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Background and purpose: We aimed to assess the course and predictors of functional outcome after single and multiple intracerebral hemorrhage (ICH) in pediatric patients with cerebral cavernous malformations (CCMs) and to conduct a risk assessment of a third bleed during the first follow-up year after second ICH. Methods: We included patients aged ≤18 years with complete baseline characteristics, a magnetic resonance imaging dataset, ≥1 CCM-related ICH and ≥1 follow-up examination, who were treated between 2003 and 2021. Neurological functional status was obtained using modified Rankin Scale scores at diagnosis, before and after each ICH, and at last follow-up. Kaplan–Meier analysis was performed to determine the cumulative 1-year risk of third ICH. Results: A total of 55 pediatric patients (median [interquartile range] age 12 [11] years) were analyzed. Univariate analysis identified brainstem cavernous malformation (BSCM; p = 0.019) as a statistically significant predictor for unfavorable outcome after second ICH. Outcome after second ICH was significantly worse in 12 patients (42.9%; p = 0.030) than after first ICH and in five patients (55.6%; p = 0.038) after a third ICH compared to a second ICH. Cumulative 12-month risk of rebleeding during the first year after a second ICH was 10.7% (95% confidence interval 2.8%–29.37%). Conclusions: Pediatric patients with a BSCM have a higher risk of worse outcome after second ICH. Functional outcome improves over time after an ICH but worsens following each ICH compared to baseline or previous ICH. Second bleed was associated with neurological deterioration compared to initial ICH, and this deteriorated further after a third ICH. in press

Background and purpose: The purpose of this study was to investigate the 5-year risk of a third bleeding event in cavernous malformations (CMs) of the central nervous system. Methods: Patients with cerebral or spinal CMs treated between 2003 and 2021 were screened using our institutional database. Patients with a complete magnetic resonance imaging dataset, clinical baseline characteristics, and history of two bleeding events were included. Patients who underwent surgical CM removal were excluded. Neurological functional status was obtained using the modified Rankin Scale score at the second and third bleeding. Kaplan–Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for a third haemorrhage. Results: Forty-two patients were included. Cox regression analysis adjusted for age and sex did not identify risk factors for a third haemorrhage. 37% of patients experienced neurological deterioration after the third haemorrhage (p = 0.019). The cumulative 5-year risk of a third bleeding was 66.7% (95% confidence interval [CI] 50.4%–80%) for the whole cohort, 65.9% (95% CI 49.3%–79.5%) for patients with bleeding at initial diagnosis, 72.7% (95% CI 39.3%–92.7%) for patients with a developmental venous anomaly, 76.9% (95% CI 55.9%–90.3%) for patients with CM localization to the brainstem and 75% (95% CI 50.6%–90.4%) for patients suffering from familial CM disease. Conclusions: During an untreated 5-year follow-up after a second haemorrhage, a significantly increased risk of a third haemorrhage compared to the known risk of a first and second bleeding event was identified. The third bleeding was significantly associated with neurological deterioration. These findings may justify a surgical treatment after a second bleeding event. in press

OBJECTIVE The objective of this study was to analyze the impact of medication intake on hemorrhage risk in patients with familial cerebral cavernous malformation (FCCM). METHODS The authors’ institutional database was screened for patients with FCCM who had been admitted to their department between 2003 and 2020. Patients with a complete magnetic resonance imaging (MRI) data set, evidence of multiple CCMs, clinical baseline characteristics, and follow-up (FU) examination were included in the study. The authors assessed the influence of medication intake on first or recurrent intracerebral hemorrhage (ICH) using univariate and multivariate logistic regression adjusted for age and sex. The longitudinal cumulative 5-year risk of hemorrhage was calculated by applying Kaplan-Meier and Cox regression analyses adjusted for age and sex. RESULTS Two hundred five patients with FCCMs were included in the study. Multivariate Cox regression analysis revealed ICH as a predictor for recurrent hemorrhage during the 5-year FU. The authors also noted a tendency toward a decreased association with ICH during FU in patients on statin medication (HR 0.22, 95% CI 0.03–1.68, p = 0.143), although the relationship was not statistically significant. No bleeding events were observed in patients on antithrombotic therapy. Kaplan-Meier analysis and log-rank test showed a tendency toward a low risk of ICH during FU in patients on antithrombotic therapy (p = 0.085), as well as those on statin therapy (p = 0.193). The cumulative 5-year risk of bleeding was 22.82% (95% CI 17.33%–29.38%) for the entire cohort, 31.41% (95% CI 23.26%–40.83%) for patients with a history of ICH, 26.54% (95% CI 11.13%–49.7%) for individuals on beta-blocker medication, 6.25% (95% CI 0.33%–32.29%) for patients on statin medication, and 0% (95% CI 0%–30.13%) for patients on antithrombotic medication. CONCLUSIONS ICH at diagnosis was identified as a risk factor for recurrent hemorrhage. Although the relationships were not statistically significant, statin and antithrombotic medication tended to be associated with decreased bleeding events.

Background and Purpose: The purpose of this study was to investigate the natural course of cerebral cavernous malformations (CCM) in the pediatric population, with special emphasis on the risk of first and recurrent bleeding over a 5-year period. Methods: Our institutional database was screened for patients with CCM treated between 2003 and 2020. Patients ≤18 years of age with complete magnetic resonance imaging data set, clinical baseline characteristics, and ≥1 follow-up examination were included. Surgically treated individuals were censored after CCM removal. We assessed the impact of various parameters on first or recurrent intracerebral hemorrhage (ICH) at diagnosis using univariate and multivariate logistic regression adjusted for age and sex. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for (re)hemorrhage. Results: One hundred twenty-nine pediatric patients with CCM were analyzed. Univariate logistic regression identified brain stem CCM (odds ratio, 3.15 [95% CI, 1.15−8.63]; P =0.026) and familial history of CCM (odds ratio, 2.47 [95% CI, 1.04−5.86]; P =0.041) as statistically significant predictors of ICH at diagnosis. Multivariate logistic regression confirmed this correlation (odds ratio, 3.62 [95% CI, 1.18−8.99]; P =0.022 and odds ratio, 2.53 [95% CI, 1.07−5.98]; P =0.035, respectively). Cox regression analysis identified ICH as mode of presentation (hazard ratio, 14.01 [95% CI, 1.80−110.39]; P =0.012) as an independent predictor for rehemorrhage during the 5-year follow-up. The cumulative 5-year risk of (re)bleeding was 15.9% (95% CI, 10.2%−23.6%) for the entire cohort, 30.2% (20.2%−42.3%) for pediatric patients with ICH at diagnosis, and 29.5% (95% CI, 13.9%−51.1%) for children with brain stem CCM. Conclusions: Pediatric patients with brain stem CCM and familial history of CCM have a higher risk of ICH as mode of presentation. During untreated 5-year follow-up, they revealed a similar risk of (re)hemorrhage compared to adult patients. The probability of (re)bleeding increases over time, especially in cases with ICH at presentation or brain stem localization.

in press Background and Purpose Analyze and compare the natural course of confirmed familial cerebral cavernous malformation (FCCM), assumed FCCM and non-familial multiple cerebral cavernous malformation (CCM) disease over a 5-year period. Methods Our institutional database was screened for patients with CCM admitted between 2003 and 2020. Patients with complete magnetic resonance imaging dataset, evidence of multiple CCM, clinical baseline characteristics, and follow-up examination were included. Patients were separated into confirmed familial cases, assumed familial cases or non-familial multiple cavernous malformations. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for hemorrhage and recurrent hemorrhage. Results A total of 238 patients with multiple CCM were analyzed; 90 individuals had a confirmed FCCM disease, 115 an assumed FCCM, and 33 were allocated to the non-FCCM group. Univariate Cox regression analysis identified intracerebral hemorrhage (ICH) as mode of presentation (p = 0.001) as a predictor for occurrence of recurrent hemorrhage during the 5-year follow-up (FU). The cumulative 5-year risk of (re)bleeding was 21.6% for the entire cohort, 30.7% for patients with ICH at diagnosis, 22.1% for those patients with a confirmed diagnosis of FCCM, 23.5% for those with an assumed FCCM, and 21% for the non-FCCM cases. Conclusions FCCM patients with ICH at diagnosis are prone to develop rebleeding. During untreated 5-year FU, FCCM patients and patients with sporadic multiple CCM reveal an almost equal susceptibility for (re)hemorrhage. Moreover, confirmed, assumed and non-FCCM patients showed an equal cumulative 5-year risk of symptomatic ICH. The probability of hemorrhage tends to increase over time, particularly in cases with ICH at presentation.

Background and ObjectivesFemale hormone therapy (oral contraception in female patients of reproductive age and menopausal hormone therapy in postmenopausal patients) is not withheld from patients with cerebral cavernous malformations (CCMs), although the effects of these drugs on the risk of intracranial hemorrhage are unknown. We investigated the association between female hormone therapy and intracranial hemorrhage in female patients with CCM in 2 large prospective, multicenter, observational cohort studies.MethodsWe included consecutive patients with a CCM. We compared the association between use of female hormone therapy and the occurrence of intracranial hemorrhage due to the CCM during up to 5 years of prospective follow-up in multivariable Cox proportional hazards regression. We performed an additional systematic review through Ovid MEDLINE and Embase from inception to November 2, 2021, to identify comparative studies and assess their intracranial hemorrhage incidence rate ratio according to female hormone therapy use.ResultsOf 722 female patients, aged 10 years or older at time of CCM diagnosis, 137 used female hormone therapy at any point during follow-up. Female hormone therapy use (adjusted for age, mode of presentation, and CCM location) was associated with an increased risk of subsequent intracranial hemorrhage (46/137 [33.6%] vs 91/585 [15.6%] and adjusted hazard ratio 1.56, 95% CI 1.09–2.24;p= 0.015). Use of oral contraceptives in female patients aged 10–44 years adjusted for the same factors was associated with a higher risk of subsequent intracranial hemorrhage (adjusted hazard ratio 2.00, 95% CI 1.26–3.17;p= 0.003). Our systematic literature search showed no studies reporting on the effect of female hormone therapy on the risk of intracranial hemorrhage during follow-up.DiscussionFemale hormone therapy use is associated with a higher risk of intracranial hemorrhage from CCMs. These findings raise questions about the safety of female hormone therapy in clinical practice in patients with CCM. Further studies evaluating clinical factors raising risk of thrombosis may be useful to determine which patients may be most susceptible to intracranial hemorrhage.Classification of EvidenceThis study provides Class III evidence that female hormone therapy use is associated with a higher risk of intracranial hemorrhage in patients with CCM.

To evaluate the predictive value of intraoperative neuromonitoring (IONM) in brainstem cavernous malformation (BSCM) surgery.Surgically treated patients with BSCM were included. All patients received IONM consisting of motor-evoked potentials (MEPs) and somatosensory-evoked potentials (SSEPs). Neurologic examination was conducted preoperatively and at discharge and follow-up3 months after BSCM removal. Demographic, radiographic, and clinical features were assessed. Study end points were new motor or somatosensory deficits and functional disability.A total of 62 patients were included. MEP decrease was associated with new motor deficits at discharge (P = 0.022), and SSEP decrease was associated with new somatosensory deficits at discharge (P0.001) and follow-up (P0.001). Sensitivity and specificity values for MEPs (discharge: 31% and 93%; follow-up: 33% and 91%) and SSEPs (discharge: 82% and 80%; follow-up: 85% and 79%) were calculated, respectively. Receiver operating characteristic analyses with area under the curve (AUC) metrics revealed acceptable performance of MEPs (AUC, 0.75; P = 0.022) and SSEPs (AUC, 0.72; P = 0.004) in predicting early deficits. Intraoperative decrease of MEPs (P = 0.047) and SSEPs (P = 0.017) was associated with early functional disability. Surgery-related subdural air accumulation impaired IONM reliability in predicting early (P = 0.048) and long-term (P = 0.013) deficits.Established IONM warning criteria may be valid for BSCM removal. However, surgical approaches in the sitting position significantly limit the predictive value of IONM, to some extent because of intraoperative pneumocephalus.

Purpose Spinal cavernous malformations (SCM) present a risk for intramedullary hemorrhage (IMH), which can cause severe neurologic deficits. Patient selection and time of surgery have not been clearly defined. Methods This observational study included SCM patients who underwent surgery in our department between 2003 and 2021. Inclusion required baseline clinical factors, magnetic resonance imaging studies, and follow-up examination. Functional outcome was assessed using the Modified McCormick scale score. Results Thirty-five patients met the inclusion criteria. The mean age was 44.7 ± 14.5 years, and 60% of the patients were male. In univariate analysis, the unfavorable outcome was significantly associated with multiple bleeding events (p = .031), ventral location of the SCM (p = .046), and incomplete resection (p = .028). The time between IMH and surgery correlated with postoperative outcomes (p = .004), and early surgery within 3 months from IMH was associated with favorable outcomes (p = .033). This association remained significant in multivariate logistic regression analysis (p = .041). Conclusions Removal of symptomatic SCM should be performed within 3 months after IMH when gross total resection is feasible. Patients with ventrally located lesions might be at increased risk for postoperative deficits.

Background and purpose: The aim was to investigate the effect of modifiable vascular risk factors on the risk of first and recurrent bleeding for patients with a cavernous malformation (CM) of the central nervous system (CNS) over a 10-year period. Methods: A retrospective review of our CM institutional database was performed spanning from 2003 to 2021. The inclusion criteria were non-missing serial magnetic resonance imaging studies and clinical baseline metrics such as vascular risk factors. The exclusion criteria were patients who underwent surgical CM removal and patients with less than a decade of follow-up. Kaplan–Meier and Cox regression analyses were performed to determine the cumulative risk (10 years) of hemorrhage. Results: Eighty-nine patients with a CM of the CNS were included. Our results showed a non-significant increased risk of hemorrhage during 10 years of follow-up in patients using nicotine (hazard ratio 2.11, 95% confidence interval 0.86–5.21) and in patients with diabetes (hazard ratio 3.25, 95% confidence interval 0.71–14.81). For the presence of modifiable vascular risk factors at study baseline different cumulative 10-year risks of bleeding were observed: arterial hypertension 42.9% (18.8%–70.4%); diabetes 66.7% (12.5%–98.2%); hyperlipidemia 30% (8.1%–64.6%); active nicotine abuse 50% (24.1%–76%); and obesity 22.2% (4%–59.8%). Overall cumulative (10-year) hemorrhage risk was 30.3% (21.3%–41.1%). Conclusions: The probability of hemorrhage in untreated CNS CM patients increases progressively within a decade of follow-up. None of the modifiable vascular risk factors showed strong indication for an influence on hemorrhage risk, but our findings may suggest a more aggressive course in patients with active nicotine abuse or suffering from diabetes. in press

Cavernous malformations (CMs) are low-flow vascular lesions of the central nervous system prone to symptomatic hemorrhage. CMs are estimated to be present in approximately 0.5% of the population. Usually, they are characterized by a relatively benign clinical course, staying asymptomatic in many patients. However, depending on the anatomic location, CMs can cause significant morbidity due to symptoms such as seizures or focal neurologic deficits (most of the time caused by symptomatic hemorrhage). This nonsystematic review aims to summarize important recent clinical research focusing on the biology and surgical management of CMs published since 2017.

OBJECTIVE The aim of this study was to investigate the functional outcome in spinal cavernous malformation (SCM) patients with single or multiple intramedullary hemorrhagic events. METHODS SCM patients who were conservatively treated between 2003 and 2021 and had complete clinical baseline characteristics, an MRI data set, at least one SCM-related intramedullary hemorrhage (IMH), and at least one follow-up examination were included in this study. Functional status was assessed using the modified McCormick Scale score at diagnosis, before and after each bleeding event, and at the last follow-up. RESULTS A total of 45 patients were analyzed. Univariate analysis identified multiple bleeding events as the only statistically significant predictor for an unfavorable functional outcome at the last follow-up (OR 15.28, 95% CI 3.22–72.47; p < 0.001). Patients significantly deteriorated after the first hemorrhage (29.0%, p = 0.006) and even more so after the second hemorrhage (84.6%, p = 0.002). Multiple bleeding events were significantly associated with functional deterioration at the last follow-up (76.9%, p = 0.003). The time between the last IMH and the last follow-up did not influence this outcome. CONCLUSIONS IMH due to SCM is linked to functional worsening. Such outcomes tend to improve after each hemorrhage, but the probability of full recovery declines with each bleeding event.

Background To determine the prevalence of cardiovascular comorbidities and allergic diseases in patients with cavernous malformations of the central nervous system compared to the normal population. Methods Clinical and magnetic resonance imaging data of 1352 patients with cerebral cavernous malformations (CCM) from an observational, cross-sectional, single-institutional study were analyzed and compared to an age-and-gender stratified and matched sample from a population-based, epidemiological study assessing cardiovascular risk factors in the local normal population of the same area (RECALL study). Results Of 1352 patients, 810 (60%) were female. Mean age was 40.4 ± 16 years. 221 patients (16%) suffered from familial disease. Presence of cardiovascular risk factors and intake of certain drugs in the overall cohort was mostly equal to the normal population reference sample (n = 786). The prevalence of allergic diseases was found to be significantly higher in all CCM patients compared to the normal population (30% vs. 20%, odds ratio [OR] 1.35 [1.12-1.63]) and in sporadic CCM cases compared to the normal population and familial cases (32% vs. 20% (OR 1.46 [1.19-1.78], p = 0.0001) and 22% vs. 20%, respectively). Conclusions We present novel data on CCM using a large single-institution and population-based setup. The study elaborates disease characteristics of CCM patients in detail. For the first time, evidence for an unexplained high prevalence of allergic diseases in this patient population is described (differing between sporadic and familial cases), supporting the hypothesis that immune response is involved in the pathogenesis of CCM.

Background and Purpose: This study aims to assess the influence of modifiable cardiovascular risk factors on hemorrhage risk of sporadic cerebral cavernous malformations (CCMs). Methods: From 1219 consecutive CCM patients (2003–2018), adult subjects with sporadic CCM and complete magnetic resonance imaging were included. We evaluated presence of intracerebral hemorrhage (ICH) as mode of presentation, occurrence of ICH during follow-up and risk factors arterial hypertension, diabetes, hyperlipidemia, nicotine abuse, and obesity (body mass index >30 kg/m 2 ). Impact of risk factors on ICH at presentation was calculated using univariate and multivariate logistic regression with age and sex adjustment. We performed Kaplan-Meier and Cox regression to analyze cumulative 5-year risk for (re)bleeding. Results: We included 682 patients with CCM. The univariate logistic regression showed a significant relationship (odds ratio=1.938 [95% CI, 1.120–3.353], P =0.018) between obesity and ICH as mode of presentation. Multivariate adjusted logistic regression confirmed significant correlation with odds ratio=1.902 (95% CI, 1.024–3.532, P =0.042). Cox regression did not identify predictors for occurrence of (re)hemorrhage ( P >0.05; hazard ratios: arterial hypertension 1.112 [95% CI, 0.622–1.990], diabetes 0.850 [95% CI, 0.208–3.482], hyperlipidemia 0.719 [95% CI, 0.261–1.981], nicotine abuse 1.123 [95% CI, 0.591–2.134], and obesity 0.928 [95% CI, 0.416–2.070]). Conclusions: This study provides evidence that obesity may be a risk factor for CCM hemorrhage. It was significantly associated with ICH as mode of presentation. Other risk factors (arterial hypertension, diabetes, hyperlipidemia, and current nicotine abuse) showed no such effect. None of the factors showed to be independent predictors for cumulative 5-year risk of (re)bleeding.

Cerebral infarction is a major contributor to poor outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). Timing of treatment has been discussed as a possible contributor. We aimed to analyze the impact of treatment timing on the risk of cerebral infarction and poor outcome after aSAH.Consecutive cases of patients with aSAH treated at our institution between January 2003 and June 2016 were included. The cohort was divided into 2 groups, depending on the treatment during (day 4-14 after ictus) or beyond the vasospasm phase. Statistical assessment included a 1:1 propensity score matching analysis and multivariable logistic regression analysis within the whole cohort.Of 943 patients with aSAH, 111 underwent treatment in the vasospasm phase. In the propensity score matching analysis, patients treated during the vasospasm phase were at higher risk of vasospasm requiring intra-arterial spasmolysis (P0.0001), cerebral infarction distal to the treated vessel (P0.0001), and poor outcome (modified Rankin Scale score2) at 6 months follow-up (P = 0.025). In the multivariable analysis, aneurysm treatment in the vasospasm phase was independently associated with higher risk of cerebral vasospasm necessitating intra-arterial spasmolysis (P0.0001; adjusted odds ratio [aOR], 3.62), cerebral infarction distal to the treated aneurysm (P = 0.01; aOR, 2.02), and poor outcome (P = 0.03; aOR, 2.05).Our data confirm a considerable risk of cerebral infarction and poor outcome in cases of aneurysm treatment between day 4 and 14 after aSAH. A more intense surveillance and prophylactic treatment of cerebral vasospasm might be necessary in cases of aneurysm treatment in the vasospasm phase.

Purpose Breast cancer (BC) is the most frequently diagnosed tumor entity in women. Occurring at different time intervals (TI) after BC diagnosis, brain metastases (BM) are associated with poor prognosis. We aimed to identify the risk factors related to and the clinical impact of timing on overall survival (OS) after BM surgery. Methods We included 93 female patients who underwent BC BM surgery in our institution (2008–2019). Various clinical, radiographic, and histopathologic markers were analyzed with respect to TI and OS. Results The median TI was 45.0 months (range: 9–334.0 months). Fifteen individuals (16.1%) showed late occurrence of BM (TI ≥ 10 years), which was independently related to invasive lobular BC [adjusted odds ratio (aOR) 9.49, 95% confidence interval (CI) 1.47–61.39, p = 0.018] and adjuvant breast radiation (aOR 0.12, 95% CI 0.02–0.67, p = 0.016). Shorter TI ( Conclusions Several factors seem to influence the period between BC and BM. Occurrence of BM within five years is independently associated with poorer prognosis after BM surgery. Patients with invasive lobular BC and without adjuvant breast radiation are more likely to develop BM after a long progression-free survival necessitating more prolonged cancer aftercare of these individuals.

Background and purpose To estimate health-related quality of life (HRQOL) in patients with untreated cavernous malformation of the CNS [cavernous cerebral malformations (CCMs)]. Methods We performed a cross-sectional observational study on patients with CCMs admitted to our department from 1 November 2017 to 10 January 2020 using standardized interviews [short-form-36 questionnaire, hospital anxiety and depression score (HADS-A/D), CCM perception questionnaire]. Included criteria were diagnosis of an untreated CCM and information about the diagnosis in a specialized CCM consultation. Health-related quality of life (HRQOL) data were analyzed and compared to the German normal population. Uni- and multivariate analyses were carried out to identify variables with impact on outcome. Results Two hundred nineteen (93%) of 229 eligible patients were included. Mean age was 46.3 ± 14.7 (18-86) years; 136 (62%) were female. Ninety-eight (45%) patients presented with symptomatic hemorrhage (SH), and 17 (8%) with repetitive SH. Ninety-two (42%) patients were asymptomatic. Thirty-seven patients (17%) suffered from cavernoma-related epilepsy. Twenty-eight patients (13%) suffered from familial CCMs. Patients showed significantly decreased component scores and subdomain scores compared to the normal population, with effects ranging from small to large. This accounted largely also for asymptomatic patients (except for physical component score and main physical subdomains). Multivariate regression analysis confirmed impact of functional impairment on physical component score. HADS-A was significantly increased. HADS-A/D strongly correlated with mental component score and individual perception of the CCM. Conclusions Patients with the diagnosis of a CCM showed decreased HRQOL compared to the normal population even when not suffering functional impairment or neurological symptoms. Our data may function as benchmarks in evaluation of different (future) management strategies.

OBJECTIVEThe object of this study was to assess outcome after surgery for brainstem cavernous malformations (BSCMs) using functional, health-related quality of life (HRQOL), and psychological surveys to analyze the interrelation of these measurements, and to compare HRQOL and anxiety and depression scores with those in a healthy population.METHODSThe authors performed a cross-sectional outcome study of all patients surgically treated for BSCM in their department between January 1, 2003, and December 31, 2019. They assessed functional outcome via the modified Rankin Scale (mRS), health-related quality of life (HRQOL) via the SF-36 and 9-item Life Satisfaction Questionnaire (LISAT-9), cranial nerve and brainstem function using a questionnaire, symptom-based psychological outcome via the Hospital Anxiety and Depression Scale (HADS), and timepoint of a return to previous employment. They analyzed the correlation between absolute (mRS score ≤ 2) and relative (postoperative deterioration in initial mRS score) outcome endpoints and the interrelation of the outcome measures and performed a comparison of HRQOL and HADS scores with findings in a healthy population.RESULTSSeventy-four patients were eligible for inclusion in the study. HRQOL was impaired after surgery for BSCM compared to that in a healthy population. This impairment was substantial in patients with an unfavorable functional outcome (mRS > 2) but was also present in those with a favorable outcome (mRS ≤ 2) in selected domains. Psychological impairment was negligible in patients with a favorable outcome and grave in those with an unfavorable outcome. LISAT-9 results revealed that brainstem and cranial nerve symptoms reduce satisfaction mainly in self-care abilities for both unfavorable and favorable outcome patients. Among the brainstem and cranial nerve symptoms, balance impairment showed the most significant impact on HRQOL. Absolute outcome endpoints were superior to relative outcome endpoints in reflecting impairment in HRQOL after surgery.CONCLUSIONSThe study data can improve patient counseling and decision-making in BSCM treatment and may function as a benchmark. The authors report outcomes after BSCM surgery in high detail, emphasizing the specific impact of cranial nerve and brainstem symptoms on HRQOL. When reporting BSCM surgery outcome, absolute outcome endpoints should be applied.

Background and purpose: This study aimed to assess the occurrence and significance of postoperative neuropathic pain (NP) in patients with surgically treated brainstem cavernous malformations (BSCMs). Methods: Seventy-four BSCM patients surgically treated between 2003 and 2019 were reviewed for the occurrence of postoperative NP and related treatment. The relevance of BSCM location, preoperative characteristics, influence on functional outcome, postoperative health-related quality of life (HRQOL) and life satisfaction was evaluated. Results: Six out of 74 patients (8%) suffered from NP. The Leeds Assessment of Neuropathic Symptoms and Signs scores ranged from 12 to 16 (mean 14.28 ± 1.6). Visual analog scale pain was 5.2 ± 2.0. NP had no effect on preoperative characteristics or functional outcome. Bodily pain (HRQOL) and vocational time (life satisfaction) were significantly decreased in NP compared to non-NP patients. Specific BSCM location (regarding brainstem nuclei involved in pain processing) and other preoperative patient- and BSCM-related parameters were not associated with the occurrence of postoperative NP. Three out of six patients were currently under NP-specific treatment. The proportion of patients suffering from postoperative NP (8%) was substantially higher compared to previously published studies. The pain affected the HRQOL of patients, most of whom were insufficiently treated and not satisfied with treatment results. Conclusion: Our findings may help to raise awareness for postoperative NP in BSCM, which is essential to improve diagnosis and initiation of proper treatment, as well as preoperative informed consent of patients.

Background: Turning during walking adds complexity to gait and has been little investigated until now. Research question What are the differences in spatiotemporal parameters between young and elderly healthy adults performing quarter-turns (90 degrees), half-turns (180 degrees) and full-turns (360 degrees)? Methods: The spatiotemporal parameters of 10 young and 10 elderly adults were recorded in a laboratory while turning at 90 degrees, 180 degrees and 360 degrees. Two-way mixed ANOVA were performed to determine the effect of age and turning amplitude. Results: Elderly were slower and needed more steps and time to perform turns of larger amplitude than young adults. Cadence did not differ across age or across turning amplitude. Generally, in the elderly, the spatial pa-rameters were smaller and the temporal parameters enhancing stability (i.e., double-support phase and stance/ cycle ratio) were larger, especially for turns of larger amplitudes. In elderly adults, the variability of some spatial parameters was decreased, whereas the variability of some temporal parameters was increased. Stride width of the external leg showed the most substantial difference between groups. Most parameters differed between turning at 90 degrees and turning at larger amplitudes (180 degrees, 360 degrees). Significance This study extends the characterization of turning biomechanics with respect to ageing. It also suggested paying particular attention to the turning amplitude. Finally, the age-related differences may pave the way for new selective rehabilitation protocols in the elderly.

The partial pressure of carbon dioxide (PaCO2) in the arterial blood is a strong vasomodulator affecting cerebral blood flow and the risk of cerebral edema and ischemia after acute brain injury. In turn, both complications are related to poor outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). We aimed to analyze the effect of PaCO2 levels on the course and outcome of aSAH. All patients of a single institution treated for aSAH over 13.5 years were included (n = 633). Daily PaCO2 values from arterial blood gas measurements were recorded for up to 2 weeks after ictus. The study endpoints were: delayed cerebral ischemia (DCI), need for decompressive craniectomy due to increased intracranial pressure > 20 mmHg refractory to conservative treatment and poor outcome at 6-months follow-up (modified Rankin scale > 2). By correlations with the study endpoints, clinically relevant cutoffs for the 14-days mean values for the lowest and highest daily PaCO2 levels were defined by receiver operating characteristic curve analysis. Association with the study endpoints for the identifies subgroups was analyzed using multivariate analysis. The optimal range for PaCO2 values was identified between 30 and 38 mmHg. ASAH patients with poor initial condition (WFNS 4/5) were less likely to show PaCO2 values within the range of 30–38 mmHg (p p = 0.042, aOR = 0.27), DCI occurrence (p = 0.035; aOR = 0.50), and poor patient outcome (p = 0.004; aOR = 0.42). The data from this study shows an independent positive association between low normal mean PaCO2 values during the acute phase of aSAH and patients’ outcome. This effect might be attributed to the reduction of intracranial hypertension and alterations in the cerebral blood flow.

There is a growing interest for turning biomechanics notably because it is a more challenging task than straight-line walking during which some gait impairments are increased. Detecting heel-strike (HS) and toe-off (TO) events using the trajectory of markers attached to the feet is common in straight-line gait analysis and could reveal very useful to evaluate turning maneuvers. Yet, a comprehensive evaluation is missing, making difficult the selection of features for temporal analysis of turning. This study aimed to compare features of foot marker trajectories to detect HS and TO. Twenty healthy participants, 10 young (5 males, 23 ± 1 years old, 21.3 ± 2.2 kg/m2) and 10 elderly (4 males, 72 ± 5 years old, 26.4 ± 6.4 kg/m2), performed quarter, half, and full turns as well as straight-line walking in a gait lab. Fourteen features, adapted from straight-line walking literature, were used to detect HS and TO based on marker trajectories. Force plate measures served as reference. One HS and one TO feature were found particularly suitable. Overall, they detected more than 99% of the 1788 events recorded, with accuracies and precisions of −3.9 ms and 9.0 ms for HS and −7.8 ms and 10.7 ms for TO, respectively. Differences in accuracy and precision were observed among walking conditions and groups, but remained small, generally below 4.0 ms. In conclusion, this study identified kinematic features that can be used to analyze both turning and straight-line walking. Further assessment could be necessary with pathologies inducing severe degradation of gait patterns.

Despite multimodal treatment, the prognosis of patients with glioblastoma (GBM) remains poor. Previous studies showed conflicting results on the effect of antiepileptic drugs (AED) on GBM survival. We investigated the associations of different AED with overall survival (OS) and progression-free survival (PFS) in a large institutional GBM cohort (n = 872) treated January 2006 and December 2018. In addition, we performed a meta-analysis of previously published studies, including this study, to summarize the evidence on the value of AED for GBM prognosis. Of all perioperatively administered AED, only the use of levetiracetam (LEV) was associated with longer OS (median: 12.8 vs. 8.77 months, p &lt, 0.0001) and PFS (7 vs. 4.5 months, p = 0.001). In the multivariable analysis, LEV was independently associated with longer OS (aHR = 0.74, p = 0.017) and PFS (aHR = 0.68, p = 0.008). In the meta-analysis with 5614 patients from the present and seven previously published studies, outcome benefit for OS (HR = 0.83, p = 0.02) and PFS (HR = 0.77, p = 0.02) in GBM individuals with LEV was confirmed. Perioperative treatment with LEV might improve the prognosis of GBM patients. We recommend a prospective randomized controlled trial addressing the efficacy of LEV in GBM treatment.

INTRODUCTION Glioblastoma is the most common primary brain tumor in adults with the worst overall survival. Post-craniotomy intracranial infections are not infrequent after surgery; however, their impact on overall survival of glioblastoma patients remains unclear. Here we report the case of an unusual longer survival of a glioblastoma patient affected by multiple infections and the review of the literature on this topic. EVIDENCE ACQUISITION PubMed, Embase and Cochrane search engines were reviewed for papers describing outcome of patients suffering from glioblastoma and associated cerebral infections. EVIDENCE SYNTHESIS Four papers accounting a total of 29 patients met the eligibility criteria. Staphylococcus aureus and Staphylococcus epidermidis resulted the most common bacteria causing post-craniotomy intracranial infections in brain tumor patients. The overall median survival rate was 18±18.12 months when adding all 29 patients. Only one study described a significant higher survival rate for the infected group. CONCLUSIONS Glioblastoma is the most frequent malignant brain tumor with a very poor outcome/survival. In the literature few cases described an exceptional longer survival often associated with a postoperative infection. To date, the pathophysiology behind this longer survival remains unclear, but it seems that Staphylococcus species could have an influence on the progression of this aggressive brain tumor.