Surgical closure of spinal cerebrospinal fluid leaks improves symptoms in patients with superficial siderosis.

BACKGROUND AND PURPOSE: Spinal cerebrospinal fluid (CSF) leaks may cause a myriad of symptoms, most common being orthostatic headache. In addition, ventral spinal CSF leaks are a possible etiology of superficial siderosis (SS), a rare condition characterized by hemosiderin deposits in the central nervous system (CNS). The classical presentation of SS involves ataxia, bilateral hearing loss, and myelopathy. Unfortunately, treatment options are scarce. This study was undertaken to evaluate whether microsurgical closure of CSF leaks can prevent further clinical deterioration or improve symptoms of SS. METHODS: This cohort study was conducted using data from a prospectively maintained database in two large spontaneous intracranial hypotension (SIH) referral centers in Germany and Switzerland of patients who meet the modified International Classification of Headache Disorders, 3rd edition criteria for SIH. Patients with spinal CSF leaks were screened for the presence of idiopathic infratentorial symmetric SS of the CNS. RESULTS: Twelve patients were included. The median latency between the onset of orthostatic headaches and symptoms attributed to SS was 9.5 years. After surgical closure of the underlying spinal CSF leak, symptoms attributed to SS improved in seven patients and remained stable in three. Patients who presented within 1 year after the onset of SS symptoms improved, but those who presented in 8-12 years did not improve. We could show a significant association between patients with spinal longitudinal extrathecal collections and SS. CONCLUSIONS: Long-standing untreated ventral spinal CSF leaks can lead to SS of the CNS, and microsurgical sealing of spinal CSF leaks might stop progression and improve symptoms in patients with SS in a time-dependent manner.

Surgery for IDH1/2 wild-type glioma invading the corpus callosum.

BACKGROUND: Glioblastoma of the corpus callosum (ccGBM) are rare tumors, with a dismal prognosis marked by a rapid clinical deterioration. For a long time, surgical treatment was not considered beneficial for most patients with such tumors. Recent studies claimed an improved survival for patients undergoing extensive resection, albeit without integration of the molecular profile of the lesions. The purpose of this study was to investigate the effect of biopsy and surgical resection on oncological and functional outcomes in patients with IDH wild-type ccGBM. METHODS: We performed a retrospective analysis of our institution's database of patients having been treated for high-grade glioma between 2005 and 2017. Inclusion criteria were defined as follows: patients older than 18 years, histopathological, and molecularly defined IDH wild-type glioma, major tumor mass (at least 2/3) invading the corpus callosum in the sagittal plane with a uni- or bilateral infiltration of the adjacent lobules. Surgical therapy (resection vs. biopsy), extent of resection according to the remaining tumor volume and adjuvant treatment as well as overall survival and functional outcome using the Karnofsky Performance Score (KPS) were analyzed. RESULTS: Fifty-five patients were included in the study, from which the mean age was 64 years and men (n = 34, 61.8%) were more often affected than women (n = 21, 38.2%). Thirty (54.5%) patients were treated with stereotactic biopsy alone, while 25 patients received tumor resection resulting in 14.5% (n = 8) gross-total resections and 30.9% (n = 17) partial resections. The 2-year survival rate after resection was 30% compared to 7% after biopsy (p = 0.047). The major benefit was achieved in the group with gross-total resection, while partial resection failed to improve survival. Neurological outcome measured by KPS did not differ between both groups either pre- or postoperatively. CONCLUSIONS: Our study suggests that in patients with corpus callosum glioblastoma, gross-total resection prolongs survival without negatively impacting neurological outcome as compared to biopsy.

Characterization of longitudinal transformation of T2-hyperintensity in oligodendroglioma.

BACKGROUND: Oligodendroglioma (ODG) are CNS resistant tumors characterized by their unique molecular signature, namely a combined deletion of 1p and 19q simultaneously to an IDH1/2 mutation. These tumors have a more favorable clinical outcome compared to other gliomas and a long-time survival that ranges between 10 and 20 years. However, during the course of the disease, multiple recurrences occur and the optimal treatment at each stage of the disease remains unclear. Here we report a retrospective longitudinal observation study of 836 MRI examinations in 44 ODG patients. METHODS: We quantified the volume of T2-hyperintensity to compute growth behavior in dependence of different treatment modalities, using various computational models. RESULTS: The identified growth pattern revealed dynamic changes, which were found to be patient-specific an did not correlate with clinical parameter or therapeutic interventions. Further, we showed that, surgical resection is beneficial for overall survival regardless the WHO grad or timepoint of surgery. To improve overall survival, an extent of resection above 50% is required. Multiple resections do not generally improve overall survival, except a greater extent of resection than in previous surgeries was achieved. CONCLUSIONS: Our data aids to improve the interpretation of MRI images in clinical practice.

Resection of recurrent glioblastoma multiforme in elderly patients: a pseudo-randomized analysis revealed clinical benefit.

INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Sonography of the optic nerve sheath diameter before and after microsurgical closure of a dural CSF fistula in patients with spontaneous intracranial hypotension - a consecutive cohort study.

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 < 0.01). In parallel, spontaneous intracranial hypotension-related symptoms resolved in 26, decreased in one and persisted in a single patient despite recovery of gait. 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.

Clinical Relevance and Interplay between miRNAs in Influencing Glioblastoma Multiforme Prognosis.

Glioblastoma multiforme (GBM) is usually treated with surgery followed by adjuvant partial radiotherapy combined with temozolomide (TMZ) chemotherapy. Recent studies demonstrated a better survival and good response to TMZ in methylguanine-DNA methyltransferase (MGMT)-methylated GBM cases. However, approximately 20% of patients with MGMT-unmethylated GBM display an unexpectedly favorable outcome. Therefore, additional mechanisms related to the TMZ response need to be investigated. As such, we decided to investigate the clinical relevance of six miRNAs involved in brain tumorigenesis (miR-181c, miR-181d, miR-21, miR-195, miR-196b, miR-648) as additional markers of response and survival in patients receiving TMZ for GBM. We evaluated miRNA expression and the interplay between miRNAs in 112 IDH wt GBMs by applying commercial assays. Then, we correlated the miRNA expression with patients' clinical outcomes. Upon bivariate analyses, we found a significant association between the expression levels of the miRNAs analyzed, but, more interestingly, the OS curves show that the combination of low miR-648 and miR-181c or miR-181d expressions is associated with a worse prognosis than cases with other low-expression miRNA pairs. To conclude, we found how specific miRNA pairs can influence survival in GBM cases treated with TMZ.

Identification of MGMT Downregulation Induced by miRNA in Glioblastoma and Possible Effect on Temozolomide Sensitivity.

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.

Cerebral Abscess Caused by Listeria monocytogenes: Case Report and Literature Review.

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.

Hydrocephalus Shunting in Supratentorial Glioblastoma: Functional Outcomes and Management.

BACKGROUND: Glioblastoma is the most common and the most challenging to treat adult primary central nervous system tumor. Although modern management strategies modestly improved the overall survival, the prognosis remains dismal associated with poor life quality and the clinical course often dotted by treatment side effects and cognitive decline. Functional deterioration might be caused by obstructive or communicating hydrocephalus but due to poor overall prognosis surgical treatment options are often limited and its optimal management strategies remain elusive. We aimed to investigate risk factors, treatment options and outcomes for tumor-associated hydrocephalus in a contemporary 10 years cohort of glioblastoma patients. METHODS: We reviewed electronic health records of 1800 glioblastoma patients operated at the Department of Neurosurgery, Medical Center - University of Freiburg from 2009 to 2019. Demographics, clinical characteristics and radiological features were analyzed. Univariate analysis for nominal variables was performed either by Fisher's exact test or Chi-square test, as appropriate. RESULTS: We identified 39 glioblastoma patients with symptomatic communicating hydrocephalus treated by ventricular shunting (incidence 2.1%). Opening of the ventricular system during a previous tumor resection was associated with symptomatic hydrocephalus (p<0.05). There was also a trend toward location (frontal and temporal) and larger tumor volume. Number of craniotomies before shunting was not considered as a risk factor. Shunting improved hydrocephalus symptoms in 95% of the patients and Karnofsky Performance Score (KPS) could be restored after shunting. Of note, 75% of the patients had a post-shunting oncological treatment such as radiotherapy or chemotherapy, most prevalently chemotherapy. Infection (7.7%) and over- or under drainage (17.9%) were the most common complications requiring shunt revision in ten patients (25.6%), No peritoneal metastasis was found. The median overall survival (OS) was 385 days and the median post shunting survival was 135 days. CONCLUSION: Ventricular system opening was identified as a risk factor for communicating hydrocephalus in glioblastoma patients. Although glioblastoma treatment remains challenging, shunting improved hydrocephalus-related functional status and may be considered even in a palliative setting for symptom relief.

How safe are elective craniotomies in elderly patients in neurosurgery today? A prospective cohort study of 1452 consecutive cases.

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 <0.001). Significant differences were found in the rate of postoperative head CT scans (group 1: 6.65% [n = 67], group 2: 7.30% [n = 23], group 3: 15.50% [n = 20]; p = 0.006), LOS (group 1: median 5 days [IQR 4; 7 days], group 2: 5 days [IQR 4; 7 days], and group 3: 7 days [5; 9 days]; p = 0.001), and rate of discharge to home (group 1: 79.0% [n = 796], group 2: 72.0% [n = 227], and group 3: 44.2% [n = 57]; p < 0.001). 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).

Insights into the natural history of spontaneous intracranial hypotension from infusion testing.

OBJECTIVE: To 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. METHODS: We 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. RESULTS: Among the 137 patients included, 69 had a confirmed CSF leak. Whereas 93.1% with <10 weeks of symptoms displayed typical orthostatic headache, only 62.5% 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. CONCLUSION: A 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.

Postural changes in optic nerve and optic nerve sheath diameters in postural orthostatic tachycardia syndrome and spontaneous intracranial hypotension: A cohort study.

BACKGROUND: Postural orthostatic tachycardia syndrome is a disorder of the autonomic nervous system. Approximately 30% of patients experience orthostatic headaches. Orthostatic headaches also are a hallmark symptom in spontaneous intracranial hypotension. While the cause of orthostatic headaches in spontaneous intracranial hypotension can be linked to the cerebrospinal fluid loss at the spinal level and consecutively reduced intracranial pressure in the upright position, the cause of orthostatic headaches in postural orthostatic tachycardia syndrome still remains unknown. The present study examined orthostatic changes of intracranial pressure using dynamic ultrasound of the optic nerve and optic nerve sheath diameter in postural orthostatic tachycardia syndrome, spontaneous intracranial hypotension and healthy subjects. METHODS: Data was obtained from postural orthostatic tachycardia syndrome patients with (n = 7) and without orthostatic headaches (n = 7), spontaneous intracranial hypotension patients (n = 5) and healthy subjects (n = 8). All participants underwent high-resolution transorbital ultrasound in the supine and upright position to assess optic nerve and optic nerve sheath diameter. RESULTS: Group differences were found in percentage deviations when changing position of optic nerve sheath diameter (p < 0.01), but not regarding the optic nerve diameter. Pairwise comparisons indicated differences in optic nerve sheath diameter only between spontaneous intracranial hypotension and the other groups. No differences were found between postural orthostatic tachycardia syndrome patients with and without orthostatic headaches. CONCLUSION: This study shows that the size of the optic nerve sheath diameter dynamically decreases during orthostatic stress in spontaneous intracranial hypotension, but not in postural orthostatic tachycardia syndrome with or without orthostatic headaches, which indicates different underlying causes.

The Impact of Surgery in IDH 1 Wild Type Glioblastoma in Relation With the MGMT Deregulation.

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.

Alimentos e preparações culinárias regionais e da sociobiodiversidade na alimentação escolar brasileira: uma revisão integrativa / Regional and sociobiodiversity foods and culinary preparations in Brazilian school meals: an integrative review

Objetivo: Discutir como a temática dos alimentos e preparações culinárias regionais e da sociobiodiversidade está inserida na alimentação escolar pública brasileira, por meio do Programa Nacional de Alimentação Escolar (PNAE). Métodos: Revisão integrativa da literatura com buscas nas bases COCHRANE Library, EMBASE, SciELO, LILACS, PubMed/MEDLINE, Scopus, Web of Science e Google Acadêmico. A coleta de artigos foi realizada durante os meses de junho e julho de 2022 e limitou-se a estudos publicados no período entre 2009 e 2022. Os artigos foram agregados em categorias segundo o enfoque ou objetivo de estudo. Resultados: Foram encontrados 2881 resultados e incluídos 21 artigos. Observou-se predominância de abrangência local nos estudos e abordagem qualitativa (42,8%; n=9), com maior recorrência da categoria "presença nos cardápios do PNAE'' (38,1%; n=8), seguido pelas categorias ''interação com os diferentes atores do PNAE" (33,3%; n=7) e "testes de aceitabilidade com estudantes do PNAE'' (28,6%; n=6).  Conclusão: Observou-se a insuficiência de estudos sobre esta temática e, dentre os artigos encontrados, pontua-se a heterogeneidade e fragilidade no arcabouço teórico e nos procedimentos metodológicos. Recomenda-se a realização de mais estudos na área com o objetivo de obter um panorama mais amplo da situação atual da temática no PNAE e explorar as potencialidades dos alimentos e preparações culinárias regionais e da sociobiodiversidade na alimentação escolar brasileira. (AU)

Objective: To discuss how the theme of regional food and culinary preparations and socio-biodiversity is inserted in Brazilian public school feeding, through the National School Feeding Program (PNAE). Method: Integrative literature review with searches in the COCHRANE Library, EMBASE, SciELO, LILACS, PubMed/MEDLINE, Scopus, Web of Science and Google Scholar databases. The collection of articles was carried out in the months of June and July 2022 and was limited to studies published in the period between 2009 and 2022. The articles were aggregated into categories according to the focus or objective of the study. Results: 2881 results were found and 21 articles were included. There was a predominance of local coverage in the studies and a qualitative approach (42.8%; n=9), with greater recurrence of the category ''presence in the PNAE menus'' (38.1%; n=8), followed by categories ''interaction with different PNAE actors'' (33.3%; n=7) and ''acceptability tests with PNAE students'' (28.6%; n=6). Conclusion: There was a lack of studies on this subject and, among the articles found, heterogeneity and fragility in the theoretical framework and methodological procedures were highlighted. It is recommended that further studies be carried out in the area with the aim of obtaining a broader view of the current situation of the theme in the PNAE and exploring the potential of regional food and culinary preparations and socio-biodiversity in Brazilian school feeding. (AU)