Cavernous venous malformations in and around the central nervous system. Part 1: Dural and extradural

J Neurosurg 140:735–745, 2024

Cavernous-type malformations are venous lesions that occur in multiple locations throughout the body, and when present in the CNS, they have canonically been referred to as cavernomas, cavernous angiomas, and cerebral cavernous malformations. Herein all these lesions are referred to as “cavernous venous malformations” (CavVMs), which is congruent with the current International Society for the Study of Vascular Anomalies classification system.

Even though histologically similar, depending on their location relative to the dura mater, these malformations can have different features. In Part 1 of this review, the authors discuss and review pertinent clinical knowledge with regard to CavVMs as influenced by anatomical location, starting with the dural and extradural malformations. They particularly emphasize dural CavVMs (including those in the cavernous sinus), orbital CavVMs, and spinal CavVMs. The genetic and histopathological features of CavVMs in these locations are reviewed, and commonalities in their presumed mechanisms of pathogenesis support the authors’ conceptualization of a spectrum of a single disease entity. Illustrative cases for each subtype are presented, and the pathophysiological and genetic features linking dural and extradural to intradural CavVMs are examined.

A new classification is proposed to segregate CavVMs based on the location from which they arise, which guides their natural history and treatment.

Safety of brainstem safe entry zones: comparison of microsurgical outcomes associated with superficial, exophytic, and deep brainstem cavernous malformations

J Neurosurg 139:113–123, 2023

Safe entry zones (SEZs) enable safe tissue transgression to lesions beneath the brainstem surface. However, evidence for the safety of SEZs is scarce and is based on anatomical studies, case reports, and small series.

METHODS A cohort of 154 patients who underwent microsurgical brainstem cavernous malformation (BSCM) treatment during a 23-year period and who had preoperative MR images and intraoperative photographs or videos was retrospectively examined. This study assessed the safety of SEZs for access to deep BSCMs, preoperative MRI to predict BSCM surface proximity, and the relationships between BSCM subtype, surgical approach, and SEZs. Lesions were characterized as exophytic, superficial, or deep on the basis of preoperative MRI and intraoperative inspection. Outcomes were scored as good (modified Rankin Scale [mRS] score ≤ 2) or poor (mRS score > 2) and relative outcomes as stable/ improved or worse relative to baseline (± 1 point).

RESULTS Resections included 34 (22%) in the midbrain, 102 (66%) in the pons, and 18 (12%) in the medulla. Of those, 23 (15%) were exophytic, 57 (37%) were superficial, and 74 (48%) were deep. Established SEZs were used for 97% (n = 72) of deep lesions; the preferred SEZ associated with its subtype was used for 91% (n = 67). MR images accurately depicted exophytic BSCMs that did not require SEZ approaches (sensitivity, 96%) but overestimated the proximity of lesions superficial to brainstem surfaces (specificity, 67%), resulting in unanticipated SEZ use. Final neurological outcomes were good in 80% of patients with follow-up data (119/149), and relative outcomes were stable/improved in 93% (139/149). Outcomes for patients with brainstem transgression through an SEZ did not differ from outcomes for patients with superficial or exophytic lesions that did not require SEZ use (final mRS score ≤ 2 in 72% of all patients with deep lesions vs 82% of all patients with superficial or exophytic lesions [p = 0.10]). Among patients with follow-up, the rates of permanent new cranial nerve deficits in patients with deep BSCMs and superficial or exophytic BSCMs were 21% and 20%, respectively (p = 0.81), with no significant change in overall cranial nerve deficit (0 and −1, p = 0.65).

CONCLUSIONS Neurological outcomes for patients with deep BSCMs were equivalent to those for superficial or exophytic BSCMs, validating the safety of SEZs for deep BSCMs. Preoperative T1-weighted MR images overestimated the lesion’s surface proximity, necessitating detailed knowledge of SEZs and readiness to use them in cases of radiologicalmicrosurgical discordance. Most patients achieved favorable outcomes despite the transgression of eloquent brainstem tissue in and around SEZs.

Presigmoid approach preserving the superior petrosal sinus in a pontine cavernous malformation associated to abnormal venous drainage of the brainstem

Acta Neurochirurgica (2023) 165:1233–1240

The presigmoid approach classically includes the ligature and section of the superior petrosal sinus to get a wider visibility window to the antero-lateral brainstem surface. In some cases, the separation of this venous structure should not be performed.

Method We present our experience getting safely to a pontine cavernous malformation through a conventional mastoidectomy presigmoid approach preserving an ingurgitated superior petrosal sinus because the association with an abnormal venous drainage of the brainstem.

Conclusions When sectioning the superior petrosal sinus in classical presigmoid approaches is contraindicated, its preservation could also offer good surgical corridors to get to small-medium anterior and lateral brainstem cavernous malformations.

Endoscope‐assisted resection of brainstem cavernous malformations

Neurosurgical Review (2022) 45:2823–2836

Targeted surgical precision and minimally invasive techniques are of utmost importance for resectioning cavernous malformations involving the brainstem region. Minimisation of the surgical corridor is desirable but should not compromise the extent of resection.

This study provides detailed information on the role of endoscopy in this challenging surgical task. A retrospective analysis of medical documentation, radiologic studies and detailed intraoperative video documentation was performed for all consecutive patients who underwent surgical resection of brainstem cavernous malformations between 2010 and 2020 at the authors’ institution.

A case-based volumetry of the corticotomy was performed and compared to cavernoma dimensions. A total of 20 procedures have been performed in 19 patients. Neuroendoscopy was implemented in all cases. The mean size of the lesion was 5.4 (± 5) mm3. The average size of the brainstem corticotomy was 4.5 × 3.7 (± 1.0 × 1.1) mm, with a median relation to the cavernoma’s dimension of 9.99% (1.2–31.39%). Endoscopic 360° inspection of the resection cavity was feasible in all cases. There were no endoscopy-related complications. Mean follow-up was 27.8 (12–89) months.

Gross-total resection was achieved in all but one case (95%). Sixteen procedures (80%) resulted in an improved or stable medical condition. Eleven patients (61.1%) showed further improvement 12 months after the initial surgery. With the experience provided, endoscopic techniques can be safely implemented in surgery for BSCM. A combination of neuroendoscopic visualisation and neuronavigation might enable a targeted size of brainstem corticotomy.

Endoscopy can currently be considered a valuable additive tool to facilitate the preparation and resection of BSCM.

A taxonomy for brainstem cavernous malformations: subtypes of midbrain lesions

J Neurosurg 136:1667–1686, 2022

Anatomical taxonomy is a practical tool that has successfully guided clinical decision-making for patients with brain arteriovenous malformations. Brainstem cavernous malformations (BSCMs) are similarly complex lesions that are difficult to access and highly variable in size, shape, and position. The authors propose a novel taxonomy for midbrain cavernous malformations based on clinical presentation (syndromes) and anatomical location (identified with MRI).

METHODS The taxonomy system was developed and applied to an extensive 2-surgeon experience over a 30-year period (1990–2019). Of 551 patients with appropriate data who underwent microsurgical resection of BSCMs, 151 (27.4%) had midbrain lesions. These lesions were further subtyped on the basis of predominant surface presentation identified on preoperative MRI. Five distinct subtypes of midbrain BSCMs were defined: interpeduncular (7 lesions [4.6%]), peduncular (37 [24.5%]), tegmental (73 [48.3%]), quadrigeminal (27 [17.9%]), and periaqueductal (7 [4.6%]). Neurological outcomes were assessed using modified Rankin Scale (mRS) scores. A postoperative score ≤ 2 was defined as a favorable outcome; a score > 2 was defined as a poor outcome. Clinical and surgical characteristics and neurological outcomes were compared among subtypes.

RESULTS Each midbrain BSCM subtype was associated with a recognizable constellation of neurological symptoms. Patients with interpeduncular lesions commonly presented with ipsilateral oculomotor nerve palsy and contralateral cerebellar ataxia or dyscoordination. Peduncular lesions were associated with contralateral hemiparesis and ipsilateral oculomotor nerve palsy. Patients with tegmental lesions were the most likely to present with contralateral sensory deficits, whereas those with quadrigeminal lesions commonly presented with the features of Parinaud syndrome. Periaqueductal lesions were the most likely to cause obstructive hydrocephalus. A single surgical approach was preferred (> 90% of cases) for each midbrain subtype: interpeduncular (transsylvian-interpeduncular approach [7/7 lesions]), peduncular (transsylvian-transpeduncular [24/37]), tegmental (lateral supracerebellar-infratentorial [73/73]), quadrigeminal (midline or paramedian supracerebellar-infratentorial [27/27]), and periaqueductal (transcallosal-transchoroidal fissure [6/7]). Favorable outcomes (mRS score ≤ 2) were observed in most patients (110/136 [80.9%]) with follow-up data. No significant differences in outcomes were observed between subtypes (p = 0.92).

CONCLUSIONS The study confirmed the authors’ hypothesis that taxonomy for midbrain BSCMs can meaningfully guide the selection of surgical approach and resection strategy. The proposed taxonomy can increase diagnostic acumen at the patient bedside, help identify optimal surgical approaches, enhance the consistency of clinical communications and publications, and improve patient outcomes.



Anatomo‑functional evaluation for management and surgical treatment of insular cavernous malformation: a case series

Acta Neurochirurgica (2022) 164:1675–1684

Insular cavernous malformations (iCMs) are very rare vascular lesions. Their surgical management is chal- lenging, due to their complex functional and vascular relationship. The continuous improvement of intra-operative tools and neuroimaging techniques has progressively enhanced the safety of iCM surgery. Nevertheless, the best surgical approach remains controversial.

Objective To analyze the potential role of an anatomo-functional classification to guide the iCMs’ management.

Methods The study included patients affected by iCMs and referred to the Senior Author (FA). All cases were divided in 2 groups, according to a mainly pial growth pattern (exophytic group) or a subcortical one (endophytic group). Endophytic iCM was further subdivided in 3 subgroups, based on the insular gyri involved. According to this classification, each patient underwent a specific additional neuroimaging investigation and surgical evaluation.

Results A total of 24 patients were included. In the surgical group, trans-sylvian (TS) approach was used in 6 patients with exophytic or Zone I endophytic iCMs. The transcortical (TC) approach with awake monitoring was used in 6 cases of Zone II endophytic vascular lesions. Both TS and trans-intraparietal sulcal (TIS) approach were used for 3 cases of Zone III endophytic iCM. At follow-up, 3 patients were fully recovered from a transient speech impairment while a permanent morbidity was observed in one case.

Conclusions ICMs represent a single entity with peculiar clinical and surgical aspects. The proposed iCM classification focuses on anatomical and functional concerns, aiming to suggest the best pre-operative work-up and the surgical evaluation.

How I do it: horizontal fissure approach to the middle cerebellar peduncle

Acta Neurochirurgica (2022) 164:763–766

The horizontal fissure approach is a workhorse for brainstem lesions in the central and dorsolateral pons and middle cerebellar peduncle (MCP). The cerebellopontine fissure is a V-shaped fissure with a superior and inferior limb between the cerebellum, pons, and MCP. The horizontal or petrosal fissure is at the apex of the cerebellopontine fissure and extends laterally to divide the petrosal surface of the cerebellum into superior and inferior parts. Splitting this fissure exposes the posterolateral aspect of the MCP without excessive retraction or transgression of the cerebellum.

Method We demonstrate and describe the horizontal fissure operative approach to the middle cerebellar peduncle for resection of a pontine cavernoma with illustrative figures and operative video.

Conclusion Splitting the horizontal (petrosal) fissure of the cerebellum brings the middle cerebellar peduncle into view behind the root entry zone of the trigeminal nerve, providing an expanded, safe corridor to the central and dorsolateral pons.


Basal ganglia cavernous malformations: case series and systematic review of surgical management and long-term outcomes

J Neurosurg 135:1113–1121, 2021

Reports on basal ganglia cavernous malformations (BGCMs) are rare. Here, the authors report on their experience in resecting these malformations to offer insight into this infrequent disease subtype.

METHODS The authors retrospectively reviewed a prospectively managed departmental database of all deep-seated cerebral cavernous malformations (CCMs) treated at Stanford between 1987 and 2019 and included for further analysis those with a radiographic diagnosis of BGCM. Moreover, a systematic literature review was undertaken using the PubMed and Web of Science databases.

RESULTS The departmental database search yielded 331 patients with deep-seated CCMs, 44 of whom had a BGCM (13.3%). Headache was the most common presenting sign (53.5%), followed by seizure (32.6%) and hemiparesis (27.9%). Lesion location involved the caudate nucleus in 21.4% of cases compared to 78.6% of cases within the lentiform nucleus. Caudate BGCMs were larger on presentation and were more likely to present to the ependymal surface (p < 0.001) with intraventricular hemorrhage and hydrocephalus (p = 0.005 and 0.007, respectively). Dizziness and diplopia were also more common with lesions involving the caudate. Because of their anatomical location, caudate BGCMs were preferentially treated via an interhemispheric approach and were less likely to be associated with worsening perioperative deficits than lentiform BGCMs (p = 0.006 and 0.045, respectively). Ten patients (25.6%) were clinically worse in the immediate postoperative period, 4 (10.2%) of whom continued to suffer permanent morbidity at the last follow-up. A longterm good outcome (modified Rankin Scale [mRS] score 0–1) was attained in 74.4% of cases compared to the 69.2% of patients who had presented with an mRS score 0–1. Relative to their presenting mRS score, 89.8% of patients had an improved or unchanged status at the last follow-up. The median postoperative follow-up was 11 months (range 1–252 months). Patient outcomes after resection did not differ among surgical approaches; however, patients presenting with hemiparesis and lesions involving the globus pallidus or posterior limb of the internal capsule were more likely to suffer neurological deficits during the immediate perioperative period. Patients who had undergone awake surgeries were more likely to suffer neurological decline at the early as well as the late follow-up. When adjusting for awake craniotomy as a potential confounder of lesion location, a BGCM involving the posterior limb was predictive of developing early postoperative deficits, but this finding did not persist at the long-term follow-up.

CONCLUSIONS Surgery is a safe and effective treatment modality for managing BGCMs, with an estimated long-term permanent morbidity rate of around 10%.


Parietal trans‑sulcal para‑fascicular approach to lateral thalamic/internal capsule cavernous malformation

Acta Neurochirurgica (2021) 163:2497–2501

The surgical management of deep brain lesions is challenging, with significant morbidity. Advances in surgical technology have presented the opportunity to tackle these lesions.

Methods We performed a complete resection of a thalamic/internal capsule CM using a tubular retractor system via a parietal trans-sulcal para-fascicular (PTPF) approach without collateral injury to the nearby white matter tracts.

Conclusion PTPF approach to lateral thalamic/internal capsule lesions can be safely performed without injury to eloquent white matter fibres. The paucity of major vessels along this trajectory and the preservation of lateral ventricle integrity make this approach a feasible alternative to traditional approaches.

Optimal access route for pontine cavernous malformation resection with preservation of abducens and facial nerve function

J Neurosurg 135:683–692, 2021

The aim of this study was to analyze the differences between posterolateral and posteromedial approaches to pontine cavernous malformations (PCMs) in order to verify the hypothesis that a posterolateral approach is more favorable with regard to preservation of abducens and facial nerve function.

METHODS The authors conducted a retrospective analysis of 135 consecutive patients who underwent microsurgical resection of a PCM. The vascular lesions were first classified in a blinded fashion into 4 categories according to the possible or only reasonable surgical access route. In a second step, the lesions were assessed according to which approach was performed and different patient groups and subgroups were determined. In a third step, the modified Rankin Scale score and the rates of permanent postoperative abducens and facial nerve palsies were assessed.

RESULTS The largest group in this series comprised 77 patients. Their pontine lesion was eligible for resection from either a posterolateral or posteromedial approach, in contrast to the remaining 3 patient groups in which the lesion location already had dictated a specific surgical approach. Fifty-four of these 77 individuals underwent surgery via a posterolateral approach and 23 via a posteromedial approach. When comparing these 2 patient subgroups, there was a statistically significant difference between postoperative rates of permanent abducens (3.7% vs 21.7%) and facial (1.9% vs 21.7%) nerve palsies. In the entire patient population, the abducens and facial nerve deficit rates were 5.9% and 5.2%, respectively, and the modified Rankin Scale score significantly decreased from 1.6 ± 1.1 preoperatively to 1.0 ± 1.1 at follow-up.

CONCLUSIONS The authors’ results suggest favoring a posterolateral over a posteromedial access route to PCMs in patients in whom a lesion is encountered that can be removed via either surgical approach. In the present series, the authors have found such a constellation in 57% of all patients. This retrospective analysis confirms their hypothesis in a large patient cohort. Additionally, the authors demonstrated that 4 types of PCMs can be distinguished by preoperatively evaluating whether only one reasonable or two alternative surgical approaches are available to access a specific lesion. The rates of postoperative sixth and seventh nerve palsies in this series are substantially lower than those in the majority of other published reports.

Intraoperative facial motor evoked potential monitoring for pontine cavernous malformation resection

J Neurosurg 132:265–271, 2020

The aim of this study was to predict postoperative facial nerve function during pontine cavernous malformation surgery by monitoring facial motor evoked potentials (FMEPs).

METHODS From 2008 to 2017, 10 patients with pontine cavernous malformations underwent total resection via the trans–fourth ventricle floor approach with FMEP monitoring. House-Brackmann grades and Karnofsky Performance Scale (KPS) scores were obtained pre- and postoperatively. The surgeries were performed using one of 2 safe entry zones into the brainstem: the suprafacial triangle and infrafacial triangle approaches. Six patients underwent the suprafacial triangle approach, and 4 patients underwent the infrafacial triangle approach. A cranial peg screw electrode was used to deliver electrical stimulation for FMEP by a train of 4 or 5 pulse anodal constant current stimulation. FMEP was recorded from needle electrodes on the ipsilateral facial muscles and monitored throughout surgery by using a threshold- level stimulation method.

RESULTS FMEPs were recorded and analyzed in 8 patients; they were not recorded in 2 patients who had severe preoperative facial palsy and underwent an infrafacial triangle approach. Warning signs appeared in all patients who underwent the suprafacial triangle approach. However, after temporarily stopping the procedures, FMEP findings during surgery showed recovery of the thresholds. FMEPs in patients who underwent the infrafacial triangle approach were stable during the surgery. House-Brackmann grades were unchanged postoperatively in all patients. Postoperative KPS scores improved in 3 patients, decreased in 1, and remained the same in 6 patients.

CONCLUSIONS FMEPs can be used to monitor facial nerve function during surgery for pontine cavernous malformations, especially when the suprafacial triangle approach is performed.

Prospective validation of a molecular prognostication panel for clival chordoma

J Neurosurg 130:1528–1537, 2019

There are currently no reliable means to predict the wide variability in behavior of clival chordoma so as to guide clinical decision-making and patient education. Furthermore, there is no method of predicting a tumor’s response to radiation therapy.

METHODS A molecular prognostication panel, consisting of fluorescence in situ hybridization (FISH) of the chromosomal loci 1p36 and 9p21, as well as immunohistochemistry for Ki-67, was prospectively evaluated in 105 clival chordoma samples from November 2007 to April 2016. The results were correlated with overall progression-free survival after surgery (PFSS), as well as progression-free survival after radiotherapy (PFSR).

RESULTS Although Ki-67 and the percentages of tumor cells with 1q25 hyperploidy, 1p36 deletions, and homozygous 9p21 deletions were all found to be predictive of PFSS and PFSR in univariate analyses, only 1p36 deletions and homozygous 9p21 deletions were shown to be independently predictive in a multivariate analysis. Using a prognostication calculator formulated by a separate multivariate Cox model, two 1p36 deletion strata (0%–15% and > 15% deleted tumor cells) and three 9p21 homozygous deletion strata (0%–3%, 4%–24%, and ≥ 25% deleted tumor cells) accounted for a range of cumulative hazard ratios of 1 to 56.1 for PFSS and 1 to 75.6 for PFSR.

CONCLUSIONS Homozygous 9p21 deletions and 1p36 deletions are independent prognostic factors in clival chordoma and can account for a wide spectrum of overall PFSS and PFSR. This panel can be used to guide management after resection of clival chordomas.


The future of open vascular neurosurgery: perspectives on cavernous malformations, AVMs, and bypasses for complex aneurysms

Despite the erosion of microsurgical case volume because of advances in endovascular and radiosurgical therapies, indications remain for open resection of pathology and highly technical vascular repairs. Treatment risk, efficacy, and durability make open microsurgery a preferred option for cerebral cavernous malformations, arteriovenous malformations (AVMs), and many aneurysms.

In this paper, a 21-year experience with 7348 cases was reviewed to identify trends in microsurgical management. Brainstem cavernous malformations (227 cases), once considered inoperable and managed conservatively, are now resected in increasing numbers through elegant skull base approaches and newly defined safe entry zones, demonstrating that microsurgical techniques can be applied in ways that generate entirely new areas of practice.

Despite excellent results with microsurgery for low-grade AVMs, brain AVM management (836 cases) is being challenged by endovascular embolization and radiosurgery, as well as by randomized trials that show superior results with medical management. Reviews of ARUBA-eligible AVM patients treated at high-volume centers have demonstrated that open microsurgery with AVM resection is still better than many new techniques and less invasive approaches that are occlusive or obliterative. Although the volume of open aneurysm surgery is declining (4479 cases), complex aneurysms still require open microsurgery, often with bypass techniques. Intracranial arterial reconstructions with reimplantations, reanastomoses, in situ bypasses, and intracranial interpositional bypasses (third-generation bypasses) augment conventional extracranial-intracranial techniques (first- and second-generation bypasses) and generate innovative bypasses in deep locations, such as for anterior inferior cerebellar artery aneurysms. When conventional combinations of anastomoses and suturing techniques are reshuffled, a fourth generation of bypasses results, with eight new types of bypasses. Type 4A bypasses use in situ suturing techniques within the conventional anastomosis, whereas type 4B bypasses maintain the basic construct of reimplantations or reanastomoses but use an unconventional anastomosis. Bypass surgery (605 cases) demonstrates that open microsurgery will continue to evolve. The best neurosurgeons will be needed to tackle the complex lesions that cannot be managed with other modalities. Becoming an open vascular neurosurgeon will be intensely competitive. The microvascular practice of the future will require subspecialization, collaborative team effort, an academic medical center, regional prominence, and a large catchment population, as well as a health system that funnels patients from hospital networks outside the region. Dexterity and meticulous application of microsurgical technique will remain the fundamental skills of the open vascular neurosurgeon.


Contralateral anterior interhemispheric transcallosal- transrostral approach to the subcallosal region

J Neurosurg 129:508–514, 2018

The authors report a novel surgical route from a superior anatomical aspect—the contralateral anterior interhemispheric-transcallosal-transrostral approach—to a lesion located in the subcallosal region. The neurosurgical approach to the subcallosal region is challenging due to its deep location and close relationship with important vascular structures. Anterior and inferior routes to the subcallosal region have been described but risk damaging the branches of the anterior cerebral artery.

METHODS Three formalin-fixed and silicone-injected adult cadaveric heads were studied to demonstrate the relationships between the transventricular surgical approach and the subcallosal region. The surgical, clinical, and radiological history of a 39-year-old man with a subcallosal cavernous malformation was retrospectively used to document the neurological examination and radiographic parameters of such a case.

RESULTS The contralateral anterior interhemispheric-transcallosal-transrostral approach provides access to the subcallosal area that also includes the inferior portion of the pericallosal cistern, lamina terminalis cistern, the paraterminal and paraolfactory gyri, and the anterior surface of the optic chiasm. The approach avoids the neurocritical perforating branches of the anterior communicating artery.

CONCLUSIONS The contralateral anterior interhemispheric-transcallosal-transrostral approach may be an alternative route to subcallosal area lesions, with less risk to the branches of the anterior cerebral artery, particularly the anterior communicating artery perforators.

Transcondylar approach for resection of lateral medullary cavernous malformation

Acta Neurochir (2018) 160:291–294

Resection of a medullary cavernous malformation requires aggressive exposure, but there is controversy on how much occipital condyle can be safely removed during the transcondylar approach.

Method We describe and demonstrate the use of the transcondylar approach to a medullary cavernous malformation, with emphasis on adequate surgical exposure while preserving the atlanto-occipital joint.

Conclusions Despite conservative handling of the occipital condyle, craniocervical stability may vary in patients after transcondylar surgery. A “dynamic” computer tomography, with views of the atlanto-occipital joint at each end-rotational extreme, may be the best postoperative assessment tool to evaluate the stability of the craniocervical junction.

Impact of Timing of Intervention Among 397 Consecutively Treated Brainstem Cavernous Malformations

Neurosurgery 81:620–626, 2017

Surgical resection of brainstem cavernous malformations (BSCMs) is challenging, and patient selection and timing of intervention remain controversial.

OBJECTIVE: To evaluate the impact of surgical timing and predictors of neurological outcome after surgical resection of BSCMs.

METHODS: Consecutive adult patients (≥18 years) with BSCMs undergoing surgical resection between 1985 and 2014 by the senior author (RFS)were retrospectively reviewed. Patient demographics, lesion characteristics, imaging results, surgical approach, and perioperative and long-term neurological morbidity were analyzed.

RESULTS: Data were analyzed for a total of 397 adult patients (160, 40% male).On univariate analysis, a greater proportion of patients treated within 6 weeks of hemorrhage had an improved Glasgow Outcome Scale score (P = .06). On logistic regression analysis, patients treated within 6weeks of hemorrhage experienced improved clinical outcomes (odds ratio = 1.73; 95% confidence interval = 1.06-2.83; P = .03).

CONCLUSIONS: Although BSCM surgery is associated with significant perioperative morbidity and mortality, favorable long-term hemorrhage rates and symptom resolution can be achieved in a carefully selected group of patients. Overall, patients treated acutely, within 6 weeks, benefited the most from surgical intervention.

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.

Endoscopic endonasal transclival resection of a ventral pontine cavernous malformation

J Neurosurg 127:553–558, 2017

Brainstem cavernous malformations are challenging due to the critical anatomy and potential surgical risks. Anterolateral, lateral, and dorsal surgical approaches provide limited ventral exposure of the brainstem.

The authors present a case of a midline ventral pontine cavernous malformation resected through an endoscopic endonasal transclival approach based on minimal brainstem transection, negligible cranial nerve manipulation, and a straightforward trajectory.

Technical and reconstruction technique advances in endoscopic endonasal skull base surgery provide a direct, safe, and effective corridor to the brainstem.

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.

Qualitative analysis of spinal intramedullary lesions using PET/CT

Qualitative analysis of spinal intramedullary lesions using PET-CT.1

J Neurosurg Spine 23:613–619, 2015

Although the usefulness of PET for brain lesions has been established, few reports have examined the use of PET for spinal intramedullary lesions. This study investigated the diagnostic utility of PET/CT for spinal intramedullary lesions.

Methods l-[methyl-11C]-methionine (MET)– or [18F]-fluorodeoxyglucose (FDG)–PET/CT was performed in 26 patients with spinal intramedullary lesions. The region of interest (ROI) within the spinal cord parenchyma was placed manually in the axial plane. Maximum pixel counts in the ROIs were normalized to the maximum standardized uptake value (SUVmax) using subject body weight. For FDG-PET the SUVmax was corrected for lean body mass (SULmax) to exclude any influence of the patient’s body shape. Each SUV was analyzed based on histopathological results after surgery. The diagnostic validity of the SUV was further compared with the tumor proliferation index using the MIB-1 monoclonal antibody (MIB-1 index).

Results A total of 16 patients underwent both FDG-PET and MET-PET, and the remaining 10 patients underwent either FDG-PET or MET-PET. Pathological diagnoses included high-grade malignancy such as glioblastoma multiforme, anaplastic astrocytoma, or anaplastic ependymoma in 5 patients; low-grade malignancy such as hemangioblastoma, diffuse astrocytoma, or ependymoma in 12 patients; and nonneoplastic lesion including cavernous malformation in 9 patients. Both FDG and MET accumulated significantly in high-grade malignancy, and the SULmax and SUVmax correlated with the tumor proliferation index. Therapeutic response after chemotherapy or radiation in high-grade malignancy was well monitored. However, a significant difference in SULmax and SUVmax for FDG-PET and MET-PET was not evident between low-grade malignancy and nonneoplastic lesions.

Conclusions Spinal PET/CT using FDG or MET for spinal intramedullary lesions appears useful and practical, particularly for tumors with high-grade malignancy. Differentiation of tumors with low-grade malignancy from nonneoplastic lesions may still prove difficult. Further technological refinement, including the selection of radiotracer or analysis evaluation methods, is needed.