Clinicopathological study of dementia with grains presenting with parkinsonism compared with a typical case.

Argyrophilic grain disease (AGD) is one of the major pathological backgrounds of senile dementia. Dementia with grains refers to cases of dementia for which AGD is the sole background pathology responsible for dementia. Recent studies have suggested an association between dementia with grains and parkinsonism. In this study, we aimed to present two autopsy cases of dementia with grains. Case 1 was an 85-year-old man who exhibited amnestic dementia and parkinsonism, including postural instability, upward gaze palsy, and neck and trunk rigidity. The patient was clinically diagnosed with progressive supranuclear palsy and Alzheimer's disease. Case 2 was a 90-year-old man with pure amnestic dementia, clinically diagnosed as Alzheimer's disease. Recently, we used cryo-electron microscopy to confirm that the tau accumulated in both cases had the same three-dimensional structure. In this study, we compared the detailed clinical picture and neuropathological findings using classical staining and immunostaining methods. Both cases exhibited argyrophilic grains and tau-immunoreactive structures in the brainstem and basal ganglia, especially in the nigrostriatal and limbic systems. However, Case 1 had more tau immunoreactive structures. Considering the absence of other disease-specific structures such as tufted astrocytes, astrocytic plaques and globular glial inclusions, lack of conspicuous cerebrovascular disease, and no history of medications that could cause parkinsonism, our findings suggest an association between AGD in the nigrostriatal system and parkinsonism.

Correlations between cerebrospinal fluid homovanillic acid and dopamine transporter SPECT in degenerative parkinsonian syndromes.

Both cerebrospinal fluid (CSF) homovanillic acid (HVA) and striatal dopamine transporter (DAT) binding on single-photon emission computed tomography (SPECT) reflect nigrostriatal dopaminergic function, but studies on the relationship between the two have been limited. It is also unknown whether the reported variance in striatal DAT binding among diseases reflects the pathophysiology or characteristics of the subjects. We included 70 patients with Parkinson's disease (PD), 12 with progressive supranuclear palsy (PSP), 12 with multiple system atrophy, six with corticobasal syndrome, and nine with Alzheimer's disease as disease control, who underwent both CSF analysis and 123I-N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl)nortropane (123I-ioflupane) SPECT. We evaluated the correlation between CSF HVA concentration and the specific binding ratio (SBR) of striatal DAT binding. We also compared the SBR for each diagnosis, controlling for CSF HVA concentration. The correlations between the two were significant in patients with PD (r = 0.34, p = 0.004) and PSP (r = 0.77, p = 0.004). The mean SBR value was the lowest in patients with PSP and was significantly lower in patients with PSP than in those with PD (p = 0.037) after adjusting for CSF HVA concentration. Our study demonstrates that striatal DAT binding correlates with CSF HVA concentration in both PD and PSP, and striatal DAT reduction would be more advanced in PSP than in PD at an equivalent dopamine level. Striatal DAT binding may correlate with dopamine levels in the brain. The pathophysiology of each diagnosis may explain this difference.

A case of neonatal lupus erythematosus in a very low-birth-weight infant that suffered intraventricular hemorrhage at birth.

This report describes the case of a very low-birth-weight male infant with neonatal lupus erythematosus. His mother had Sjögren's syndrome, and her previous child had suffered a complete heart block. Accordingly, maternal steroid (betamethasone) therapy was administered to prevent a congenital heart block for 15 weeks (from 13 to 27 weeks' gestation). At 28 weeks' gestation, the mother was weaned off the steroid therapy, and an emergency cesarean section was carried out at 29 weeks and 6 days' gestation because of a nonreassuring fetal status (NRFS). At birth, the infant exhibited grade-III intraventricular hemorrhage (IVH). Although it is unclear why the infant developed a NRFS and IVH, the condition of the fetus should be carefully monitored during and after long-term maternal steroid treatment.

Anti-neurofascin 155 Antibody-positive Neuropathy in a Human Immunodeficiency Virus-infected Patient.

Human immunodeficiency virus (HIV)-associated neuropathy is a common complication of HIV infection and has several clinical subtypes. HIV-associated chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a demyelinating neuropathy whose clinical features are known to differ from those of CIDP in the HIV-uninfected population. We herein report a case of CIDP in an HIV-infected patient who was finally diagnosed with anti-neurofascin 155 (NF155) antibody-positive neuropathy. The clinical features, including clinical findings and therapeutic responses, were typical of paranodal antibody-mediated neuropathy. To our knowledge, this is the first case of anti-NF155 antibody-associated neuropathy in an HIV-infected patient.

Gait rhythm analysis as a new continuous scale for cerebellar ataxia: Power law and lognormal components represent the ataxic gait quantity.

We estimated the severity of cerebellar ataxia by analyzing gait rhythm. We measured the step times in patients with pure cerebellar ataxia and healthy controls and then analyzed the distribution of the ratios of adjacent times. Gait rhythm displayed the best adaptation when expressed as the sum of the power law and lognormal distributions in both groups, and the groups could be distinguished by the exponent of the power law distribution, reflecting the fractal property of gait rhythm. Gait rhythm might reflect different features of impairment in patients with cerebellar ataxia, making it a useful continuous scale for cerebellar ataxia.

Cerebrospinal fluid analysis is associated with enhancement on MRI in bacterial and tuberculous meningitis: A retrospective observational study.

OBJECTIVE: Along with cerebrospinal fluid (CSF) analysis, enhancement on contrast-enhanced MRI is useful to diagnose meningitis. However, the conditions for its appearance have not been clarified. This study aimed to investigate the association between CSF parameters and enhancement on contrast-enhanced head or spinal MRI in patients with bacterial meningitis (BM) or tuberculous meningitis (TM). METHODS: A total of 12 patients with BM and 23 patients with TM who underwent both CSF analysis and contrast-enhanced MRI were included. The correlation between CSF analysis and MRI findings has been examined using receiver operating characteristic (ROC) analysis. RESULTS: Contrast enhancement was found in 7 and 10 patients with BM and TM, respectively. Both CSF analysis and MRI were useful to distinct between BM and TM, and the enhancement implied the severity of them. In patients with BM, higher CSF protein and lower CSF glucose were associated with enhancement on MRI, while not only CSF protein and glucose but also leukocyte and lymphocyte counts were associated with it in TM. CSF adenosine deaminase (ADA) did not show discriminant ability of the MRI findings. CONCLUSIONS: CSF analysis is associated with enhancement on contrast-enhanced MRI both in BM and TM. Our findings indicate the importance of CSF analysis in assessing the need to perform contrast-enhanced MRI, which may be useful in diagnosis, distinction, and estimation of prognosis in those patients.

An Autopsy Report of a Case with Cerebral Infarction Complicated by Coronavirus Disease 2019 Infection.

We herein report a case of cerebral infarct in a patient with coronavirus disease 2019 (COVID-19) infection who died of aspiration pneumonia. The postmortem examination of the brain revealed embolic infarct with negative findings on quantitative reverse transcription polymerase chain reaction (qRT-PCR) as well as immunohistochemistry to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The systemic examination only revealed low copy numbers of SARS-CoV-2 in the bronchus. This is the first and so far only autopsy case of COVID-19 infection with pathologic and virologic findings of the postmortem brain in Japan.

Liver fibrosis in an extremely small infant for gestational age.

Premature infants with intrauterine growth restriction (IUGR) are at greater risk for an adverse perinatal outcome. IUGR affects hepatocyte function, but the histopathological changes in the postnatal liver are not well known. We report a male infant with severe IUGR. His mother was transferred to our hospital at 26 weeks of gestation because of preterm labor and severe IUGR. An emergency cesarean section was carried out because of a non-reassuring fetal status. The birth weight of the infant was 332 g. He showed congestive heart failure and marked hepatomegaly from birth. After 1 week, blood examinations showed hyperbilirubinemia with high direct bilirubin. Because of liver dysfunction, he received the minimal total parenteral nutrition for 7 days. After 1 month, he progressively developed ascites and coagulopathy, and died 3 months after birth. Liver autopsy showed diffuse perisinusoidal fibrosis. Fibrosis was also prominent around the central vein. Immunohistochemical study revealed many alpha-smooth muscle actin-positive cells, which represent activated hepatic stellate cells, and a few transforming growth factor-beta1-positive cells in the perisinusoidal fibrotic area. These results indicate that the infant developed chronic (end stage) liver failure by 3 months of age. We excluded congenital infection, metabolic syndrome and citrin deficiency. It is therefore conceivable that intrauterine cardiac failure may be responsible for liver fibrosis. Early detection of liver dysfunction soon after birth is a key to predict the prognosis of severe IUGR in preterm infants.

Associations of snoring frequency with blood pressure among the lean Japanese population: the Toon Health Study.

To date, there are few studies in Asian populations on the association between snoring (a major clinical symptom of sleep apnea) and hypertension. This study aims to examine whether snoring frequency is associated with blood pressure and hypertension in the general Japanese population, after adjustment for major confounding factors. A cross-sectional study of 2021 middle-aged Japanese men and women enrolled in the Toon Health Study between 2009-2012 was conducted. Snoring frequency was assessed using a self-reported questionnaire, and was classified into four categories: never, ≤2 times/week, ≥3 times/week, and unknown. Multivariable regression coefficients for each snoring category were calculated for systolic and diastolic blood pressure, and their odds ratios (ORs) and 95% confidence intervals (95% CIs) for hypertension were calculated after adjusting for major confounding factors. The same analyses were also conducted after stratification by several major confounding factors. Multivariable-adjusted means of systolic and diastolic blood pressure among individuals who snored ≥3 times/week were 4.57 mmHg and 2.58 mmHg higher, respectively, than in individuals who never snored (p < 0.05). The multivariable-adjusted OR (95% CI) for hypertension in the group that snored ≥3 times/week was 1.79 (1.29-2.48), compared with the group that never snored. We also found a significant positive association between snoring frequency and hypertension not only in normal and overweight individuals, but also in lean individuals (body mass index ≤22.8 kg/m2). Higher snoring frequency was associated with higher blood pressure and hypertension among both lean and non-lean Japanese.

Relationship between free T4 levels and postnatal steroid therapy in preterm infants.

BACKGROUND: Transient hypothyroxinemia is the most common thyroid dysfunction in preterm infants. Hypothalamic-pituitary-thyroid immaturity and non-thyroidal illness contribute to its etiology. The aim of the present study was therefore to determine the relationship between thyroid hormone status and early postnatal steroid therapy in preterm infants. METHODS: A prospective study of premature infants born at <28 weeks of gestation between July 2001 and June 2007 was conducted. Selective postnatal steroid (dexamethasone) therapy was used in lung disease treatment if the infants needed high mean airway pressure-assisted ventilation and supplemental oxygen at 2 weeks of age. Free T4 (FT4) and thyroid-stimulating hormone (TSH) levels were assessed at 2 weeks after birth. Blood samples in eight infants were available after starting steroid therapy. Infants receiving steroids (steroid (+); n= 8) were compared to those not receiving steroids (steroid (-); n= 73). RESULTS: The demographic data were not significantly different between the two groups. The neonatal illnesses and drug use were also not significantly different between the groups. The steroid (+) group had significantly lower FT4 and TSH levels at 2 weeks after birth than the steroid (-) group. The increase in FT4 levels after steroid withdrawal was greater than that during the same period in the steroid (-) patients. CONCLUSION: Even if it cannot be excluded that reduced FT4 and TSH concentrations are caused by non-thyroidal illness, the present study suggests that postnatal steroid treatment reduces the FT4 and TSH levels in premature infants born at <28 weeks of gestation.

Increased numbers of macrophages in tracheal aspirates in premature infants with funisitis.

BACKGROUND: Funisitis is a manifestation of the fetal inflammatory response syndrome, and intrauterine inflammation is involved in the pathogenesis of lung injury in premature infants. The aim of the present paper was to examine the relationship between funisitis and lung injury in premature infants born at <28 weeks gestation. The present study focuses on the number of macrophages in tracheobronchial aspirate fluid (TAF). METHODS: The numbers of CD68-positive cells in cell cytopreps in TAF collected at <24 h of age were determined on immunocytochemistry. The funisitis (+) group (n > 8) was compared with the funisitis (-) group (n > 16). RESULTS: There were no significant differences in gestational age and birthweight between these groups. The duration of intermittent positive pressure ventilation was significantly longer in the funisitis (+) group compared with the funisitis (-) group (P < 0.05). Funisitis (+) infants had increases of CD68+ macrophages in their TAF. The appearance of Wilson-Mikity syndrome (WMS), characteristic of the severe variant of chronic lung disease (CLD), was associated with funisitis (+) infants with higher numbers of macrophages. CONCLUSION: The presence of macrophages at birth plays an important role in the neonatal lung with funisitis.

Low level of tracheal cellular fibronectin in extremely premature infants with funisitis: relationship with respiratory distress 1 month after birth.

BACKGROUND: Funisitis reflects the fetal systemic inflammatory response in premature infants. Macrophages and neutrophils have been identified as key elements in the inflammatory process of the lungs, and secrete proteases that cause the destruction of the extracellular matrix (ECM). Fibronectin (FN) is the major constituent of the pulmonary ECM and exists in multiple isoforms arising from alternative RNA splicing. Extra domain A (EDA) is the major alternatively spliced segment, and the expression of EDA containing FN (EDA + FN) in the lungs is associated with distal pulmonary cell proliferation during alveolar formation. OBJECTIVE: To study the relationship between the presence of funisitis and EDA + FN levels in the tracheal aspirate fluid (TAF) of infants of less than 28 weeks' gestation. METHODS: The subjects included in this study were 26 extremely premature infants of <28 weeks' gestation at <24 hr of age, from whom the TAF was collected. These preterm infants were divided into two groups according to placental histology. The funisitis (+) group (n = 9) was compared with the funisitis (-) group (n = 17). The TAF supernatants were analyzed for IL-1ß, IL-6, IL-8, neutrophil elastase, and EDA + FN using enzyme-linked immunosorbent assay (ELISA). RESULTS: There were no significant differences in gestational age or birthweight between these groups. The funisitis (+) group had a significantly higher ventilator setting (inspired O(2) × mean airway pressure) at Day 28 than the funisitis (-) group. In the TAF, the concentrations of IL-1ß were significantly higher in the funisitis (+) group than in the funisitis (-) group, as were the concentrations of neutrophil elastase. The concentrations of EDA + FN were significantly lower in the funisitis (+) group than in the funisitis (-) group. CONCLUSIONS: Decreased EDA + FN in TAF might be one of the risk factors leading to respiratory distress in extremely premature infants with funisitis.

Fluorotetraphenylbismuth: a new reagent for efficient regioselective alpha-phenylation of carbonyl compounds.

Synthesis and X-ray crystallographic characterization of fluorotetraphenylbismuth (1) has been achieved for the first time, revealing that the bismuth center of 1 adopts a distorted trigonal bipyramidal geometry with three ipso carbons at the equatorial sites and one ipso carbon and fluorine atom at the apical sites. Contrary to the previous common understanding of this type of organobismuth(V) compound, 1 was found to be thermally stable, maintaining its amphiphilic property. Hence, 1 can be used as an off-the-shelf reagent in organic synthesis, and its utility has been clearly demonstrated in applications to the efficient alpha-phenylation of ketones and esters. For instance, simple mixing of 1 and 1-trimethylsiloxy-3,4-dihydronaphthalene in THF at -40 degrees C and stirring at room temperature for 10 min gave rise to 2-phenyl-1-tetralone almost quantitatively without formation of the polyphenylated products. In addition to the generality of this method, applicability of our approach to the selective alpha-alkenylation of carbonyl compounds was also demonstrated by the use of fluoro(2-phenylethenyl)tris(p-tolyl)bismuth (2) as a representative reagent. These results imply the vast potential of organobismuth(V) compounds of type 1 and 2 as useful precursors of a wide variety of pentavalent organobismuth compounds based on the utilization of the eminent fluorine-silicon interaction or the inherent basicity of the fluorine atom.