Prevalence and Risk Factors
The predominance of CN palsies in middle-aged adults, along with a slight female predominance, aligns with previously reported data. The slight female predominance is thought to be influenced by hormonal and genetic factors (34). As of now, no established causal link exists between the rupture of cerebral aneurysms and systemic hypertension in humans. However, this relationship has been experimentally explored in mice by some researchers (35, 36). However, in some experimental research on mice, one team uncovered the crucial involvement of systemic hypertension and the local renin-angiotensin system in the development of aneurysmal rupture. Meanwhile, another team found that inducing hypertension alongside elastic lamina degeneration led to the formation of large aneurysms, offering valuable insights into potential therapeutic targets for patients with unruptured intracranial aneurysms (35, 36). The current review identified a lower prevalence of hypertension as a risk factor (9.2%) compared to some previous studies that reported higher rates.
Recognizing the importance of the aneurysm's status, whether ruptured or unruptured, and its relation to CN palsies, it is intended in this review to group the incidence of these occurrences. This approach facilitates a thorough examination to determine whether the presence of CN palsies correlates with the status of aneurysm rupture.
Association between nerve palsy and cerebral aneurysms
CN palsies involving nerves other than the third or sixth are associated with aneurysms, with 16.5% occurring in cases of ruptured aneurysms and 83.5% in cases of intact aneurysms.
Olfactory CN I and Optic CN II:
There are no documented cases in the literature of olfactory nerve palsy due to aneurysmal cerebrovascular diseases. Affection of the optic nerve occurred in 8.5% of our cohort and is most likely not due to direct pressure from the aneurysmal sac or rupture, as all reported cases of optic nerve involvement present with intact aneurysmal sacs (37–39). A homonymous hemianopsia, a condition where half of the visual field is lost in both eyes, can occur due to a partially thrombosed aneurysm in the right posterior cerebral artery. Subsequent PCA thrombosis, the blockage of this artery, results in reduced blood flow to the rear part of the brain. Consequently, symptoms commonly include visual disturbances such as homonymous hemianopsia (37, 38). Thrombosis in the cavernous sinus can affect the visual field by compressing the optic nerve or its pathways near the optic chiasm, potentially leading to homonymous hemianopsia due to disrupted visual information transmission from the eye to the brain (37, 38, 40). In both cases, after treatment, whether through embolization or microsurgical clipping, there has been improvement. In PCA aneurysms, the improvement may be partial, while in ICA aneurysms, it has been total (37, 38).
Trochlear Nerve CN IV:
Trochlear nerve dysfunction occuered in 14.9% of our cohort and it can arise from various causes, including aneurysms or carotid-cavernous sinus syndromes like fistulas and thrombosis (41–43). The trochlear nerve courses along the lateral aspect of the midbrain, situated between the superior cerebellar artery and the posterior cerebral artery and in near contact with posterior communicating artery aneurysms. This anatomical positioning renders it particularly vulnerable to compression by aneurysms originating from these vessels (38, 44–47). Trochlear nerve palsy has been documented as the primary presenting symptom of an aneurysm affecting the superior cerebellar artery (30). Cavernous sinus thrombosis and carotid-cavernous fistulas (CCFs) both have the potential to cause CN IV palsy, similar to how they can induce CN II palsy. In cavernous sinus thrombosis, the formation of a blood clot within the cavernous sinus results in increased pressure within the sinus, which can compress nearby structures, including the trochlear nerve (CN IV), leading to dysfunction and CN IV palsy (40). Similarly, CCFs create an abnormal connection between the ICA and the cavernous sinus, elevating pressure within the sinus and potentially compressing the trochlear nerve, resulting in trochlear nerve dysfunction and subsequent palsy (48). In other cases, the trochlear nerve palsy can happen incidentally due to other causes than the coincidenting aneurysms, which is out of scope of this review (49).
Trigiminal Nerve CN V:
A reported case of trigeminal neuralgia due to aneurysmal cerebrovascular disease was associated with a giant carotid-posterior communicating artery aneurysm, which also affected CN III and VII (50). The presence of a 3 cm giant thrombosed aneurysmal sac in this location is susceptible to pressing on CN III, V, and VII without rupture. Slight variations in nerve tracts may predispose to such rare cases, as this combination of nerve involvement is not commonly reported in other literature (51). The aneurysm was successfully clipped, and the patient made a full recovery (50). Trigeminal neuralgia palsy occurred in 6.3% of our cohort and was only observed in conjunction with other palsies.
Abducens Nerve VI:
There is a higher association between abducens nerve palsies and intracerebral aneurysms compared to CN other than the oculomotor nerve. Abducens nerve palsy was observed in 70% of our cohort, making it the most frequently affected cranial nerve after excluding the oculomotor nerve. Our review found that 48% of abducens nerve palsy cases occur in ruptured aneurysms, while 52% occur in intact aneurysms. This may indicate that the incidence of abducens nerve palsies does not significantly change with the aneurysmal sac status (Fig. 2) (52).
In our review, we found that more than 80% of unruptured aneurysms causing CN VI palsy originated from ICA. These aneurysms were primarily treated using endovascular coiling techniques. Despite the unruptured status of these aneurysms, the recovery rate for CN VI palsy was nearly 70%. This suggests that even though endovascular coiling is a minimally invasive procedure compared to surgical clipping, it may be effective in alleviating the CN dysfunction in similar cases (53–63). However, a wider study is needed to determine the most feasible management approach for better understanding.
Patients with ruptured aneurysms were primarily treated with clipping and/or trapping. These aneurysms originated from arteries other than the ICA, such as the ACOM, BA, or VA. The palsy recovery rate was nearly 90%, despite the aneurysmal rupture, suggesting that the specific artery affected plays a more critical role in recovery than the rupture itself (32, 55, 64–71).
Facial Nerve VI, Vestibulo-cochlear Nerve VIII, Glossopharengeal Nerve IX, Vagus Nerve X, Accessory Nerve XI:
Affection of the facial nerve due to cerebrovascular aneurysmal disease has been reported in two cases due to direct pressure by vertebral-posterior inferior cerebellar artery or IC-PCA aneurysms, totally in 4.2% of our cohort. One case was treated by coiling and the other by clipping, with complete resolution of symptoms in both treatment maneuvers (44, 50).
There have been no reported cases of isolated or mixed vestibulocochlear nerve palsy. However, giant proximal ICA aneurysms or distal vertebral artery unruptured aneurysms can affect CN IX, X, and XI due to direct pressure, sometimes resulting in unilateral bulbar syndrome, which occurred in 4.2% of the cohort (72, 73). Conservative management was chosen in one case due to the complete thrombosis of the aneurysm. Additionally, in a case involving bilateral extracranial ICA aneurysms to avoid further possible neurological deficits, where unilateral symptoms were present, the asymptomatic side underwent intracranial-extracranial bypass, while the symptomatic side was treated with stent-assisted coil embolization. Improvement of symptoms was observed one year later on the affected side (72).
Hypoglossal Nerve XII:
Of the total 4 cases (8.4% of the cohort) of hypoglossal nerve palsy, 75% occurred in individuals aged around 40 years or younger, predominantly as an isolated condition. However, in rare instances, it can be mixed with lower CN involvement causing bulbar palsy, as mentioned earlier. Aneurysms in the petrous part of the ICA can exert pressure on the hypoglossal nerve (73–76). Treatment approaches for these aneurysms include endovascular techniques, surgical decompression, and conservative management. Unfortunately, cases with isolated hypoglossal nerve palsy typically do not show improvement following any treatment mentioned.
The aneurysms that cause CN palsies are often giant, consistent with the high proportion of giant aneurysms observed (77). The frequent involvement of the abducent nerve, as highlighted in the introduction section, is corroborated by findings in the present review (1). It is noted that while aneurysm rupture can influence the distribution of nerve involvement, it does not significantly impact long-term outcomes or recovery rates. Certain aneurysms affecting specific arteries can target particular nerves, but variations in nerve pathways together with aneurysm size can sometimes be misleading.
Treatment approaches and outcomes
The treatment modalities and outcomes observed in the current review are consistent with previous literature, showing that most cases achieve recovery. Several studies have documented improvement in CN palsies following both microsurgical and endovascular interventions for related aneurysms, or both in cases of complex cerebral aneurysms (1, 78, 79). Better outcomes at 1 year are expect to occur with those treated with endovascular more than those treated with open surgery, emphasizing the efficacy of endovascular interventions (80). The same with induced CN III palsy by posterior communicating artery aneurysm, it is shown that improvement was achieved following coiling in most patients (81).
Favorable outcomes are anticipated in cases where coiling is applied to small and intradural cerebral aneurysms. Specifically, in patients presenting with multiple CN palsies, including five cases involving the abducent nerve, complete recovery was achieved following endovascular management (32).
Endovascular complete or near-complete obliteration of aneurysms showed symptomatic improvement of the associated CN palsies at follow-up (6). However, in certain cases where the radiological and clinical outcomes of microsurgical and endovascular treatments were closely monitored, occlusive treatment was associated with higher morbidity and mortality rates during follow-up (82).
Analysis of recovery outcomes:
An analysis of recovery outcomes in this cohort demonstrated that clinical characteristics such as aneurysm type (giant vs non-giant) did not significantly impact recovery rates. However, treatment strategies—including microsurgical, endovascular, combined approaches, and conservative management—showed a statistically significant difference (p = 0.01) in recovery outcomes. However, it's important to consider that other factors, including potential confounding variables, may influence the recovery process, as evidenced by the lack of statistical significance related to aneurysm type and rupture status. The correlation between treatment methods and the duration of CN palsy underscores the critical role of timely interventions. Nevertheless, expanding the sample size would bolster the reliability and validity of these findings.
Limitations and Future Directions:
The study's reliance on case reports introduces inherent biases that complicate the synthesis of robust evidence. These reports, while informative, often come with limitations that restrict our ability to effectively interpret findings and synthesize comprehensive conclusions. Moreover, the small sample size limits how broadly we can apply the findings to the larger population affected by CN palsies due to aneurysms.
Furthermore, the absence of randomized controlled trials and the short follow-up periods reported in the literature weaken the overall strength of evidence. To address these shortcomings, future research should prioritize longitudinal studies with larger and more diverse sample sizes. These studies are essential to validate findings, enhance reliability, and ensure that the evidence generated can effectively guide clinical practices in managing CN palsies associated with aneurysms.