The clinico-pathological characterisation of focal cortical dysplasia type IIb genetically defined by MTOR mosaicism.

AIMS: Focal cortical dysplasia (FCD) is a major cause of drug-resistant paediatric epilepsy and is amenable to successful neurosurgical resection. FCD ILAE Type IIb is the most common FCD subtype, and brain somatic mutations affecting the mTOR pathway play a major pathogenic role. The aim of this study was to comprehensively describe the genotype-phenotype association of 20 patients with histopathologically confirmed FCDIIb using next generation sequencing (NGS) of paired blood-brain samples. METHODS: Clinical and neuropathological data were retrospectively reviewed from the hospital archive. The NGS panel included 11 mTOR-pathway-related genes with maximum coverage of 2000×. The detected variants were validated by digital droplet PCR. RESULTS: Pathogenic MTOR variants were identified in 10 patients (50%). Further comparison with MTOR-wildtype FCDIIb suggested a profound genotype-phenotype association characterised by (1) a non-temporal lobe lesion on MRI, (2) a larger lesion volume occupying grey and white matter (3.032 ± 1.859 cm3 vs 1.110 ± 0.856 cm3 , p = 0.014), (3) more balloon cells (50.20 ± 14.40 BC/mm2 vs 31.64 ± 30.56 BC/mm2 , p = 0.099) and dysmorphic neurons (48.72 ± 19.47DN/mm2 vs 15.28 ± 13.95DN/mm2 , p = 0.000) and (4) a positive correlation between VAF and the lesion volume (r = 0.802, p = 0.017). CONCLUSIONS: Our study identified frequent MTOR mutations in the cell-rich FCDIIb phenotype, clinically characterised by a non-temporal location and large lesion volume. Comprehensive genotype-phenotype associations will help us further explore and define the broad spectrum of FCD lesions to make more targeted therapies available in the realm of epileptology.

Mechanistic Analysis of Micro-Neurocircuits Underlying the Epileptogenic Zone in Focal Cortical Dysplasia Patients.

We aim to explore the microscopic neurophysiology of focal cortical dysplasia (FCD) induced epileptogenesis in specific macroscopic brain regions, therefore mapping a micro-macro neuronal network that potentially indicates the epileptogenic mechanism. Epileptic and relatively non-epileptic temporal neocortex specimens were resected from FCD and mesial temporal lobe epilepsy (mTLE) patients, respectively. Whole-cell patch-clamping was performed on cells from the seizure onset zone (SOZ) and non-SOZ inside the epileptogenic zone (EZ) of FCD patients, as well as the non-epileptic neocortex of mTLE patients. Microscopic data were recorded, including membrane characteristics, spontaneous synaptic activities, and evoked action potentials. Immunohistochemistry was also performed on parvalbumin-positive (PV+) interneurons. We found that SOZ interneurons exhibited abnormal neuronal expression and distribution as well as reduced overall function compared with non-SOZ and mTLE interneurons. The SOZ pyramidal cells experienced higher excitation but lower inhibition than the mTLE controls, whereas the non-SOZ pyramidal cells exhibited intermediate excitability. Action potential properties of both types of neurons also suggested more synchronized neuronal activity inside the EZ, particularly inside the SOZ. Together, our research provides evidence for a potential neurocircuit underlying SOZ epileptogenesis and non-SOZ seizure susceptibility. Further investigation of this microscopic network may promote understanding of the mechanism of FCD-induced epileptogenesis.

Hartnup disease presenting as hereditary spastic paraplegia and severe peripheral neuropathy.

Hartnup disease cases were rare, and the genotype-phenotype correlation was not fully understood. Here we reported two unrelated young men diagnosed as Hartnup disease, who carried novel compound heterozygote mutations in the SLC6A19 gene and presented with new phenotypes. Other than intermittent encephalopathy and photosensitive rashes, they displayed symptoms and signs of spastic paraplegia and severe peripheral nerve damages. Magnetic resonance imaging showed mild bilateral cerebellar atrophy and thinning of the thoracic spinal cord. Electromyogram detected mixed sensorimotor polyneuropathy in lower limbs. Sural nerve biopsy and pathological study indicated the moderately reduced neural fibers in the periphery nerves. Urinary amino acid analysis showed increased levels of multiple neutral amino acids. Moreover, muscle strengths in the lower limbs and the walking ability have been improved in both cases (MRC 3/5 to 4/5 in Patient 1; walking distance elongated from 50 to 100 m in Patient 2) after the treatment with oral nicotinic acid and intravenous injection of multiple amino acids. Exome sequencing revealed and confirmed the existence of the novel compound heterozygous SLC6A19 mutations: c.533G>A (p.Arg178Gln) and c.1379-1G>C mutations in patient1, and c.1433delG (p.Gly478AlafsTer44) and c.811G>A (p.Ala271Thr) in patient 2. Taken together, these findings expanded the clinical, neuroimaging, pathology, and genetic spectrum of Hartnup disease. However, the co-existence of HSP and peripheral neuropathy was only inferred based on clinical observations, and pathological and molecular studies are needed to further dissect the underlying mechanisms.

The ILAE consensus classification of focal cortical dysplasia: An update proposed by an ad hoc task force of the ILAE diagnostic methods commission.

Ongoing challenges in diagnosing focal cortical dysplasia (FCD) mandate continuous research and consensus agreement to improve disease definition and classification. An International League Against Epilepsy (ILAE) Task Force (TF) reviewed the FCD classification of 2011 to identify existing gaps and provide a timely update. The following methodology was applied to achieve this goal: a survey of published literature indexed with ((Focal Cortical Dysplasia) AND (epilepsy)) between 01/01/2012 and 06/30/2021 (n = 1349) in PubMed identified the knowledge gained since 2012 and new developments in the field. An online survey consulted the ILAE community about the current use of the FCD classification scheme with 367 people answering. The TF performed an iterative clinico-pathological and genetic agreement study to objectively measure the diagnostic gap in blood/brain samples from 22 patients suspicious for FCD and submitted to epilepsy surgery. The literature confirmed new molecular-genetic characterizations involving the mechanistic Target Of Rapamycin (mTOR) pathway in FCD type II (FCDII), and SLC35A2 in mild malformations of cortical development (mMCDs) with oligodendroglial hyperplasia (MOGHE). The electro-clinical-imaging phenotypes and surgical outcomes were better defined and validated for FCDII. Little new information was acquired on clinical, histopathological, or genetic characteristics of FCD type I (FCDI) and FCD type III (FCDIII). The survey identified mMCDs, FCDI, and genetic characterization as fields for improvement in an updated classification. Our iterative clinico-pathological and genetic agreement study confirmed the importance of immunohistochemical staining, neuroimaging, and genetic tests to improve the diagnostic yield. The TF proposes to include mMCDs, MOGHE, and "no definite FCD on histopathology" as new categories in the updated FCD classification. The histopathological classification can be further augmented by advanced neuroimaging and genetic studies to comprehensively diagnose FCD subtypes; these different levels should then be integrated into a multi-layered diagnostic scheme. This update may help to foster multidisciplinary efforts toward a better understanding of FCD and the development of novel targeted treatment options.

Progressive multifocal leukoencephalopathy in a patient with mediastinal teratoma: a case report.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating lytic brain infection caused by the John Cunningham virus (JCV). JCV manifests primarily in patients with innate immunodeficiency or taking immunomodulatory medications. In this case study, we report a PML patient with comorbid mediastinal teratoma and mild lymphopenia. CASE PRESENTATION: A 73-year-old female presented with a 3-month history of progressive hemiplegia, hemianopsia, and cognitive impairment. She was diagnosed as PML by cerebrospinal fluid metagenomics sequencing and brain biopsy. Extensive immunological tests did not reveal an apparent immunodeficiency, but further work-up revealed that the PML was most likely the first presentation of mediastinal teratoma and the mild lymphopenia. Mirtazapine and immunoglobulin were started, the patient's condition was relatively stable and approved to be discharged from hospital. But unfortunately, she died of the lung infection 10 months after first presentation. CONCLUSIONS: This case confirms that mediastinal teratoma may induce the lymphopenia and trigger PML, delayed or incorrect diagnosis may worsen the course of the disease and result in poor prognosis.

Meningeal carcinomatosis secondary to neurenteric cysts with malignant transformation: a case report.

BACKGROUND: Meningeal carcinomatosis is mainly associated with breast cancer, lung cancer, and melanoma. However, meningeal carcinomatosis secondary to a neurenteric cyst with malignant features is extremely rare. CASE PRESENTATION: We report the case of a 35-year-old woman who was admitted to the hospital with a 10-month history of headache, 6-month history of diplopia, 4-month history of hearing loss, and 1-month history of back pain, suggesting a diagnosis of chronic meningitis. Notably, enhanced brain and spinal cord magnetic resonance imaging (MRI) revealed extensive lesions with enhancement signals in the pia mater of the pons and cervical, thoracic, and lumbar spinal cord. The cerebral spinal fluid profile showed that pressure was significantly elevated, with a slight increase in leukocytes that mostly comprised mononuclear cells and decreased glucose concentration. Cytology evaluation showed a small cluster of atypical nuclei, which were suspected to be tumor cells arising from the epithelium. However, no primary tumor was found through comprehensive body and skin screening. After a histopathological biopsy of subarachnoid meninx of the thoracic spinal canal, the cause of meningeal carcinomatosis of this patient was determined as neurenteric cysts with malignant features, which is extremely rare. CONCLUSION: This is the first case to ever report neurenteric cysts as a cause of leptomeningeal carcinomatosis and the first ever report of neurenteric cysts presenting as leptomeningeal carcinomatosis without typical cyst visible on brain MRI. This extremely rare case provided a novel view on the pathogenesis of meningeal carcinomatosis and clinical presentation of neurenteric cysts, highlighting the value of meningeal biopsy in chronic meningitis of unknown causes.

Diffuse midline glioma with H3 K27M mutation of the spinal cord: A series of 33 cases.

We investigated the risk factors for diffuse midline gliomas of the spinal cord (DMGSCs). Seventy patients with spinal cord gliomas in two hospitals were analyzed retrospectively. Sixty-nine patients that underwent surgery achieved partial or gross total removal. The patients were subdivided into some groups, based on age, WHO grade, tumor location within the cord, tumor size, and molecular profile: immunohistochemical expression of p53 and ATRX, and mutational status of Histone 3 (H3), and BRAF. Thirty-three patients had an H3 K27M mutation (47%). Some clinical characteristics were significantly different between H3 K27M mutant and H3 wild-type tumors. The main risk factors for DMGSCs were male sex, glioblastomas, and ≤ 2 spinal cord segments. The median survival period of patients with H3 K27M mutant tumors was significantly shorter than those with H3 wild-type tumors (17.0 ± 3.7 months vs censored, P < 0.0001). In the DMGSC subgroup, patients with thoracic cord tumors had a significantly better prognosis than those with cervical cord tumors (31.0 ± 6.0 vs 10.0 ± 4.8 months). Patients > 45 years of age survived significantly longer than patients < 19 years (P = 0.001). In conclusion, H3 K27M mutation significantly predicts a worse outcome of spinal cord gliomas. Anatomical location and age are the main risk factors for DMGSCs.

Neuroimaging characteristics and long-term prognosis of myxoma-related intracranial diseases.

PURPOSE: Myxoma-related intracranial diseases were rarely documented in history. The main purpose of our study is to provide a more comprehensive and detailed understanding of the pathogenesis, imaging features, surgical procedures and pathology of such patients through long-term follow-up. METHODS: From March 2012 to July 2018, baseline information that included neuroimaging and neuropathology data from 12 cardiac myxoma patients with neurological symptoms were retrospectively analysed, and the treatment options were discussed. Nine patients underwent long-term postoperative follow-up. RESULTS: Twelve cardiac myxoma patients with neurological symptoms were identified, and among them, 10 patients were postoperative patients who had undergone excision of cardiac myxoma, 5 patients had received craniotomy, and the others had received conservative treatment. Positive neuroimaging findings were found in all patients, including cerebral infarction (12/12, 100%), multiple intracranial aneurysms (8/12, 67%), and extravascular metastasis (6/12, 50%). After a long-term average follow-up of 27 months, an increased number of metastatic lesions or an enlargement of the intracranial aneurysms was found in 4 patients. CONCLUSIONS: Neuroimaging findings of myxoma-related intracranial lesions were diversed and usually presented as multiple cerebral infarction, aneurysm formation, focal intracranial haemorrhage and space-occupying lesions. Progress is over a long period of time after primary tumour resection. It is necessary for patients to be regularly examined within 2 years after cardiac myxoma resection using MRI+CTA/MRA/DSA in order to be ruled out. Stable and effective chemotherapy drugs are urgently needed.

MYB-QKI rearrangement in angiocentric glioma.

AIMS: To evaluate the occurrence and diagnostic value of MYB-QKI rearrangement status in angiocentric glioma (AG) in Chinese patients. MATERIALS AND METHODS: 27 cases were collected from six hospitals, followed by a retrospective analysis of clinical, radiological, and morphological data. MYB protein expression was assessed by immunohistochemical staining (IHC), and the MYB-QKI rearrangement was detected by fluorescence in situ hybridization (FISH). RESULTS: Among the 27 cases (16 males), the median age at surgery was 17 years (range 3 - 43 years); 24 (88.9%) cases had a history of refractory epilepsy, and the mean history of pre-surgical epilepsy was 13 years (range 1.5 - 27 years); 26 (96.3%) cases had lesions located in the superficial cerebrocortical regions, and 1 (3.7%) case had a lesion in the brainstem. Except for the classic histological features, the involvement of superficial cortex extending to the leptomeninges, microcalcification, and cystic pattern with microcystic formations was observed in 11 (40.7%), 3 (11.1%), and 4 (14.8%) cases, respectively. IHC showed that all 27 cases were positive for glial fibrillary acidic protein (GFAP) and vimentin, and negative for neuronal nuclear antigen (NeuN). The positive rates of epithelial membrane antigen (EMA) and D2-40 were 81.5% (22/27) and 74.1% (20/27), respectively. A total of 14 (51.9%) cases were positive for MYB. The rate of Ki-67 proliferation was 1 - 5% in 25 cases, and in 2 cases with anaplastic features it was 10 and 20%. MYB-QKI rearrangement was revealed by FISH examination in 95.8% (23/24) of the AGs, including 3 cases with atypical histological appearance. CONCLUSION: Compared to IHC, FISH was more appropriate for detecting MYB-QKI rearrangement. MYB-QKI rearrangement was detected in the majority of Chinese AG cases, and therefore represents a potential diagnostic biomarker for AG.

An adult case of diffuse midline glioma with H3 K27M mutation.

Cartilaginous metaplasia is rare in primary central nervous system (CNS) neoplasms and has not been described in the histone 3 (H3) gene (H3) with a substitution of lysine to methionine (H3 K27M mutant) diffuse midline glioma before. Here, we report a case of H3 K27M mutant diffuse midline glioma with cartilaginous metaplasia in a 56-year-old woman. Magnetic resonance imaging (MRI) revealed a ring-enhanced lesion located in the medulla oblongata and extended superiorly into the fourth ventricle. The tumor was macroscopically completely resected. Histologically, the tumor was composed of a gliomatous component and a well-differentiated cartilaginous component. Microvascular proliferation and necrosis were noted. According to immunohistochemical staining, glial cells were diffusely and strongly positive for glial fibrillary acidic protein (GFAP), oligodendrocyte lineage transcription factor 2 (Olig2), H3 K27M, and S-100 protein but negative for H3K27me3. The chondrocytes also were positive for GFAP and S-100 protein. The H3 K27M mutation was confirmed by sequencing in both the gliomatous and cartilaginous components, suggesting a common origin from the same progenitor cells. Based on these findings, the tumor was diagnosed as a diffuse midline glioma with H3 K27M mutation with widespread cartilaginous metaplasia, corresponding to WHO grade IV. This is an extremely rare H3 K27M mutant diffuse midline glioma with cartilaginous metaplasia, and reporting this unusual case adds to the understanding of this tumor type.

The specificity and role of microglia in epileptogenesis in mouse models of tuberous sclerosis complex.

OBJECTIVE: Microglial abnormalities have been reported in pathologic specimens from patients with tuberous sclerosis complex (TSC), a genetic disorder characterized by epilepsy, intellectual disability, and autism. However, the pathogenic role of microglia in epilepsy in TSC is poorly understood, particularly whether microglia defects may be a primary contributor to epileptogenesis or are secondary to seizures or simply epiphenomena. In this study, we tested the hypothesis that Tsc1 gene inactivation in microglia is sufficient to cause epilepsy in mouse models of TSC. METHODS: Using a chemokine receptor, Cx3cr1, to target microglia, conventional Tsc1Cx3cr1-Cre CKO (conditional knockout) mice and postnatal-inducible Tsc1Cx3cr1-CreER CKO mice were generated and assessed for molecular and histopathologic evidence of microglial abnormalities, mechanistic target of rapamycin 1 (mTORC1) pathway activation, and epilepsy. RESULTS: Tsc1Cx3cr1-Cre CKO mice exhibited a high efficiency of microglia Tsc1 inactivation, mTORC1 activation, increased microglial size and number, and robust epilepsy, which were rapamycin-dependent. However, Cre reporter studies demonstrated that constitutive Cx3cr1 expression affected not only microglia, but also a large percentage of cortical neurons, confounding the role of microglia in epileptogenesis in Tsc1 Cx3cr1-Cre CKO mice. In contrast, postnatal inactivation of Tsc1 utilizing a tamoxifen-inducible Cx3cr1-CreER resulted in a more-selective microglia Tsc1 inactivation with high efficiency, mTORC1 activation, and increased microglial size and number, but no documented epilepsy. SIGNIFICANCE: Microglia abnormalities may contribute to epileptogenesis in the context of neuronal involvement in TSC mouse models, but selective Tsc1 gene inactivation in microglia alone may not be sufficient to cause epilepsy, suggesting that microglia have more supportive roles in the pathogenesis of seizures in TSC.

A distinct clinicopathological variant of focal cortical dysplasia IIId characterized by loss of layer 4 in the occipital lobe in 12 children with remote hypoxic-ischemic injury.

OBJECTIVE: In 2011, the International League Against Epilepsy (ILAE) proposed a consensus classification system of focal cortical dysplasia (FCD) to distinguish clinicopathological subtypes, for example, "isolated" FCD type Ia-c and IIa-b, versus "associated" FCD type IIIa-d. The histopathological differentiation of FCD type I and III variants remains, however, a challenging issue in everyday practice. We present a unique histopathological pattern in patients with difficult-to-diagnose FCD, which highlights this dilemma, but also helps to refine the current ILAE classification scheme of FCD. METHODS: We present a retrospective series of 11 male and one female patient with early onset pharmacoresistant epilepsy of the posterior quadrant (mean age at seizure onset = 4.6 years). All surgical specimens were reviewed. Clinical histories were retrieved and extracted from archival patient files. RESULTS: Microscopic inspection revealed abnormalities in cortical architecture with complete loss of layer 4 in all surgical samples of the occipital lobe, as confirmed by semiquantitative measurements (p < 0.01). Clinical history reported early transient hypoxic condition in nine patients (75%). Magnetic resonance imaging (MRI) revealed abnormal signals in the occipital lobe in all patients, and signal changes suggestive of subcortical encephalomalacia were found in seven patients. Surgical treatment achieved favorable seizure control (Engel class I and II) in seven patients with an available follow-up period of 6.1 years. SIGNIFICANCE: Prominent disorganization of cortical layering and lack of any other microscopically visible principle lesion in the surgical specimen would result in this neuropathological pattern hitherto being classified as FCD ILAE type Ib. However, perinatal hypoxia with distinctive MRI changes suggested primarily a hypoxemic lesion and acquired pathomechanism of neuronal cell loss in the occipital lobe of our patient series. We propose, therefore, classifying this distinctive clinicopathological pattern as a separate variant of FCD ILAE type IIId.

Glioneuronal tumours with features of rosette-forming glioneuronal tumours of the fourth ventricle and dysembryoplastic neuroepithelial tumours: a report of three cases.

AIMS: To study three atypical glioneuronal tumours (GNTs), in order to shed light on the clinical and pathological features of this diverse tumour group. METHODS AND RESULTS: Clinical and neuropathological data for each case were retrospectively reviewed. Case 1 involved a 17-year-old boy with left leg movement difficulty. A mass lesion in the basal ganglia was detected radiologically; histopathological features included neurocytic/perivascular rosettes and a pilocytic astrocytoma component. Case 2 involved a 33-year-old man with intractable epilepsy. His left parietal lobe contained a cyst-like mass, resembling dysembryoplastic neuroepithelial tumour and rosette-forming glioneuronal tumour of the fourth ventricle microscopically. Case 3 involved a 21-year-old woman with a mass lesion in the mesencephalic tegmentum extending to the third and fourth ventricles and the suprasellar region. The lesion contained perivascular/neurocytic rosettes and an oligodendroglioma-like component. None of the tumours expressed an isocitrate dehydrogenase I mutation of the R132H type or contained a 1p/19q deletion, a BRAF(V600E) mutation, or KIAA1549-BRAF fusion. CONCLUSIONS: We describe three GNTs with atypical histopathology and locations. Additional cases and molecular studies are needed to better understand the biological nature of GNTs and to refine their classification system.

Angiocentric glioma: a report of nine new cases, including four with atypical histological features.

AIMS: Angiocentric glioma (AG) is a rare, slow-growing tumour of the central nervous system. It is often associated with refractory epilepsy and occurs most commonly in children and young adults. We herein report nine cases of AG, including four with atypical histological findings. METHODS: The clinical data and clinicopathological findings of nine cases with AG histological features were described. RESULTS: All nine patients had a history of refractory epilepsy with a mean history of 4.4 years and a median age of 17.6 years at surgery. The AG lesions were located in the superficial cerebrocortical region. Histological examination of these cases revealed characteristic structural features of AG, including bipolar spindle-shaped cells with an angiocentric growth pattern. However, four cases also exhibited atypical histological features: one had astroblastoma-like characteristics, two had a distinct cystic region with an onion-like structure and myxoid changes, and the other one had a region involving many abnormal neurones reminiscent to ganglioglioma. All were positive for glial fibrillary acidic protein and vimentin. Eight cases were positive for epithelial membrane antigen (EMA), with a dot-like staining pattern. A diffuse D2-40 staining was visible in these cases, with two having similar staining pattern to EMA. All cases were immunonegative for BRAF V600E and isocitrate dehydrogenase-1 R132H mutations. CONCLUSIONS: Our results demonstrate that atypical histological features can be present in AG. A collection of more cases and further molecular analyses are required to confirm our findings.

Longitudinal three-dimensional-T2WI-SPACE study on wallerian degeneration in cat corticospinal tract and underlying pathology changes.

PURPOSE: To investigate the feasibility of T2W-SPACE technique in early detection of WD, the signal evolutions of degenerated corticospinal tract (CST) on T2W-SPACE, and their underlying pathological changes. MATERIALS AND METHODS: The WD model of the CST was established in 23 cats through excision of cortical origins of the tract. Eight cats were scanned with the T2W-SPACE technique at 8 sequential time points, i.e. 0 (before modeling), 2, 4, 6, 8, 10, 20 and 30 days after modeling, and then they were pathologically examined. The remaining 15 cats (3 per group) also underwent pathological examination at 2, 4, 6, 10 and 20 days after modeling, respectively. The ratios of T2 signal intensity (rT2s) between the affected and unaffected sides of CST were analyzed. RESULTS: During the first 4 days, SPACE could not detect any significant changes of the affected CST, although axonal degeneration was pathologically observed at the second day. From 6 to 10 days, the rT2s decreased monotonously, which is corresponded to histological findings of myelin degeneration and phagocyte proliferation. From 10 to 20 days, rT2s kept relatively stable at a low level and started to recover after that; the pathological changes of this period was characterized by marked phagocytizing activities. CONCLUSION: SPACE technique can detect Wallerian degeneration at an early stage, and the signal evolution is consistent with the pathological processes.

[Clinicopathological study of non-Langerhans cell histiocytosis in central nervous system].

OBJECTIVE: To explore the clinicopathological features and imaging characteristics of non-Langerhans cell histiocytosis in central nerve system, thus to facilitate the diagnosis and differential diagnosis. METHODS: A total of ten cases were enrolled in the study, with seven cases of Rosai-Dorfman disease (RDD) and three cases of xanthoma disseminatum (XD). Data on the clinicopathological features, imaging, immunophenotype and prognosis were collected and analyzed. RESULTS: Seven patients with RDD, 5 males and 2 females with the mean age of 46.7 years old, all presented as dural-based or intraparenchymal hypo- to isointense lesions on T1 and T2 with post-contrast enhancement. The polymorphous admixture of histiocytes, lymphocytes and plasma cells was observed in a fibrous stroma, with emperipolesis of some histiocytes. The immunohistostaining of CD11c, CD68, MAC387 and S-100 was positive in the histiocytes, while the staining of CD1α was negative. Five patients recovered after the operation, while one patient died of the disease. All the 3 XD patients were female, with the median age of 20.7 years old. All XD patients presented as multiple intraparenchymal hypointense lesions on T1 and hyperintense lesions on T2 with post-contrast enhancement. The infiltration of foam-like histiocytes, a few Touton giant cells, lymphocytes and eosnophils was observed in all XD patients. The immunohistostaining of CD68 and CD11c was positive in the histiocytes and that of MAC387 partly positive, while the staining of S-100 and CD1α was negative. One XD patient survived well, while another one died of the disease. CONCLUSIONS: The diagnosis of RDD and XD should be based on their typical morphology and immunophenotype and should be differentiated from Langerhans cell histiocytosis and other non-Langerhans cell histiocytosis. Non-Langerhans cell histiocytosis in central nerve system often presents untypical clinical presentation and imaging features, thus the communication and cooperation between clinician and pathologist is needed.

[Expression of autophagy-related proteins in malformations of cortical development].

OBJECTIVE: To study the expression of autophagy-related proteins (Beclin-1, LC3 and p62) in brain tissue with malformations of cortical development and related molecular pathogenesis. METHODS: The 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. RESULTS: Immunohistochemical 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. CONCLUSIONS: The 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.

Delineating structural and metabolic abnormalities in amygdala and hippocampal subfields for different seizure-onset patterns via stereotactic electroencephalography.

AIMS: We aimed to investigate mesial temporal lobe abnormalities in mesial temporal lobe epilepsy (MTLE) patients with hypersynchronous (HYP) and low-voltage fast rhythms (LVF) onset identified by stereotactic electroencephalography (SEEG) and evaluate their diagnostic and prognostic value. METHODS: Fifty-one MTLE patients were categorized as HYP or LVF by SEEG. High-resolution MRI volume-based analysis and 18F-FDG-PET standard uptake values of hippocampal and amygdala subfields were quantified and compared with 57 matched controls. Further analyses were conducted to delineate the distinct pathological characteristics differentiating the two groups. Diagnostic and prognostic prediction performance of these biomarkers were assessed using receiver operating characteristic curves. RESULTS: LVF-onset individuals demonstrated ipsilateral amygdala enlargement (p = 0.048) and contralateral hippocampus hypermetabolism (p = 0.042), pathological results often accompany abnormalities in the temporal lobe cortex, while HYP-onset subjects had significant atrophy (p < 0.001) and hypometabolism (p = 0.013) in ipsilateral hippocampus and its subfields, as well as amygdala atrophy (p < 0.001), pathological results are highly correlated with hippocampal sclerosis. Severe fimbria atrophy was observed in cases of HYP-onset MTLE with poor prognosis (AUC = 0.874). CONCLUSION: Individuals with different seizure-onset patterns display specific morphological and metabolic abnormalities in the amygdala and hippocampus. Identifying these subfield abnormalities can improve diagnostic and prognostic precision, guiding surgical strategies for MTLE.

Chordoid glioma of the third ventricle: four cases including one case with papillary features.

Chordoid glioma is a rare, slowly growing tumor of the CNS, which is always located in the third ventricle of adults. Chordoid glioma has classic histological features consisting of clusters and cords of epithelioid tumor cells embedded within a mucinous stroma with rich lymphoplasmacytic infiltrate. The important distinctive immunohistochemical feature of this neoplasm is strong and diffuse reactivity for GFAP. Here, we report four cases of chordoid glioma that occupied the anterior portion of the third ventricle or suprasellar region. These four cases were all adult females with almost typical clinical, radiological, histologic and immunohistochemical characteristics of chordoid glioma. However, in one case there was an unusual histologic finding with regard to the papillary region. In this region, elongated tumor cells were observed radiating toward a central vessel to form characteristic papillary structures. Immunohistochemically, three cases showed strong reactivity for GFAP, and one exhibited weak reactivity. All cases were focally positive for epithelial membrane antigen, CD34 and D2-40, but negative for neurofilament protein (NFP). Several ultrastructural investigations have supported the ependymal origin of chordoid glioma. In some cases of immunoreactivity for NFP, some authors have supposed that chordoid glioma originates from a multipotential stem cell with glial and neuronal cell differentiation. With regard to the present four cases with immunoreactivity for D2-40 (an ependymal marker) and CD34 (undifferentiated neural precursors) and based on previously published data, we considered that the majority of chordoid gliomas had an ependymal origin, and that a small minority might have originated from a multipotential stem cell having ependymal and neuronal cell differentiation.

Case report: Late in-stent thrombosis in a patient with vertebrobasilar dolichoectasia after stent-assisted coil embolization due to the discontinuation of antiplatelet therapy.

Vertebrobasilar dolichoectasia (VBD) is a rare type of cerebrovascular disorder with high rates of morbidity and mortality. Due to the distinct pathological characteristics that fragmented internal elastic lamina and multiple dissections, VBD is difficult to treat and cured. Stent-assisted coil embolization is one of the main treatment modalities for such lesions. However, the duration of healing remained questionable, and there were no effective measures for evaluating endothelial coverage. Before complete endothelial coverage, the discontinuation of antiplatelet therapy may lead to fatal in-stent thrombosis; however, continued antiplatelet therapy could also result in bleeding complications. Thus, we present an autopsy case of late in-stent thrombosis due to the discontinuation of antiplatelet therapy and systematically review the literature to provide a reference for endovascular treatment and antiplatelet regimen of VBD.