C1 PATIENT SUPPORT IN JAPAN
Kimura I
Tohoku University Graduate School of Medicine, Tohoku, Japan
E‐mail address for correspondence: [email protected]
Background of ALS care in Japan: ALS has been considered as a most symbolic intractable disease in Japan. It is a cardinal subject of political grant governance both for basic science and on health and welfare research.
Patients with ALS prefer long‐term admission to hospital rather than home care and 30 to 40% of patients request artificial ventilation at home or in hospital. Conditions for stable home care are unsatisfactory.
Problems to be solved: There is insufficient awareness of autonomy in each patient. Patients tend to depend upon long‐term hospital admission rather than attempt independent life at home. However, there are insufficient hospital beds available for patients who request admission, especially in the case of long‐term admissions to general hospitals.
Almost all prefectures have only a small number of neurologists and an insufficient number of home care nurses and caregivers. An increasing number of patients are living with ventilation under unsatisfactory conditions.
Strategy: 1) Increased availability of hospital beds for emergency use, respite for caregivers and occasional long‐term admission; 2) Establishment of medical networks for the total management of ALS patients by neurologists and general practitioners with the keen cooperation of nurses, caregivers and other health and social care professionals; 3) Clinical pathways committing hospitals, care homes and patients' homes to stable long‐term management of patients; 4) Construction of reasonable ward models in hospitals of the National Hospital Organisation and assessment of their effectiveness; 5) Promotion of autonomy, with the cooperation of JALSA and other patient support groups; 6) Mental and spiritual education through workshops and conferences; 7) Promotion of the Patients Support Bureau (PSB) project in all prefectures, focusing especially on the training of a coordinator.
Short term goals: With nationwide patient support, people with ALS will be able to select their way of life, whether at home or in a hospital or care home, from the earliest stages of the disease through to the final stage, and be able to maintain a meaningful personal life. They will be provided with sufficient palliative care without any bias on economic, legal or ethical grounds. Ultimately, all patients will be able to enjoy life with their families and maintain a higher quality of life.
C2 GUAM ALS: EPIDEMIOLOGICAL AND GENETIC OBSERVATIONS IN RELATION TO PDC AND DEMENTIA
Galasko D
University of California, San Diego, La Jolla, USA
E‐mail address for correspondence: [email protected]
Background: ALS had an extremely high incidence among the Chamorros of Guam from 1945 to 1960. ALS is related to Parkinson‐dementia complex (PDC), another endemic disease in Chamorros, and both show tau pathology of neurofibrillary tangles. The incidence of ALS declined over the next 40 years, as the environment and lifestyle of Guam became westernized. The rapid decline implicates an environmental factor, but specific environmental trigger(s) remain uncertain. Theories have included consumption of cycad products (directly, and possibly indirectly by eating fruit bats that are presumed to ingest cycad fruits) and low mineral concentration in the water supply. Genetic risk is implicated, because the population is inbred and went through a bottleneck. Asymptomatic Chamorros show an excess of tangles in cortical brain regions, suggesting that Chamorros are predisposed to form tau pathology.
Our research group studies the epidemiology and molecular genetics of ALS and PDC. We have also examined clinical and neuropathological aspects of late‐life dementia among Chamorros.
Studies and results: The prevalence of ALS has continued to decline and currently is similar to that of sporadic ALS worldwide. PDC has declined but had a point prevalence of 1.5% in Chamorros aged 65 years and older in 2004. Late‐life dementia (which we have termed Guam dementia) had a point prevalence of 12.4% in Chamorros of 65 years and older in 2004. Clinical features of late‐life dementia resemble those of Alzheimer's Disease, but there appears to be prominent tau (tangle) pathology relative to amyloid pathology.
The APO‐E e4 allele has a low frequency in Chamorros in general, and is not increased in ALS, PDC or Guam dementia. We previously found significant statistical association between a tau STRP and ALS/PDC. Ongoing genetic studies focus on tau, and a genome‐wide linkage study of ALS/PDC.
Another research group reported that BMAA, a plant amino‐acid found in cycads, occurs in high concentration in soluble and protein‐associated pools in brains of patients who died from PDC. However, we have been unable to detect BMAA in frozen brain tissue from Chamorros with PDC.
Conclusions: 1) ALS, PDC and late‐life dementia in Chamorros are a spectrum of disorders linked by tau pathology. 2) A gene‐environment interaction may best explain the altered pattern of incidence of these disorders over time. 3) The tau gene may provide clues regarding genetic predisposition) 4. Ongoing studies of PDC and late‐life dementia may help to clarify neuronal vulnerability and genetic factors, and may provide clues regarding the environment.
C3 OVERVIEW OF ALS VARIANTS IN THE KII PENINSULA OF JAPAN: EPIDEMIOLOGICAL, GENETIC AND CLINICOPATHOLOGICAL OBSERVATIONS IN RELATION TO ALS‐PARKINSONISM‐DEMENTIA COMPLEX
Kuzuhara S
Mie University School of Medicine, Tsu, Japan
E‐mail address for correspondence: [email protected]
Objective: To provide an overview and update on the epidemiology, genetics, clinical variations, and neuropathological findings of ALS and Parkinsonism‐dementia complex (PDC) of the Kii peninsula of Japan.
Background: The southern coast area of the Kii peninsula is one of the highest incidence ALS foci in the western Pacific. The first description of Kii ALS was in an old book published in 1689 and pioneer neurologists in modern Japan paid attention to its high prevalence rates in this area. In 1950s Kimura and Yase found extremely high ALS prevalence rates in two villages, Hohara and Kozagawa. These high incidence ALS foci were reported to have disappeared in early 1980s. However, our recent survey disclosed not only continuing high incidence rates of ALS but also high incidence rates of PDC.
Materials and methods: We analysed clinical features and neuropathological findings of 12 autopsy cases. Epidemiological study on the five years' average incidence rates of major clinical phenotypes were investigated in approximately 80 registered cases whose onset of the disease had been between 1945 and 2003. Genetic analysis was performed in recent cases in which family history had been investigated precisely.
Results: 1) According to the clinical phenotypes, the 12 autopsy cases were subgrouped into four ‘pure ALS’ cases, four ‘ALS with marked dementia’ cases, two ‘PDC’ cases and two “PDC followed by ALS” cases. All phenotypes showed the common neuropathological findings of a combination of ALS pathology and neurofibrillar tangles (NFTs) without senile plaques. Numerous NFTs were present in all cases of ALS with dementia, PDC and PDC followed by dementia, while NFTs of pure ALS cases varied from a few to numerous although the pattern of NFT distribution was similar to PDC. These findings suggest that pure ALS, ALS with dementia and PDC with or without ALS are on a spectrum of a single entity of ALS‐Parkinsonism‐dementia complex. 2) Descriptive epidemiology showed mild decline of the classic ALS phenotype, mild increase of the ALS with dementia phenotype and marked increase of the PDC phenotype. Low incidence rates of the PDC phenotype before 1990 may be due to the fact that the surveys before 1990 had been focused on ALS and little attention had been paid to PDC. 3) Genetic studies disclosed that family history was positive for ALS/PDC in approximately 80% of the cases although the pattern of transmission did not show Mendelian inheritance. We found 10 patients who developed ALS or PDC 24 to 50 years after having moved away from the village. Family history was positive for ALS/PDC in all of them.
Conclusion: ALS in the Kii peninsula is one of the clinical phenotypes of an entity of ALS‐Parkinsonism‐dementia complex that is neuropathologically characterized by a combination of ALS pathology and many NFTs. High incidence rates seem to have continued over the 50 years we studied, and the rates of familial occurrence are high. These findings suggest that genetic predisposition is important in the pathogenesis of ALS‐Parkinsonism‐dementia complex in the Kii peninsula.