The evaluation of brain perfusion SPECT using an easy Z-score imaging system in the mild cognitive impairment subjects with brain amyloid-ß deposition.

OBJECTIVE: The analysis of 99mTc-ECD single-photon emission computed tomography (SPECT) images using the easy Z-score imaging system (eZIS) program is useful for the diagnosis of early AD in daily medical practice. However, it remains unclear whether eZIS analysis can identify the amnestic mild cognitive impairment (MCI) subjects with brain amyloid-ß deposition. The aim of this study was to evaluate the usefulness of an eZIS analysis for predicting amnestic MCI subjects with brain amyloid ß deposition. PATIENTS AND METHODS: Twenty-three subjects with MCI (10 men and 13 women, mean age; 74.2 years) underwent brain perfusion SPECT and 11C-Pittsburgh Compound B positron emission tomography (PiB-PET). MCI subjects were divided into PiB-positive and PiB-negative subgroups. SPECT data was analyzed using the Specific Volume of interest Analysis of the eZIS program. Three indicators (severity, extent, and ratio) were calculated automatically and compared between the two subgroups. RESULTS: Five of 12 (41.7%) subjects in the PiB-positive subgroup and three of 11 (27.3%) subjects in the PiB-negative subgroup showed the abnormal value for each indicator. The frequency of subjects with abnormal ratio values was significantly higher in the PiB-positive subgroup compared to the PiB-negative subgroup (p=0.02), whereas that of subjects with abnormal values in severity and extent did not differ among the two subgroups. In particular, all subjects in the PiB-negative subgroup showed normal ratio values. Moreover, the subjects with abnormal values on two indicators, including ratio, or on all three indicators, showed PiB-positive. CONCLUSION: The analysis of brain perfusion SPECT using an eZIS program cannot identify the amnestic MCI subjects with brain amyloid-ß deposition. However, abnormal three indicators or normal ratio values may be helpful SPECT findings for predicting the results of PiB-PET in the amnestic MCI subjects.

Relationship between cytokine levels in the cerebrospinal fluid and 11C-Pittsburgh compound B retention in patients with mild cognitive impairment.

AIM: In the present study, we examined the relationship between cytokine levels in the cerebrospinal fluid (CSF) and 11 C-Pittsburgh compound B (PiB) retention in patients with mild cognitive impairment. METHODS: A total of 33 participants (12 men and 21 women; mean age 76.5 years) with mild cognitive impairment underwent neuropsychological assessments, PiB positron emission tomography and analysis of cytokine levels in the CSF. The CSF levels of 48 cytokines and growth factors were measured using multiplex immunoassays. PiB retention was assessed based on a standardized uptake value ratio. Mild cognitive impairment participants were classified as PiB-positive and PiB-negative, with a cut-off level of 1.4. We compared the CSF cytokine levels and Alzheimer's disease biomarkers, including ß-amyloid 1-42, total tau and tau phosphorylated at threonine 181, between the two subgroups, and evaluated the correlation between PiB retention or CSF Alzheimer's disease biomarkers and CSF cytokine levels. RESULTS: Cytokine levels in the CSF did not differ between the two subgroups. Macrophage inflammatory protein-1ß levels in the CSF significantly correlated with PiB retention only in the PiB-positive subgroup, whereas stem cell growth factor-ß levels significantly correlated with PiB retention in the PiB-negative subgroup. Furthermore, stem cell growth factor-ß levels significantly correlated with total tau and tau phosphorylated at threonine 181 levels in only the PiB-negative subgroup. CONCLUSION: The present findings suggest that macrophage inflammatory protein-1ß and stem cell growth factor-ß are associated with chronic inflammatory processes accompanied by amyloid deposition or AD pathophysiology. Geriatr Gerontol Int 2017; 17: 1907-1913.

Brain Perfusion in Corticobasal Syndrome with Progressive Aphasia.

BACKGROUND: Brain perfusion may differ between patients with corticobasal syndrome (CBS) with and without aphasia. METHODS: Twenty-six (9 males and 17 females; mean age 76 ± 5.3 years) patients with CBS were enrolled in the study. Brain MRI and single-photon emission computed tomography were performed in all subjects. Language was evaluated using the Standard Language Test of Aphasia. The patients were divided into two subgroups according to the presence or absence of progressive aphasia. Differences in the regional cerebral blood flow (rCBF) between the two groups were detected based on voxel-by-voxel group analysis using Statistical Parametric Mapping 8. RESULTS: All patients exhibited asymmetric motor symptoms and signs, including limb apraxia, bradykinesia, and akinetic rigidity. Of 26 patients, 9 had a clinically obvious language disturbance, characterized as nonfluent aphasia. Almost all CBS patients with aphasia exhibited cortical atrophy predominantly in the left frontal and temporal lobes with widening of the Sylvian fissure on MRI. The rCBF in the left middle frontal gyrus differed significantly between CBS patients with and without aphasia. CONCLUSION: CBS patients with aphasia exhibit motor symptoms predominantly on the right side and cortical atrophy mainly in the left perisylvian cortices. In particular, left frontal dysfunction might be related to nonfluent aphasia in CBS.

Role of ubiquitin-proteasome proteolysis in muscle fiber destruction in experimental chloroquine-induced myopathy.

Previous studies have documented the presence of rimmed vacuoles, atrophic fibers, and increased lysosomal cathepsin activity in skeletal muscle from animal models of chloroquine-induced myopathy, suggesting that muscle fibers in this type of myopathy may be degraded via the lysosomal-proteolysis pathway. Given recent evidence of abnormal ubiquitin accumulation in rimmed vacuoles, in this study we chose to examine the significance of the ubiquitin-proteasome proteolytic system in the process of muscle fiber destruction in experimental chloroquine myopathy. Expression of ubiquitin, 26S proteasome proteins, and ubiquitin ligases, such as muscle-specific RING finger-1 (MuRF-1) and atrogin-1/muscle atrophy F-box protein (MAFbx), was analyzed in innervated and denervated rat soleus muscles after treatment with either saline or chloroquine. Abnormal accumulation of rimmed vacuoles was observed only in chloroquine-treated denervated muscles. Ubiquitin and proteasome immunostaining, and ubiquitin, MuRF-1, and atrogin-1/MAFbx mRNAs were significantly increased in denervated soleus muscles from saline- and chloroquine-treated rats when compared with contralateral innervated muscles. Further, ubiquitin and ubiquitin ligase mRNA levels were higher in denervated muscles from chloroquine-treated rats when compared with saline-treated rats. These data demonstrate increased proteasomes and ubiquitin in denervated muscles from chloroquine-treated rats and suggest that the ubiquitin-proteasome proteolysis pathway as well as the lysosomal-proteolysis pathway mediate muscle fiber destruction in experimental chloroquine myopathy.

[A case of hematomyelia caused by coagulation--fibrinolysis abnormality accompanied with colon cancer and its metastasis].

A 76-year-old woman developed weakness and sensory loss in the lower limbs and urinary disturbance in four days. She had a history of operation for the ascending colon cancer and lung metastasis one year ago. Neurological examination revealed flaccid paraplegia, absent Achilles tendon reflex, severe disturbance of superficial and deep sensation below the L3 level, and vesicorectal abnormality. Magnetic resonance imaging (MRI) studies showed an intramedullary T1-iso, T2-low lesion with Gd-DTPA contrast enhancement in conus medullaris at LI level. The laboratory examination revealed the elevated level of serum FDP. D-dimer and TAT. She was diagnosed as hematomyelia, which may be caused by the activation of coagulation and fibrinolysis system. We suggested that the ascending colon cancer and lung metastasis may contribute to the coagulation-fibrinolysis abnormality.