infection as a direct risk factor of stroke

1. IN FECTI0N AS A RISK
FACTOR OF STROKE
Osama A. Ragab
Neurology, MD
2016

2. • Although established risk factors for stroke exist, some infectious
pathogens might confer additional risk either by aggravating
theses factors or having a direct causal role.

3. • Several findings suggest a possible association between systemic infection and
stroke.
• Some patients who had stroke lack traditional cerebrovascular risk factors.
• stroke incidence rises during cold months, which leads to speculation that
infections contribute to this seasonal fluctuation

5. MECHANISM OF STROKE RELATED INFECTION
• Stimulation of the inflammatory response is thought to be the predominant
mechanism linking ischaemic stroke with infection .
• Inflammatory cascades promote atherosclerosis, plaque rupture, and
thrombosis, leading to ischaemic stroke.
• High-sensitivity C-reactive protein in the blood might be an independent
predictor of ischaemic stroke, but its precise association is unsettled.
• A systemic inflammatory response to infection can injure vascular endothelial
cells and predispose patients to intracranial haemorrhage.

6. INFECTIONS CAUSING STROKE
BACTERIAL
VIRAL
FUNGAL
PARASITES

7. BACTERIAL INFECTIONS

8. INFECTIVE ENDOCARDITIS
• Stroke occurred in 17% of adult inpatients with infective endocarditis enrolled in a study done
in 25 countries.
• The risk of stroke was highest at presentation of infective endocarditis and declined within 1–
2 weeks after antibiotics were initiated.

9. • S aureus, β-haemolytic streptococci, and Streptococcus viridans are the most
frequently identified pathogens in infective endocarditis complicated by
intracranial haemorrhage.
• Degradation of the arterial wall by bacteria or septic embolisation causes
abnormal dilatations or mycotic aneurysms.
• These aneurysms can be numerous and occur at distal portions of the middle
cerebral artery, and their rupture is associated with a high mortality rate.
INFECTIVE ENDOCARDITIS

10. • Transesophageal echocardiogram at the level of the midesophagus demonstrating a large vegetation on the
left atrial side of the mitral valve (arrow). The patient reported no neurological symptoms, and a detailed
neurological examination was normal. Right, Axial MRI of the brain using a fluid-attenuation inversion
recovery sequence. The bright lesion in the left frontal cortex (arrow) represents ABE. LV indicates left
ventricle.

11. • T2* cerebral magnetic resonance imaging shows corticomeningeal small black dots related to
microhemorrhages (A). At the corresponding site of a left frontal microhemorrhage (white arrow),
axial and sagittal magnetic resonance angiography views (B and C) suggest the presence of a
fusiform mycotic aneurysm; arterial origin was confirmed by using cerebral angiography (D)

12. BACTERIAL MENINGITIS
• Brain infarction occurred in (25%) of patients with bacterial meningitis.
• venous infarction also complicates bacterial meningitis in 3–5% of patients.
• One prominent mechanism for arterial infarction is vasculitis, most commonly
associated with inflammation of large and medium cerebral blood vessels.
• Concentrations of interleukin-6 were notably elevated in the cerebrospinal fluid of
the patients.
• Reactive oxygen species and reactive nitrogen intermediates have been identified as
critical mediators of the pathogenesis of bacterial meningitis related stroke.

14. • Bacterial meningitis may be complicated by intracranial haemorrhage in 1–3% of patients.
• Causative bacteria include S pneumoniae in 67% of patients, S aureus in 21% of patients, and
Pseudomonas aeruginosa or Listeria monocytogenes in a few patients .
• Intracranial haemorrhage might be evident at presentation, but in about two-thirds of cases,
the haemorrhage is diagnosed later in the clinical course.
• the most frequent types of cerebral haemorrhage are intraparenchymal (42%) and
subarachnoid (21%), followed by haemorrhagic transformation of infarction (17%) and
microhaemorrhages (13%).
BACTERIAL MENINGITIS

15. • D, Apparent diffusion coefficient maps showing an acute ischemic lesion involving the
complete MCA stroke territory.
• E ,MR angiography reveals a severe stenosis and reduced flow within the right distal internal
carotid artery and the proximal MCA (arrow) of the same patient.
• H, Ischemic infarct involving left posterior, inferior temporal, and occipital lobe. Additional
involvement of the splenium of the corpus callosum

16. • A 36 year old lady with meningitis showing A) normal cranial MRI but her B) MR venography
shows thrombosis of superior sagittal sinus (white arrow).

17. • Cerebral CT scan without contrast showing a hematoma in the basal ganglia in a patient with
meningitis due to S. pneumoniae.

18. TUBERCULOSIS
• In tuberculous meningitis, a necrotising meningoencephalitis develops with
leptomeningeal exudates that surround the brainstem and infiltrate the walls
of arteries and veins.
• The hypercoagulable state might be associated with low blood concentrations
of protein S and increased concentrations of factor VIII.
• The sites that are susceptible to cerebral infarction in patients with TB
meningitis are the basal ganglia, internal capsule, thalamus, cerebral cortex,
pons, and cerebellum
• Aneurysmal dilatation, ruptured mycotic aneurysm, and granulomatous septic
embolism have also been noted.

19. • Stroke occurs in 45% of patients with TBM both in early and later stage, mostly in basal
ganglia region, and predicts pooroutcome at 3 months.
• Stroke was significantly related to stage of meningitis, hydrocephalus, exudate, and
hypertension.

20. • Cranial MRI of patient with Tuberculosis meningitis (TBM) shows cortical and subcortical
infarcts in Diffusion weighted Imaging (DW1) (A) and T2 images (B).

22. VIRUSES

23. HERPES SIMPLEX
• HSV-1, when causing meningoencephalitis, can lead to petechial cerebral haemorrhages and
intracranial haemorrhage in severe cases.
• Disruption of the blood–brain barrier, cerebral oedema, and necrosis, particularly involving
the temporal lobe, orbital gyrus, insula, and angular cortex are well described.
• The outcome of fulminant cerebral haemorrhage in the setting of HSV encephalitis is generally
poor, even with antiviral therapy .
• Areterial ischaemic stroke may occur but less frequent than haemorrhage.

24. An axial T2W MRI image shows an area of left medial temporal lobe encephalitis (left). On
the right, an axial CT image without contrast shows the presence of bleeding in the same
encephalitic area, with brainstem compression and obliteration of the lateral ventricle horn

25. • Brain MRI (T1 post-IV contrast) showing enhancement in the area of the ischemic
stroke.

26. VZV can spread to arteries in the central nervous system and
cause hemorrhagic or ischemic complications due to an
inflammatory vasculopathy.
VARICELLA ZOSTER VIRUS

27. Their findings provide evidence that HZ carries an increased risk of stroke or
TIA and that the effect of HZ on stroke decreases with increasing age.

28. • VaricStrokes related to VZV infection tend to affect the deep structures of the brain, including
the basal ganglia and internal capsules, as well as the cerebral cortex supplied by the
branches of the middle cerebral artery.
VARICELLA ZOSTER VIRUS

29. • Hepatitis C virus (HCV) could increase the long-term risk of stroke and stroke
death.
• This increase might occur either through cryoglobulinaemia, which leads to a
rise in deposition of immune complexes in the vessel wall or atherosclerosis
provoked by inflammation.
• It has been demonstrated that HCV lives and replicates within carotid plaque
and the virus enters and replicates inside human brain endothelial cells
• It is important to consider that a significant number of patients with HCV and
stroke did not show liver disease or had only a moderate disease.
HEPATITIS C VIRUS

31. CNS vasculitis in a patient with HCV infection.
Brain MRI showed a left caudate nucleus and
lenticulocapuslar recent ischemic lesion in DWI
(a); an old infarction in, the right ACA territory,
and other white matter changes were visible in
FLAIR (b). Time of flight MR angiography
revealed multiple intracranial stenosis in the
proximal ACA, left ACP and basilar artery
segments (c). Conventional cerebral
angiography documented right ACA occlusion
(d), critical stenosis at the left A1/A2 segment
(e), and occlusion of the inferior 1/3 and of the
distal segment of right vertebral artery (f),

32. HIV
• HIV can directly invade the CNS as early as 8 days after systemic infection, producing
increased inflammatory markers in CSF and brain parenchymal inflammation.
• Thinning of the arterial media layer and fragmentation of internal elastic lamina occurs in
patients with chronic HIV .
• Several case series have reported aneurysmal and non-aneurysmal dilatation of arteries.
• Protein S deficiency is often identified in HIV,
• Other coagulopathies, namely antiphospholipid antibody syndrome, have been reported.

35. FUNGI

36. FUNGI
• Fungal meningitis typically cause vasculopathy of the large vessels traversing
the subarachnoid space,
• venous outflow obstruction, and endarteritis mechanistically account for
stroke.
• Fungi can also form focal brain parenchymal abscesses associated with
haemorrhage.
• The highly destructive organisms can invade the walls of major intracranial
arteries, including the basilar artery, predisposing to stroke and aneurysmal
rupture.

37. • Sagittal T2 and postcontrast sagittal and axial T2 images showing
heterogeneous T2 signal intensity lesion in the sphenoid sinus destroying the
posterior wall and with enhancing soft tissue extending into prepontine
cisterns encasing basilar artery and causing basilar artery thrombosis.

38. PARASITES

39. CHAGAS DISEASE
• Chagas disease, caused by the Trypanosoma cruzi, is the third most common parasitic
infection worldwide, with the largest infected population living in South America, Africa and
Iraq.
• Chagas disease is associated with cardioembolic stroke.
• Cerebral embolism most commonly occurs to the middle cerebral artery territory, affecting
70% of patients with Chagas cardiomyopathy.

41. • Brain scans of patients with Chagas disease
• (A) MRI (fluid-attenuated inversion recovery sequence) showing several previous ischaemic strokes in
the territory of both middle cerebral arteries in a 37-year-old man. (B) MRI (T2 sequence) showing
cerebellar ischaemic infarction (in region of the posterior inferior cerebellar artery) in a 32-year-old
man.

42. NEUROCYSTICERCOSIS
• CNS infection with Taenia solium occurs when cysticerci lodge in the subarachnoid space,
brain parenchyma, or cerebral ventricles, causing local inflammation.
• Neurocysticerci can remain for years before undergoing degeneration, which stimulates an
inflammatory reaction with surrounding leptomeningeal deposition of exudative material.
This stage of infection is generally associated with seizure activity, increased intracranial
pressure, and ischaemic and haemorrhagic infarcts.

43. • (A) MRI fast imaging employing steady state
acquisition (FIESTA) axial image showing intra-
ventricular cystic lesions with ipsilateral
ventricular dilatation. (B) MRI T2W coronal
image displaying a left side temporo-parietal
infarction. (C) Computer tomography
angiography shows decrease blood flow
through LMCA (dotted arrow) and contralateral
ICA aneurism (white arrow). (D) Digital
substraction angiography confirmation of right
ICA aneurism (black arrow).

45. SCHISTOSOMIASIS
• Cerebrovascular events can occur during any stage of schistosomiasis, but occur most often in
the subacute and chronic stages.
• Schistosomal ectopic eggs reach the CNS through retrograde flow through the venous plexus.
• Eosinophil-mediated toxicity may lead to vasculitis and small-vessel thrombosis in acute
schistosome vasculitis.
• Cerebral haemorrhage typically occurs in the setting of a meningitic granulomatous reaction
around schistosomal ova.

47. MALARIA
• the mechanical theory claims that the obstruction of the capillaries and cerebral venules by
parasitized erythrocytes is caused by direct action of the parasite on the erythrocyte, distorting its
morphology.
• The results are thrombosis, anoxia, stroke, and tissue necrosis. In more serious cases, further
endothelial damage produces increase in capillary permeability and even hemorrhages.
• There is also a discoloration of the cortex due to hemozoine (malarial pigment).
Malaria digest haemoglobin and release high quantities of free heme, which is the non-protein
component of hemoglobin. Free heme is toxic to cells, so the parasites convert it into an insoluble
crystalline form called hemozoin.
Since the formation of hemozoin is essential to the survival of these parasites, it is an attractive target
for developing drugs .
Several currently used antimalarial drugs, such as chloroquine and mefloquine, are thought to kill
malaria parasites by inhibiting haemozoin biocrystallization.

48. • Cerebral malaria can cause cerebral edema, diffuse or focal compromise of the
subcortical white matter, and cortical, cerebellar and pontine infarctions .

49. • Brain vessels from four different cases of fatal falciparum malaria showing accumulations of
different parasite stages. A, late trophozoites, B, schizonts with abundant pigment; C, mid-stage
trophozoites; D; ring forms containing no intraerythrocytic pigment.

50. WHEN TO INVESTIGATE FOR INFECTIOUS
CAUSES
• Patients who have had strokes caused by infection might be misdiagnosed if lumbar puncture
is not done.
• However, lumbar puncture is not indicated when evaluating a typical patient (an elderly
person with atherosclerotic risk factors with sudden-onset focal neurological deficits).
• The clinical symptoms that might indicate infectious causes include a history of antecedent
fever, rash, and known prior infections.
• For immunocompromised patients, the suspicion should be higher and CSF should be obtained
in immunosuppressed patients.
• Meningeal enhancement or multifocal infarctions, particularly ones that do not respect
traditional arterial or venous territories, could raise the suspicion for infectious or
inflammatory pathologies.

51. TREATMENT
• Treatment of systemic infections that precede or accompany stroke requires prompt initiation
of effective antimicrobial therapy.
• The treatment of specific pathogens should generally follow established guidelines wherever
they exist.
• The role of oral or intravenous steroids alongside antibiotics with infections and new stroke is
also unclear.
• Infection is not an official contraindication for thrombolytic therapy; however, formal
recommendations for treatment cannot be made because of insufficient clinical data.

52. • No convincing evidence proves that anticoagulation prevents embolisation in either native or
prosthetic valve-related infectious endocarditis; in fact, the risk of intracranial haemorrhage
is probably increased with anticoagulation.
• Stable, unruptured, cerebral aneurysms are often sufficiently treated with antimicrobials
alone; however, surgery or endovascular therapy can be considered for ruptured aneurysms
or enlarging unruptured aneurysms.
TREATMENT

53. THANKS