Objective:To investigate the clinical, imaging and neuropathological characteristics of neuronal intranuclear inclusion disease (NIID) with symptoms of the central nervous system, and to improve the diagnosis and treatments of NIID.Methods:The clinical data of 7 patients with NIID diagnosed by brain biopsy in Xuanwu Hospital, Capital Medical University, Beijing, China from February 2009 to December 2024 were collected. The characteristics of clinical manifestations, imaging, and histology on brain biopsy were retrospectively analyzed.Results:Among the 7 patients, 5 were male and 2 were female. Their ages ranged from 44 to 70 years, median 56 (52, 65) years. Patients were classified into three types of tumor, stroke and encephalitis according to the onset symptoms, imaging manifestations and pathological changes. The chief complaint of the 5 patients was headache, while 4 patients had paroxysmal convulsions, 3 had speech disorders, 2 had abnormal mental behaviors, 2 had memory decline, and 1 had fever accompanied by consciousness disorders. Diffusion-weighted magnetic resonance imaging of the head showed the "ribbon sign" at the junction of the cortex and medulla in 2 cases. Most of the patients had white matter lesions, gyrus swelling and cerebral atrophy. Occasionally gyrus-like enhancement was observed. Brain biopsy reveals the histological changes that matched those on images and initial symptoms. There were proliferation of oligodendrocytes and astrocytes in the white matter, leukoaraiosis and edema, cortical disintegration and lamellar necrosis, as well as infiltration of lymphocytes and microglia, etc. However, the characteristic changes were eosinophilic hyaline inclusions in the nuclei of neurons and astrocytes. Immunohistochemical staining of p62 and ubiquitin showed homogeneous staining in round or ring-shaped nuclei.Conclusions:The clinical manifestations of NIID are highly variable, and a correct diagnosis of NIID requires careful integration of clinical, imaging and histopathologic data. For patients with a high suspicion of NIID, immunohistochemical staining of p62 and ubiquitin is diagnostically valuable.

Objective:To investigate the clinical, imaging and neuropathological characteristics of neuronal intranuclear inclusion disease (NIID) with symptoms of the central nervous system, and to improve the diagnosis and treatments of NIID.Methods:The clinical data of 7 patients with NIID diagnosed by brain biopsy in Xuanwu Hospital, Capital Medical University, Beijing, China from February 2009 to December 2024 were collected. The characteristics of clinical manifestations, imaging, and histology on brain biopsy were retrospectively analyzed.Results:Among the 7 patients, 5 were male and 2 were female. Their ages ranged from 44 to 70 years, median 56 (52, 65) years. Patients were classified into three types of tumor, stroke and encephalitis according to the onset symptoms, imaging manifestations and pathological changes. The chief complaint of the 5 patients was headache, while 4 patients had paroxysmal convulsions, 3 had speech disorders, 2 had abnormal mental behaviors, 2 had memory decline, and 1 had fever accompanied by consciousness disorders. Diffusion-weighted magnetic resonance imaging of the head showed the "ribbon sign" at the junction of the cortex and medulla in 2 cases. Most of the patients had white matter lesions, gyrus swelling and cerebral atrophy. Occasionally gyrus-like enhancement was observed. Brain biopsy reveals the histological changes that matched those on images and initial symptoms. There were proliferation of oligodendrocytes and astrocytes in the white matter, leukoaraiosis and edema, cortical disintegration and lamellar necrosis, as well as infiltration of lymphocytes and microglia, etc. However, the characteristic changes were eosinophilic hyaline inclusions in the nuclei of neurons and astrocytes. Immunohistochemical staining of p62 and ubiquitin showed homogeneous staining in round or ring-shaped nuclei.Conclusions:The clinical manifestations of NIID are highly variable, and a correct diagnosis of NIID requires careful integration of clinical, imaging and histopathologic data. For patients with a high suspicion of NIID, immunohistochemical staining of p62 and ubiquitin is diagnostically valuable.

With rapid development of genetic testing techniques, neuroimaging and neuroelectrophysiological technologies, our understanding of malformations of cortical development continues to be deepened and updated. In particular, mutations in genes related to the mammalian target of rapamycin (mTOR) signaling pathway have been successively discovered in focal cortical dysplasia (FCD). At the same time, the classification consensus on FCD issued by the International League Against Epilepsy (ILAE) in 2011 has encountered problems and challenges in diagnostic practice. Therefore, in 2022, ILAE proposed an updated version of the FCD classification based on the progress in molecular genetics over the past decade. The main addition to the classification system is "white matter lesions, " and it is also suggested to integrate histopathological, neuroimaging, and molecular testing results for multi-level integrated diagnosis to achieve reliable, clinically relevant, and therapeutic targeted final diagnosis.

Objective:To investigate the clinical, radiological, and pathological features of anaplastic gangliogliomas (AGGs) and to determine whether these tumors represent a distinct entity.Methods:Consecutive 667 cases of ganglioglioma (GG) diagnosed at the Xuanwu Hospital, Capital Medical University, Beijing, China between January 2015 and July 2023 were screened. Among these cases, 9 pathologically confirmed AGG cases were identified. Their clinical, radiological, treatment, and outcome data were analyzed retrospectively. Most of the tumor samples were subject to next-generation sequencing, while a subset of them were subject to DNA methylation profiling.Results:Among the 9 patients, there were five males and four females, with a median age of 8 years. Epileptic seizures (5/9) were the most frequently presented symptom. Radiological examinations showed three types of radiological manifestations: four cases showed abnormal MRI signals with no significant mass effects and mild enhancement; two cases demonstrated a mixed solid-cystic density lesion with peritumoral edema, which showed significant heterogeneous enhancement and obvious mass effects, and one case displayed cystic cavity formation with nodules on MRI, which showed evident enhancements. All cases exhibited mutations that were predicted to activate the MAP kinase signaling pathway, including seven with BRAF p.V600E mutation and two with NF1 mutation. Five AGGs with mutations involving the MAP kinase signaling pathway also had concurrent mutations, including three with CDKN2A homozygous deletion, one with a TERT promoter mutation, one with a H3F3A mutation, and one with a PTEN mutation.Conclusions:AGG exhibits a distinct spectrum of pathology, genetic mutations and clinical behaviors, differing from GG. Given these characteristics suggest that AGG may be a distinct tumor type, further expansion of the case series is needed. Therefore, a comprehensive integration of clinical, histological, and molecular analyses is required to correctly diagnose AGG. It will also help guide treatments and prognostication.

Objective:To investigate the clinicopathological features, diagnosis and prognosis of diffuse leptomeningeal glioneuronal tumor (DLGNT).Methods:Five cases of DLGNT diagnosed from January 2016 to January 2020 were collected from Xuanwu Hospital, Capital Medical University. The clinical features, histopathologic characteristics, immunohistochemical and molecular genetic findings and prognosis were analyzed and the relevant literature was reviewed.Results:The five patients (two males and three females) were aged 2 to 52 years (median 11 years), and had history of increased intracranial pressure (headache and vomiting) or limb weakness. Three of them were younger than 16 years of age. The imaging studies showed diffuse intracranial and intraspinal nodular leptomeningeal thickening and enhancement, with or without parenchymal involvement. At times there were associated small cyst-like lesions. Imaging interpretations were inflammatory lesions in three cases and space occupying lesions in two. Microscopically, in three cases the tumors showed low to moderate cellularity, consisting of relatively monomorphous oligodendrocyte-like cells arranged in small nests or diffusely distribution. No mitosis and necrosis were observed. In two cases there were increased cellularity with a diffuse honeycomb pattern. The tumor showed mild to moderate polymorphism with hyperchromatic nuclei. Mitosis, endothelial vascular proliferation and glomeruloid vessels were seen. Necrosis was absent. The tumor cells in all five cases were positive for synaptophysin,Olig2 and negative for IDH1 and H3 K27M. GFAP was focally positive in four cases and only one case expressed NeuN partly. The Ki-67 labeling index was 1%-35%. BRAF fusion was detected in four cases. Genetic analysis showed solitary 1p deletion in two cases (2/5), while all cases were negative for 1p/19q co-deletion (0/5). The five patients were followed up for 13 to 28 months (median 15 month). One patient died after 27 months. There was no evidence of tumor progression in the remaining four patients.Conclusions:DLGNT is rare and easily confused with other central nervous system tumors and inflammatory lesions. Therefore, the diagnosis of DLGNT should be made based on comprehensive information including imaging, morphologic and corresponding immunohistochemical examinations and molecular genetics to avoid misdiagnosis and delay in management.

Objective? To explore the effects of applying Information-Motivation-Behavioral skills model (IMB) on the improvement of life quality for patients with chronic heart failure (CHF). Methods? Totally 90 patients with CHF were selected by convenient sampling and divided into two groups based on random number table with 45 cases in each group. The control group received routine nursing care, while the experiment group received the nursing invention guided by the IMB besides the routine nursing care. The Minnesota Living with Heart Failure Questionnaire (MLHFQ) was used to evaluate the CHF patients＇ improvment status of their life quality before and after intervention. Results? Before intervention, there were not statistical differences between the experimental group(65.11±11.31) and control group(66.05±14.72) in terms of their life quality (P＞0.05). After intervention, the score from MLHFQ in the experiment group (50.99±14.56) was lower than the control group (58.57±12.95) with statistical significance (P＜0.05). Conclusions? The application of IMB model can effectively improve life quality of CHF patients.

Objective: To investigate the clinicpathologic features and probable mechanisms of massive subcortical heterotopia. Methods: Clinical data, histologic features and neuropathologic data were analyzed in five cases of massive subcortical heterotopia collected from Xuanwu Hospital, Capital Medical University from January 2014 to October 2017. Results: All five patients (three males and two females) had a history of refractory epilepsy with a mean period of 15.4 years (range 7 to 21 years). The median age at surgery was 28.6 years(range 20 to 39 years). Magnetic resonance imaging showed that the lesions were located in the temporal lobe (two cases), parietal lobe (one case), both temporal and occipital lobes (one case) and both temporal and parietal lobes (one case). Pathologic examination disclosed that massive gray matter in subcortical and deep white matter with various shape and size. Moreover, one case also showed subpial and periventricular heterotopias and polymicrogyria. Polymicrogyria or hippocampal sclerosis were seen in the remaining three cases. None of the five patients experienced seizure attacks during the follow-up period. Conclusions Heterotopia is malformations due to abnormal neuronal migration. Massive subcortical heterotopia due to widespread abnormal neuronal migration is relatively rare. The mechanism of heterotopia together with polymicrogyria needs further discussion.

Objective: To investigate the usefulness of loss of CIC expression as the prescreening detection of 1p/19q co-deletion in the diagnosis of oligodendroglial tumors and its prognostic implication. Methods: The retrospective study included 113 oligodendroglial tumors diagnosed in the Department of Pathology, Xuanwu Hospital, Capital Medical University. Expression of CIC protein was detected by immunohistochemistry, and the 1p/19q co-deletion by fluorescence in situ hybridization in all the tumors; and the correlation of the loss of protein and 1p/19q co-deletion with prognosis was assessed. Results: The rate of negative CIC protein expression was 59.3% (67/113) in 113 oligodendroglial tumors. CIC protein expression was differentially lost in various gliomas, 85.7% (42/49) in pure oligodendrogliomas and 39.1% (25/64) in mixed oligodendroglial tumors (P<0.01). The loss of CIC protein expression showed a sensitivity of 76.1% (54/71), specificity 71.1% (27/38), false positive rate of 16.9% (11/65), and a false negative rate of 38.6% (17/44). In 63 cases integrated diagnosis as oligodendroglial tumors with mutant IDH and 1p/19q co-deletion, the loss of CIC protein expression was 81.0% (51/63); the sensitivity and specificity were increased to 81.0% (51/63) and 76.9% (20/26), and the false positive rate and false negative rate decreased to 10.5% (6/57) and 37.5% (12/32), respectively. By using Kaplan-Meier analysis, the CIC negative group showed a trend towards better outcome than the CIC positive group, but there was no statistical difference (overall survival: P=0.218; progression free survival: P=0.249). Conclusions Detection of the lost CIC protein expression can predict the chromosome 1p/19q co-deletion. In oligodendroglial tumors with IDH mutant and 1p/19q co-deletion, there is no relation between prognosis and CIC protein expression.

Objective: To investigate the diagnostic and prognostic implications of ATRX mutation and p53 mutation in patients with glioma. Methods: The clinicopathologic and molecular features of Chinese adult glioma patients, including diffuse and anaplastic astroastrocytoma with IDH mutation, oligodendroglioma and anaplastic oligodendroglioma with IDH mutation and 1p/19q co-deletion and diffuse astroastrocytoma with IDH wild type were reviewed and tested for ATRX loss expression and p53 overexpression. Results: Loss of ATRX expression was seen in 85.19% (23/27) diffuse and anaplastic astroastrocytoma with IDH mutation, higher than that of oligodendroglial tumors (0/53; P<0.01). Loss of ATRX expression was strongly linked to p53 overexpression(69.57%, 16/23). The patients who lost ATRX expression combined with normal p53 expression survived longer(P=0.013). Conclusions ATRX mutation is a molecular marker for astrocytic tumors. ATRX mutation combined with p53 mutation can predict prognosis of patients with glioma.

OBJECTIVETo study the expression of autophagy-related proteins (Beclin-1, LC3 and p62) in brain tissue with malformations of cortical development and related molecular pathogenesis.

METHODSThe brain tissue of 18 cases with epileptogenic foci resection, including 6 cases of tuberous sclerosis complex (TSC), 6 cases of focal cortical dysplasia type IIb (FCD IIb) and 6 cases of focal cortical dysplasia type I (FCD I), were retrieved. Immunohistochemical study for Beclin-1, LC3 and p62 proteins was performed. The degree of positivity for Beclin-1 and LC3 proteins was compared. Western blot was used to quantitatively analyze the LC3 protein in focal lesion of each disease groups.

RESULTSImmunohistochemical study showed that the three proteins were mainly expressed in the dysmorphic neurons and balloon cells/giant cells of TSC and FCD IIb. The positivity was more intense in the dysmorphic neurons than the other cell types. Immunostaining for Beclin-1 showed granular or diffuse cytoplasmic positivity, in addition to the strong expression in axons. On the other hand, LC3 showed diffuse or perinuclear cytoplasmic expression. The staining for p62 was mainly cytoplasmic or perinuclear and sometimes nuclear. In FCD type I, only individual cells showed positive expression for the three proteins. The number of Beclin-1 and LC3-positive cells was larger in TSC group, followed by FCD IIb group and FCD I group.And there were significant differences between TSC group and FCD I group, as well as FCD IIb group and FCD I group (P<0.05). Quantitative expression of LC3 protein by Western blot showed smaller amount in TSC group, followed by FCD IIb group and FCD I group.

CONCLUSIONSThe dysmorphic neurons and balloon cells/giant cells of TSC and FCD IIb show abnormality in autophagy, resulting in intracytoplasmic protein accumulation. There are differences in molecular pathogenesis in these cell types.