fluid of Patients With Alzheimer's Disease by Color-Coded Bead Technology

Background and purpose: The availability and promise of effective treatments for neurodegenerative disorders are increasing the importance of early diagnosis. Having molecular and biochemical markers of Alzheimer's disease (AD) would complement clinical approaches, and further the goals of early and accurate diagnosis. Combining multiple biomarkers in evaluations significantly increases the sensitivity and specificity of the biochemical tests. Methods: In this study, we used color-coded bead-based Luminex technology to test the potential of using chemokines and cytokines as biochemical markers of AD. We measured the levels of 22 chemokines and cytokines in the serum and cerebrospinal fluid (CSF) of 32 de novo patients (13 controls, 11 AD, and 8 Parkinson's disease [PD]). Results: MCP-1 was the only cytokine detectable in CSF, and its levels did not differ between control and disease groups. However, the serum concentration of eotaxin was significantly higher in AD patients than in the control group. Conclusions: The analysis of multiple inflammatory mediators revealed marginal differences in their CSF and serum concentrations for the differential diagnosis of AD and PD. These results provide evidence that immunological responses are not major contributors to the pathogenesis of AD and PD.

Clinical and Genetic Characteristics in Patients of Charcot-Marie-Tooth type 2A with Mitofusin 2 (MFN2) Mutations

BACKGROUND: Mitofusin 2 (MFN2) is a membrane protein and is an essential component of mitochondrial fusion machinery. Mitochondrial fusion is essential for various biological functions in mammalian cells. Thus mutations in MFN2 are the underlying cause of Charcot-Marie-Tooth neuropathy type 2A (CMT2A). However, there has been no reports investigating the MFN2 genes in Korean CMT patients. Therefore, we investigated to find the clinical and genetic characteristics in Korean patients with the MFN2 gene mutation. METHODS: We examined the mutations of the MFN2 gene in 137 Korean CMT families. According to criteria from the European CMT consortium, CMT2 was 45 families. Mutations were confirmed by both strands sequencing. Nerve conduction studies were carried out in CMT patients having each mutation. RESULTS: Eight pathogenic mutations were found in 10 families. Six mutations (Leu92Pro, Gly127Asp, His165Arg, Ser263Pro, Arg364Trp, Met376Thr) were determined to be novel, and those were not detected in the 100 healthy controls. A de novo missense mutation was found in three CMT families (30%). The frequency of the MFN2 mutation was 22.2%, which was higher than those found in the Cx32 mutation. In CMT2A, the frequencies with early age at onset (<10 years) and flat feet were 46.2%. CONCLUSIONS: We found MFN2 mutations in patients with sporadic or dominantly inherited CMT. In the majority of cases with CMT type 2, the axonal neuropathy, may be due to MFN2 mutations.