Application of Suggestive Biomarkers in Dementia With Lewy Bodies With Masking of Typical Clinical Symptoms by Alzheimer Disease-type Pathology.

Dementia with Lewy bodies (DLB) is strongly associated with Alzheimer disease (AD)-type pathology and tends to mask the core clinical features of DLB. Therefore, there may be cases of undiagnosed DLB without suggestive biomarkers of DLB. We describe the case of a 63-year-old woman who was initially diagnosed as having AD and later diagnosed with DLB based on suggestive biomarkers of DLB. In this case, transient sleep talking with physical movements for several days led to the assessment of suggestive biomarkers for DLB in the absence of the core clinical features of DLB. For clinicians, diagnosing DLB in patients with AD-type pathology is challenging. However, the application of biomarkers suggestive of DLB to all patients with dementia is not realistic. To overcome the difficulties of clinical diagnosis of DLB, further research is needed regarding strategies for the application of suggestive biomarkers for DLB to appropriately diagnose DLB.

[Effects of ramelteon on a patient with circadian rhythm sleep disorder and mood disorder].

Ramelteon is a novel hypnotic characterized by its action as a melatonin receptor (MT1/MT2) agonist. It has been reported that ramelteon can alter the phase of the sleep period. We report a patient with circadian rhythm sleep disorder and mood disorder who improved with ramelteon. A 25-year-old man had a 5-year history of emotional instability, excessive daytime sleepiness, and difficulty awakening. He had been diagnosed with mood disorder and narcolepsy by a psychiatrist. Sertraline, milnacipran, valproate, and methylphenidate were ineffective, and so he presented to our hospital. Interview data and a sleep log demonstrated a delayed sleep phase. As other examinations such as actigraphy and video-polysomnography indicated no other diseases, the patient was diagnosed with circadian rhythm sleep disorder, delayed sleep phase type (ICSD-2). In addition, his mental symptoms were consistent with the criteria for cyclothymia (ICD-10). After the administration of ramelteon, the phase of his sleep period gradually advanced and his emotional instability improved. Because of the high rate of comorbidity between these two diseases, we should be aware of circadian rhythm sleep disorders that are masked by mood disorders.

Prediction of Co-Occurrence of Lewy Body Disease with Alzheimer's Disease.

Identifying the coexistence of Lewy body (LB) pathology with Alzheimer's disease (AD) in clinical practice is important in the era of anti-amyloid-ß antibody therapy. However, few studies have predicted the presence of comorbid LB pathology with AD using indicative biomarkers of dementia with Lewy bodies or by collecting detailed clinical symptoms. We report the clinical progression of a 67-year-old patient diagnosed with AD who developed rapid eye movement sleep disorder-like symptoms and transient visual hallucinations 10 years after AD onset and was considered to have comorbid LB pathology based on imaging indicative biomarkers of dementia with Lewy bodies.

Micrographia after midbrain infarction alleviated by Japanese calligraphy-style writing: A case report.

•A 77-year-old right-handed man experienced an infarct in the right midbrain.•Ipsilesional progressive micrographia occurred after the midbrain infarct.•Micrographia improved when the patient wrote as if practicing Japanese calligraphy.•Further studies should confirm the utility of Japanese calligraphy in such cases.

Syntactic Impairment Associated with Hypoperfusion in the Left Middle and Inferior Frontal Gyri after Right Cerebellar Hemorrhage.

Cerebellar injuries can cause syntax impairments. Cortical dysfunction due to cerebello-cerebral diaschisis is assumed to play a role in this phenomenon. Functional magnetic resonance imaging studies have repeatedly shown the activation of Broca's area in response to syntactic tasks. However, there have been no reports of selective syntax impairment and hypoperfusion restricted to this area after cerebellar injury. We herein report a patient with right cerebellar hemorrhage that led to marked syntax impairment along with severe hypoperfusion confined to the Brodmann area (BA) 45 (anterior part of Broca's area) and BA46.

A Patient with a Unilateral Insular Lesion Showing Bilaterally Reduced Perception of Noxious Stimulation.

No study has reported a unilateral localized cerebral lesion of the posterior insula bilaterally reducing noxious stimuli perception. A 57-year-old man with an infarct involving the right posterior insula presented with reduced somatosensory response in the upper and lower left extremities. Furthermore, there was a reduced response to noxious stimulation in the right upper and lower limbs. We noted reductions in pain, noxious heat and cold perceptions, and sensitivity to increasing temperature. Other somatic sensations, including non-noxious temperatures, remained intact in the right upper and lower extremities. These findings in our patient with a unilateral insular lesion indicated a bilaterally reduced perception of noxious stimulation.

Comparing Medial Temporal Atrophy Between Early-Onset Semantic Dementia and Early-Onset Alzheimer's Disease Using Voxel-Based Morphometry: A Multicenter MRI Study.

BACKGROUND: Early-onset Semantic dementia (EOSD) and early-onset Alzheimer's disease (EOAD) are often difficult to clinically differentiate in the early stages of the diseases because of the overlaps of clinical symptoms such as language symptoms. We compared the degree of atrophy in medial temporal structures between the two types of dementia using the voxel-based specific regional analysis system for Alzheimer's disease (VSRAD). METHODS: The participants included 29 (age: 61.7±4.5 years) and 39 (age: 60.2±4.9 years) patients with EOSD and EOAD, respectively. The degree of atrophy in medial temporal structures was quantified using the VSRAD for magnetic resonance imaging data. Receiver operating characteristic (ROC) analysis was performed to distinguish patients with EOSD and EOAD using the mean Z score (Z-score) in bilateral medial temporal structures and the absolute value (laterality score) of the laterality of Z-score (| right-left |) for indicating the degree of asymmetrical atrophy in medial temporal structures. RESULTS: The EOSD group had significantly higher Z and laterality scores than the EOAD group (Zscores: mean ± standard deviation: 3.74±1.05 vs. 1.56±0.81, respectively; P<0.001; laterality score: mean ± standard deviation: 2.35±1.23 vs. 0.68±0.51, respectively; P<0.001). In ROC analysis, the sensitivity and specificity to differentiate EOSD from EOAD by a Z-score of 2.29 were 97% and 85%, respectively and by the laterality score of 1.05 were 93% and 85%, respectively. CONCLUSION: EOSD leads to more severe and asymmetrical atrophy in medial temporal structures than EOAD. The VSRAD may be useful to distinguish between these dementias that have several clinically similar symptoms.

Primary human bone marrow adipocytes support TNF-α-induced osteoclast differentiation and function through RANKL expression.

PURPOSE: In previous reports, it was demonstrated that bone marrow adipocytes were related to steroid osteoporosis through osteoclastogenesis induced by Receptor Activator of Nuclear factor κ-B Ligand (RANKL) expression. The purpose of this study was to evaluate the effect of Tumor necrosis factor-alpha (TNF-α) on RANKL expression in bone marrow adipocytes, and osteoclast differentiation supported by human bone marrow adipocytes. METHODS: RANKL, osteoprotegerin (OPG), and macrophage-colony stimulating factor (M-CSF) mRNA expression in bone marrow adipocytes and their regulation by TNF-α treatment were measured by real-time RT-PCR. Co-cultures of bone marrow adipocytes and osteoclast precursors were performed with or without TNF-α, and osteoclast differentiation was evaluated morphologically and functionally. RESULTS: RANKL expression and an increase in the RANKL/OPG ratio in bone marrow adipocytes were stimulated by TNF-α treatment. In co-culture of bone marrow adipocytes and osteoclast precursors with TNF-α, the number of TRAP-positive multinuclear cells and resorption cavity formations of calcium phosphate film were increased. Osteoclast differentiation was suppressed by anti-RANKL antibody treatment. In co-culture with non-cell-contact conditions, no TRAP-positive cells or resorption cavity formations were observed. CONCLUSIONS: TNF-α increased RANKL expression in primary human bone marrow adipocytes. TNF-α induced the ability of bone marrow adipocytes to promote osteoclast differentiation and activity in a manner directly related to RANKL expression.

Simvastatin suppresses dexamethasone-induced secretion of plasminogen activator inhibitor-1 in human bone marrow adipocytes.

BACKGROUND: Osteonecrosis of the femoral head is a common complication of high-dose glucocorticoid treatment. Intravascular thrombosis is thought to be associated with the ischemic state of the femoral head. Plasminogen activator inhibitor-1 (PAI-1) is an adipokine, which are physiologically active substances secreted from visceral and subcutaneous adipocytes. PAI-1 suppresses fibrinolysis by binding tissue-type plasminogen activator. Several reports have described the relationship between PAI-1 and steroid-induced osteonecrosis of the femoral head, and the preventive effects of lipid-lowering agents (statins) against steroid-induced osteonecrosis of the femoral head. We previously reported that adipokines and dexamethasone induced PAI-1 secretion from bone marrow adipocytes. The purpose of the present study is to examine the effects of simvastatin on PAI-1 secretion from human bone marrow adipocytes in vitro. METHODS: Primary bone marrow adipocytes were extracted from collagenase-treated bone marrow fluid obtained from the femoral necks of 40 patients (6 men, 34 women; age range, 52-81 years) undergoing hip joint replacement surgery. After suspended culture with or without dexamethasone or simvastatin, PAI-1 mRNA expression was assessed by real-time RT-PCR. Total PAI-1 protein secretion in culture medium was assessed by enzyme-linked immunosorbent assay. RESULTS: PAI-1 mRNA expression was up-regulated by 388% (P=0.002) with dexamethasone, and down-regulated by 45% (P=0.002) with simvastatin, as compared to control levels. Dexamethasone increased total PAI-1 secretion by 166% (P=0.001) and simvastatin decreased total PAI-1 secretion by 64% (P=0.002). No significant changes were observed in adiponectin mRNA expression and secretion by dexamethasone and simvastatin, while pre-treatment with simvastatin reversed dexamethasone induced PAI-1 secretion by 89%, as compared to control levels. CONCLUSION: The present study confirmed the suppressive effects of simvastatin on PAI-1 expression and secretion from bone marrow adipocytes. Furthermore, pre-treatment with simvastatin reversed dexamethasone induced PAI-1 secretion. Simvastatin may thus exhibit preventive effects against steroid-induced osteonecrosis of the femoral head by suppressing PAI-1 secretion.

Numbsense of shape, texture, and objects after left parietal infarction: A case report.

Numbsense is a phenomenon, wherein patients can correctly respond to somatosensory stimuli at a higher rate than expected by chance, but cannot perceive the same stimuli consciously. Previously, numbsense has been reported in tactile localization of stimuli on the patient's own body. Here, we describe a patient with numbsense that involved touched objects. The patient could not recognize the majority of somatosensory stimuli after left parietal infarction, but could correctly select shape, texture, and object stimuli more frequently than expected by chance.

Aerobic oxygenation of α-methylene ketones under visible-light catalysed by a CeNi3 complex with a macrocyclic tris(salen)-ligand.

A hetero-tetranuclear CeNi3 complex with a macrocyclic ligand catalysed the aerobic oxygenation of a methylene group adjacent to a carbonyl group under visible-light radiation to produce the corresponding α-diketones. The visible-light induced homolysis of the Ce-O bond of a bis(enolate) intermediate is proposed prior to aerobic oxygenation.

[Frontotemporal Lobar Degeneration: A Historical Overview of the Concept].

Arnold Pick described a focal cortical syndrome caused by focal temporal and/or frontal cortical atrophy, later reffered to as Pick's disease (PiD), a prototype of frontotemporal lobar degeneration (FTLD). In contrast to the current concept of PiD, the presence of Pick bodies (tau-positive inclusions) was not thought to be necessary for the diagnosis of PiD. Four out of the seven patients in his original paper had predominant left temporal atrophy and language related symptoms corresponding to semantic dementia. It is now known that most patients with semantic dementia have transactive response DNA-binding protein 43kDa (TDP-43) pathology rather than tau pathology. The original concept of PiD was substantially similar to the current concept of FTLD, which has heterogeneous molecular pathology including tau, TDP-43 and fused in sarcoma (FUS).