Pathology of Meningitis & CNS infections

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.

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• Ix skin scraping from lesion : gram negative

diplococci; CSF gram negative diplococci; FBC wcc 18 (polymorhic leucocytosis)

Neck Stiffness:Neck Stiffness:

* Pathogenesis: Meningeal irritation.

Brudzinski Sign of Meningitis:Brudzinski Sign of Meningitis:

* Pathogenesis: Meningeal irritation.

Kernig’s Sign of Meningitis:Kernig’s Sign of Meningitis:

* Pathogenesis: Meningeal irritation.

Dr. Venaktesh M. ShashidharDr. Venaktesh M. ShashidharAssociate Professor & Head of PathologyAssociate Professor & Head of Pathology

Pathology of Pathology of MeningitisMeningitis

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 3rd day in hospital - respiratory arrest..

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.

Septic Meningitis: common causesSeptic Meningitis: common causes

AgeAge CausesCauses

Neonates Group B Streptococci, Escherichia coli, Listeria monocytogenes

Infants Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae

Children N. meningitidis, S. pneumoniae

Adults S. pneumoniae, N. meningitidis, Mycobacteria, Cryptococci

Septic MeningitisSeptic Meningitis

Septic MeningitisSeptic Meningitis

Septic MeningitisSeptic Meningitis

Septic MeningitisSeptic Meningitis

Septic MeningitisSeptic Meningitis

Septic MeningitisSeptic Meningitis

Pneumococcal Meningitis:Pneumococcal Meningitis:

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

Septic MeningitisSeptic Meningitis

Septic Meningitis-MicroscopySeptic Meningitis-Microscopy

Septic Meningitis-Spinal fluidSeptic Meningitis-Spinal fluid

Septic Meningitis-Spinal fluidSeptic Meningitis-Spinal fluid

Viral Meningitis:Viral Meningitis:

Perivascular cuffs of lymphocytes and Microglial nodules

HIV Meningoencephalitis:HIV Meningoencephalitis:

Perivascular Lymphocytes Microglial nodule and multinucleated giant cells

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

Herpes Encephalitis:Herpes Encephalitis:

Destruction of inferior frontal and anterior temporal lobes – necrotizing inflammation

Septic Meningitis - OrganismsSeptic Meningitis - Organisms

ORGANISM PEAK AGE INCIDENCE GRAM STAIN

Escherichia coli Neonates Gram negative rodsHemophilus influenzae Infants and Children Gram negative coccobacilliNeisseria meningitidis Adolescents and Young adultsGram negative diplococciStreptococcus pneumoniae Older adults or Children Gram positive cocci in chains

Organism causing meningitis vary with the age of the patient

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

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.

Brain Abscess:Brain Abscess:

Brain Abscess: CT ScanBrain Abscess: CT Scan

Ring enhancement.Surrounding area of inflammation & edema

Hydrocephalus:Hydrocephalus:

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

CSF-ExaminationCSF-Examination

Cells Protein Glucose Appearance

0-4 lympho 0.1-0.4(n) 2.7-4.0 (n) Clear colorless

> Poly High Low Turbid

> Lymph High normal Clear

> lymph High Low Opalescent (cob-web)

Norm

Septic

Viral

TB

• 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)

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 3rd day in hospital - respiratory arrest• Brain sections after limited autopsy.

AutopsyAutopsy

• Marked inflammtory infiltrate in meninges

• Superficial Cerebral edema (cortex)

Meningitis - CryptococciMeningitis - Cryptococci

• Round capsulated fungal organisms

• Lymphocytic infiltrate around

Tiny refractile yeasts

Cryptococcal Encephalitis:Cryptococcal Encephalitis:

Special stains for cryptococci: PAS; Silver stain

India Ink: Double refractile spherules with clear halo

Cryptococcal Meningitis:Cryptococcal Meningitis:

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.

Cryptococcal meningoencephalitis:Cryptococcal meningoencephalitis:

Cryptococcal meningoencephalitis:Cryptococcal meningoencephalitis:

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.

Kernictirus:Kernictirus:

Kernictirus:Kernictirus:

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…!

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

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

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

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.

66y Woman rapid dementia… 66y Woman rapid dementia… ? diagnosis? diagnosis

1 2 3 4 5

20% 20% 20%20%20%

1.1. Primary Amyloidosis.Primary Amyloidosis.

2.2. Alzheimers disease.Alzheimers disease.

3.3. Creutzfeldt-Jakob diseaseCreutzfeldt-Jakob disease

4.4. Multi-infarct dementiaMulti-infarct dementia

5.5. Pick’s diseasePick’s disease

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

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

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

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

Case-1Case-1An 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.

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 meningitis2.2. Candida albicansCandida albicans3.3. Cryptococcus meningitisCryptococcus meningitis4.4. CMV encephalitisCMV encephalitis5.5. Neonatal HSV Neonatal HSV

encephalitis.encephalitis.

1 2 3 4 5

Case-2Case-2A 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.

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 meningitis2.2. Candida albicansCandida albicans3.3. Cryptococcus meningitisCryptococcus meningitis4.4. CMV encephalitisCMV encephalitis5.5. Neonatal HSV Neonatal HSV

encephalitis.encephalitis.

1 2 3 4 5

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.

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 meningitis2.2. Candida albicansCandida albicans3.3. Cryptococcus meningitisCryptococcus meningitis4.4. CMV encephalitisCMV encephalitis5.5. Neonatal HSV Neonatal HSV

encephalitis.encephalitis.

1 2 3 4 5

Case-4Case-4A 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.

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 meningitis2.2. Candida albicansCandida albicans3.3. Cryptococcus meningitisCryptococcus meningitis4.4. CMV encephalitisCMV encephalitis5.5. Neonatal HSV Neonatal HSV

encephalitis.encephalitis.

1 2 3 4 5

Case-5Case-5A 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.

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 meningitis2.2. Candida albicansCandida albicans3.3. Cryptococcus meningitisCryptococcus meningitis4.4. CMV encephalitisCMV encephalitis5.5. Neonatal HSV Neonatal HSV

encephalitis.encephalitis.

1 2 3 4 5

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…!

Pathology of: Pathology of: Raised Intracranial PressureRaised Intracranial Pressure

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

•

Raised ICP: EtiologyRaised ICP: Etiology

• Cerebral Edema.

• Cerebral venous obstruction.

• Mass lesions - Tumors, Hematoma.

• Obstruction to CSF.

• Impaired absorption of CSF.

Raised ICP: Clinical FeaturesRaised ICP: Clinical Features• Headache.

• Impaired consciousness.

• Papilledema.

• Vomiting.

• Bradycardia.

• Arterial hypertension.

Raised ICP: Clinical FeaturesRaised ICP: Clinical Features

Raised ICP: ComplicationsRaised ICP: Complications

• Temporal coning.

• Tonsillar coning. • Duret hemorrhages.

• 3rd/6th nerve lesion - Uni/bilat.

• Ipsilateral Hemiparesis (UMN)• Bilateral extensor plantar responses

Brain Herniation in Raised ICP:Brain Herniation in Raised ICP:

1.1. SubfalcineSubfalcine – Cingulate gyrus below falx cerebri.

2.2. UncalUncal herniation tentorial hiatus.

3.3. CaudalCaudal dispacement of brain stembrain stem.

4.4. TonsillarTonsillar herniation through foramen magnum.

Uncal herniation:Uncal herniation:

Raised ICP: ComplicationsRaised ICP: Complications

• Temporal coning.

• Tonsillar coning. • Duret hemorrhages.

• 3rd/6th nerve lesion - Uni/bilat.

• Ipsilateral Hemiparesis (UMN)• Bilateral extensor plantar responses

Tonsillar or Cerebellar coning:Tonsillar or Cerebellar coning:

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

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

Duret Hemorrhages: Duret Hemorrhages: (Tonsillar Coning)(Tonsillar Coning)