Tag: natural history

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Natural History of Sporadic Cerebral Cavernous Malformations by Zabramski Classification: Hemorrhage Risk and Functional Outcomes Over 5 Years

Neurosurgery 98:376–383, 2026

This prospective cohort study examines sporadic cerebral cavernous malformations (CCMs) categorized by Zabramski MRI types I–IV, reporting lesion features, presentation, hemorrhage rates, and mRS outcomes over a mean follow-up of 4.7 years. Type I lesions had the highest symptomatic presentation, largest size, brainstem predominance, and elevated hemorrhage risks.

Functional outcomes improved for some patients, but Type I had the poorest outcomes. Severe symptomatic hemorrhage was the strongest predictor of sustained disability (mRS ≥3). Types III and IV had low hemorrhage rates and favorable prognoses, supporting conservative management and tailored follow-up imaging.

Zabramski Classification: Stratifies cerebral cavernous malformations (CCMs) into Types I–IV based on MRI features, which correlate with clinical presentation, hemorrhage risk, and functional outcomes.

Type I Lesions: Show the highest annual symptomatic hemorrhage (SH) rate (13.9%), a 5-year cumulative risk of 50.6%, are mostly symptomatic at presentation, often located in the brainstem, and have the poorest long-term functional outcomes (mRS ≥2 in 35.4% at last follow-up).

Type II and III Lesions: Exhibit lower annual hemorrhage rates (2.9% and 1.8%, respectively), more frequently present with seizures or focal neurological deficits rather than hemorrhage, and have better long-term functional outcomes (Type II: mRS ≥2 in 11.2%; Type III: mRS ≥2 in 7.5% at last follow-up).

Type IV Lesions: Are exclusively asymptomatic, detected incidentally, have no observed hemorrhagic events during follow-up, and show no functional impairment (no cases of mRS ≥2).

Severe Symptomatic Hemorrhage: Is the strongest independent predictor of poor functional outcome (mRS ≥3), outweighing lesion type, age, location, or surgical intervention in multivariate analysis (HR 10.88, P < .001).

Dynamic Lesion Evolution: Zabramski type can change over time, particularly for Type I lesions, highlighting the need for longitudinal imaging and dynamic risk assessment rather than reliance on a single timepoint classification.

Clinical Management Implications: Conservative management is appropriate for most Type III and IV lesions due to their benign natural history, while Type I lesions require closer monitoring and individualized intervention strategies due to higher risk.

Study Limitations: Small sample sizes for Types III and IV, potential MRI protocol variability, and single-center design may limit generalizability; multicenter studies are needed for broader validation.

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Natural history and management outcomes of patients with ruptured Spetzler-Martin grade IV and V brain arteriovenous malformations

J Neurosurg 142:667–675, 2025

Study Objective: To explore the natural history and management outcomes of patients with ruptured Spetzler-Martin grade IV and V brain arteriovenous malformations (bAVMs).

• Patient Selection: The study involved 84 patients with ruptured high-grade bAVMs, identified from a database spanning 1990 to 2020.

• Hemorrhagic Risk: Annual hemorrhagic risk was 2.68% for cortical bAVMs and 8.37% for deep-seated bAVMs during natural history.

• Treatment Outcomes: Surgery reduced hemorrhagic risk significantly in cortical bAVMs, while radiosurgery was effective for deep-seated bAVMs. Embolization alone increased hemorrhagic risk.

• Predictors of Success: Surgery and radiosurgery were significant predictors of bAVM obliteration for cortical and deep-seated bAVMs, respectively.

• Management Strategies: Conservative management was compared to surgical interventions, showing similar functional outcomes but differing in obliteration rates.

• Conclusion: Surgery and radiosurgery may be viable options for certain patients, while embolization alone should be avoided

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Contemporary cohort of cerebral cavernous malformations: natural history and utility of follow-up MRI

J Neurosurg 141:1159–1167, 2024

This study reports the natural history of cerebral cavernous malformations (CCMs) in a contemporary cohort with prospectively collected data from multiple sources, access to follow-up imaging, integrated electronic medical records, and detailed imaging review by study investigators. The authors aimed to define the first prospective symptomatic hemorrhage (SH) and severe SH rates, determine the risk of a second prospective SH, and identify risk factors for SH.

METHODS From a prospectively maintained database of adult patients with radiologically defined CCM, those with radiation-induced CCM, those who underwent surgery within 3 months postdiagnosis, and those with < 1 year of followup were excluded. The patients’ medical history and radiological features of the CCM were recorded at the time of diagnosis. Follow-up annual written surveys were completed for 5 years after the initial diagnosis and then semiannually thereafter in addition to medical record and follow-up imaging review. Outcomes of interest included SH and severe SH.

RESULTS Of 315 patients, 58.7% were female and 19.7% had familial CCMs. At diagnosis, 37.1% of patients had ruptured CCMs and 28.9% of the CCMs were located in the brainstem. The 5-year cumulative rates of prospective SH and severe SH in those with ruptured CCMs at diagnosis were 41.2% and 12.8%, respectively, compared with 6.1% and 2.5% in patients with unruptured CCMs at diagnosis (p < 0.0001). Risk factors for prospective SH included a ruptured CCM at diagnosis and persistent or new hyperintensity on T1-weighted MRI performed > 3 months after baseline MRI. For those with a ruptured CCM at diagnosis, the risk of developing a second prospective SH was similar to that of developing a first SH.

CONCLUSIONS In a contemporary cohort of adult patients with CCM, the authors report 5-year SH and severe SH rates, rates of second prospective hemorrhage, and predictors of SH. Persistent or new hyperintensity on T1-weighted MRI may be a useful marker of disease activity.

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Nomogram for predicting an individual prospective hemorrhage risk in untreated brainstem cavernous malformations

J Neurosurg 138:910–921, 2023

In this study, the authors aimed to create a nomogram for precisely predicting the 5-year prospective hemorrhage risk in brainstem cavernous malformations (BSCMs).

METHODS Patients with confirmed BSCMs in a single-center prospective observational series from January 2012 to December 2016 were included in the present study for nomogram building and validation. The concordance index (C-index), calibration curves, and decision curve analysis were used to evaluate the predictive accuracy, discriminative ability, and clinical usefulness of the nomogram. Then, a nomogram-based risk stratification model for untreated BSCMs was developed.

RESULTS In total, 600 patients were included in the study; 417 patients who had been enrolled before July 2015 were divided into the training and validation cohorts, and 183 subsequently enrolled patients were used as the external validation cohort. By applying a backward stepwise procedure in the multivariable Cox model, variables, including prior hemorrhage (HR 1.69), hemorrhage on admission (HR 3.33), lesion size > 1.5 cm (HR 1.84), lesion depth (HR 2.35), crossing the axial midpoint (HR 1.94), and developmental venous anomaly (HR 2.62), were incorporated to develop a nomogram. The Harrell C-index values for a 5-year prospective hemorrhage were 0.752 (95% CI 0.687–0.816), 0.801 (95% CI 0.665–0.936), and 0.758 (95% CI 0.674–0.842) in the training, internal validation, and external validation cohorts, respectively. The nomogram performed well in terms of consistency between prediction and actual observation according to the calibration curve. The patients could be classified into three distinct (low, medium, and high) risk groups using the final score of this nomogram.

CONCLUSIONS Independent predictors of the 5-year hemorrhage risk in untreated BSCMs were selected to create the first nomogram for predicting individual prospective hemorrhage. The nomogram was able to stratify patients into different risk groups and assist in clinical decision-making.

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Natural history of meningiomas: a serial volumetric analysis of 240 tumors

J Neurosurg 137:1639–1649, 2022

The management of asymptomatic intracranial meningiomas is controversial. Through the assessment of growth predictors, the authors aimed to create the basis for practicable clinical pathways for the management of these tumors.

METHODS The authors volumetrically analyzed meningiomas radiologically diagnosed at their institution between 2003 and 2015. The primary endpoint was growth of tumor volume. The authors used significant variables from the multivariable regression model to construct a decision tree based on the exhaustive Chi-Square Automatic Interaction Detection (CHAID) algorithm.

RESULTS Of 240 meningiomas, 159 (66.3%) demonstrated growth during a mean observation period of 46.9 months. On multivariable logistic regression analysis, older age (OR 0.979 [95% CI 0.958–1.000], p = 0.048) and presence of calcification (OR 0.442 [95% CI 0.224–0.872], p = 0.019) had a negative predictive value for tumor growth, while T2-signal iso-/hyperintensity (OR 4.415 [95% CI 2.056–9.479], p < 0.001) had a positive predictive value. A decision tree model yielded three growth risk groups based on T2 signal intensity and presence of calcifications. The median tumor volume doubling time (Td) was 185.7 months in the low-risk, 100.1 months in the intermediate-risk, and 51.7 months in the highrisk group (p < 0.001). Whereas 0% of meningiomas in the low- and intermediate-risk groups had a Td of ≤ 12 months, the percentage was 8.9% in the high-risk group (p = 0.021).

CONCLUSIONS Most meningiomas demonstrated growth during follow-up. The absence of calcifications and iso-/ hyperintensity on T2-weighted imaging offer a practical way of stratifying meningiomas as low, intermediate, or high risk. Small tumors in the low- or intermediate-risk categories can be monitored with longer follow-up intervals.

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Dural arteriovenous fistulas without cortical venous drainage

J Neurosurg 136:942–950, 2022

Current evidence suggests that intracranial dural arteriovenous fistulas (dAVFs) without cortical venous drainage (CVD) have a benign clinical course. However, no large study has evaluated the safety and efficacy of current treatments and their impact over the natural history of dAVFs without CVD.

METHODS The authors conducted an analysis of the retrospectively collected multicenter Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database. Patient demographics and presenting symptoms, angiographic features of the dAVFs, and treatment outcomes of patients with Borden type I dAVFs were reviewed. Clinical and radiological follow-up information was assessed to determine rates of new intracranial hemorrhage (ICH) or nonhemorrhagic neurological deficit (NHND), worsening of venous hyperdynamic symptoms (VHSs), angiographic recurrence, and progression or spontaneous regression of dAVFs over time.

RESULTS A total of 342 patients/Borden type I dAVFs were identified. The mean patient age was 58.1 ± 15.6 years, and 62% were women. The mean follow-up time was 37.7 ± 54.3 months. Of 230 (67.3%) treated dAVFs, 178 (77%) underwent mainly endovascular embolization, 11 (4.7%) radiosurgery alone, and 4 (1.7%) open surgery as the primary modality. After the first embolization, most dAVFs (47.2%) achieved only partial reduction in early venous filling. Multiple complementary interventions increased complete obliteration rates from 37.9% after first embolization to 46.7% after two or more embolizations, and 55.2% after combined radiosurgery and open surgery. Immediate postprocedural complications occurred in 35 dAVFs (15.2%) and 6 (2.6%) with permanent sequelae. Of 127 completely obliterated dAVFs by any therapeutic modality, 2 (1.6%) showed angiographic recurrence/recanalization at a mean of 34.2 months after treatment. Progression to Borden-Shucart type II or III was documented in 2.2% of patients and subsequent development of a new dAVF in 1.6%. Partial spontaneous regression was found in 22 (21.4%) of 103 nontreated dAVFs. Multivariate Cox regression analysis demonstrated that older age, NHND, or severe venous-hyperdynamic symptoms at presentation and infratentorial location were associated with worse prognosis. Kaplan-Meier curves showed no significant difference for stable/improved symptoms survival probability in treated versus nontreated dAVFs. However, estimated survival times showed better trends for treated dAVFs compared with nontreated dAVFs (288.1 months vs 151.1 months, log-rank p = 0.28). This difference was statistically significant for treated dAVFs with 100% occlusion (394 months, log-rank p < 0.001).

CONCLUSIONS Current therapeutic modalities for management of dAVFs without CVD may provide better symptom control when complete angiographic occlusion is achieved.

 

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Natural History of Spinal Cord Cavernous Malformations

Neurosurgery 90:390–398, 2022

The natural history of spinal cord cavernous malformations (SCCMs) remains relatively unclear.

OBJECTIVE: To investigate the natural history for hemorrhagic risks and neurological outcomes, as well as relevant predicting factors, of SCCMs.

METHODS: All patients between 2002 and 2019 with diagnosis of SCCMs were identified retrospectively. An observational study of patients with conservative management was performed to reveal the natural history of SCCMs.

RESULTS: We identified 305 patients in the full cohort, including 126 patients who were conservatively treated for at least 6 months (median observational period, 24.0 months). Forty-five hemorrhage events occurred during 527 person-years of follow-up, yielding an annual hemorrhage rate of 8.5% per person-year. The 1-, 2-, and 5-year cumulative risks of hemorrhage were 13.9%, 26.1%, and 35.1%, respectively. Prior hemorrhage (hazard ratio [HR] = 12.948, P = .012) and pediatric patients (HR = 2.841, P = .031) were independent predictors of hemorrhage in the long-term follow-up. Familial form (adjusted odds ratio [OR] = 30.695, P = .010) and subsequent hemorrhage events (adjusted OR = 16.333, P = .000) were independent risk factors for worsening of neurological function, and baseline neurological status (adjusted OR = 78.984, P = .000) and presence of subsequent hemorrhage (adjusted OR = 9.611, P = .001) were significantly associated with neurological outcomes.

CONCLUSION: The natural history of SCCMs varies. Baseline characteristics, such as pediatric patients, familial form, and baseline neurological status, as well as prior and subsequent hemorrhagic events, significantly affect the natural history of the SCCMs, which prompts a differentiated treatment strategy.

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Subclinical imaging changes in cerebral cavernous angiomas during prospective surveillance

J Neurosurg 134:1147–1154, 2021

The purpose of this study was to systematically assess asymptomatic changes (ACs), including subclinical hemorrhage, growth, or new lesion formation (NLF) during longitudinal follow-up of cerebral cavernous angiomas (CAs), and to correlate these with symptomatic hemorrhage (SH) during the same period and with clinical features of the disease.

METHODS One hundred ninety-two patients were included in this study, among 327 consecutive patients with CA, prospectively identified between September 2009 and February 2019. Included patients had undergone clinical and MRI follow-up, in conjunction with institutional review board–approved biomarker studies, and harbored ≥ 1 CA with a maximum diameter of ≥ 5 mm on T2-weighted MRI. Rates of AC and SH per lesion-year and patient-year were assessed using prospectively articulated criteria. In multifocal/familial cases, rates of NLF were also assessed.

RESULTS There were no differences in demographic or disease features among cases included or excluded in the study cohort, except for a higher proportion of included patients with CCM3 mutation. Follow-up was 411 patient-years (2503 lesion-years). The rate of AC was higher than the rate of SH (12.9% vs 7.5% per patient-year, and 2.1% vs 1.2% per lesion-year, both p = 0.02). Patients presenting with a prior history of SH had a higher rate of AC than those with other forms of presentation (19.7% and 8.2% per patient-year, respectively; p = 0.003). A higher rate of NLF on T2-weighted MRI (p = 0.03) was observed in patients with prior SH. Three of 6 solitary/sporadic and 2 of 28 multifocal/familial patients underwent resection of the lesion after AC.

CONCLUSIONS Rates of AC are greater than SH during prospective follow-up of CAs, and greater in cases with prior SH. AC may be a more sensitive biomarker of lesional activity, and a more efficient surrogate outcome in clinical trials than SH. Patients experiencing an AC are more likely to undergo a surgical intervention when CAs are solitary/sporadic than when they are multifocal/familial.

 

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Natural history of brainstem cavernous malformations

J Neurosurg 134:917–928, 2021

Given the paucity of data on the natural history of brainstem cavernous malformations (CMs), the authors aimed to evaluate the annual hemorrhage rate and hemorrhagic risk of brainstem CMs.

METHODS Nine hundred seventy-nine patients diagnosed with brainstem CMs were referred to Beijing Tiantan Hospital from 2006 to 2015; 224 patients were excluded according to exclusion criteria, and 47 patients were lost to follow-up. Thus, this prospective observational cohort included 708 cases (324 females). All patients were registered, clinical data were recorded, and follow-up was completed.

RESULTS Six hundred ninety (97.5%) of the 708 patients had a prior hemorrhage, 514 (72.6%) had hemorrhagic presentation, and developmental venous anomaly (DVA) was observed in 241 cases (34.0%). Two hundred thirty-seven prospective hemorrhages occurred in 175 patients (24.7%) during 3400.2 total patient-years, yielding a prospective annual hemorrhage rate of 7.0% (95% CI 6.2%–7.9%), which decreased to 4.7% after the 1st year. Multivariate Cox regression analysis after adjusting for sex and age identified hemorrhagic presentation (HR 1.574, p = 0.022), DVA (HR 1.678, p = 0.001), mRS score ≥ 2 on admission (HR 1.379, p = 0.044), lesion size > 1.5 cm (HR 1.458, p = 0.026), crossing the axial midpoint (HR 1.446, p = 0.029), and superficially seated location (HR 1.307, p = 0.025) as independent adverse factors for prospective hemorrhage, but history of prior hemorrhage was not significant. The annual hemorrhage rates were 8.3% and 4.3% in patients with and without hemorrhagic presentation, respectively; the rate was 9.9%, 6.0%, and 1.0% in patients with ≥ 2, only 1, and 0 prior hemorrhages, respectively; and the rate was 9.2% in patients with both hemorrhagic presentation and focal neurological deficit on admission.

CONCLUSIONS The study reported an annual hemorrhage rate of 7.0% exclusively for brainstem CMs, which significantly increased if patients presented with both hemorrhagic presentation and focal neurological deficit (9.2%), or any other risk factor. Patients with a risk factor for hemorrhage needed close follow-up regardless of the number of prior hemorrhages. It should be noted that the referral bias in this study could have overestimated the annual hemorrhage rate. This study improved the understanding of the natural history of brainstem CMs, and the results are important for helping patients and physicians choose a suitable treatment option based on the risk factors and stratified annual rates. Clinical trial registration no.: ChiCTR-POC-17011575 (http://www.chictr.org.cn/).

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Natural history of cavernous sinus meningiomas

J Neurosurg 130:435–442, 2019

Meningiomas confined to the cavernous sinus (MCSs) are benign tumors. Due to the high risk of severe complications, the intracavernous surgical procedure was abandoned in favor of radiotherapy. However, the choice of treatment remains complicated due to the fact that the natural history of this lesion has not yet been described.

METHODS The authors studied the natural history of this lesion using a prospective series of 53 consecutive patients suffering from MCSs. The median follow-up duration was 10.2 years (range 2–25 years), from 1990 to 2016.

RESULTS Patients ranged in age from 30 to 72 years (mean 53 years). The meningiomas were diagnosed by major symptoms (mainly oculomotor palsy and neuralgia experienced in 28 patients), minor symptoms (headache, intermittent diplopia in 15 patients), or incidental findings (10 patients). Simple symptomatic treatment (short courses of cortico- steroids and carbamazepine) allowed patients to become asymptomatic in 19 (67.9%) of 28 cases experiencing major symptoms, and for 12 (80%) of 15 patients with initial minor symptoms (p < 0.0001). All patients with incidental findings remained asymptomatic. Forty four (83%) of 53 MCSs did not show any significant growth and 42 (80%) of 53 patients were not symptomatic at the end of follow-up (p < 0.001). The radiographic progression-free survival rates (± SD) at 5, 10, and 20 years were 90% ± 4.2%, 82% ± 5.7%, and 70% ± 10.2%, respectively. Five patients (9.4%) with no evidence of any effect of the initial medical treatment desired additional conventional radiation therapy.

CONCLUSIONS Because of the capricious, unpredictable, and slow growth of MCSs, together with high growth variability from one patient to the next, the symptomatic medical treatment of these tumors is a highly effective method. This series shows that these lesions are naturally, clinically, and radiologically indolent.

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Unruptured intracranial aneurysms in patients over 80 years

Acta Neurochirurgica (2018) 160:1773–1777

Patients over the age of 80 years when diagnosed with an unruptured intracranial aneurysm (UIA) pose unique decisionmaking challenges due to shortened life-expectancy and increased risk of treatment. Thus, we investigated the risk of rupture and survival of a consecutive series of patients who were diagnosed with an UIA after the age of 80 years.

Methods Data of consecutive patients with an UIA were reviewed, and patients were included in our study if they were first evaluated for a UIA by the senior author during their ninth decade of life. Outcomes were aneurysm rupture and overall survival after diagnosis. Survival was estimated from a Kaplan-Meier survival curve. Incidence of risk factors was compared to a population of patients less than 65 years who were seen by the senior author over the same time period.

Results Eighty-three patients who were over 80 years when diagnosed with a UIA were included in this study. In our population, there is a risk of rupture of 3.2% per patient-year. One-, three-, and five-year survival rates for our population were estimated to be 92, 64, and 35%, respectively. When compared to patients under 65 years diagnosed with a UIA, Bover 80^ patients had a significantly higher incidence of hypertension, and a significantly lower incidence of smoking history and familial aneurysm history.

Conclusions In our study population, UIAs greater than 7 mm carry a non-negligible risk of rupture of 3.2% per patient-year, and further studies investigating the risk-to-benefit ratio of treatment in this population are warranted.

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Brainstem Cavernous Malformations: Surgical Indications Based on Natural History and Surgical Outcomes

World Neurosurg. (2018) 110:55-63

Cavernous malformations (CMs) are uncommon lesions occurring in the central nervous system, with an incidence of approximately 0.5% in the general population and constituting 5%e10% of all intracranial vascular malformations. Among CMs, prevalence within the brainstem as reported in the literature has ranged from 4% to 35%. With their precarious location and potentially devastating clinical events, brainstem CMs have attracted attention from neurosurgeons, and with these surgeons’ unrelenting efforts, the microsurgical techniques to treat these lesions in the brainstem have greatly improved in recent decades. Although surgical outcomes reported in the literature have been satisfying, surgical intervention has become increasingly contraindicated because of the tendency for a benign clinical course in brainstem CMs, after weighing this fact against the high risk of surgical morbidity. Thus, it is advisable to operate on patients with symptomatic lesions abutting the pial or ependymal surface of the brainstem or where lesions are accessible to safe entry zones, which have caused more than 1 significantly symptomatic hemorrhage and can be defined as aggressive. However, treatment remains controversial for deep-seated lesions away from the surface of the brainstem or lesions that are inaccessible to safe entry zones. Other treatments, such as radiosurgery and medication, are still debatable, which might be as an alternative for lesions amenable to but at high risk with surgery.

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A novel weighted scoring system for estimating the risk of rapid growth in untreated intracranial meningiomas

J Neurosurg 127:971–980, 2017

Advances in neuroimaging techniques have led to the increased detection of asymptomatic intracranial meningiomas (IMs). Despite several studies on the natural history of IMs, a comprehensive evaluation method for estimating the growth potential of these tumors, based on the relative weight of each risk factor, has not been developed. The aim of this study was to develop a weighted scoring system that estimates the risk of rapid tumor growth to aid treatment decision making.

METHODS The authors performed a retrospective analysis of 232 patients with presumed IM who had been prospectively followed up in the absence of treatment from 1997 to 2013. Tumor volume was measured by imaging at each follow-up visit, and the growth rate was determined by regression analysis. Predictors of rapid tumor growth (defined as ≥ 2 cm3/year) were identified using a logistic regression model; each factor was awarded a score based on its own coefficient value. The probability (P) of rapid tumor growth was estimated using the following formula:

[Eq. 1]

RESULTS Fifty-nine tumors (25.4%) showed rapid growth. Tumor size (OR per cm3 1.07, p = 0.000), absence of calcification (OR 3.87, p = 0.004), peritumoral edema (OR 2.74, p = 0.025), and hyperintense or isointense signal on T2- weighted MRI (OR 3.76, p = 0.049) were predictors of tumor growth rate. In the Asan Intracranial Meningioma Scoring System (AIMSS), tumor size was categorized into 3 groups of < 2.5 cm, ≥ 2.5 to < 4.0 cm, and ≥ 4.0 cm in diameter and awarded a score of 0, 3, and 6, respectively; the parameters of calcification and peritumoral edema were categorized into 2 groups based on their presence or absence and given a score of 0 or 2 and 1 or 0, respectively; and the signal on T2-weighted MRI was categorized into 2 groups of hypointense and hyperintense/isointense and given a score of 0 or 2, respectively. The risk of rapid tumor growth was estimated to be < 10% when the total score was 0–2, 10%–50% when the total score was 3–6, and ≥ 50% when the total score was 7–11 (Hosmer-Lemeshow goodness-of-fit test, p = 0.9958). The area under the receiver operating characteristic curve was 0.86.

CONCLUSIONS The authors suggest a weighted scoring system (AIMSS) that predicts the specific probability of rapid tumor growth for patients with untreated IM. This scoring system will aid treatment decision making in clinical settings by screening out patients at high risk for rapid tumor growth.

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Clinical course of untreated thalamic cavernous malformations: hemorrhage risk and neurological outcomes

J Neurosurg 127:480–491, 2017

The natural history of cerebral cavernous malformations (CMs) has been widely studied, but the clinical course of untreated thalamic CMs is largely unknown. Hemorrhage of these lesions can be devastating. The authors undertook this study to obtain a prospective hemorrhage rate and provide a better understanding of the prognosis of untreated thalamic CMs.

METHODS This longitudinal cohort study included patients with thalamic CMs who were diagnosed between 2000 and 2015. Clinical data were recorded, radiological studies were extensively reviewed, and follow-up evaluations were performed.

RESULTS A total of 121 patients were included in the study (56.2% female), with a mean follow-up duration of 3.6 years. The overall annual hemorrhage rate (subsequent to the initial presentation) was calculated to be 9.7% based on the occurrence of 42 hemorrhages over 433.1 patient-years. This rate was highest in patients (n = 87) who initially presented with hemorrhage and focal neurological deficits (FNDs) (14.1%) (c2 = 15.358, p < 0.001), followed by patients (n = 19) with hemorrhage but without FND (4.5%) and patients (n = 15) without hemorrhage regardless of symptoms (1.2%). The initial patient presentations of hemorrhage with FND (hazard ratio [HR] 2.767, 95% CI 1.336–5.731, p = 0.006) and associated developmental venous anomaly (DVA) (HR 2.510, 95% CI 1.275–4.942, p = 0.008) were identified as independent hemorrhage risk factors. The annual hemorrhage rate was significantly higher in patients with hemorrhagic presentation at diagnosis (11.7%, p = 0.004) or DVA (15.7%, p = 0.002). Compared with the modified Rankin Scale (mRS) score at diagnosis (mean 2.2), the final mRS score (mean 2.0) was improved in 37 patients (30.6%), stable in 59 patients (48.8%), and worse in 25 patients (20.7%). Lesion size (odds ratio [OR] per 0.1 cm increase 3.410, 95% CI 1.272–9.146, p = 0.015) and mRS score at diagnosis (OR per 1 point increase 3.548, 95% CI 1.815–6.937, p < 0.001) were independent adverse risk factors for poor neurological outcome (mRS score ≥ 2). Patients experiencing hemorrhage after the initial ictus (OR per 1 ictus increase 6.923, 95% CI 3.023–15.855, p < 0.001) had a greater chance of worsened neurological status.

CONCLUSIONS This study verified the adverse predictors for hemorrhage and functional outcomes of thalamic CMs and demonstrated an overall annual symptomatic hemorrhage rate of 9.7% after the initial presentation. These findings and the mode of initial presentation are useful for clinicians and patients when selecting an appropriate treatment, although the tertiary referral bias of the series should be taken into account.

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Intracranial Aneurysm Parameters for Predicting a Future Subarachnoid Hemorrhage

Neurosurgery 81:432–440, 2017

Retrospective studies have suggested that aneurysm morphology is a risk factor for subarachnoid hemorrhage (SAH).

OBJECTIVE: To investigate whether various morphological indices of unruptured intracranial aneurysms (UIAs) predict a future rupture.

METHODS: A total of 142 patients with UIAs diagnosed between 1956 and 1978 were followed prospectively until SAH, death, or the last contact. Morphological UIA indices from standard angiographic projections weremeasured at baseline and adjusted inmultivariable Cox proportional hazards regression analyses for established risk factors for SAH.

RESULTS: During a follow-up of 3064 person-years, 34 patients suffered froman aneurysm rupture. In multivariable analyses, aneurysm volume, volume-to-ostium area ratio, and the bottleneck factor separately as continuous variables predicted aneurysm rupture. All the morphological indices were higher (P < .01) after the rupture than before. In final multivariable analyses, current smoking (adjusted hazard ratio 2.50, 95% CI 1.03-6.10, P = .044), location in the anterior communicating artery (4.28, 1.38-13.28, P=.012), age (inversely; 0.95 per year, 0.91-1.00, P = .043), and UIA diameter ≥7 mm at baseline (2.68, 1.16-6.21, P = .021) were independent risk factors for a future rupture. Aneurysm growth during the followup was associated with smoking (P < .05) and SAH (P < .001), but not with the aneurysm indices.

CONCLUSION: Of the morphological indices, UIA volume seems to predict a future rupture. However, as volume correlates with the maximum diameter of the aneurysm, it seems to add little to the predictive value of the maximum diameter. Retrospective studies using indices that are measured after rupture are of little value in risk prediction.

 

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Hemorrhage from cerebral cavernous malformations

J Neurosurg 126:1079–1087, 2017

The aim of this paper is to define an overall cavernous malformation (CM) hemorrhage rate and risk factors for hemorrhage.

METHODS The authors performed a systematic, pooled analysis via the PubMed database through October 2015 using the terms “cavernoma,” “cavernous malformation,” “natural history,” “bleeding,” and “hemorrhage.” English-language studies providing annual rates and/or risk factors for CM hemorrhage were included. Data extraction, performed independently by the authors, included demographic data, hemorrhage rates, and hemorrhage risk factors.

RESULTS Across 12 natural history studies with 1610 patients, the mean age at presentation was 42.7 years old and 52% of patients (95% CI 49%–55%) were female. Presentation modality was seizure in 30% (95% CI 25%–35%), hemorrhage in 26% (95% CI 17%–37%), incidental in 17% (95% CI 9%–31%), and focal deficits only in 16% of cases (95% CI 11%–23%). CM location was lobar in 66% (95% CI 61%–70%), brainstem in 18% (95% CI 13%–24%), deep supratentorial in 8% (95% CI 6%–10%), and cerebellar in 8% (95% CI 5%–11%). Pooling 7 studies that did not assume CM presence since birth, the annual hemorrhage rate was 2.5% per patient-year over 5081.2 patient-years of follow-up (95% CI 1.3%–5.1%). Pooling hazard ratios across 5 studies that evaluated hemorrhage risk factors, prior CM hemorrhage was a significant risk factor for hemorrhage (HR 3.73, 95% CI 1.26–11.1; p = 0.02) while younger age, female sex, deep location, size, multiplicity, and associated developmental venous anomalies (DVAs) were not.

CONCLUSIONS Although limited by the heterogeneity of incorporated reports and selection bias, this study found prior hemorrhage to be a significant risk factor for CM bleeding, while age, sex, CM location, size, multiplicity, and associated DVAs were not. Future natural history studies should compound annual hemorrhage rate with prospective seizure and nonhemorrhagic neurological deficit rates.

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Unruptured internal carotid artery bifurcation aneurysms: general features and overall results after modern treatment

bicaa

Acta Neurochir (2016) 158:2053–2059

Internal carotid artery bifurcation aneurysms (ICAbifAs) present unique challenges to endovascular and surgical operators, and little is known about their natural history. We reviewed our institution’s experience with ICAbifAs studying outcomes of surgical and endovascular management and natural history.

Methods Consecutive patients with unruptured ICAbifAs evaluated and/or treated over an 8-year interval were studied. Baseline demographics, neurovascular risk factors, aneurysm location and size, clinical presentation, treatment recommendations, and outcomes were prospectively collected and retrospectively analyzed. Continuous variables were compared with Student’s t test and categorical variables with Chisquare tests.

Results Fifty-nine patients with 61 unruptured ICAbifAs were included. Seven aneurysms were treated surgically (11.5 %), 22 underwent endovascular treatment (36 %), and 32 were managed conservatively (52.5 %). In the surgical group, short- and long-term complete aneurysm occlusion rates were 100 % with no cases of perioperative or long-term permanent morbidity or treatmentrelated mortality. In the endovascular group, two patients (11.7 %) with giant aneurysms had perioperative thromboembolic events with transient morbidity. There was one case of aneurysm rupture at follow-up in a giant aneurysm treated with partial coil embolization. Complete/near-complete occlusion rates were 63 %. There was one case of aneurysm rupture after 114 aneurysm-years of follow-up in the conservative management group (0.89 %/year), but no ruptures were observed in small aneurysms selected for conservative management.

Conclusions Unruptured small ICAbifAs have a benign natural history. In patients selected for treatment, excellent results can be achieved in the vast majority of patients with judicious use of endovascular and surgical therapy.

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Surgically managed idiopathic intracranial hypertension in adults

Idiopathic intracranial hypertension

Acta Neurochir (2015) 157:2099–2103

Idiopathic intracranial hypertension (IIH) is a rare condition that is often managed conservatively. In patients with aggressive progression of the disease surgical options are considered. There are few data on the outcomes of these patients when surgically managed. We describe our experience of surgically managed IIH and the outcomes of these patients, in particular the surgical revision rate and interventions required for resolution of symptoms.

Methods A retrospective review of all patient files coded with benign intracranial hypertension, idiopathic intracranial hypertension or pseudotumour cerebri was undertaken. Files were searched with the date of diagnosis and the date these patients were referred for surgical intervention. The surgical interventions and complications were then documented and note was made of the number of inpatient admissions and days spent in hospital.

Results From 2000–2013, 79 patients were identified as patients with IIH that had required surgical intervention; 52 % required further surgical intervention. The average number of surgical interventions was 5.6. For patients requiring further intervention the average number of surgical interventions was 8.6. On average patients with IIH also spent 42 inpatient days in neurosurgical beds, whilst those patients who required further intervention spent 63 days on average in neurosurgical beds. The length of the average individual admission was longer for patients requiring repeated surgical interventions.

Conclusion Based on our experience, patients that require surgical management of IIH frequently require further surgical interventions to control symptoms and manage complications of CSF diversion surgery. Those that require such further intervention on average will have six further operations and spend significantly longer in hospital. Lumboperitoneal (LP) shunting is an effective first line surgical intervention for 52% of our patient cohort. This sub-group of patients therefore requires specialist neurosurgical input for this long-term and challenging pathological process.

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Hemorrhage risks and functional outcomes of untreated brainstem cavernous malformations

brainstem cavernous malformations

J Neurosurg 121:32–41, 2014

Cerebral cavernous malformations have been studied widely, but the natural history of brainstem cavernous malformations (CMs) is not well defined, and hemorrhages caused by brainstem CMs are devastating. The goal of this study was to quantify the hemorrhage risks and functional outcomes of patients with brainstem CMs.

Methods. This prospective, longitudinal, cohort study included patients with brainstem CMs diagnosed between 1985 and 2012. The clinical courses of all patients were recorded. Predictors of hemorrhage and the overall untreated outcomes were evaluated.

Results. A total of 331 patients (46.5% female) were included, with a mean follow-up duration of 6.5 years. The annual hemorrhage rates in patients initially presenting with hemorrhage with (n = 215) or without (n = 34) focal neurological deficits were 15.9% and 12.4%, respectively. However, the annual hemorrhage rate was 8.7% in patients initially presenting without hemorrhage (n = 82). The risk factors for hemorrhage were female sex (hazard ratio [HR] 1.445, p = 0.041), prior hemorrhage (HR 1.277, p = 0.029), and perilesional edema (HR 1.830, p = 0.002). Overall, neurological function at the most recent assessment was improved compared with neurological function at diagnosis. Additionally, 307 patients (92.7%) improved or stabilized, 268 (81.0%) lived independently, and 95 (28.7%) completely recovered. Predictors favoring complete recovery were no prospective hemorrhage (HR 1.958, p = 0.001), younger age (HR 1.268, p = 0.001), and small lesion size (HR 1.578, p = 0.004).

Conclusions. Patients’ initial presentation predicts their prospective annual hemorrhage rate. This study suggests that several strong risk factors for hemorrhage and predictors of brainstem CM outcomes may enable clinicians to evaluate the potential hemorrhage risks of their patients and design personalized treatments.

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Long-term natural history of incidentally discovered cavernous malformations in a single-center cohort

cavmal2_600

J Neurosurg 120:1188–1192, 2014

The aim of this study was to determine the prospective hemorrhage rate in a group of retrospectively identified patients in whom symptoms had an unclear relationship to an intracerebral cavernous malformation (ICM) or the malformation itself was an incidental finding.

Methods. Patients with incidentally discovered ICMs diagnosed between 1989 and 1999 were identified from a previously published cohort. Those with ICMs having an unclear relationship with existing symptoms were also eligible for analysis. Updated clinical and radiographic data pertaining to symptomatic intracerebral hemorrhage related to the ICM or new seizures were obtained through medical chart review and mail survey. In select patients, phone calls were made and death certificates were obtained when possible. The prospective hemorrhage rate was calculated as the number of prospective hemorrhages divided by the number of patient-years of follow-up.

Results. There were 1311 patient-years of follow-up among the 107 patients (49.5% male; mean age at diagnosis 52 years) eligible for this study. Forty-four patients died in the follow-up period, and the cause of death could be determined in 34 (77%). Two patients had a prospective hemorrhage, which was definitively related to the ICM in only one. Thus, the definitive prospective bleed rate was 0.08% per patient-year. No new seizures developed in any of the patients during the follow-up period.

Conclusions. The risk of prospective hemorrhage in patients presenting asymptomatically with ICM is very low. This information can be useful in managing such patients and may be most applicable to those with a single ICM.

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