Central Nervous System Gliomas Research Articles

Cerebrospinal fluid cfDNA sequencing for classification of central nervous system glioma.

Primary central nervous system (CNS) gliomas can be classified by characteristic genetic alterations. In addition to solid tissue obtained via surgery or biopsy, cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) is an alternative source of material for genomic analyses. We performed targeted next-generation sequencing (NGS) of CSF cfDNA in a representative cohort of 85 patients presenting at two neurooncological centers with suspicion of primary or recurrent glioma. Copy-number variation (CNV) profiles, single nucleotide variants (SNVs), and small insertions/ deletions (indels) were combined into a molecular-guided tumor classification. Comparison with the solid tumor was performed for 38 cases with matching solid tissue available. Cases were stratified into four groups: glioblastoma (n = 32), other glioma (n = 19), non-malignant (n = 17) and non-diagnostic (n = 17). We introduced a molecular-guided tumor classification, which enabled identification of tumor entities and/ or cancer specific alterations in 75.0 % (n = 24) of glioblastoma and 52.6 % (n = 10) of other glioma cases. The overlap between CSF and matching solid tissue was highest for CNVs (26-48 %) and SNVs at pre-defined gene loci (44 %), followed by SNVs/ indels identified via uninformed variant calling (8-14 %). A molecular-guided tumor classification was possible for 23.5 % (n = 4) of non-diagnostic cases. We developed a targeted sequencing workflow for CSF cfDNA as well as a strategy for interpretation and reporting of sequencing results based on a molecular-guided tumor classification in glioma.

Characterization of central nervous system gliomas in adult patients using radiomics as an emerging technology for precision medicine

Characterization of central nervous system gliomas in adult patients using radiomics as an emerging technology for precision medicine

LMAP-10 RE-IRRADIATION FOR RECURRENT ADULT DIFFUSE GLIOMA

Abstract OBJECTIVE To investigate the efficacy of re-irradiation and prognosticators for recurrent adult diffuse glioma diagnosed per 2022 WHO diagnostic criteria for central nervous system tumors. METHODS Patients older than 18 years with recurrent diffuse glioma confirmed by functional imaging or secondary surgical histopathology in Guangdong Sanjiu Brain Hospital from January 1, 2016, to December 31, 2022, were retrospectively analyzed. All patients were re-diagnosed per the 2022 WHO classification of central nervous system gliomas. All patients received re-radiotherapy after tumor recurrence, including conventional fractionation, hypofractionation, and stereotactic radiosurgery. RESULTS A total of 61 patients were included in this analysis, male to female ratio was 34:27, median age of 45 (ranging from 18-64) years. There were 35 cases of grade IV glioblastoma, 5 cases of grade IV astrocytoma, 3 cases of grade III astrocytoma, 13 cases of grade II astrocytoma, 3 cases of grade III oligodendroglioma, and 2 cases of grade II oligodendroglioma. Twenty-four patients (39.3%) underwent re-operative surgery after recurrence. Forty-one patients (67.2%) received concurrent re-irradiation and chemotherapy, and 26 (42.6%) received concurrent bevacizumab. The median interval from the first to the second radiotherapy was 19 months. The median overall survival (OS) of 61 patients was 47 months, and the median OS following re-irradiation was 13 months. Univariate analysis showed that WHO grading (p = 0.007), IDH status (p = 0.026), reoperation after recurrence (p = 0.019), re-irradiation with or without concurrent chemotherapy (p = 0.026), maintenance chemotherapy (p = 0.038), and antiangiogenic therapy (p = 0.011) were the significant prognosticators. CONCLUSIONS Re-radiotherapy is feasible and safe for recurrent adult diffuse glioma. Re-irradiation subsequent to the re-operative surgery after recurrence combined with other therapies are favorable prognosticators. Patients with IDH mutation could benefit more from re-irradiation after recurrence.

Liquid biopsy and tumor DNA/RNA detection in the cerebrospinal fluid of patients diagnosed with central nervous system glioma - A review article.

Gliomas are the most common primary malignant neoplasms of the central nervous system and their characteristic genetic heterogeneity implies in a prominent complexity in their management. The definition of the genetic/molecular profile of gliomas is currently essential for the classification of the disease, prognosis, choice of treatment, and it is still dependent on surgical biopsies, which in many cases become unfeasible. Liquid biopsy with detection and analysis of biomarkers such as deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) from the tumor and circulating in the bloodstream or cerebrospinal fluid (CSF) has emerged as a minimally invasive alternative to aid in diagnosis, follow-up, and response to treatment of gliomas. Through a systematic search in the PubMed MEDLINE, Cochrane Library, and Embase databases, we reviewed the evidence on the use of liquid biopsy to detect tumor DNA/RNA in the CSF of patients diagnosed with central nervous system gliomas. After a systematic review applying all inclusion and exclusion criteria, as well as a double review by independent authors, 14 studies specifically addressing the detection of tumor DNA/RNA in the CSF of patients diagnosed with central nervous system glioma were selected in the final analysis. Sensitivity and specificity of liquid biopsy in CSF are still very variable depending on factors such as the diagnostic method, collection timing, biomarker (DNA and RNA), tumor type, extension and volume of the tumor, collection method, and contiguity from neoplasm to CSF. Despite the technical limitations that still exist and prevent the routine and validated use of liquid biopsy in CSF, the growing number of studies around the world is increasingly improving this technic, resulting in promising prospects for its use in diagnosis, evolutionary follow-up, and response to the treatment of complex diseases such as central nervous system gliomas.

Association of Traumatic Brain Injury and Glioblastoma Multiforme: A Case Series.

Glioblastoma multiforme (GBM) is an aggressive variant of central nervous system gliomas that carries a dismal prognosis. Although GBM is the most frequently occurring and malignant type of glioma accounting for more than 60% of all brain tumors in adults, its overall incidence is rare, occurring at a rate of 3.21 per 100,000 persons. Little is known about the etiology of GBM, but one proposed theory is that GBM pathogenesis may be linked to a chronic inflammatory course initiated by traumatic injury to the brain. Limited case reports have suggested an association between GBMs and traumatic brain injury (TBI), but larger case-control and epidemiologic studies have been inconclusive. We present three service members (two active duty and one retired) who developed GBM near the original site of prior head trauma. Each service member's military occupation was in the special operations community and shared a common theme of TBI following head trauma/injury. The current research on the association between TBI and GBM is limited and conflicting, predominantly due to the low incidence of the disease in the general population. Evidence has indicated that TBI should be considered a chronic disease with long-term health impacts, including long-term disability, dementia, epilepsy, mental health conditions, and cardiovascular diseases. With the addition of our patients, as well as a recently published study proposing a molecular association between trauma and GBM, further research is needed to better understand the potential relationship.

Mismatch repair-deficient glioma with spatially distinct IDH-mutant and IDH-wild type components arising in the setting of Lynch syndrome.

Pathogenic mutations in MLH1, MSH2, PMS2, and MSH6 compromise DNA mismatch repair mechanisms and in the heterozygous state result in Lynch syndrome, which is typified by a predisposition to endometrial, ovarian, colorectal, gastric, breast, hematologic, and soft tissue cancers. Rarely, germline pathogenic aberrations in these genes are associated with the development of primary central nervous system tumors. We present a report of an adult female with no prior cancer history who presented with a multicentric, infiltrative supratentorial glioma involving both the left anterior temporal horn and left precentral gyrus. Surgical treatment and neuropathological/molecular evaluation of these lesions revealed discordant isocitrate dehydrogenase (IDH) status and histologic grade at these spatially distinct disease sites. A frameshift alteration within the MLH1 gene (p.R217fs*12, c.648delT) was identified in both lesions and subsequently identified in germline testing of a blood sample, consistent with Lynch syndrome. Despite distinct histopathologic features and divergent IDH status of the patient's tumors, the molecular findings suggest that both sites of intracranial neoplasia may have developed as a consequence of underlying monoallelic germline mismatch repair deficiency. This case illustrates the importance of characterizing the genetic profile of multicentric gliomas and highlights the oncogenic potential of germline mismatch repair gene pathogenic alterations within central nervous system gliomas.

Simple approach for the histomolecular diagnosis of central nervous system gliomas based on 2021 World Health Organization Classification

The classification of central nervous system (CNS) glioma went through a sequence of developments, between 2006 and 2021, started with only histological approach then has been aided with a major emphasis on molecular signatures in the 4th and 5th editions of the World Health Organization (WHO). The recent reformation in the 5th edition of the WHO classification has focused more on the molecularly defined entities with better characterized natural histories as well as new tumor types and subtypes in the adult and pediatric populations. These new subclassified entities have been incorporated in the 5th edition after the continuous exploration of new genomic, epigenomic and transcriptomic discovery. Indeed, the current guidelines of 2021 WHO classification of CNS tumors and European Association of Neuro-Oncology (EANO) exploited the molecular signatures in the diagnostic approach of CNS gliomas. Our current review presents a practical diagnostic approach for diffuse CNS gliomas and circumscribed astrocytomas using histomolecular criteria adopted by the recent WHO classification. We also describe the treatment strategies for these tumors based on EANO guidelines.

Clinical Trial Enrollment Among Adolescent and Young Adults with Primary Central Nervous System Tumors Treated at the Dana-Farber Cancer Institute.

Purpose: In recent decades, the survival outcomes among adolescent and young adults (AYAs, 15-39 years) have not improved substantially, especially among AYAs with primary central nervous system (CNS) tumors. While this is likely multifactorial, low participation in clinical trials among AYAs is thought to be a critical contributing factor. In this study, we describe the pattern of clinical trial enrollment among AYAs with primary CNS tumors at our institution. Methods: We performed a retrospective, IRB-approved chart review of AYAs with CNS tumors treated at the Dana-Farber Cancer Institute (DFCI) between January 2009 and December 2018. We used logistic regression analyses and descriptive statistics to analyze this sample and determine the clinical trial enrollment at the pediatric affiliate (Dana-Farber/Boston Children's Cancer and Blood Disorders Center) and adult affiliate (Dana-Farber/Brigham and Women's Cancer Center). Results: Ninety-three AYA patients with primary CNS tumors were treated at the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, while 507 patients with primary CNS gliomas were treated at the Dana-Farber/Brigham and Women's Cancer Center. At the pediatric affiliate, 35.4% (33/93) of AYAs were enrolled in a therapeutic clinical trial, while at the adult affiliate, 15.8% (80/507) of AYAs were enrolled in a clinical trial. High-grade gliomas were associated with significantly higher rates of enrollment in the adult affiliate. Conclusions: Clinical trial enrollment remains poor among AYAs with CNS tumors, and clinical trial enrollment participation is modestly higher in the pediatric setting. Our study demonstrates the continued need to evaluate and address factors associated with clinical trial enrollment among AYAs with CNS tumors.

Semi-synthesis and cytotoxicity evaluation of pyrimidine, thiazole, and indole analogues of argentatins A–C from guayule (Parthenium argentatum) resin

Argentatins A–C (1–3), the major cycloartane-type triterpenoids of guayule resin, a byproduct of commercial rubber production, were converted into their pyrimidine (7–12), thiazole (13–15), and indole (16–18) analogues by a molecular hybridization approach. The cytotoxic activities of these fused heterocyclic analogues 7–18 were compared with those of argentatins A–C (1–3) against a panel of three sentinel human cancer cell lines [NCI-H460 (non-small cell lung), MCF-7 (breast adenocarcinoma), and SF-268 (central nervous system glioma)], and normal human fibroblast (WI-38) cells. The cytotoxicity data suggest that the pyrimidine analogues 7 and 8 (derived from 1), 9 and 10 (derived from 2), and 12 (derived from 3) had significantly enhanced activity compared to the parent compounds or their thiazole (13–15) and indole (16–18) analogues. These findings indicate that triterpenoid constituents of guayule resin may be exploited to obtain value-added products with potential applications in anticancer drug discovery.

The efficacy of immunohistochemistry in the diagnosis of molecular genetic alterations in central nervous system gliomas: Next-generation sequencing of 212 mutations in 112 patients.

Identification of molecular genetic alterations has become an important part of diagnosis and care of patients with brain tumors. Comparisons of immunohistochemistry (IHC) with DNA sequencing techniques have suggested that IHC is useful for identifying surrogates of mutations in gliomas; however, studies of the efficacy are relatively few. Our aim was to compare IHC in our neuropathology laboratory with a commercially available next-generation sequencing (NGS) platform, Tempus xT. We studied 212 immunohistochemically stained sections of gliomas to identify mutations of isocitrate dehydrogenase (IDH), p53, BRAF, the α-thalassemia/mental retardation syndrome X-linked protein (ATRX), and histone H3. Tempus xT NGS confirmed the IHC diagnosis of IDH1/R132H in 102 of 102 patients (100%), BRAF/V600E in 14 of 14 (100%) patients and H3/K27M in 10 of 10 (100%) patients. For p53, NGS confirmed the IHC diagnosis of mutation in 47 of 53 (87%) patients. For 6 patients, IHC was interpreted as wild-type while NGS indicated a mutation. NGS confirmed the IHC diagnosis of ATRX mutation in 29 of 31 (94%) patients. In 1 patient, IHC predicted a mutation that was not confirmed by NGS, and in another, IHC predicted wild-type, but NGS showed mutant. In 2 other patients, IHC diagnosis of ATRX mutation was equivocal; 1 was mutant and 1 was wild-type by NGS. Our single-center study suggests that IHC for IDH1/R132H, BRAF/V600E, and H3/K27M is highly reliable and may be used confidently in clinical practice. IHC for p53 and ATRX mutations is often reliable but possibly problematic, and genetic studies may be necessary to determine astrocytic or oligodendroglial differentiation.

The role of neurophysiological assessments during the combined treatment of patients with malignant brain tumors

Introduction. Dynamic monitoring and evaluation of the results of therapy of patients with malignant brain diseases is a complex and urgent problem in modern medicine. The aim of the study was to assess the reliability of the transcranial magnetic stimulation technique as a tool for neurophysiological monitoring in patients with malignant brain tumors. Material and methods. Two groups of patients were formed: adults with large focal solitary lesions of the central nervous system (glioma) (n=20), who underwent radiotherapy, and a control comparison group (n=16). All patients underwent diagnostic transcranial magnetic stimulation before and after treatment. Results. In the main group the application of transcranial magnetic stimulation in dynamics allowed to reveal reliable improvement of conduction along the central motor pathways (increase in amplitude of the evoked motor response). The obtained data of neurophysiological examination correlated with clinical improvement in the patient group. Discussion. Some parameters of the motor evoked response (MEP) changed reliably, as after the radiation treatment performed. Obtained changes (amplitude of MEP and, especially, its threshold) to the greatest extent reflect functional state of cortical motoneurons, as well as their anatomical preservation in case of organic changes. Before therapy in all cases there was a reliable tendency to a smaller amplitude and a higher threshold of cortical MEPs, which reflects a decrease in the functional activity of motor cortex neurons; a slower central motor conduction time also draws attention. These changes had a universal character and were registered in all patients. Conclusion. Diagnostic transcranial magnetic stimulation, taking into account age limitations inherent to it as a technique, is a valuable additional neurophysiological technique. It is safe, inexpensive and does not require expensive consumables, and is applicable to a wide range of diseases.

Neurological manifestations of neurofibromatosis type 1: our experience

IntroductionNeurofibromatosis type 1 (NF1) is a progressive multisystem disorder following an autosomal dominant inheritance pattern that presents with multiple neurological manifestations. MethodsWe reviewed medical histories of patients with NF1 followed up at our hospital’s paediatric neurology department from May 1990 to 31 December 2018. We collected data on neurological symptoms. ResultsA total of 128 patients with NF1 were identified. Mean age (SD) at NF1 diagnosis was 4.43 (3.38) years (range, 0.5-14.5 years). There was a slight female predominance (53.1%). Macrocephaly (head circumference over 2 SDs above average for age) was present in 37.5% of cases. Attention-deficit/hyperactivity disorder was recorded in 28.9% of patients (37): combined type in 20 patients, predominantly inattentive in 15, and predominantly impulsive/hyperactive in 2. Other manifestations included headache (18.6%), cognitive impairment (7.8%), motor deficit (6.2%), and epilepsy (4.68%). Brain MRI was performed in 85 patients, revealing T2-weighted hyperintensities in the basal ganglia and/or cerebellum in 60 patients (70.5%), Chiari malformation type 1 in 4 cases, and arachnoid cysts in 3. Optic nerve gliomas were identified by MRI in 22 patients (25.8%). Other MRI findings included plexiform neurofibromas (9.3%) and central nervous system gliomas (3.1%). ConclusionsThe neurological manifestations identified in our sample are consistent with those reported in the literature. Effective transfer strategies from paediatric neurology departments and subsequent clinical follow-up by adult neurology departments are needed to prevent loss to follow-up in adulthood.

RARE-17. SURVIVAL BENEFIT FOR INDIVIDUALS WITH CONSTITUTIONAL MISMATCH REPAIR DEFICIENCY SYNDROME AND BRAIN TUMORS WHO UNDERGO SURVEILLANCE PROTOCOL. A REPORT FROM THE INTERNATIONAL REPLICATION REPAIR CONSORTIUM

BACKGROUNDConstitutional mismatch repair deficiency syndrome (CMMRD) is a severe cancer predisposition syndrome resulting in early onset central nervous system (CNS) and other cancers. International guidelines for surveillance exist but no study has systematically evaluated the efficacy of this protocol.METHODSWe surveyed all confirmed CMMRD patients in the International Replication Repair Deficiency Consortium. A surveillance protocol consisting of frequent biochemical, endoscopic and imaging (CNS and total body MRI) studies were employed. Survival analyses and efficacy of each method were assessed.RESULTSSurveillance data were collected from 105 CMMRD individuals from 41 countries. Of the 193 malignant tumors, CNS malignancies were the most common (44%). The surveillance protocol uncovered 49 asymptomatic tumors including 16 glioblastomas and medulloblastomas. Five-year overall survival was 89% for tumors discovered by surveillance, and 61% for symptomatic tumors (p<0.004). Similarly, 5-year survival was 82+/-11% and 24+/-6% for surveillance and non-surveillance of brain tumors (p=0.005). Yearly total body and q6 month brain MRI detected asymptomatic cancers in all but 3 symptomatic CNS gliomas. These were tumors uncovered when time between scans was >6 months as per protocol. Finally, of the low grade tumors identified asymptomatically, 5 were low grade gliomas. All of the low grade gliomas, which were not resected transformed to high grade tumors at a median of 1.6 ± 0.9 years.CONCLUSIONThese data support a survival benefit in CMMRD patients undergoing a surveillance protocol. Adherence to protocol and resection of lower grade lesions may improve survival for patients with CNS tumors.

Brain Glioma Localization Diagnosis Based on Magnetic Resonance Imaging

We used dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) technology and its perfusion parameters to diagnose central glioma high-grade glioma (HGG), primary central nervous system glioma low-grade glioma (LGG), brain metastases, and meningioma and make differential diagnoses. Forty-one cases of brain tumors (8 cases of LGG, 17 cases of HGG, 5 cases of "primary central nervous system lymphoma" [PCNSL], 6 cases of brain metastases, and 5 cases of meningiomas) were subjected to routine and DCE-MRI scans. The DCE-MRI quantitative parameters of the tumor parenchymal area and peripheral enema area of each tumor were measured and recorded as t-Ktrans value, t-Ve value, t-Vp value, t-Kep value and p-Ktrans value, p-Ve value, p-Vp value, and p-Kep value. Compared with other tumor types, LGG showed lower t-Ktrans value (P < 0.01, sensitivity= 89%, specificity= 99%) and low t-Ve value (P < 0.01, sensitivity= 94%, specificity= 100%); PCNSL showed a high t-Ve value (P < 0.01, sensitivity= 100%, specificity= 88%), but other perfusion parameters overlap more obviously with other tumors. Compared with LGG, the difference between t-Ktrans value, t-Ve value, and t-Kep value is statistically significant. Among them, t-Ktrans value distinguishes the highest sensitivity and specificity (when t-Ktrans value= when 0.154 is the cutoff value, the area under the curve is 1.000, P= 0.000, specificity= 100%, sensitivity= 94.1%); compared with PCNSL, the difference of t-Ve value between HGG and PCNSL is statistically significant, t-Ve of PCNSL. The value is slightly higher, and its specificity and sensitivity are not high. DCE-MRI can distinguish HGG and LGG more accurately, of which t-Ktrans value has higher specificity and sensitivity, although the difference of t-Ve value between PCNSL and HGG is statistically significant but the sensitivity and specificity are not high; the p-Ktrans value and p-Kep value of metastatic tumors are lower than HGG and have higher specificity, but meningiomas and HGG and PCNSL, meningiomas and metastases are not accurate identification.

Laparoscopic Right Adrenalectomy After Superior Heminephrectomy in a Child

Introduction: Laparoscopic adrenalectomy (LA) is widely described in adult population since its first report by Gagner et al. in 1992.1 In contrast, its applicability in pediatric malignancy remains unsettled. According to current evidence, LA in children is acceptable for resection of pheochromocytomas,2 benign tumors, and adrenal hyperplasia.3 The authors present a video of a challenging laparoscopic right adrenalectomy in a child after homolateral superior polar heminephrectomy. Materials and Methods: This is a case of an 11-year-old girl with LiFraumeni syndrome. She had a past medical history of a central nervous system glioma treated when she was 4 years old. Six years later, a nodule on the upper pole of the right kidney with malignant features on imaging was diagnosed, and she underwent right superior heminephrectomy through a subcostal retroperitoneal approach. The specimen revealed that it was an eosinophilic renal carcinoma. One year later, during follow-up, a new nodule on the right adrenal gland was found. Because of the patient's history and malignant risk, she was proposed to tumor excision using a minimally invasive approach. During laparoscopy, important adhesions between the abdominal wall, the kidney, and the right lobe of the liver were found. After careful liberation and dissection, the adrenal tumor was found and excised. The postoperative course was uneventful and was discharged on the second postoperative day. After 1 year, the girl is doing well and is still under surveillance for further tumor development. Conclusion: A laparoscopic approach transforms a major surgery that requires a significant abdominal incision to operate in a difficult access area into a relatively simple and safe procedure. Particularly in patients in whom further surgeries are expected during their lifetime, a minimally invasive approach grants less future iatrogenic complications because of diminished risk for adhesion formation. No competing financial interests exist. Runtime of video: 7 mins 29 secs

Manifestaciones neurológicas en neurofibromatosis tipo 1. Nuestra experiencia

IntroductionNeurofibromatosis type 1 (NF1) is a progressive multisystem disorder following an autosomal dominant inheritance pattern that presents with multiple neurological manifestations. MethodsWe reviewed medical histories of patients with NF1 followed up at our hospital's paediatric neurology department from May 1990 to 31 December 2018. We collected data on neurological symptoms. ResultsA total of 128 patients with NF1 were identified. Mean age (SD) at NF1 diagnosis was 4.43 (3.38) years (range, 0.5-14.5 years). There was a slight female predominance (53.1%). Macrocephaly (head circumference over 2 SDs above average for age) was present in 37.5% of cases. Attention-deficit/hyperactivity disorder was recorded in 28.9% of patients (37): combined type in 20 patients, predominantly inattentive in 15, and predominantly impulsive/hyperactive in 2. Other manifestations included headache (18.6%), cognitive impairment (7.8%), motor deficit (6.2%), and epilepsy (4.68%). Brain MRI was performed in 85 patients, revealing T2-weighted hyperintensities in the basal ganglia and/or cerebellum in 60 patients (70.5%), Chiari malformation type 1 in 4 cases, and arachnoid cysts in 3. Optic nerve gliomas were identified by MRI in 22 patients (25.8%). Other MRI findings included plexiform neurofibromas (9.3%) and central nervous system gliomas (3.1%). ConclusionsThe neurological manifestations identified in our sample are consistent with those reported in the literature. Effective transfer strategies from paediatric neurology departments and subsequent clinical follow-up by adult neurology departments are needed to prevent loss to follow-up in adulthood.

Acute acquired comitant esotropia in children: A benign entity or an ominous sign?

Purpose: The purpose is to study the clinical features of acute acquired comitant esotropia (AACE) in children and analyze the course and outcome. Materials and Methods: A retrospective, clinical study of all patients under the age of 18 years with acute onset, nonaccommodative comitant esotropia in a tertiary eye care center from September 2013 to December 2016. Parameters studied were age, sex, visual acuity, eye involved, age of onset, precipitating event, amount of deviation, presence or absence of amblyopia, cycloplegic refraction, systemic involvement, surgical or nonsurgical intervention, course, and outcome. All patients underwent magnetic resonance imaging of brain and orbits, and systemic evaluation was done in suspicious cases. Minimum follow-up period was 6 months. Results: Out of 12 patients, 8 were male. Average age of the patients was 7.9 years. The mean esodeviation was 33.75 PD, and mean age of onset was 6.14 years (range: 2–15 years). There was left eye preponderance. Three patients (25%) had a history of a precipitating event. Cycloplegic refraction ranged from +0.50 DS to −6.75 DS, with majority having <+2.00 DS. Amblyopia was noted in 8 (66.6%) patients. Systemic involvement was seen in three patients in the form of ocular myasthenia, central nervous system glioma, and viral fever, respectively. Esotropia disappeared in one patient with overcorrected, high myopia following atropinization, and change of glass. Eight patients (66.6%) underwent strabismus surgery with good postoperative alignment, and the rest were managed conservatively. Conclusion: AACE is an unusual ocular alignment disorder characterized by a nonaccommodative esodeviation which can occur in older children, adults, and even the elderly. Although most children with this form of esotropia are otherwise healthy, systemic diseases must be considered and ruled out before planning surgery. Prompt amblyopia therapy and timely surgery can result in a satisfactory outcome in those without systemic involvement.

Outcomes following cerebrospinal fluid shunting in high-grade glioma patients.

The clinical course of high-grade central nervous system gliomas is occasionally complicated by hydrocephalus. The risks of shunt placement and clinical outcome following CSF diversion in this population are not well defined. The authors retrospectively reviewed the outcomes of patients with pathologically confirmed WHO grade III or IV gliomas with shunt-treated hydrocephalus at their institution. Outcomes of patients in this cohort were compared with those of patients who underwent shunt treatment for normal pressure hydrocephalus (NPH). Hospital-reported outcomes in a national database for malignant primary brain tumor patients undergoing a ventricular shunt procedure were also reviewed. Forty-one patients undergoing CSF shunting between 2001 and 2016 at the authors' institution were identified. Noncommunicating and communicating hydrocephalus occurred at similar rates (51.2% vs 48.8%). Symptomatic improvement after shunting was observed in 75.0% of patients. A major complication occurred in 17.1% of cases, with 2 patients suffering an intracranial hemorrhage. Prior administration of bevacizumab was significantly associated with the incidence of hemorrhage (p = 0.026). Three patients (7.3%) died during admission, and 8 (19.5%) died within 30 days of shunt placement. The presence of ependymal or leptomeningeal enhancement was more common in patients who died within 30 days (75.0% vs 11.1%, p = 0.001). Six patients (18.1%) required readmission to the hospital within 30 days of discharge. Revision surgery was necessary in 7 patients (17.1%). The median time from shunt placement to death was 150.5 days. In comparison with patients with NPH, shunt-treated high-grade glioma patients had increased in-hospital (7.3% vs 0.5%, p = 0.008) and 30-day (19.5% vs 0.8%, p < 0.001) mortality but no difference in the incidence of revision surgery (17.1% vs 17.5%, p = 0.947). Similarly, in the national Vizient Clinical Database Resource Manager, shunt-treated patients with malignant primary brain tumors had an increased length of stay (6.9 vs 3.5 days, p < 0.001), direct cost of admission ($15,755.80 vs $9871.50, p < 0.001), and 30-day readmission rates (20.6% vs 2.4%, p < 0.001) compared with patients without brain tumors who received a shunt for NPH. Shunting can be an effective treatment for the symptoms of hydrocephalus in patients with high-grade gliomas. However, the authors' results suggest that this procedure carries a significant risk of complications in this patient population.

CSF and clinical data are useful in differentiating CNS inflammatory demyelinating disease from CNS lymphoma

Background: It is often difficult to diagnose central nervous system (CNS) inflammatory demyelinating diseases (IDDs) because they are similar to CNS lymphoma and glioma. Objective: To evaluate whether cerebrospinal fluid (CSF) analysis can differentiate CNS IDDs from CNS lymphoma and glioma. Methods: We measured CSF cell counts; concentrations of proteins, glucose, interleukin (IL)-6, IL-10, soluble IL-2 receptor (sIL-2R), and myelin basic protein; and IgG index in patients with multiple sclerosis (MS, n = 64), neuromyelitis optica spectrum disorder (NMOSD, n = 35), tumefactive demyelinating lesion (TDL, n = 17), CNS lymphoma (n = 12), or glioma (n = 10). We detected diagnostic markers using logistic regression and receiver operating characteristic (ROC) analyses. Results: Median CSF IL-10 and sIL-2R levels were higher in CNS lymphoma patients than in MS, NMOSD, or TDL patients. Logistic regression revealed that CSF sIL-2R levels predicted CNS lymphoma. In the ROC analysis of CSF sIL-2R levels, the area under the curve was 0.867, and the sensitivity and specificity were 83.3% and 90.0%, respectively. Conclusion: CSF sIL-2R levels can be used to differentiate CNS lymphoma from CNS IDDs. Further studies may identify other applications of CSF as a diagnostic biomarker.

Susceptibility Imaging in Glial Tumor Grading; Using 3 Tesla Magnetic Resonance (MR) System and 32 Channel Head Coil.

SummaryBackgroundSusceptibility weighted imaging (SWI) is a velocity compensated, high-resolution three-dimensional (3D) spoiled gradient-echo sequence that uses magnitude and filtered-phase data. SWI seems to be a valuable tool for non-invasive evaluation of central nervous system gliomas. Relative cerebral blood volume (rCBV) ratio is one of the best noninvasive methods for glioma grading. Degree of intratumoral susceptibility signal (ITSS) on SWI correlates with rCBV ratio and histopathological grade. This study investigated the effectiveness of ITSS grading and rCBV ratio in preoperative assessment.Material/MethodsThirty-one patients (17 males and 14 females) with histopathogical diagnosis of glial tumor undergoing routine cranial MRI, SWI, and perfusion MRI examinations between October 2011 and July 2013 were retrospectively enrolled. All examinations were performed using 3T apparatus with 32-channel head coil. We used ITSS number for SWI grading. Correlations between SWI grade, rCBV ratio, and pathological grading were evaluated. ROC analysis was performed to determine the optimal rCBV ratio to distinguish between high-grade and low-grade glial tumors.ResultsThere was a strong positive correlation between both pathological and SWI grading. We determined the optimal rCBV ratio to discriminate between high-grade and low-grade tumors to be 2.21ConslusionsIn conclusion, perfusion MRI and SWI using 3T MR and 32-channel head coil may provide useful information for preoperative glial tumor grading. SWI can be used as an accessory to perfusion MR technique in preoperative tumor grading.