Substitution of Glu to Lys at Codon 332 on the GFAP Gene Alone Is Causative for Adult-onset Alexander Disease.

A 57-year-old man whose mother had been pathologically diagnosed with Alexander disease (ALXDRD), presented with cerebellar ataxia, pyramidal signs, and mild dysarthria. Brain magnetic resonance imaging revealed typical ALXDRD alterations, such as atrophy of the medulla oblongata (MO) and cervical spinal cord, a reduced sagittal diameter of the MO, and garland-like hyperintensity signals along the lateral ventricular walls. A genetic analysis of GFAP by Sanger sequencing revealed a single heterozygous mutation of Glu to Lys at codon 332 (c.994G>A) in the GFAP gene. Our results newly confirmed that p.E332K alone is the pathogenic causative mutation for adult-onset ALXDRD.

[Change in end-of-life care and staff thinking at a geriatric health services facility after the introduction of the "My Wishes" notebook].

AIM: A geriatric health services facility had been working to improve end-of-life care since 2014. In 2017, the facility introduced the My Wishes notebook, which confirms individual's medical choices and distributed the Explaining Practices and Intentions of End-of-life Care book in 2018, in order to help their staff improve care for older adults. Care staff used their learning in caregiving for older adults. This study aimed to clarify the change in end-of-life care and staff thinking at a geriatric health services facility after the introduction of the My Wishes notebook. METHODS: We requested cooperation from all care staff at a geriatric health services facility, and focus group interviews were conducted with 13 staff members over two days in June 2019. The responses in relation to two parameters, the staff members' thoughts and the change in end-of-life care, following the introduction of My Wishes were recorded and qualitatively analyzed. RESULTS: Six categories of responses were extracted from the qualitative analysis: "Difficulty in using My Wishes", "Effects of the use of My Wishes ", "The practice of sought care", "Intentional involvement with patients' families", "Self-confidence in end-of-life care", and "End-of-life care becoming common practice". CONCLUSION: After the introduction of My Wishes, the care staff found that there were difficulties in using My Wishes, such as writing on paper and difficulties in them hearing. On the other hand, they felt the effects of using My Wishes, such as knowing a new side, feeling further possibilities of care, and activating communication among interdisciplinary healthcare providers. Then, while intentionally engaging with patients' families, they will seek and practice the care that the older adults want. Furthermore, while repeatedly searching for and practicing the care that older adults want, they will gain confidence in providing care and change to normalize these care practices.

[Decision-making support for elderly individuals with dementia in a geriatric health service facility: A questionnaire survey on concrete care methods to draw wills of individuals].

PURPOSE: The purpose of this study was to clarify the care methods used by healthcare staff in service facilities to draw up wills for elderly individuals with dementia in daily life and the final stage in decision-making support. METHODS: A questionnaire survey was conducted among healthcare staff in a geriatric health service facility in August 2020. RESULTS: There were 45 subjects (16 males [35.6%]; 29 females [64.4%]). The average age was 42.2 (±12.3) years old, and the mean number of years of experience in a geriatric health service facility was 17.4 (±10.7) years. Deathbed care was provided to ≥90% of the subjects. A factor analysis of items related to decision making in elderly individuals with dementia revealed the first factor to be "support and communication to draw wills", the second factor to be "support and communication for expression to realize decision making", and the third factor to be "understanding, communication, and family support for decision-making realization." The totals of each of these three factors and "having confidence in care focusing on the viewpoint of elderly individuals with dementia" were significantly different. The correction between the Personhood of Approaches to Dementia Questionnaire Japanese version and the three subscales of decision making in elderly individuals with dementia had a significant coefficient of correlation. CONCLUSION: More polite communication methods are necessary for the formation, expression, and realization of the intentions of elderly individuals with dementia to support their decision making.

On-Reading (Chinese-Style Pronunciation) Predominance Over Kun-Reading (Native Japanese Pronunciation) in Japanese Semantic Dementia.

Japanese kanji (morphograms) have two ways of reading: on-reading (Chinese-style pronunciation) and kun-reading (native Japanese pronunciation). It is known that some Japanese patients with semantic dementia read kanji with on-reading but not with kun-reading. To characterize further reading impairments of patients with semantic dementia, we analyzed data from a total of 9 patients who underwent reading and writing tests of kanji and kana (Japanese phonetic writing) and on-kun reading tests containing two-character kanji words with on-on reading, kun-kun reading, and specific (so-called Jukujikun or irregular kun) reading. The results showed that on-reading preceding (pronouncing first with on-reading) and kun-reading deletion (inability to recall kun-reading) were observed in nearly all patients. In the on-kun reading test, on-reading (57.6% correct), kun-reading (46.6% correct), and specific-reading (30.0% correct) were more preserved in this decreasing order (phonology-to-semantics gradient), although on-reading and kun-reading did not significantly differ in performance, according to a more rigorous analysis after adjusting for word frequency (and familiarity). Furthermore, on-substitution (changing to on-reading) errors in kun-reading words (27.0%) were more frequent than kun-substitution (changing to kun-reading) errors in on-reading words (4.0%). These results suggest that kun-reading is more predominantly disturbed than on-reading, probably because kun-reading and specific-reading are closely associated with the meaning of words.

[Application of dementia care mapping (DCM) for one year in a geriatric health services facility: Effects of developmental evaluation based on collaboration by medical and welfare staff aimed at person-centred care].

PURPOSE: This study aimed to clarify the effects of dementia care mapping (DCM) for one year in a healthcare center for older adults. DCM was conducted between September 2016 and August 2017. The care staff include nurses and caregivers in a narrow sense, medical staff, such as a physician, physical therapists, and occupational therapists worked on DCM as care staff in this study. RESULTS: There were 24 participants, with an average work experience of 7.21 (±4.74) years. In comparison to the baseline evaluation, the final assessment of self-efficacy through person-centred care showed significant improvement in 'Forecasting and Problem Solving on the Job' within 'Perceived Job Competence of Care Workers'. Six main categories of content were extracted from focus group interviews: 'Awareness,' 'Change of Elderly People under the Care of Staff throughout the Development of Mapping', 'Affirmative Feelings of Care Staff for Mapping', 'Negative Feelings for Mapping', 'Need for the Efficacy and Efficiency of the Mapping', and 'Mapping Based on the Age of the Participant and Future Prospects for Mapping'. The results of person-centred care showed that both the older patients and the staff noticed changes through the development of mapping. CONCLUSION: The developmental evaluation, based on collaboration by medical and welfare staff can improve self-efficacy through the practice of person-centred care and improves the ability to solve problems during the provision of care.

Metachronous primary cancer of the tongue and malignant lymphoma of the small intestine: A case report.

RATIONALE: Oral cancer often causes secondary primary cancers in the upper gastrointestinal tract. However, there are no reports of secondary primary cancers in patients with oral squamous cell carcinoma and malignant lymphoma of the small intestine. This report describes a case of metachronous multiple primary cancers of the tongue and small intestine malignant lymphoma. PATIENTS CONCERNS: The patient was admitted to our department with the chief complaint of pain in the right tongue. Partial tongue resection and supraomohyoid neck dissection were performed. One year after surgery, the patient experienced abdominal pain and bloody stools. DIAGNOSIS: Diffuse large B-cell lymphoma (DLBCL) was diagnosed via histological examination. INTERVENTIONS: A terminal ileum resection was performed. Postoperatively, the patient received 6 courses of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP). OUTCOMES: Five years after his initial diagnosis, there is no evidence of recurrence, metastasis, or other primary cancer. LESSONS: Oral cancer patients should always be followed up owing to a possibility of malignant tumors in other areas.

Ischemic Stroke due to Virologically-Confirmed Varicella Zoster Virus Vasculopathy: A Case Series.

BACKGROUND: Limited data are available regarding the characteristics and prognosis of patients with stroke due to varicella zoster virus (VZV) vasculopathy. METHODS: We studied 4 patients (2 men and 2 women; age, 38-63 years) from a single center who developed acute ischemic stroke due to VZV vasculopathy. The virological diagnosis was confirmed by detecting VZV DNA and/or the IgG antibody to VZV in the cerebrospinal fluid. RESULTS: Three patients were taking immunosuppressive agents, including prednisolone and/or methotrexate, at baseline. Each patient had a characteristic skin rash prior to stroke, with the interval from rash to stroke onset ranging from 13 to 122 days. Two patients experienced antecedent cranial nerve palsies; one had the third, seventh, ninth, and 10th nerve palsies and the other had the fourth nerve palsy before stroke. Cerebral infarctions were located in the anterior circulation lesion (n = 1), in the posterior circulation lesion (n = 2), and in both lesions (n = 1). Intracranial arterial stenosis was only identified in one patient on magnetic resonance angiography. A high plasma d-dimer level was detected in 1 patient, whereas high ß-thromboglobulin and platelet factor 4 levels were detected in 2 patients. As a result of combined therapies with acyclovir, steroid, and antithrombotic agents, neurological symptoms markedly improved in 3 patients, whereas 1 patient was left with moderate hemiplegia. CONCLUSIONS: Cranial nerve palsies may be prodromal symptoms of VZV-associated stroke. Increased levels of thrombotic markers may support the use of antithrombotic agents, although the benefit of combined treatment should be determined through larger studies.

Attenuation and scatter correction in I-123 FP-CIT SPECT do not affect the clinical diagnosis of dopaminergic system neurodegeneration.

The purpose of this study was to assess the influence of different reconstruction factors in N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-I-123 iodophenyl)nortropane (I-123 FP-CIT) single-photon emission computed tomography (SPECT) images for the diagnosis of dopaminergic system neurodegeneration (DSND).Seventy-three patients (38 females, 35 males) suspected of DSND were included in this study. The patients were divided into 3 groups on the basis of their final clinical diagnoses; patients with Parkinson disease (group 1, n = 36), patients with other DSND (group 2, n = 19), patients without DSND (group 3, n = 18). FP-CIT accumulation in the striata was evaluated visually and semiquantitatively. SPECT images were classified visually as normal or abnormal based on the previous report. For semiquantitative analysis, we used DaTView software (Aze Corporation), and specific binding ratios (SBR) and asymmetry indices (AI) were calculated. Visual and semiquantitative evaluations for different reconstruction factors were compared among the 3 groups.In the visual evaluation, there were no differences among DSND diagnostic capabilities of attenuation and scatter correction by computed tomography attenuation correction scatter correction, computed tomography attenuation correction, Chang attenuation correction, and non-attenuation and -scatter correction. In the semiquantitative evaluation, receiver operating characteristic analysis of SBR and AI for clinical DSND diagnostic ability (group 1+2 vs 3) showed no significant difference among the reconstruction factors by multiple comparisons.Although the values of SBR and AI were changed and image quality could be improved when attenuation correction and/or scatter correction were applied, the clinical impact of these reconstruction factors for the diagnosis of DSND was negligible.

Dietary supplementation with (-)-epigallocatechin-3-gallate reduces inflammatory response in adipose tissue of non-obese type 2 diabetic Goto-Kakizaki (GK) rats.

(-)-Epigallocatechin gallate (EGCG), a major catechin in green tea, is an antioxidant associated with the reduction of oxidative stress in vitro. However, the mechanisms underlying the effects of EGCG on adipose tissue-related metabolic disturbances in vivo are not understood. This study examined whether dietary supplementation of EGCG reduces the oxidative stress-associated inflammatory response in the mesenteric adipose tissue of non-obese type 2 diabetic Goto-Kakizaki (GK) rats. GK rats were fed a normal diet or diet containing 0.1, 0.2, or 0.5% EGCG (w/w) for 25 weeks. The mRNA levels of IL-1ß were significantly reduced in GK rats given 0.1% EGCG (0.059 ± 0.008; means ± SEM in arbitrary unit) compared with those in GK rats given a control diet (0.135 ± 0.011), but not in those given 0.2% EGCG (0.123 ± 0.012) or 0.5% EGCG (0.112 ± 0.019). The mRNA and protein level of other genes for inflammatory responses such as IL-18, TNF-α, MCP-1, CD11s, CD18, and resistin were also significantly reduced in rats given 0.1% EGCG, but not in those given ≥ 0.2% EGCG. This suggests that supplementation with EGCG at relatively low concentrations (0.1%) in GK rats reduces expression of genes and proteins involved in inflammation in adipose tissue.

Novel humanized anti-CD20 antibody BM-ca binds to a unique epitope and exerts stronger cellular activity than others.

Cellular activity of BM-ca, a novel humanized anti-CD20 antibody, was quantitatively compared with that of two other anti-CD20 antibodies used for clinical practice, rituximab and ofatumumab. The results of a complement-dependent cytotoxicity (CDC) assay revealed that the strongest antibody was ofatumumab, followed by BM-ca, with rituximab being the weakest. Ofatumumab and BM-ca were effective not only against rituximab-sensitive SU-DHL-4 cells but also against rituximab-resistant RC-K8 cells. In an antibody-dependent cell-mediated cytotoxicity (ADCC) assay, although the effective concentrations against SU-DHL-4 cells were almost the same among these three antibodies, the maximum cytotoxic level was the highest for BM-ca. In an anti-cell proliferation assay using SU-DHL-4 cells, BM-ca was the most effective and ofatumumab, the weakest. Against RC-K8 cells, only BM-ca was effective. When combined with each of four cancer chemotherapeutics (prednisolone, vincristine, hydroxydaunorubicin, and cisplatin), BM-ca exerted the most effective combinatorial anti-cell proliferation activity. To assess the in vivo effect of BM-ca, we intravenously administered BM-ca into cynomolgus monkeys and found that the peripheral B-cell levels did not decrease in half of the animals. Sequencing of cDNA encoding CD20 of cynomolgus monkeys revealed that the responders and nonresponders had Leu/Pro (hetero) and Leu/Leu (homo) at amino acid (a.a.) position 160, respectively, suggesting that the epitope recognized by BM-ca was around this a.a. By analyzing reactivity to synthetic peptides, the epitope recognized by BM-ca was estimated to be a.a.'s 156-166, not shared with rituximab and ofatumumab. These results suggest BM-ca to be a promising anti-CD20 antibody having superior properties and recognizing a unique epitope.

Dietary supplementation with a low dose of (-)-epigallocatechin-3-gallate reduces pro-inflammatory responses in peripheral leukocytes of non-obese type 2 diabetic GK rats.

(-)-Epigallocatechin-3-gallate (EGCG), which is largely found in green tea, is known to eliminate reactive oxygen species and associated inflammatory responses in vitro and in cells. However, the in vivo mechanisms underlying the effects of EGCG on the amelioration of metabolic disorders are not fully understood. In this study, we examined whether dietary supplementation with EGCG reduces inflammatory responses in peripheral leukocytes of a non-obese type 2 diabetes animal model, Goto-Kakizaki (GK) rats. GK rats at 9 wk of age were fed a control high-fat diet (46 energy % from lard and corn oil) or a high-fat diet containing 0.1%, 0.2%, or 0.5% EGCG (w/w) for 25 wk. The oxidative stress markers 8-hydroxydeoxyguanosine (OHdG) and total malondialdehyde (MDA) were reduced by supplementation with EGCG at 0.1%, but not at 0.2% or more. Significant reductions in the mRNA levels of genes related to inflammatory responses (TNF-α, IFN-γ, IL-1ß, IL-6, IL-18, MCP-1, CD11b, and S100a6), 8-OHdG, and total MDA were induced in peripheral leukocytes of GK rats by EGCG supplementation at 0.1%, but not at 0.2% or more, compared with rats fed the control diet. The present results suggest that supplementation with a low dose of EGCG reduces oxidative stress and the expressions of genes involved in inflammation in peripheral leukocytes of GK rats.

Simultaneous development of acute disseminated encephalomyelitis and Guillain-Barré syndrome associated with H1N1 09 influenza vaccination.

A 36-year-old man was admitted to our hospital because of urinary retention and muscle weakness affecting all 4 limbs after receiving a H1N1 09 influenza vaccination. Magnetic resonance imaging demonstrated multiple lesions in his brain and spinal cord. Furthermore, nerve conduction study showed acute sensorimotor neuropathy, and anti-GM2 antibodies were detected in his serum. Based on the temporal association and exclusion of alternative etiologies, we made a diagnosis of acute disseminated encephalomyelitis (ADEM) and Guillain-Barré syndrome (GBS). To our knowledge, this is the first case of co-morbid ADEM and GBS after influenza vaccination with positive anti-ganglioside antibodies.

Comparison of parameters of (123)I-metaiodobenzylguanidine scintigraphy for differential diagnosis in patients with parkinsonism: correlation with clinical features.

OBJECTIVES: The purpose of this study was to estimate the diagnostic accuracy of (123)I-metaiodobenzylguanidine (MIBG) scintigraphy to diagnose Lewy body disease (LBD), including Parkinson's disease (PD) and dementia with Lewy bodies, and to clarify the relationship between MIBG parameters and the clinical findings. METHODS: One hundred-and-forty-four patients with parkinsonism without diabetes mellitus or a history of cardiac disease were retrospectively selected in the study. Clinical diagnosis was confirmed by follow-up during more than 6 months by neurologists. All patients underwent MIBG imaging at 15 min (initial) and 4 h (delayed) after the tracer injection, and clinical features such as Hoehn and Yahr (H-Y) classification or symptoms specific to parkinsonism were also investigated. The heart to mediastinum ratio (H/M) and the washout ratio (WR) of MIBG were calculated, and correlation with the clinical features was analyzed. RESULTS: Ninety-seven and 47 patients were diagnosed as LBD and Parkinson's syndrome (PS), respectively. Initial and delayed H/M were significantly lower and WR was significantly higher in LBD than in PS (p < 0.0001). The initial H/M was independently correlated with tremor (F value 10.45), hesitation (F = 4.49), and hallucinations (F = 5.09) (p < 0.0001). The sensitivity and specificity for the diagnosis of LBD were 64.9 and 87.2% with initial H/M, 78.4 and 68.1% with delayed H/M, and 80.4 and 61.7% with WR, respectively. Using multivariate analysis, initial H/M (F = 39.33) and tremor (F = 10.46) were independently correlated to the diagnosis of LBD (r = 0.562, p < 0.0001) among the MIBG and various clinical parameters. CONCLUSION: The initial H/M was the most useful of the 3 different parameters of MIBG for the diagnosis of LBD, but had low sensitivity. WR and delayed H/M had no incremental value to initial H/M for the diagnosis of PD. Careful long-term follow-up is needed for patients with parkinsonism who are clinically diagnosed as LBD with normal initial H/M, or diagnosed as no LBD with low initial H/M.