J Neurosurg 48:369-382, 1978

Bacterial intraeranial aneurysm GEORGE L. BOHMFALK, M.D., JIM L. STORY, M . D . , JOHN P. WISSINGER, M.D., AND WILLIS E. BROWN, JR., M . D .

Division of Neurosurgery. University of Texas Health Science Center, Bexar County Hospital, San Antonio, Texas The authors tabulate and analyze cases of bacterial intracranial aneurysm documented since 1954, and add four of their own. In 85 cases the overall mortality was 46%. Elimination of patients dying before reaching the hospital makes this figure spuriously low. Figures for patients hospitalized for endocarditis before neurological symptoms occurred suggest a true mortality of 80% from aneurysms that rupture and 30% if the aneurysm remains intact. Multiple reports of spontaneously resolving, enlarging, diminishing, multiple, and sequentially appearing aneurysms, all of which occurred in our fourth case, clarify the need for complete and sequential angiography. Computerized tomographic (CT) scanning in this disease has not been reported, but our experience with these scans demonstrates considerable potential value. A protocol of complete cerebral angiography and CT scanning of these neurologically asymptomatic patients is proposed, in order to assess the true incidence of bacterial intracranial aneurysm, to learn more of its natural history, and to prevent some neurological catastrophes. KEY WORDS 9 bacterial endocarditis 9 cerebral aneurysm 9 cerebral angiography 9 cerebral hemorrhage 9 infectious aneurysm mycotic aneurysm 9 subarachnoid hemorrhage

B

ACTERIAL intracranial aneurysm is generally an unsuspected lesion that manifests itself by inflicting a devastating and often fatal neurological illness upon a patient who is otherwise recovering from bacterial endocarditis. Rarely is there a " w a r n i n g l e a k " indicating its presence. However, associated vascular phenomena, such as embolic occlusions and vasculitis, may produce signs or symptoms that may lead to a thorough neurological evaluation, and discovery of an unruptured treatable aneurysm. The pathophysiology of bacterial aneurysms is a dynamic process, such that they require complete and sequential cerebral angiography for evaluation and management. Computerized tomographic (CT) scanning appears to be of considerable J. Neurosurg. / Volume 48 / March, 1978

additive value in appreciating more completely the pathologic process. Historical aspects of this complex were reviewed recently by Hourihane. TM Credit for naming these lesions " m y c o t i c " is generally ascribed to Osler, who used the term in his "Gulstonian Lectures on Malignant Endocarditis" in 1885. `0 However, at that time, mycotic referred to any infectious process, and Osler used the term only to describe the endocarditis, commenting that the debris in an aortic arch aneurysm was very similar to that found on the heart valves in a ease of "malignant (mycotic) endocarditis." Apparently, Eppinger was the first to call the aneurysms a s s o c i a t e d with e n d o c a r d i t i s "mycotic-embolic, ''45 although the association had previously been noted by several 369

G. L. Bohmfalk, et al. others. TM The term has evolved into a misnomer, and recent reports of true mycotic (fungal) intracranial aneurysms 9,17,3',55 warrant the use of a more specific term; we prefer "bacterial intracranial aneurysm." Stengel and Wolferth, in 1923) ~ and Shnider and Cotsonas, in 1954,48reviewed the literature on all bacterial aneurysms, and reported 34 and 16 cerebral lesions, respectively. All but two of these had bled, and only four patients survived. Many of these cases were incompletely documented and in several the diagnosis was presumptive. We could find no recent report of a large series of well documented bacterial intracranial aneurysms. Most reports of the last two decades involve only a few cases from which it is difficult to draw conclusions regarding this class of aneurysm. This paper tabulates and analyzes cases of bacterial intracranial aneurysm documented since 1954, and presents four new cases. In the first patient the presence of an aneurysm is presumed since autopsy was not performed. The second patient harbored an unruptured bacterial aneurysm discovered at autopsy. In the third case, a single peripheral aneurysm was excised. The fourth patient developed multiple, sequentially appearing, enlarging, diminishing, and spontaneously resolving aneurysms in addition to separate areas of small vessel occlusion and infarcts. Based on the literature review and experience with these four cases, we offer suggestions for evaluation and management of patients at risk from these lesions.

Case Reports Case 1

This 40-year-old man had a vague history of rheumatic heart disease at 16 years of age. He complained of lethargy and weight loss for 6 months, and a few days before admission on June 20, 1975, he developed a dull biparietal headache. Physical examination revealed a temperature of 103 ~ F, Roth's spots in both fundi, and petechiae over the oral mucosa and extremities. The patient was slightly confused, but neurological examination was otherwise unremarkable. He had a grade 3/6 systolic cardiac murmur. Admitting diagnosis was probable endocarditis. On the second hospital day, the patient suddenly became unresponsive and developed 370

weakness on the left side with head and eye deviation to the right. This episode was believed to represent a seizure, possibly from an embolus. A lumbar puncture revealed a cerebrospinal fluid (CSF) opening pressure of 120 mm H20, 15 red blood cells (RBC's), 1 white blood cell (WBC), a glucose of 62 mg/dl, and a protein of 26 mg/dl. Later that day the patient developed severe congestive heart failure. He responded to appropriate treatment, and within the next 2 days blood cultures drawn on admission grew microaerophilic Streptococcus. Intravenous penicillin, 18 million units/24 hours was begun. On the fourth hospital day electroencephalogram (EEG) and brain scan were normal. The patient's condition was then stable until the seventh day, when he complained of sudden severe headache. Within 30 minutes he developed a left central seventh nerve paresis, followed shortly by progressive deterioration of his level of consciousness, with dilation of first the right pupil and, minutes later, the left. Angiography within the hour revealed nonfilling of the intracranial vessels. The patient died several hours later, and permission for autopsy was refused. Case 2

This 40-year-old woman with suspected mitral stenosis was admitted on October 23, 1975, with a 1-week history of fever, chills, dysuria, vomiting, and right flank pain. She had also noted weakness and numbness of her left side for 2 days. On questioning she recalled having frequent bitemporal headaches and intermittent blurred vision during the previous month. On physical examination, her temperature was 102 ~ F. She was lethargic and slightly disoriented. No cardiac murmurs or focal neurological deficits were noted. Serum glucose was 408 mg/dl. Admitting diagnosis was diabetic ketoacidosis with urinary tract infection. She was treated with intravenous fluids and insulin. The following morning her temperature spiked to 103 ~ F. Spinal fluid at that time, from a slightly traumatic tap, was under normal pressure and contained 62 WBC's, 50% polymorphonuclear cells, and 1300 RBC's/cu mm; CSF glucose was 126 mg/dl and protein 50 mg/dl. That evening she was more stuporous, and Roth's spots, left homonymous hemianopsia, and very mild J. Neurosurg. / Volume 48 / March, 1978

Bacterial intracranial aneurysm

F~G. 1. Case 3. Right carotid angiogram, anteroposterior (left) and lateral (right) views, showing an aneurysm (arrows) of a cortical branch of the middle cerebral artery.

left-sided weakness were noted. Angiography at that time disclosed occlusions of the right lenticulostriate vessels, with delayed venous drainage in the right temporoparietal region. The left carotid study was normal. On the following day, blood cultures drawn on admission grew alpha Streptococcus, and intravenous penicillin, 20 million units/24 hours, was begun. Over the next several days the patient developed other embolic complications with loss of some peripheral pulses, and severe pulmonary edema occurred on the fifth day. During this period her hemiparesis and mental status improved, but on the 22nd day her cardiorespiratory status deteriorated rapidly and she died within 2 hours. At autopsy, massive vegetative mitral valvulitis was found, with multiple pulmonary, splenic, and renal infarcts. The brain contained multiple, diffuse, small infarcts of varying age, predominantly in the right centrum semiovale. An unruptured bacterial aneurysm 5 mm in diameter was present on an insular branch of the left middle cerebral artery. Case 3 This 29-year-old heroin addict with no history of heart disease was admitted to the hospital on March 10, 1976, with a 2-day history of fever, bifrontal headache, and right knee arthralgia. On the morning of admission he awoke with painful, purplish lesions on the plantar surfaces of his left hand and foot. J. Neurosurg. / Volume 48 / March, 1978

On examination he was alert and oriented, but acutely ill with a temperature of 104 ~ F. Petechiae, Janeway lesions, and Osier nodes were seen. Cardiac examination was normal with no murmur. An admitting diagnosis of acute bacterial endocarditis was made. A skin lesion was aspirated and Gram stain showed Gram-positive cocci in clumps. Lumbar puncture revealed an opening pressure of 210 mm H~O with CSF glucose of 78 mg/dl, protein of 50 mg/dl, 9 neutrophils, and 21 RBC's/cu mm. Intravenous oxacillin, 12 gin/24 hours, and gentamicin, 240 mg/24 hours, were begun. All blood cultures grew Staphylococcus aureus. On the fifth day the patient experienced a focal seizure beginning in the left hand. Bilateral carotid angiograms revealed a single aneurysm of a distal parietal branch of the right middle cerebral artery, associated with a small mass effect (Fig. 1). At operation, after 3 weeks of antibiotic therapy, the aneurysm was found on the cortex, surrounded by a capsule containing purulent material. The abscess was evacuated and the aneurysm excised. Gram stain and culture of the abscess were negative. The postoperative course was unremarkable. Case 4 This 22-year-old college student had been hospitalized elsewhere with dense hemiparesis and obtundation at 13 years of age. Diagnoses of bacterial endocarditis and rheumatic heart disease were made. Cerebral angiog371

G. L. Bohmfalk, et al.

FIG. 2. Case 4. Initial right carotid angiogram showing two aneurysms (arrows) in the mid-arterial phase, lateral view (upper left) and anteroposterior projection (upper right) in early venous phase, and lateral view in the late venous phase (lower left).

raphy was not performed. He recovered completely during a 6-week hospitalization. Nine days before admission on March 2, 1976, he noted a flu-like illness with chills, fever, malaise, diarrhea, nausea, and vomiting. On the evening before admission he became lethargic and confused and was brought to this hospital. On physical examination his temperature was 102.4 ~ F, and he was lethargic and confused with a faint rash over most of his body. Roth spots, Janeway lesions, splinter hemorrhages, and numerous petechiae over his skin and soft palate were observed. A grade 5/6 systolic cardiac murmur was heard. The neurological examination was otherwise un372

remarkable. A diagnosis of endocarditis was made, cultures drawn, and intravenous antibiotic therapy begun with penicillin, 20 million units, oxacillin, 12 gm, and gentamicin 240 mg per 24 hours. The spinal fluid contained 26 neutrophils and 571 RBC's/cu mm; CSF glucose was 68 mg/dl, and protein 72 mg/dl. On the third hospital day he experienced a generalized major motor seizure with postictal aphasia. Spinal fluid at that time was under a pressure of 150 m m H~O and contained 13 neutrophils/cu mm, with no change from the earlier chemistries. Multiple blood cultures drawn on admission grew Staphylococcus aureus. The penicillin and gentamicin J. Neurosurg. / Volume 48 / March, 1978

Bacterial intracranial aneurysm

FIG. 3. Case 4. Anteroposterior films of vertebral angiograms done 2 weeks (left) and 5 weeks (right) after a normal vertebral study. An aneurysm (arrows) is seen on the posterior temporal branch of the right posterior cerebral artery. This aneurysm appears to be smaller on the later study. The aneurysms seen in Fig. 2 did not appear on carotid angiograms done at these times.

were discontinued, and oxacillin, 2 gm every 4 hours was given intravenously. Radionuclide brain scan showed three areas of increased uptake. On the 22nd day an angiogram revealed small vessel occlusions in the left posterior frontal opercular vessels, and two slowly filling a n e u r y s m s on peripheral branches of the right middle cerebral artery (Fig. 2). The vertebral study was normal. Two days later he experienced sudden onset of extremely severe headache without other symptoms or physical findings. Angiography was repeated as an emergency procedure, and showed very slight enlargement of the more rostral aneurysm, but no mass effect. Lumbar puncture at this time again revealed clear CSF, which now contained 380 WBC's, 84% neutrophils, and 1400 R B C ' s / c u mm. His headache cleared over the next 48 hours, and he had no further neurological or cardiac symptoms. On the 36th day angiograms showed no change in the occluded small vessels on the left, but the aneurysms on the right were no longer visible. However, a new aneurysm was seen on the posterior temporal branch of the right posterior cerebral artery (Fig. 3). Intravenous oxacillin was continued for 7 weeks. A C T scan on April 28 demonstrated a small low-density lesion of the left frontotemporal area and a larger area

J. Neurosurg. / Volume 48 / March, 1978

of low density in the right parietal region, both of which enhanced slightly (Fig. 4). Angiograms done the following day demonstrated slight decrease in the size of the posterior cerebral artery aneurysm and no other lesion. The lesions on the C T scan were felt to represent small infarcts, and several blood cultures after discontinuation of antibiotics were sterile. The patient was asymptomatic upon discharge and has continued to do well. Results

Since 1954, 82 patients with documented bacterial intracranial aneurysms have been reported. In a n o t h e r 13 instances the aneurysm was assumed to be present in cases of subarachnoid hemorrhage ( S A H ) and bacterial endocarditis, but these were not confirmed by either angiography or autopsy. ls,2~176 In addition, four true mycotic (fungal) aneurysms 9,17,34,5s and one phytotic (plant) 51 a n e u r y s m are described. T h e patients' ages ranged from 7 months to 78 years. The a g e distribution was essentially uniform below the sixth decade (Fig. 5). The following data include our three confirmed cases, for a total of 85, summarized in Table 1. 373

G. L.

Bohmfalk, et

al.

TABLE 1

Chronological listing by author of 85 documented cases o f bacterial intracranial aneurysms with clinical features* Case No. 1 2 3

Authors, Year Ray & Wahal, 1957

4 5 6 7 8 9 10 11

Alajouanine, et al., 1959 Morgan & Bland, 1959

King, 1960

12 13 14

Pankey, 1962

15

Roach & Drake, 1965

16 17 18 19 20

21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36

Matson, 1965

Cantu, et al., 1966

Ojemann, et al., 1966 Harrison & H a m p t o n , 1967 Bell & Butler, 1968 Heidelberger, et al., 1968 Noonan, et al., 1968 Ziment & Johnson, 1968

Age

Location

State of Aneurysm

Etiology

Treatmerit for Course Aneurysm

Remarks

11 55 18

? bled peripheral bled proximal bled

SBE SBE SBE

cons. cons. cons.

died died died

44

proximal

SBE

cons.

died

33

peripheral intact

SBE

cons.

42

proximal

intact

SBE

?

?

bled

SBE

?

? ? ? 23

? ~ ? peripheral

bled bled intact bled

SBE SBE SBE SBE

10 9 4

? bled ? bled peripheral bled

43

peripheral bled

17 40

proximal multiple

49 49 41

peripheral bled peripheral bled proximal bled

SBE SBE SBE

el. surg. el. surg. cons.

22 46 39 41 67 46 27

peripheral peripheral proximal proximal peripheral multiple 9

bled bled bled bled bled intact bled

SBE ABE SBE SBE SBE men. SBE

cons. cons. cons. cons. cons. cons. el. surg.

8 4 18

peripheral bled multiple intact multiple bled

RHD CHD men.

el. surg. cons. cons.

rec. rec. died

negative cultures negative cultures post-traumatic

10 52

peripheral bled peripheral bled

SBE SBE

em. surg. cons.

rec. died

Corynebacterium

peripheral proximal C.S. peripheral

SBE SBE tbph. SBE

el. surg. el. surg. cons. em. surg.

rec. rec. rec. rec.

negative cultures

9

47 32 Devadiga, et al., 1969 1 2/12 Jones, et al., 1969 22

bled

intact bled

intact intact intact bled

? ? ? el. surg.

ABE cons. ABE cons. C H D , S B E em. surg. SBE

em. surg.

ABE,men. era. surg. SBE el. surg.

Enterococcus

infected berry aneurysm infected berry aneurysm

no follow-up ? occurred 2 yrs after endocarditis died died died died rec. died died died

formed subdural hematoma recovered from surgery, died o f cardiac complications

partialEnterococcus ly rec. died rec. rebled from 2nd aneurysm, reoperated, recovered rec. enlarged rec. rec. not seen on 1st angiogram, disappeared on subsequent angiogram died died died died died rec. disappeared rec.

disappeared

*ABE = acute bacterial endocarditis, CHD = congenital heart disease, cons. = conservative, C.S. = cavernous sinus, el. surg. = elective surgery, era. surg. = emergency surgery, men. = meningitis, rec. = recovered, R H D = rheumatic heart disease, SBE = subacute bacterial endocarditis, and tbph. = thrombophlebitis.

374

J. Neurosurg. / Volume 48 / March, 1978

Bacterial intracranial aneurysm TABLE 1 (Continued)*

Case No.

Authors, Year

Age

37 38 39 40

9 ? 38 17

McNeel, et al., 1969

41 42-49

50 51

Location ?

State of Aneurysm bled

multiple bled multiple intact peripheral intact

5 peripheral bled see remarks

Morin & Talalla, 1969 Hourihane, 1970

Etiology

Treatment for Course Aneurysm

BE

cons.

died

BE men. BE

cons. cons. cons.

? rec. rec.

SBE

em. surg.

rec.

30 22

proximal multiple

bled bled

SBE SBE

cons. el. surg.

died died

52

35

multiple

intact/ bled

SBE

em. surg.

died

53 54 55

peripheral bled peripheral bled peripheral bled

SBE SBE men.

cons. em. surg. el. surg.

died died rec.

56 57 58

46 Agnoli & Bethag, 1971 55 Hannesson & Sachs, 53 1971 Suwanwela, et al., 1972 6 6 33

C.S. C.S. C.S.

intact intact intact

tbph. tbph. tbph.

cons. cons. el. surg.

rec. rec. rec.

59

10

C.S./ intact multiple 10 mos peripheral intact

tbph.

cons.

60 61 62 63 64 65 66 67 68 69

70 71

Sypert & Young, 1972 Gilroy, et aL, 1973 Montrieul, et al., 1973 Ishikawa, et al., 1974 Katz, et al., 1974

22 36 23 25 18 40 27 19 25

Moskowitz, et al., 1974 34 28

multiple proximal multiple multiple peripheral peripheral peripheral peripheral proximal

men. & cons. osteomyelitis intact TB men. cons. bled men. el. surg. bled SBE cons. bled SBE em. surg. bled ?SBE em. surg. bled SBE el. surg. intact SBE el. surg. bled SBE cons. intact RHD, cons. SBE

peripheral intact peripheral intact

SBE SBE

cons. cons.

Remarks not seen on anglogram enlarged evacuated contralateral hematoma, aneurysm decreased in size confirmed but not detailed, ages 7 mos to 78 years, 4 died, 2 had negative cultures sequential aneurysms, recovered f r o m both, died of cardiac complications sequential aneurysms, recovered f r o m 1st, died f r o m 2nd

disappeared decreased in size calcified 10 yrs after thrombophlebitis; ligated cervical carotid artery

no follow-up rec. disappeared died rec. rec. died died rec. rec. rec. rec.

Neisseria Pseudomonas decreased in size

not seen on 1st angiogram, occurred at site o f arterial occlusion by embolus; smaller on 3rd angiogram reg. disappeared partial- disappeared ly rec.

*ABE = acute bacterial endocarditis, C H D = congenital heart disease, cons. = conservative, C.S. = cavernous sinus, el. surg. = elective surgery, em. surg. = emergency surgery, men. = meningitis, rec. = recovered, R H D = rheumatic heart disease, SBE = subacute bacterial endocarditis, and tbph. = thrombophlebitis.

J. Neurosurg. / Volume 48 / March, 1978

375

G. L. Bohmfalk, et al. TABLE 1 (Continued)* State of Aneurysm

Authors, Year

Age

Location

72

North-Coombes & Schonland, 1974 Yarnell & Stears, 1974

12

proximal

bled

SBE

cons.

died

peripheral peripheral peripheral multiple

bled bled bled intact

era. surg. em. surg. cons. cons.

rec. died died rec.

peripheral bled

SBE ABE ABE cardiac myxoma SBE

cons.

died

not seen on 1st angiogram;

73 74 75 76

Castaigne, et al., 1975

22 58 35 42

77

Laguna, et al., 1975

65

78

Lansky & Maxwell, 1975 Ng, et al., 1975 Shibuya, et al., 1976

7

79 80 81 82 83 84 85

Bingham, 1977 Bohmfalk, et al., 1978

C.S.

Etiology

Treatment for Course Aneurysm

Case No.

Remarks rebled in 10 days

Cardiobacterium

intact

tbph.

el. surg.

rec.

enlarged

15 42

peripheral bled C.S. intact

SBE tbph.

em. surg. el. surg.

died rec.

31 8 40

proximal bled multiple bled peripheral intact

29 22

peripheral intact multiple intact

negative cultures enlarged in 10 days, trapped disappeared disappeared, smaller not seen on angiogram

SBE cons. CHD,SBE cons. SBE none ABE RHD, SBE

el. surg. cons.

rec. rec. died rec. rec.

one enlarged, later disappeared; another decreased in size

*ABE = acute bacterial endocarditis, C H D = congenital heart disease, cons. = conservative, C.S. = cavernous sinus, el. surg. = elective surgery, em. surg. = emergency surgery, men. = meningitis, rec. = recovered, R H D = rheumatic heart disease, SBE = subacute bacterial endocarditis, and tbph. = thrombophlebitis.

FIG. 4. C a s e 4. C o m p u t e r i z e d t o m o g r a m d o n e 5 weeks after the initial a n g i o g r a m , without (upper) and with (lower) c o n t r a s t e n h a n c e m e n t . L o w - d e n s i t y lesions t h o u g h t to r e p r e s e n t infarcts in the left midfrontal and right parietal areas d e m o n s t r a t e e n h a n c e m e n t . 376

J. Neurosurg. / Volume 48 / March, 1978

Bacterial intracranial aneurysm Bacteriology All but 13 patients were thought to have endocarditis. Blood cultures grew Streptococcus species in 28, Staphylococcus in 11, and other bacteria in five. Seven patients had persistently negative blood cultures, usually after partial antibiotic therapy. Aneurysms second a r y to e x t r a - a r t e r i a l infection were demonstrated in cases of meningitis, osteomyelitis of the skull, and cavernous sinus thrombophlebitis. Multiple nonbacterial embolic aneurysms were associated with a cardiac myxoma, with no S A H (Case 76).

16

14. 13

.

12

11

10 =

9 8

7

6

3

I

2

A rteriography The location of the aneurysm was specified in 69 of the 85 cases. In 34 cases single aneurysms were peripheral to the first bifurcation of a m a j o r intracranial artery, and 20 were at or proximal to that point, seven of these in the cavernous sinus. N o n e of the six patients with cavernous sinus aneurysms had endocarditis; these aneurysms were secondary to cavernous sinus thrombophlebitis from a variety of causes. Fifteen patients (17.6%) had multiple aneurysms, and in three cases (Cases 17, 51, and 52) the second aneurysm did not appear until after t r e a t m e n t of the first. Repeat angiography was performed on 25 patients, usually after a period of conservative therapy. A n e u r y s m s disappeared in 10 cases, appeared only on a second study in three cases, and in others a n e u r y s m s enlarged, appeared smaller, or remained the same. It is not clear in m o s t cases whether complete cerebral angiography was performed. Clinical Presentation and Mortality Information f r o m l u m b a r puncture, surgery, and autopsies indicates rupture of an aneurysm in 50 of 77 cases (65%). Two patients since 1954 (Cases 5 and 6) and four patients prior to that date 5a5,42 did not develop neurological s y m p t o m s until after completion of their antibiotic therapy for endocarditis, one as long as 2 years after. Slightly more patients were admitted to the hospital with (33) than without (25) neurological s y m p t o m s (Table 2). The mortality of 80% in those patients whose aneurysms bled into the subarachnoid s p a c e during hospitalization for t r e a t m e n t of endocarditis J. Neurosurg. / Volume 48 / March, 1978

'

0

L

.

.

0-I0

.

11-20

.

.

21-30 31-40 41-50 Age by decade

51-60

>61

FIG. 5. Age distribution of 70 patients with bacterial intracranial aneurysms. must represent the most accurate m o r t a l i t y figure for rupture of these aneurysms. The much lower figure, 42.1%, for those patients with evidence of S A H on admission to the hospital p r o b a b l y results from the elimination of m a n y patients who died before reaching the hospital; thus, the overall m o r tality, both with and without S A H , is around 60%, as seen in the 25 patients who were in the hospital with endocarditis before developTABLE 2 Mortality of bacterial intracranial aneurysm based on onset of neurological symptoms in 58 patients* Groupt on or before admission (33) SAH no SAH during hospitalization for treatment of endocarditis (25) SAH no SAH

No. of % Each % Cases Died Category Total 19 14

8 2

15 10

12 3

42.1 14.3

13.8 3.5

80 30

21 5

*Neurological symptoms other than mild or moderate headache, lethargy, or other nonspecific symptoms. tSAH = subarachnoid hemorrhage, indicated by description of "bloody CSF" or presence of more than 100 RBC's in CSF from an atraumatic tap. 377

G. L. B o h m f a l k , e t al. TABLE 3 Mortality based on location of aneurysms in 69 patients Location peripheral proximal cavernous sinus multiple

Total Cases No. ~o

Deaths No. 7o

34 13 7 15

14 7 0 5

49.3 18.8 10.2 21.7

42.4* 58.3* 0 38.5*

*Based on follow-up information available on 33, 12, and 13 patients.

docarditis. Estimates range from 4% to 15%. a,20,41,49 These figures most likely are underestimates, since some aneurysms are asymptomatic, as demonstrated in our Cases 2 and 4. The 18% incidence of multiple aneurysms is probably also a low figure, since all patients were not completely or sequentially studied. In view of the embolic origin of these aneurysms over an extended period of time, one might expect the true incidence of multiple lesions to be even higher. Pathophysiology

ing neurological symptoms. The mortality differences between the groups with and without S A H were significant (Ptot = 0.018).* With few exceptions (Cases 14, 51, and 83), death was due to neurological, and not cardiac or other system involvement. Treatment and M o r t a l i t y

No death was intimately related to surgery in the 17 patients who had elective operations for their aneurysms. Of 13 patients requiring emergency operations for ruptured aneurysm, eight (61%) died. Follow-up information was available on 38 patients whose aneurysms were treated conservatively; 20 (52.6%) died, but several of these patients were agonal on admission and actually received no specific treatment. None of the seven patients with cavernous sinus aneurysms died, but fungal aneurysms were fatal in all cases. Proximal ane'urysms, excluding those of the cavernous sinus, were fatal in seven of the 12 patients, or 58% for whom follow-up information was given. Patients with multiple or single peripheral aneurysms had nearly equal mortality rates, 38.5% and 42% (Table 3).

Discussion Incidence

The true incidence of bacterial intracranial aneurysms is unknown. Older aneurysm and autopsy series yielded widely disparate figures, from 6.2% of 1125 intracranial aneurysms 27 to 29% of 51.11 The important figure is the incidence in patients with en*Fisher's exact test for 2 • 2 contingency. 378

M a n y of the early observers of bacterial aneurysms believed that the process began with embolization of septic particles into the vasa vasorum, followed by a focal arteritis and, in some instances, small periarterial abscess formation. Some authors thought that the process begins within the arterial lumen and spreads centrifugally, 48 but Eppinger 45 in 1887 observed that the inflammation affected the adventitia first and then spread inward, finally attacking the internal elastic membrane. This was confirmed in experimental bacterial intracranial aneurysms in dogs by Molinari, et al. 29,8~ Clinical Presentation

Patients with bacterial intracranial aneurysms are encountered in several distinct settings, and their evaluation and management differ accordingly. The most familiar presentation is the patient with known endocarditis who suffers a subarachnoid or intracerebral hemorrhage. Another common manifestation is a focal neurological event without evidence o f hemorrhage, such as a seizure, in a patient with endocarditis, as occurred in three of our cases. Similarly, ischemic events m a y result f r o m vegetative emboli or vasculitis in areas of the brain at a distance from a silent aneurysm, as in our fourth case. In the course of endocarditis, focal neurological symptoms should be regarded as serious warning signs of bacterial aneurysm, and should be investigated by urgent, complete angiography. Several authors ~8,86,55have urged prompt and complete angiography in all patients with bacterial endocarditis and signs or symptoms of cerebral emboli. In contrast to the above patients, many present with neurological symptoms who are not known to have endocarditis. ~6 In younger J. Neurosurg. / Volume 48 / March, 1978

Bacterial intracranial aneurysm patients the diagnosis is suggested by Jochmann's maxim, "in hemiplegia in young adults always think of SBE" (subacute bacterial endocarditis)?5 If cardiac murmurs are heard, one should suspect endocarditis and proceed with cerebral angiography more promptly than might otherwise be indicated. Patients without murmurs or other suggestion of endocarditis who are found to have peripheral aneurysms should be considered to have endocarditis until proved otherwise. Roach and Drake 4e emphasized that the absence of a heart murmur does not exclude bacterial endocarditis, which was diagnosed after the aneurysms were discovered in all five of their patients. The third major category of patients with bacterial intracranial aneurysms includes those with recognized endocarditis who are neurologically asymptomatic. These are the 3% to 30% who, if their aneurysms rupture, have a mortality rate of 80% (Table 3). These patients have never been identified prospectively, and their number is most likely underestimated, since some aneurysms remain asymptomatic and heal. Considering the low risk of cerebral angiography and the severe consequences of ruptured bacterial aneurysms, complete cerebral angiography should be performed on these patients as early as their condition permits. In view of the occasional development of aneurysms following a normal angiogram or after treatment of one aneurysm, it would be prudent to repeat the angiogram after an interval of 7 to 14 days, "even in the absence of fresh neurologic signs," as suggested by Hourihane, TM and recently reiterated by Bingham.4 A program of complete cerebral angiography on neurologically asymptomatic patients with endocarditis would serve at least three purposes: a more accurate estimate of the incidence of bacterial intracranial aneurysm would emerge; prospective protocols to elucidate the natural history and evaluate different methods of management could be designed; and, above all, some neurological disasters would be avoided. Computed tomographic scanning was used in only one of our cases, and there are no reports in the literature of its use in endocarditis. Our single experience indicates that this noninvasive, safe technique may provide a great deal of information not otherwise available. With improved resolution, one J. Neurosurg. / Volume 48 / March, 1978

might anticipate detecting areas of inflammation around intact aneurysms or the aneurysms themselves, in view of the adventitial inflammation which occurs in their formation. Similarly, small hematomas, abscesses, and infarcts might be seen, recognition of which might influence management of a case. Until their respective roles are defined, it would appear reasonable to couple CT scans with angiograms on these patients. Treatment

Methods of treatment of bacterial aneurysms are based mainly on experience with symptomatic lesions, since the true incidence of spontaneously resolving asymptomatic aneurysms is not known. The general feeling is that these aneurysms almost always rupture, but, as suggested by the l0 cases in which the lesions were not visualized on subsequent angiograms, this may not be the case. Observing these cases with medical cures, Bingham recently suggested that surgical therapy does not offer a significant advantage over adequate antibiotic treatment alone? However, there is no sound, rational treatment plan based on a controlled series of these aneurysms. Our experiences, complemented by those of others reviewed here, have led us to formulate a general outline of therapy for the various categories of bacterial intracranial aneurysms (Fig. 6). Aneurysms with mass lesions should be excised according to the usual management of intracranial mass lesions. The mass may be an abscess. Single superficial aneurysms should also be excised. The experiences reviewed here show that the likelihood of serious neurological deficit is generally very small and mortality of elective surgery is very low. Superficial aneurysms could be treated through a trephine and under local anesthesia, if necessary, for cardiac reasons. Multiple peripheral aneurysms should be monitored with serial angiography, perhaps as frequently as every 7 to 10 days, based on cases showing substantial enlargement over several days (Cases 39 and 85). Peripheral aneurysms that are seen to enlarge should be treated surgically. Patients with stable aneurysms on a second study appear to have a good probability of spontaneous healing, which can be monitored by less frequent angiography. Another index of propensity toward spontaneous resolution may be the 379

G. L. Bohmfalk, et al. EARLY ANGIOGRAPHY AND CT SCANNING SURGICAL TREATMENT

NON-SURGICAL TREATMENT

1. Mass lesions 2. Single peripheral aneurysms 3. ? Multiple superficial aneurysms

1. Intact proximal aneurysms 2. Most multiple aneurysms 3. Negative studies

REPEAT ANGIOGRAPHY AND CT SCANNING BEFORE DISCHARGE 1. Detect new or enlarging aneurysms 2. Monitor recognized aneurysms 3. Confirm surgical treatment

FIG. 6. Scheme for evaluation and management of patients with bacterial endocarditis.

rapidity of opacification and washout of contrast medium during angiography. Aneurysms that fill and empty slowly, as did those in our fourth patient, seem to pose less risk of rupture than those that opacify promptly. Proximal bacterial aneurysms, with a 58% mortality, are more threatening than peripheral aneurysms and are much less amenable to direct surgical treatment in the acute phase. Manipulation of the inflamed friable wall may result in its fragmentation, and the necessity to occlude the parent artery? ,4e Most proximal aneurysms arise from major vessels, and occlusion of the parent vessel will frequently produce severe neurological deficit. Carotid ligation was not effective in relieving severe headache in the one case reported, although the patient did survive) Proximal aneurysms should be monitored angiographically, and all reasonable measures to minimize risk of hemorrhage, such as bedrest, sedation, and hypotension, should be used. There is no report of successful direct surgical treatment of a proximal bacterial aneurysm in the acute phase. Proximal aneurysms that persist after completion of antibiotic therapy may have acquired a sufficient degree of fibrosis to allow surgical manipulation. On the other hand, this healing decreases the risk of hemorrhage and supports a position of further angiographic observation, in anticipation of spontaneous resolution, as occurred in Cases 6 and 8. Our review of the literature yielded no good solution for the enlarging proximal aneurysm. Extra- to intracranial 380

arterial anastomosis may provide collateral circulation before excising enlarging proximal aneurysms, in order to protect against loss of the parent artery which may be sacrificed. Otherwise, one might consider carotid ligation for enlarging proximal aneurysms.5 Aneurysms of the cavernous sinus in all cases developed in the course of orbital and cavernous sinus thrombophlebitis and not endocarditis. Two of the seven aneurysms in this location enlarged, and these were successfully treated by a trapping procedure (Case 80) and common carotid artery ligation (Case 78). Another decreased in size (Case 57), and two disappeared (Cases 35 and 56). None of these patients died. It appears reasonable to monitor these aneurysms angiographically, and trap those that enlarge. Summary

Three documented cases and one presumed case of bacterial intracranial aneurysm are reported, one of which demonstrated multiple, sequentially appearing, enlarging, diminishing, and spontaneously resolving aneurysms. Eighty-two cases from the literature since 1 9 5 4 plus our three documented cases are analyzed. The overall mortality was 46%, with the highest mortality, 80%, found in those patients whose aneurysms ruptured during the course of treatment for endocarditis. Almost one-fifth of the patients had multiple aneurysms. Complete and sequential cerebral angiography is necessary in order to detect multiple J. Neurosurg. / Volume 48 / March, 1978

Bacterial intraeranial aneurysm and sequentially appearing aneurysms and to monitor those aneurysms treated medically. In 10 of 25 patients (40%) who had a second a n g i o g r a m after c o n s e r v a t i v e treatment, previously seen a n e u r y s m s no longer appeared. There were no surgical deaths in 17 patients whose aneurysms were electively excised. Single and, perhaps in some instances, multiple accessible aneurysms should be excised. Proximal aneurysms on or near the circle of Willis should be followed angiographically or, if seen to enlarge, perhaps treated with carotid ligation. Acknowledgments

The authors are grateful to Dr. Phillip Craven, Division of Infectious Diseases, and Dr. Robert O'Rourke, Division of Cardiology, for reviewing the manuscript; to Barbara Maaskant, Scientific Computer Section, Department of Bioengineering, for the statistical analysis; to Mrs. Dalyce Franks for typing the manuscript; and to the Medical Photography and Illustration Services of the Health Science Center and Audie L. Murphy Veterans Hospital for the preparation of the figures. References 1. Agnoli A, Bettag W: Endokarditis und Subarachnoidalblutung. Z Neurol 199: 295-305, 1971 2. Alajouanine T, Castaigne P, Lhermitte F, et al: Cerebral arteritis of bacterial endocarditis" its late complications. JAMA 170:1858, 1959 (Abstract) 3. Bell WE, Butler C 2nd: Cerebral mycotic aneurysms in children. Two case reports. Neurology 18:81-86, 1968 4. Bingham WF: Treatment of mycotic intracranial aneurysms. J Neurosurg 46:428-437, 1977 5. Campbell E, Burklund CW: Aneurysms of the middle cerebral artery. Ann Surg 137:18-28, 1953 6. Cantu RC, LeMay M, Wilkinson HA: The importance of repeated angiography in the treatment of mycotic-embolic intracranial aneurysms. J Neurosurg 25:189-193, 1966 7. Castaigne P, Laplane D, Ricou P, et al: [Multiple intraeranial arterial aneurysm of mycotic appearance. Repeated vascular embolic accidents. Myxoma of the left ventricle.] Rev Neurol 131:339-346, 1975 (Fr) 8. Cates JE, Christie RV: Subacute bacterial endocarditis. Q J Med 20:93-130, 1951 9. Davidson P, Robertson DM: A true mycotic (Aspergillus) aneurysm leading to fatal sub-

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44. Ray H, Wahal KM: Subarachnoid hemorrhage in subacute bacterial endocarditis. Neurology 7:265-269, 1957 45. Richey WG, MacLachlan WWG: Mycotic embolic aneurysms of peripheral arteries. Arch Intern Med 29:131-140, 1922 46. Roach MR, Drake CG: Ruptured cerebral aneurysms caused by micro-organisms. N Engl J Med 273:240-244, 1965 47. Shibuya S, Igarashi S, Amo T, et al: Mycotic aneurysms of the internal carotid artery. Case report. J Neurosurg 44:105-108, 1976 48. Shnider BI, Cotsonas NJ Jr: Embolic mycotic aneurysms, a complication of bacterial endocarditis. Am J Med 16:246-255, 1954 49. Snow RM, Cobbs CG: Treatment of complications of infective endocarditis, in Kaye D (ed): Infective Endocarditis. Baltimore: University Park Press, 1976, pp 213-228 50. Starrs RA: Subacute bacterial endocarditis presenting as a subarachnoid hemorrhage (report of a case - - with recovery). Ann Intern Meal 31:139-145, 1949 51. Steele JJ, Kilburn HL, Leech RW: Phytotic (mycotic) intracranial aneurysm with an unusual pathogenesis: A case report. Pediatrics 50:936-939, 1972 52. Stengel A, Wolferth CC: Mycotic (bacterial) aneurysms of intravascular origin. Arch Intern Meal 31:527-554, 1923 53. Suwanwela C, Suwanwela N, Charuchinda S, et al: Intracranial mycotic aneurysms of extravascular origin. J Neorosurg 36:552-559, 1972 54. Sypert GW, Young HF: Ruptured mycotic pericallosal aneurysm with meningitis due to Neisseria meningitidis infection. Case report. J Neurosurg 37:467-469, 1972 55. Visudhiphan P, Bunyaratavej S, Khantanaphar S: Cerebral aspergillosis. Report of 3 cases. J Neurosurg 38:472-476, 1973 56. Whipple RL Jr: Subacute bacterial endocarditis presenting as a subarachnoid hemorrhage: report of a case with recovery. Ann Intern Med 35:1351-1358, 1951 57. Yarnell PR, Stears J: Intracerebral hemorrhage and occult sepsis. Neurology 24: 870-873, 1974 58. Ziment I, Johnson BL Jr: Angiography in the management of intracranial mycotic aneurysms. Arch Intern Med 122:349-352, 1968 This paper was presented in part at the Annual Meeting of the American Association of Neurological Surgeons in Toronto, Canada, April 24-28, 1977. Address reprint requests to: Jim L. Story, M.D., Division of Neurosurgery, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, Texas 78284.

J. Neurosurg. / Volume 48 / March, 1978