Novel Ferritin Light Chain Gene Mutation in a Korean Patient with Neuroferritinopathy

No abstract available.

Tau Positron Emission Tomography Imaging in Degenerative Parkinsonisms

In recent years, several radiotracers that selectively bind to pathological tau proteins have been developed. Evidence is emerging that binding patterns of in vivo tau positron emission tomography (PET) studies in Alzheimer's disease (AD) patients closely resemble the distribution patterns of known neurofibrillary tangle pathology, with the extent of tracer binding reflecting the clinical and pathological progression of AD. In Lewy body diseases (LBD), tau PET imaging has clearly revealed cortical tau burden with a distribution pattern distinct from AD and increased cortical binding within the LBD spectrum. In progressive supranuclear palsy, the globus pallidus and midbrain have shown increased binding most prominently. Tau PET patterns in patients with corticobasal syndrome are characterized by asymmetrical uptake in the motor cortex and underlying white matter, as well as in the basal ganglia. Even in the patients with multiple system atrophy, which is basically a synucleinopathy, ¹⁸F-flortaucipir, a widely used tau PET tracer, also binds to the atrophic posterior putamen, possibly due to off-target binding. These distinct patterns of tau-selective radiotracer binding in the various degenerative parkinsonisms suggest its utility as a potential imaging biomarker for the differential diagnosis of parkinsonisms.

Increased Uptake of AV-1451 in a Subacute Infarction Lesion

¹⁸F-AV-1451 is a tau PET ligand that has high affinity for paired helical filament tau. However, various off-target bindings unrelated to tau have also been reported. Herein, we report a case of 83-year-old woman, who showed abnormal uptake of AV-1451 that was shown to be subacute infarction. Clinicians should recognize that increased uptake of AV-1451 may be related to stroke.

Clinical Features Indicating Nigrostriatal Dopaminergic Degeneration in Drug-Induced Parkinsonism

OBJECTIVE: Patients with drug-induced parkinsonism (DIP) may have nigrostriatal dopaminergic degeneration. We studied the clinical features that may indicate nigrostriatal dopaminergic degeneration in patients with DIP. METHODS: Forty-one DIP patients were classified into normal and abnormal [¹⁸F] FP-CIT scan groups. Differences in 32 clinical features and drug withdrawal effects were studied. RESULTS: Twenty-eight patients had normal (Group I) and 13 patients had abnormal (Group II) scans. Eight patients of Group I, but none of Group II, had taken calcium channel blockers (p = 0.040). Three patients of Group I and six of Group II had hyposmia (p = 0.018). After drug withdrawal, Group I showed greater improvement in Unified Parkinson's Disease Rating Scale total motor scores and subscores for bradykinesia and tremors than Group II. Only hyposmia was an independent factor associated with abnormal scans, but it had suboptimal sensitivity. CONCLUSION: None of the clinical features were practical indicators of nigrostriatal dopaminergic degeneration in patients with DIP.

A Patient with Recurrent Dyskinesia and Hyperpyrexia Syndrome

Dyskinesia hyperpyrexia syndrome is a rare medical emergency in Parkinson's disease. It is characterized by continuous dyskinesia associated with hyperthermia, rhabdomyolysis, and alteration of the mental state. We present the case of a 74-year-old woman who presented with recurrent dyskinesia hyperpyrexia syndrome. Although some provocation factors and clinical manifestations seem to be shared with parkinsonism hyperpyrexia syndrome, a clear distinction in management should be considered.

Anti-LGI1 Antibody Limbic Encephalitis Presented with Amnestic Mild Cognitive Impairment

No abstract available.

Anti-LGI1 Antibody Limbic Encephalitis Presented with Amnestic Mild Cognitive Impairment

No abstract available.

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.

Cortical Hypometabolism in Opsoclonus-Myoclonus Syndrome

Opsoclonus-myoclonus syndrome (OMS) is characterized by opsoclonus and arrhythmic myoclonic jerks predominantly involving the trunk, limbs, and head. We present two patients with OMS after respiratory tract infection who exhibited diffuse cerebral hypometabolism, particularly in the parieto-occipital cortex on 18F-fluorodeoxyglucose positron-emission tomography (F-FDG PET). This metabolic change might be a consequence rather than a direct cause of motor symptoms, which may be attributable to brainstem or cerebellar pathology.

A Computed Tomography-Based Spatial Normalization for the Analysis of 18F Fluorodeoxyglucose Positron Emission Tomography of the Brain

OBJECTIVE: We developed a new computed tomography (CT)-based spatial normalization method and CT template to demonstrate its usefulness in spatial normalization of positron emission tomography (PET) images with [18F] fluorodeoxyglucose (FDG) PET studies in healthy controls. MATERIALS AND METHODS: Seventy healthy controls underwent brain CT scan (120 KeV, 180 mAs, and 3 mm of thickness) and [18F] FDG PET scans using a PET/CT scanner. T1-weighted magnetic resonance (MR) images were acquired for all subjects. By averaging skull-stripped and spatially-normalized MR and CT images, we created skull-stripped MR and CT templates for spatial normalization. The skull-stripped MR and CT images were spatially normalized to each structural template. PET images were spatially normalized by applying spatial transformation parameters to normalize skull-stripped MR and CT images. A conventional perfusion PET template was used for PET-based spatial normalization. Regional standardized uptake values (SUV) measured by overlaying the template volume of interest (VOI) were compared to those measured with FreeSurfer-generated VOI (FSVOI). RESULTS: All three spatial normalization methods underestimated regional SUV values by 0.3-20% compared to those measured with FSVOI. The CT-based method showed slightly greater underestimation bias. Regional SUV values derived from all three spatial normalization methods were correlated significantly (p < 0.0001) with those measured with FSVOI. CONCLUSION: CT-based spatial normalization may be an alternative method for structure-based spatial normalization of [18F] FDG PET when MR imaging is unavailable. Therefore, it is useful for PET/CT studies with various radiotracers whose uptake is expected to be limited to specific brain regions or highly variable within study population.

A Patient with Genetically Confirmed Myoclonus-Dystonia Responded to Anticholinergic Treatment and Improved Spontaneously

BACKGROUND: The various medical treatments applied to myoclonus-dystonia patients with a mutation of the epsilon-sarcoglycan gene (SGCE) have not been beneficial in most cases. Most patients experience progressive deterioration or static clinical courses, with only rare cases of spontaneous remission. CASE REPORT: A 19-year-old girl presented with a 14-year history of myoclonus and dystonia that severely affected her left arm, neck, and trunk. Genetic studies showed a mutation in SGCE [deletion in exon 6 (c.771_772delAT, Cys258X)]. Both myoclonus and dystonia responded to anticholinergic treatment for 7 years and improved spontaneously. CONCLUSIONS: The possibility of spontaneous improvement should be kept in mind when considering the therapeutic strategy in myoclonus-dystonia patients, especially when contemplating deep-brain stimulation.

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.

Three Patients With Classic and Atypical Neurodegeneration With Brain Iron Accumulation

Neurodegeneration with brain iron accumulation (NBIA) is a disorder characterized by various mixtures of extrapyramidal, pyramidal or psychiatric abnormalities associated with iron accumulation in the basal ganglia. The mutations in the pantothenate kinase gene (PANK2) were found in approximately two thirds of the patients with NBIA. We report three patients wtih NBIA, and two of them showed mutations in the PANK2 gene.

Subthalamic Deep Brain Stimulation for Parkinson's Disease

The recent progress in the basic knowledge of basal ganglia pathways and advances in the techniques of the neuroimaging studies enabled subthalamic deep brain stimulation (STN DBS). In Korea, more than three hundreds and fifty patients with PD have been treated with STN DBS since the first trial at March 2000. STN DBS effectively improves all parkinsonian deficits occurring especially during levodopa 'off' period and decreases the daily 'off' time. The daily requirement of levodopa dosage can be reduced to about half of the preoperative one. The favorable responses to the STN DBS can be maintained even after five years. However, parkinsonian deficits during levodopa 'on' period can not be controlled as effectively as those during the levodopa 'off' period. The axial symptoms including gait disturbance and postural instability during the levodopa 'on' period cannot be improved or even are worsen by STN DBS. Patients aged over 70 frequently show less remarkable improvement of parkinsonian deficits than the younger ones. Therefore, selection of appropriate candidate for STN DBS is the most important factor deciding the outcome of the STN DBS.

Parkin Gene Mutation in Korean Patients with Young Age Onset Sporadic Parkinson's Disease

BACKGROUND: Abnormalities of the parkin gene is the most frequently found genetic abnormality in patients with sporadic young age onset of Parkinson's disease (PD). We investigated the frequency of abnormalities of the parkin gene in Korean patients with young age onset PD (YOPD). METHODS: This study included 18 patients (M : F=10:8) who developed PD before the age of 45. DNA was isolated from peripheral blood leukocytes. Exonal deletion and nucleotide sequence changes in the parkin gene was searched by quantitative PCR and sequencing of all coding regions. RESULTS: Only one patient had a heterozygous mutation at the nucleotide position 1473 in exon 12 (A1473C). The remaining 17 patients showed no mutations in the coding region of the parkin gene. In all 18 patients, we could not find any compound heterozygotic as well as homozygotic exonal deletion. The patient who had the heterozygotic point mutation in the parkin gene did not present any clinical features differentiating the patient from the others with YOPD. The frequency of parkin mutation in patients with YOPD in our series was 5.6 percent. CONCLUSIONS: In Korean patients with YOPD, the frequency of parkin mutation seems to be lower than that of other ethnic groups. Further studies with a larger number of patients with YOPD are needed to support this suggestion.

The Quantitative 18-fluorodeoxyglucose PET Study in the Differential Diagnosis between Idiopathic Parkinson's Disease and Multiple System Atrophy

BACKGROUND: Overlapping clinical features of idiopathic Parkinson's disease (IPD) and multiple system atrophy (MSA) make it difficult to conduct an accurate differential diagnosis. We performed a quantitative F18- fluorodeoxyglucose PET (FDG PET) and measured the striatal and cerebellar glucose metabolism to evaluate the efficacy of a FDG PET study in the differential diagnosis between IPD and MSA. METHODS: This study included 19 patients with IPD, 28 patients with MSA (MSA-P : MSA-C = 19 : 9) and 12 age matched normal controls. A FDG PET study was performed in all subjects and the original PET image was corrected with the radioactivity curve obtained by repetitive sampling of the radial arterial blood. RESULTS: The measurements of striatal and cerebellar glucose metabolisms of the patients with MSA-P were significantly lower than those of the patients with IPD (P<0.001). However, the measurement of the caudate nucleus provided the most reliable clue for the differential diagnosis between IPD and MSA-P (sensitivity 94.7% and specificity 94.7%). In the patients with MSA-C, the glucose metabolism of the cerebellar vermis (P<0.001), cerebellar cortex (P<0.001) and putamen (P<0.05) was significantly lower than those of the patients with IPD. CONCLUSIONS: Quantitative FDG PET is a useful and reliable method in making a differential diagnosis between IPD and MSA.

Inadequate Efficacy of Deep Brain Stimulation in a Patient with Parkinson's disease due to Partial Breakage of Electrode Lead

A patient with Parkinson's disease developed fluctuation in the deep brain stimulation (DBS) effect, an unpleasant left facial paresthesia and the left limb dystonia. Impedance of the right DBS was over 2000 ohm in three proximal contacts. Skull X-ray studies showed partial breakage of right electrode lead below the mastoid process. Partial electrode breakage must be considered when there is a deterioration of the DBS effect, an unexpected side effect of DBS, and an alteration of impedance.

A Familial Case of Myoclonus-Dystonia

BACKGROUND: Myoclonus-dystonia is a rare familial disease characterized by autosomal dominant inheritance, nonor slowly progressive axial myoclonus combined with dystonic posture, normal electroencephalography (EEG) finding, and dramatic response to alcohol intake. METHODS: Clinical manifestations were studied in a family with myoclonus-dystonia. Response to alcohol intake was investigated in affected adult patients. Brain magnetic resonance imaging (MRI) and other laboratory examination were performed in 3 patients. RESULTS: Eight (male: 5, female: 3) of the 14 biological family members through 4 generations were found to be affected by myoclonus-dystonia on neurological examinations. Another 5 members (male: 3, female: 2) were suspected to be affected in family history. All eight affected members showed axial myoclonus affecting the neck, trunk, and proximal muscles of the limbs. Six of them also had dystonia affecting the neck or the distal part of the arm. Myoclonus and dystonia were ameliorated dramatically after small dose of alcohol intake. Brain MRI, EEG study, and ophthalmologic examination showed no abnormalities. CONCLUSIONS: Our patients showed clinical features compatible with myoclonus-dystonia. This is the first Korean family with myoclonus-dystonia.

The Effect of Subthalamic Nucleus Stimulation in Patients with Advanced Idiopathic Parkinson's Disease

BACKGROUND: To determine the efficacy and safety of subthalamic nucleus (STN) stimulation in patients with advanced Parkinson's disease (PD). METHODS: In 5 patients with PD, we evaluated the effect of bilateral STN stimula-tion. Using the Unified PD Rating Scale (UPDRS), Clinical Dyskinesia Rating Scale, Activities of Daily Living(ADL) Score and patient's diary, we evaluated the patients before and at one, three and 12 months after surgery. We examined the patients while they were drug "off" and "on". RESULTS: While patients were "off", stimulation induced a signifi-cant reduction in the UPDRS part III score by 46% at 12 months after the operation, compared to the baseline state. During drug "on" state, levodopa-induced dyskinesias were reduced by 88% at 12 months after the operation. Off-peri-od dystonia was reduced by 45% at 12 months after the operation. ADL scores also improved after the stimulation. Patients' diaries showed significant reduction in the "off" period while awake (73% reduction at 12 months). The daily dose of levodopa was reduced by 56% at 12 months after the operation. There was no significant complication related to the surgical procedure or electrical stimulation. CONCLUSIONS: We conclude that STN stimulation is an effective and safe treatment strategy for the patients with advanced PD.

Apolipoprotein E Polymorphism in Schizophrenic Patients / 신경정신의학

OBJECTIVES: To explore the role of apolipoprotein E in schizophrenia, we investigated apoli-poprotein E polymorphism in groups of patients with schizophrenia and normal controls. We also examined the relationship of clinical characteristics of schizophrenia to apolipoprotein E genotypes. METHODS: Samples were obtained from 101 schizophrenic patients and 96 controls in Korea and apolipoprotein E polymorphisms were analysed using polymerase chain reaction. RESULTS: The genotype and allele frequencies did not differ from those of controls. The clinical variables of schizophrenia, such as positive and negative groups by PANSS, subtypes by DSM-IV, family history were not associated with each genotypes. CONCLUSION: We could not find the association of apolipoprotein E in Korean schizophrenic patients and it could be suggested that apolipoprotein E isoforms might not play a main role in expression of schizophrenia.