Expanded Endoscopic Endonasal Transtuberculum Approach for Resection of Germ Cell Tumor.

We present the case of a 16-year-old with short stature, fatigue, memory impairment, and pituitary gland failure. Imaging and cerebrospinal fluid (CSF) studies supported the diagnosis of a suprasellar nongerminomatous germ cell tumor with no clear radiologic disease in the spine; however, a single atypical cell was present in the CSF. After a period of external drainage via an Ommaya device, he was treated with chemotherapy, followed by craniospinal radiation. Three months post completion of chemoradiotherapy, he had ongoing residual macroscopic enhancing disease anatomically located in the basal third ventricle and intimately related to pituitary stalk and basal thalamoperforators. In order to maximize his chance of progression-free survival, a decision was made to surgically resect the lesion via an expanded endoscopic endonasal approach with planned stalk sacrifice because of the known pituitary gland failure. In Video 1, the technical nuances underpinning the use of an expanded endoscopic endonasal transtuberculum transchiasmatic sulcus approach to resect the adherent lesion in a postradiated field in its entirety are presented. We emphasize the strategies for perforator preservation including thalamoperforators and superior hypophyseal arteries to avoid ischemic injury and visual dysfunction, respectively. Postoperative scans demonstrated gross total resection without any ischemic injury. The patient was discharged without any neurologic deficit, visual dysfunction, or CSF leak.

Case Report: Recurrent pediatric cavernous malformation of the trigeminal nerve.

Background: Most cavernous malformations (CM) usually involve the parenchyma and rarely occur in cranial nerves. Recurrence of CM associated with cranial nerves after surgical resection has not been previously reported. Case description: This paper describes the case of an 11-year-old girl who presented with left otalgia and headache because of a left trigeminal cavernous malformation. She underwent radical resection via a left retrosigmoid approach while sparing the trigeminal nerve. Surveillance imaging at 18 months demonstrated recurrence along the length of the trigeminal nerve into Meckel's cave with significant extension into the middle cerebellar peduncle. Subsequent re-operation via an extended middle fossa approach with anterior petrosectomy enabled complete resection with division of the trigeminal nerve. Postoperatively, she had a transient left facial paresis, and right hemiparesis that resolved within 48 h. Conclusion: This case highlights the importance of close postoperative surveillance in CM associated with cranial nerves as recurrence after nerve-sparing resection is possible. Surgical treatment due to the morphology of significant recurrence required the use of a complex skull base approach through a new corridor to achieve optimal clinical outcome.

Paediatric Cavernous Malformation of the Trigeminal Nerve: Case Report and Review of the Literature.

INTRODUCTION: Intradural, extra-axial cerebral cavernous malformations (CCMs) are rare entities and are mostly reported in relation to the optic apparatus or the facial/vestibulocochlear complex. Cranial nerve CCMs tend to follow a clinically aggressive course, with a tendency to progressive neurological dysfunction following intra-lesional haemorrhage or less commonly due to the effects of subarachnoid haemorrhage. CASE PRESENTATION: We report the first case of a trigeminal CCM presenting in a child with otalgia and left-sided headaches. The patient was initially managed with radiological surveillance but required surgical management following deterioration. We describe the successful treatment of the lesion with microsurgical resection. CONCLUSION: A CCM should be considered in the differential diagnosis of mass lesions arising in the region of the trigeminal nerve. Surgical resection is recommended to prevent neurological deterioration and may result in significant symptomatic improvement.

Postoperative speech impairment and surgical approach to posterior fossa tumours in children: a prospective European multicentre cohort study.

BACKGROUND: Brain tumours are the most common solid tumours in childhood. Half of these tumours occur in the posterior fossa, where surgical removal is complicated by the risk of cerebellar mutism syndrome, of which postoperative speech impairment (POSI) is a cardinal symptom, in up to 25% of patients. The surgical approach to midline tumours, mostly undertaken by transvermian or telovelar routes, has been proposed to influence the risk of POSI. We aimed to investigate the risk of developing POSI, the time course of its resolution, and its association with surgical approach and other clinical factors. METHODS: In this observational prospective multicentre cohort study, we included children (aged <18 years) undergoing primary surgery for a posterior fossa tumour at 26 centres in nine European countries. Within 72 h of surgery, the operating neurosurgeon reported details on the tumour location, surgical approach used, duration of surgery, use of traction, and other predetermined factors, using a standardised surgical report form. At 2 weeks, 2 months, and 1 year after surgery, a follow-up questionnaire was filled out by a paediatrician or neurosurgeon, including neurological examination and assessment of speech. Speech was classified as mutism, reduced speech, or habitual speech. POSI was defined as either mutism or severely reduced speech. Ordinal logistic regression was used to analyse the risk of POSI. FINDINGS: Between Aug 11, 2014, and Aug 24, 2020, we recruited 500 children. 426 (85%) patients underwent primary tumour surgery and had data available for further analysis. 192 (45%) patients were female, 234 (55%) patients were male, 81 (19%) patients were aged 0-2 years, 129 (30%) were aged 3-6 years, and 216 (51%) were aged 7-17 years. 0f 376 with known postoperative speech status, 112 (30%) developed POSI, 53 (14%) developed mutism (median 1 day [IQR 0-2]; range 0-10 days), and 59 (16%) developed reduced speech after surgery (0 days [0-1]; 0-4 days). Mutually adjusted analyses indicated that the independent risk factors for development of POSI were younger age (linear spline, p=0·0087), tumour location (four levels, p=0·0010), and tumour histology (five levels, p=0·0030); surgical approach (six levels) was not a significant risk factor (p=0·091). Tumour location outside the fourth ventricle and brainstem had a lower risk of POSI (with fourth ventricle as reference, odds ratio (OR) for cerebellar vermis 0·34 [95% CI 0·14-0·77] and OR for cerebellar hemispheres 0·23 [0·07-0·70]). Compared with pilocytic or pilomyxoid astrocytoma, a higher risk of POSI was seen for medulloblastoma (OR 2·85 [1·47-5·60]) and atypical teratoid rhabdoid tumour (10·30 [2·10-54·45]). We did not find an increased risk of POSI for transvermian surgical approach compared with telovelar (0·89 [0·46-1·73]). Probability of speech improvement from mutism reached 50% around 16 days after mutism onset. INTERPRETATION: Our data suggest that a midline tumour location, younger age, and high-grade tumour histology all increase the risk of speech impairment after posterior fossa tumour surgery. We found no evidence to recommend a preference for telovelar over transvermian surgical approach in the management of posterior fossa tumours in children in relation to the risk of developing POSI. FUNDING: The Danish Childhood Cancer Foundation, the Swedish Childhood Cancer Foundation, the UK Brain Tumour Charity, the Danish Cancer Society, Det Kgl Kjøbenhavnske Skydeselskab og Danske Broderskab, the Danish Capitol Regions Research Fund, Dagmar Marshall Foundation, Rigshospitalet's Research Fund, and Brainstrust.

Giant Juvenile Ectopic Schwannoma of the Temporal Bone.

BACKGROUND: Ectopic intracranial schwannomas (those that do not arise from a named cranial nerve) are rare. They account for <2% of surgically resected central nervous system schwannomas. CASE DESCRIPTION: We report the case of a 14-year-old boy presenting with a left conductive hearing loss and temporal bone deformity. No facial or cranial nerve deficits were present. Cross-sectional imaging demonstrated a large expansile extra-axial temporal bone mass, extending into and distorting the middle cranial fossa. At surgical resection the tumor was functionally and anatomically distinct from the facial nerve or any other identifiable neural structure within the middle ear or temporal bone. Histology confirmed a World Health Organization grade 1 schwannoma. CONCLUSIONS: This is the first reported case of a giant juvenile ectopic schwannoma within the temporal bone.

Monitoring intraventricular vancomycin for ventriculostomy access device infection in preterm infants.

PURPOSE: Ventriculitis is a known complication during external CSF drainage in preterm infants with posthaemorrhagic ventricular dilatation. Staphylococci are most frequently isolated in device-associated ventriculitis, and hence, intraventricular vancomycin is a commonly used therapy. Our aim was to study the CSF vancomycin level pattern and drug safety in ventriculostomy access device infection in preterm infants less than 28 weeks gestation. METHODS: This single-centre, retrospective case series included seven infants with a median gestational age of 25 + 4 weeks (range 23 + 6 to 27 + 5 weeks). Ventriculitis was defined as elevated CSF white cell count of > 20/mm3 or positive CSF culture. The CSF vancomycin concentrations following intraventricular vancomycin administration were studied. RESULTS: Forty treatment episodes of intraventricular vancomycin administration were studied in seven preterm infants. Maximum CSF vancomycin concentrations were 24.9 mg/L (3 mg, n = 8, observed concentration-time (OCT), hours (h) = 19), 96.3 mg/L (5 mg, n = 17, OCT(h) = 14), 94 mg/L (10 mg, n = 14, OCT(h) = 24), and 230.7 mg/L (15 mg, n = 1, OCT(h) = 24). The threshold for re-dosage is set at CSF vancomycin level of < 10 mg/L. In all patients, ventriculitis resolution (defined as sterile CSF and CSF WCC of < 20/mm3) was achieved in a median of 5.5 days (range 2-31 days). Individual microbiology data is provided in the online resource. CONCLUSION: Intraventricular vancomycin is an effective treatment for ventriculostomy access device infection in preterm infants. In doses ranging from 3 to 15 mg, sufficient CSF vancomycin level is generated to achieve microbiological cure without any reported adverse effects. Daily CSF drug monitoring is recommended to define dosage interval to maintain drug concentration above breakpoint of minimum inhibitory concentration.

(1) H 2D MRSI tissue type analysis of gliomas.

PURPOSE: To decompose 1H MR spectra of glioma patients into normal and abnormal tissue proportions for tumor classification and delineation. METHODS: Anatomical imaging and 1H magnetic resonance spectroscopic imaging data have been acquired from 11 grade II and 13 grade IV glioma patients. LCModel was used to decompose the magnetic resonance spectroscopic imaging data into normal brain, grade II, and grade IV tissue proportions using a tissue type basis set. Simulations were conducted to evaluate the accuracy of the methodology. Results were visualized using colormaps and abnormality contours showing tumor grade and extent. RESULTS: Simulations suggest that infiltrative tumor proportions as low as 20% can be identified at the typical 1H magnetic resonance spectroscopy signal-to-noise found in vivo. Tumor grading according to the highest estimated tumor grade within a lesion gave a classification accuracy of 86% discriminating between grade II and grade IV glioma. Voxels with significant proportions of tumor type spectra were found beyond the margins of contrast enhancement for most grade IV cases consistent with infiltration whereas the abnormality contours show that some tumors are confined within the hyperintensities shown by both post contrast T1 weighted and T2 weighted imaging. CONCLUSION: LCModel can be used to decompose 1H MR spectra into proportions of normal and abnormal tissue to identify tumor extent, infiltration, and overall grade.

Community acquired Panton-Valentine Leukocidin (PVL) positive Methicilin Resistant Staphylococcal aureus cerebral abscess in an 11-month old boy: a case study.

BACKGROUND: Brain abscess are uncommon childhood infection. Brain abscess caused by Panton-Valentine Leukocidin positive Community acquired Methicillin Resistant Staphylococcal aureus have never been reported in the United Kingdom. CASE PRESENTATION: We report a case of a previously well 11-month old boy of Indian origin who developed a parietal lobe abscess from PVL positive CA-MRSA. CONCLUSION: This case is one of the few described cases of brain abscess caused by PVL CA-MRSA in children. The unusual (insidious) presentation, the absence of a clear staphylococcal focus and the unexpected finding of a CA-MRSA in this patient highlight the challenges of managing such cases in clinical settings and the potential future risk to public health.

Anosmin-1 contributes to brain tumor malignancy through integrin signal pathways.

Anosmin-1, encoded by the KAL1 gene, is an extracellular matrix (ECM)-associated protein which plays essential roles in the establishment of olfactory and GNRH neurons during early brain development. Loss-of-function mutations of KAL1 results in Kallmann syndrome with delayed puberty and anosmia. There is, however, little comprehension of its role in the developed brain. As reactivation of developmental signal pathways often takes part in tumorigenesis, we investigated if anosmin-1-mediated cellular mechanisms associated with brain tumors. Our meta-analysis of gene expression profiles of patients' samples and public microarray datasets indicated that KAL1 mRNA was significantly upregulated in high-grade primary brain tumors compared with the normal brain and low-grade tumors. The tumor-promoting capacity of anosmin-1 was demonstrated in the glioblastoma cell lines, where anosmin-1 enhanced cell motility and proliferation. Notably, anosmin-1 formed a part of active ß1 integrin complex, inducing downstream signaling pathways. ShRNA-mediated knockdown of anosmin-1 attenuated motility and growth of tumor cells and induced apoptosis. Anosmin-1 may also enhance the invasion of tumor cells within the ECM by modulating cell adhesion and activating extracellular proteases. In a mouse xenograft model, anosmin-1-expressing tumors grew faster, indicating the role of anosmin-1 in tumor microenvironment in vivo. Combined, these data suggest that anosmin-1 can facilitate tumor cell proliferation, migration, invasion, and survival. Therefore, although the normal function of anosmin-1 is required in the proper development of GNRH neurons, overexpression of anosmin-1 in the developed brain may be an underlying mechanism for some brain tumors.

Combined use of neuroradiology and 1H-MR spectroscopy may provide an intervention limiting diagnosis of glioblastoma multiforme.

PURPOSE: To evaluate the accuracy of (1)H-MR spectroscopy ((1)H-MRS) as an intervention limiting diagnostic tool for glioblastoma multiforme. GBM is the most common and aggressive primary brain tumor, with mean survival under a year. Oncological practice currently requires histopathological diagnosis before radiotherapy. MATERIALS AND METHODS: Eighty-nine patients had clinical computed tomography (CT) and MR imaging and 1.5T SV SE (1)H-MRS with PRESS localization for neuroradiological diagnosis and tumor classification with spectroscopic and automated pattern recognition analysis (TE 30 ms, TR 2000 ms, spectral width 2500 Hz and 2048 data points, 128-256 signal averages were acquired, depending on voxel size (8 cm(3) to 4 cm(3)). Eighteen patients from a cohort of 89 underwent stereotactic biopsy. RESULTS: The 18 stereotactic biopsies revealed 14 GBM, 2 grade II astrocytomas, 1 lymphoma, and 1 anaplastic astrocytoma. All 14 biopsied GBMs were diagnosed as GBM by a protocol combining an individual radiologist and an automated spectral pattern recognition program. CONCLUSION: In patients undergoing stereotactic biopsy combined neuroradiological and spectroscopic evaluation diagnoses GBM with accuracy that could replace the need for biopsy. We do not advocate the replacement of biopsy in all patients; instead our data suggest a specific intervention limiting role for the use of (1)H-MRS in brain tumor diagnosis.

Ex-vivo HRMAS of adult brain tumours: metabolite quantification and assignment of tumour biomarkers.

BACKGROUND: High-resolution magic angle spinning (HRMAS) NMR spectroscopy allows detailed metabolic analysis of whole biopsy samples for investigating tumour biology and tumour classification. Accurate biochemical assignment of small molecule metabolites that are "NMR visible" will improve our interpretation of HRMAS data and the translation of NMR tumour biomarkers to in-vivo studies. RESULTS: 1D and 2D 1H HRMAS NMR was used to determine that 29 small molecule metabolites, along with 8 macromolecule signals, account for the majority of the HRMAS spectrum of the main types of brain tumour (astrocytoma grade II, grade III gliomas, glioblastomas, metastases, meningiomas and also lymphomas). Differences in concentration of 20 of these metabolites were statistically significant between these brain tumour types. During the course of an extended 2D data acquisition the HRMAS technique itself affects sample analysis: glycine, glutathione and glycerophosphocholine all showed small concentration changes; analysis of the sample after HRMAS indicated structural damage that may affect subsequent histopathological analysis. CONCLUSIONS: A number of small molecule metabolites have been identified as potential biomarkers of tumour type that may enable development of more selective in-vivo 1H NMR acquisition methods for diagnosis and prognosis of brain tumours.