Brain tissue consists of two types of cells: nerve cells and glial cells. While nerve cells are responsible for the processing and transmission of information, glial cells (including astrocytes, oligodendrocytes and ependymal cells) have a variety of supporting tasks. They contribute to metabolic processes and participate in the blood-brain barrier.
If errors in cell division occur, glial cells can degenerate and tumours can develop. These are then referred to as gliomas and they make up the largest proportion of all tumor formations of central nervous tissue. Depending on the individual cell of origin, gliomas can be further categorised as e.g. astrocytoma, oligodendroglioma or ependymoma.
Gliomas are histologically classified based on cell composition and growth behaviour. Low-grade gliomas include pilocytic astrocytomas (WHO grade I), which grow very slowly and occur almost only in childhood, as well as diffuse astrocytomas (WHO grade II) and oligodendrogliomas (grade II). Higher grade gliomas, i.e. the anaplastic astrocytoma (WHO grade III) and the glioblastoma (WHO grade IV) are defined by aggressive, infiltrative growth. In 2016, the WHO criteria were updated and expanded to include molecular genetic alterations, as these play an increasingly important role in diagnostics and prognosis.
Clinically relevant genetic markers are
- The MGMT (Methylguanine Methyltransferase (MGMT) gene. Methylation of the MGMT promoter gene is a prognostic marker for the response to alkylating chemotherapeutics.
Isocytrate Dehydrogenase (IDH) molecule. The IDH gene mutation (a point
mutation in codon 132 for IDH1 and in codon 172 for IDH2) is both a diagnostic
and a prognostic marker. The IDH mutation is mainly found in grade II or III
gliomas and in about 90% of secondary glioblastomas, which are those
originating from astrocytomas. An IDH 1 mutation is prognostically positive for
patients with an anaplastic glioma or glioblastoma.
- The 1p/19q deletion is a diagnostic marker to differentiate between astrocytoma and oligodendroglioma and a positive prognostic marker for patients with oligodendroglial tumors.
Gliomas can manifest themselves in two different ways. On the one hand, the tumour increases the pressure inside the skull and as a consequence typical cerebral pressure symptoms can occur: fatigue, headaches, nausea, vomiting, confusion and clouding of consciousness.
On the other hand, the specific localisation of the tumour can lead to functional failure of structures in whose vicinity the glioma is growing, either by local pressure of by infiltrative tissue destruction: paralysis, speech disorders, visual disturbances, difficulties with spatial perception, personality changes or epileptic seizures.
Magnetic resonance imaging (MRI) with all its technical facets provides the most accurate information in the diagnosis of gliomas. In lesions near functionally important areas of the brain, functional MRI imaging (task-activation MRI, f-MRI) is helpful in order to optimise surgical planning or radiotherapy. Important neuronal paths in the depth of the brain can be displayed two- and three-dimensionally with Diffusion Tensor Imaging.
Positron emission tomography (PET) with amino acid tracers (FET-PET) measures the metabolic activity of tumor tissue compared to the surrounding brain tissue. This is particularly valuable for the differential diagnosis of slow-growing and diffuse gliomas as well as recurrent lesions, especially having undergone radiation therapy or chemotherapy. A tumour zone with increased activity (HOT spot) can be fused three-dimensionally with MRI and thus it is possible to tailor an operation or a biopsy towards the most aggressive tumour areas.
The first and most important therapy of gliomas is the microsurgical resection - as complete as possible while preserving neurological and cognitive functions.
In the case of benign WHO grade I gliomas, a cure can be achieved if the tumour is completely removed.
In the case of malignant gliomas, i.e. anaplastic astrocytoma (WHO grade III) and glioblastoma (WHO grade IV), there is a consensus among experts that by far the most important factor in extending survival time is complete resection of those tumour parts that show MRI contrast enhancement. This can be significantly improved by fluorescence-assisted resection, which enables tumour tissue to be selectively visualised during surgery. This surgical technique is usually combined with 3D navigation, electrophysiological monitoring and often the operation is performed while being awake.
Also in case of diffuse astrocytomas (WHO grade II), numerous studies have shown that the prognosis in terms of progression-free interval and overall survival is decisively influenced by the degree of surgical resection. WHO II gliomas usually don’t show MRI contrast enhancement and they cannot be detected by intra-operative fluorescence. However, they are unmasked by a change in signal intensity in the MRI T2 or FLAIR image. The aim of microsurgical resection is to remove these tumor parts as completely as possible with the aid of navigation and electrophysiological monitoring, ultrasound, intra-operative MRI and, if necessary, awake surgery.
Gliomas do not have a clear border to the healthy brain, which means there is a transition zone in which tumor tissue is mixed with still functionally active brain tissue. This zone may not show MRI contrast enhancement. Several studies have shown that after resection of the visible glioma tissue (supported by fluorescence, navigation and intra-operative imaging) about 80% of recurrences occur in close proximity to the resection cavity. When operating on a glioma, the aim should therefore be to remove the transitional tumor zone and to go as far as possible until the functional limit is reached. This procedure is only possible if the patient's neurological functions are carefully controlled during the operation. By intraoperative electrophysiological monitoring it is possible to operate even in functionally very active brain regions (movement, vision, speech). Important neuronal pathways can be monitored by continuous signals (MEP, SSEP), which are sent from the brain to the body and from the body to the brain. Furthermore, electrical stimuli can be sent with small hand-held probes beyond the visible resection border into the brain, comparable to radar or sonar. The signals recorded allow recognizing important brain areas and neuronal tracts before endangering them in the course of resection. Finally, diffusely growing tumours often require surgery while being awake in order to be able to operate as radically as possible while preserving neurological functions. Electrophysiological monitoring with direct cortical and subcortical stimulation is then performed while the patient is awake and is able to talk, move and see – and this is naturally providing the most sophisticated intra-operative functional information.
A specialized team of anaesthesiologists, neurologists and neuropsychologists is required for awake surgery. With a well-experienced team the surgery can be carried out completely pain-free despite not being under general anaesthesia. The patient is woken up only during the resection in functionally delicate areas. This enables testing neurological functions in regions close to the tumor with great efficiency and safety.
After an operation, the further therapy is defined individually in our interdisciplinary tumour board. In many cases a combination of radiation and chemotherapy has proven to be a powerful combination. The drug temozolomide is often the preferred chemotherapy and depending on the tumour other chemotherapeutic agents such as CCNU, Procarbazine, Lomustine and Vincristine may also be applied.
In addition to this, the Center of Microneurosurgery is very well connected to the worlds leading medical institutions and we may provide access to on-going clinical studies with novel drugs.