Pathology of Meningitis & CNS infections.

Pathology of Meningitis, CNS infections, increased cerebral pressure, brain herniations etc. for pre clinical medical students.

1. Applied Faith with PMAApplied Faith with PMA
(Positive Mental Attitude)(Positive Mental Attitude)
Faith is state of mind through which your Faith is state of mind through which your
aims, desires, plans and purposes may be aims, desires, plans and purposes may be
translated into their physical or financial translated into their physical or financial
equivalent. But Faith without work is dead so equivalent. But Faith without work is dead so
BIBLEBIBLE says.. You should not simply have says.. You should not simply have
faith, you must add to your faith hard and faith, you must add to your faith hard and
consistent work.consistent work.

2. Scenario: MeningitisScenario: Meningitis
•ABC breathing spontaneously rr 18/min 4l O2
via mask, sats 90%; pulse 110 bpm reg small
volume; BP 90/60 mmHg T39.6C
•GCS - E2V3M4
•Detailed check - petechiae non blanching rash
trunk, buttocks, Neck stiffness
•Small contusion L temperoparietal area
•Capillary refill time > 3 secs, peripheral
cyanosis+
•Brudzinski sign positive
•Ixskin scraping from lesion : gram negative
diplococci; CSF gram negative diplococci; FBC
wcc 18 (polymorhic leucocytosis)

3. Neck Stiffness:Neck Stiffness:
* Pathogenesis: Meningeal irritation.

4. Brudzinski Sign of Meningitis:Brudzinski Sign of Meningitis:
* Pathogenesis: Meningeal irritation.

5. Kernig’s Sign of Meningitis:Kernig’s Sign of Meningitis:
* Pathogenesis: Meningeal irritation.

6. Dr. Venaktesh M. ShashidharDr. Venaktesh M. Shashidhar
Associate Professor & Head of PathologyAssociate Professor & Head of Pathology
Pathology of Pathology of
MeningitisMeningitis

7. Case:Case:
•38 Year Fijian male
•Headache, Photophobia since 2 months.
•Past history of diabetes – irregular treatment.
•3 days back, drowsy, seizure, vomiting.
•On examination: Bil. Papillary edema
•Responded to Mannitol + steroids
•Died 3
rd
day in hospital - respiratory arrest..

8. Meningitis: Meningitis:
•Inflammation of Meninges.
•Leptomeningitis – Subarachnoid & Pia.
•Pachymeningitis – Dura (Local trauma)
•Meningoencephalitis – + Brain.
•Aetiologic Types:
–Infective – Septic & Aseptic (B, V, F & TB)
–Chemical – Drugs.
–Carcinomatous – metastasis.

9. Septic Meningitis: common causesSeptic Meningitis: common causes
S. pneumoniae, N. meningitidis,
Mycobacteria, Cryptococci
Adults
N. meningitidis, S. pneumoniaeChildren
Neisseria meningitidis, Haemophilus
influenzae, Streptococcus pneumoniae
Infants
Group B Streptococci, Escherichia coli,
Listeria monocytogenes
Neonates
CausesCausesAgeAge

10. Septic MeningitisSeptic Meningitis

11. Septic MeningitisSeptic Meningitis

12. Septic MeningitisSeptic Meningitis

13. Septic MeningitisSeptic Meningitis

14. Septic MeningitisSeptic Meningitis

15. Septic MeningitisSeptic Meningitis

16. Pneumococcal Meningitis:Pneumococcal Meningitis:
Retraction of dura reveals leptomeninges which are edematous and have
multiple small hemorrhagic foci (red) note greenish pus covering brain.

17. Septic MeningitisSeptic Meningitis

18. Septic Meningitis-MicroscopySeptic Meningitis-Microscopy

19. Septic Meningitis-Spinal fluidSeptic Meningitis-Spinal fluid

20. Septic Meningitis-Spinal fluidSeptic Meningitis-Spinal fluid

21. Viral Meningitis:Viral Meningitis:
Perivascular cuffs of lymphocytes and Microglial nodules

22. HIV Meningoencephalitis:HIV Meningoencephalitis:
Perivascular Lymphocytes
Microglial nodule
and multinucleated giant cells

23. HIV Encephalitis:HIV Encephalitis:
Perivascular lymphocytic cuff, Microglial nodule & Perivascular lymphocytic cuff, Microglial nodule &
Giant Cells.Giant Cells.

24. Herpes Encephalitis:Herpes Encephalitis:
Destruction of inferior frontal and
anterior temporal lobes –
necrotizing inflammation

25. Septic Meningitis - OrganismsSeptic Meningitis - Organisms
ORGANISM PEAK AGE INCIDENCE GRAM STAIN
Escherichia coli Neonates Gram negative rods
Hemophilus influenzae Infants and ChildrenGram negative coccobacilli
Neisseria meningitidis Adolescents and Young adultsGram negative diplococci
Streptococcus pneumoniae Older adults or ChildrenGram positive cocci in chains
Organism causing meningitis vary with the age of the patient

26. Meningitis: Meningitis:
•Clinical Features:
–Headache + Neck stiffness.
–Neurological deficits.
•Complications:
–Acute : Encephalitis, Cerebral infarction,
Edema, herniation.
–Late: Abscess, subdural empyema, epilepsy.
–Leptomeningeal fibrosis and consequent
hydrocephalus

27. Brain Abscess:Brain Abscess:
Cerebral abscess. Ring enhancement
of developing pseudocapsules,
budding of ‘daughter’ lesions, and
marked hypodensity of adjacent white
matter reflecting severe edema are all
characteristic of cerebral abscesses
on CT or MR study.

28. Brain Abscess:Brain Abscess:

29. Brain Abscess: CT ScanBrain Abscess: CT Scan
Ring enhancement.
Surrounding area of inflammation &
edema

30. Hydrocephalus:Hydrocephalus:

31. Infarction Meningoencephalitis: Infarction Meningoencephalitis:
Mucormycosis in a Diabetic.Mucormycosis in a Diabetic.

32. CSF-ExaminationCSF-Examination
Opalescent
(cob-web)
LowHigh> lymph
Clear normalHigh> Lymph
TurbidLowHigh> Poly
Clear
colorless
2.7-4.0 (n)0.1-0.4(n)0-4 lympho
AppearanceGlucoseProteinCells
Norm
Septic
Viral
TB

33. •What is a Problem?What is a Problem?
•Gap between where you are now and
where you want to be. (Hayes 1989)
•How do you solve Problem?How do you solve Problem?
•Mental activity leading from where you
are to a more desired ‘goal state’
(Kurfiss 1988)

34. Clinical details:Clinical details:
•38 Year Fijian male
•Headache, Photophobia since 2
months.
•Past history of diabetes – irregular
treatment.
•3 days back, drowsy, seizure, vomiting.
•On examination: Bil. Papillary edema
•Responded to Mannitol + steroids
•Died 3
rd
day in hospital - respiratory
arrest
•Brain sections after limited autopsy.

35. AutopsyAutopsy
•Marked
inflammtory
infiltrate in
meninges
•Superficial
Cerebral
edema
(cortex)

36. Meningitis - CryptococciMeningitis - Cryptococci
•Round
capsulated
fungal
organisms
•Lymphocytic
infiltrate
around

37. Tiny refractile yeasts
Cryptococcal Encephalitis:Cryptococcal Encephalitis:

38. Special stains for cryptococci: PAS;
Silver stain
India Ink: Double refractile spherules
with clear halo
Cryptococcal Meningitis:Cryptococcal Meningitis:

39. Cryptococcal Meningitis:Cryptococcal Meningitis:
•chronic basal leptomeningitis.
•Opaque thick fibrotic
•CSF obstruction - hydrocephalus.
•Gelatinous material within the
subarachnoid space and small cysts within
the parenchyma ("soap bubbles")
•Specially in the basal ganglia.

40. Cryptococcal meningoencephalitis:Cryptococcal meningoencephalitis:

41. Cryptococcal meningoencephalitis:Cryptococcal meningoencephalitis:

42. Summary:Summary:
•Leptomeningitis, Pachymeningitis.
•Head ache, Neck stiff ness.
•Common causes, organisms.
•Septic, Viral & TB – CSF findings.
•Infective, Chemical Carcinomatous
•Complications – Acute / Chronic
•Edema, herniation, infarction,
abscess, hydrocephalus.

43. Kernictirus:Kernictirus:

44. Kernictirus:Kernictirus:

45. Formerly, when religion was strong and Formerly, when religion was strong and
science weak, men mistook science weak, men mistook magic for magic for
medicine.medicine.
Now when science is strong and religion Now when science is strong and religion
weak, men mistake weak, men mistake medicine for magic…!medicine for magic…!

46. CPC-3.7– CNS –Tumors/men.CPC-3.7– CNS –Tumors/men.
•Pathology - Core Learning Issues:
–Pathology of common Primary and secondary CNS tumours in
different age groups.
–Over view of epilepsy – include rare causes like neurofibromatosis,
sturge weber, tuberous sclerosis - x.
–Genetic basis for idiopathic epilepsy - x
–Increased intracranial pressure – Pathogenesis & pathology.
–Meningitis – Overview, common types & Pathology.
•Basic science - Core Learning Issues:
–Causes ‘break through’ seizures in patients with epilepsy
–Mechanism of action for seizures caused by drug/alcohol
withdrawal
–Mechanism of action for seizures caused by drug overdose
(cocaine, amphetamine, tricyclic antidepressants)
–Mechanism of action for seizures caused by metabolic disturbance
: hypoglycaemia; hypo + hyper natraemia; hypo- and
hypercalcaemia; uraemia

47. 28y M, Fever, meningitis 28y M, Fever, meningitis ? type? type
1 2 3 4 5
2%
21%
0%
2%
76%
1.1.Viral Viral
2.2.Fungal Fungal
3.3.BacterialBacterial
4.4.CarcinomatousCarcinomatous
5.5.Pick’s diseasePick’s disease

48. 28y M, Fever, meningitis 28y M, Fever, meningitis ? type? type
1 2 3 4 5
18%
0% 0%0%
82%
1.1.Viral Viral
2.2.Fungal Fungal
3.3.BacterialBacterial
4.4.CarcinomatousCarcinomatous
5.5.Pick’s diseasePick’s disease

49. 60 Year rapid dementia…60 Year rapid dementia…
A 66-year-old woman vocalist complains of
difficulty remembering her favorite songs. This
problem continues to worsen over the next several
months, and the patient becomes increasingly
withdrawn from her family. When examined, she
evidences dementia and gait disturbance. MRI
demonstrates mild cerebral atrophy. Analysis of
CSF shows no inflammatory cells and normal
levels of glucose and protein. An EEG reveals
periodic spike-wave complexes. One month later,
the patient is bedridden and nonresponsive. A
brain biopsy is performed and the results are
shown.

50. 66y Woman rapid dementia… 66y Woman rapid dementia… ? diagnosis? diagnosis
1 2 3 4 5
20%20% 20%20%20%
Primary Amyloidosis.Primary Amyloidosis.
Alzheimers disease.Alzheimers disease.
Creutzfeldt-Jakob diseaseCreutzfeldt-Jakob disease
Multi-infarct dementiaMulti-infarct dementia
Pick’s diseasePick’s disease

51. 28y M, Fever, meningitis 28y M, Fever, meningitis CSF ? typeCSF ? type
1 2 3 4 5
98%
0% 0%0%
2%
1.1.Viral Viral
2.2.Fungal Fungal
3.3.BacterialBacterial
4.4.CarcinomatousCarcinomatous
5.5.Pick’s diseasePick’s disease
Cells - Lymphocytosis
Glucose – Normal
Protein – High
Appearance - Clear

52. 28y M, Fever, meningitis 28y M, Fever, meningitis CSF ?typeCSF ?type
1 2 3 4 5
0%
5%
0%0%
95%
1.1.Viral Viral
2.2.Fungal Fungal
3.3.BacterialBacterial
4.4.CarcinomatousCarcinomatous
5.5.Pick’s diseasePick’s disease
Cells - Neutrophils
Glucose – Low
Protein – High
Appearance - Turbid

53. Normal Intracranial pressure (mmH2O)Normal Intracranial pressure (mmH2O)??
1 2 3 4 5
20%20% 20%20%20%
1.1.0-10 0-10
2.2.< 200 < 200
3.3.200-400200-400
4.4.< 500< 500
5.5.>500>500

54. Raised Intracranial Pr.Raised Intracranial Pr.?Early Symp.?Early Symp.
1 2 3 4 5
2%
93%
2%
0%
4%
1.1.TachycardiaTachycardia
2.2.BradycardiaBradycardia
3.3.HypotensionHypotension
4.4.ShockShock
5.5.DiplopiaDiplopia

55. Case-1Case-1
An 80-year-old man was admitted to the hospital
unresponsive and febrile. Several years earlier, he had been
diagnosed as having an “organic brain syndrome” and he
had also sustained a subdural hematoma. The past several
days, family members noted that he was becoming
increasingly lethargic and did not eat or drink. On admission,
the patient had purulent material in the pharynx. His neck
was stiff. There was a pleural rub on the left. Brain MRI
showed mild dilatation of the ventricles. A CSF was cloudy
with 300 WBC (96% polys, 4% lymphocytes). Protein was
1080 mg/dl and glucose was 2 mg/dl. Gram stains revealed
gram-positive diplococci. Blood cultures grew
pneumococcus. Treatment with ampicillin and gentamicin
was started. The patient remained unresponsive and had a
cardiorespiratory arrest one day after admission.

56. Case-3: What is the most likely Case-3: What is the most likely organism?organism?
1 2 3 4 5
20%20% 20%20%20%
1.1.Bacterial meningitisBacterial meningitis
2.2.Candida albicansCandida albicans
3.3.Cryptococcus meningitisCryptococcus meningitis
4.4.CMV encephalitisCMV encephalitis
5.5.Neonatal HSV Neonatal HSV
encephalitis.encephalitis.
1 2 3 4 5

57. Case-2Case-2
A 56-year-old woman was admitted to the hospital with
fever, aching, dizziness and disorientation. She was an
insulin dependent diabetic and had a history of hypertension.
One month earlier, she had the left adrenal gland removed
for an adenoma that had caused Cushing’s syndrome. She
was receiving replacement corticosteroids. Mental status
deteriorated and she became comatose and had intractable
seizures. CSF, on admission, had 17 cells, all lymphocytes,
protein 53 mg/dl and glucose 77 mg/dl. CSF cultures were
negative. Urine cultures grew Candida albicans. Blood
cultures were negative. Initially, brain MRI was normal.
Later, it revealed diffuse encephalomalacia.

58. Case-3: What is the most likely Case-3: What is the most likely organism?organism?
1 2 3 4 5
20%20% 20%20%20%
1.1.Bacterial meningitisBacterial meningitis
2.2.Candida albicansCandida albicans
3.3.Cryptococcus meningitisCryptococcus meningitis
4.4.CMV encephalitisCMV encephalitis
5.5.Neonatal HSV Neonatal HSV
encephalitis.encephalitis.
1 2 3 4 5

59. Case-3Case-3
29-year-old truck driver was investigated for
persistent malaise, cough and diarrhea. Chest x-
rays revealed pneumonia with pleural effusion.
Fiberoptic bronchoscopy with lung biopsy revealed
pneumocystis. He
also had diarrhea due to cryptosporidiosis. Helper
T-cells were diminished to undetectable levels. He
was discharged on Bactrim, Flagyl and antibiotics.
Six weeks later, he developed headache,
obtundation and seizures. CSF had 11 WBC’s, all
lymphocytes, protein 137 mg/dl and glucose 26 mg/
dl. Cryptococcal antigen was positive.

60. Case-3: What is the most likely Case-3: What is the most likely organism?organism?
1 2 3 4 5
20%20% 20%20%20%
1.1.Bacterial meningitisBacterial meningitis
2.2.Candida albicansCandida albicans
3.3.Cryptococcus meningitisCryptococcus meningitis
4.4.CMV encephalitisCMV encephalitis
5.5.Neonatal HSV Neonatal HSV
encephalitis.encephalitis.
1 2 3 4 5

61. Case-4Case-4
A 56-year-old woman was admitted to the hospital with
fever, aching, dizziness and disorientation. She was an
insulin dependent diabetic and had a history of hypertension.
One month earlier, she had the left adrenal gland removed
for an adenoma that had caused Cushing’s syndrome. She
was receiving replacement corticosteroids. Mental status
deteriorated and she became comatose and had intractable
seizures. CSF, on admission, had 17 cells, all lymphocytes,
protein 53 mg/dl and glucose 77 mg/dl. CSF cultures were
negative. Urine cultures grew Candida albicans. Blood
cultures were negative. Initially, brain MRI was normal.
Later, it revealed diffuse encephalomalacia.

62. Case-4: What is the most likely Case-4: What is the most likely organism?organism?
1 2 3 4 5
20%20% 20%20%20%
1.1.Bacterial meningitisBacterial meningitis
2.2.Candida albicansCandida albicans
3.3.Cryptococcus meningitisCryptococcus meningitis
4.4.CMV encephalitisCMV encephalitis
5.5.Neonatal HSV Neonatal HSV
encephalitis.encephalitis.
1 2 3 4 5

63. Case-5Case-5
A 56-year-old woman was admitted to the hospital with
fever, aching, dizziness and disorientation. She was an
insulin dependent diabetic and had a history of hypertension.
One month earlier, she had the left adrenal gland removed
for an adenoma that had caused Cushing’s syndrome. She
was receiving replacement corticosteroids. Mental status
deteriorated and she became comatose and had intractable
seizures. CSF, on admission, had 17 cells, all lymphocytes,
protein 53 mg/dl and glucose 77 mg/dl. CSF cultures were
negative. Urine cultures grew Candida albicans. Blood
cultures were negative. Initially, brain MRI was normal.
Later, it revealed diffuse encephalomalacia.

64. Case-5: What is the most likely Case-5: What is the most likely organism?organism?
1 2 3 4 5
20%20% 20%20%20%
1.1.Bacterial meningitisBacterial meningitis
2.2.Candida albicansCandida albicans
3.3.Cryptococcus meningitisCryptococcus meningitis
4.4.CMV encephalitisCMV encephalitis
5.5.Neonatal HSV Neonatal HSV
encephalitis.encephalitis.
1 2 3 4 5

65. A pleasing Personality with PMAA pleasing Personality with PMA
(Positive Mental Attitude)(Positive Mental Attitude)
Assembling a attractive personality is a must.Assembling a attractive personality is a must.
Your personality is your greatest asset or Your personality is your greatest asset or
greatest liability. For it embraces everything greatest liability. For it embraces everything
that you control, Mind body soul & spirit. that you control, Mind body soul & spirit.
Learn to be pleasant even when others are Learn to be pleasant even when others are
unpleasant to you.unpleasant to you.
Some bring happiness where ever they go & some whenever…!Some bring happiness where ever they go & some whenever…!

66. Pathology of: Pathology of:
Raised Intracranial PressureRaised Intracranial Pressure

67. Raised ICPRaised ICP
• Pressure of CSF within cranium.
• Limited space - Cranial vault
•Normal -2 to 15 mm of Hg
• >30 mm of Hg - poor prognosis
•

68. Raised ICP: EtiologyRaised ICP: Etiology
•Cerebral Edema.
•Cerebral venous obstruction.
•Mass lesions - Tumors, Hematoma.
•Obstruction to CSF.
•Impaired absorption of CSF.

69. Raised ICP: Clinical FeaturesRaised ICP: Clinical Features
• Headache.
•Impaired
consciousness.
•Papilledema.
•Vomiting.
•Bradycardia.
•Arterial
hypertension.

70. Raised ICP: Clinical FeaturesRaised ICP: Clinical Features

71. Raised ICP: ComplicationsRaised ICP: Complications
• Temporal coning.
• Tonsillar coning.
• Duret hemorrhages.
• 3rd/6th nerve lesion - Uni/bilat.
• Ipsilateral Hemiparesis (UMN)
• Bilateral extensor plantar responses

72. Brain Herniation in Raised ICP:Brain Herniation in Raised ICP:
•SubfalcineSubfalcine –
Cingulate gyrus
below falx cerebri.
•UncalUncal herniation
tentorial hiatus.
•CaudalCaudal dispacement
of brain stembrain stem.
•TonsillarTonsillar herniation
through foramen
magnum.

73. Uncal herniation:Uncal herniation:

74. Raised ICP: ComplicationsRaised ICP: Complications
• Temporal coning.
• Tonsillar coning.
• Duret hemorrhages.
• 3rd/6th nerve lesion - Uni/bilat.
• Ipsilateral Hemiparesis (UMN)
• Bilateral extensor plantar responses

75. Tonsillar or Cerebellar coning:Tonsillar or Cerebellar coning:

76. Temporal / uncal coning: Temporal / uncal coning: (CN3)(CN3)

77. Temporal / uncal coning: Temporal / uncal coning: (CN3/6)(CN3/6)

78. Duret Hemorrhages: Duret Hemorrhages: (Tonsillar Coning)(Tonsillar Coning)