
==== Front
Radiol Case Rep
Radiol Case Rep
Radiology Case Reports
1930-0433
Elsevier

S1930-0433(24)00724-6
10.1016/j.radcr.2024.07.139
Case Report
Intracerebral hemorrhage and subarachnoid hemorrhage as a manifestation of ruptured intracranial mycotic aneurysms: A report of 2 cases
Biyang Yunita Ch. yunita_ch.biyang@ymail.com
ab⁎
Sani Achmad F. cd
Kurniawan Dedy cd
a Department of Neurology, Faculty of Medicine, Airlangga University, Surabaya, Indonesia
b Department of Neurology, Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
c Neurointervention Division, Department of Neurology, Faculty of Medicine, Airlangga University, Surabaya, Indonesia
d Neurointervention Division, Department of Neurology, Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
⁎ Corresponding author. yunita_ch.biyang@ymail.com
17 8 2024
11 2024
17 8 2024
19 11 49834988
27 3 2024
23 7 2024
24 7 2024
© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.
2024

https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Intracranial mycotic aneurysms (IMA) are caused by abnormal dilatation of brain vessels due to infective dissemination, most often associated with endocarditis vegetation. This condition is relatively rare, accounting for approximately 0.7%-5.4% of all intracranial aneurysms. However, the related morbidity and mortality levels are high due to the occurrence of intracranial (ICH) and subarachnoid hemorrhage (SAH). We report 2 cases of intracranial mycotic aneurysms that presented to us with features of ICH and SAH and were managed successfully with endovascular therapy. Presently, there are no standardized recommendations for determining the clinical diagnosis and therapy of intracranial mycotic aneurysms. Hence, the treatment given to patients varies greatly. However, it is crucial to achieve a proper diagnosis and initiate early aggressive therapy to improve the prognosis of patients. Endovascular therapy and surgical techniques are safe and effective options with higher survival rates than single-conservative management.

Keywords

Intracranial mycotic aneurysms
Intracerebral hemorrhage
Subarachnoid hemorrhage endovascular therapy
Case report
==== Body
pmcIntroduction

Intracranial mycotic aneurysms (IMA) are uncommon neurovascular abnormalities, representing a small percentage of all cerebral aneurysms, ranging from 0.7% to 5.4% worldwide and an incidence of 1.6%-18% in developing countries [[1], [2], [3], [4], [5]]. The term "mycotic" is actually inaccurate, as intracranial mycotic aneurysms can be caused by a variety of infectious organisms, not just fungi [2,6]. Aneurysms in this population are more common in males and typically occur between the ages of 35 and 50 [6].

The majority of IMAs result from bacterial infections (72.8%), with fungal infections accounting for 13.2%. Infective endocarditis is the most common cause of IMA. Cases of IMA caused by bacterial meningitis and resulting intracranial hemorrhage are uncommon. There have been only a small number of reported cases of ruptured IMA secondary to bacterial meningitis [2,5].

IMA have distinctive natural history and pathological characteristics, along with unique angiographic features, and often form at the end of arterial branches. Their spontaneous rupture leads to subarachnoid and intracerebral hemorrhage, causing significant morbidity and mortality, reaching as high as 60%-90% in earlier case studies, and 12%-32% in more recent literature reviews, necessitating urgent intervention [3,4].

We report 2 cases, who presented to us with features of ICH and SAH and were successfully treated with endovascular therapy. Written informed consent was obtained from the 2 patients for reporting the findings and consequent management.

Patient and observation

Case 1

A 30-year-old man was referred to the Emergency Department (ED) with a complaint of a sudden severe headache that persisted for the past 2 days. This headache was described to be the worst ever experienced, with a Numeric Rating Scale (NRS) score of 8 to 9. There was no previous history of hypertension, diabetes, and head trauma.

The patient exhibited total paralysis of the left hand. Facial asymmetry was observed, and other neurological examinations yielded normal results. A holosystolic murmur of grade 2/6 was detected at the apex of the heart, along with a diastolic murmur of grade 2/4 at the left parasternal linea, specifically at the third intercostal space.

The patient had a history of infective endocarditis 10 years before, which was established from transthoracic echocardiography (TTE) examination, was found, showing Posterior Mitral Leaflet (PML) and Anterior Mitral Leaflet (AML) vegetation along with mild mitral regurgitation. Follow-up TTE indicated severe aortic and mild mitral regurgitation, eccentric left ventricular hypertrophy, and grade I diastolic dysfunction. Furthermore, laboratory examination showed leukocytosis (12,690/mm3), neutrophilia (76.2%), elevated C-reactive protein (11.2 mg/L), and prolonged erythrocyte sedimentation rate (97 mm/h), but no pathogenic organisms were detected in the cultures. Noncontrast head Computerized Tomography (CT) scan showed SAH in the right temporoparietal lobe (Fig. 1A). A follow-up CT scan 1 week later detected SAH of the right parietal region with surrounding perifocal edema (Fig. 1B). Two weeks later, cerebral angiography was performed and showed ruptured mycotic cerebral aneurysms of the right distal MCA (M4) as well as unruptured types at the left distal PCA (P4) (Fig. 1, Fig. 1).Fig. 1 (A) Noncontrast head CT scan when the patient was first brought to the hospital showed SAH in the right temporoparietal lobe. (B) Noncontrast head CT scan 1 week later showed SAH of the right parietal region with perifocal edema around it. (C, E) Cerebral angiography showing ruptured mycotic cerebral aneurysm of distal media cerebral artery (MCA segment M4) before embolization. (D, F) Cerebral angiography showing ruptured mycotic cerebral aneurysms of distal media cerebral artery (MCA segment M4) after embolization.

Fig 1:

The patient was then treated with curative embolization after 2 days onset of ruptured IMA. During the treatment, the patient received nimodipine, warfarin, dexamethasone, and a 4-week course of antibiotics, including 2 grams of Ceftriaxone and 1 gram of Vancomycin every 12 hours.

The angiographic evaluation showed the ruptured mycotic cerebral aneurysms in MCA segment M4 were no longer visible, indicating successful treatment (Figs. 1D-F). The intensity of the headache was significantly reduced, and there were no neurologic deficits or complaints after the procedure.

Case 2

The second case was a 29-year-old man who was referred to the ED with a chief complaint of general onset tonic seizure. The duration of the seizure was approximately 10 seconds, after which consciousness was regained. One hour later, another incident of seizure was reported with the same form. There was no history of hypertension, diabetes, heart disease, head trauma, or head surgery. On admission to the ED, the GCS was 456, and other neurological examinations were within normal limits.

Laboratory examination showed slightly elevated leukocytes (11,730/mm3). Noncontrast head CT scan displayed ICH of 2.7 cc volume in the subcortex of the left parietal lobe and SAH filling the cerebral falk (Fig. 2A). CTA demonstrated a fusiform aneurysm in the distal segment of the left ACA (A4) (Fig. 2, Fig. 2). Cerebral angiography indicated the presence of multiple mycotic aneurysms. The first one was found in the right ACA (A3) (Fig. 3C). The second mycotic aneurysm was obtained at the distal left MCA (middle trunk), specifically at the angular artery branch (Fig. 3A). The third unruptured mycotic aneurysm was found in the right distal PCA (P4) (Fig. 3, Fig. 3).Fig. 2 (A) Noncontrast head CT scan when the patient was first brought to the hospital showing ICH vol ± 2.7 cc in the subcortex of the left parietal lobe with surrounding perifocal edema and SAH filling the falx cerebri. (B,C) CT Angiography showed fusiform aneurysms in the ACA (segment A4) sinistra with a size of 1.6 mm wide and 8.3 mm long.

Fig 2

Fig. 3 (A) Cerebral angiography showed a ruptured mycotic cerebral aneurysm in the distal left MCA (middle trunk) at the angular artery branch, and then (B) the aneurysm was embolized. (C) Cerebral angiography showed an unruptured mycotic cerebral aneurysm in the right ACA (A3), which was then (D,E) coiled with a 90% packing coil, and the blood vessels around the aneurysm appeared patent. (F) Cerebral angiography showed packing coil (white circle) and cast from glue/histoacryl (red circle). (G,H) Cerebral angiography shows an unruptured mycotic cerebral aneurysm in the right distal PCA (P4) (small aneurysm).

Fig 3

The aneurysm in the right ACA (A3) was then coiled with 90% packing coil (Figs. 3D-F). The aneurysm dome at the distal left MCA was then embolized, leaving the neck and parent vessel (Fig. 3B). During treatment, the patient also received nimodipine and antibiotics, including Ceftriaxone 2 grams every 12 hours and Vancomycin 1 gram every 12 hours, given for 4 weeks.

The patient was then discharged with no recurrent seizures and no neurologic deficits or complaints.

Discussion

IMA refers to an infectious process that causes degradation and dilation of the arterial wall. This term was first introduced by Osler in 1885 to describe aneurysms that develop as a consequence of infective endocarditis, where fragile cardiac vegetations lead to the formation of septic emboli that become lodged in the branching points and distal branches of intracranial vessels [5,7]. Risk factors for development include arterial injury, previous or antecedent infection, impaired immunity, atherosclerosis, or preexisting aneurysms [6]. The first patient had a history of infective endocarditis 10 years prior to hospital admission, whereas the second patient had no history of infective endocarditis or any other sources of infection.

The vasa vasorum theory is the predominant pathogenic mechanism, suggesting that bacteria from septic emboli exit through the vasa vasorum, leading to significant inflammation of the adventitia. This infection subsequently progresses inwardly. Initially, acute inflammation causes neutrophil infiltration, leading to the degradation of the media and adventitia, fragmentation of the internal elastic lamina, and proliferation of the intima. The weakened vessel wall, combined with pulsatile pressure in the vasculature, ultimately results in the formation of an aneurysm and subsequent growth. While some authors prefer the term pseudoaneurysm, both are commonly used in the medical literature [4,6].

After the bacteria inoculate in vasa—vasorum, proinflammatory mediators was released that attract neutrophils to the arterial wall. The bacteria release proteases that activate human matrix metalloproteinases (proMMP 1,8,9) and inactivate human plasma α1-proteinase inhibitor, resulting in the breakdown of the extracellular matrix and activation of neutrophil elastase. Neutrophils, in turn, release enzymes that further contribute to the degradation of the arterial wall. Neutrophil infiltration of the vasa vasorum weakens the adventitia, muscularis, and eventually the internal elastic membrane. This process is followed by the early dilation of the proximal and distal ends of the affected arterial wall, leading to the progressive dilation of the entire segment. The pulsation of the dilated and weakened arteries can result in the formation of an aneurysm, which may eventually rupture [[2], [3], [4], [5]].

Infected aneurysms are most commonly caused by cardioembolic factors, particularly bacterial endocarditis. Intracranial mycotic aneurysms are seen in 25% to 30% of patients with infective endocarditis. While viruses and fungi can also be causes, bacterial infections, especially S. aureus and Streptococcus species, are the primary cause. The anterior circulation, particularly the MCA and its distal branches, is the most common location for IMA, accounting for 50%-78% of cases. Although the risk of hemorrhage is low (<2%), it results in significant morbidity and mortality in 80% of patients [2,6,7]. A recent meta-analysis revealed a 13% mortality rate among patients with IMAs, and a mortality rate of up to 80% in cases of rupture, necessitating urgent intervention [3].

Intracranial mycotic aneurysm, like its primary cause infective endocarditis, is frequently a difficult diagnosis to make [8]. In a comprehensive study of 25 individuals diagnosed with IMA exhibited a range of initial symptoms. These symptoms included headache (83% of patients), fever (67%), vomiting (50%), ocular palsy (25%), seizures (21%), behavioral changes (21%), hemiparesis (21%), drowsiness (17%), and loss of consciousness (17%) [4]. Headache and neurological deficits are commonly cited as the primary concerns among patients with ruptured IMA, while headache and fever are identified as the prevailing symptoms in individuals with unruptured IMAs [1]. Neurological complications that may arise have the potential to be life-threatening, such as intracerebral bleeds, subarachnoid hemorrhages, ischemic stroke, seizures, and europathies [2,5]. This corresponds with the clinical presentation of the first patient, who experienced severe headaches, and the second patient, who had seizures.

A scoring system based on the presence of specific clinical and radiographic findings has been proposed for the diagnosis of IMA. The diagnostic criteria consisted of one mandatory criterion and 12 supportive criteria (Table 1). A score of 3 or higher indicates a clinically definite diagnosis of IMA, a score of 2 suggests a probable IMA, and a score of 1 suggests a possible IMA [4,5]. Based on these criteria, we can conclusively evaluate both patients as having definitive IMA.Table 1 Proposed diagnostic criteria for infective intracerebral aneurysm.

Table 1Mandatory criterion:	Supportive criteria:	
Intracranial aneurysm on Neurovascular imaging	1.Infective endocarditis
2.Meningitis
3.Orbital cellulitis
4.Cavernous sinus thrombophlebitis
5.Multiplicity
6.Distal location
7.Fusiform shape
8.Change is the shape and size of a new aneurysm on follow-up imaging
9.Age less than 45 y
10.Fever/history of fever ≥ 7 days
11.Recent lumbar puncture
12.Intraparenchymal hemorrhage in brain imaging	
	
Diagnosis of IMA based on the above criteria:	
	
Definitive	Mandatory criterion plus 3 or more supportive criteria satisfied	
Probable	Mandatory criterion plus 2 or more supportive criteria satisfied	
Possible	Mandatory criterion plus one supportive criteria satisfied	

The diagnosis of IMA depends on the presence of an underlying infectious process along with an aneurysm that is confirmed through vascular imaging. Imaging is critical in the assessment of this rare condition—especially because earlier diagnosis may afford the opportunity for prompt intervention to improve the otherwise poor outcome of this disease [8].

While digital subtraction angiography (DSA) remains the preferred method for diagnosing IMA, CT angiography, and magnetic resonance imaging (MRI) can also be utilized. DSA findings indicative of IMA include distal location on middle cerebral artery (MCA) (less frequently on posterior cerebral artery (PCA) branches), irregular contours, and multiplicity. A positive culture from the aneurysm wall can serve as confirmation of the diagnosis. Additional indicators include positive blood culture (found in only 35.6% of cases), leukocytosis, elevated erythrocyte sedimentation rate (ESR), and increased C-reactive protein (CRP) levels [[1], [2], [3],5]. These findings are consistent with the results of the cerebral angiography conducted on both patients. The first patient presented with a ruptured aneurysm in the right distal MCA and an unruptured aneurysm in the left distal PCA. The second patient presented with a ruptured aneurysm in the right ACA and the left distal MCA, as well as an unruptured aneurysm in the right distal PCA. The first patient also exhibited leucocytosis, elevated CRP level, and prolonged ESR. In contrast, the second patient demonstrated a slight increase in leukocyte count.

At present, there are no established guidelines to direct clinical decision-making for managing IMA. IMA are usually fragile and thin-walled, often with a wide or missing neck, which makes them challenging to treat. Treatment options consist of antimicrobial medications, surgery, endovascular treatment, or a combination of treatments [9]. Ruptured aneurysms should be promptly secured through open surgical procedures or endovascular methods, with the decision tailored to the aneurysm morphology, patient comorbidities, and the presence of associated intracerebral hemorrhage [2,3].

Endovascular treatment has quickly advanced in its effectiveness and capability to reach more distal aneurysms. The safety assessment of this procedure is challenging due to its reliance on anecdotal and case-report information. A meta-analysis of 16 patients from prior cases where endovascular therapy was administered revealed that 69% experienced positive results, and there were no procedural-related complications [4].

Endovascular treatment may offer a higher level of safety and efficacy compared to open craniotomy when conducted at a high volume tertiary center and in the absence of elevated intracranial pressure (ICP), mass effect, hypotension, hematoma, or involvement of eloquent territory [4]. Embolization using coils or liquid embolization agents (Onyx, NBCA, or others) account for the majority of endovascular procedures for the treatment of IMA [1].

Medical management with 6 weeks of IV antibiotic should be reserved for patients with aneurysms that have not yet ruptured and should be followed closely with serial cerebral angiograms [4]. The evolution of MA with antibiotic therapy can be unpredictable: they may disappear, regress, persist, enlarge, or rupture. Antimicrobial therapy can be continued without intervention for aneurysms that resolve or regress. However, endovascular or surgical methods should be considered for aneurysms that increase in size despite antimicrobial therapy. For unruptured MA with low surgical risk, invasive treatment is advised [3]. Given that both patients experienced rupture of intracranial mycotic aneurysms, leading to ICH and SAH, they both subsequently underwent endovascular treatment and received a 4-week course of antibiotic therapy.

The critical factors for achieving a successful outcome in the management of this rare and challenging intracranial mycotic aneurysm are early diagnosis and rigorous, aggressive treatment [4,10]. The headache symptoms in the first patient have alleviated, and no neurological deficits are observed. This is consistent with the findings from the cerebral angiography evaluation, which indicated that the mycotic aneurysm in the right distal MCA was no longer detectable following endovascular therapy and antibiotic treatment. The second patient also did not experience recurrent seizures after receiving endovascular therapy and antibiotic treatment.

Conclusion

The case report outlines the successful treatment of ruptured intracranial mycotic aneurysms in both patients using endovascular therapy and antibiotics. Although intracranial mycotic aneurysms are infrequent, their spontaneous rupture can lead to subarachnoid and intracerebral hemorrhage, resulting in significant morbidity and mortality rates, which can reach as high as 60%-90%. The manuscript highlights the critical need for early diagnosis and aggressive treatment of intracranial mycotic aneurysms. Endovascular therapy has been demonstrated to be an effective treatment modality for these aneurysms. It is anticipated that future developments will lead to the establishment of standardized diagnostic and therapeutic protocols for intracranial mycotic aneurysms, thereby improving patient outcomes.

Patient consent

I have obtained consent from the patients, and their legal representatives for use their radiology images and their case to publication in journal.

Author contribution

All authors contributed to the manuscript writing and agreed to the final version of the manuscript for publication.

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments: The authors thank Dr. Soetomo General-Academic Hospital and Faculty of Medicine, Airlangga University, Surabaya, Indonesia.
==== Refs
References

1 The outcomes of endovascular treatment for intracranial mycotic aneurysms: a retrospective data analysis of a tertiary center Cerrahpasa Med J [Internet] 8 1 2024 1 7 [Accessed July 2024] Available from: https://cerrahpasamedj.org/en/the-outcomes-of-endovascular-treatment-for-intracranial-mycotic-aneurysms-a-retrospective-data-analysis-of-a-tertiary-center-131150
2 Zanaty M Chalouhi N Starke RM Tjoumakaris S Gonzalez LF Hasan D Endovascular treatment of cerebral mycotic aneurysm: a review of the literature and single center experience Biomed Res Int 2013 2013 1 8
3 John S Walsh KM Hui FK Sundararajan S Silverman S Bain M. Dynamic angiographic nature of cerebral mycotic aneurysms in patients with infective endocarditis Stroke [Internet] 47 1 2016 e8 e10 10.1161/STROKEAHA.115.011198 [Accessed July 22, 2024]Available from: 26604253
4 Kuo I Long T Nguyen N Chaudry B Karp M Sanossian N. Ruptured intracranial mycotic aneurysm in infective endocarditis: a natural history Case Rep Med 2010 2010 1 7
5 Gowda S. Ruptured infective (mycotic) intracranial aneurysm secondary to bacterial meningitis: a case report and review of literature. 2021;
6 Desai B Soldozy S Desai H Kumar J Shah S Raper DM Evaluating the safety and efficacy of various endovascular approaches for treatment of infectious intracranial aneurysms: a systematic review World Neurosurg 144 2020 293 298.e15 32818695
7 Dokponou YCH Hakkou M Ouambi O Bankole NDA Ouahabi AE. A rare cause of hemiparesis: intracranial mycotic aneurysm: a case report, and review of the literature OJMN 11 03 2021 171 179
8 Wang TKM Griffin B Cremer P Shrestha N Gordon S Pettersson G Diagnostic utility of CT and MRI for mycotic aneurysms: a meta-analysis Am J Roentgenol 215 5 2020 1257 1266 32930605
9 Kumar S Tiwary R Bhatia L. Mycotic aneurysm of the posterior cerebral artery IJNS 05 03 2016 193 195
10 Jain R Mathur T Srivastava T Jain R Sannegowda R. Mycotic aneurysms of the intracranial and peripheral circulation: a rare complication of bacterial endocarditis Ann Indian Acad Neurol 17 1 2014 82 24753666
