Chifumi Iseki

Cerebral small vessel disease and chronic kidney disease (CKD): results of a cross-sectional study in community-based Japanese elderly.

Chronic kidney disease (CKD) is known as a risk factor for cardiovascular disease. In recent years, several experimental and epidemiological studies have suggested that CKD is associated with endothelial dysfunction; thereby, a CKD state may initiate both large and small vessel damage. The association between renal dysfunction and asymptomatic lacunar infarction was reported in a hospital-based study, whereas the relationship between cerebral small vessel disease (SVD)-related lesions and CKD could not be clarified in a community-based study. We performed a cross-sectional study to determine the relationship between silent cerebral SVD-related lesions and CKD in a total of 625 community-based Japanese elderly. In this study, subjects with lower estimated glomerular filtration rate levels tended to have more lacunar infarcts and higher grades of white matter lesions (WMLs). In addition, the mean grades of WMLs or the mean numbers of lacunar infarction in the subjects with albuminuria were greater than those in subjects without albuminuria. In the logistic regression analysis, the association between the presence of CKD and lacunar infarction or moderate WMLs (Fazekas grades 2 and 3) was statistically significant (odds ratio [OR]: 1.86 and 1.50, respectively). Furthermore, as we performed additional analysis, excluding the subjects with stage 2 hypertension (those with casual blood pressure >or=160/100 mm Hg) or diabetes, CKD remained to be an independent risk for cerebral SVD-related lesions. This is the first study showing the relationship between silent SVD-related brain lesions and the presence of CKD, independently of conventional cardiovascular risk factors, in community-based elderly.

Incidence of idiopathic normal pressure hydrocephalus (iNPH): A 10-year follow-up study of a rural community in Japan

BACKGROUND The epidemiology and pathophysiology of iNPH remain unclear. We aimed to investigate the incidence of iNPH in elderly inhabitants of the community, and to identify how ventriculomegaly develops on brain MRIs and how symptoms develop in iNPH patients. METHODS In 2000, 350 inhabitants, all 70-year-olds living in the community of Takahata in Japan, were asked to participate in a survey that included a questionnaire, physical examinations, cognitive screenings, and brain MRI studies. Using brain MRI as a screening, we defined having both Evans index of >0.3 and a narrow subarachnoid space and cortical sulci at high convexity (tight high convexity, THC) as suspicious findings for iNPH. Among the subjects who showed the iNPH feature on brain MRI, those who had gait disturbance and/or dementia were defined as possible iNPH. Twice during the 10 years, we administered the same check-up. RESULTS In the first survey, 271 inhabitants participated. During the 10 years, three new possible iNPH patients were found. The incidence of iNPH above 70 years old was estimated at 1.2/1000 persons per year. The iNPH patients developed their symptoms and brain MRI findings as follows; first, only THC without ventriculomegaly was observed on their brain MRIs, next, asymptomatic ventriculomegaly with features of iNPH on brain MRIs (AVIM) was seen, and then a final expression of symptoms of iNPH was shown. CONCLUSIONS The estimated incidence of iNPH in a community was higher than those estimated by previous studies where they collected patients at hospitals. There were subclinical or preclinical states before the development of iNPH.

Familial normal pressure hydrocephalus (NPH) with an autosomal-dominant inheritance: A novel subgroup of NPH

Normal pressure hydrocephalus (NPH) has two clinical forms: secondary NPH and idiopathic NPH (iNPH). Most patients with NPH occur sporadically: until now, only two families have been reported to have sibling cases of NPH. We here report a large family with 4 patients with elderly-onset NPH in three generations. All of them had cognitive impairment, gait disturbance, and urinary problems, along with normal pressure of cerebrospinal fluid. Their brain MRI showed enlargement of the ventricles and a disproportional narrowing of the subarachnoid space and cortical sulci at the high convexity of the cerebrum, which are the features of iNPH on MRI. The family interview also disclosed additional 4 patients who were suspected as having NPH. The disease seems to be inherited in an autosomal-dominant fashion. No known causes of secondary NPH were found in any of the patients. This is the first report to show a large family with NPH patients in three generations, who had clinical and MRI features indistinguishable from iNPH. This seems to represent a novel subgroup of NPH, familial NPH.

Carpal tunnel syndrome as an initial manifestation in a case of transthyretin-related familial amyloid polyneuropathy with a novel A120T mutation.

Transthyretin-related familial amyloid polyneuropathy (TTRAP) is an autosomal dominant disorder, involving the peripheral ervous system and visceral organs [1]. A valine-to-methionine ubstitution at position 30 (V30M) in the TTR gene is the most ommon mutation; however, genetic diagnosis has identified umerous non-V30M TTR variants in both familial and sporadic ases [1]. We report here a probably sporadic case presenting with ilateral carpal tunnel syndrome (CTS) as an initial symptom, with novel A120T mutation in the TTR gene.

Acupuncture Alleviated the Nonmotor Symptoms of Parkinson’s Disease including Pain, Depression, and Autonomic Symptoms

A woman started to feel intractable pain on her lower legs when she was 76. At the age of 78, she was diagnosed as having Parkinsons disease (PD). The leg pain was suspected to be a symptom of PD after eliminating other causes. The patient also suffered from nonmotor symptoms, depression, anxiety, hot flashes, and paroxysmal sweating. Though the patient had received pharmacotherapy including levodopa for 5 years, she still suffered from the nonmotor symptoms and was referred to our department. We treated her with acupuncture based on the Chinese traditional medicine and electroacupuncture five times per week. After the 2-week treatment, the assessment for the symptoms was as follows; visual analogue scale (VAS) score of the leg pain was 16 mm (70 mm, before), Hamiltons rating scales for depression (HAM-D) score was 9 (18, before), timed 3 m Up and Go took 20 steps in 30 sec (24 steps in 38 sec, before), and the Movement Disorder Society-sponsored revision of the Unified Parkinsons Disease Rating Scale (MDS-UPDRS) Part 1 score was 13 (21, before). Autonomic symptoms, hot flashes and paroxysmal sweating, were also alleviated. Acupuncture may be a good treatment modality for nonmotor symptoms in PD.

A segmental copy number loss of the sfmbt1 gene is a genetic risk for shunt-responsive, idiopathic normal pressure hydrocephalus (inph): A case-control study

Little is known about genetic risk factors for idiopathic normal pressure hydrocephalus (iNPH). We examined whether a copy number loss in intron 2 of the SFMBT1 gene could be a genetic risk for shunt-responsive, definite iNPH. Quantitative and digital PCR analyses revealed that 26.0% of shunt-responsive definite iNPH patients (n = 50) had such a genetic change, as compared with 4.2% of the healthy elderly (n = 191) (OR = 7.94, 95%CI: 2.82–23.79, p = 1.8 x 10−5) and 6.3% of patients with Parkinson’s disease (n = 32) (OR = 5.18, 95%CI: 1.1–50.8, p = 0.038). The present study demonstrates that a copy number loss within intron 2 of the SFMBT1 gene may be a genetic risk factor for shunt-responsive definite iNPH.

Pleiotropic effect of common variants at ABO glycosyltranferase locus in 9q32 on plasma levels of pancreatic lipase and angiotensin converting enzyme

For forty-three clinical test values presumably associated to common complex human diseases, we carried out a genome-wide association study using 600K SNPs in a general Japanese population of 1,639 individuals (1,252 after quality control procedures) drawn from a regional cohort, followed by a replication study for statistically significant SNPs (p = 1.95×10−9–8.34×10−39) using an independent population of 1,671 from another cohort. In this single two-stage study, we newly found strong and robust associations of common variants at the ABO histo-blood glycosyltransferase locus in 9q32 with the plasma levels of pancreatic lipase (P-LIP), in addition to successful confirmation of the known ABO association of angiotensin converting enzyme (ACE) independent of the ACE1 gene in 17q23.2 with the ACE level. Our results are compatible with the previously reported association between the ABO gene and pancreatic cancer, and show that the effect of these common variants at the ABO locus on the P-LIP and ACE levels is largely opposing and pleiotropic.