Clinical Diversity of SCN4A-Mutation-Associated Skeletal Muscle Sodium Channelopathy

BACKGROUND AND PURPOSE: Mutations of the skeletal muscle sodium channel gene SCN4A, which is located on chromosome 17q23-25, are associated with various neuromuscular disorders that are labeled collectively as skeletal muscle sodium channelopathy. These disorders include hyperkalemic periodic paralysis (HYPP), hypokalemic periodic paralysis, paramyotonia congenita (PMC), potassium-aggravated myotonia, and congenital myasthenic syndrome. This study analyzed the clinical and mutational spectra of skeletal muscle sodium channelopathy in Korean subjects. METHODS: Six unrelated Korean patients with periodic paralysis or nondystrophic myotonia associated with SCN4A mutations were included in the study. For the mutational analysis of SCN4A, we performed a full sequence analysis of the gene using the patients' DNA. We also analyzed the patients' clinical history, physical findings, laboratory tests, and responses to treatment. RESULTS: We identified four different mutations (one of which was novel) in all of the patients examined. The novel heterozygous missense mutation, p.R225W, was found in one patient with mild nonpainful myotonia. Our patients exhibited various clinical phenotypes: pure myotonia in four, and PMC in one, and HYPP in one. The four patients with pure myotonia were initially diagnosed as having myotonia congenita (MC), but a previous analysis revealed no CLCN1 mutation. CONCLUSIONS: Clinical differentiating between sodium-channel myotonia (SCM) and MC is not easy, and it is suggested that a mutational analysis of both SCN4A and CLCN1 is essential for the differential diagnosis of SCM and MC.

Multicenter Investigation on Clinical Characteristics, Cognitive Impairments, Behavioral and Psychological Symptoms of Demented Elderly in Busan-Gyeongnam Province

OBJECTIVES: The purpose of this study is to examine the state of demographic findings with clinical characteristics, cognitive impairment and behavioral psychological symptoms of demented elderly in Busan-Gyeongnam Province. METHODS: Patients with dementia who were registered at nine medical centers in Busan Metropolitan City and Gyeongnam Province were the major subjects of this study. Data was collected by face-to-face interview. The final sample consisted of 144 cases after eliminating several incomplete questionnaires. Based on the collected data, the authors evaluated demographic findings, clinical characteristics, and cognitive impairment and behavioral psychological symptoms of the patients with dementia using statistical analyses. All of the patients were taken the Korean version of Mini-Mental State Examination(K-MMSE), the Clinical Dementia Rating Scale(CDR) and the the Korean version of Neuropsychiatric Inventory(K-NPI). RESULTS: Approximately 61% of the patients with dementia in Busan-Gyeongnam Province were women, and their mean age was 72.9(SD=8.3) years old. Their average education level was 2.3(SD=1.3) years. Among the demented elderly, Alzheimer's disease accounted for 68% compared with vascular dementia(32%) and the proportion of mild stage of dementia was above 50%. The mean K-MMSE score was 16.7(SD=6.2), the mean CDR score was 1.3(SD=0.8), and the Barthel Index with K-IADL score were 16.7(SD=5.4) and 1.5(SD=0.9). The average score of K-NPI was 22.6(SD=22.5) and the number of manifested K-NPI was 4.9(SD=2.8). The K-NPI score has increased in demented elderly as the severity of dementia getting worse according to the CDR score. The number of manifested K-NPI was significantly more prevalent in patients with AD than that of patients with VD. CONCLUSION: This study is a meaningful approach to the state of demographic findings, clinical characteristics, cognitive impairment and behavioral psychological symptoms associated with the dementied elderly who were comprehensively examined in Busan-Gyeongnam Province. Based on this study, we found that the demographic information was comparable with other epidemiologic study in Korea and our study patients were relatively mild stage of demenitia according to the assessment of cognition and behavioral symptom scales.

The Differences of Clinical Features between Alzheimer's Disease and Vascular Dementia According to Progression

BACKGROUND: The differences in clinical features are important when differentiating between Alzheimer's disease (AD) and vascular dementia (VD). There have been many studies comparing the severity of progression in both diseases. They have assessed individual symptoms but have not explained the differences and global change of progression comprehensively. We have evaluated the cognitive and non-cognitive functions at the same time and evaluated the differences between AD and VD. METHODS: One hundred and thirty-eight dementia patients from Busan?Gyeongnam Dementia Association outpatient clinics were analyzed. All of the patients underwent the Korean version of the Mini-Mental State Examination (K-MMSE), the expanded version of the Korean Clinical Dementia Rating Scale (CDR), the Korean version of the Neuropsychiatric Inventory (K-NPI), the scales for activity of daily living, and the Short form of the Samsung Dementia Questionnaire (S-SDQ). RESULTS: There were 93 patients with AD and 45 with VD. VD patients revealed more severe Barthel Index of Activity of Daily Living (B-ADL) deficits. AD patients had more severe memory and orientation deficiency in CDR 1 and CDR 2. VD patients revealed much faster decline of K-MMSE score between CDR 2 and CDR 3. CONCLUSIONS: These results suggest that VD patients display more severe B-ADL difficulty, while AD patients display more severe memory difficulty and disorientation. B-ADL progresses in the earlier stages in VD and in the later stages in AD. Global cognitive dysfunction progression is the opposite: in the earlier stages in AD and in the later stages in VD.

The Differences of Behavioral and Psychological Symptoms in the Patients of Alzheimer's Disease and Vascular Dementia

BACKGROUND: Behavioral and psychological symptoms (BPSD) are common in dementia. These may be helpful for clinical differentiation between Alzheimer's disease (AD) and vascular dementia (VD). Most previous studies have reported the prevalence and severity of BPSD regardless of severity of progression. However, we evaluated the differences of BPSD by grading dementia progression and including severe cases only. METHODS: 141 dementia outpatients from clinics of Busan-Gyeongnam Dementia Association in Korea were analyzed. All patients were administered the Korean version of the Neuropsychiatric Inventory (K-NPI), the expanded version of Korean Clinical Dementia Rating Scale (CDR), and the Korean version of Mini-Mental State Examination (K-MMSE). RESULTS: There were 95 patients with AD and 46 patients with VD. AD patients revealed higher frequency of manifested BPSD symptoms and most of subscales showed higher composite scores also. But apathy was more severely and frequently manifested in VD. AD patients had more frequent night-time behavior and aberrant motor symptoms above 3 point in CDR 0.5 and VD patients had more frequent apathy symptom above 3 point in CDR 1. CONCLUSIONS: These results suggest that generally AD patients revealed more frequent and severe BPSDs than VD patients. Apathy was a more dominant symptom in VD. It seemed that some of the symptoms were valuable clues for the differential diagnosis even though a better designed study was required.

Factors Affecting Depression and Life Satisfaction in Family Caregivers of Patients with Dementia

BACKGROUND: The purposes of this study were to examine the state of depression and life satisfaction of family caregivers and to find out which factors would be significant in determining depression and life satisfaction of caregivers for the elderly with dementia. METHODS: Caregivers of patients with dementia who were registered at nine medical centers in Busan Metropolitan City and Gyeongnam Province were the major subjects of this study. Data was collected by face-to-face interviews. The final sample consisted of 144 cases after eliminating several incomplete questionnaires. Based on the collected data, the authors evaluated demographic findings, general characteristics, and factors influencing depression and life satisfaction of the caregivers using statistical analyses. RESULTS: The severity of depression and the degree of life satisfaction in family caregivers were low. We found that caregiver's anxiety, monthly income, caregiver burden, non-relative network, self-confidence of caregiving, and the degree of the Barthel index of activity of daily living (B-ADL) were significant factors in determining depression of the caregivers (p<0.05). The following two variables were significant factors in determining the caregiver's level of life satisfaction: burden of caregiving costs and patient's Korean mini-mental state examination (K-MMSE) score (p<0.05). CONCLUSIONS: Our results showed that the level of anxiety, caregiver burden and social support, rather than the conditions of dementia patients, influenced depression and life satisfaction for the caregivers of patients with dementia. Therefore, in order to improve the quality of life for caregivers, we should consider psychosocial factors as well as patient's medical factors in influencing depression and life satisfaction.

The Difference of Caregiver Burden in Patients with Alzheimer's Disease and Vascular Dementia

BACKGROUND: The burden on caregivers of patients with dementia has an impact on medical, economic, and social areas. However, not enough attention is given to this burden in Korea. There are also very few reports comparing the burden experienced by caregivers of patients with Alzheimer's disease (AD) and vascular dementia (VD). METHODS: One hundred and forty four Alzheimer's and vascular dementia patients were recruited by nine medical centers in the metropolitan city of Busan and the Gyeongnam province. We evaluated the global dementia state of patients in terms of cognitive functions, behavioral and psychological symptoms of dementia, and the activity of daily living along with caregiver burden with the length of care time per day. The Burden Interview, Caregiver Burden Inventory (CBI), Life Satisfaction Index-Z, Beck Depression Inventory, and Beck Anxiety Inventory were conducted by face-to-face interviews with the caregivers. We compared the differences of caregiver burden related to the cause of dementia and according to dementia severity. RESULTS: There were 98 AD patients (68.1%) and 46 VD patients (31.9%). There were 89 females (61.8%) and 55 males (38.2%). Most of the global dementia states did not differ between AD and VD except for the Barthel index (p<0.05). Most of the caregiver burden tests were scored worse in VD. The differences of CBI-time dependent burden and CBI-developmental burden were statistically significant in all the patients (p<0.05). CONCLUSIONS: Our study suggests that VD patients have more caregiver burden than AD patients and that the physical activity of daily living influences caregiver burden.

The Change of Behavioral and Psychological Symptoms according to the Progression of Alzheimer's Disease

BACKGROUND: The evaluation of behavioral and psychological symptoms (BPSD) is important for the diagnosis and management of Alzheimer's disease (AD). Previous studies have reported the prevalence and severity of BPSD changes. However, these studies have mainly focused on the AD patients with mild to moderate severity. Our study investigated the BPSD in AD patients with more advanced stages and looked at the prevalence and severity of BPSD with the progression of disease. METHODS: One hundred thirty six patients with probable AD received the Korean version of the neuropsychiatric inventory along with the expanded version of the Korean Clinical Dementia Rating Scale (CDR) and the Korean version of the Mini-Mental State Examination (K-MMSE). RESULTS: The mean K-MMSE, CDR and NPI scores were 10.1 (SD=7.1), 2.0 (SD=1.5) and 32.7 (SD=26.2), respectively. CDR and K-MMSE scores did not correlate with the total NPI score but did correlate with some of the subscale NPI scores. Apathy had the highest relationship to CDR (r=0.39, p<0.01). Aberrant motor was most correlated with the total score of NPI (r=0.65, p<0.01). The mean number of positive NPI items was 4.3, which ranged from 2.1 (CDR 5 group) to 5.4 (CDR 2 group). The most frequent symptom was apathy and the least was euphoria. The severity of BPSD increased as the dementia severity increased to CDR 2 except apathy. Night-time behavior and anxiety were frequent in the early stages whereas apathy and aberrant motor were frequent symptoms in later stages. CONCLUSIONS: These observations suggest that BPSD is relatively independent of cognitive functions. The prevalence and severity of BPSD with the exclusion of apathy, increased as the dementia severity increased from CDR 0.5 to CDR 2 and then declined declined except apathy.

Development of the Korean Stroop Test and Study of the Validity and the Reliability

BACKGROUND: The Stroop color word test is useful to examines the frontal lobe function of selective attention and inhibition. The Korean Color Word Stroop Test(K-CWST) was widely used in Korea. But, it was difficult in elderly individual with low educational level and visual problem and in patients with more progressed dementia. So we developed the Korean Stroop Test(KST). METHODS: The KST consist of word reading(WR), color naming(CN), interference word reading(IWR) and interference color naming (ICN). The interference tasks are naming the ink color of color words which were mismatched with word meaning. We measured reaction time and number of error. This study used the K-CWST to assess and compare the KST in eighteen probable alcohol related dementia patients and nineteen normal control. All subjects received the Korean version of Mini-Mental State Examination (K-MMSE) and the K-CWST and the KST. We tested reliability and validity of the KST. Also we enrolled normal adult from 41 to 80 year old for evaluating the change of the KST test with age. RESULTS: The KST tasks were correlated with K-MMSE -0.33(p<0.05) to -0.63(p<0.001) and K-CWST correlated with K-MMSE 0.37 (p<0.05) to 0.55(p<0.01). The interference color naming of KST was correlated the most to K-MMSE -0.78(p<0.001). The interference color naming of KST and interference color naming of K-CWST was correlated by 0.81(p<0.001). The internal consistency were 0.78 (Cronbach's alpha). The KST score was statistically different between alcohol related dementia patients and normal subjects in CN, ICN and ICN error. The KST was not differ in old age group except some tasks. CONCLUSION: The KST has a excellent reliability and validity. It takes less time and easy than the K-CWST. So the KST is a good test for evaluating frontal lobe function in elderly with low educational level of older people.

Current Epidemiologic Status of Stroke

OBJECTIVE: To evaluate the epidemiological data of stroke patients admitted to Dong-Eui Hospital. METHOD: We performed a prospective study on 1370 cases of stroke consecutively admitted to the hospital from June, 2001 to May, 2002 during hospitalization by medical records and questionaire. RESULT: The highest incidence of the stroke was noted in the group of 60 years of age. The proportion of stroke subtypes were infarct (75.2%), intracranial hemorrhage (21.2%), and subarachnoid hemorrhage (3.6%). Sixteen percents of patients arrived over 24 hours after onset of stroke. The seasonal incidence was in order of frequency of spring, winter, autumn, and summer. The highest occurrence of the stroke was noted in May. The onset time of stroke was highest between 7: 00 am and 8: 00 am. Risk factors in stroke by the order of frequency were hypertension (61.1%), abnormal EKG at admission (45.5%), hyperlipidemia (38.3%), smoking (36.6%), previous stroke history (24.7%), and diabetes mellitus (24.7%). The common complications during hospitalization were pneumonia (7.6%), gastritis (5.6%), depression (4.8%), and hepatitis (4.6%). CONCLUSION: Although the results of this study obtained from one local hospital in Korea, they are valuable as basic epidemiologic data of stroke for the rospective community- based study in the future.

The Clinical Efficacy of Subcutaneous Sumatriptan (Imigran) for Acute Treatment of Migraine

Sumatripan is a selective agonist at the 5-hydroxytryptamine (5HT,) -like receptor. An open, uncontrolled study was conducted to evaluate the therapeutic response of Korean patients to sumatriptan 6mg using an autoinjector for acute migraine attacks. 38 migraineurs were diagnosed by neurologists and included in the study. However, 7 patients were withdrawn as they failed to have an attack and one more or one additional patient was withdrawn due to syncope immediately after the first injection Patients recorded details of each attack and the response to treatment in a diary card. A total of 64 attacks in 30 patients were finally 'mcluded to evaluate the efficacy of treatment. Sumatriptan was very effective at relieving acute migraine attacks of various severity and the associated symptoms (nausea, vomiting, photophobia and phonophobia). Within two and a half hours after injection, 97% (62/64) showed a significant improvement of symptoms from moderate/severe at baseline to mild/none after treatment. There is no significant statistical difference of response of treatment about each type of migraine (classic migraine vs common migraine, chisquare test, ;? = 3. 84, p = 0. 650). Adverse events occurred 46% (30/65) of attacks. These were usually mild and transient, the most common being chest discomfort, pain at site of injection, nausea/vomiting, neck pain/stiffness, dizziness, sensation of weakness and tingling. In conclusion, sumatriptan taken by subcutaneous injection using an automjector was highly effective, fast acting and well tolerated in the treatment of acute migraine.

Clinical Experience of Subacute Sclerosing Panencephalitis treated with Alpha-interferon and Ionsiplex

Subacute sclerosing panencephalitis (SSPE) is a slowly progressing, chronic persistent fatal central nervous system disease, involving gray and white matter, especially white matter caused by measles virus that affecting children and young adult. 45 to 68% of affected individuals had measles before the age of 2. Current knowledge of the pathogenesis of SSPE involves mutation of the measles virus, resulting in lack of production of the M(Matrix)-protein. No therapeutic maneuvour gas been proven conclusively to be of value. But recently intraventricular alpha-interferon (a-IFN) injection combined with oral inosiplex increase the length of survival and may bring remission or stabilization in SSPE. We report a case of SSPE which was diagnosed by history, clinical manifestation, typical EEG findings, high titer of measles antibodies in cerebrospinal fluid and serum by hemagglutinin inhibition method. We tried intraventricular a-IFN injection via Ommaya reservoir and oral inosiplex.