Risk factors for poor outcome after aneurysmal subarachnoid hemorrhage in patients with initial favorable neurological status.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) remains a devastating diagnosis. A poor outcome is known to be highly dependent on the initial neurological status. Our goal was to identify other parameters that favor the risk of complications and poor outcome in patients with aSAH and initially favorable neurologic status. METHODS: Consecutive aSAH cases treated at our hospital between 01/2003 and 06/2016 with the initial World Federation of Neurosurgical Societies grades I-III were included. Data on demographic characteristics, previous medical history, initial aSAH severity, and functional outcome after aSAH were collected. The study endpoints were the occurrence of cerebral infarcts, in-hospital mortality, and unfavorable outcome at 6 months after aSAH (modified Rankin scale > 3). RESULTS: In the final cohort (n= 582), the rate of cerebral infarction, in-hospital mortality, and unfavorable outcome was 35.1%, 8.1%, and 17.6% respectively. The risk of cerebral infarction was independently related to the presence of acute hydrocephalus (adjusted odds ratio [aOR]=2.33, p<0.0001), aneurysm clipping (aOR=1.78, p=0.003), and use of calcium channel blockers concomitant to nimodipine (aOR=2.63, p=0.002). Patients' age (>55 years, aOR=4.24, p<0.0001), acute hydrocephalus (aOR=2.43, p=0.036), and clipping (aOR=2.86, p=0.001) predicted in-hospital mortality. Baseline characteristics associated with unfavorable outcome at 6 months were age (aOR=2.77, p=<0.0001), Fisher grades III-IV (aOR=2.81, p=0.016), acute hydrocephalus (aOR=2.22, p=0.012), clipping (aOR=3.98, p<0.0001), admission C-reactive protein>1mg/dL (aOR=1.76, p=0.035), and treatment intervals (aOR=0.64 per-5-year-intervals, p=0.006). CONCLUSIONS: Although cerebral infarction is a common complication in aSAH individuals with favorable initial clinical condition, >80% of these patients show favorable long-term outcome. The knowledge of outcome-relevant baseline characteristics might help to reduce the burden of further complications and poor outcome in aSAH patients who tolerated the initial bleeding event well.

The influence of radiological tumor growth pattern on sino­nasal health in pituitary adenomas.

Pituitary adenomas are one of the most common mass lesions of the brain and are associated with a reduced quality of life. While transnasal and transsphenoidal endoscopic approaches are considered to deliver similar recovery rates for sino-nasal health (SNH), the impact of radiological tumor growth patterns on SNH has not been evaluated. In the present study, the influence of radiological tumor growth on SNH was examined before and after endoscopic transsphenoidal tumor resection. Patient data were prospectively collected between August 1, 2016 and August 31, 2022. The Knosp and Hardy classifications were used to dichotomize pituitary adenoma lesions into low- and high-graded lesions. SNH was assessed shortly before surgery and at follow-up examinations 3-6 months after operation using the Sino-Nasal Outcome Test for Neurosurgery (SNOT-NC) questionnaire. Fully completed SNOT-NC questionnaires were collected before and after surgery from a total of 101 patients. Independent t-tests showed significantly higher rates of deterioration after surgery in patients with Knosp low-graded lesions compared with those with high-graded tumors for the SNOT-NC total score P=0.048, nasal discomfort P=0.034, sleep problems P=0.024 and visual impairment P=0.042. Pre- and post-operative comparisons for the Knosp low-graded tumor cohort showed an increase of nasal discomfort (P=0.004), while the Knosp high-graded tumor cohort reported decreased visual impairment (P=0.016) after surgery. Assessing the Hardy classification, increased nasal discomfort was reported in patients with high-graded infrasellar tumors after surgery (P=0.046). Growth characteristics of pituitary adenomas based on Knosp and Hardy classifications may influence SNH. Patients with less invasive lesions were revealed to be more prone to experiencing a decrease in SNH, which went beyond the assumed deterioration of 1-3 months. These findings indicate the importance of detailed information regarding SNH as part of every pre-operative patient briefing.

The role of previous medical history and secondary complications for the outcome of aneurysmal subarachnoid hemorrhage in elderly patients.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) presents a devastating diagnosis for elderly individuals, resulting in high morbidity and mortality rates. The aim of the study was to analyze the impact of medical history and complications during SAH on the outcome of elderly patients. METHODS: Consecutive SAH cases aged ≥ 65 years old treated in our hospital between 01/2003 and 06/2016 were included (n = 218). Data on comorbidities, previous medication, initial severity, secondary complications, and the outcome were collected. Study endpoints were occurrence of cerebral infarcts, in-hospital mortality, and unfavorable outcome at 6 months after SAH. RESULTS: Cerebral infarcts were documented in 111 (51.2 % ) individuals. Multivariate analysis showed that angiographic vasospasm caused an increase (adjusted odds ratio [aOR] = 3.11, p = 0.022) in the risk of infarction, whereas aspirin treatment decreased (aOR = 0.25, p = 0.001) the risk of infarction. In turn, increasing age (aOR = 1.11, p = 0.002), intracranial hypertension (>20 mmHg, aOR = 3.32, p = 0.006) and acute kidney failure (aOR = 6.65, p = 0.035) during SAH were independently related to the risk of in-hospital mortality (n = 50; 22.9 % ). Finally, patients' age (aOR = 1.09, p = 0.022), high initial SAH burden (WFNS ≥ 4: aOR = 7.5, p < 0.0001; intraventricular hemorrhage: aOR = 4.38, p = 0.007), aneurysm clipping (aOR = 4.07, p = 0.018), and intracranial hypertension during SAH (aOR = 4.08, p = 0.006) were independent predictors of unfavorable outcome (n = 106/192; 55.5 % ). Previous medical history showed no negative impact on the severity, course and outcome of SAH. CONCLUSION: About half of elderly SAH patients face poor outcomes after aneurysm securing. The initial severity of and complications during SAH are the major contributors to poor treatment results. Our findings might help to optimize the treatment strategies.

Natural course of cerebral and spinal cavernous malformations: a complete ten-year follow-up study.

Knowledge of the bleeding risk and the long-term outcome of conservatively treated patients with cavernous malformations (CM) is poor. In this work, we studied the occurrence of CM-associated hemorrhage over a 10-year period and investigated risk factors for bleeding. Our institutional database was screened for patients with cerebral (CCM) or intramedullary spinal cord (ISCM) CM admitted between 2003 and 2021. Patients who underwent surgery and patients without completed follow-up were excluded. Analyses were performed to identify risk factors and to determine the cumulative risk for hemorrhage. A total of 91 CM patients were included. Adjusted multivariate logistic regression analysis identified bleeding at diagnosis (p = 0.039) and CM localization to the spine (p = 0.010) as predictors for (re)hemorrhage. Both risk factors remained independent predictors through Cox regression analysis (p = 0.049; p = 0.016). The cumulative 10-year risk of bleeding was 30% for the whole cohort, 39% for patients with bleeding at diagnosis and 67% for ISCM. During an untreated 10-year follow-up, the probability of hemorrhage increased over time, especially in cases with bleeding at presentation and spinal cord localization. The intensity of such increase may decline throughout time but remains considerably high. These findings may indicate a rather aggressive course in patients with ISCM and may endorse early surgical treatment.

Benign peripheral nerve sheath tumors: an interdisciplinary diagnostic and therapeutic challenge.

A benign peripheral nerve sheath tumor (bPNST) is a rare lesion associated with peripheral nerval structures. Symptoms may be heterogeneous, complicating diagnosis finding. Additionally, management concepts of bPNST may vary. In some cases, initial misdiagnosis leads to mistreatment resulting in severe functional deficits and chronic pain syndromes. Therefore, we analyzed patients treated for bPNST in our specialized institution with a primary focus on prior misdiagnosis and possible mistreatment. Patients with bPNSTs (schwannomas, neurofibromas, hybrid nerve sheath tumors, and perineuriomas) treated at the Neurosurgical Department between January 1, 2015, and July 31, 2021, were included. Assessment of demographics, tumor entity, tumor location, symptoms, the interval between the onset of symptoms and surgery, involved medical specialties, and outpatients' treatment, with particular focus on initial misdiagnosis and inappropriate medical treatment, was performed. Eighty-five patients were included in the final analysis with schwannoma being the most prevalent histopathological diagnosis (schwannoma (75.3%, n=64), neurofibroma (12.9%, n=11), hybrid nerve sheath tumor (5.9%, n=5), and perineurioma (5.9%, n=5)). An incorrect primary diagnosis was detected in 44.7% (n=38), leading to suboptimal or insufficient treatment in these cases. Of those, 28.9% (n=11/38) were treated suboptimal, while 18.5% (n=7/38) underwent unnecessary invasive diagnostics. Inappropriate surgery based on prior misdiagnosis, which led to severe neurological deficits in all these cases, was reported in 26.3% (n=10/38). For the first time, our data shows the quantity and impact of incorrect initial diagnosis in bPNST causing a delay in causative treatment or resulting in unnecessary or potentially harmful treatment.

Central nervous system cavernous malformations: cross-sectional study assessing rebleeding risk after a second haemorrhage.

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.

Impact of Treatment Timing on the Risk of Cerebral Infarction in Patients with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (P < 0.0001), cerebral infarction distal to the treated vessel (P < 0.0001), and poor outcome (modified Rankin Scale score >2) 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 (P < 0.0001; 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). CONCLUSIONS: 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.

Quality of life and mood assessment in conservatively treated cavernous malformation-related epilepsy.

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.

Medication intake and hemorrhage risk in patients with familial cerebral cavernous malformations.

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.

Effects of medication intake on the risk of hemorrhage in patients with sporadic cerebral cavernous malformations.

Objective: Recurrent intracerebral hemorrhage (ICH) poses a high risk for patients with cerebral cavernous malformations (CCMs). This study aimed to assess the influence of medication intake on hemorrhage risk in sporadic CCMs. Methods: From a database of 1,409 consecutive patients with CCM (2003-2021), subjects with sporadic CCMs and complete magnetic resonance imaging data were included. We evaluated the presence of ICH as a mode of presentation, the occurrence of ICH during follow-up, and medication intake, including beta blockers, statins, antithrombotic therapy, and thyroid hormones. The impact of medication intake on ICH at presentation was calculated using univariate and multivariate logistic regression with age and sex adjustment. The longitudinal cumulative 5-year risk for (re-)hemorrhage was analyzed using the Kaplan-Meier curves and the Cox regression analysis. Results: A total of 1116 patients with CCM were included. Logistic regression analysis showed a significant correlation (OR: 0.520, 95% CI: 0.284-0.951, p = 0.034) between antithrombotic therapy and ICH as a mode of presentation. Cox regression analysis revealed no significant correlation between medication intake and occurrence of (re-)hemorrhage (hazard ratios: betablockers 1.270 [95% CI: 0.703-2.293], statins 0.543 [95% CI: 0.194-1.526], antithrombotic therapy 0.507 [95% CI: 0.182-1.410], and thyroid hormones 0.834 [95% CI: 0.378-1.839]). Conclusion: In this observational study, antithrombotic treatment was associated with the tendency to a lower rate of ICH as a mode of presentation in a large cohort of patients with sporadic CCM. Intake of beta blockers, statins, and thyroid hormones had no effect on hemorrhage as a mode of presentation. During the 5-year follow-up period, none of the drugs affected the further risk of (re-)hemorrhage.