Hyeeun Shin

Decreased Metabolism in the Cerebral Cortex in Early-Stage Huntington's Disease: A Possible Biomarker of Disease Progression?

Background and Purpose Huntingtons disease (HD) is an autosomal-dominant inherited neurodegenerative disorder. Genetic analysis of abnormal CAG expansion in the IT15 gene allows disease confirmation even in the preclinical stage. However, because there is no treatment to cure or delay the progression of this disease, monitoring of biological markers that predict progression is warranted. Methods FDG-PET was applied to 13 patients with genetically confirmed HD in the early stage of the disease. We recorded the initial and follow-up statuses of patients using the Independence Scale (IS) of the Unified Huntingtons Disease Rating Scale. The progression rate (PR) was calculated as the annual change in the IS. The patients were divided into two groups with faster and slower progression, using the median value of the PR as the cut-off. FDG-PET data were analyzed using regions of interest, and compared among the two patient groups and 11 age- and sex-matched controls. Results The mean CAG repeat size in patients was 44.7. The CAG repeat length was inversely correlated with the age at onset as reported previously, but was not correlated with the clinical PR. Compared with normal controls, hypometabolism was observed even at very early stages of the disease in the bilateral frontal, temporal, and parietal cortices on FDG-PET. The decreases in metabolism in the bilateral frontal, parietal, and right temporal cortices were much greater in the faster-progression group than in the slower-progression group. Conclusions A decrease in cortical glucose metabolism is suggested as a predictor for identifying a more rapid form of progression in patients with early-stage HD.

Caregiver Burden in Parkinson Disease With Dementia Compared to Alzheimer Disease in Korea

We compared caregiver burden in Parkinson disease with dementia (PDD) to that in Alzheimer disease (AD) and examined the factors contributing to the burden in PDD. Totally, 42 patients with PDD and 109 patients with AD and their caregivers participated in this study. The caregiver burden was measured using the Burden Interview (BI). Scores of Barthel activities of daily living (BADLs), Mini-Mental State Examination, Clinical Dementia Rating of patients, and score of Center for Epidemiologic Studies Depression scale, and Euro-quality of life of the caregivers were examined. The Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn and Yahr stage of the patients were administered to assess burden relating to parkinsonism on PDD. We used multiple linear regression to assess the predictors. The BI of caregivers was higher in PDD (47.9, Standard deviation [SD]: 3.8) than in AD (36.3, SD:2.1). In the AD group, the BI was predicted by cognitive function ((β ± SE: −0.8 ± 0.4, P value =.04) and basic ADL status of patients (β ± SE: −1.3 ± 0.1, P < .001), depressive symptoms (β ± SE: 1.1 ± 0.1, P < .001), and poor quality of life (β ± SE: −0.2 ± 0.1, P = .017) in caregivers. In PDD group, BI was predicted only by scores of Part 1 on the UPDRS (β ± SE: 2.9 ± 1.3, P = .03) of patients and depressive symptoms (β ± SE: 1.1 ± 0.2, P < .001) of the caregivers. We concluded the caregiver burden is higher in PDD than in AD and factors predicting burden are different in AD and PDD. In patients with PDD, the neuropsychiatric problems are the major contributor to caregiver burden.

Factors Contributing to Spousal and Offspring Caregiver Burden in Parkinson’s Disease

Background/Aims: Parkinson’s disease (PD) is a common neurodegenerative disease with a chronic disease course. The increase in life expectancy of humans worldwide is expected to increase the prevalence and duration of PD; therefore, it is important to determine factors that contribute to the caregiver burden for both clinical and social reasons. Methods: We surveyed 91 main caregivers of patients, and compared factors contributing to caregiver burden between 50 spouses and 41 offspring of patients. We determined Burden Interview, Depression Scale, Health-Related Quality of Life, and Obligation Scale scores, as well as the degree of functional social support of caregivers. Results: Interestingly, the burden scores of the two groups were not significantly different. Correlation analysis revealed that depression, health-related quality of life, social support, subdivided parts of the Unified Parkinson’s Disease Rating Scale (UPDRS), Hoehn and Yahr Scale, score of Mini-Mental State Examination, and Barthel index were correlated with burden in both spouses and offspring. However, in multiple regression, depression score and part 1 of the UPDRS were more significant predictors of burden in the spousal group, whereas social support of community and part 3 of the UPDRS were more important correlated factors in the offspring group. Conclusions: The caregiver burden of spousal and offspring caregivers of PD patients was not significantly different. However, different factors contributed to caregiver burden according to the caregiver’s relationship with the patient.

Globus pallidus interna deep brain stimulation improves chorea and functional status in a patient with chorea-acanthocytosis.

We report a 39-year-old woman with chorea-acanthocytosis (ChAc) who was referred with refractory hyperkinetic movement and truncal bending spasm. She was diagnosed with ChAc with clinical features and laboratory findings of acanthocytosis in peripheral blood smear, and genetic studies revealed novel mutations in the VPS13 gene. Because her symptoms did not respond well to medical treatment, she was in a totally dependent state. We decided to perform globus pallidus interna deep brain stimulation (GPi-DBS) for symptom control. After the operation her hyperkinetic movement, bradykinesia, and truncal bending motion were improved, the preoperative total score of the motor section on the Unified Huntington’s Disease Rating Scale (UHDRS) was 44, the independence scale was 50, and functional capacity was 1. However, a year after GPi-DBS, the postoperative score on the motor section was 12, the independence scale was 80, functional capacity was 9, and she had become capable of independent daily life. Although there is currently no curative treatment for ChAc, GPi-DBS represents a promising option for symptomatic control.

Atrophy of the Cerebellar Vermis in Essential Tremor: Segmental Volumetric MRI Analysis

Postmortem studies of essential tremor (ET) have demonstrated the presence of degenerative changes in the cerebellum, and imaging studies have examined related structural changes in the brain. However, their results have not been completely consistent and the number of imaging studies has been limited. We aimed to study cerebellar involvement in ET using MRI segmental volumetric analysis. In addition, a unique feature of this study was that we stratified ET patients into subtypes based on the clinical presence of cerebellar signs and compared their MRI findings. Thirty-nine ET patients and 36 normal healthy controls, matched for age and sex, were enrolled. Cerebellar signs in ET patients were assessed using the clinical tremor rating scale and International Cooperative Ataxia Rating Scale. ET patients were divided into two groups: patients with cerebellar signs (cerebellar-ET) and those without (classic-ET). MRI volumetry was performed using CIVET pipeline software. Data on whole and segmented cerebellar volumes were analyzed using SPSS. While there was a trend for whole cerebellar volume to decrease from controls to classic-ET to cerebellar-ET, this trend was not significant. The volume of several contiguous segments of the cerebellar vermis was reduced in ET patients versus controls. Furthermore, these vermis volumes were reduced in the cerebellar-ET group versus the classic-ET group. The volume of several adjacent segments of the cerebellar vermis was reduced in ET. This effect was more evident in ET patients with clinical signs of cerebellar dysfunction. The presence of tissue atrophy suggests that ET might be a neurodegenerative disease.

Seizures Related to Vitamin B6 Deficiency in Adults

Vitamin B6 is closely associated with functions of the nervous, immune, and endocrine systems. Its deficiency may result in neurological disorders including convulsions and epileptic encephalopathy. Until today, this has only been reported in infants, children, and critically ill adult patients. We report a case of a 36year-old man with chronic alcoholism who presented with seizures after gastrointestinal disturbance. His seizures persisted even after treatment with antiepileptic drugs, but eventually disappeared after administration of pyridoxine. Hence, vitamin B6 deficiency may cause seizures in adult patients with chronic alcoholism.

A Korean Parkinson's disease family with the LRRK2 p.Tyr1699Cys mutation showing clinical heterogeneity

Although leucine‐rich repeat kinase 2 (LRRK2) is the gene most commonly linked to autosomal dominant inherited Parkinsons disease (PD), there have been few reports in Asia, probably because of population‐specific differences in allele frequencies.

A novel PANK2 gene mutation with sudden-onset dystonia.

formerly known as Hallervorden–Spatz syndrome, is an autosomal recessive disorder typically caused by mutations in the pantothenate kinase 2 gene (PANK2) on chromosome 20p13. The PANK2 gene encodes pantothenate kinase, a key regulatory enzyme in the biosynthesis of coenzyme A. Classic PKAN presents in the first decade of life with extrapyramidal dysfunction, dystonia, and retinopathy, and progresses rapidly with loss of ambulation and restriction of activities by midadolescence.1 Atypical PKAN presents in the second or third decade of life with variable clinical phenotype including speechrelated issues or psychiatric problems. All reported cases have featured insidious onset with progressive course regardless of subtype. In this report, we describe a compound heterozygous PANK2 mutation in a patient with sudden-onset and stationary course of dystonia mimicking a psychogenic movement disorder.

Hashimoto’s encephalopathy: South Korean experiences

Abstract Hashimoto’s encephalopathy (HE) is a rare neurological disorder. Early diagnosis and treatment are critical to prevent irreversible brain damage. In the present study, we aimed to describe and classify HE on the basis of clinical, neuroimaging, and EEG findings. We retrospectively reviewed the clinical, radiological, and electrophysiological findings in patients who showed both neurological symptoms and high titers of anti-thyroid antibodies, and who were admitted between 2006 and 2012. Our patients were classified into two groups: those presenting seizures (group 1) and those with diffuse encephalopathies (group 2). Group 1 contained two patients. Patient 1, who showed verbal memory disturbance, focal MRI lesions, and partial seizure activity on EEG, recovered with antiepileptic and steroid treatments. Five of six patients assigned to group 2 were treated with steroids and showed significant improvement. One patient treated with azathioprine showed moderate improvement. Four of these patients had accompanying metabolic disturbances. HE is a treatable neurologic disorder with different subtypes, each with its own clinical manifestations and treatment options. HE can be difficult to identify and requires careful and attentive clinical observation for diagnosis.

Preliminary study of intravenous amantadine treatment for ataxia management in patients with probable multiple system atrophy with predominant cerebellar ataxia.

Background and Purpose: Multiple system atrophy with predominant cerebellar ataxia is a disabling neurologic disease. However, effective management has not yet been established. We conducted a short-term, open-label preliminary study to assess the benefits of intravenous amantadine treatment in patients with probable multiple system atrophy with predominant cerebellar ataxia. Methods: Twenty patients (10 male, 10 female) with probable multiple system atrophy with predominant cerebellar ataxia received 400 mg of amantadine by intravenous per day for 5 days. Ataxia severity was evaluated by the International Cooperative Ataxia Rating Scale before and after intravenous amantadine therapy and all subjects reported subjective improvement after intravenous amantadine treatment using a patient global impression scale. We analyzed the total and subscale scores by the ataxia scale and patient global impression scale. Results: The mean age was 57.4 years (range: 47–72) and the mean disease duration was 30.8 months (range: 11–79). The ataxia severity significantly decreased after intravenous amantadine therapy from 42.5 to 37.3 (p < 0.001). The mean patient global impression scale for improvement was 2.9 and there were no side effects of intravenous amantadine treatment observed. When we assessed responders, the duration of intravenous amantadine effect was more than 1 month in 4 subjects of 7 responders. Conclusions: Our findings suggest that intravenous amantadine treatment can be a safe management option in cerebellar ataxia, although the mechanism is unclear. Thus, further double-blind, long-term studies with a larger sample size are needed.