Identification of epithelial membrane protein 2 (EMP2) as a molecular marker and correlate for angiogenesis in meningioma.

PURPOSE: Although intracranial meningiomas are the most common primary brain tumor in adults, treatment options are few and have traditionally been limited to surgical resection and radiotherapy. Additional targeted therapies and biomarkers are needed, especially as complete surgical resection is frequently not feasible in many patients. METHODS: Non-pathologic brain tissue from 3 patients undergoing routine autopsies and tumor specimens from 16 patients requiring surgical resection for meningioma were collected. EMP2 protein expression was evaluated by immunohistochemistry and western blot analysis. EMP2 mRNA expression was also investigated using surgical specimens and validated by analysis of several independent NCBI GEO databases. RESULTS: EMP2 mRNA expression levels were found to be higher in meningioma relative to non-pathologic meninges (P = 0.0013) and brain (P = 0.0011). Concordantly, strong EMP2 protein expression was demonstrated in 100% of meningioma specimens from all 16 patients, with no observable protein expression in normal brain tissue samples from 3 subjects (P < 0.001). EMP2 expression was confirmed by western blot analysis in five samples, with EMP2 protein intensity positively correlating with histologic staining score (R2 = 0.780; P = 0.047). No association was found between EMP2 mRNA or protein levels and WHO grade or markers of proliferation. However, EMP2 expression was positively associated with an angiomatous pattern on histologic evaluation (P = 0.0597), VEGF-A mRNA expression (P < 0.001), and clinical markers of tumor vascularity such as operative blood loss (P = 0.037). CONCLUSIONS: EMP2 is not found in normal brain tissue, yet has shown consistently high mRNA and protein expression in meningiomas, and may serve as a useful molecular marker for these tumors.

A Case of Cerebral Cysticercosis in Thailand.

Cysticercosis and sparganosis are not uncommon parasitic infections in the developing world. Central nervous system infection by both cestodes can present with neurological signs and symptoms, such as seizure and mass effect, including brain hernia. Early detection and accurate diagnosis can prevent a fatal outcome. Histological examinations of brain tissues can confirm the diagnosis of cerebral cysticercosis, which differs from sparganosis by the presence of a cavitated body. We report here a case of cerebral cysticercosis which has the similar clinical and imaging findings as sparganosis.

Preoperative Transarterial Embolization of a Large Petrotentorial Angiomatous Meningioma Using Combination of Liquid Embolic Materials: A Case Report.

Intracranial angiomatous meningiomas are a rare WHO grade I histological variant of meningioma whose vascular component exceeds 50% of the total tumor area. Preoperative embolization of angiomatous meningiomas has rarely been reported previously. A 58-year-old woman was referred to our institute for a large petrotentorial hypervascular tumor presented with progressively worsening right facial paralysis and hearing loss for 6 months. Cranial computed tomography scan and magnetic resonance imaging revealed a large homogenously enhancing multilobulated mass involving middle and posterior cranial fossae with marked brainstem compression. The tumor extended into a right internal auditory canal and labyrinthine structures with destructive changes of bony structures. Magnetic resonance angiography showed hypervascularity in the tumor. Preoperative transarterial embolization using liquid embolic materials was successfully performed with resulting in almost complete devascularization of the tumor. Adequate hemostasis was achieved following gross total resection of the tumor (Simpson grade II). A histopathological examination confirmed the diagnosis of an angiomatous meningioma. Preoperative transarterial embolization of angiomatous meningioma with liquid embolic material was safe and effective in reducing perioperative blood loss and facilitating total tumor resection.

Sacral dural arteriovenous fistula of the filum terminale coexisting with partially thrombosed filum vein: A case report and literature review.

Background: Filum terminale arteriovenous fistulas (FTAVFs) are rare and usually classified as intradural ventral AVFs or Type IVa perimedullary fistulas, located on the pia surface along the course of filum terminale internum (FTI). We report an extremely rare case of sacral dural arteriovenous fistula of the FT. We also review the occurrence of FTAVFs in the sacral region. Case Description: A 64-year-old man presented with progressive weakness of the lower extremities for 3 months and bowel/bladder dysfunction following long history of back pain radiating to both legs. Magnetic resonance imaging of the lumbosacral and thoracic spine showed spinal cord congestion, extending from the conus medullaris to the level of T3, and partial thrombosis within the abnormal tortuous and dilated flow void, running from the sacral area to conus medullaris. Further findings were compression fracture of L2 vertebra, Grade I degenerative spondylolisthesis at the level of L2-3, and L3-4, and spinal stenosis at L2-3, L3-4, and L4-5. Spinal angiography, maximum intensity projection reformatted image of angiographic computerized tomography, and three-dimensional reconstructed image clearly demonstrated dural AVF of the FT at the level of S2 supplied by bilateral lateral sacral and middle sacral arteries with cranial drainage to perimedullary vein through the enlarged vein of the filum. The patient was indirectly treated by transection of the filum terminale and the draining vein at the level of L5 rostral to the fistula. Conclusion: Sacral DAVFs of the FT are extremely rare. In our case, the formation of fistula may cause by venous hypertension secondary to partial thrombosis within the filum vein, probably resulting from long-standing spinal canal stenosis. Sacral FTAVFs may be found on the pia surface of the terminal FTI, dural component at the area of dural sac termination, or dural extension covering the filum terminale externum.

Simplified approach for pathological diagnosis of diffuse gliomas in adult patients.

The most recent WHO classification (2016) for gliomas introduced integrated diagnoses requiring both phenotypic and genotypic data. This approach presents difficulties for countries with limited resources for laboratory testing. The present study describes a series of 118 adult Thai patients with diffuse gliomas, classified by the WHO 2016 classification. The purpose was to demonstrate how a diagnosis can still be achieved using a simplified approach that combines clinical, morphological, immunohistochemical, and fewer molecular assays than typically performed. This algorithm starts with tumor location (midline vs. non-midline) with diffuse midline glioma identified by H3 K27M immunostaining. All other tumors are placed into one of 6 categories, based on morphologic features rather than specific diagnoses. Molecular testing is limited to IDH1/IDH2 mutations, plus co-deletion of 1p/19q for cases with oligodendroglial features and TERT promoter mutation for cases without such features. Additional testing for co-deletion of 1p/19q, TERT promoter mutation and BRAF mutations are only used in selected cases to refine diagnosis and prognosis. With this approach, we were able to reach the integrated diagnosis in 117/118 cases, saving 50 % of the costs of a more inclusive testing panel. The demographic data and tumor subtypes were found to be similar to series from other regions of the world. To the best of our knowledge, this is to the first reported series of diffuse gliomas in South-East Asia categorized by the WHO 2016 classification system.

Neuropathology of COVID-19 (neuro-COVID): clinicopathological update.

Coronavirus disease 2019 (COVID-19) is emerging as the greatest public health crisis in the early 21stcentury. Its causative agent, Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), is an enveloped single stranded positive-sense ribonucleic acid virus that enters cells via the angiotensin converting enzyme 2 receptor or several other receptors. While COVID-19 primarily affects the respiratory system, other organs including the brain can be involved. In Western clinical studies, relatively mild neurological dysfunction such as anosmia and dysgeusia is frequent (~70-84%) while severe neurologic disorders such as stroke (~1-6%) and meningoencephalitis are less common. It is unclear how much SARS-CoV-2 infection contributes to the incidence of stroke given co-morbidities in the affected patient population. Rarely, clinically-defined cases of acute disseminated encephalomyelitis, Guillain-Barré syndrome and acute necrotizing encephalopathy have been reported in COVID-19 patients. Common neuropathological findings in the 184 patients reviewed include microglial activation (42.9%) with microglial nodules in a subset (33.3%), lymphoid inflammation (37.5%), acute hypoxic-ischemic changes (29.9%), astrogliosis (27.7%), acute/subacute brain infarcts (21.2%), spontaneous hemorrhage (15.8%), and microthrombi (15.2%). In our institutional cases, we also note occasional anterior pituitary infarcts. COVID-19 coagulopathy, sepsis, and acute respiratory distress likely contribute to a number of these findings. When present, central nervous system lymphoid inflammation is often minimal to mild, is detected best by immunohistochemistry and, in one study, indistinguishable from control sepsis cases. Some cases evince microglial nodules or neuronophagy, strongly supporting viral meningoencephalitis, with a proclivity for involvement of the medulla oblongata. The virus is detectable by reverse transcriptase polymerase chain reaction, immunohistochemistry, or electron microscopy in human cerebrum, cerebellum, cranial nerves, olfactory bulb, as well as in the olfactory epithelium; neurons and endothelium can also be infected. Review of the extant cases has limitations including selection bias and limited clinical information in some cases. Much remains to be learned about the effects of direct viral infection of brain cells and whether SARS-CoV-2 persists long-term contributing to chronic symptomatology.

Complete Resolution of a Large Hemorrhagic Lumbar Synovial Cyst Following Spinal Fusion Alone.

The authors reported complete regression of a large hemorrhagic lumbar synovial cyst following posterior spinal fusion without direct cystic resection. A 64-year-old woman suffered from sudden onset of the left buttock pain radiating to the left leg after waking up in the morning following the previous history of a minor accident 2 months ago. Magnetic resonance imaging (MRI) of the lumbosacral spine showed a large extradural round mass originating from the left facet joint at the level of L3-L4. The mass was hyperintense on T1-weighted images and hypointense on T2-weighted images, probably compatible with hemorrhagic joint-related cyst. Surgical treatment was chosen for her because of persistent left radicular pain with no responding to medications. The patient underwent decompressive laminectomy, subtotal facetectomy, instrumented fusion, and only tissue biopsy due to severe adherence of the mass and dura. Histopathological examination was consistent with a hemorrhagic synovial cyst. The radicular pain completely disappeared after the surgery. Follow-up MRI of the lumbosacral spine obtained 6 months after the surgery demonstrated complete resolution of the hemorrhagic cyst. Complete resolution of hemorrhagic synovial cyst seems to correlate with subtotal facetectomy, probably resulting in leakage of cyst content and subsequent resorption of the cyst wall. In addition, hematoma within the synovial cyst may resolve spontaneously over time.

Spontaneous Spinal Osseous Epidural Arteriovenous Fistula with Long Segments of Prominent Epidural Venous Drainage Causing Severe Compressive Thoracic Myelopathy Successfully Treated with Combined Endovascular and Surgical Treatments: A Case Report and Review of the Literature.

The authors describe an extremely rare case of spinal osseous epidural arteriovenous fistulas (SOEAVFs) with unique characteristic features. A 25-year-old man presented with progressive weakness and paresthesia of the lower extremities for 1 month. Magnetic resonance imaging of the thoracic spine showed an extradural dilated vascular flow void structure extending from T4 to T8 levels with abnormal hyperintense T2 signal from T6 to T8 levels. Magnetic resonance angiography and spinal angiography revealed unique features of SOEAVF supplied by multiple small arterial feeders of intercostal arteries converging into a dilated round venous sac corresponding to a bony defect of T7 lamina and spinous process. The venous drainage directly drained into prominent epidural venous plexus extending from the level of T4 to T8 without intradural venous drainage, causing severe compressive myelopathy. Transarterial embolization was performed using N-butyl cyanoacrylate through the main feeder. Subsequently, he successfully underwent laminectomy and total excision of the fistula and large epidural draining venous plexus. Histopathology confirmed spinal vascular malformations with evidence of previous embolization. He gradually improved until being ability to walk independently 3 months later. Follow-up spinal angiography confirmed complete resection of SOEAVF. The patient has remained clinically asymptomatic 5 years after operation.

Sacral Extradural Angiolipoma Associated with Tight Filum Terminale and Spina Bifida Coexisting with Spinal Arteriovenous Fistula.

BACKGROUND: Spinal arteriovenous fistula (AVF) may rarely associate with spinal dysraphism, that is, tethered spinal cord and spinal intradural lipoma. Spinal extradural angiolipoma coexisting with spinal AVF has not been reported in the literature. We reported an extremely rare case of sacral angiolipoma associated with tight filum terminale and sacral spina bifida coexisting with spinal AVF within this tumor. CASE DESCRIPTION: A 55-year-old women presented with progressive myelopathy for 10 months. She had a painless, slow-growing mass at her left buttock since birth. Magnetic resonance imaging of the lumbosacral spine showed an extradural mass at the level of S3-S4, extending from the spinal canal through the spina bifida to the subcutaneous fat of the left buttock. There was a low conus medullaris at S2. Magnetic resonance imaging of the thoracic spine disclosed venous congestion with tortuous intradural flow voids along both ventral and dorsal surfaces of the spinal cord. Magnetic resonance angiography and spinal angiography revealed a hypervascular mass at the sacral level and associated arteriovenous shunt with cranial drainage into an enlarged medullary vein. Due to an infected pressure sore on the mass, endovascular treatment was initially performed with minimal recovery. Six months after complete healing of her infected pressure ulcer, the patient underwent surgical removal of extradural mass containing the AVF, and subsequent release of the tight filum. Histologic findings were consistent with angiolipoma. CONCLUSIONS: Sacral extradural angiolipoma in the present case may be congenital in origin with development of an acquired spinal AVF within the tumor.

Spinal Sparganosis Coexisting with Acquired Arteriovenous Fistula of the Filum Terminale.

BACKGROUND: Spinal sparganosis associated with filum terminale arteriovenous fistula (FTAVF) has not been reported in the literature. In previous studies, these 2 rare diseases were usually reported separately. We report the first case of spinal sparganosis with concomitant FTAVF. CASE DESCRIPTION: Spinal sparganosis associated with FTAVF manifested in a middle-aged man with progressive back pain and paraparesis. Magnetic resonance imaging of the lumbosacral spine revealed large intradural mass-like lesions involving the conus medullaris and entire cauda equina. Additionally, there was degenerative spinal stenosis at the level of L2-3 to L5-S1. Magnetic resonance imaging of the thoracic spine disclosed abnormal hypersignal intensity extending from the level of the conus medullaris to T7 with tortuous intradural flow voids along the ventral more than dorsal surfaces of the spinal cord. Magnetic resonance angiography and spinal angiography confirmed FTAVF at the level of L3-4. The patient underwent surgical removal of the granulation tissues with lysis adhesions and obliteration of the FTAVF simultaneously in the same surgical session. Histologic findings were consistent with sparganosis. CONCLUSIONS: The formation of FTAVF in the present case may have resulted from severe spinal canal stenosis caused by lumbar spondylosis and spinal sparganosis, inducing chronic inflammation and severe adhesion of spinal nerve roots. This evidence indicates that FTAVF may have been acquired.

Increased epithelial membrane protein 2 expression in glioblastoma after treatment with bevacizumab.

BACKGROUND: Antiangiogenic therapy with bevacizumab has failed to provide substantial gains in overall survival. Epithelial membrane protein 2 (EMP2) is a cell surface protein that has been previously shown to be expressed in glioblastoma, correlate with poor survival, and regulate neoangiogenesis in cell lines. Thus, the relationship between bevacizumab and EMP2 was investigated. METHODS: Tumor samples were obtained from 12 patients with newly diagnosed glioblastoma at 2 time points: (1) during the initial surgery and (2) during a subsequent surgery following disease recurrence post-bevacizumab treatment. Clinical characteristics and survival data from these patients were collected, and tumor samples were stained for EMP2 expression. The IVY Glioblastoma Atlas Project database was used to evaluate EMP2 expression levels in 270 samples by differing histological areas of the tumor. RESULTS: Patients with high EMP2 staining at initial diagnosis had decreased progression-free and overall survival after bevacizumab (median progression-free survival 4.6 months vs 5.9 months; log-rank P = .076 and overall survival 7.7 months vs 14.4 months; log-rank P = .011). There was increased EMP2 staining in samples obtained after bevacizumab treatment in both unpaired (mean H-score 2.31 vs 1.76; P = .006) and paired analyses (mean difference 0.571; P = .019). This expression increase correlated with length of bevacizumab therapy (R 2  = 0.449; Pearson P = .024). CONCLUSIONS: Bevacizumab treatment increased EMP2 protein expression. This increase in EMP2 correlated with reduced mean survival time post-bevacizumab therapy. We hypothesize a role of EMP2 in clinical bevacizumab resistance and as a potential antiangiogenic therapeutic target in glioblastoma.

Carboplatin-based regimen in pediatric intracranial germ-cell tumors (IC-GCTs): effectiveness and ototoxicity.

BACKGROUND: Induction chemotherapy with carboplatin followed by radiotherapy has been used for many years for treating intracranial germ-cell tumors (IC-GCTs) in Thailand. The objective of this study was to assess treatment outcomes, focusing on survival and ototoxicity. METHODS: The outcomes of all patients with IC-GCT treated at Ramathibodi Hospital and the Prasat Neurological Institute between 2000 and 2017 were reviewed and analyzed, including all patient characteristics and treatment modalities. Five-year overall survival (OS) and event-free survival (EFS) were analyzed using the Kaplan-Meier method, and factors affecting survival were compared using the log-rank test. RESULTS: Fifty-three patients age 1-14 years (median, 11 years) were included in this study. The median follow-up time was 63 months. The 5-year EFS and OS rates were 94.3% and 96.2% for all patients, respectively. No statistical difference in OS or EFS was observed between the data of recipients in the carboplatin-based and historical cisplatin-based therapies in our institutes. Concerning radiotherapy, omission of radiotherapy or focal irradiation results in worse long-term survival outcomes, but reduction in dose of radiotherapy to less than 40 Gy did not cause any negative impact on survival rates. Furthermore, carboplatin was associated with lower rates of hearing loss than cisplatin (5.7% vs 87.5%). CONCLUSIONS: Induction chemotherapy with carboplatin-based regimens was associated with excellent survival rates and low ototoxicity in patients with IC-GCT. Radiotherapy should be given to all patients with a minimal volume equivalent to whole-ventricular radiotherapy, during which doses of lower than 40 Gy can be effectively used.