Genome-Wide DNA Methylation Profiling as a Prognostic Marker in Pituitary Adenomas-A Pilot Study.

BACKGROUND: The prediction of the regrowth potential of pituitary adenomas after surgery is challenging. The genome-wide DNA methylation profiling of pituitary adenomas may separate adenomas into distinct methylation classes corresponding to histology-based subtypes. Specific genes and differentially methylated probes involving regrowth have been proposed, but no study has linked this epigenetic variance with regrowth potential and the clinical heterogeneity of nonfunctioning pituitary adenomas. This study aimed to investigate whether DNA methylation profiling can be useful as a clinical prognostic marker. METHODS: A DNA methylation analysis by Illumina's MethylationEPIC array was performed on 54 pituitary macroadenomas from patients who underwent transsphenoidal surgery during 2007-2017. Twelve patients were excluded due to an incomplete postoperative follow-up, degenerated biobank-stored tissue, or low DNA methylation quality. For the quantitative measurement of the tumor regrowth rate, we conducted a 3D volumetric analysis of tumor remnant volume via annual magnetic resonance imaging. A linear mixed effects model was used to examine whether different DNA methylation clusters had different regrowth patterns. RESULTS: The DNA methylation profiling of 42 tissue samples showed robust DNA methylation clusters, comparable with previous findings. The subgroup of 33 nonfunctioning pituitary adenomas of an SF1-lineage showed five subclusters with an approximately unbiased score of 86%. There were no overall statistically significant differences when comparing hazard ratios for regrowth of 100%, 50%, or 0%. Despite this, plots of correlated survival estimates suggested higher regrowth rates for some clusters. The mixed effects model of accumulated regrowth similarly showed tendencies toward an association between specific DNA methylation clusters and regrowth potential. CONCLUSION: The DNA methylation profiling of nonfunctioning pituitary adenomas may potentially identify adenomas with increased growth and recurrence potential. Larger validation studies are needed to confirm the findings from this explorative pilot study.

The Influence of Size on the Intracranial Distribution of Biomedical Nanoparticles Administered by Convection-enhanced Delivery in Minipigs.

Because of the blood-brain barrier (BBB), successful drug delivery to the brain has long been a key objective for the medical community, calling for pioneering technologies to overcome this challenge. Convection-enhanced delivery (CED), a form of direct intraparenchymal microinfusion, shows promise but requires optimal infusate design and real-time distribution monitoring. The size of the infused substances appears to be especially critical, with current knowledge being limited. Herein, we examined the intracranial administration of polyethylene glycol (PEG)-coated nanoparticles (NPs) of various sizes using CED in groups of healthy minipigs (n = 3). We employed stealth liposomes (LIPs, 130 nm) and two gold nanoparticle designs (AuNPs) of different diameters (8 and 40 nm). All were labeled with copper-64 for quantitative and real-time monitoring of the infusion via positron emission tomography (PET). NPs were infused via two catheters inserted bilaterally in the putaminal regions of the animals. Our results suggest CED with NPs holds promise for precise brain drug delivery, with larger LIPs exhibiting superior distribution volumes and intracranial retention over smaller AuNPs. PET imaging alongside CED enabled dynamic visualization of the process, target coverage, timely detection of suboptimal infusion, and quantification of distribution volumes and concentration gradients. These findings may augment the therapeutic efficacy of the delivery procedure while mitigating unwarranted side effects associated with nonvisually monitored delivery approaches. This is of vital importance, especially for chronic intermittent infusions through implanted catheters, as this information enables informed decisions for modulating targeted infusion volumes on a catheter-by-catheter, patient-by-patient basis.

Treatment of Meningiomas Involving the Optic Canal with Endoscopic Transnasal Decompression of the Optic Nerve.

BACKGROUND: Management of patients with optic nerve sheath meningiomas (ONSMs) is controversial and the treatment strategy in this patient group is still up for discussion. Transnasal endoscopic orbital and optic nerve decompression aims to reduce the pressure in the orbit and on the optic nerve and thereby prevent vision loss. This article presents material from 7 cases of transnasal endoscopic orbital decompression. METHODS: The study design is a retrospective cohort study. The aim was to include all patients with a meningioma residing along the nerve sheath and who were operated using endoscopic transnasal decompression of the orbit and if needed the optic canal at Odense University Hospital. Data from the medical records were collected and pre- and postoperative eye examinations were compared. In addition, it was recorded whether there were complications to the procedure and whether additional treatments were given. RESULTS: In total, 4 women and 3 men were included in the study. Four out of 7 patients experienced improvement in vision after the operation. One patient experienced unchanged vision and 2 patients experienced deterioration of vision after surgery. CONCLUSIONS: The current report of 7 patients with ONSM shows promising results for this surgical procedure as 4 out of 7 patients experienced improvement in their vision at follow-up examinations. The 2 patients who experienced deterioration of vision already had severely reduced vision preoperatively, which indicates that surgery should be considered before the vision becomes significantly reduced.

Evaluating the Efficacy of Perfusion MRI and Conventional MRI in Distinguishing Recurrent Cerebral Metastasis from Brain Radiation Necrosis.

Differentiating recurrent cerebral metastasis (CM) from brain radiation necrosis (BRN) is pivotal for guiding appropriate treatment and prognostication. Despite advances in imaging techniques, however, accurately distinguishing these conditions non-invasively is still challenging. This single-center retrospective study reviewed 32 cases (28 patients) with confirmed cerebral metastases who underwent surgical excision of lesions initially diagnosed by MRI and/or MR perfusion scans from 1 January 2015 to 30 September 2020. Diagnostic accuracy was assessed by comparing imaging findings with postoperative histopathology. Conventional MRI accurately identified recurrent CM in 75% of cases. MR perfusion scans showed significantly higher mean maximum relative cerebral blood volume (max. rCBV) in metastasis cases, indicating its potential as a discriminative biomarker. No single imaging modality could definitively distinguish CM from BRN. Survival analysis revealed gender as the only significant factor affecting overall survival, with no significant survival difference observed between patients with CM and BRN after controlling for confounding factors. This study underscores the limitations of both conventional MRI and MR perfusion scans in differentiating recurrent CM from BRN. Histopathological examination remains essential for accurate diagnosis. Further research is needed to improve the reliability of non-invasive imaging and to guide the management of patients with these post-radiation events.

Urinary bladder catheterisation of female pigs: Influence of bladder content and Escherichia coli urinary tract infection on procedural outcome.

Catheterisation of the urinary bladder is needed in many types of human disease models in pigs. Based on our extensive experience with the pig as an infection model, we here demonstrate an approach of catheterising domestic pigs (40 attempts) and Göttingen minipigs (10 attempts) using a blinded method, that is, without speculums or videoscopes to visualise the urethral opening. The procedure was tested on control animals and pigs with experimental Escherichia coli urinary tract infection (UTI) to assess the potential influence of this condition on procedural outcome. Lastly, we performed cystoscopy in three animals to visualise the route to the urethra and to localise potential anatomical obstacles. All domestic pigs were catheterised successfully in an average of 2 minutes and 23 seconds, and this was not influenced by UTI (p = 0.06) or bladder urine content at the time of catheterisation (p = 0.32). All Göttingen minipigs were successfully catheterised in an average of 4 minutes and 27 seconds. We conclude that blinded catheterisation is a fast and reliable approach that can be performed in pigs with or without UTI with minimal risk of trauma or contamination.

Meningioma animal models: a systematic review and meta-analysis.

BACKGROUND: Animal models are widely used to study pathological processes and drug (side) effects in a controlled environment. There is a wide variety of methods available for establishing animal models depending on the research question. Commonly used methods in tumor research include xenografting cells (established/commercially available or primary patient-derived) or whole tumor pieces either orthotopically or heterotopically and the more recent genetically engineered models-each type with their own advantages and disadvantages. The current systematic review aimed to investigate the meningioma model types used, perform a meta-analysis on tumor take rate (TTR), and perform critical appraisal of the included studies. The study also aimed to assess reproducibility, reliability, means of validation and verification of models, alongside pros and cons and uses of the model types. METHODS: We searched Medline, Embase, and Web of Science for all in vivo meningioma models. The primary outcome was tumor take rate. Meta-analysis was performed on tumor take rate followed by subgroup analyses on the number of cells and duration of incubation. The validity of the tumor models was assessed qualitatively. We performed critical appraisal of the methodological quality and quality of reporting for all included studies. RESULTS: We included 114 unique records (78 using established cell line models (ECLM), 21 using primary patient-derived tumor models (PTM), 10 using genetically engineered models (GEM), and 11 using uncategorized models). TTRs for ECLM were 94% (95% CI 92-96) for orthotopic and 95% (93-96) for heterotopic. PTM showed lower TTRs [orthotopic 53% (33-72) and heterotopic 82% (73-89)] and finally GEM revealed a TTR of 34% (26-43). CONCLUSION: This systematic review shows high consistent TTRs in established cell line models and varying TTRs in primary patient-derived models and genetically engineered models. However, we identified several issues regarding the quality of reporting and the methodological approach that reduce the validity, transparency, and reproducibility of studies and suggest a high risk of publication bias. Finally, each tumor model type has specific roles in research based on their advantages (and disadvantages). SYSTEMATIC REVIEW REGISTRATION: PROSPERO-ID CRD42022308833.

USP25 Inhibits Neuroinflammatory Responses After Cerebral Ischemic Stroke by Deubiquitinating TAB2.

Cerebral ischemic stroke is a leading cause of morbidity and mortality globally. However, the mechanisms underlying ischemic stroke injury remain poorly understood. Here, it is found that deficiency of the ubiquitin-specific protease USP25 significantly aggravate ischemic stroke injury in mice. USP25 has no impact on neuronal death under hypoxic conditions, but reduced ischemic stroke-induced neuronal loss and neurological deficits by inhibiting microglia-mediated neuroinflammation. Mechanistically, USP25 restricts the activation of NF-κB and MAPK signaling by regulating TAB2. As a deubiquitinating enzyme, USP25 removeds K63-specific polyubiquitin chains from TAB2. AAV9-mediated TAB2 knockdown ameliorates ischemic stroke injury and abolishes the effect of USP25 deletion. In both mouse and human brains, USP25 is markedly upregulated in microglia in the ischemic penumbra, implying a clinical relevance of USP25 in ischemic stroke. Collectively, USP25 is identified as a critical inhibitor of ischemic stroke injury and this data suggest USP25 may serve as a therapeutic target for ischemic stroke.

Virtual magnetic resonance elastography predicts the intraoperative consistency of meningiomas.

BACKGROUND AND PURPOSE: Virtual magnetic resonance elastography (vMRE) is an experimental imaging modality designed to non-invasively predict the haptic properties of tissues. The modality is sensitive to tissue stiffness and fibrosis. Information about meningioma consistency prior to resection is of great interest in neurological surgery as the surgical plan and outcome may be affected by the tumor's stiffness. In this study, we assessed the ability of vMRE to predict the intraoperative consistency and mechanical heterogeneity of intracranial meningiomas. MATERIALS AND METHODS: We included 12 patients scheduled for meningioma resection, of which one patient was found to have a solitary fibrous tumor on histological examination. All participants underwent preoperative vMRE and intraoperative consistency grading. RESULTS AND CONCLUSIONS: Intraoperative qualitative consistency correlated positively with vMRE-based consistency assessment (odds ratio 5.63, 95% CI 1.12-28.30, p = 0.04) at b1000. Mechanically homogenous tumors had significantly lower ∆ mean stiffness than heterogeneous tumors (8.13 vs 18.07 kPa, p = 0.01). This study thus demonstrates a possible clinical application of vMRE in predicting the intraoperative consistency and mechanical heterogeneity of meningiomas.

MIF in the cerebrospinal fluid is decreased during relapsing-remitting while increased in secondary progressive multiple sclerosis.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is involved in the function of both the innate and adaptive immune systems and in neuroprotection and has recently been implicated in multiple sclerosis (MS). OBJECTIVES: Determination of MIF levels in the cerebrospinal fluid (CSF) of patients with distinct subtypes of MS and the cellular localization of MIF in human brain tissue. METHODS: The levels of MIF were investigated in CSF from patients with clinically isolated syndrome (CIS) (n = 26), relapsing-remitting MS (RRMS) (n = 22), secondary progressive MS (SPMS) (n = 19), and healthy controls (HCs) (n = 24), using ELISA. The effect of disease-modifying therapies in the RRMS and SPMS cohorts were examined. Cellular distribution of MIF in the human brain was studied using immunochemistry and the newly available OligoInternode database. RESULTS: MIF was significantly decreased in treatment-naïve CIS and RRMS patients compared to HCs but was elevated in SPMS. Interestingly, MIF levels were sex-dependent and significantly lower in women with CIS and RRMS. MIF expression in the human brain was localized to neurons, astrocytes, pericytes, and oligo5 oligodendrocytes but not in microglia. CONCLUSION: The finding that MIF was decreased in newly diagnosed CIS and RRMS patients but was high in patients with SPMS may suggest that MIF levels in CSF are regulated by local MIF receptor expression that affects the overall MIF signaling in the brain and may represent a protective mechanism that eventually fails.

Diagnosis, treatment, and outcome of primary CNS lymphoma-a single-center experience.

BACKGROUND: Primary CNS lymphoma (PCNSL) is a highly aggressive non-Hodgkin lymphoma (NHL) that occurs in the CNS (e.g. brain, meninges, spinal cord, cerebrospinal fluid, or intraocular involvement) in the absence of systemic NHL. Tumor resection does not improve survival, and neurosurgical intervention is generally limited to stereotactic biopsy to provide a histopathological diagnosis. OBJECTIVE: The objective of this single-center study was to evaluate the management and outcome of PCNSL patients diagnosed by biopsy, using overall survival and progression-free survival as endpoints. METHODS: At our department of neurosurgery, 140 patients were diagnosed with PCNSL by biopsy between January 1, 2009, and December 31, 2018. Of these, 37 patients were included in the study and were divided into three groups according to their postoperative therapy. RESULTS: Median OS was 35.7 months for the intensive treatment group, 29.5 months for the moderate treatment group, and 8.6 months for the palliative treatment group. The intensive and moderate treatment groups had similar progression-free survival, while the palliative treatment group had poor overall and progression-free survival. Six patients were long-term survivors (> 80 months). Age under 65 years was the main significant parameter affecting overall survival. CONCLUSION: In this cohort, patients with PCNSL had an overall fair prognosis if they (1) were under 65 years old, (2) had a performance score < 2 at the time of diagnosis, and (3) received either intensive or moderate chemotherapeutic treatment. Biopsy is still the primary diagnostic tool; other methods have been investigated but are not yet recommended.

Endonasal Endoscopic Approach for Minimally Invasive Orbital Decompression in Nonthyroid Proptosis-A Scoping Review.

OBJECTIVE: The endoscopic endonasal approach (EEA) was originally performed to treat thyroid orbitopathy and proptosis. Since then, this approach also has been used to treat other causes of proptosis. This review systematically identifies surgical outcome and complication rates in patients without thyroid proptosis who underwent endoscopic endonasal orbital decompression. METHODS: Databases were searched using the following search terms: orbital disease, surgical decompression, and endoscopic endonasal approach. Two independent reviewers screened all abstracts and titles for relevance and all articles passing this screen were subjected to full-text review. To assess risk of bias, we used ROBINS-I (Risk Of Bias in Non-randomized Studies-of Interventions). RESULTS: Eight studies with a total of 74 patients with nonthyroid proptosis were included. Pre- and postoperative eye examination was performed in all studies, but the extent of examination was varying. With a mean age of 35.7 years, most patients were adolescent, and most pathologies induced unilateral proptosis Complications to EEA for orbital decompression were transient diplopia (5 patients/6.8%), transient facial dysesthesia (2 patients/2.7%), ptosis (1 patient/1.4%), infarction (1 patient/1.4%), sinus obstruction (1 patient/1.4%), and enophtalmos (1 patient/1.4%). The authors reported successful reduction of proptosis in all but 2 patients (97.2%), and only 2 authors reported a need for secondary decompression. CONCLUSIONS: Medial orbital decompression using EEA is a feasible approach for orbital decompression in patients with nonthyroid proptosis. While being comparable in primary outcome to transorbital approaches, the EEA seems superior in terms of complication rates.

Magnetic Resonance Elastography in Intracranial Neoplasms: A Scoping Review.

BACKGROUND: Magnetic resonance elastography (MRE) allows noninvasive assessment of intracranial tumor mechanics and may thus be predictive of intraoperative conditions. Variations in the use of technical terms complicate reading of current literature, and there is need of a review using consolidated nomenclature. OBJECTIVES: We present an overview of current literature on MRE relating to human intracranial neoplasms using standardized nomenclature suggested by the MRE guidelines committee. We then discuss the implications of the findings, and suggest approaches for future research. METHOD: We performed a systematic literature search in PubMed, Embase, and Web of Science; the articles were screened for relevance and then subjected to full text review. Technical terms were consolidated. RESULTS: We identified 12 studies on MRE in patients with intracranial tumors, including meningiomas, glial tumors including glioblastomas, vestibular schwannomas, hemangiopericytoma, central nervous system lymphoma, pituitary macroadenomas, and brain metastases. The studies had varying objectives that included prediction of intraoperative consistency, histological separation, prediction of adhesiveness, and exploration of the mechanobiology of tumor invasiveness and malignancy. The technical terms were translated using standardized nomenclature. The literature was highly heterogeneous in terms of image acquisition techniques, post-processing, and study design and was generally limited by small and variable cohorts. CONCLUSIONS: MRE shows potential in predicting tumor consistency, adhesion, and mechanical homogeneity. Furthermore, MRE provides insight into malignant tumor behavior and its relation to tissue mechanics. MRE is still at a preclinical stage, but technical advances, improved understanding of soft tissue rheological impact, and larger samples are likely to enable future clinical introduction.

Preclinical cerebral cryoablation in non-tumor bearing pigs.

Patients with brain metastases, the most common intracranial tumor, have an average survival ranging from a few months to 40 months, and new treatment initiatives are needed. Cryoablation is a minimally invasive, well-tolerated, and effective procedure commonly applied for treatment of renal tumors and certain other malignancies. We aimed to examine the clinical usefulness of this procedure in a step-by-step program starting with cerebral cryoablation in healthy pigs. In four terminal and four non-terminal non-tumor bearing pigs, we studied immediate and delayed effects of cerebral cryoablation. Safety was assessed by computed tomography (CT), and clinical observation of behavior, neurological deficits, and wellbeing. Effects were assessed by histological and immuno-histochemical analyses addressing structural and metabolic changes supported by additional magnetic resonance imaging (MRI) and positron emission tomography (PET) in the non-terminal animals. Using CT-guidance, cryoablation probes were successfully inserted without complications, and ice formation could be monitored real-time with CT. No animal developed neurological deficits or signs of discomfort. Histological and immunohistochemical analyses, MRI, and PET revealed profound structural and biological damage within the lesion. MRI and PET revealed no long-term damage to healthy tissue outside the cryoablation zone. Cerebral cryoablation appears to be a feasible, safe, and controllable procedure that can be monitored successfully with CT. The net effect is a dead brain lesion without damage of either nearby or remote healthy structures. Immediate changes are local hemorrhage and edema; delayed effects are perfusion defects, immune system activation, and astrogliosis.

Surgical resection of glioblastomas induces pleiotrophin-mediated self-renewal of glioblastoma stem cells in recurrent tumors.

BACKGROUND: Glioblastomas are highly resistant to therapy, and virtually all patients experience tumor recurrence after standard-of-care treatment. Surgical tumor resection is a cornerstone in glioblastoma therapy, but its impact on cellular phenotypes in the local postsurgical microenvironment has yet to be fully elucidated. METHODS: We developed a preclinical orthotopic xenograft tumor resection model in rats with integrated 18F-FET PET/CT imaging. Primary and recurrent tumors were subject to bulk and single-cell RNA sequencing. Differentially expressed genes and pathways were investigated and validated using tissue specimens from the xenograft model, 23 patients with matched primary/recurrent tumors, and a cohort including 190 glioblastoma patients. Functional investigations were performed in vitro with multiple patient-derived cell cultures. RESULTS: Tumor resection induced microglia/macrophage infiltration, angiogenesis as well as proliferation and upregulation of several stem cell-related genes in recurrent tumor cells. Expression changes of selected genes SOX2, POU3F2, OLIG2, and NOTCH1 were validated at the protein level in xenografts and early recurrent patient tumors. Single-cell transcriptomics revealed the presence of distinct phenotypic cell clusters in recurrent tumors which deviated from clusters found in primary tumors. Recurrent tumors expressed elevated levels of pleiotrophin (PTN), secreted by both tumor cells and tumor-associated microglia/macrophages. Mechanistically, PTN could induce tumor cell proliferation, self-renewal, and the stem cell program. In glioblastoma patients, high PTN expression was associated with poor overall survival and identified as an independent prognostic factor. CONCLUSION: Surgical tumor resection is an iatrogenic driver of PTN-mediated self-renewal in glioblastoma tumor cells that promotes therapeutic resistance and tumor recurrence.

Fluorescein-guided resection of cerebral metastases is associated with greater tumor resection.

BACKGROUND: Sodium fluorescein (fluorescein) crosses a disrupted blood-brain barrier similarly to gadolinium contrast in contrast-enhancing cerebral tumors. When exposed to light with 560 nm wavelength during surgery, fluorescein emits a yellow-green fluorescent light that can be visualized through an operating microscope equipped with an appropriate emission filter. The distribution of the fluorescence correlates with the contrast on a gadolinium contrast-enhanced MRI. OBJECTIVE: The objective of this single-center retrospective study was to investigate if the use of fluorescein would increase the extent of resection and to examine if fluorescein guided resection influences postoperative neurological status. METHODS: During the study period from August 2014 to August 2018, 117 patients were operated for cerebral metastases. Of these, 56 operations were guided by fluorescein and 61 by traditional white light. All patients had an early postoperative MRI within 72 h after surgery. RESULTS: The use of fluorescein increased the extent of resection in patients with cerebral metastases. The use of fluorescein was not associated with increased postoperative sequelae or neurological damage regardless of underlying primary cancer. CONCLUSION: Fluorescein is a helpful supplement in the neurosurgical treatment of cerebral metastases.

Magnetic resonance elastography in normal pressure hydrocephalus-a scoping review.

BACKGROUND: Magnetic resonance elastography (MRE) of the brain allows quantitative measurement of tissue mechanics. Multiple studies are exploring possible applications in normal pressure hydrocephalus (NPH) in clinical and paraclinical contexts. This is of great interest in neurological surgery due to challenges related to diagnosis and prediction of treatment effects. In this scoping review, we present a topical overview and discuss the current literature, with particular attention to clinical implications and current challenges. METHODS: The protocol was based on the PRISMA extension for scoping reviews. After a systematic database search (PubMed, Embase, and Web of Science), the articles were screened for relevance. Thirty articles were subject to detailed screening, and key technical and clinical data items were extracted. The inclusion criteria included the use of MRE on human subjects with NPH. RESULTS: Seven articles were included in the final study. These studies had various objectives including the role of MRE in the assessment of regional elastic changes in NPH, shunt effect, and evaluation of NPH symptoms. MRE revealed patterns of mechanical changes in NPH that differed from other dementias. Regional MRE changes were associated with specific NPH signs and symptoms. Neurosurgical shunting caused partial normalization in tissue scaffold parameters. The studies were highly heterogeneous in technical aspects and design. CONCLUSION: MRE studies in NPH are still limited by few participants, variable cohorts, inconsistent methodologies, and technical challenges, but the approach shows great potential for future clinical application.

[Magnetic resonance elastography of the brain].

Magnetic resonance elastography (MRE) is a novel imaging modality allowing quantification of tissue consistency. Multiple trials have focused on the use of MRE to describe meningioma consistency prior to surgery and on improving diagnostic accuracy of normal pressure hydrocephalus and other dementias. MRE shows promising results, but still lacks direct clinical translational value. Within neurosurgery and neurosciences MRE could contribute and improve decision-making, diagnosis and treatment. Furthermore, the use of MRE will improve the basic understanding of neuroanatomy, physiology and pathology.

[Intraoperative neuromonitoring during brain surgery].

Intraoperative neuromonitoring is a perioperative method, supplementary to stealth navigation and fluorescence microscopic imaging in brain surgery. It allows cortical and subcortical mapping, hence real time identification of eloquent brain areas through electrical stimulation of the cerebral cortex and subcortical areas. The method allows for functional guidance during both awake and asleep neurosurgery and aids in optimizing the extent of resection of the relevant pathology while preserving neurological function as summarised in this review.

The levels of the serine protease HTRA1 in cerebrospinal fluid correlate with progression and disability in multiple sclerosis.

BACKGROUND: High Temperature Requirement Serine Protease A1 (HTRA1) degrades extracellular matrix molecules (ECMs) and growth factors. It interacts with several proteins implicated in multiple sclerosis (MS), but has not previously been linked to the disease. OBJECTIVE: Investigate the levels of HTRA1 in cerebrospinal fluid (CSF) in different subtypes of MS and brain tissue. METHODS: Using ELISA, HTRA1 levels were compared in CSF from untreated patients with relapsing-remitting MS (RRMS, n = 23), secondary progressive MS (SPMS, n = 26) and healthy controls (HCs, n = 26). The effect of disease modifying therapies (DMTs) were examined in both patient groups. Cellular distribution in human brain was studied using immunochemistry and the oligointernode database, based on a single-nuclei RNA expression map. RESULTS: HTRA1 increased in RRMS and SPMS compared to HCs. DMT decreased HTRA1 levels in both types of MS. Using ROC analysis, HTRA1 cut-offs could discriminate HCs from RRMS patients with 100% specificity and 82.6% sensitivity. In the brain, HTRA1 was expressed in glia and neurons. CONCLUSION: HTRA1 is a promising CSF biomarker for MS correlating with disease- and disability progression. Most cell species of the normal and diseased CNS express HTRA1 and the expression pattern could reflect pathological processes involved in MS pathogenesis.

Endoscopic vs. microscopic transsphenoidal pituitary surgery: a single centre study.

Endoscopic pituitary surgery has shown promising results. This study reports the experiences of experienced microscopic pituitary surgeons changing to the endoscopic technique, and the beneficial effects on the postoperative outcomes. 45 transsphenoidal endoscopic-assisted surgeries performed in 2016-2017 were compared with 195 microscope-assisted surgeries performed in 2007-2017 for pituitary adenoma. Tumour size, hormonal status and vision were assessed preoperatively and 3-5 months postoperatively. Cases were identified through electronic patient records. GTR was achieved in 39% of the endoscopic operations vs. 22% of microscopic operations, p = 0.018. Mean duration of surgery was 86 min (77-95) with the endoscopic technique vs. 106 min (101-111) with the microscopic technique, p < 0.001. New hypothalamus-pituitary-adrenal axis deficiencies were observed after 3% of endoscopic vs. 34% microscopic operations, p = 0.001, and overall fewer postoperative pituitary deficiencies were observed in the endoscope-assisted group. Complications within 30 days of surgery occurred in 17% of endoscopic operations vs. 27% of microscopic operations (p > 0.05). Normalization of visual impairment occurred in 37% of the cases with preoperative visual impairment in the endoscopic group vs. 35% of those in the microscopic group (p > 0.05). The endoscopic technique performed better as a surgical procedure for pituitary adenomas. We found no statistically significant differences in complication rate or visual improvement between the two techniques.