Objective:To analyze the clinical phenotype, imaging characteristics and genetic characteristics of a family of early-onset dementia caused by a new mutation in the triggerring receptor expressing on myeloid cells 2 gene (TREM2).Methods:Clinical data were collected from a patient with early-onset dementia. Then whole exome sequencing was performed for the proband, followed by Sanger sequencing for the family members.Results:The clinical manifestations of the proband (a 49-year-old female) was personality changes, mental and behavioral abnormalities, memory loss, ataxia, and seizures. Whole-exon sequencing revealed a novel homozygous mutation in exon 2 of TREM2, namely c.154C>T (p.R52C) heterozygosity in four family members, and one patient with similar clinical manifestations was deceased. The proband′s brain magnetic resonance imaging showed bilateral frontotemporal atrophy, bilateral white matter hyperintensity, thin corpus callosum. No bone cysts of the hands and feet were found by digital radiographic imaging.Conclusions:A homozygous mutation in TREM2 gene was detected in a patient with frontotemporal dementia-like dementia, epilepsy, but without bone cysts. This mutation is probably pathogenic. This research highlights the importance of TREM2 gene mutation screening in early-onset dementia, especially in those with atypical presentations.

Primary angiitis of the central nervous system (PACNS) is a rare inflammatory disease of the central nervous system with unknown etiology affecting the brain and spinal cord. As the incidence of PACNS is low, the clinical manifestations are diverse, the cerebrospinal fluid examination lacks specificity, its diagnosis mainly depends on the "gold standard" pathological biopsy. However, due to the subjectivity of the sampling site, tissue staining and microscopic reading, some patients may be misdiagnosed. In addition, the potentially aggressive course of PACNS may reduce disability and mortality through appropriate immunosuppressive therapy, so the early diagnosis of PACNS is conducive to the prognosis of patients. Imaging examination is convenient, non-invasive, and can provide important information for the diagnosis and differential diagnosis of PACNS from various aspects. Therefore, it is very important to explore the imaging features of the disease. This paper reviews the current research status of imaging examination in PACNS and summarizes the different types of imaging findings in PACNS.

Objective To investigate the effectiveness and safety of intravenous immunoglobulin combined with oral glucocorticoid in the treatment of myasthenia gravis in elderly patients.Methods A total of 235 elderly patients diagnosed as myasthenia gravis in our hospital were enrolled in our study from January 2012 to December 2016,and randomly divided into observation group (intravenous immunoglobulin combined with oral glucocorticoid n =118) and control group (oral glucocorticoid only,n =117).The clinical curative effect,immune function index,QMG scale,symptom remission time,length of hospitalization,and adverse reactions in both groups were recorded and analyzed after two-week treatment.Results The total effective rate was significantly higher in observation group (106/117,90.6％) than in control group (84/118,71.2％) (x2=5.621,P=0.000).The levels of serum IgG1,IgG3,and complement C3 were significantly higher in observation group than in control group (P ＜0.05).The QMG scale,symptom remission time,and length of hospitalization were lower in observation group [(9.2 ± 4.0) score,(6.2 ± 1.6) d,(14.4 ± 3.3) d]than in the control group [(13.4 ± 6.1) score,(11.6 ± 2.4) d,(25.1 ± 4.8) d] (t =6.158,19.797,and 20.078,P=0.000,0.002 and 0.009).No serious adverse reaction was observed in both groups.Conclusions The combined therapies of intravenous immunoglobulin and oral glucocorticoid for myasthenia gravis in the elderly have remarkable effectiveness.It is close to an ideal treatment because it effectively inhibits a disease progression in time,regulates an immune function,and shortens a hospitalization time.

Objective:To evaluate the efficacy and safety of fasudil on vasospasm caused by subarachnoid hemorrhage in elderly patients.Methods:A total of 100 elderly patients with subarachnoid hemorrhage admitted to our hospital from January 2015 to May 2018 were enrolled as research objects.They were randomly divided into the Fasudil group(n=50, receiving the Rho kinase inhibitor Fasudil therapy)and the Nimodipine group(n=50, receiving Nimodipine therapy). The cerebral vasospasm and cerebral infarction lesions, the ability of daily life, clinical prognostic score, the incidence of symptomatic cerebral vasospasm and adverse reactions during treatment were evaluated and compared between the two groups.Results:After treatment, the incidences of cerebral vasospasm and cerebral infarction in Fasudil group were 2.04%(1/49)and 6.12%(3/49), respectively, which were lower than those in the Nimodipine group[12.50%(6/48)and 20.83%(10/48), respectively]( χ2=6.134 and 6.794, P=0.047 and 0.033). The scores of daily living ability was better in the Fasudil group than in the Nimodipine group(16.09±1.06 vs.22.91±1.66, t=7.721, P=0.026). The incidence of adverse reactions was lower in the Fasudil group than in the Nimodipine group(4.08% or 2/49 vs.16.7% or 8/48, χ2=6.362, P=0.040). There was no statistically significant difference in the proportion of patients with good prognosis between Fasudil group and Nimodipine group. Conclusions:Rho kinase inhibitor Fasudil can effectively prevent and improve cerebral vasospasm caused by subarachnoid hemorrhage, which is beneficial for improving the clinical prognosis and quality of life of the elderly patients with subarachnoid hemorrhage.

Objective To investigate the clinical manifestations,imaging features,molecular genetic characteristics and possible pathogenic mechanisms of hereditary cerebral small vessel disease (CSVD) caused by heterozygous mutation of HtrA serine protease-1 (HTRA1) gene.Methods The clinical data of a Chinese Han family with CSVD carrying a heterozygous mutation of HTRA 1 gene,which came from the Department of Neurology,Henan Provincial People's Hospital in March 2018,were analyzed retrospectively.The clinical and radiographic features were summarized.Several high-throughput whole exon high-throughput sequencing was used to capture the mutation sites and the Sanger sequencing was used to validate the results.The family diagram was drawn and the 3D model construction and mutation function prediction were performed using silico tools.The relevant literature was reviewed and the pathogenesis was explored.Results The pedigree map showed that the family had an autosomal dominant inheritance pattern.Three generations of the family were investigated,and three family members in the same generation suffered from the disease.The first symptom of the proband was diplopia at the age of 39,accompanied by recurrent stroke,cognitive impairment and mood disorders,without alopecia.Head magnetic resonance imaging revealed bilateral diffuse,symmetric lesions,multiple lacunar infarcts,perivascular space,and microbleeds.The elder sister of the proband developed symptoms of left limb weakness at the age of 46,whose other clinical and imaging features were similar to those of the proband.The proband's mother died at the age of 59 due to repeated strokes.Whole exon sequencing indicated heterozygous missense mutation at c.821G＞A locus of HTRA1 gene in the proband and her 4th elder sibling,which was a new pathogenic mutation after consulting several mutation sites of databases.Function prediction suggested pathogenicity.Conclusions The heterozygous mutation of c.821G＞A in HTRA1 gene may lead to autosomal dominant CVSD.This genetic type should be given clinical attention.

Objective To analyze clinical characteristics of four cases with primary intraspinal lymphoma to achieve early diagnosis of the disease.Methods Clinical data including the clinical presentation,imaging features and pathological characteristics of four patients diagnosed as primary intraspinal lymphoma confirmed surgically and pathologically from February 2014 to February 2017 in Henan Provincial People's Hospital were analyzed retrospectively,and literatures were reviewed.Results The major clinical manifestations of the primary intraspinal lymphoma were as following:persistent or intermittent waist (back) pain,accompanied with both lower limb weakness,dysfunction of motion,loss or disappearance of sensation,incontinence,followed by an acute progressive neurological function deterioration.The imaging showed a single fusiform shape or irregular lump.The T1 WI signal was equal or slightly lower,and T2WI showed equal or slightly higher signal,and the general signal uniform;The lump showed mild or moderate homogeneous enhancement.The group of four cases were B cell non-Hodgkin lymphoma confirmed by pathological biopsy.Conclusions The clinical and imaging features of primary intraspinal lymphoma are lack of specificity and are easy to be misdiaguosed.The diagnosis is mainly based on pathological biopsy.

Objective To explore the clinical,imaging,genetic features in a case of fatal familial insomnia (FFI),and review related literatures.Methods A case of middle-aged woman diagnosed as frontotemporal dementia based on the preliminary manifestation of abnormal mental behavior was reported.The clinical features,imaging characteristics,electroencephalogram and polysomnogram of the patient were analyzed,and the blood samples from the patient and some of her familial members were collected for the sequencing of prion protein gene (PRNP).Results This patient was a middle-aged woman,whose clinical manifestations were abnormal mental behavior,rapid progressive dementia and intractable insomnia,abnormal night sleep behavior and laryngeal stridor.Brain MRI indicated frontotemporal lobe atrophy.Non-sleep disturbance was observed in polysomnography.The cerebrospinal fluid was negative for 14-3-3 protein.The results of PRNP sequencing revealed that the mutation of gene D178N/129M was detected.Conclusions Detection of PRNP plays an important role in the diagnosis of FFI.Patients suspected of FFI in clinic should be detected for genetic testing.Whether the frontotemporal lobe atrophy was caused by FFI or concurrent with FFI remains to be further verified.

Objective:To report 8 patients of sporadic Creutzfeldt-Jakob disease (sCJD) with real-time quaking-induced conversion (RT-QuIC) positive and analyze their clinical characteristics.Methods:The medical records of patients discharged from Henan Provincial People′s Hospital from January 2018 to May 2021 who were diagnosed with clinically probable sCJD and had RT-QuIC test were retrospectively analyzed. General information (gender, age, initial symptom, main clinical manifestations), accessory examination [brain magnetic resonance imaging (MRI), electroencephalogram, cerebrospinal fluid 14-3-3 protein, prion protein gene, antibodies related to autoimmune encephalitis and paraneoplastic syndrome] were collected. By a telephone-based follow-up survey, data about morality and total duration of course were collected. The patients were divided into two groups according to electroencephalogram, 14-3-3 protein, duration of disease and MRI results, and the differences of fluorescence peak time and fluorescence peak value in RT-QuIC results between groups were compared.Results:Among 8 patients, 7 patients had subacute onset and 1 patient had chronic onset. Main clinical manifestations included progressive cognitive decline (8/8), pyramid sign (5/8), walking instability (4/8), mental and behavior disorder (4/8), myoclonus (4/8), akinetic mutism (4/8), dizziness (3/8), limb shaking (2/8), dysarthria (2/8), visual hallucination (1/8), impaired vision (1/8). All cases had abnormal electroencephalogram and typical periodic sharp slow compound waves (PSWCs) were observed in 5 cases. Brain MRI showed high signal intensity in the cerebral cortex and/or basal ganglia on diffusion-weighted imaging in 7 cases, of which 6 cases involved bilateral basal ganglia. Cerebrospinal fluid 14-3-3 protein was positive in 2 cases, and RT-QuIC was positive in all cases. The fluorescence peak time of RT-QuIC was shorter in patients with PSWCs [(7.617±2.164) h vs (10.602±2.247) h, t=2.84, P=0.010] and high total MRI score [ (7.600±1.907) h vs (9.760±2.457) h, t=2.26, P=0.032]. Conclusions:RT-QuIC detection is a reliable method for early diagnosis of sCJD. RT-QuIC results were related to PSWCs and degree of MRI involvement.

Objective:To summarize the clinical and imaging features of 10 patients with genetically diagnosed neuronal intranuclear inclusion disease (NIID) to avoid clinical misdiagnosis and mismanagement of NIID.Methods:Ten patients with NIID, admitted to our hospital from January 2020 to March 2022, were chosen in our study. All patients were confirmed as having NIID by NOTCH2NLC gene assay. Their clinical data, gene detection results and skin pathological results were collected and anlyzed. Results:These patients aged from 57 to 84 years, including 8 females. The episodic symptoms as main symptoms were noted in 6 patients, including 3 patients with encephalopathy, 1 patient with TGA, 1 patient with stroke-like episode, and 1 patient with migraine-like symptoms. Chronic progressive symptoms as main symptoms were noted in 4 patients, including 3 patients with dementia and 1 patient with Parkinson's disease. There were characteristic linear hyper-intensities in diffusion weighted imaging (DWI) in the corticomedullary junction predominantly in the frontal lobes. White matter lesions appeared in T2 Flair might have been noted years before lesions appeared in DWI, with wider ranges. All had GGC repeated expansion in NOTCH2NLC gene in non-coding area, with mutation number>60. Skin biopsy was performed in 6 patients, showing the formation of intranuclear inclusion bodies in different cells; and ubiquitin and P62 were found positive in immunohistochemical staining. Conclusions:NIID patients have large clinical heterogeneity; most patients have episodic symptoms as main manifestations, often accompanied by chronic progressive symptoms; stroke attack and migraine are rare clinical phenotypes of NIID. The high signal at the cortical medullary junction in DWI is a characteristic imaging change.