Mitochondrial malfunction in vanishing white matter disease： a disease of the cytosolic translation machinery

Vanishing white matter （VWM） disease - a disease of the cytosolic translation machinery： VWM is a recessive genet- ic neurodegenerative disease caused by mutations in any of the five genes encoding the subunits of translation initiation factor 2B （eIF2B） （Leegwater et al., 2001; OMIM 306896）.

Concepts and opportunities for repair in cerebral microvascular disease and white matter stroke

Diffuse changes in white matter resulting from cerebral microvascular disease contribute to cognitive impairment （Jokinen et al., 2011）, declines in global functionality （Inzitari et al., 2009）, and even death （Debette and Markus, 2010）. Twenty years ago, estimations of the clinical incidence of ce- rebral microvascular disease approached 11 million per year in the US alone （Leary and Saver, 2003）. More recent estima- tions suggest the prevalence of diffuse white matter disease and silent brain infarction approaches 20% and increases dramatically in the presence of cardiovascular risk factors （Fanning et al., 2014）.

A Retrospective Study of Branch Atheromatous Disease： Analyses of Risk Factors and Prognosis

The theory of branch atheromatous disease（BAD） has been commonly underused in clinical practice and research since it was proposed in 1989. In this study, we sought to explore clinical characteristics of its substypes and biomarkers for prognosis of BAD. A total of 176 consecutive patients with BAD were classified into two groups： paramedianpontine artery group（PPA group, n=70） and lenticulostriate artery group（LSA group, n=106）. Bivariate analyses were used to explore the relationship between white matter hyperintensities（WMHs）, National Institutes of Health Stroke Scale（NIHSS） scores and prognosis evaluated by the modified Rank Scale（m RS） at 6th month after stroke. The differences in prevalence of diabetes mellitus and a history of ischemic heart disease were statistically significant between PPA group and LSA group（χ~2=8.255, P=0.004; χ~2=13.402, P〈0.001）. The bivariate analyses demonstrated a positive correlation between NIHSS and poor prognosis in patients with BAD and in the two subtype groups, and a positive correlation between WMHs and poor prognosis in the PPA group. It is concluded that a significantly higher prevalence of diabetes mellitus and a history of ischemic heart disease exist in the PPA group than in the LSA group. In addition, high grades of NIHSS scores imply poor prognosis in patients with BAD and in the two subtype groups. Moreover, WMHs are a positive predictor for poor prognosis in patients in the PPA group.

Atlas-based deep gray matter and white matter analysis in Alzheimer's disease: diffusion abnormality and correlation with cognitive function

Objective To identify the diffusion alterations of deep gray matter(GM)and white matter(WM)among Alzheimer’s disease(AD),mild cognitive impairment(MCI)and healthy people by atlas-based analysis(ABA),and to investigate the respective relationship with cognitive function.Methods Twenty-one AD patients(AD group),8 MCI patients(MCI group)and

Microstructural white matter lesion in Alzheimer's disease: a diffusion tensor imaging study using voxel-based analysis

Objective To study the microscopic changes of white matter and the relationship between white matter changes and cognitive impairment in Alzheimer’s disease(AD)using voxel-based analysis of DTI.Methods Thirty-seven patients with probable AD,and 32 normal controls(NC)were all examined by MMSE scores,and un-

Paraneoplastic neurological syndrome caused by cystitis glandularis: A case report and literature review

BACKGROUND Paraneoplastic neurological syndrome(PNS)is an unusual event.PNS caused by cystitis glandularis(CG)or a bladder tumor is extremely rare;hence,missed diagnosis or misdiagnosis can easily occur.To date,approximately 21 cases have been reported in PubMed.CASE SUMMARY We report a case of PNS caused by CG and describe the clinical and imaging features.The main clinical feature was advanced cognitive impairment,and early clinical features were memory impairment,decreased computational ability,and abnormal behavior.Later clinical features were dementia,vomiting,inability to eat and walk,urinary incontinence,and hematuria.Imaging features on cranial magnetic resonance imaging were diffuse white matter lesions.Paraneoplastic tumor markers were normal.A total abdominal computed tomography scan showed multiple thickened areas on the bladder wall with local prominence.Cystoscopy revealed a volcanic protuberance on the posterior wall of the bladder with a diameter of 6 cm and no pedicle.The postoperative pathological diagnosis was CG.The patient recovered well following resection of CG.PNS cases caused by previous bladder tumors can be retrieved from PubMed to describe the clinical signs and prognosis of PNS.CONCLUSION The main clinical feature of PNS caused by CG was dementia,and the imaging features were diffuse cerebral white matter lesions.Resection of CG lesions is the fundamental treatment for PNS induced by CG.This case highlights the importance of etiological treatment.

Different Eukaryotic Initiation Factor 2Be Mutations Lead to Various Degrees of Intolerance to the Stress of Endoplasmic Reticulum in Oligodendrocytes

Vanishing white matter disease （VWM）, a human atitosomal recessive inherited leukoencephalopathy, is due to mutations in eukaryotic initiation factor 2B （elF2B）. elF2B is responsible for tile initiation of protein synthesis by its guanine nucleotide exchange lhctor （GEF） activity. Mutations ofelF2B impair GEF activity at different degree. Previous studies implied improperly activated unlblded protein response （UPR） and endoplasmic reticulum stress （ERS） participated in the pathogenesis ofVWM. Autophagy relieves endoplasmic reticulum load by eliminating the unfolded protein. It is still unknown the effects of genotypes on the pathogenesis. In this work, UPR and autophagy flux were analyzed with different mutational types. Methods： ERS tolerance, reflected by apoptosis and cell viability, was detected in human oligodendrocyte cell line transfected with the wild type, or different mutations of p. Argl 13 His, p. Arg269＊ or p. Ser610-Asp613del in el F2 Be. A representative U PR-PERK component of activating transcription lhctor 4 （ATF4） was measured under the basal condition and ERS induction. Autophagy was analyzed the flux in the presence of lysosomal inhibitors. Results： The degree of ERS tolerance varied in different genotypes. The truncated or deletion mutant showed prominent apoptosis cell viability declination after ERS induction. The most seriously damaged GEF activity ofp. Arg269＊ group underwent spontaneous apoptosis. The truncated or deletion mutant showed elevated ATF4 under basal as well as ERS condition. Decreased expression of LC3-1 and LC3-11 in the mutants reflected an impaired autophagy flux, which was more obvious in the truncated or deletion mutants alter ERS induction. Conclusions： GEF activities in dilt;erent genotypes could influence the cell ERS tolerance as well as compensatory pathways of UPR and autophagy. Oligodendrocytes with truncated or deletion inutants showed less tolerable to ERS.