Validation Study of the Official Korean Version of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale

Background@#and Purpose: The Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) is widely used for estimating the symptoms of Parkinson’s disease. Translation and validation of the MDS-UPDRS is necessary for non-English speaking countries and regions. The aim of this study was to validate the Korean version of the MDS-UPDRS. @*Methods@#Altogether, 362 patients in 19 centers were recruited for this study. We translated the MDS-UPDRS to Korean using the translation-back translation method and cognitive pretesting. We performed both confirmatory and exploratory factor analyses to validate the scale.We calculated the comparative fit index (CFI) for confirmatory factor analysis, and used unweighted least squares for exploratory factor analysis. @*Results@#The CFI was higher than 0.90 for all parts of the scale. Exploratory factor analysis also showed that the Korean MDS-UPDRS has the same number of factors in each part as the English version. @*Conclusions@#The Korean MDS-UPDRS has the same overall structure as the English MDSUPDRS. Our translated scale can be designated as the official Korean MDS-UPDRS.

Pregnancy and Delivery in a Generalized Dystonia Patient Treated with Internal Globus Pallidal Deep Brain Stimulation: a Case Report

Internal globus pallidus (GPi) deep brain stimulation (DBS) has been widely accepted as an effective treatment modality of medically refractory dystonia. However, there have been few studies regarding the safety issue of pregnancy and childbirth related with DBS. This report describes a female patient who was pregnant and delivered a baby after GPi DBS surgery. A 33-year-old female patient with acquired generalized dystonia underwent bilateral GPi DBS implantation. She obtained considerable improvement in both movement and disability after DBS implantation. Four years later, she was pregnant and the obstetricians consulted us about the safety of the delivery. At 38-weeks into pregnancy, a scheduled caesarian section was carried out under general anesthesia. After induction using thiopental and succinylcholine, intubation was done quickly, followed by DBS turn off. For hemostasis, only bipolar electrocautery was used. Before awakening from the anesthesia, DBS was turned on as the same parameters previously adjusted. After delivery, she could feed her baby by herself, because the dystonia of left upper extremity and hand was improved. Until now, she has been showing continual improvement and being good at housework, carrying for children, with no trouble in daily life. This observation indicates that the patients who underwent DBS could safely be pregnant and deliver a baby.

Malignant Neuroleptic Syndrome following Deep Brain Stimulation Surgery of Globus Pallidus Pars Internus in Cerebral Palsy / 대한구급학회지

Neuroleptic malignant syndrome (NMS) is a rare but potentially lethal outcome caused by sudden discontinuation or dose reduction of dopaminergic agents. We report an extremely rare case of NMS after deep brain stimulation (DBS) surgery in a cerebral palsy (CP) patient without the withdrawal of dopaminergic agents. A 19-year-old girl with CP was admitted for DBS due to medically refractory dystonia and rigidity. Dopaminergic agents were not stopped preoperatively. DBS was performed uneventfully under monitored anesthesia. Dopaminergic medication was continued during the postoperative period. She manifested spasticity and muscle rigidity, and was high fever resistant to anti-pyretic drugs at 2 h postoperative. At postoperative 20 h, she suffered cardiac arrest and expired, despite vigorous cardiopulmonary resuscitation. NMS should be considered for hyperthermia and severe spasticity in CP patients after DBS surgery, irrespective of continued dopaminergic medication.

Malignant Neuroleptic Syndrome following Deep Brain Stimulation Surgery of Globus Pallidus Pars Internus in Cerebral Palsy / 대한중환자의학회지

Neuroleptic malignant syndrome (NMS) is a rare but potentially lethal outcome caused by sudden discontinuation or dose reduction of dopaminergic agents. We report an extremely rare case of NMS after deep brain stimulation (DBS) surgery in a cerebral palsy (CP) patient without the withdrawal of dopaminergic agents. A 19-year-old girl with CP was admitted for DBS due to medically refractory dystonia and rigidity. Dopaminergic agents were not stopped preoperatively. DBS was performed uneventfully under monitored anesthesia. Dopaminergic medication was continued during the postoperative period. She manifested spasticity and muscle rigidity, and was high fever resistant to anti-pyretic drugs at 2 h postoperative. At postoperative 20 h, she suffered cardiac arrest and expired, despite vigorous cardiopulmonary resuscitation. NMS should be considered for hyperthermia and severe spasticity in CP patients after DBS surgery, irrespective of continued dopaminergic medication.

Clinical Heterogeneity of Atypical Pantothenate Kinase-Associated Neurodegeneration in Koreans

OBJECTIVE: Neurodegeneration with brain iron accumulation (NBIA) represents a group of inherited movement disorders characterized by iron accumulation in the basal ganglia. Recent advances have included the identification of new causative genes and highlighted the wide phenotypic variation between and within the specific NBIA subtypes. This study aimed to investigate the current status of NBIA in Korea. METHODS: We collected genetically confirmed NBIA patients from twelve nationwide referral hospitals and from a review of the literature. We conducted a study to describe the phenotypic and genotypic characteristics of Korean adults with atypical pantothenate kinase-associated neurodegeneration (PKAN). RESULTS: Four subtypes of NBIA including PKAN (n = 30), PLA2G6-related neurodegeneration (n = 2), beta-propeller protein-associated neurodegeneration (n = 1), and aceruloplasminemia (n = 1) have been identified in the Korean population. The clinical features of fifteen adults with atypical PKAN included early focal limb dystonia, parkinsonism-predominant feature, oromandibular dystonia, and isolated freezing of gait (FOG). Patients with a higher age of onset tended to present with parkinsonism and FOG. The p.R440P and p.D378G mutations are two major mutations that represent approximately 50% of the mutated alleles. Although there were no specific genotype-phenotype correlations, most patients carrying the p.D378G mutation had a late-onset, atypical form of PKAN. CONCLUSIONS: We found considerable phenotypic heterogeneity in Korean adults with atypical PKAN. The age of onset may influence the presentation of extrapyramidal symptoms.

Hemimasticatory spasm misdiagnosed as other mimickers: Report of two cases

Hemimasticatory spasm is a rare neurologic disorder characterized by unilateral, paroxysmal involuntary contraction of the masticatory muscles. It can be confused with other unilateral facial spasms. In this report, we present two patients with hemimasticatory spasm who were initially misdiagnosed with other disorders. The first patient was a 54-year-old man with a 9-year history of right facial spasm. He underwent microvascular decompression, without benefit, at another hospital with the diagnosis of hemifacial spasm two years prior to presenting at our hospital.On examination, right masseter and temporalis muscles had irregular contractions with twitches and prolonged spasms. His brain magnetic resonance imaging was normal.He showed a good response to carbamazepine. The second case was a 60-year-old man presented with a 10-year history of jaw-closing movement. Previous treatment for temporomandibular joint disorder was ineffective. He was previously diagnosed as oromandibular dystonia at another hospital, and biperiden and diazepam treatment resulted in slight improvement. There was tonic contraction and hypertrophy of the left masseter. He improved with carbamazepine. These cases illustrate the importance of hemimasticatory spasm as differential diagnosis, and the good response to carbamazepine.

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.

The first case report of fragile X-associated tremor

We present the first case report of fragile X-associated tremor ataxia syndrome (FXTAS) in the Republic of Korea. A 75-year-old male developed progressive gait ataxia, parkinsonism, and a mood disorder. Magnetic resonance imaging revealed T2 high signal intensity within the middle cerebellar peduncles. Analysis of the fragile X mental retardation 1 gene revealed a CGG trinucleotide repeat number of 136. FXTAS should be considered when a patient has atypical parkinsonism, cerebellar ataxia, and specific MRI abnormalities.

Influence of Propofol and Fentanyl on Deep Brain Stimulation of the Subthalamic Nucleus

We investigated the effect of propofol and fentanyl on microelectrode recording (MER) and its clinical applicability during subthalamic nucleus (STN) deep brain stimulation (DBS) surgery. We analyzed 8 patients with Parkinson's disease, underwent bilateral STN DBS with MER. Their left sides were done under awake and then their right sides were done with a continuous infusion of propofol and fentanyl under local anesthesia. The electrode position was evaluated by preoperative MRI and postoperative CT. The clinical outcomes were assessed at six months after surgery. We isolated single unit activities from the left and the right side MERs. There was no significant difference in the mean firing rate between the left side MERs (38.7+/-16.8 spikes/sec, n=78) and the right side MERs (35.5+/-17.2 spikes/sec, n=66). The bursting pattern of spikes was more frequently observed in the right STN than in the left STN. All the electrode positions were within the STNs on both sides and the off-time Unified Parkinson's Disease Rating Scale part III scores at six months after surgery decreased by 67% of the preoperative level. In this study, a continuous infusion of propofol and fentanyl did not significantly interfere with the MER signals from the STN. The results of this study suggest that propofol and fentanyl can be used for STN DBS in patients with advanced Parkinson's disease improving the overall experience of the patients.

Mitochondrial Dysfunction of Immortalized Human Adipose Tissue-Derived Mesenchymal Stromal Cells from Patients with Parkinson's Disease

Mitochondrial dysfunction in dopaminergic neurons of patients with idiopathic and familial Parkinson's disease (PD) is well known although the underlying mechanism is not clear. We established a homogeneous population of human adipose tissue-derived mesenchymal stromal cells (hAD-MSCs) from human adult patients with early-onset hereditary familial Parkin-defect PD as well as late-onset idiopathic PD by immortalizing cells with the hTERT gene to better understand the underlying mechanism of PD. The hAD-MSCs from patients with idiopathic PD were designated as "PD", from patients with Parkin-defect PD as "Parkin" and from patients with pituitary adenomas as "non-PD" in short. The pGRN145 plasmid containing hTERT was introduced to establish telomerase immortalized cells. The established hTERT-immortalized cell lines showed chromosomal aneuploidy sustained stably over two-years. The morphological study of mitochondria in the primary and immortalized hAD-MSCs showed that the mitochondria of the non-PD were normal; however, those of the PD and Parkin were gradually damaged. A striking decrease in mitochondrial complex I, II, and IV activities was observed in the hTERT-immortalized cells from the patients with idiopathic and Parkin-defect PD. Comparative Western blot analyses were performed to investigate the expressions of PD specific marker proteins in the hTERT-immortalized cell lines. This study suggests that the hTERT-immortalized hAD-MSC cell lines established from patients with idiopathic and familial Parkin-defect PD could be good cellular models to evaluate mitochondrial dysfunction to better understand the pathogenesis of PD and to develop early diagnostic markers and effective therapy targets for the treatment of PD.

Deep brain stimulation: mechanism, surgical procedure, and clinical applications

Advances in deep brain stimulation (DBS) in relation to neuroimaging techniques and with intraoperative electrophysiological microrecordings and stimulations have replaced ablative procedures for medication-refractory movement disorders such as Parkinson's disease, dystonia, and essential tremor. DBS is an effective surgical treatment for these conditions and is now being extended to psychiatric diseases such as obsessive-compulsive disorder, depression, and addiction. Despite the proven clinical improvement by DBS, its precise mechanism of action remains unclear. Clinical improvement depends on the selection of the appropriate patients and the precise implantation of the stimulation electrodes, which is based on careful stereotactic targeting and extensive electrophysiological monitoring of the target area. Further studies are being performed to better understand the mechanism of action and identify new anatomical targets and clinical applications of DBS. We briefly introduce the surgical procedure and current clinical applications of DBS in this review.

Electrode Position and the Clinical Outcome after Bilateral Subthalamic Nucleus Stimulation

We compared the surgical outcome with electrode positions after bilateral subthalamic nucleus (STN) stimulation surgery for Parkinson's disease. Fifty-seven patients treated with bilateral STN stimulations were included in this study. Electrode positions were determined in the fused images of preoperative MRI and postoperative CT taken at six months after surgery. The patients were divided into three groups: group I, both electrodes in the STN; group II, only one electrode in the STN; group III, neither electrode in the STN. Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr stage, and activities of daily living scores significantly improved at 6 and 12 months after STN stimulation in both group I and II. The off-time UPDRS III speech subscore significantly improved (1.6 +/- 0.7 at baseline vs 1.3 +/- 0.8 at 6 and 12 months, P < 0.01) with least L-dopa equivalent daily dose (LEDD) (844.6 +/- 364.1 mg/day at baseline; 279.4 +/- 274.6 mg/day at 6 months; and 276.0 +/- 301.6 mg/day at 12 months, P < 0.001) at 6 and 12 months after STN deep brain stimulation (DBS) in the group I. Our findings suggest that the better symptom relief including speech with a reduced LEDD is expected in the patients whose electrodes are accurately positioned in both STN.

Nutrients Intake and Dietary Quality of Korean Parkinson's Disease Patients According to the Duration of Disease / 대한지역사회영양학회지

Both genetic and environmental factors play important roles in the pathogenesis of Parkinson Disease (PD). The contribution of many environmental factors including dietary factor remains unproven. The purpose the study was to investigate the dietary habits, nutrient intake and dietary quality of Korean PD patients according to the duration of disease. PD patients were recruited from K and S university hospitals from May 2005 to January 2006. This study was carried out after approval by the Institute Review Board (IRB). British Brain Bank criteria was used to diagnose PD. The subjects were classified into 2 groups based on the duration of PD: or = 25 months groups. General characteristics, anthropometric measurements, food habits and dietary intakes were investigated. The results of this study were as follows: 1) The mean age of or = 25 months group (62.2 +/- 8.8 yr) (p or = 25 months group. 4) Daily intakes of most nutrients were very low compared with DRI. 5) The MAR score was significantly lower in < 25 months group (p < 0.05;) however, the scores of DVS, DDS and DQI were not significantly different. As a conclusion an overall nutrient intake and dietary quality of the Parkinson's Disease patients need to be improved regardless of duration of the disease and a well-balanced diet should be emphasized.

Nutrients Intake and Dietary Quality of Korean Parkinson's Disease Patients According to the Duration of Disease / 대한지역사회영양학회지

Both genetic and environmental factors play important roles in the pathogenesis of Parkinson Disease (PD). The contribution of many environmental factors including dietary factor remains unproven. The purpose the study was to investigate the dietary habits, nutrient intake and dietary quality of Korean PD patients according to the duration of disease. PD patients were recruited from K and S university hospitals from May 2005 to January 2006. This study was carried out after approval by the Institute Review Board (IRB). British Brain Bank criteria was used to diagnose PD. The subjects were classified into 2 groups based on the duration of PD: or = 25 months groups. General characteristics, anthropometric measurements, food habits and dietary intakes were investigated. The results of this study were as follows: 1) The mean age of or = 25 months group (62.2 +/- 8.8 yr) (p or = 25 months group. 4) Daily intakes of most nutrients were very low compared with DRI. 5) The MAR score was significantly lower in < 25 months group (p < 0.05;) however, the scores of DVS, DDS and DQI were not significantly different. As a conclusion an overall nutrient intake and dietary quality of the Parkinson's Disease patients need to be improved regardless of duration of the disease and a well-balanced diet should be emphasized.

STN DBS of Advanced Parkinson's Disease Experienced in a Specialized Monitoring Unit with a Prospective Protocol

OBJECTIVE: In the evaluation of patients with Parkinson's disease (PD), most neurologists only see their patients during a limited period of their fluctuating 24-hour-a-day lives. This study aimed to assess the short-term outcome of STN stimulation for patients with advanced PD evaluated in a 24-hour monitoring unit for movement disorder (MUMD) using a prospective protocol. METHODS: Forty-two patients with advanced PD consecutively treated with bilateral STN stimulation using multi-channel microelectrode recording were included in this study. All patients were evaluated using a 24-hour MUMD with a video recording/editing system and were evaluated with a prospective protocol of the Unified Parkinson's Disease Rating Scale, Hoehn and Yahr Staging, Schwab and England Activities of Daily Living, levodopa equivalent daily dose (LEDD), Short Form-36 Health Survey, and neuropsychological tests. Magnetic resonance (MR) images of the brain were performed prior to and six months after surgery. RESULTS: All patients were evaluated at three and six months after surgery. There was a rapid and significant improvement of the motor symptoms, especially in tremor and rigidity, after STN stimulation with low morbidity. Dyskinesia was markedly decreased with much lowered LEDD values by 50% after STN stimulation. 1.5T MR images were safely taken according to the manufacturer's guidelines at six months after surgery without any adverse effects in 41 patients treated with STN stimulations. CONCLUSION: Evaluations in a 24-hour monitoring unit could reduce the dose of medication efficiently to an optimal level with patients'comfort and improve the clinical symptoms in harmony with STN stimulation.

Episodic Ataxia Type 2 due to a Deletion Mutation in the CACNA1A Gene in a Korean Family

Episodic ataxia type 2 (EA-2) is an inherited disorder that is characterized by intermittent vertigo, ataxia, and interictal gaze-evoked nystagmus. Although abnormalities associated with this disorder have been found in the CACNA1A gene encoding the alpha1A (Cav2.1) subunit of the P/Q-type calcium channel, there are few reports of genetically confirmed EA-2 in Korea. In 1998, a Korean family with acetazolamide-responsive hereditary paroxysmal ataxia was reported, but the genetic background was not defined at that time. In the present study we performed direct sequencing of the entire exons and their flanking intronic sequences of the CACNA1A gene and found a deletion mutation (c.2042_2043delAG).

Efficacy of Embryonic Stem Cell-derived Dopaminergic Neurons and E12 Mesencephalic Neuronal-precursor Derived Dopaminergic Neurons as a Source for Transplantation in Parkinsonian Rats

BACKGROUND: This study was performed to compare efficiency of embryonic stem (ES) cell-derived dopaminergic (DA) neurons from E12 mesencephalic neuronal-precursor derived DA neuron, and to assess the value of these neurons as a donor cells to transplant in Parkinson's disease. METHODS: ES cell-derived DA neurons from E12 mesencephalic neuronal-precursor derived DA neuron were transplanted in Parkinsonian rats and analyzed TH immunoreactivity and apomorphin-induced rotation test. RESULTS: Transplanting of ES cell derived DA neurons into the rat striatum caused gradual increase of expression of tyrosine hydroxylase (TH) immunoreactivity 6 weeks after transplant in host striatum. Rotation behavior was gradually on the decrease, 6 weeks after transplant of ES cell derived DA neurons. In case of E12 mesencephalic precursor derived DA neurons, the TH immunoreactivity expressed 6 weeks after transplant in striatum, and the behavioral restoration of DA-mediated motor asymmetry sustained gradually. However, transplanted ES cell derived DA neurons appeared in wide regions among the needle tract with a relatively high density of TH immunoreactivity in comparison to the E12 mesencephalic precursor DA neurons, and graft volume of ES cell derived DA neurons were larger than E12 mesencephalic precursor derived DA neuron. In addition, both cells did not appear cancerous change after transplantation. CONCLUSIONS: These results suggest that ES cell is more efficient than E12 mesencephalic precursor derived dopaminergic neuron and will supply efficient donor cells for transplantation in Parkinson's disease.

New Variant Creutzfeldt-Jakob Disease

No abstract available.

Chronological Changes in the Rotational Behavior in Response to Apomorphine Administration in 6-Hydroxydopamine Parkinsonian Rat

BACKGROUND: Apomorphine-induced rotational behavior of unilateral 6-hydroxydopamine (OHDA) lesioned rat is widely used to develop anti-Parkinsonian treatments including drugs, neuroprotective therapy, and neural graft. Time course of changes in rotational behavior after lesioning, however, has not been fully elucidated. The aim of this study was to observe the chronological changes in the rotational response and to find the optimal period when this model is used for investigation of various therapies. METHODS: 6-OHDA was stereotaxically delivered to the unilateral substantia nigra in 13 rats. Rotational responses to apomorphine administrations were counted in the rotomotor on 2, 4, 8, 12, and 14 weeks after lesioning. RESULTS: The total turns for two hours increased continuously up to eight weeks, and then plateaued. CONCLUSIONS: Apomorphine-induced rotations increase until eight weeks after 6-OHDA lesioning. Therefore, this Parkinsonian model should be used at least eight weeks after lesioning. Even though priming was not excluded as an explanation in the experiment, we reason that progressive degeneration of dopaminergic neurons may explain the chronological changes in rotational behavior.

Clinical Features and Outcomes from Diagnostic Work-up in Definite Multiple Sclerosis

BACKGROUND: To observe the clinical features and the outcomes from diagnostic work-up in definite multiple sclero-sis (MS) which was diagnosed by using a Poser's criteria. METHODS: We retrospectively evaluated 43 cases who were diagnosed as multiple sclerosis in Seoul National University Hospital by using Poser's criteria from January 1st, 1991 to December 30th , 1995. Among the 43 cases, 35 patients were classified to definite MS group, clinically or laboratory supported. We analyzed age, sex, initial symptom, age of onset, duration between initial symptom and definite MS diagnosis, total numbers of recurrence and symptoms, CSF profile, evoked potential study, follow-up duration and the MRI findings of the definite MS patients. RESULTS: Of 35 cases who were diagnosed as definite MS, 15 patients were male and 20 patients were female. The mean age of onset was 34.6 years, the mean duration between initial symptom onset and diagnosis of definite MS was 16.9 months, and the mean follow-up duration was 34.8 months. The most common site of initial involvement was spinal cord (24 cases), and then optic nerve (5 cases), brain stem (4 cases), and cerebrum (2 cases) were followed. Thoracic spinal cord (24 lesions) was more frequently involved than cervical cord (18 lesions). Moreover 32 cases (91.4%) had at least one time of spinal cord involvement and there is a tendency that the proportion of double spinal cord lesion is increasing with the number of spinal cord recurrence. CONCLUSIONS: Spinal cord involvement in multiple sclerosis is the most common symptom and double spinal cord involvement in MRI is frequently observed. We think that it would be the characteristics of the multiple sclerosis in Korea.