BackgroundEpilepsy is a prevalent neurological disorder worldwide. It is characterized by an enduring predisposition to generate seizures and its development is accompanied by alterations in many cellular processes. Organotypic slice cultures represent a multicellular environment with the potential to assess biological mechanisms, and they are used as a starting point for refining molecules for in vivo studies. Here, we investigated organotypic slice cultures as a model of epilepsy.MethodsWe assessed, by electrophysiological recordings, the spontaneous activity of organotypic slices maintained under different culture protocols. Moreover, we evaluated, through molecular-based approaches, neurogenesis, neuronal death, gliosis, expression of proinflammatory cytokines, and activation of NLRP3 inflammasome (nucleotide-binding, leucine-rich repeat, pyrin domain) as biomarkers of neuroinflammation.ResultsWe demonstrated that organotypic slices, maintained under a serum deprivation culture protocol, develop epileptic-like activity. Furthermore, throughout a comparative study with slices that do not depict any epileptiform activity, slices with epileptiform activity were found to display significant differences in terms of inflammation-related features, such as (1) increased neuronal death, with higher incidence in CA1 pyramidal neurons of the hippocampus; (2) activation of astrocytes and microglia, assessed through western blot and immunohistochemistry; (3) upregulation of proinflammatory cytokines, specifically interleukin-1β (IL-1β), interleukin-6, and tumor necrosis factor α, revealed by qPCR; and (4) enhanced expression of NLRP3, assessed by western blot, together with increased NLRP3 activation, showed by IL-1β quantification.ConclusionsThus, organotypic slice cultures gradually deprived of serum mimic the epileptic-like activity, as well as the inflammatory events associated with in vivo epilepsy. This system can be considered a new tool to explore the interplay between neuroinflammation and epilepsy and to screen potential drug candidates, within the inflammatory cascades, to reduce/halt epileptogenesis.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1225-2) contains supplementary material, which is available to authorized users.
Penfield’s motor homunculus describes a caricaturised yet useful representation of the map of various body parts on the pre-central cortex. We propose a supplemental map of the clinically represented areas of human body in pre-central cortex and a novel subcortical corticospinal tract map. We believe this knowledge is essential for safe surgery in patients with eloquent brain lesions. A single-institution retrospective cohort study of patients who underwent craniotomy for motor eloquent lesions with intraoperative motor neuromonitoring (cortical and subcortical) between 2015 and 2020 was performed. All positive cortical and subcortical stimulation points were taken into account and cartographic maps were produced to demonstrate cortical and subcortical areas of motor representation and their configuration. A literature review in PubMed was performed. One hundred and eighty consecutive patients (58.4% male, 41.6% female) were included in the study with 81.6% asleep and 18.4% awake craniotomies for motor eloquent lesions (gliomas 80.7%, metastases 13.8%) with intraoperative cortical and subcortical motor mapping. Based on the data, we propose a supplemental clinical cortical and a novel subcortical motor map to the original Penfield’s motor homunculus, including demonstration of localisation of intercostal muscles both in the cortex and subcortex which has not been previously described. The supplementary clinical cortical and novel subcortical motor maps of the homunculus presented here have been derived from a large cohort of patients undergoing direct cortical and subcortical brain mapping. The information will have direct relevance for improving the safety and outcome of patients undergoing resection of motor eloquent brain lesions.
BACKGROUND A recent influx of intraoperative technology is being used in neurosurgery, but few reports investigate the accuracy and safety of these technologies when used simultaneously. OBJECTIVE To assess the ability to use an electromagnetic navigation system alongside multimodal intraoperative neurophysiological monitoring (IONM). METHODS Single-institution prospective cohort study of patients requiring craniotomy for brain tumor resection operated using an electromagnetic navigation system (AxiEM, Medtronic®). motor evoked potentials, somatosensory evoked potentials (SSEPs), electroencephalography, and electromyography were recorded and analyzed with AxiEM on (with/without filters) and off. The neurological outcomes of the patients were recorded. RESULTS A total of 15 patients were included (8 males/7 females, mean age 52.13 yr). Even though the raw acquisition is affected by the electromagnetic field (particularly SSEPs), no significant difference was detected in the morphology, amplitude, and latency of the different monitoring modalities (AxiEM off vs on) after the appropriate software filter application. Adjustments to the frequency of SSEP stimulation and number of averages, and reductions to the low-pass filters were applied. Notch filters were used appropriately and changes to the physical setup of the IONM and electromagnetic navigation system equipment reduced noise. Postoperatively, none of the patients developed new focal deficits; 7 patients showed improvement in their motor deficit (4 recovered fully). CONCLUSION The information provided by the IONM in intracranial neurosurgery patients whilst also using electromagnetic navigation systems is reliable for monitoring, mapping, and detecting intraoperative complications, provided that the appropriate software filters and tools are applied.
Deep-seated brain tumours represent a unique neurosurgical challenge as they are often surrounded by eloquent structures. We describe a minimally invasive technique using tubular retractors and intraoperative neurophysiology monitoring for open biopsy of a deep-seated lesion surrounded by the corticospinal tract. We used preoperative functional mapping with diffusion tensor imaging tractography and navigated transcranial magnetic stimulation to identify a safe surgical corridor. We also used 5-Aminolevulinic Acid induced fluorescence to identify the lesion intraoperatively and optimize tissue samples obtained for histopathological diagnosis. We found the use of these tools improved the safety of surgery and reduced the risk of surgical morbidity.
Background The use of intraoperative monitoring (IOM) in glioma surgery is a widely adopted and clinically validated adjunct to define safe zones of resection for the neurosurgeon. However, the role of IOM in cases of a significant preexisting motor deficit is questionable. Case Description We describe a case of a 25-year-old with a recurrent presentation of a left paracentral glioblastoma, admitted with intratumoral hemorrhage and subsequent acute severe right-sided weakness. The patient underwent a redo left parietal craniotomy and 5-aminolevulinic acid–guided resection with IOM. The severity of the weakness was not reflected by the pre- and intraoperative cortical motor evoked potentials (MEPs) that were reassuring. The patient's hemiparesis recovered to full power postoperatively. Conclusions Preoperative weakness is traditionally accepted as a relative contraindication to IOM and therefore its usefulness is questioned in this context. Our case challenges this assumption. We present the clinical course, review the cranial and spinal literature including the reliability of IOM in cases of preoperative motor deficit, and discuss the need for tailor-made IOM strategies.
Objectives Haemangiopericytoma of the trigemimal nerve is extremely rare, with only two previous cases described to our knowledge. We present the surgical approach to this tumour, and describe a previously poorly reported method of monitoring the function of the branches of the trigeminal nerve: mapping of the sensory roots through transcranial somatosensory cortex sensory evoked potentials (SSEPs), motor evoked potentials (MEP) for the motor root and blink reflex. Design Case and technical reports Subjects 32 year-old male patient presenting with headaches and vomiting, found to have a mixed cystic-solid tumour of the left middle skull base region, in close relation with the foramen ovale and Meckel’s cave. Methods The radiological features of the tumour, technical aspects of the technical approach and neurophysiologic monitoring will be described. Results A pterional craniotomy with fronto-temporal extradural-interdural-intradural approach, and the tumour was debulked with MEP, SSEP and blink reflex monitoring of the branches of the trigeminal nerve. Complete tumour removal was achieved with no post-operative cranial nerve deficits. The histopathology revealed a cystic haemangiopericytoma. Conclusions Haemangiopericytoma is a rare entity. MEP and SSEP monitoring of the trigeminal nerve can be used to achieve complete and safe removal of the tumour.
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