CNS infections- bacterial and viral-1.pptx

CNS INFECTIONS BACTERIAL AND VIRAL

1. MODERATOR: DR. MANUPRATAP N. SIR PRESENTER: DR.SUSHMITA CNS INFECTIONS - BACTERIAL AND VIRAL

2. The concept that the brain was an "immune privileged" organ in which the blood-brain barrier (BBB) was a relative fortress that restricted pathogen entry and limited inflammation has recently undergone significant revision. A surprising large number of pathogens, including many neurotropic viruses, can infect the CNS. Routes of entry include Transsynaptic spread ( e.g , herpes viruses), By "hiding" within blood-borne lymphocytes that access the brain (e.g., HIV and JC viruses), By using the choroid plexus as a gateway into the CNS.

3. ACQUIRED CNS INFECTIONS CONGENITAL/NEONATAL TORCH(S) INFECTIONS: Toxoplasma Rubella Others: HIV Rubella Cytomegalovirus Herpes Syphilis Bacterial Viral Fungal Parasitic and miscellaneous

4. Parenchymal calcifications are the hallmark of most congenital infections. Infections early in fetal development (e.g., during the first trimester) usually result in miscarriage, severe brain destruction, and/or profound malformations such as anencephaly, agyria, and lissencephaly. When infections occur later in pregnancy, encephaloclastic manifestations and myelination disturbance (e.g., demyelination, dysmyelination, and hypomyelination) predominate. With few exceptions (toxoplasmosis and syphilis), most congenital/perinatal infections are viral and are usually secondary to transplacental passage of the infectious agent. CONGENITAL INFECTIONS-TORCH(S)

5. TORCH Infections Congenital Cytomegalovirus

6. Congenital Toxoplasmosis Imaging Scattered parenchymal calcifications. Multiple subcortical cysts. Porencephaly. Ventriculomegaly (hydrocephalus) often due to inflammatory debris and aqueductal obstruction. Lack of cortical malformations.

7. Herpes Simplex Virus Imaging Unlike childhood or adult HSE, neonatal HSV CNS infection is much more diffuse. Both gray and white matter are affected. Consider neonatal HSV encephalitis when cranial imaging at 2-3 weeks of neonatal life shows unexplained diffuse cerebral edema, with leptomeningeal enhancement, without or with cerebral parenchymal hemorrhage.

8. Congenital (Perinatal) HIV Imaging Atrophy, particularly in the frontal lobes. Bilaterally symmetric basal ganglia calcifications. Ectasia and fusiform enlargement of intracranial arteries. Strokes with foci of restricted diffusion and subarachnoid hemorrhage may occur as complications of the underlying vasculopathy.

9. Acquired Pyogenic Infections Meningitis Meningitis is an acute or chronic inflammatory infiltrate of meninges and CSF. Pachymeningitis – duraarachnoid Leptomeningitis - pia and subarachnoid spaces. Three bacteria account for the majority of cases - Haemophilus influenzae , Streptococcus pneumoniae , Neisseria meningitidis

10. Bacteria may arise at the CNS as a result of Direct implantation, Contagious infection from a local septic process (e.g. sinusitis) or an infected foreign body (e.g. a shunting catheter), Haematogenous spread Imaging General Features- The "gold standard" for the diagnosis of bacterial meningitis is CSF analysis . Imaging is neither sensitive nor specific for the detection of meningitis!

11. Compli c a tions The complications of meningitis can be remembered using the mnemonic HACTIVE : H : hydrocephalus A : abscess C : cerebritis / cranial nerve lesion T : thrombosis I : infarct V : ventriculitis / vasculopathy E : extra-axial collection: empyema and hygroma

12. Abscess Abscess is initiated by focal intracranial infection as an area of cerebritis and evolves into a collection of pus surrounded by a vascularized capsule. Size- 5 mm up to several centimetres. Age – most common in 3rd and 4th decades. Infants and neonates - its rare (may occur as complication of bacterial meningitis )

13. Causative agents Adults : Streptococci, Staphylococci Gram-negative (Escherichia coli, Klebsiella, Proteus, Pseudomonas, H. influenzae) Neonates and children : Citrobacter, Proteus, Pseudomonas, Serratia and Staphyloccocus aureus HIV patient – toxoplasmosis, Mycobacterium tuberculosis. Mostly the causative agents are bacteria but there can be fungal or granulomatous or Parasitic agents .

14. Lo c a t i on Typically supra-tentorial, up to 14% infratentorial Grey-White junction is common ( usually if hematogenous) Subdural space Frontal lobe – sinusitis, odontogenic infection Temporal lobe - OM & mastoiditis Multiple uncommon except in immunocompromised

15. V e n tricul i tis A collection of purulent material in the ventricle is more likely due to intraventricular rupture of a brain abscess (IVRBA), a catastrophic complication. Ventriculitis also occurs as a complication of meningitis and neurosurgical procedures such as external ventricular drainage. Ventriculitis is also called ependymitis, pyocephalus, and (less commonly) ventricular empyema.

16. I m a g ing CT Ventriculomegaly with a debris level in the dependent part of the occipital horns. Periventricular hypodensity . The ventricular walls may enhance on CECT. MRI Irregular ventricular debris that appears hyperintense to CSF on T1WI and hypointense on T2WI with layering in the dependent occipital horns. A "halo" of periventricular hyperintensity is usually present on both T2WI and FLAIR scans. DWI shows striking diffusion restriction of the layered debris. Ependymal enhancement is seen in only 60% of cases and varies from minimal to moderate.

17. Em p y emas Extraaxial infections of the CNS are rare but potentially life threatening conditions Empyemas are pus collections that can occur in either the subdural or epidural space. Empyemas in infants and young children are most commonly secondary to bacterial meningitis . In older children and adults , over two-thirds of empyemas occur as extension of infection from paranasal sinus disease . Approximately 20% of empyemas in older children and adultsare secondary to otomastoiditis . Subdural empyemas (SDEs) are much more common than epidural empyemas (EDEs).

18. Imaging NECT scans may be normal or show a hypodense extraaxial collection that demonstrates peripheral enhancement on CECT. Bone CT should be evaluated for signs of sinusitis and otomastoiditis. MR is the procedure of choice for evaluating potential empyemas . T1 scans show an extraaxial collection that is mildly hyperintense relative to CSF. SDEs are typically crescentic and lie over the cerebral hemisphere. SDEs often extend into the interhemispheric fissure but do not cross the midline. EDEs are biconvex and usually more focal than SDEs. EDEs may cross the midline, confirming their epidural location

19. CNS Tuberculous Tuberculous meningitis is the most common presentation of intracranial tuberculosis, and usually refers to infection of the leptomeninges. Tuberculous meningitis, although seen in all age groups, has a peak incidence in childhood (particularly 0-4 years of age) in high prevalence areas .

20. PATHOGENESIS Meningitis Tuberculoma/granuloma Abscess Basal cisterns Cranial nerves 2,3,4,6 and 7 Vasculitis and its complications Majority are <2.5cm Giant –4-6cm Few can be miliary Mature tuberculoma: central caseating necrosis with or without AFB and outer fibrotic rim Can occur anywhere in brain parenchyma Central caseating necrosis with AFB and outer rim of granulation tissue

21. Imaging features C TBM TB GRANULOMA TB ABSCESS NCCT Blurred ventricular margins, basal exudates and hydrocephalus Iso-hyperdense lobulated masses with perilesional edema. Calcification in healed granulomas Hypodense lesions with significant mass effect and surrounding edema. CECT Basal meningeal enhancement Punctate, solid, or ring-like enhancement Ring enhancement T1 Dirty CSF Hypo- or isointense Hypointense T2/FLAIR Hyperintensity of sulci and cisterns Hypointense hyperintense DWI - Solid – no DR Liquified- DR+ DR+++ T1+C Linear/ nodular basal meningeal enhancement Punctate, solid, or ring-like enhancement ring-like enhancement MRS/ others Irregular flow voids Infarcts- DR Thickened and enhancing cranial nerves Lipid lactate NAA:Cr NAA:Cho Lipid lactate

22. Acquired Viral Infections Eight members of the herpes virus family are known to cause disease in humans. These are Herpes simplex virus 1 (HSV-1) and HSV-2, Varicella-zoster virus (VZV), Epstein-Barr virus (EBV), Cytomegalovirus (CMV), and Human herpes virus (HHV)-6, HHV-7, and HHV-8. Each has its own disease spectrum, clinical setting, and imaging findings.

23. Herpes Simplex Encephalitis

24. HHV-6 Encephalopathy

25. CNS MANIFESTATIONS OF HIV

26. HIV & CENTRAL NERVOUS SYSTEM 5 – 10 % present with CNS manifestations as the initial symptom 40 – 50 % of people infected with HIV develop neurological manifestations 75- 90% have demonstrable HIV induced brain injury at autopsy

27. manifestations BRAIN Dementia, Space occupying lesions, Encephalitis Stroke like syndromes MENINGES Meningitis SPINAL CORD Myelopathy , Radiculopathy PERIPHERAL NERVES Peripheral Neuropathy Inflammatory Demyelinating Polyneuropathies Toxic Neuropathy MUSCLE Polymyosistis , Pyomyositis HIV associated Wasting Syndrome

28. HIV ENCEPHALITIS HIV encephalitis (HIVE) & HIV leukoencephalopathy (HIVL) – direct effects HIV – associated neurocognitive disorders (HANDS) are most frequent neurological manifestations of HIVE & HIVL “ Acquired Immunodeficiency dementia complex ” refers specifically to HIV-associated dementia.

29. presentation HANDs develop as intermediate and long-term complication. Early brain infection with HIV is often asymptomatic. Slowly progressive impairment of fine motor control, verbal fluency and short term memory is characteristic. Severe deterioration and subcortical dementia with near vegetative state may develop in final stages

30. Imaging features Generalized progressive volume loss that is disproportionate to the patient's age is the most common presentation. Cortical thinning and bilateral white matter lesions are the most common parenchymal abnormalities. No mass effect Usually no enhancement

31. Ct findings Normal in early stages Mild to moderate atrophy Bilateral & symmetric Patchy or confluent white matter hypodensities

32. mri findings T1W Generalized volume loss with enlarged ventricles and sulci is best appreciated on T1WI Reduced gray matter volume in the medial and superior frontal gyri has been identified as a possible early imaging marker for HIVE White matter signal intensity is generally normal or near-normal on T1WI. T2W / FLAIR Bilateral, patchy, relatively symmetric white matter hyper intensities With time, confluent “hazy,” ill-defined hyperintensity in the subcortical and deep cerebral white matter develops, and volume loss ensues

33. No enhancement on T1 C+ No restriction on DWI In fulminant cases, periventricular enhancement indicate acute demyelination mri findings

34. Axial T1-weighted MR image (a) does not reveal any abnormal signal intensity. Symmetrical and diffuse hyperintensity of the white matter is demonstrated on axial T2-weighted MR image (b); there is a T2 shine-through effect on trace diffusion-weighted image (c), and no apparent change of apparent diffusion coefficient (ADC) value on ADC map (d), and no mass affect compatible with HIV encephalopathy.

35. Hiv vasulopathy HIV-related vasculitis including a primary HIV vasculitis has been described The lenticulostriate vessels are the most vulnerable Exact pathogenesis is unclear Elastic lamina of vessels may be injured by elastases because of repeated infections. Inflammation begins in the adventitia and involves the vasa vasorum , which leads to ischemia of the arterial wall, resulting in the destruction of elastic lamina and subintimal fibrosis. This panarteritis could then lead to stenosis and/or aneurysmal dilatation. Resultant infarcts or haemorrhages occur DIFFERENTIAL DIAGNOSIS Varicella – Zoster Vasculopathy Strokes with VZV – V are small, deep seated subcortical infarcts

36. A 41-year-old male with numbness of the whole left side. T1-weighted axial MR images (a, b) demonstrate HIV vasculitis as hemorrhagic infarct of the right anterior temporal lobe and lentiform nucleus. There is also chronic infarct of the posterior temporal lobe. A small saccular small aneurysm at the middle cerebral artery (MCA) bifurcation is depicted (a). On axial T2-weighted MR image obtained a few months later (c), chronic stage of the previous hemorrhagic subacute infarct is seen with peripheral hemosiderin rim on the anterior temporal lobe; posterior chronic infarct is depicted again. MR angiography (d) shows occluded right MCA and a small saccular aneurysm on the anterior trunk of the left MCA.

37. PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY Causative organism : JC virus (Papovaviridae) Reactivation in immunocompromised patients Neurotropic; Invades Oligodendrocytes causing multifocal demyelination

38. Imaging features PML can appear as multifocal widespread lesions. supratentorial lobar white matter is the most commonly affected site. The posterior fossa white matter—especially the middle cerebellar peduncles—is the second most common location small scattered subcortical foci to large bilateral but asymmetric confluent WM lesions At later stages, encephaloclastic changes with atrophy and volume loss predominate.

39. CT FINDINGS More than 90% of cPML cases show hypodense areas in the subcortical and deep periventricular WM on NECT 70% are multifocal. PML lesions generally do not enhance on CECT. Axial unenhanced CT image reveals a focal area of low attenuation within the white matter of the right hemisphere. The subcortical U fibers are involved, and no mass effect is present.

40. MRI FINDINGS T1W Multifocal, bilateral but asymmetric, irregularly shaped hypointensities on T1WI are typical T2W The lesions are heterogeneously hyperintense on T2WI Involves subcortical U- fibers with sparing of cortex T1 C+ PML generally does not enhance on T1 C+ scans Faint peripheral rim-like enhancement occurs in 5% of all cases

41. DWI Varies according to disease stage Newly active lesions, DWI restricts strongly Chronic “burned out” lesions show increased diffusion due to disorganized cellular architecture MR perfusion As PML lesions are comparatively avascular, pMR demonstrates reduced rCBV compared to unaffected white matter MRS Nonspecific, with decreased NAA reflecting neuronal loss. Increased choline, consistent with myelin destruction Myoinositol may be elevated, consistent with inflammatory change .

42. Axial T2-weighted image depicts hyperintensity involving the white matter of the right hemisphere, including the subcortical U fibers . No mass effect is seen. Axial postcontrast T1-weighted image demonstrates hypointensity and no evidence of associated enhancement .

43. OTHER PRESENTATIONs Inflammatory PML ( iPML ) Imaging findings in iPML are identical to those of cPML except that the lesions demonstrate peripheral enhancement and/or mass effect. Acute iPML may have relatively increased vascularity and rCBV In some patients, lesions may demonstrate features of iPML early and then evolve to cPML later in the disease course.

44. PML in a 25-year-old man with AIDS. (a) Axial T1- weighted image demonstrates an area of low signal intensity involving the white matter of the right frontal lobe that crosses the corpus callosum to the white matter of the left frontal lobe. Mild mass effect is present. (b) Axial postcontrast T1-weighted image demonstrates peripheral enhancement, which is more confluent than typically seen in patients with PML

45. JCV meningitis No distinguishing features from other meningitis, demonstrating nonspecific sulcal-cisternal hyperintensity on FLAIR and enhancement on T1 C+ FS scans. JCV granule cell neuronopathy JCV infection of the cerebellar granular layer is seen as cerebellar atrophy with T2 hyperintensity in the affected folia.

46. Differential diagnosis HIVE PML CLINICAL AIDS-Dementia Complex Focal neurological deficit ORGANISM HIV-1 JC virus CT Isodense Hypodense T1W MR Isointense Hypointense CONTRAST None Rarely DISTRIBUTION Bilateral, symmetrical, periventricular Can be unilateral, asymmetric, subcortical MRS Myoinositol Cho, Naa Higher choline, variable myoinositol

47. NEUROSYPHILIS Neurosyphilis has a wide variety of imaging findings. Mild to moderate atrophy, White matter lesions, Gummas , Leptomeningeal enhancement, Arteritis, Cortical and subcortical infarctions

48. Gummas are uncommon. They are usually located peripherally in the cerebral hemisphere cortex. On CT images, they appear as peripherally located lesions that are isoattenuating relative to the cortex. On MR images, they are isointense relative to gray matter with T1-weighted sequences and hyperintense with T2-weighted sequences. These lesions will enhance with contrast material. Overlying leptomeningeal enhancement may also be seen. Regions of nonspecific T2 hyperintensity may be seen in the white matter.

49. Syphilitic gumma in a 32-year-old man with HIV infection and a positive VDRL test. (a) Axial T2-weighted image shows an extraaxial , predominantly hyperintense lesion with a central focus of low signal intensity (arrow). (b) On a coronal postcontrast T1-weighted image, the lesion heterogeneously enhances and demonstrates a mild degree of dural enhancement.

50. Immune reconstitution inflammatORy syndrome (iris ) CNS immune reconstitution inflammatory syndrome (IRIS) is a recently recognized T-cell-mediated encephalitis that occurs in the setting of treated HIV IRIS occurs when restored immunity causes an exaggerated immune response to infectious or noninfectious antigens

51. TYPES OF IRIS Unmasking IRIS Occurs when antiretroviral therapy reveals a subclinical, previously undiagnosed opportunistic infection. Immune restoration leads to an immune response against a living pathogen. Here brain parenchyma is damaged by both the replicating pathogen and the incited immune response. Paradoxical IRIS occurs when a patient who has been successfully treated for a recent opportunistic infection unexpectedly deteriorates after initiation of antiretroviral therapy. Here there is no newly acquired or reactivated infection. The recovering immune response targets persistent pathogen-derived antigens or self-antigens and causes tissue damage.

52. Several different underlying pathogens have been identified with IRIS The most common are JC virus (PML-IRIS), Tuberculosis (TB-IRIS) Fungal infections especially Cryptococcus (crypto-IRIS) Some parasitic infections—such as toxoplasmosis

53. presentation The most common presentation is clinical deterioration of a newly treated HIV-positive patient despite rising CD4 counts and diminishing viral loads Patients with neuro-IRIS may die within days to weeks. Mortality from PML-IRIS exceeds 40% while that of crypto-IRIS is about 20%. TB-IRIS mortality is slightly lower (13%).

54. Imaging features Imaging manifestations of neuro-IRIS vary depending on the “provoking pathogen” Bizarre-looking parenchymal masses and progressively enlarging, enhancing lesions are typical of PML-IRIS TB-IRIS patients can develop florid TB pseudoabscesses (TB “gone wild”) and/or rapidly increasing enhancement in the basilar meninges

55. IRIS in a patient with biopsy-proved PML. (a) Axial T2-weighted FLAIR image demonstrates T2 hyperintensity in the bilateral (right greater than left) periatrial white matter. (b) Axial postcontrast T1-weighted image reveals diffuse patchy enhancement in the region of the T2 hyperintensity. (c) Axial T2-weighted FLAIR image obtained 2 weeks later demonstrates progression of the T2 hyperintensity, with an increase in mass effect. (d) Axial postcontrast T1-weighted image reveals progression of the patchy enhancement in the 2-week interval

56. references Osborn’s Brain; Imaging, pathology & Anatomy; chapter 14 N A Sibtain , and R J S Chinn; Imaging of the central nervous system in HIV infection; The British Institute of Radiology 2002