Progress in neurological surgery最新文献

The neural connections of the basal ganglia provide important insights into their function. Here, we discuss the current perspective on basal ganglia connections with the cerebral cortex and with the cerebellum. We review the evidence that the basal ganglia participate in functionally segregated circuits with motor and non-motor areas of the cerebral cortex. We then discuss the data that the basal ganglia are interconnected with the cerebellum. These results provide the anatomical substrate for basal ganglia contributions not only to the control of movement, but also to a variety of cognitive and affective functions. Furthermore, these findings indicate that abnormal activity in basal ganglia circuits with the cerebral cortex and with the cerebellum may contribute to both motor and non-motor deficits associated with several neurologic and psychiatric conditions.

Transcranial magnetic resonance-guided focused ultrasound (MRgFUS) surgery has recently gained favor as a novel, noninvasive alternative to conventional neurosurgery. In contrast to traditional ablative interventions, transcranial MRgFUS surgery is entirely imaging-guided and uses continuous temperature measurements at the target and surrounding tissue taken in real-time. Unlike Gamma Knife radiosurgery, MRgFUS surgery can make a lesion immediately and does not use ionizing radiation. Moreover, since no metallic device is implanted, MR imaging-based diagnosis is not restricted throughout life. An additional strength of transcranial MRgFUS surgery is its ability to focus acoustic energy through the intact skull onto deep-seated targets, while minimizing adjacent tissue damage. Even though the established indications of MRgFUS include bone metastases, uterine fibroids, and breast lesions, several promising preclinical and phase I clinical trials of neuropathic pain, essential tremor, Parkinson's disease (PD), and obsessive-compulsive disorder have demonstrated that the delivery of focused ultrasound energy promises to be a broadly applicable technique. For instance, this technique can be used to generate focal intracranial thermal ablative lesions of brain tumors, or to silence dysfunctional neural circuits and disrupt the blood-brain barrier for targeted drug delivery and the modulation of neural activity. Here we review the general principles of MRgFUS and its current applications, with a special focus on movement disorders such as essential tremor and PD, and discuss controversies and limitations of this technique.

Current cell-based immunotherapeutic strategies attempt to produce and maintain an immune response against glioma cells by artificially stimulating the immune system using passive and/or active approaches. Cellular immunotherapy is taken to mean the administration of live immune cells that either have immune effector capabilities themselves (passive immunotherapy) or engender a downstream antitumor response (active immunotherapy). Passive cellular immunotherapy most often takes the form of the adoptive transfer of a range of cell types, whereby antitumor immune cells from a patient (or allogeneic donor) are created, activated, and/or expanded ex vivo and subsequently administered back to the patient to directly attack the neoplasm. Active cellular immunotherapy approaches for the treatment of malignant gliomas have most often taken the form of dendritic cell (DC)-based vaccines.

Are truly effective therapies for glioma finally within reach? An explosion of technologies and treatments in recent years brings with it the hope that the revolution is nigh, but decades of gains that can at best be considered incremental understandably temper optimism. Concepts such as "targeted therapy" and "personalized medicine" have grabbed the attention of the oncology community for over a decade; yet when applied to glioblastoma, our initial efforts have amounted to running into battle with limited armaments and an incomplete understanding of the enemy. Still, there is reason to believe that recent insights and advances have changed the equation, with real gains just over the horizon.

Significant advances in the design and understanding of the materials and systems of 1-100 nm have provided unprecedented tools to probe, diagnose, and treat diseases at the molecular level with greater efficiency and accuracy. In particular, optical and chemical properties of nanomaterials are being exploited to improve the effectiveness of neuro-oncological and neurosurgical interventions. Modern nanotechnology-driven clinical applications may have significant impact on management of brain tumors.

Interstitial implantation of radioactive materials (brachytherapy [BT]) has been designed to protractedly deliver a high radiation dose to a well-defined target volume, while minimizing irradiation of the adjacent normal tissues. Even though promising results have been reported over time, the role of this treatment modality in the management of brain tumors is still poorly defined, and only a few centers worldwide apply it in clinical practice. Nevertheless, temporary or permanent interstitial implantation of low activity (<20 mCi) and low dose rate (≤10 cGy/h) iodine-125 (125I) seeds as possible therapy of intracranial gliomas is currently undergoing a definite revival, and several indications for its use have been identified. Generally, 125I-BT may be considered a reasonable option in cases of unresectable, well-circumscribed, either newly diagnosed or recurrent tumors with a diameter of ≤4 cm, virtually in any location within the brain. Importantly, this treatment does not narrow down the spectrum of the possible subsequent salvage therapeutic options, since neither repeated interstitial nor additional external beam irradiation at the time of tumor progression after BT is associated with a significantly increased risk of radiogenic complications. Using correct patient selection criteria, appropriate surgical technique, and established treatment parameters, would make BT a truly minimally invasive procedure with a low risk of complications and reasonable efficacy.

Current World Health Organization (WHO) classification of the neuroepithelial tumors is cell lineage-oriented and based on a presumed developmental tree of the central nervous system (CNS). It defines three main groups of gliomas, namely astrocytomas, oligodendrogliomas, and ependymomas, and additionally presumes their 4-tiered histopathological grading (WHO grades I to IV). Nevertheless, the impact of tumor pathology on clinically related parameters may be frequently much better predicted by genetics, than by histological appearance of the lesion. Recent studies have revealed several major molecular alterations typical for different types of neoplasms, such as IDH1/IDH2 mutations in diffusely infiltrating gliomas, mutations of TP53 and ATRX in astrocytomas, 1p/19q co-deletion in oligodendrogliomas, mutations of TERT promoter in oligodendrogliomas and IDH wild-type glioblastomas, and mutations or fusions of BRAF in circumscribed astrocytomas, particularly in children. Identification of those and several other genetic abnormalities in the tumor is clinically important and may help clinicians to determine proper treatment strategy and to predict prognosis. Therefore, the updated WHO classification of CNS tumors (2016) considers not only phenotype, but also some genetic characteristics of gliomas.

Under specific indications, chemotherapy may play an important role in the treatment of pediatric patients with intracranial gliomas. It can be effectively administered in inoperable low-grade tumors, particularly with the use of combination regimens based on carboplatin and vincristine. In very young children with high-grade gliomas (HGG), chemotherapy may result in control of tumor growth, which allows to postpone fractionated radiation therapy (FRT). At the same time, in difference with adults, there is no current evidence that addition of chemotherapy to aggressive surgical resection followed by FRT has any positive impact on survival of pediatric patients with non-pontine HGG. Similarly, chemotherapy is seemingly non-effective in the management of diffuse intrinsic pontine gliomas. Novel treatment strategies in such cases are desperately needed.

In comparison to photon irradiation, particle therapy of cancer performed either with protons or with carbon ions, offers the advantage of their distinct physical characteristics, and through delivery of high linear energy transfer (LET) particles, exploits greater relative biological effectiveness (RBE). There is strong rationale for applying such treatment in patients with intracranial gliomas. In cases of low-grade tumors, the main benefits may be related to potential decrease of long-term morbidity, whereas in cases of high-grade neoplasms, the use of modalities with greater RBE may lead to better tumor control and improve patient survival. Nevertheless, to date, there are no convincing data that confirm the superior effects of particle therapy (either with protons or carbon ions) in comparison to advanced photon fractionated radiotherapy (FRT) in patients with either newly diagnosed or recurrent intracranial gliomas. Therefore, the real clinical benefit of such treatment should be evaluated further in prospective clinical trials.

In cases of recurrent gliomas, the treatment options are limited and not yet standardized. Choices usually include re-operation, systemic chemotherapy, salvage re-irradiation, and supportive care, which can be used either separately or in combination. From a surgical perspective, management of recurrent brain tumor poses a significant challenge, as the desire to attain aggressive lesion resection must be balanced against the need to preserve neurological functions and to maximize the quality of life. Additionally, specific practical difficulties in performing repeat craniotomies and significant risk of perioperative morbidity in such cases necessitate careful selection of the optimal candidates for surgery.