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 »  Introduction
 »  Material and methods
 »  Results
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Year : 2001  |  Volume : 49  |  Issue : 1  |  Page : 41-6

Neuropathological complications of infective endocarditis : study of autopsy material.

Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh - 160012, India.

Correspondence Address:
Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh - 160012, India.

  »  Abstract

78 autopsy proven cases of infective endocarditis (IE) seen during 1983 to 1995 were retrospectively reviewed. The brain was available for examination in 44 cases. In the remaining cases, brain was not examined because examination of it was not requested due to lack of neurological findings. Brain lesions were observed in 35 out of 44 cases of IE. Assuming remaining 34 cases to be without brain lesions, the brain involvement in IE would be 44.87% (35 out of 78 cases). Mean age of all cases of IE and those with brain lesions was similar i.e. 26.5+/-16.6 years and 26.6+/-13.06 years respectively. Largest number of cases with neuropathological lesions were associated with normal valve IE (48.57%). Mitral valve was most commonly involved in cases with CNS complications (57.14%) (p<0.05). The various types of brain lesions were infarction (68.57%), haemorrhage (57.14%), cerebral micro-abscess (31.42%) and focal meningitis (14.28%). More than one type of lesion was observed in 19 cases, indicating complicated nature of brain lesions in fatal cases of IE. Left sided middle cerebral artery (MCA) territory was the commonest site of infarction and haemorrhage. Staphylococcus aureus appeared to be the most common organism in fatal cases of IE. Normal valve IE with or without CNS complications constitutes a significant group in India and is different from the west as far as the predisposing conditions are concerned.

How to cite this article:
Patel F M, Das A, Banerjee A K. Neuropathological complications of infective endocarditis : study of autopsy material. Neurol India 2001;49:41

How to cite this URL:
Patel F M, Das A, Banerjee A K. Neuropathological complications of infective endocarditis : study of autopsy material. Neurol India [serial online] 2001 [cited 2023 Mar 27];49:41. Available from: https://www.neurologyindia.com/text.asp?2001/49/1/41/1303

   »   Introduction Top

Despite the availability of a wide range of antibiotics,
infective endocarditis (IE) continues to be a major
problem all over the world.[1] The main reasons
include emergence of newer infective organisms and
extracardiac complications. Among the extracardiac
complications, involvement of the central nervous
system (CNS) is possibly the most serious. The
association of IE and neurological complications has
been recognised for more than a century. Sir William
Osler2 in his series of Gulstonian lectures,
underscored the clinical triad of fever, heart murmur
and hemiplegia. He was first to suggest that
neurological symptoms can be the initial manifestation of IE. The clinical profile and
expression of IE has undergone profound changes in
the past half century due to natural evolution of the
disease, although some changes relate to newer
therapies and newer population at risk. Recent studies
of IE3-7 have emphasized the changing pattern of
neurological complications due to advancing age of
the patients, increase of nosocomial infections,
increasing incidence of non-rheumatic heart disease,
as rheumatic heart disease has virtually disappeared
outside the developing countries, intravenous drug
abuse and decreasing incidence of infection due to
streptococcus viridans with the concomitant increase
in infection due to staphylococcus aureus, Group D
streptococci and other organisms. It has also been
observed that IE is an important cause of stroke in the
young.[8] The present study was undetaken to
analyse the spectrum and relative frequency of brain
lesions in IE in autopsy material.

   »   Material and methods Top

The patients who succumbed to IE at Nehru Hospital,
Postgraduate Institute of Medical Education and
Research (PGIMER), Chandigarh and in whom
consent was available, were subjected to partial or
complete autopsy. Brain was examined in the cases
in which specific consent was available. Complete
autopsy records and the tissues of all cases of IE seen
from 1983 to 1995 were re-examined, both grossly
and microscopically. Microscopic examination was
performed on paraffin embedded section with routine
haematoxylin and eosin stain and special stains
including those for organisms as necessary. The brain
of each case was examined in the standard manner.[9]
The blood vessels were examined in detail particularly
in cases with haemorrhage. The heart was explored
by inflow-outflow tract method in each case and
examined grossly and microscopically for the
presence or absence of congenital or acquired disease,
the size of vegetations and their location. The cases
having vegetations composed of fibrin and
inflammatory cells, with or without demonstrable
bacterial colonies, were considered as infective
endocarditis. The data was expressed as mean
percentage and standard deviation. The categorical
variables were analysed by Chi-square test.

   »   Results Top

There were 78 autopsy proven cases of IE during the
period 1983-1995. The brain was available for
examination in 44 cases. In the remaining 34 cases,
the examination of the brain was not requested, as
none of them had neurological symptoms clinically.
Out of 44 cases in whom brain was examined, the
lesions were observed in 35 cases. The results are
described under group A i.e. all cases of IE
irrespective of brain lesion (78 cases) and Group B i.e.
cases of IE showing brain lesions (35 cases). A
comparative analysis [Table I] showed similar age
distribution of cases in both the groups and relative
female preponderance in group B. While pre-existing
heart disease was observed in both groups, normal
valve endocarditis was more frequent in group B
cases. Patients of group B exhibited more left sided
value (80%) and isolated valve (85.71%) involvement.
Isolated mitral value (MV) involvement was most
common (60%) followed by involvement of aortic
valve (AV) (17.14%) and others.
Vegetations : Vegetations measuring 0.5 cm or more
were considered as large and less than 0.5 cm as
small. Brain lesions were more commonly associated
with small vegetations than IE with large vegetation
(25 versus 10 cases).
Causative Agents : Gram's stain and PAS stain were
performed on paraffin embedded sections of
vegetation in all 44 cases. Gram positive cocci were
found in 26 cases and demonstrable bacterial colonies
without further categorisation in another 5 cases. Two
cases of aspergillous endocarditis were also detected.
However, special stains failed to demonstrate any
organisms in 11 cases. The blood culture reports were
available in 14 cases. Staphylococcus aureus was
positive in 6 and Klebsiella pneumoniae in 2 cases.
Culture was sterile in 6 cases.
Neuropathological complications : Spectrum of
neurological lesions in IE were embolism, infarction,
haemorrhage and infective complications like
meningitis and cerebral abscess. Single as well as
multiple lesions were observed. Multiple lesions were
more common than single type (19 versus 16 cases)
[Table II].
Infarction : Infarction [Figure - 1] was the most frequently
observed brain lesion in 24 cases, of which 15 were
associated with other lesions. The middle cerebral
artery (MCA) territory was involved in 19 cases with
left MCA in 8, right MCA in 5 and both in 6 cases.
The posterior cerebral artery (PCA) territory was
involved in 2 cases. Infarction in the water shed area
of MCA and anterior cerebral artery (ACA) was found
in 3 cases. Out of 24 cases, multiple small infarcts
were seen in 9, multiple large infarcts in 7, single large
infarcts in 7 and single small infarct in one case. On
microscopic examination, 15 were recent infarcts
(less than 1 week) as characterised by inflammatory
cell infiltration and other features. In 4 cases, the
infarct was older (over one week), as characterised by
collection of macrophages and cystic changes. Five
cases showed old as well as recent infarcts. Isolated
MV endocarditis was more commonly associated with
infarction in 15 cases followed by isolated AV (4
cases) and multiple valve endocarditis (5 cases).
Haemorrhage (Mycotic aneurysm/arteritis) : Twenty
cases of haemorrhage [Figure - 2] with or without arteritis
and 3 cases of arteritis without haemorrhage were
noted. The relative proportion of anatomical
distribution of haemorrhage in 20 cases was intracerebral
haemorrhage (ICH) (9 cases), sub-arachnoid
haemorrhage (SAH) + intra-ventricular haemorrhage
(IVH) + ICH (7 cases), SAH+ICH (2 cases), SAH
(one case) and SAH+IVH (one case). The
intracerebral haemorrhage (ICH) of more than 1.5 cm
diameter in brain stem and more than 3 cm diameter
in rest of the brain was classified as large
haemorrhage.10 Accordingly, 7 cases showed small
ICH and the remaining 2 cases showed large
haemorrhage. Another 7 cases of ICH along with
SAH and IVH were invariably of large haemorrhage
type. Two cases of ICH associated with SAH were of
small haemorrhage type. Out of these 20 cases of
haemorrhage, only seven showed mycotic aneurysm
[Figure - 3], involving both major arteries (4 cases) and
minor branches (3 cases) of the middle cerebral
arteries. Majority of these cases of haemorrhage were
associated with mitral valve endocarditis (11 out of 20
cases). Nine cases of haemorrhage were noted in
endocarditis of normal valve and 7 in endocarditis in
Infection : Twelve cases showed infective
complication including 4 cases of focal meningitis
with microabscesses [Figure - 4], 7 cases of microabscess
and a case of solitary cerebellar abscess with diffuse
meningitis. These microabscesses were multiple,
small and non-encapsulated. Confluent lesions of this
kind are sometimes designated as suppurative
encephalitis and were seen typically in association
with septicaemia. These lesions were seen in 8 cases
of MV endocarditis, 2 cases of AV endocarditis. In 2
cases, other valves were involved. Cerebral
microabscesses were most commonly observed in
normal valve endocarditis (7 cases) which appears to
be a component of septicaemia. The remaining 5 cases
had RHD (3 cases), CHD (1 case) and prosthetic valve
endocarditis (1 case).
A single case of solitary cerebellar abscess with
diffuse meningitis was found in association with
tricuspid valve (TV) endocarditis. The endocarditis in
this case appeared to be secondary to cerebellar
abscess leading to thrombophlebitis of lateral sinus
and internal jugular vein and direct extension to the
right atrium and TV.

   »   Discussion Top

Despite advancement in chemotherapeutic measures,
IE continues to be as enigmatic as ever with a world
wide distribution. The CNS complications today
remain remarkably similar to the picture described in
the pre-antibiotic era.[1],[6],[17] Most of the recent
reports1,[7],[11],[12],[13],[14],[15] indicate the incidence of CNS
complications, in the antibiotic era, between 20-40%
with an average of 30% as compared to 12-31%1,16,17
in the pre-antibiotic era. The pattern and background
of IE in the western countries differs in many respects
from those in the developing or underdeveloped
countries. In a developing country, like India, with
higher incidence of infections as well as RHD,
combined with inadequate facilities of detection and
poor availability of newer antibiotics, the pattern of
IE may not be the same as in the developed countries.
The present study comprised of fatal cases of IE with
high incidence of brain lesion (35 out of 44 cases in
which brain was examined). If we assume that the 34
cases in which the brain was not examined, were free
of any brain lesion, even then the percentage of
neuropathological complication in this series would
be at least 44.87%. However, the figure could have
been higher if we had examined those cases as well.
The figure seems to be higher than any other series,
because these were all fatal cases of IE.
The mean age of the patients in this series was 26.[5]
years and the majority were under 40 years of age,
similar to those reported by Santoshkumar et al7 and
Choudhury et al.[18] In contrast, a higher age incidence
was reported by Bayliss et al[19] and Salgado et al.[20]
This difference in the age distribution of patients was
due to decreasing incidence of RHD and greater
longevity of the population in latter series from the
developed countries. Male preponderance among
cases of IE was similar to that observed by Choudhury
et al[18] and Salgado et al,[20] but Von Reyn et al[21]
showed equal sex distribution. The reason for male
preponderance is not clear. In contrast, brain lesions
in this study were more commonly found in the
females [Table I].
Pre-existing heart disease : Normal valve IE was more
common than diseased valve IE in this study in
contrast to most Indian studies where the diseased
valve IE was more common.[7],[18],[22],[23] Among the
diseased valve IE, CHD predominated in this study in
contrast to RHD seen in other Indian clinical
studies.[7],[18],[22],[23] The difference may be due to smaller
sample size in our study but it should also be noted
that normal valve IE may remain clinically undetected
because of the predominant manifestations of
septicaemia, neurological illness and short survival.
CNS complications were more commonly found in
normal valve IE in this study. 48.57% of cases with
brain lesions had normal valve endocarditis. The
reasons are unclear but iatrogenic causes like use of
infected needles for therapeutic purposes is a strong
possibility. Currently cardiac prosthesis and
intravenous drug abuse accounted for a significant
identifiable source of infection in the western
literature,[24] but these were uncommon in our setting
and none of the patients in the present series was IV
drug abuser. The left sided valve involvement was
more commonly associated with brain lesions than
right, because the septic emboli from the left sided
valve can directly go to the brain. CNS lesions were
noted more frequently in mitral valve endocarditis (21
cases) than aortic valve (6 cases) in this study, which
is similar to the findings of Pruitt et al15 and LeCam
et al,[25] however, but different observation was made
by Garvey and Neu.[26] Since this institute is a referral
centre of north-west India, the majority of patients had
probably received antibiotics prior to hospitalisation,
which could be the reason for negative blood culture.
Staphylococcus aureus, however, was the most
common causative agent. Two cases of aspergillous
endocarditis detected by histopathological
examination of vegetations appeared to be a
manifestation of acute disseminated aspergillosis, a
common finding in our autopsy material.
Neuropathological complications : Cerebral infarction
was the most common neuropathological
complication found in this study, similar to the
findings of Pruitt et al.[15] The middle cerebral artery
territory was most commonly involved. The cerebral
infarction was generally due to embolic occlusion of
the arteries. In majority of cases (15 out of 24 cases),
emboli could not be demonstrated grossly as well as
microscopically. The likely explanation is disintegration
of the emboli after initial lodgment[27] and
involvement of smaller branches. Normal valve IE
was more commonly associated with embolic
complication in comparison to diseased valve IE. In
normal valve IE, the process is rapidly destructive
without evidence of healing and results in large
friable vegetations.
Intracranial haemorrhage remained the second
common neuropathological complication of IE and
was usually caused by rupture of an aneurysm,
presumably secondary to localised arteritis
subsequent to a septic embolus. Occasionally, arterial
wall destruction secondary to septic embolus may
occur before formation of either true or false
aneurysm. The middle cerebral arterial system has
been reported to be the predominant site of
involvement. Mycotic aneurysm was found in nearly
equal number of cases in normal valve and diseased
valve IE. A similar observation was made by
Pankey[28],[29] and Kernohan et al (Cited by Lerner[1]). In
contrast, other studies[30],[31],[32],[33],[34] showed higher incidence
of mycotic aneurysm in diseased valve IE. Low
virulent organism like streptococcus viridans was
found in the diseased valve.[1],[15] Large number of
mycotic aneurysm in diseased valve IE reported in
western literature[30],[31],[32],[33],[34] may be related to subacute
course. In the present study, small sized vegetations
were more commonly associated with aneurysm and
arteritis, in comparison to large ones.
Infective complications were more common in normal
valve than diseased valve IE, similar to the findings of
Pankey et al.[28],[29] Multiple microabscesses were
commonest infective complication. A similar
observation was made by Jones and Siekert35 Other
studies however,[3],[14],[15] showed meningitis to be more
common than cerebral microabscesses. Small sized
vegetations and mitral valve involvement were
commonly associated with infective complications.
These were generally a reflection of acute course
and septicaemic nature of these cases. High
proportion of cases had multiple type of lesions. This
is relevant, because such combinations are difficult to
document on clinical studies.
A significant number of cases of endocarditis,
particularly on a normal valve, may be clinically
silent. A confirmation of the diagnosis of IE, as well
as the various CNS lesions, is more accurate in
autopsy series. It is also worth noting that normal
valve IE with or without CNS complications
constitutes a significant group in India and is
different from the west as far as the predisposing
conditions are concerned.

  »   References Top

1.Lerner PI : Neurological complications of infective endocarditis. Symposium on infections of the central nervous system. Med Clin North Am1985; 69 : 385-398.  Back to cited text no. 1    
2.Osler W : Gulstonian lectures on malignant endocarditis. Lancet1885; 1 : 415-418, 459-464.  Back to cited text no. 2    
3.Lerner PI, Weinstein L : Infective endocarditis in the antibiotic era. N Engl J Med1966; 274 : 199-206, 323-331 & 388-393.  Back to cited text no. 3    
4.Rabinovich S, Evans J, Smith IM et al : A long term view of bacterial endocarditis. Ann Intern Med1965; 63 : 185-198.  Back to cited text no. 4    
5.Weinstein L, Rubin RH : Infective endocarditis -1973. Prog Cardiovasc Dis 1973; 16 : 239-274.  Back to cited text no. 5    
6.Weinstein L, Schlesinger JJ : Pathoanatomic, pathophysiologic and clinical correlations in endocarditis.  Back to cited text no. 6    
7.N Engl J Med 1974; 291 : 832-837.  Back to cited text no. 7    
8.Santoshkumar B, Radhakrishnan K, Balakrishnan KG et al : Neurologic complications of infective endocarditis observed in a South Indian referral hospital. J Neurol Sci 1996; 137 : 139-144.  Back to cited text no. 8    
9.Banerjee AK, Varma M, Vashista RK et al : Cerebrovascular disease in north-west India; a study of necropsy material. J Neurol Neurosurg Psychiatry 1989; 52 : 512-515.  Back to cited text no. 9    
10.Banerjee AK : Postmortem examination of Nervous System. Neurol India1997; 45 : 120-125.  Back to cited text no. 10    
11.Weller RO : Spontaneous intracranial haemorrhage. In: Green field's Neuropathology, Eds JH Adams and LW Duchan, 5th ed., Edward Arnold, London 1992; 269.  Back to cited text no. 11    
12.Harrison MJG, Hampton JR : Neurological presentation of bacterial endocarditis. BMJ1967; 2 : 148-151.  Back to cited text no. 12    
13.Ziment I : Nervous system complications in bacterial endocarditis. Am J Med 1969; 47 : 593-607.  Back to cited text no. 13    
14.Greenlee JE, Mandell GL : Neurological manifestation of infective endocarditis : A review. Stroke 1973 ; 4 : 958-963.  Back to cited text no. 14    
15.Jones Jr. HR, Siekert RG, Geraci JE : Neurologic manifestations of bacterial endocarditis. Ann Intern Med 1969; 71 : 21-28.  Back to cited text no. 15    
16.Pruitt AA, Rubin RH, Karchmer AW et al : Neurologic complications of bacterial endocarditis. Medicine 1978; 57 :329-343.  Back to cited text no. 16    
17.Blumer G : Subacute bacterial endocarditis. Medicine 1923; 2 :105-170.  Back to cited text no. 17    
18.Krinsky CM, Merritt HH : Neurological manifestations of subacute bacterial endocarditis. N Engl J Med 1938; 218 :563-566.  Back to cited text no. 18    
19.Choudhury R, Grover A, Varma J et al : Active infective endocarditis observed in an Indian hospital 1981-1991. Am J Cardiol 1992; 70 : 1453-1458.  Back to cited text no. 19    
20.Bayliss R, Clarke C, Oakley CM et al : The microbiology and pathogenesis of infective endocarditis. Br Heart J 1983; 50: 513-519.  Back to cited text no. 20    
21.Salgado AV, Furlan AJ, Keys TF et al : Neurologic complications of endocarditis : A 12 years experience. Neurology1989; 39 : 173-178.  Back to cited text no. 21    
22.Von Reyn CF, Levy BS, Arbeit RD et al : Infective endocarditis; an analysis based on strict case definitions. Ann Intern Med 1981; 94 : 505-518.  Back to cited text no. 22    
23.Mehta AP, Dave KM, Kinare SG : Infective endocarditis. J Postgrad Med1978; 24 : 40-49.  Back to cited text no. 23    
24.Datta BN, Khattri HN, Bidwai PS et al : Infective endocarditis at autopsy in northern India - a study of 120 cases. Japan Heart J1982; 23 : 329-337.  Back to cited text no. 24    
25.Keyser DL, Biller J, Coffman TT et al : Neurologic complications of late prosthetic valve endocarditis. Stroke 1989; 21 : 471-475.  Back to cited text no. 25    
26.LeCam B, Guviarch JM, Boles JM et al : Neurologic complications in a group of 86 bacterial endocarditis. Eur Heart J 1984; 5 (Suppl.C) : 97-100.  Back to cited text no. 26    
27.Garvey GJ, Neu HC : Infective endocarditis - an evolving disease : a review of endocarditis at the Columbia presbyterian Medical Centre, 1968-1973. Medicine Baltimore 1978; 57 : 105-127.  Back to cited text no. 27    
28.Siekert RG, Jones Jr. HR : Transient cerebral ischaemic attacks associated with subacute bacterial endocarditis. Sroke 1970; 1 : 178-193.  Back to cited text no. 28    
29.Pankey GA : Subacute bacterial endocarditis at the university of Minnesota Hospitals 1939 through 1959. Ann Intern Med1961; 55 : 550-561.  Back to cited text no. 29    
30.Pankey GA : Acute bacterial endocarditis at the university of Minnesota Hospitals 1939-1959. Am Heart J 1962; 64 :583-591.  Back to cited text no. 30    
31.Cates JE, Christie RV : Subacute bacterial endocarditis. A review of 442 patients. QJM 1951; 20 : 93.  Back to cited text no. 31    
32.Morgan WL, Bland EF : Bacterial endocarditis in the antibiotic era. Circulation1959; 19 : 753-765.  Back to cited text no. 32    
33.Roach MR, Drake CG : Ruptured cerebral aneurysm caused by micro-organisms. N Engl J Med1965; 273 : 240-244.  Back to cited text no. 33    
34.Cantu RC, Le May M, Wilinson HA : The importance of repeated angiography in the treatment of mycotic embolic intracranial aneurysm. J Neurosurg1966; 25 : 189-193.  Back to cited text no. 34    
35.Wann LS, Dillon JC, Weyman AE et al : Echocardiography in bacterial endocarditis. N Engl J Med1976; 295 : 135-139.  Back to cited text no. 35    
36.Jones Jr. HR, Siekert RG : Neurological manifestations of infective endocarditis. Review of clinical and therapeutic challenges. Brain 1989; 112 : 1295-1315.  Back to cited text no. 36    


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