Clinical and imaging features of idiopathic intracranial hypertension / 中南大学学报(医学版)

OBJECTIVES@#Idiopathic intracranial hypertension (IIH) is a syndrome that excludes secondary causes such as intracranial space-occupying lesion, hydrocephalus, cerebrovascular disease, and hypoxic ischemic encephalopathy. If not be treated promptly and effectively, IIH can cause severe, permanent vision disability and intractable, disabling headache. This study aims to explore the clinical and image features for IIH, to help clinicians to understand this disease, increase the diagnose rate, and improve the outcomes of patients.@*METHODS@#We retrospectively analyzed 15 cases of IIH that were admitted to Xiangya Hospital, Central South University, during January 2015 to September 2020. The diagnosis of IIH was based on the updated modified Dandy criteria. We analyzed clinical data of patients and did statistical analysis, including age, gender, height, weight, medical history, physical examination, auxiliary examination, treatment and outcome.@*RESULTS@#There were 10 females and 5 males. Female patients were 22 to 42 years old with median age of 39.5. Male patients were 27 to 52 years old with the median age of 44.0. The BMI was 24.14-34.17 (28.71±2.97) kg/m@*CONCLUSIONS@#IIH primarily affects women of childbearing age who are overweight. The major hazard of IIH is the severe and permanent visual loss. Typical image signs have high specificity in IIH diagnosis. Prompt diagnosis and effective treatment are significantly important to improve the outcomes of patients.

The latest research progress: Exosomal microRNAs as biomarkers for diagnostic and therapeutic application in Alzheimer’s disease / 中华老年医学杂志

Exosomes are spherical microvesicles(30-100 nm)secreted by a variety of cells and contain a variety of proteins, lipids, mRNAs, and microRNAs.These molecules into exosomes can be transferred to adjacent cells and distant tissues or cells by exosomes to develop full effects.Exosomes-released microRNAs are involved in the pathogenesis of Alzheimer's disease(AD)by regulating the abnormal expression of amyloid β-protein(Aβ)and p-Tau protein, initiating the inflammatory response by interacting with toll-like receptors.In addition, exosomal microRNAs can be used as a potential therapeutic target for AD.Exosomes as good carriers have great research values.This review summarized the literatures related to the role of exosomal microRNAs in the development of AD and the potential therapeutic effect on AD.A large amount of evidence indicates that expression disorder of exosomal microRNA plays an important role in the pathogenesis of AD and can be used as a new potential biomarker and therapeutic target for the diagnosis and treatment of AD.

Myopathy associated with anti-signal recognition peptide antibodies: Five case reports / 中南大学学报(医学版)

Five patients with myopathy associated with anti-signal recognition peptide antibodies, admitted to our hospital from December 2015 to June 2018, were chosen in our study, and their clinical and pathological manifestations and treatments were retrospectively analyzed. Five patients showed subacute or chronic onset and proximal limb muscle weakness. Serum creatine kinase level was significantly elevated. Immunoblotting assay confirmed the positive anti-signal recognition particle antibody. EMG prompted myogenic damage. Pathological features included muscle degeneration, necrosis with regeneration, visible atrophy and hypertrophic of muscle fiber, connective tissue hyperplasia and a small amount of inflammatory cell infiltration. Immunohistochemical staining showed necrotizing muscle fiber infiltrated with CD4-positive and CD8-positive lymphocytes and CD68-positive macrophages, and no CD20-positive lymphocytes and CD303-positive dendritic cells were observed. Two patients had expressed a bit of c5b-9 positive capillary. Anti-sarcoglycans staining, anti-dysferlin staining and dystrophin staining showed continuous strong positive expression. Follow-up study found that all patients were response to glucocorticoid, and a combination therapy of immunoglobulin and immunosuppression were necessary for some patients.

Clinical and image features for 12 cases of cerebral autosomal dominant arteriopathy with the subcortical infarcts and leukoencephalopathy / 中南大学学报(医学版)

To analyze the clinical and image features for 12 patients of cerebral autosomal dominant arteriopathy with subcortical infarct and leucoencephalopathy (CADASIL).
 Methods: A total of 12 CADASIL patients were collected in Xiangya Hospital of Central South University from January 2013 to December 2018. The clinical manifestation, risk factors, MRI imaging data and NOTCH3 mutations were analyzed retrospectively.
 Results: The mean age of 12 patients was (47.25±9.49) years. The clinical manifestation was most common in cognitive impairment (75%) and stroke events (58.3%), and 2 cases showed cerebral hemorrhage. Migraine was only seen in 25% patients. All MRI showed white matter hyperintensity (WMH), lacune and enlarged perivascular space (PVS). WMH mainly occurred in the frontal parietal lobe (100%), temporal lobe (83.3%), external capsule (66.7%), occipital lobe (41.6%), callosum 41.6% and the temporal pole (33.3%), while lacune mainly appeared in frontal lobe (91.6%), parietal lobe(83.3%), temporal lobe(66.7%), basal ganglia (66.7%), brain stem (41.6%), occipital lobe (33.3%), cerebellum (8.3%). Enlarged PVS located in the basal ganglia (100%), partly under the cortex (45.4%). WMH of the patient with intracerebral hemorrhage was mild (Fezakas score 1-2), which was not found in external capsule. 16.7% of the patients had intracranial arterial stenosis. In 12 patients, 8 different Notch3 mutations were detected. The c1013G>c p.(Cys338Ser) located in exon 6, which was a new pathogenic mutation of CADASIL.
 Conclusion: The patients with cerebral hemorrhage have mild WMH and specific genotype, indicating that the clinical characteristics of CADASIL with cerebral hemorrhage may be related to image features and genotype.

Etiologies and risk factors for young people with intracerebral hemorrhage / 中南大学学报(医学版)

To determine the etiologies and risk factors of intracerebral hemorrhage in young people.
 Methods: A total of 401 young patients with intracerebral hemorrhage were enrolled, and they were assigned into a 20-29 , a 30-39, and a 40-45 age group. The differences of various etiologies and risk factors among the three groups were analyzed.
 Results: There were 273 men and 128 women in the 401 young patients. The etiologies of 294 patients (73.32%) were identified while 107 patients (26.68%) were unknown. Among those with identified etiology, 226 patients (56.36%) suffered from hypertension, 41 patients (10.22%) congenital cerebrovascular malformation (including 25 patients with cerebral arteriovenous malformation, 8 intracranial cavernous hemangioma, and 8 intracranial aneurysm), and 27 other etiologies (including 9 patients with moyamoya disease, 6 cerebral venous sinus thrombosis, 4 drug abuse, 3 hemorrhagic brain tumor, 2 intracranial infection, 1 systemic lupus erythematosus, 1 drug-induced, and 1 eclampsia). Risk factors included hypertension (237 cases, 59.10%), smoking (123 cases, 30.67%), alcohol consumption (74 cases, 18.45%), and others (19 cases, 4.74%; including 8 cases of pregnancy or in the puerperium, 8 family history of intracerebral hemorrhage, and 3 taking anti-platelet aggregation/anticoagulation agents). The rate of hypertension induced hemorrhage significantly increased with age (P<0.01); the rate of vascular malformations in 20-29 age group was obviously higher than other groups (P<0.01); the rate of unknown cause in the 40-45 age group was significantly lower than other groups (P<0.01) and the rate of other etiologies showed no significant difference in the 3 groups. The rate of hypertension was significantly elevated with the age (P<0.01), while smoking, alcohol consumption, and other risk factors showed no significant difference in the 3 groups.
 Conclusion: The rate of intracerebral hemorrhage in young people increases with the increasing of age and hemorrhage affects men more than women; hypertension may be the main cause and congenital cerebrovascular malformation is the second cause, which may be more common in younger patients. Hypertension, smoking, and alcohol consumption may be the major controllable risk factors in intracerebral hemorrhage in young people.

Clinical characteristics of hemichorea associated with non-ketotic hyperglycemia in 3 patients: case report and literature review / 中南大学学报(医学版)

Objective:To investigate the pathophysiology,clinical manifestation and neuroimaging characteristics and therapeutic experiences for hemichore associated with non-ketotic hyperglycemia (HC-NH).Methods:Clinical data of three patients with HC-NH from Xiangya Hospital,Central South University were analyzed retrospectively,and the related literature was reviewed.Results:The core clinical features of HC-NH were characterized by acute/subacute onset of hemichorea with non-ketotic hyperglycemia in the elderly females.Radiologic findings associated with HC-NH were characterized by hyperattenuation on computed tomographic (CT) scans and hyperintensity on Tl-weighted magnetic resonance imaging (MRI) at unilateral basal ganglion region.Blood glucose control was the foundation of treatment.Dopamine receptor antagonists and benzodiazepine sedative were helpful in controlling hemichorea.Conclusion:Hemichorea-hemiballismus is a rare complication of nonketotic hyperglycaemia in elderly type 2 diabetes.It is associated with contralateral striatal radiological abnormality and typically T1 hyperintensity on MRI.The pathophysiology of HC-NH is not clear.The prognosis of HC-NH is favorable.Antidiabetic drugs combined with dopamine receptor antagonists can effectively relieve the hemichorea symptoms.

NOTCH3 gene mutations in two Chinese families featuring cerebral autosomal dominant arteriopathy with subcortical infarct and leucoencephalopathy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze potential mutations of the NOTCH3 gene in two Chinese families featuring cerebral autosomal dominant arteriopathy with subcortical infarct and leucoencephalopathy (CADASIL).</p><p><b>METHODS</b>The two probands and related family members and 100 healthy controls were recruited. Potential mutations of the NOTCH3 gene were screened by PCR and direct sequencing. PolyPhen-2 and SIFT software were used to predict the protein function.</p><p><b>RESULTS</b>The conditions of both probands were adult-onset, with main clinical features including recurrent transient ischemic attacks and/or strokes, cognitive impairment. MRI findings suggested multiple cerebral infarcts and severe leukoencephalopathy. A heterozygous mutation c.328C>T (p.Arg110Cys), which was located in exon 3 of the NOTCH3 gene and known as a causative mutation, was identified in proband 1. A novel heterozygous mutation c.1013 G>C (p.Cys338Ser) located in exon 6 of the NOTCH3 gene was identified in the proband 2, which was not reported previously. The same mutations were not detected among the 100 unrelated healthy controls. Function analysis suggested that heterozygous mutation c.1013G>C can severely affect the functions of NOTCH3 protein.</p><p><b>CONCLUSION</b>Two heterozygous missense mutations in the NOTCH3 gene have been identified in two families affected with CADASIL. The novel heterozygous Cys338Ser mutation in exon 6 of the NOTCH3 gene probably underlies the CADASIL.</p>

Establishment of transgenic mouse models expressing human HSP22 protein / 中华老年医学杂志

Objective To establish transgenic mouse models expressing human HSP22 protein.Methods pCAGGS-HA-Wt HSP22 transgenic expressing vector carrying human HSP22 gene was constructed by gene recombination technology.The linearized DNA was got by SalI、Hind Ⅲ and BsaⅪ digestion of PCAGGS-HA-Wt HSP22,purified and microinjected into fertilized eggs from C57BL mice.The tail DNA of pups was tested by PCR and DNA sequencing.Expression of human HSP22 protein was detected by western blot with anti-HA tag monoclonal antibody.Results 4 transgenic founder mice (Tg646,Tg648,Tg649,Tg661) carrying human HSP22 gene were identified by PCR and DNA sequencing.The human HSP22 protein was expressed in the lines Tg646,Tg648 and Tg649 founder mice,but was not expressed in the line Tg661 founder mouse.Conclusions The mouse models expressing human HSP22 protein are established successfully and provide the foundation for HSP22 gene research in vivo.

Association of plasma t-PA and PAI-1 with carotid atherosclerosis in patients with type 2 diabetes / 中华内分泌代谢杂志

The association of plasma tissue type plasmingogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) with carotid atherosclerosis in patients with type 2 diabetes was explored.The subjects with type 2 diabetes (n =91) and control subjects (n =30) were enrolled for this study.According to carotid artery intima media thickness in Color Doppler Ultrasonography,the subjects with type 2 diabetes were divided into four groups:normal carotid group(group 1,n =25),lining thickening group (group 2,n =30),stable plaques group (group 3,n =23),carotid stenosis group(group 4,n =13).Plasma t-PA and PAI-1 levels were measured by ELISA.Compared with the control group,there was no significant change in the levels of plasma t-PA and PAI-1 in group 1 (P＞0.05),plasma t-PA activity was decreased significantly(P＜0.05) and PAI-1 activity increased obviously (P＜0.05) in group 2,group 3,and group 4.Carotid atherosclerosis degree was negatively correlated with t-PA(r=-0.723,P＜0.01) and positively correlated with PAI-1 (r=0.851,P＜0.01).The results suggested that the abnormal fibrinolysis function may take part in the development of atherosclerosis of carotid arteries in patients with type 2 diabetes.

Studies on the CAG repeat expansion in patients with hereditary spinocerebellar ataxia from Chinese Han / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the CAG trinucleotide repeat expansion in spinocerebellar ataxia (SCA) types 1, 2, 3, 6, 7, 12, and 17 from Chinese Han.</p><p><b>METHODS</b>The pathological CAG triplet repeat expansions of the SCA1, SCA2, SCA3/Machado-Joseph disease (MJD), SCA6, SCA7, SCA12 and SCA17 genes were analyzed in a cohort of 559 Mainland Chinese patients affected by spinocerebellar ataxia, including 363 probands from families with autosomal dominant SCA and 196 sporadic cases. Polymerase chain reaction, agarose gel electrophoresis, recombinant DNA technology by T-vector cloning and direct sequencing were performed to detect the CAG-repeat number of abnormal allele.</p><p><b>RESULTS</b>Among the 559 SCA patients, twenty-three were positive for SCA1, the ranges of expanded CAG repeats were from 39 to 60 (mean:51.09+/-4.88); thirty-two were positive for SCA2, the ranges of expanded CAG repeats were from 36 to 51 (mean:40.34+/-4.40); three hundred and five were positive for SCA3/MJD, the ranges of expanded CAG repeats were from 49 to 86 (mean:73.84+/-5.07); nine were positive for SCA6, the ranges of expanded CAG repeats were from 23 to 29 (mean:25.56+/-1.94); twenty-seven were positive for SCA7, the ranges of expanded CAG repeats were from 38 to 71(mean:58.22+/-10.90); three were positive for SCA12, the ranges of expanded CAG repeats were from 51 to 52 (mean:51.33+/-0.58); and finally, two were positive for SCA17, the range of expanded CAG repeats were from 53 to 55 (mean:54.00+/-1.41).</p><p><b>CONCLUSION</b>The 39 CAG repeats of SCA1, 49 CAG repeats of SCA3 and 51 CAG repeats of SCA12 are all the shortest known causative expanded alleles, while the 86 CAG repeats of SCA3/MJD is the largest full expanded allele that has never been reported. Furthermore, it is the first report of SCA17 subtype in Mainland Chinese and first research that established the abnormal reference standard of CAG repeat number of different subtypes of SCA in Chinese Han.</p>

Frequency of spinocerebellar ataxia types 1, 2, 3, 6, 7, 8, 10, 12, 17 and dentatorubral-pallidoluysian atrophy in Chinese Han population / 中华神经科杂志

Objective To assess the frequency of different subtype of spinocerebellar ataxias (SCAs) in Chinese Han population. Methods The nueleotide repeat mutations of SCA1, SCA2, SCA3/ MJD, SCA6, SCAT, SCA8, SCA10, SCA12, SCA17 and dentatorubral-pallidoluysian atrophy (DRPLA) were detected by the polymerase chain reaction (PCR), denaturing polyacrylamide gel electrophoresis (PAGE), Southern blot, recombinant DNA technology by T-vector cloning and direct sequencing technique in a cohort of 559 Mainland Chinese patients affected by spinocerebellar ataxia, including 363 families with autosomal dominant SCA (AD-SCA) and 196 sporadic cases. Results Among the 363 AD-SCA families, 15 families (4. 13%) were positive for SCA1, 26 (7. 16%) for SCA2, 187 (51.52%) for SCA3/MJD, 6 (1.65%) for SCA6, 7 (1.93%) for SCA7, 1 (0. 28%) for SCA12 and 1 (0. 28%) positive for SCA17; 120(33. 06%) were negative for all the tested SCAs. There were 2 (1.02%) SCAI, 3 (1.53%) SCA2, 15 (7. 65%) SCA3/MJD, 3 (1.53%) SCA6 and 173 (88.27%) not identified in the 196 sporadic SCA patients. None of the SCA8, SCA10 and DRPLA mutation was found. Conclusions SCA3/MJD is a substantially common subtype of AD-SCAs and sporadic SCA in Chinese Han patients with SCAs, subsequently followed by SCA2, SCA1, SCAT and SCA6; SCA12 and SCA17 are uncommon subtypes, while SCA8, SCA10, and DRPLA are rare, if not absent. SCA17 subtype was initially identified in mailand China. Some other genes might be causative in those unidentified AD-SCA pedigrees, and other etiological factors besides genetic cause might contribute for those sporadic cases.

Study on the single-nucleotide substitution (c.-16C to T) of the PURATROPHIN-1 gene in Chinese patients with spinocerebellar ataxia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the single-nucleotide substitution (c.-16C to T) of the PURATROPHIN-1 gene in spinocerebellar ataxia (SCA) patients in China.</p><p><b>METHODS</b>The single-nucleotide substitution (c.-16C to T) of the PURATROPHIN-1 gene was detected by PCR, digested with EcoN I, separated on 8% polyacrylamide gel in 68 probands of autosomal dominant SCA families and 119 sporadic SCA patients, who had been excluded CAG/CAA repeat expansion at the SCA1, 2, 3, 6, 7, 17 and dentatorubral-pallidolluysian atrophy (DRPLA) loci. The results were confirmed in four patients by direct sequencing.</p><p><b>RESULTS</b>The single-nucleotide substitution (c.-16C to T) of the PURATROPHIN-1 gene was not identified in authors' cohort.</p><p><b>CONCLUSION</b>The mutation of c.-16C to T of the PURATROPHIN-1 gene might be rare in SCA patients in China.</p>