DNA methylation-based classification of glioneuronal tumours synergises with histology and radiology to refine accurate molecular stratification.

AIMS: Glioneuronal tumours (GNTs) are poorly distinguished by their histology and lack robust diagnostic indicators. Previously, we showed that common GNTs comprise two molecularly distinct groups, correlating poorly with histology. To refine diagnosis, we constructed a methylation-based model for GNT classification, subsequently evaluating standards for molecular stratification by methylation, histology and radiology. METHODS: We comprehensively analysed methylation, radiology and histology for 83 GNT samples: a training cohort of 49, previously classified into molecularly defined groups by genomic profiles, plus a validation cohort of 34. We identified histological and radiological correlates to molecular classification and constructed a methylation-based support vector machine (SVM) model for prediction. Subsequently, we contrasted methylation, radiological and histological classifications in validation GNTs. RESULTS: By methylation clustering, all training and 23/34 validation GNTs segregated into two groups, the remaining 11 clustering alongside control cortex. Histological review identified prominent astrocytic/oligodendrocyte-like components, dysplastic neurons and a specific glioneuronal element as discriminators between groups. However, these were present in only a subset of tumours. Radiological review identified location, margin definition, enhancement and T2 FLAIR-rim sign as discriminators. When validation GNTs were classified by SVM, 22/23 classified correctly, comparing favourably against histology and radiology that resolved 17/22 and 15/21, respectively, where data were available for comparison. CONCLUSIONS: Diagnostic criteria inadequately reflect glioneuronal tumour biology, leaving a proportion unresolvable. In the largest cohort of molecularly defined glioneuronal tumours, we develop molecular, histological and radiological approaches for biologically meaningful classification and demonstrate almost all cases are resolvable, emphasising the importance of an integrated diagnostic approach.

Seizures and Epilepsy in Childhood.

PURPOSE OF REVIEW: This article highlights basic concepts of seizures and epilepsy in pediatric patients, as well as basic treatment principles for this age group. RECENT FINDINGS: Epilepsy is the most common neurologic disorder in childhood. Accurate diagnosis is key; in older children, epileptic seizures need to be differentiated from various paroxysmal nonepileptic events, whereas in neonates, the majority of seizures are subclinical (electroencephalographic). Antiseizure medications remain the first-line treatment, but ketogenic diet and epilepsy surgery have also shown positive outcomes and can decrease drug burden. Genetic causes account for approximately 30% of cases, and the recognition of electroclinical syndromes is being replaced by the concept of genetic spectrums. Precision medicine therapies are promising, but wide application in daily practice still has a long way to go. Early access to specialist centers and optimal treatments positively affects prognosis and future neurodevelopment. SUMMARY: Although novel findings from all fields of research are being incorporated into everyday clinical practice, a better quality of life for children with seizures and epilepsy and their families is the ultimate priority.

Classification of complications of epilepsy surgery and invasive diagnostic procedures: A proposed protocol and feasibility study.

OBJECTIVE: In epilepsy surgery, which aims to treat seizures and thereby to improve the lives of persons with drug-resistant epilepsy, the chances of attaining seizure relief must be carefully weighed against the risks of complications and expected adverse events. The interpretation of data regarding complications of epilepsy surgery and invasive diagnostic procedures is hampered by a lack of uniform definitions and method of data collection. METHODS: Based on a review of previous definitions and classifications of complications, we developed a proposal for a new classification. This proposal was then subject to revisions after expert opinion within E-pilepsy, an EU-funded European pilot network of reference centers in refractory epilepsy and epilepsy surgery, later incorporated into the ERN (European Reference Network) EpiCARE. This version was discussed with recognized experts, and a final protocol was agreed to after further revision. The final protocol was evaluated in practical use over 1 year in three of the participating centers. One hundred seventy-four consecutive procedures were included with 35 reported complications. RESULTS: This report presents a multidimensional classification of complications in epilepsy surgery and invasive diagnostic procedures, where complications are characterized in terms of their immediate effects, resulting permanent symptoms, and consequences on activities of daily living. SIGNIFICANCE: We propose that the protocol will be helpful in the work to promote safety in epilepsy surgery and for future studies designed to identify risk factors for complications. Further work is needed to address the reporting of outcomes as regards neuropsychological function, activities of daily living, and quality of life.

Acute Scrotal Pain and a Different Use of an Old Imaging Method.

ABSTRACT: The differential diagnosis of scrotal pain in childhood is a challenge for every primary care physician. We report the case of a 5-year-old boy presenting to the emergency department owing to acute left scrotal pain. Ultrasound screening revealed a Morgagni hydatid in the left testis, which was surgically removed. X-rays revealed microcalcifications of the cyst wall and stroma, signs indicative of chronic inflammation. Results of histological examination confirmed radiographic evaluation. No similar use of x-rays has been described in literature before, to the best of our knowledge. A brief discussion also follows about Morgagni hydatid in childhood.

Charcot-Marie-Tooth 1A concurrent with anaplastic ependymoma in a toddler: when an acute event unmasks a chronic condition.

Gogou M, Pavlidou E, Pavlou E, Papageorgiou T, Tragiannidis A, Giannopoulos A, Hatzipantelis E. Charcot-Marie -Tooth 1A concurrent with anaplastic ependymoma in a toddler: when an acute event unmasks a chronic condition. Turk J Pediatr 2019; 61: 428-430. We report a 14-month-old toddler admitted to the Pediatric Oncology Department after surgical resection of supratentorial anaplastic ependymoma. The child was treated with International Society of Pediatric Oncology Ependymoma II 2015 chemotherapy protocol (vincristine, carboplatin, cisplatin, cyclophosphamide and methotrexate). At the end of the first cycle the child presented with symptoms such as unsteadiness and ataxic gait along with decreased motor and sensory action potentials of the limbs. As the father of the child was diagnosed with Charcot-Marie-Tooth 1A disease, a genetic analysis of the PMP22 gene was performed confirming the diagnosis of Charcot- Marie-Tooth 1A in the child, too. This case gently reminds the possibility of vincristine-induced neurotoxicity and underscores the significance of an appropriate neurological assessment before vincristine initiation.