Clinical features and CACNA1A gene mutation in a family with episodic ataxia type 2 / 中南大学学报(医学版)

Episodic ataxia (EA) is a group of disorders characterized by recurrent spells of vertigo, truncal ataxia, and dysarthria. Episodic ataxia type 2 (EA2), the most common subtype of EA, is an autosomal dominant disease caused by mutation of the CACNA1A gene. EA2 has been rarely reported in the Chinese population. Here we present an EA2 family admitted to Xiangya Hospital in October 2018. The proband was a 22-year-old male who complained of recurrent spells of vertigo, slurred speech, and incoordination for 4 years. Brain magnetic resonance imaging (MRI) showed cerebellar atrophy. He had neuropsychological development disorder in childhood, and cognitive assessment in adulthood showed cognitive impairment. The proband's mother and grandmother had a similar history. Peripheral blood samples from the proband and family members were collected, and genomic DNA was isolated. Whole exome sequencing of the proband detected a heterozygous frameshift mutation c.2042_2043del (p.Q681Rfs*100) of CACNA1A gene. This mutation was verified in the proband and 2 family members using Sanger sequencing. One family member carrying this mutation was free of symptoms and signs, suggesting an incomplete penetrance of the mutation. We reported a variant c.2042_2043del of CACNA1A gene as the pathogenic mutation in a Chinese EA2 family for the first time. This case enriched the clinical spectrum of CACNA1A related EA2, and contributed to the understanding of clinical and genetic characteristics of EA2 to reduce misdiagnosis.

Research advances in clinical scales for essential tremor / 中华老年医学杂志

Essential tremor(ET)is one of the most common movement disorders, with a prevalence of 4.6% in people over 65 years old.Action tremor of both upper limbs at 4-12 Hz action tremor in both upper limbs is the main clinical feature of ET patients.ET was previously considered to be a benign isolated symptomatic disease, but in recent years, researches have found that ET is a family of diseases with high clinical and genetic heterogeneities.In addition to tremor, it can also be accompanied by soft neurological signs and various non-motor symptoms, leading to different degrees of function impairment in patients.Early comprehensive evaluation and long-term follow-up of patients with ET are essential.The standardized scale is the most important tool for ET assessment.This article reviews various tremor assessment scales.

Research advances in the treatment of essential tremor / 中华神经科杂志

Essential tremor (ET) is a common movement disorder. It is characterized by a distinctive 4-12 Hz action tremor typically affecting bilateral upper limbs. Existing drugs for ET mainly include β-blockers, anticonvulsants, benzodiazepines, etc. However, the efficacy of existing drugs is limited. With the development of the medical research, some progress has been made in the treatment of ET. The review will explore the recent advances in the treatment of ET,such as new drugs, surgical treatment, repetitive transcranial magnetic stimulation, rehabilitation treatment, etc., in order to provide clinical application prospects.

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.

Research progress of oculomotor disorder in Parkinson's disease / 中华神经科杂志

Parkinson's disease (PD) is a common neurodegenerative disease characterized by bradykinesia,resting tremor,muscle rigidity,and abnormal gait posture.Ocular motor function test plays an important part in neurological examinations.It has been widely accepted that specific ocular motor patterns contribute to diagnosis of Parkinsonian syndrome including progressive supranuclear palsy and multiple system atrophy.However,recent studies have shown that patients of PD may also exhibit specific eye movement disorders,which will be helpful in the early diagnosis,evaluation and differential diagnosis of PD.In 2015,the Movement Disorder Society clinical diagnostic criteria for Parkinson's disease suggested that sustained staring evoked nystagmus could be used as an exclusive criterion for PD.The clinical features,detection methods and clinical significance of oculomotor dysfunction in PD are reviewed in this article.

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.

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.

The clinical characteristics and risk factors of frozen gait in Parkinson's disease / 中国医师杂志

Objective o investigate the clinical characteristics and relevant risk factors of freezing gait in patients with Parkinson's disease (PD).Methods A total of 570 consecutive PD patients were registered basic information and evaluated by Unified Parkinson's Disease Rating Scale (UPDRS) and New Freezing of gait questionnaire (NFOG-Q).They were divided into the PD with freezing gait group (188 cases) and non-freezing gait group.Results UPDRS score in each part (UPDRS-Ⅰ,UPDRS-Ⅱ,UPDRS-Ⅲ,UPDRS-Ⅳ) and Hoehn & Yahr stage of the PD freezing gait group was significantly higher than that of the non frozen gait group (P ＜ 0.05).Conclusions PD patients with frozen gait group experience more rapid PD progression than those without freezing of gait.The appearance of FOG is associated with the mental behavior and emotion,treatment complication,disease severity,and course of PD.

Study on fatigue symptoms and related factors in Parkinson's disease patients / 中国医师杂志

Objective To investigate the prevalence of fatigue symptoms and investigate its related factors in patients with Parkinson's disease (PD).Methods The Parkinson's Fatigue Scale (PFS-16) was used to assess the fatigue status of 453 PD patients.These patients were divided into fatigue group (mean PFS-16≥3.3 defined as fatigue) and non-fatigue group.All of them completed the assessment of the relevant scale.Results Among 453 PD patients,there were 169 patients (37.3％) in fatigue group and 284 patients (62.7％) in non-fatigue group.Unified Parkinson's disease Rating Scale (UPDRS) and HoehnYahr (H-Y) staging in fatigue group were significantly higher than non-fatigue group (P ＜0.05).Motor symptoms,mental and emotional status and daily living ability are positively correlated with fatigue symptoms.Conclusions The motor symptoms and non-motor symptoms are more serious in PD patients with fatigue.The motor symptoms,mental and emotional status,daily living ability and Hoehn-Yahr (H-Y) stage are the main related factors of fatigue symptoms in PD patients.

Study on the clinical features and related factors of cognitive impairment in Parkinson's disease / 中国医师杂志

Objective To explore the correlated factors and clinical features of cognitive impariment in parkinson's disease (PD).Methods A total of 419 patients with PD were collected from Xiangya Hospital of Centre-South University during Mar 1st,2017 to Nov 30th,2017.The cognitive functions of patients were assessed with the Mini-Mental State Examination (MMSE),and the basic information and the motor symptoms of 419 PD patients were selected at the same time.The PD patients were classified into three groups according to the MMSE score:PD with no cognitive impairment (PD-NC),mild cognitive impairment in PD (PD-MCI),and Dementia in PD (PD-D).The data were analyzed by SPSS 20.0.Results There were 156 patients with PD-MCI (37.2％) and 64 patients with PD-D (15.3％).The difference of sex and disease duration among three groups were not statistically significant (P ＞ 0.05).The significant difference was found among PD-D,PD-MCI,and PD-NC groups in age of onset,age,educational attainment,Unified Parkinson's disease Rating Scale (UPDRS)-Ⅱ score,UPDRS-Ⅲ score and Hoehn-Yahr stage (P ＜ 0.05).There were significant differences among three groups in MMSE score and its items (P ＜ 0.01).Logistics regression analysis found that the age of onset,educational attainment,and Hoehn-Yahr stage were the risk factors of cognitive impairment in PD patients (P ＜ 0.05).Conclusions Cognitive impairment is common in PD patients,and it is relevant to the age of onset,educational attainment and the severity of illness of PD patients.

Analysis of body mass index changes in Parkinson's disease and its association with disease severity / 中国医师杂志

Objective To investigate the change of body mass index (BMI) in Parkinson's disease (PD) and its association with disease severity.Methods SPSS 22.0 was used for data analysis of one hundred and sixty-eight PD patients and one hundred and fifteen healthy controls.Results BMI value was obviously declined in PD (P =0.001).Decrease of BMI in PD was associated with increase of disease duration (r =-0.270,P =0.001),total score of Unified Parkinson~ Disease Rating Scale (UPDRS) (r =-0.195,P =0.008),score of UPDRS part Ⅱ (r =-0.147,P =0.045),score of UPDRS part Ⅲ (r =-0.159,P =0.030),H-Y grading (r =-0.256,P =0.001),and mini-mental state examination (MMSE) (r =0.291,P =O.001).Conclusions BMI declines more obviously in PD patients than in healthy controls.PD Patients with longer disease duration and severe motor symptoms have a higher risk of BMI loss.

Study on the clinical features and related factors of constipation in patients with Parkinson's disease / 中国医师杂志

Objective To investigate the clinical features of constipation in patients with Parkinson 's disease (PD) and explore the relationship between constipation and motor symptoms.Methods The data of 221 PD patients were collected.Patients were evaluated with following scales:Rome Ⅲ criteria for diagnosis of functional constipation,unified Parkinson's disease rating scale part Ⅲ (UPDRS Ⅲ),and simple mental status examination scale (MMSE).Results Among 221 PD patients,132 (59.7％) had constipation,and 48 (36.4％) experienced constipation before motor symptoms.Compared to those without constipation,PD patients with constipation had a higher UPDRS Ⅲ scores,posture/gait scores,and axis scores (P ＜ O.05).The most common symptoms of PD patients with constipation were defecation straining (93.9％).Conclusions PD patients with constipation have severer motor symptoms than those without constipation.Defecation straining is the most common subtypes of PD patients with constipation.

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.

Progress in genetic research on essential tremor / 中华医学遗传学杂志

Essential tremor (ET) is one of the most common movement disorders. Its clinical manifestations not only include typical kinetic and/or postural tremors, but also other non-motor symptoms such as cognitive dysfunction, sleep disturbance, and dysosmia. The exact etiology and pathogenesis of ET is still unknown. Approximately 60% of ET patients have a family history, and genetic factor plays an important role in the onset of the disease. Researchers have so far identified 3 genetic loci (ETM 1-3) through family studies, and proposed additional causative genes such as FUS, HTRA2, TENM4, NOS3 and susceptibility genes such as LINGO, SLC1A2, and GABA. This review focuses on the progress made in genetic research on ET.

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>

Mutation analysis of microRNA-7 gene in Chinese patients with Parkinson's disease / 中南大学学报(医学版)

OBJECTIVE@#To investigate the mutation of small sequence changes in microRNA-7 gene in Chinese patients with Parkinson's disease (PD).@*METHODS@#We analyzed miR-7 variants in 225 PD patients from Chinese Han group by DNA sequence.@*RESULTS@#None of the patients had miR-7 variants.@*CONCLUSION@#MiR-7 variation is not associated with PD in Chinese patients.