Guillain-Barré syndrome in a local area in Japan, 2006-2015: an epidemiological and clinical study of 108 patients.

BACKGROUND AND PURPOSE: Many epidemiological studies of Guillain-Barré syndrome (GBS) and Fisher syndrome (FS) have been conducted in Europe and America. In contrast, epidemiological studies are rare in Asia where the GBS subtypes differ from those in Western countries. This study was undertaken to clarify the incidence of GBS and FS in a local area in Japan as well as their seasonal trends. METHOD: Seventy-one GBS and 37 FS patients were recorded from 2006 to 2015 in an area of approximately 1.5 million inhabitants in Japan. The incidence, seasonal trends and clinical features of GBS and FS were examined. RESULTS: The incidence rate of GBS was 0.42 cases per 100 000 person-years and that of FS was 0.22 cases per 100 000 person-years. The incidence of GBS increased with age and FS affected predominantly patients aged from 45 to 64 years old. There was some seasonal clustering of acute motor axonal neuropathy (AMAN) and FS in spring and summer, but it was not significant. AMAN and FS patients had a high frequency of preceding infection (AMAN, 68% gastrointestinal infection; FS, 65% upper respiratory infection). Antecedent respiratory infection was significantly associated with FS as an outcome. Serum antibodies to ganglioside GM1 were detected in 71% of AMAN patients and antibodies to GQ1b were detected in 81% of FS patients. CONCLUSIONS: Our study offers evidence of a lower incidence of GBS and a higher incidence of FS in a local area in Japan than in Western countries.

Preferential changes of skeletal muscle echogenicity in myotonic dystrophy type 1.

BACKGROUND AND PURPOSE: In myotonic dystrophy type 1 (DM1), weakness of distal limb muscles affects quality of life. Non-invasive evaluation of muscular involvement by muscle sonography could be useful for characterizing muscle-specific involvement. METHODS: Sonography of the lower leg and forearm was performed in 19 patients with DM1 and 10 control subjects. The mean echo intensities (EIs) of seven limb muscles were obtained by computer-assisted histogram analysis and compared within DM1 according to the overall clinical severity. RESULTS: The EIs of the muscles were significantly higher in DM1 than in the controls (P < 0.01), except for the soleus (P = 0.4). Comparison of adjacent muscles showed the following: (i) greater EIs in flexor digitorum profundus than flexor carpi ulnaris (P < 0.01) and flexor digitorum superficialis (P = 0.02), and (ii) greater EIs in the medial head of the gastrocnemius than the soleus (P < 0.00001). In a subgroup analysis of DM1 according to the modified Rankin Scale (mRS), the more severe subgroup (mRS = 4-5) had lower mean EIs than the less severe subgroup (mRS from 1-3) (P = 0.01) in the flexor digitorum superficialis but not in other muscles. CONCLUSIONS: Preferential high echogenicity in the medial gastrocnemius and deep finger flexors is suggestive of DM1. Muscle echogenicity is not generally related to functional dysfunction in DM1.

Intramuscular dissociation of echogenicity in the triceps surae characterizes sporadic inclusion body myositis.

BACKGROUND AND PURPOSE: Differential diagnosis of sporadic inclusion body myositis (s-IBM) and polymyositis (PM)/dermatomyositis (DM) is difficult and can affect proper disease management. Detection of heterogeneous muscular involvement in s-IBM by muscle sonography could be a unique diagnostic feature. METHODS: Sonography of the lower leg and forearm was performed in patients with s-IBM, PM/DM and control subjects (n = 11 each). Echo intensities (EIs) of the adjacent muscles [medial head of the gastrocnemius versus soleus and the flexor digitorum profundus (FDP) versus flexor carpi ulnaris (FCU)] were scored by three blinded raters. The mean EIs of these muscles were compared using computer-assisted histogram analysis. RESULTS: Both evaluation methods showed high echoic signals in the gastrocnemius of patients with s-IBM. EIs were significantly different between the gastrocnemius and soleus in patients with s-IBM, but not in those with DM/PM and the controls. In the forearm, although the EI of the FDP was higher in the s-IBM group than in the other groups, the EI differences between the FDP and FCU did not differ significantly between disease groups. The difference in area under the curves to differentiate between s-IBM and DM/PM was greatest between the gastrocnemius-soleus EIs (0.843; P = 0.006). CONCLUSIONS: High echoic signals in the medial gastrocnemius compared with those of the soleus are suggestive of s-IBM over PM/DM.

REG Iα is a biomarker for predicting response to chemotherapy with S-1 plus cisplatin in patients with unresectable stage IV gastric cancer.

BACKGROUND: The regenerating gene Iα (REG Iα) is involved in gastric carcinogenesis as an antiapoptotic factor. Therefore, we investigated whether REG Iα confers resistance to chemotherapeutic drugs in gastric cancer (GC) cells and whether REG Iα expression is useful for predicting the response to chemotherapy and outcome in patients with GC. METHODS: A total of 70 patients with unresectable stage IV GC received first-line chemotherapy with S-1 and cisplatin (S-1/CDDP). The expression of REG Iα was evaluated immunohistochemically using biopsy samples obtained before chemotherapy, and its relationship to clinicopathological parameters was analysed statistically. The effects of REG Iα gene induction on resistance to 5-FU or CDDP treatment were examined by cell survival assay and flow cytometry. RESULTS: Of the 70 patients with unresectable stage IV GC, 19 (27%) were positive for REG Iα expression. The expression of REG Iα was independently predictive of poorer progression-free and overall survival in such patients (hazard ratio (HR) 2.46; P=0.002 and HR 1.89; P=0.037, respectively). The gene induction of REG Iα conferred resistance to cell death induced by 5-FU or CDDP in GC cells. CONCLUSION: In patients with stage IV GC, REG Iα, which confers resistance to chemotherapeutic drugs in GC cells, is a potential biomarker for predicting resistance to S-1/CDDP treatment.

Prevalence of Parkinson's disease and atypical parkinsonian syndromes in a rural Japanese district.

OBJECTIVES: To investigate the prevalence of Parkinson's disease (PD) and atypical parkinsonian syndromes (APS) in a rural Japanese district. METHOD: Collaboration with the medical institutions, the long-term care insurance system facilities, and the public health office. RESULTS: The crude prevalence rates were 175 per 100,000 (95% CI: 143-206) for PD, 18 (8-28) for progressive supranuclear palsy, 17 (7-26) for multiple system atrophy (MSA), and 9 (2-16) for corticobasal degeneration. The age-adjusted prevalence rates were 109 per 100,000 (88-134), 10 (2-17), 13 (4-21), and 6 (0-12), for each condition. There was a preponderance of women with PD and of men with APS. Nine of the 116 PD patients and 7 of the 29 APS patients were newly diagnosed in this study. CONCLUSIONS: There are high prevalence rates for PD and APS and suboptimal recognition of APS. This is the first epidemiological prevalence study of MSA from Japan.

A phase-II trial of dose-dense chemotherapy in patients with disseminated thymoma: report of a Japan Clinical Oncology Group trial (JCOG 9605).

BACKGROUND: To evaluate the safety and efficacy of dose-dense weekly chemotherapy in the treatment of advanced thymoma. METHODS: Subjects comprised patients with histologically documented chemotherapy-naïve thymoma with stage-IVa or IVb disease. Thymic carcinoma, carcinoid or lymphoma cases were excluded. Patients received 9 weeks of chemotherapy: cisplatin (25 mg m(-2)) on weeks 1-9; vincristine (1 mg m(-2)) on weeks 1, 2, 4, 6 and 8; and doxorubicin (40 mg m(-2)) and etoposide (80 mg m(-2)) on days 1-3 of weeks 1, 3, 5, 7 and 9. Chemotherapy courses were supported by granulocyte colony-stimulating factor. Post-protocol local therapy was allowed. RESULTS: From July 1997 to March 2004, 30 patients were entered. Three were ineligible due to different histology. Chemotherapy-associated toxicity was mainly haematological and was well tolerated, with no deaths due to toxicity, and 87% of patients completed the planned 9-week regimen. Overall response rate was 59%, with 16 of the 27 eligible patients achieving partial response. Median progression-fee survival (PFS) was 0.79 years (95% confidence interval: 0.52-1.40 years), and PFS at 1 and 2 years was 37 and 15%, respectively. Overall survival rates at 2 and 5 years were 89 and 65%, respectively. CONCLUSION: In stage-IV thymoma patients, weekly dose-dense chemotherapy offers similar activity to conventional regimens.

Association of genetic polymorphisms with interferon-induced haematologic adverse effects in chronic hepatitis C patients.

Interferon (IFN)-based combination therapy with ribavirin has become the gold standard for the treatment of chronic hepatitis C virus infection. Haematologic toxicities, such as neutropenia, thrombocytopenia, and anaemia, however, frequently cause poor treatment tolerance, resulting in poor therapeutic efficacy. The aim of this study was to identify host genetic polymorphisms associated with the efficacy or haematologic toxicity of IFN-based combination therapy in chronic hepatitis C patients. We performed comprehensive single nucleotide polymorphism detection in all exonic regions of the 12 genes involved in the IFN signalling pathway in 32 healthy Japanese volunteers. Of 167 identified polymorphisms, 35 were genotyped and tested for an association with the efficacy or toxicity of IFN plus ribavirin therapy in 240 chronic hepatitis C patients. Multiple logistic regression analysis revealed that low viral load, viral genotypes 2 and 3, and a lower degree of liver fibrosis, but none of the genetic polymorphisms, were significantly associated with a sustained virologic response. In contrast to efficacy, multiple linear regression analyses demonstrated that two polymorphisms (IFNAR1 10848-A/G and STAT2 4757-G/T) were significantly associated with IFN-induced neutropenia (P = 0.013 and P = 0.011, respectively). Thrombocytopenia was associated with the IRF7 789-G/A (P = 0.031). In conclusion, genetic polymorphisms in IFN signalling pathway-related genes were associated with IFN-induced neutropenia and thrombocytopenia in chronic hepatitis C patients. In contrast to toxicity, the efficacy of IFN-based therapy was largely dependent on viral factors and degree of liver fibrosis.

Transcranial magnetic stimulation for differential diagnostics in patients with parkinsonism.

OBJECTIVE: We investigated transcranial magnetic stimulation (TMS) parameters in patients with parkinsonism, particularly in the early stages of the disease. SUBJECTS AND METHODS: We performed TMS in 48 patients with PD, progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). We measured motor threshold (MT), latency (L), motor-evoked potential amplitude and central motor conduction time (CMCT) and cortical silent period (CSP). Furthermore, we selected and compared 27 patients with a disease duration of less than 3 years. RESULTS: CMCT, MT, L and CSP were different among the three groups. Post hoc analyses revealed that CMCT and CSP were the shortest in PD, and that MT was significantly lower in PD than in MSA. In patients whose disease duration was less than 3 years, CMCT and CSP were different among the three groups. Post hoc analyses showed significantly shorter CMCT in PD. CONCLUSIONS: TMS can detect the pathophysiological difference among the groups in the early stages of the disease.

Adolescent smoking behaviour and cigarette brand preference in Japan.

OBJECTIVES: As part of efforts to develop a smoking control strategy for Japanese adolescents, the results of two nationwide surveys on adolescent smoking behaviour were compared. DESIGN: Descriptive study on smoking behaviour among high school students was conducted. Self-reporting anonymous questionnaires were administered to 115,814 students in 1996 and 106,297 in 2000 through randomly sampled junior and senior high schools throughout Japan. MAIN OUTCOME MEASURES: Smoking prevalence, proportion of smokers by usual sources of cigarettes, national estimated cigarettes consumed by minors, share of cigarette brands smoked by high school students. RESULTS: The experiment rate among junior high school boys decreased in 2000 compared with that in 1996, whereas current and daily smoking rates did not. Although prevalence among Japanese girls was much lower than that among boys, prevalence among girls increased in 2000. The main source of cigarettes among high school smokers was vending machines. The proportion of smokers who usually purchased cigarettes from vending machines increased in 2000, in spite of the 1998 introduction of restrictions on night-time operations. Japanese adolescents were more likely than adults to smoke American cigarette brands, and the adolescent market share of American brands has increased rapidly, especially for menthol brands. CONCLUSIONS: This survey revealed the seriousness of the problem of smoking behaviour among Japanese high school students, and suggested that this behaviour may be influenced by social environmental factors, including the marketing strategies of the tobacco industry. Action should be taken to reduce the prevalence and impact of pro-tobacco marketing messages and to abolish cigarette vending machines.

Treatment of implanted peritoneal cancer in rats by continuous hyperthermic peritoneal perfusion in combination with an anticancer drug.

To study the feasibility of combined hyperthermic and anticancer drug treatment for peritoneal cancer, we devised a continuous hyperthermic peritoneal perfusion system in combination with mitomycin C. The model uses i.p.-transplantable rat ascites hepatoma 100B cells. Hyperthermic peritoneal perfusion alone or combined with mitomycin C was performed after i.p. inoculation of the tumor cells into rats. In rats treated with combined peritoneal perfusion (41.5 degrees) and mitomycin C, the mean survival times were significantly prolonged as compared to those of rats treated with peritoneal perfusion at 41.5 degrees alone. Our results suggest that combined hyperthermic peritoneal perfusion and mitomycin C treatment may represent a therapeutic and prophylactic treatment for peritoneal metastasis after gastric cancer surgery in humans.

Specific requirement for inorganic phosphate for induction of bilayer membrane conductance by the cationic uncoupler carbocyanine dye.

The trinucleous divalent cationic cyanine dye triS-C4(5) was shown to be an uncoupler of oxidative phosphorylation in mitochondria only in reaction medium containing inorganic phosphate (Pi). This dye also induced marked increase in the electrical conductance of a phospholipid bilayer membrane in bathing solution containing Pi, but not in solution containing Tris-HCl buffer without Pi. Time-dependent fluctuation of the electrical current across the bilayer membrane was observed in the presence of triS-C4(5) only in bathing solution containing Pi. This fluctuation could be due to perturbation of the bilayer membrane structure induced by the cooperative action of the cyanine dye and Pi, and this perturbation should be directly related to their effects in increasing membrane conductance and also causing uncoupling in mitochondria.

Do published criteria improve clinical diagnostic accuracy in multiple system atrophy?

OBJECTIVE: To assess the accuracy of a clinical diagnosis of multiple system atrophy (MSA) and compare it to the Quinn and Consensus criteria for MSA using neuropathologically examined cases from the Queen Square Brain Bank for Neurological Disorders. METHODS: Fifty-nine cases with a neurologic diagnosis of MSA when last assessed prior to death were studied. RESULTS: In 51 (86%) of these cases, the diagnosis of MSA was confirmed pathologically. False positive diagnoses included PD (n = 6), progressive supranuclear palsy (n = 1), and cerebrovascular disease (n = 1). When applying either set of diagnostic criteria, a diagnosis of probable MSA gave lower sensitivity but higher positive predictive value than one of possible MSA. Application of either set of diagnostic criteria was superior to actual clinical diagnosis made early in the disease, but there was little difference by the last clinic visit. CONCLUSIONS: This study shows a high diagnostic accuracy for the clinical diagnosis of MSA by neurologists, with PD accounting for most of the false positive diagnoses. Application of either Quinn or Consensus criteria was superior to actual clinical diagnosis made early in the disease, but there was little difference by last clinic visit.

Immunocytochemical study of collagen in epidermal growth factor (EGF)-treated osteoblastic cells.

The alteration of collagen components in clone MC3T3-E1 cells by epidermal growth factor (EGF) was investigated immunocytochemically, using antibodies to type I and type III collagens. EGF transformed those cells that had become more slender than those of control cultures. Type I and type III collagens were observed in the same cells in both EGF-treated and control cultures. Type I collagen was decreased by EGF, whereas type III collagen appeared to be increased. However, no cells with only type III collagen were observed, suggesting that EGF influences collagen metabolism in clone MC3T3-E1 cells.

A U-shaped association between home systolic blood pressure and four-year mortality in community-dwelling older men.

BACKGROUND: Several studies in older people have found a U-shaped or J-shaped association of blood pressure with mortality. The increased mortality associated with the lowest levels of blood pressure in older people have been explained by concurrent illnesses and frailty, but previous studies used blood pressure measured on a single occasion. Such a casual value is different from the long-term average of blood pressure. We investigated the relation between the average level of 5-day consecutive home blood pressure and mortality in older people while adjusting for potential confounding factors including morbidity and frailty at baseline. METHODS: In 1992, 1186 community residents of a rural Japanese town, Kahoku, aged 65 or older, measured their blood pressure in their homes 20 times (four times per day, 5 consecutive days). The mean value of the 20 measurements was used to examine the association between home BP and subsequent 4-year mortality. A proportional hazards model was fitted while adjusting for activities of daily living impairment, medical history, antihypertensive medication, smoking, use of alcohol, and depression. RESULTS: A total of 134 persons died during the four-year follow-up period. There was no significant evidence that frailty is more prevalent in the lowest or highest systolic BP group than in intermediate groups. A U-shaped association between the average level of home systolic blood pressure and mortality was found in men while adjusting for potential confounding factors, including morbidity and frailty. We also showed the U-shaped curve of the association of systolic BP with all cause and noncardiovascular mortality in the whole population and the linear association of systolic BP with cardiovascular mortality. CONCLUSIONS: We showed a U-shaped association between the average level of systolic blood pressure measured at home and mortality in older men while adjusting for potential confounding factors including morbidity and frailty. Not only high home systolic BP, but also low home systolic BP, is an independent risk factor for mortality in older men. The mechanisms underlying the association between BP and mortality differ by levels of systolic BP. Cardiovascular deaths tended to be higher in the highest SBP group, and only noncardiovascular deaths were increased in the lowest SBP group. The latter finding suggests that low SBP may be not only an independent risk of mortality but also an indicator of a subclinical noncardiovascular comorbid condition.

Post-stroke hypertension correlates with neurologic recovery in patients with acute ischemic stroke.

To examine the clinical implications of post-stroke hypertension, defined as the rise in blood pressure on admission after the onset of ischemic stroke as compared with the blood pressure before stroke, and to assess the relationship between the value of post-stroke hypertension and neurologic recovery, we retrospectively studied 28 patients admitted to the hospital within 24 h (mean+/-SD, 6.7+/-7.0 h) after a first-ever, acute non-embolic ischemic stroke, whose blood pressure had been recorded at the outpatient clinic within 3 mo before stroke. The Canadian Neurological Scale was used to assess stroke severity, and neurologic recovery during the acute phase was calculated. The average duration of hospitalization was 18+/-9 d. The value of post-stroke hypertension and stroke severity on admission independently and significantly correlated with neurologic recovery (odds ratio, 1.06; 95% confidence interval, 1.00-1.12 and odd ratio, 0.20; 95% confidence interval, 0.06-0.72, respectively). There was also a significant linear correlation between the value of post-stroke hypertension and neurologic recovery (r= 0.50, p< 0.01). Furthermore, blood pressure after the onset of ischemic stroke was quite independent of blood pressure before stroke. We conclude that the value of post-stroke hypertension correlates with neurologic recovery in patients with acute non-embolic ischemic stroke. These results suggest that blood pressure control mechanisms change after the onset of acute ischemic stroke.

Chronic active VZV infection manifesting as zoster sine herpete, zoster paresis and myelopathy.

After lumbar-distribution zoster, an HTLV-1-seropositive woman developed chronic radicular sacral-distribution pain (zoster sine herpete), cervical-distribution zoster paresis and thoracic-distribution myelopathy. Detection of anti-varicella zoster virus (VZV) IgM and VZV IgG antibody in cerebrospinal fluid (CSF), with reduced serum/CSF ratios of anti-VZV IgG compared to normal serum/CSF ratios for albumin and total IgG, proved that VZV caused the protracted neurological complications. Diagnosis by antibody testing led to aggressive antiviral treatment and a favorable outcome.

Waveform changes of compound muscle action potential (CMAP) with muscle length.

Changes in finger positions influence the waveform of CMAP recorded from the muscle that moves that finger. The present study suggested that the muscle length, dependent on the finger position, was a main factor affecting the waveform. On shortening the muscle length, the amplitude of CMAP increased with concomitant reduction in the duration, and on lengthening, the amplitude decreased with concomitant increase in the duration. These changes are considered due to changes in propagation velocities of muscle fibers dependent on the muscle length. In nerve conduction studies, it is important to carefully monitor the finger position to distinguish the waveform changes with muscle length from those due to nerve lesions.