Clinical and genetic study of ataxia with vitamin E deficiency: A case report

BACKGROUND Ataxia with vitamin E deficiency(AVED)is a type of autosomal recessive cerebellar ataxia.Clinical manifestations include progressive cerebellar ataxia and movement disorders.TTPA gene mutations cause the disease.CASE SUMMARY We report the case of a 32-year-old woman who presented with progressive cerebellar ataxia,dysarthria,dystonic tremors and a remarkably decreased serum vitamin E concentration.Brain magnetic resonance images showed that her brainstem and cerebellum were within normal limits.Acquired causes of ataxia were excluded.Whole exome sequencing subsequently identified a novel homozygous variant(c.473T>C,p.F158S)of the TPPA gene.Bioinformatic analysis predicted that F185S is harmful to protein function.After supplementing the patient with vitamin E 400 mg three times per day for 2 years,her symptoms remained stable.CONCLUSION We identified an AVED patient caused by novel mutation in TTPA gene.Our findings widen the known TTPA gene mutation spectrum.

N6-methyladenine-modified DNA was decreased in Alzheimer’s disease patients

BACKGROUND In recent years,the prevalence of Alzheimer’s disease(AD)has increased,which places a great burden on society and families and creates considerable challenges for medical services.N6-methyladenine(m6A)deoxyribonucleic acid(DNA)adenine methylation is a novel biomarker and is abundant in the brain,but less common in AD.We support to analyze the relationship between DNA m6A and cognition in patients with AD and normal controls(NCs)in China.AIM To analyze the relationship between the novel m6A DNA and cognition in patients with AD and NCs in China.METHODS A total of 179 AD patients(mean age 71.60±9.89 years;males:91;females:88)and 147 NCs(mean age 69.59±11.22 years;males:77;females:70)who were age-and sex-matched were included in our study.All subjects underwent neuropsychological scale assessment and magnetic resonance imaging examination.Apolipoprotein E(APOE)genotypes were measured through agarose gel electrophoresis.Global m6A levels were evaluated by a MethylFlash m6A DNA Methylation ELISA Kit(colorimetric).Global m6A levels in total DNA from ten AD patients with 18F-AV-45(florbetapir)positron emission tomography(PET)positivity and ten NCs with PET negativity were analyzed by dot blotting to determine the results.RESULTS Our ELISA results showed that the global m6A DNA levels in peripheral blood were different between patients with AD and NCs(P=0.002;<0.05).And ten AD patients who were PET positive and ten NCs who were PET negative also showed the same results through dot blotting.There were significant differences between the two groups,which indicated that the leukocyte m6A DNA levels were different(P=0.005;<0.05).The m6A level was approximately 8.33%lower in AD patients than in NCs(mean 0.011±0.006 vs 0.012±0.005).A significant correlation was found between the Montreal Cognitive Assessment score and the peripheral blood m6A level in the tested population(r=0.143,P=0.01;<0.05).However,no relationship was found with APOEε4(P=0.633,>0.05).Further studies should be performed to validate these findings.CONCLUSION Our results show that reduced global m6A DNA methylation levels are significantly lower in AD patients than in NCs by approximately 8.33%in China.

Amide Proton Transfer Magnetic Resonance Imaging of Alzheimer＇s Disease at 3.0 Tesla： A Preliminary Study

Background：Amide proton transfer （APT） imaging has recently emerged as an important contrast mechanism for magnetic resonance imaging （MRI） in the field of molecular and cellular imaging.The aim of this study was to evaluate the feasibility of APT imaging to detect cerebral abnormality in patients with Alzheimer＆#39;s disease （AD） at 3.0 Tesla.Methods：Twenty AD patients （9 men and 11 women; age range,67-83 years） and 20 age-matched normal controls （11 men and 9 women; age range,63-82 years） underwent APT and traditional MRI examination on a 3.0 Tesla MRI system.The magnetic resonance ratio asymmetry （MTRasym） values at 3.5 ppm of bilateral hippocampi （Hc）,temporal white matter regions,occipital white matter regions,and cerebral peduncles were measured on oblique axial APT images.MTRasym （3.5 ppm） values of the cerebral structures between AD patients and control subjects were compared with independent samples t-test.Controlling for age,partial correlation analysis was used to investigate the associations between mini-mental state examination （MMSE） and the various MRI measures among AD patients.Results：Compared with normal controls,MTRasym （3.5 ppm） values of bilateral Hc were significantly increased in AD patients （right 1.24% ± 0.21% vs.0.83% ± 0.19%,left 1.18% ± 0.18% vs.0.80%± 0.17%,t =3.039,3.328,P =0.004,0.002,respectively）.MTRasym （3.5 ppm） values of bilateral Hc were significantly negatively correlated with MMSE （right r =-0.559,P =0.013; left r=-0.461,P =0.047）.Conclusions：Increased MTRasym （3.5 ppm） values of bilateral Hc in AD patients and its strong correlations with MMSE suggest that APT imaging could potentially provide imaging biomarkers for the noninvasive molecular diagnosis of AD.

Chinese expert consensus on the diagnosis of cardiogenic stroke(2019)

Cardioembolic stroke(CES),also known as cardiogenic stroke,refers to a clinical syndrome caused by a cardiogenic embolus from the heart,leading to cerebral artery embolism through circulation,and it consequently results in corresponding brain dysfunction.CES is associated with greater severity,poor outcomes,and a relatively high recurrence rate,compared with other subtypes of ischemic stroke.

Chinese expert consensus statement for diagnosis and treatment of dementia with Lewy bodies 2020

Dementia with Lewy bodies(DLB)is the second most common type of neurodegenerative dementia,and prone to misdiagnosis and missed diagnosis in the clinic.Based on the evidence about DLB.