Cerebral cavernous malformations (CCMs) are common vascular malformations of the central nervous system. CCMs occur in both sporadic and familial forms, frequently affecting young adults, typically between the ages of 20 and 50 (1–3). The sporadic form is generally associated with a single isolated lesion, while the familial form is linked to multiple lesions and mutations in three specific genes: CCM1, CCM2, and CCM3. Familial cerebral cavernous malformations (FCCM) are inherited in an autosomal dominant manner due to heterozygous mutations in one of these three genes, with approximately 40-60% of FCCM cases being attributed to this mode of inheritance (4–6). The natural course of cavernous malformations is relatively benign, with about 21% of patients remaining asymptomatic. However, depending on the location and size of the lesions, patients may present with clinical symptoms such as seizures, headaches, neurological deficits, and intracerebral hemorrhage (7–9). Most cavernous malformations are supratentorial, with the incidence of midbrain CCMs being around 9%-35% (10, 11). Here, we report two rare cases of midbrain aqueductal CCMs and discuss them in the context of a literature review.

A total of 14 articles, encompassing 15 cases, met these criteria (12–25), with details summarized in Table 1 . In these cases, nearly all patients presented with hydrocephalus caused by CCM mass effect, with no specific neurological deficits directly attributable to the tumor itself. Among the 15 reported cases, 7 patients received treatment solely targeting hydrocephalus symptoms, including endoscopic third ventriculostomy (ETV) and ventriculoperitoneal (VP) shunting. Of these, 6 cases achieved favorable outcomes with significant symptom improvement, while 1 case had a poor prognosis due to postoperative hemorrhage within hours after surgery. In Case 5, although surgical resection was performed, only the thalamic lesion among multiple CCMs was removed for diagnostic purposes. The midbrain lesion causing hydrocephalus was left untreated and managed instead with ETV to address the hydrocephalus. Excluding Case 5, 6 cases involved CCM resection. Among them, Cases 9 and 15 underwent simultaneous CCM resection and ETV, both achieving good outcomes. However, 4 patients showed no significant postoperative improvement and even had poor prognoses. Notably, Case 4 required a second surgery for VP shunting due to postoperative hydrocephalus. Additionally, one patient with multiple CCMs presenting with vertigo achieved satisfactory outcomes and long-term follow-up through conservative management alone.

In conclusion, for CCMs located in the midbrain and adjacent structures, neurosurgeons should exercise caution when choosing treatment options. The literature review suggests that the benefits of resective treatment for tumors in such conditions are relatively limited. In contrast, treatments targeting the primary issue, hydrocephalus, through approaches like ETV, often result in better prognoses.

Based on imaging examinations and intraoperative endoscopic exploration, both cases were ultimately diagnosed as cavernous malformations (CCMs). Case 1 involved multiple lesions, while Case 2 featured a solitary lesion in an elderly patient. In both cases, the midbrain lesions obstructed the cerebral aqueduct, leading to obstructive hydrocephalus. The progression of hydrocephalus was gradual, with significant dilation of the third ventricle. In Case 1, the patient’s improvement in vision progressed slowly post-surgery. We believe this is due to the gradual progression of the patient’s hydrocephalus, which differs from the effects caused by acute intracranial pressure elevation in the short term. Therefore, the treatment of obstructive hydrocephalus alone did not show immediate effectiveness. However, the imaging results and the complete resolution of the patient’s headache symptoms also confirm the efficacy of our treatment. In Case 2, despite the obvious mass effect causing corticospinal tract symptoms, such as ptosis and restricted eye movement, the primary cause of the patient’s symptoms was obstructive hydrocephalus, which significantly impacted the patient’s quality of life. Recent studies suggest that conservative treatment also has a positive impact on CCM (26). In a recent cohort study involving 265 CCM patients treated conservatively with a follow-up period of at least 6 months, the results showed that most conservatively treated CCM patients did not experience symptomatic hemorrhage during the follow-up, and few required intervention, with death due to CCM being rare (27). Additionally, for symptomatic or recurrently hemorrhaging brainstem CCMs, surgical treatment is an important option (28). In conclusion, for our patient, choosing endoscopic third ventriculostomy (ETV) to treat obstructive hydrocephalus effectively alleviated the patient’s symptoms while avoiding the potential harm caused by surgery itself. This approach is both reasonable and meaningful.

The diagnosis of familial multiple cavernous malformations (FCCM) requires meeting one or more of the following criteria: (1) presence of multiple CCMs (≥5); (2) at least two family members diagnosed with CCM; (3) mutation in one of the three genes associated with FCCM (29). Typically, CCMs appear as “popcorn-like” lesions with mixed high and low signals on T1- and T2-weighted MRI sequences (30). The MRI appearance of CCMs is influenced by the time interval since hemorrhage, leading Zabramski et al. to classify CCMs into four types (2). Although CCMs are generally considered to have a relatively benign natural course, some patients may experience focal neurological deficits, which can sometimes be irreversible (1, 31, 32).

In recent years, cohort studies on surgical treatment of CCMs have increased, with treatment options including traditional craniotomy, neuroendoscopic surgery, gamma knife, and laser interstitial thermal therapy, all showing favorable outcomes (33–36). For incidentally discovered, asymptomatic CCMs, conservative management—primarily periodic monitoring considering the patient’s age and lesion location—is generally preferred over immediate surgical resection (37–40). The timing of surgical intervention for symptomatic CCMs, especially those causing neurological deficits, remains controversial (11, 41, 42). This is particularly true for midbrain CCMs, where some reports suggest that aggressive surgical treatment does not significantly increase the risk of adverse outcomes (43–45). For intraventricular CCMs, although studies have indicated a high hemorrhage propensity (46), the resection of CCMs in the fourth ventricle or nearby areas carries significant risks (17). This is particularly unacceptable for patients whose primary symptoms are hydrocephalus or those who are asymptomatic. Therefore, when making treatment decisions, factors such as the size, location, mass effect, and surgical risks associated with the CCM must be carefully considered. For symptomatic CCMs located in superficial brain areas, or for patients with recurrent symptomatic hemorrhages even when the lesion is deep-seated, surgical resection is a reasonable choice (47, 48).

Certainly, this study also has objective limitations. Most notably, the sample size is small, with only two patients. This is a retrospective study rather than a standard cohort study or a controlled trial. Factors such as the surgical skills and decision-making ability of the lead surgeon may also influence the generalizability of the final results. Furthermore, the lack of preoperative quality-of-life assessments for the patients further limits the conclusions of this study. Future research will focus on larger-scale prospective studies, with comprehensive quality-of-life indicators and longitudinal follow-up, to better understand the impact of surgery on patient outcomes and improve clinical strategies in future studies. Finally, we also hope for multicenter studies, especially those including diverse nationalities and ethnicities, as this will provide more generalizable and meaningful results for this type of research.

As a slow-progressing central nervous system lesion with a relatively benign natural course, the treatment strategy for CCMs is influenced by various factors. While the hemorrhage risk of CCMs cannot be overlooked, overly aggressive surgical approaches may cause greater harm to patients. Our cases and the literature review offer new perspectives and insights into surgical decision-making, contributing to better treatment outcomes and prognosis. By demonstrating the effectiveness of addressing hydrocephalus as the primary cause of symptoms rather than pursuing aggressive surgical resection of cavernous malformations, this study supports a more conservative treatment approach in similar cases. This approach not only reduces the risk of potential surgical complications but also emphasizes the importance of individualized patient care. Clinicians are encouraged to carefully evaluate the primary cause of symptoms and consider less invasive options when appropriate. This is particularly important when dealing with younger patients or elderly patients, where optimizing treatment outcomes while preserving quality of life is especially crucial. The patients we reported on benefitted from the surgeries and have been followed up long-term, further supporting the value of this conservative approach.