Mortality trend and predictors of mortality in dysphagic stroke patients postpercutaneous endoscopic gastrostomy.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) feeding is widely used in stroke patients suffering from persistent dysphagia; however, predicting the risks and benefits of PEG insertion in the individual patient is difficult. The aim of our study was to investigate if candidate risk factors could predict short-term mortality risk in poststroke patients who had PEG tube insertion for persistent dysphagia. METHODS: This was a retrospective study of 3504 consecutive stroke patients admitted to two metropolitan hospitals during the period January 2005 to December 2013 and who also underwent PEG insertion for feeding due to persistent dysphagia. RESULTS: A total of 102 patients were included in the study. There were 22 deaths in 6 months after insertion of PEG tubes and 20 deaths of those occurred within 3 months post PEG. Those who survived beyond 6 months showed significantly lower mean age (75.9 ± 9.0 years vs. 83.0 ± 4.9 years, P < 0.001), a lower mean American Society of Anesthesia (ASA) score (3.04 ± 0.63 vs. 3.64 ± 0.58, P < 0.001) compared to nonsurvivors. In multiple Logistic, age (P = 0.004, odds ratio [OR] = 1.144; 95% confidence interval [CI]: 1.044-1.255); ASA (P = 0.002, OR = 5.065; 95% CI: 1.815-14.133) and albumin level pre-PEG insertion (P = 0.033, OR = 0.869; 95% CI: 0.764-0.988) were the independent determinants of mortality respectively. CONCLUSIONS: We propose that age, ASA score and albumin level pre-PEG insertion to be included as factors to assist in the selection of patients who are likely to survive more than 3 months post PEG insertion.

Staging of argyrophilic grains: an age-associated tauopathy.

We have reported that the ambient gyrus is the site with the greatest accumulation of argyrophilic grains (AGs) and that the degeneration of the ambient gyrus is responsible for dementia with grains. Here we analyzed 1,405 serial autopsy cases from 2 hospitals and detected AGs only in cases older than 56 years of age. The distribution of AGs followed a stereotypic regional pattern. Thus, we propose the following staging paradigm: stage I: AGs restricted to the ambient gyrus and its vicinity; stage II: AGs more apparent in the anterior and posterior medial temporal lobe, including the temporal pole, as well as the subiculum and entorhinal cortex; and stage III: abundant AGs in the septum, insular cortex, and anterior cingulate gyrus, accompanying spongy degeneration of the ambient gyrus. Sixty-three of 65 (96.9%) argyrophilic grain stage III cases without other dementing pathology were classified as 0.5 or higher in the clinical dementia rating. Forty-seven of 50 dementia with grains cases (94%) were stage III and 3 were stage II. No association with apoE genotyping was detected. Our study further confirms that dementia with grains is an age-associated tauopathy with relatively uniform distribution and may independently contribute to cognitive decline in the elderly.

Lewy body-related alpha-synucleinopathy in aging.

To clarify the significance of Lewy body (LB)-related alpha-synucleinopathy in aging, we investigated the incidence of LBs in 1,241 consecutive autopsy cases (663 males and 578 females). LB pathology was identified histologically in sections stained with hematoxylin and eosin and with anti-ubiquitin and anti-alpha-synuclein antibodies. Cases without LBs were classified as LB stage 0 (987 cases). Cases with LBs were classified as follows: LB stage I = incidental LBs (149 cases); LB stage II = LB-related degeneration without attributable clinical symptoms (47 cases); LB stage III = Parkinson disease without dementia (10 cases); LB stage IV = dementia with Lewy bodies (DLB) transitional (limbic) form (25 cases); and LB stage V = DLB neocortical form (23 cases). The average age at death was greater for those cases with LBs. There were no gender differences in the LB pathology. G842A polymorphism in the paraoxonase I gene was associated with men in LB stage II or above and suggests a gender-specific risk factor. LB stage V had higher stages of neurofibrillary tangle and senile plaque involvement and also had a higher frequency of apolipoprotein E epsilon4. Our findings indicate that LBs are associated with cognitive decline, either independently or synergistically with neurofibrillary tangles and senile plaques.

Association of estrogen receptor alpha gene polymorphisms with neurofibrillary tangles.

Estrogen receptor alpha (ERalpha) may be implicated in the pathogenesis of Alzheimer's disease (AD). The aim of this study was to clarify the association between ERalpha gene polymorphisms and AD-related pathologic changes. The staging of neurofibrillary tangles (NFT) and senile plaques (SP) was performed according to the method by Braak and Braak and two polymorphisms, PvuII (P or p) and XbaI (X or x), of the ERalpha gene were typed in 551 Japanese cadavers (294 men and 257 women; mean age, 80.8 years). Distributions of the NFT and SP stages significantly correlated with age (NFT: r = 0.306, p < 0.0001; SP: r = 0.237, p < 0.0001) and were significantly higher in patients with the apolipoprotein E epsilon4 allele (p < 0.0001). Possession of the P allele showed a trend to be associated with a more serious NFT stage, but had no relationship with the SP stage. In men, a significant association between PvuII polymorphism and the NFT stage (p = 0.002) was found, revealing a gene- dose effect of the P allele. Similar results were obtained in the men without the epsilon4 allele (p = 0.011). Multiple regression analyses demonstrated that age was the strongest determinant of the NFT stage, possession of the epsilon4 allele was the next strongest, and PvuII polymorphism was the third strongest (p < 0.0001, R(2) = 0.144). The XbaI polymorphism did affect neither the NFT stage nor the SP stage. In conclusion, the PvuII polymorphism of the ERalpha gene is associated with Braak NFT stages and possession of the P allele may act as a risk factor for AD in Japanese men, especially in those without the epsilon4 allele.

Granulomatous meningitis as a late complication of iodized oil myelography.

The present report is an autopsy case of an 83 year old man with severe kyphoscoliosis and granulomatous meningitis as a late complication of iodized oil myelography. He suffered from mild cognitive impairment and died of pneumonia. At autopsy, the brain showed yellow-brown granular material on its surface, mainly in the Sylvian fissure. Microscopically, granulation tissue was seen around areas of ossification encasing the foreign material. Iodized oil apparently changed into two types of foreign bodies: eosinophilic membranous lipodystrophy-like features and homogenous yellow crystals of various sizes. The pathology was identical to foreign-body granulomatous meningitis, caused by iodized oil myelography, and caused cognitive impairment in this patient.

In situ detection of apolipoprotein E epsilon 4 in archival human brain.

A monoclonal antibody specific to apolipoprotein E 4 (apoE4) was applied immunohistochemically to archival human brain tissue. The examined 30 cases comprised four epsilon/epsilon4, 10 epsilon3/epsilon4, one epsilon2/epsilon4, 10 epsilon3/epsilon3 and five epsilon2/epsilon3 genotypes. The anti apoE4 antibody visualized senile plaques, neurofibrillary tangles and reactive astrocytes, as well as serum in the blood vessels and vascular smooth muscle cells in the cases of epsilon4. Moreover, the staining intensity was stronger in the cases carrying the epsilon4 homozygosity than in those cases of epsilon4 heterozygosity. Specific immunoreactivity was not obtained in those cases not carrying the epsilon4 allele. This method will allow in situ detection of apoE epsilon4 and contribute to studies of the effect of epsilon4 on Alzheimer's disease.

Accumulation of phosphorylated alpha-synuclein in aging human brain.

Alpha-synuclein in Lewy bodies (LBs) is phosphorylated at Ser129. We raised monoclonal and polyclonal antibodies to this phosphorylation site (psyn) and examined 157 serial autopsy brains from a geriatric hospital. Anti-psyn immunoreactivity was observed in 40 of these cases (25.5%). Immunohistochemistry revealed 4 novel types of pathology: diffuse neuronal cytoplasmic staining (pre-LB); neuropil thread-like structures (Lewy threads); dot-like structures similar to argyrophilic grains (Lewy dots); and axons in the white matter (Lewy axons). This novel pathology was abundantly present around LBs and also involved the limbic subcortical white matter, the cerebral cortical molecular layer, and the spongiform changes of the medial temporal lobe associated with cases of dementia with LBs (DLB). The phosphorylated alpha-synuclein was limited to the temporal lobe in cases of Parkinson disease, spread from the temporal lobe to the frontal lobe in cases of DLB transitional form and further spread to the parietal and occipital lobes in DLB neocortical form. Our findings suggest that LB-related pathology initially involves the neuronal perikarya, dendrites, and axons, causes impairment of axonal transport and synaptic transmission, and later leads to the formation of LBs, a hallmark of functional disturbance long before neuronal cell death.