Gadolinium based contrast agents are commonly used as MRI contrast agents. Gadolinium is toxic to living organisms and it is used as a contrast agent due to its ability to impart a chelate structure. Gadolinium contrast agents have been used safely for a long time ; however, unfortunately, in recent years we have several reports that gadolinium contrast agents remain in the brain. This revelation is presently drawing world wide attention as to whether the little gadolinium that remains in the human body is harmful or not.
The World Health Organization (WHO) Classification of Tumors of the Central Nervous System needed to be revised due to the advances in many diagnostic technology since the first edition appeared in 1979, and in 2016 a revised edition of the fourth edition was published. In this revision, the molecular classification was introduced for the first time in diffuse gliomas and embryonal tumors, and the pathological diagnosis concept was greatly changed from one based on classical histological classification to one based more on molecular and genetic classification. This change reflects a policy wherein the tumor definition should be rigid and objectively defined as much as possible, and any tumor cases where genetic analysis cannot be performed or diagnostic evidence are ambiguous are now categorized as NOS (not otherwise specified). Unfortunately, this has led to problems where too many NOS diagnoses are generated.
The 2016 World Health Organization Classification of Tumors of the Central Nervous System (WHO 2016) is the latest revision of the internationally recognized standard of brain tumor classification. WHO 2016 uses genetic and molecular parameters in addition to histopathology parameters to define multiple pediatric brain tumor entities for the first time. Brain tumor diagnosis is thereby conceptually adjusted to the molecular era.
WHO 2016 presents a major restructuring of the diffuse gliomas, medulloblastomas and other embryonal tumors. New pediatric entities defined by both histopathology and molecular features include the following glioma, H3 K27M-mutant ; ependymoma, RELA fusion-positive ; medulloblastoma, WNT-activated and medulloblastoma, SHH-activated ; and embryonal tumor with multilayered rosettes, C19MC-altered.
WHO 2016 will facilitate precision medicine that will lead to an improvement of treating children with brain tumors.
The recent development of next-generation sequencing has enabled comprehensive genomic and epigenetic analyses in a variety of diseases, which has facilitated the understanding of the molecular biological mechanisms underpinning such diseases. The big data accumulated in this process has revealed the whole picture in glioma as well. Gliomas consist of various subtypes that are molecularly distinct from each other, and key molecules or aberrations have been identified. Such molecules are now being focused on as drug-targets. In this article, new technologies will be introduced and the future perspective is also discussed.
Molecular diagnosis has become an important part of malignant brain tumor management. Molecular testing for some of the mutations or deletions, such as the isocitrate dehydrogenase (IDH) mutation, 1p19q co-deletion or H3 K27M mutation are now mandatory in WHO2016 for making a diagnosis. Also, some of the new treatment strategies for malignant brain tumor are tested in clinical trials based on molecular data. In this manuscript, we focused on IDH mutations, H3 K27M mutations, 1p/19q codeletion and O6-methylguanine-DNA methyltransferase (MGMT) CpG island methylation, presenting tips and pitfalls to understand the molecular data, as well as how to use them in clinical settings. There are however limitations in each methodology that we need to know. For example, to detect total deletion of the whole arm is most important in determining 1p19q codeletion, however fluorescence in situ hybridization (FISH) may detect only a small region of deletion. Additionaly, tumor heterogeneity and tumor cell contents are always a problem for accurate genome sequencing. Therefore, sequence results need to be interpreted with caution in a clinical setting. An accurate understanding of molecular tests will hopefully enable us to better manage malignant brain tumor patients.
The authors reported the 10-year change in board certified neurosurgeons as recorded by the Japan Neurosurgical Society. The number of doctors increased, including those who acquired certification by the Japan Stroke Society, the Japanese Society of Neuroendovascular Therapy, and Neurospinal Society of Japan as well as our certification. As for subspecialty domains, “Brain tumor”, “Cerebrovascular”, “Spine”, “Pediatrics”, “Function”, and “Trauma” decreased, but “Neuroendovascular”, “Neuroendoscope”, “Epilepsy”, “Rehabilitation”, and “Emergency/Neuro Critical Care” all increased.
The redefinition of certified neurosurgeons that occured in 1999 may have influenced this phenomenon. Many respondents complained of severe working conditions and overtime that was causing death of “Karoshi”. The decrease in new members and examinees in addition to this environment of overwork makes us feel anxious about the futures of our conventional neurosurgical treatment system. A move to centralize institutions and trainees, provide a more sophisticated rotation scheme, and create an intensified and efficient research and training program should be implemented.
We describe a case of a healthy 13-year-old boy presenting with right hemiparesis and aphasia. MRI demonstrated a DWI high signal in the left corona radiata and basal ganglia. MRA revealed a left middle cerebral artery proximal occlusion. He was treated 4.5 hours after the onset of symptoms with intravenous rt-PA. In addition, the patient was immediately taken for endovascular thrombectomy. A conventional angiogram showed occlusion of the left angular artery. We performed selective thrombus aspiration with a Penumbra system for the occluded angular artery. Sufficient recanalization was achieved and the patient recovered dramatically with no neurological deficits. The occurrence of cerebral infarction in children is relatively rare. This is rare case of a cerebrovascular infarction in a young patient, treated with intravenous thrombolysis and endovascular thrombectomy. There is no evidence concerning the use of intravenous rt-PA and endovascular thrombectomy for strokes in pediatric patients. But in our case, intravenous rt-PA and endovascular thrombectomy were useful treatments and were performed without severe adverse events.