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Background Listeria monocytogenes is an opportunistic gram-positive, facultative intracellular bacterium that causes invasive diseases mostly in pregnant women and immunosuppressed patients. Despite the predilection toward the central nervous system (CNS), it usually causes meningitis and meningoencephalitis, whereas brain abscesses are very uncommon.Case presentation We describe the case of a 69-year-old homeless patient with a brain abscess due to L. monocytogenes who was successfully treated surgically by a guided stereotactic aspiration and antibiotic therapy with ampicillin and gentamicin. Our patient was discharged after 4 weeks of therapy without neurologic deficits. Additionally, we provide a review of the literature of brain abscesses caused by L. monocytogenes.Conclusions This case highlights the need to drain cerebral abscesses and culture pus to correctly treat patients with antibiotics, especially given the high mortality rate of this infectious entity.

OBJECTIVE With global aging, elective craniotomies are increasingly being performed in elderly patients. There is a paucity of prospective studies evaluating the impact of these procedures on the geriatric population. The goal of this study was to assess the safety of elective craniotomies for elderly patients in modern neurosurgery. METHODS For this cohort study, adult patients, who underwent elective craniotomies between November 1, 2011, and October 31, 2018, were allocated to 3 age groups (group 1, < 65 years [n = 1008], group 2, ≥ 65 to < 75 [n = 315], and group 3, ≥ 75 [n = 129]). Primary outcome was the 30-day mortality after craniotomy. Secondary outcomes included rate of delayed extubation (> 1 hour), need for emergency head CT scan and reoperation within 48 hours after surgery, length of postoperative intensive or intermediate care unit stay, hospital length of stay (LOS), and rate of discharge to home. Adjustment for American Society of Anesthesiologists Physical Status (ASA PS) class, estimated blood loss, and duration of surgery were analyzed as a comparison using multiple logistic regression. For significant differences a post hoc analysis was performed. RESULTS In total, 1452 patients (mean age 55.4 ± 14.7 years) were included. The overall mortality rate was 0.55% (n = 8), with no significant differences between groups (group 1: 0.5% [95% binominal CI 0.2%, 1.2%]; group 2: 0.3% [95% binominal CI 0.0%, 1.7%]; group 3: 1.6% [95% binominal CI 0.2%, 5.5%]). Deceased patients had a significantly higher ASA PS class (2.88 ± 0.35 vs 2.42 ± 0.62; difference 0.46 [95% CI 0.03, 0.89]; p = 0.036) and increased estimated blood loss (1444 ± 1973 ml vs 436 ± 545 ml [95% CI 618, 1398]; p CONCLUSIONS Mortality following elective craniotomy was low in all age groups. Today, elective craniotomy for well-selected patients is safe, and for elderly patients, too. Elderly patients are more dependent on discharge to other hospitals and postacute care facilities after elective craniotomy. Clinical trial registration no.: NCT01987648 (clinicaltrials.gov).

ObjectiveTo assess the pathophysiologic changes in patients with spontaneous intracranial hypotension (SIH) based on measures of CSF dynamics, and on the duration of symptoms, in a retrospective case-controlled study.MethodsWe included consecutive patients investigated for SIH at our department from January 2012 to February 2018. CSF leak was considered confirmed if extrathecal contrast spillage was seen on imaging (CT or MRI) after intrathecal contrast application, or dural breach was detected by direct intraoperative visualization. We divided patients with a confirmed CSF leak into 3 groups depending on the symptom duration, as follows: ≤10, 11–52, and >52 weeks. Clinical characteristics and measures of CSF fluid dynamics obtained by computerized lumbar infusion testing were analyzed over time and compared with a reference population.ResultsAmong the 137 patients included, 69 had a confirmed CSF leak. Whereas 93.1% with 10 weeks of symptoms did (p = 0.004). Analysis of infusion tests revealed differences between groups with different symptom duration for CSF outflow resistance (p < 0.001), lumbar baseline pressure (p = 0.013), lumbar plateau pressure (p < 0.001), baseline pressure amplitude (p = 0.021), plateau pressure amplitude (p = 0.001), pressure–volume index (p = 0.001), elastance (p < 0.001), and CSF production rate (p = 0.001). Compared to the reference population, only patients with acute symptoms showed a significantly altered CSF dynamics profile.ConclusionA CSF leak dramatically alters CSF dynamics acutely, but the pattern changes over time. There is an association between the clinical presentation and changes in CSF dynamics.

Glioblastoma multiforme (GBM) remains one of the tumors with the worst prognosis. In recent years, a better overall survival (OS) has been described in cases subjected to Gross Total Resection (GTR) that were presenting hypermethylation of Methylguanine-DNA methyltransferase (MGMT) promoter. Recently, also the expression of specific miRNAs involved in MGMT silencing has been related to survival. In this study, we evaluate MGMT expression by immunohistochemistry (IHC), MGMT promoter methylation and miRNA expression in 112 GBMs and correlate the data to patients’ clinical outcomes. Statistical analyses demonstrate a significant association between positive MGMT IHC and the expression of miR-181c, miR-195, miR-648 and miR-767.3p between unmethylated cases and the low expression of miR-181d and miR-648 and between methylated cases and the low expression of miR-196b. Addressing the concerns of clinical associations, a better OS has been described in presence of negative MGMT IHC, in methylated patients and in the cases with miR-21, miR-196b overexpression or miR-767.3 downregulation. In addition, a better progression-free survival (PFS) is associated with MGMT methylation and GTR but not with MGMT IHC and miRNA expression. In conclusion, our data reinforce the clinical relevance of miRNA expression as an additional marker to predict efficacy of chemoradiation in GBM.

INTRODUCTION The CeTeG/NOA-09 trial demonstrated superior median overall survival (mOS, 48.1 months) in MGMT-methylated glioblastoma treated with lomustine/temozolomide compared to temozolomide. We retrospectively analyzed an off-study cohort of patients treated with lomustine/temozolomide to gather real-world data on this new regimen. METHODS Adult patients from 20 centers in Germany, Austria and Switzerland were included. Inclusion criteria were MGMT-methylated IDHwt glioblastoma newly diagnosed prior to end of 2020, and lomustine/temozolomide treatment as part of first-line therapy. RESULTS 321 patients with a median age of 57 years (range, 21-78) and a median follow-up of 19.9 months were included. In the whole cohort, mOS was 41.0 months (95%CI, 33.0 – not reached). In patients starting lomustine/temozolomide immediately upon initiation of radiotherapy strictly following the CeTeG protocol (88%), mOS was 52.8 months (35.8 – not reached) as compared to 24.6 months (17.6 – not reached) in patients starting lomustine/temozolomide after completion of radiotherapy/concomitant temozolomide (12%, logrank test: p = 0.06). Patients with a KPS < 80 had a shorter mOS of 19.7 months (95%CI, 16.6 – not reached) compared to 41.0 months (33.0 – not reached, p = 0.009) in KPS 80-100. Gross total resection (GTR, 53.9%) was associated with longer mOS (52.8 months, 95%CI 24.1 – not reached) compared to partial resection/biopsy (30.5 months, 95%CI 36.8 – not reached, p=0.004). Multivariable Cox regression analysis confirmed GTR (HR 0.66, p = 0.033) and younger age ( ≤ 50 years: HR 0.42, p = 0.001), but not KPS (80-100 vs. lower: HR 0.66, p = 0.12) as independent prognostic factors. DISCUSSION In this real-world multicenter cohort, survival was similar to the promising results of CeTeG/NOA-09. Further analyses should investigate a potentially reduced benefit from lomustine/temozolomide in patients with low KPS/no GTR and a possible detrimental effect from deferred lomustine/temozolomide initiation. The median follow-up is admittedly short, updated data will be presented.

Elderly patients constitute an expanding part of our society. Due to a continuously increasing life expectancy, an optimal quality of life is expected even into advanced age. Glioblastoma (GBM) is more common in older patients, but they are still often withheld from efficient treatment due to worry of worse tolerance and have a significantly worse prognosis compared to younger patients. Our retrospective observational study aimed to investigate the therapeutic benefit from a second resection in recurrent glioblastoma of elderly patients. We included a cohort of 39 elderly patients (> 65 years) with a second resection as treatment option in the case of a tumor recurrence. A causal inference model was built by multiple non- and semiparametric models, which was used to identify matched patients from our elderly GBM database which comprises 538 patients. The matched cohorts were analyzed by a Cox-regression model adjusted by time-dependent covariates. The Cox-regression analysis showed a significant survival benefit (Hazard Ratio: 0.6, 95% CI 0.36–0.9, p-value = 0.0427) for the re-resected group (18.0 months, 95% CI 13.97–23.2 months) compared to the group without re-resection (10.1 months, 95% CI 8.09–20.9 months). No differences in the co-morbidities or hemato-oncological side effects during chemotherapy could be detected. Anesthetic- and surgical complications were rare and comparable to the complication rate of patients undergoing the first-line resection. Taken together, in elderly patients, re-resection is an acceptable treatment option in the recurrent state of a glioblastoma. The individual evaluation of the patients′ medical status as well as the chances of withstanding general anesthesia needs to be done in close interdisciplinary consultation. If these requirements are met, elderly patients benefit from a re-resection.

Acta neurochirurgica 163(4), 937-945 (2021). doi:10.1007/s00701-020-04623-z special issue: "Tumor - Glioma", Published by Springer, Wien [u.a.]

BMC cancer 20, 818 (2020). doi:10.1186/s12885-020-07290-6, Published by BioMed Central, London

Object: The treatment of choice in glioblastoma (GBM) is the maximal surgical extent of resection (EOR) followed by adjuvant chemo-radiotherapy. Furthermore, methylguanine-DNA methyltransferase (MGMT) promoter methylation is associated with prolonged overall survival (OS) and progression free survival (PFS). The objective of the present study is correlate the biomolecular aspects in relation with EOR. Materials and methods: We analyzed a series of 116 patients with IDH-1 wild type GBM and different EOR (Gross Total Resection—GTR-, Partial Resection—PR- and Biopsy), treated with adjuvant chemo-radiotherapy. The MGMT status was analyzed in terms of promoter methylation and protein expression. Results: When GTR was possible, OS and PFS were significantly better compared to the other two groups (p = 0.001 and p = 0.035, respectively). MGMT methylation was significantly associated with better OS in the biopsy group (p = 0.022) and better OS and PFS in PR (p = 0.02 and p = 0.012, respectively), but not in the GTR group (p = 0.252 for OS, p = 0.256 for PFS) nor the PFS in the biopsy group (p = 0.259). MGMT protein expression levels do not show any association with OS and PFS, regardless of the type of surgery. Conclusions: Our study confirms the positive association of a safe maximal EOR with better OS and PFS, and indicates a positive prognostic value of MGMT methylation status only in case of the presence of residual tumor tissue. MGMT protein expression seems not to play a clinical role in relation with the type of surgery.

Objective Spontaneous intracranial hypotension is caused by spinal cerebrospinal fluid leakage. Patients with orthostatic headaches and cerebrospinal fluid leakage show a decrease in optic nerve sheath diameter upon movement from supine to upright position. We hypothesized that the decrease in optic nerve sheath diameter upon gravitational challenge would cease after closure of the leak. Methods We included 29 patients with spontaneous intracranial hypotension and refractory symptoms admitted from 2013 to 2016. The systematic workup included: Optic nerve sheath diameter sonography, spinal MRI and dynamic myelography with subsequent CT. Microsurgical sealing of the cerebrospinal fluid leak was the aim in all cases. Results Of 29 patients with a proven cerebrospinal fluid leak, one declined surgery. A single patient was lost to follow-up. In 27 cases, the cerebrospinal fluid leak was successfully sealed by microsurgery. The width of the optic nerve sheath diameter in supine position increased from 5.08 ± 0.66 mm before to 5.36 ± 0.53 mm after surgery ( p = 0.03). Comparing the response of the optic nerve sheath diameter to gravitational challenge, there was a significant change from before (−0.36 ± 0.32 mm) to after surgery (0.00 ± 0.19 mm, p Conclusions The sonographic assessment of the optic nerve sheath diameter with gravitational challenge can distinguish open from closed spinal cerebrospinal fluid fistulas in spontaneous intracranial hypotension patients. A response to the gravitational challenge, that is, no more collapse of the optic nerve sheath while standing up, can be seen after successful treatment and correlates with the resolution of clinical symptoms. Sonography of the optic nerve sheath diameter may be utilized for non-invasive follow-up in spontaneous intracranial hypotension.