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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.

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.

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.

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.

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.

Background: To estimate the quality of life, anxiety, depression, and illness perception in patients with medically treated cerebral cavernous malformation (CCM) and associated epilepsy. Methods: Nonsurgically treated patients with CCM-related epilepsy (CRE) were included. Demographic, radiographic, and clinical features were assessed. All participants received established questionnaires (short-form 36 health survey, SF-36; hospital anxiety and depression score, HADS-A/D; visual analogue scale score, VAS) assessing the functional and psychosocial burden of disease. To some extent, calculated values were compared with reference values from population-based studies. Test results were related to seizure control. Results: A total of 37 patients were included. Mean age was 45.8 ± 14.4 years, and 54.1% were female. Diagnosis of CRE was significantly associated with attenuated quality of life and increased level of anxiety, affecting physical and psychosocial dimensions. The assessment of illness perception identified considerable burden. HADS was significantly associated with VAS and SF-36 component scores. Efficacy of antiepileptic medication had no restoring impact on quality of life, anxiety, depression, or illness perception. Conclusions: CRE negatively influences quality of life and mood, independent of seizure control due to antiepileptic medication. Screening for functional and psychosocial deficits in clinical practice might be useful for assessing individual burden and allocating surgical or drug treatment. OA Förderung 2022

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.