Pathology of CNS

DR Naila AwalDepartment of pathology

Structure of brain

1) Cerebrum- Center for high complex function- memory, learning, emotion , language. Parts- Frontal, Parietal, Temporal & Occipital lobes.2) Cerebellum- Movement, balance & posture3) Medulla oblongata-• Controls automatic & homeostatic function such as swallowing, digestion,

breathing.• GM- neural cell bodies It process & stores information• WM- nerve fiber Carry information from 1 tract of brain to another.

Cells of CNS

1) Neuron Injury- Apoptotsis (Brain tumor) Necrosis (Red neuron- Hypoxic damage) Neuronal loss( neurodegenerative disease) Axonal degeneration Inclusions (Alzheimer’s – Neurofibrillary Tangles Parkinson’s - Lewy body)2) Glial cell-• Astrocyte- • Star shaped• Nuclei- round –oval with peripheral nucleoli,• Cytoplasm –highly branched• Tissue injury- Hypertrophy & hyperplasia (astrogliosis)• Oligodendrocyte-• Relatively large cell lymphocyte-like nuclei with perinuclear halo.

• Ependyma cell• Cuboidal to columnar cells having cilia/microvilli lining the ventricle

3) Microglial cell-Act as a macrophage/ monocyte system in the brain • infection/injury- Proliferate

Disease of CNS

• Congenital anomalies• Perinatal brain injury• Trauma• Cerebrovascular disease• Infection• Demyelinating disease• Degenerative disease• Tumors

Congenital anomalies

• Neural tube defect• Anencephaly-• absence of cranial vault.

• Encephalocele- • Herniation of brain tissue through defective cranium.

• Spina bifida occulta- •  incomplete closing of the vertebra and membranes around the spinal cord.• Meningocele – • Meninges protude through small opening.• Meningomyeocele- • Herniation of spinal cord & meningeal tissue through vertebral defect

• Forebrain anomalies`-Megalencephaly- Volume of brain is abnormally large.

Microcephaly- Volume of brain is small.• Cause- Chromosomal abnormalities Fetal alcohol syndrome HIV infection acquired in utero.

Lissencephaly (Agyria)- ↓ number of gyri or total absence of gyri

Polymicrogyria- • ↑ number of small irregular gyri

Holoprosencephaly-• Incomplete seperation of cerebral hemisphere across midline. (Trisomy 13)

Neuronal heterotopias- • Collection of neuron in abnormal location. (Periventricular- usually WM)Agenesis of corpus callosum-

• Posterior fossa anomalies• Dandy Walker malformation- • Enlarged posterior fossa.• Absence of cerebellar vermix or• Presence in rudimentary form in anterior portion• Replaced by large midline cyst lined by ependyma

• Arnold Chiari malformation-• Small posterior fossa• Downward extension of vermis or displacement through foramen magnum

• Hydromyelia- Multisegmental expansion of central canal of spinal cord.

• Syringomyelia- Formation of fluid filled cleft like cavity in spinal cord.

Perinatal brain injury

• Important cause of childhood neurological disability.• Common cause-• Maternal disease• Placental abnormalities• Most Common underlying pathology-• Hemorrhage • Infraction

Trauma

• Site & consequence-• Frontal lobe- Clinically silent

• Spinal cord- Severely disable

• Brain stem- Fatal

• Types of injury-• Skull fracture• Parenchymal injury• Traumatic vascular injury

• Skull fracture-• Cause- Stepping off a lader Fall due to unconsciousness

• Parenchymal injury-• Concussion- Altered consciousness, secondary to head injury.• Contusion (Bruise)• Coup & Contre-coup injury- When the head is struck ,the impact causes contusion at the point of the contact(coup injury) & on the opposite side of the brain (Contre-coup injury)

• Diffuse axonal injury• During rapid acceleration of head, some parts of the brain can move separately

from other parts destroy axon necessary for brain functioning

• Epidural hematomaSite- B/w skull & DMTemporal skull fracture ↓Injury to middle meningeal artery ↓Extravasation of blood ↓Seperation of DM from inner surface of skull ↓Accumulation of blood (Haematoma)

• Subdural hematomaSite-B/w DM & AM• Venous bleeding is self limitedSequence-• Lysis of clot-1 wk• Growth of fibroblast into hematoma2wks• Development of hyalinized connective tissue1-3 months.

• Sequelae of brain trauma• Post traumatic hydrocephalus• Post traumatic dementia• Punch drunk syndrome• Hydrocephalus• Diffuse axonal injury• Post traumatic epilepsy• Psychiatric disorder

Cerebrovascular Diseaese

• 3rd leading cause of death (1st heart disease, 2nd -carcinoma)• Cerebral Infraction-• Types-• (Red infract)-multiple, sometimes confluent petechial haemorrhage, associated

with embolic event• Non haemorrhagic (pale infract)- associated with thrombosis.• Gross-• 1st 6hrs- minimal change• 48 hrs-pale, swollen• corticomedullary junction –indistinct• 2-10 days- gelatinous, friable, distinct infract border.• 10 days-3wks- liquefaction begins.

• M/E-1st 12 hrs- Red neuron (eosinophilic degeneration of neuron) Swelling of astrocyte48hrs- Neutrophilic infiltration 2-3wks- Macrophage predominant. Lipid laden macrophage Fluid filled cavityAfter several months- Dense glial scar.

• Hypertensive Cerebrovascular diseaseMost important effect of HTN-1) lacunar infract2)Slit haemorrhage3) Hypertensive encephalopathy• Lacunar infract-Gross-Single/ multiple cavitary infract (Infract)M/E-Areas of tissue loss with scattered lipid laden macrophage& surrounding gliosis.

• Hypertensive encephalopathy-• Gross-• Edematous brain with or without transtentorial or tonsillar herniation.• M/E-• Petechiae & fibrinoid necrosis of arteriole in GM & WM.

• Intracranial haemorrhage-• Intracerebral haemorrhage-• Acute hemorrhage- Extravasation of blood with compression of adjacent

parenchyma.• Old hemorrhage- Cavitary destruction of brain with rim of brownish discoloration.• M/E-Central core- clotted blood Surrounded brain tissue- odematous, anoxic neuronal & glial change.Eventualy edema resolves, pigment & lipid laden macrophage& reactive astrocyte is seen in the periphery of the lesion.

• Sub arachnoid haemorrhage-• Most common cause- Rupture of saccular aneurysm.• Saccular aneurysm-• Common sites-

• Morphology-• Unruptured anurysm thin walled, outpouching along the circles of Wilis• 2-3cm in diameter• Bright red, shiny surface & thin translucent wall.• Wall or lumen of aneurysm- Atheromatous plaque, Calcification or thrombotic

occlution.• The neck of aneurysm wide/ narrow.• Ruptured usually occurs at the apex of sac.• The sac is made up of thickened hyaline intima.

• Vascular malformation-1)AV malformation2)Cavernous malformation3) Capillary telengiectasia4)Venous angioma (varices)

Infection of CNS

• Meningitis- Infection of meninges• Types-• Infectious-Acute pyogenic Chronic Aseptic• Chemicals- drugs

• Acute meningitis• Cause-• Neonate- E . Coli, G-B strep• Adolesence & adult- Neisseria meningitidis• Elder- Streptococcus pneumoniae, Liesteria monocytogens.• Gross-• Exudate- within leptomeniges & over the surface of the brain • H. influenzae- basal• Pneumococcal- over the cerebral convexities near the sagittal sinus.

A thick layer of suppurative exudate covers the brain stem & cerebellum & thickens the leptomeninges

M/E- neutrophilic exudate involving the meninges at the left, with prominent dilated vessels. There is edema and focal inflammation in the cortex to the right.

• Acute focal suppurative• Cerebral abscess-• Direct implantation of micro organism• Local-mastoiditis,Paranasal sinusitis• Haematogenous spread- from heart, lung,distal bone or after tooth extraction• Predisposing factor-• Acute bacterial endocarditis-multiple abscess• Congenital cyanotic Heart disease -Rt to Lt shunt• Chronic pulmonary sepsis- bronchiectasis• Immunosuppression.

•  Gross-• There is a liquefactive center with • yellow pus surrounded by a thin wall.• M/E-• Liquefactive necrosis • Around the necrosis, exuberent granulation tissue with neovascularization• Fibrous capsule• Outside the capsule, zone of reactive gliosis with numerous gemistocytic astrocytes.

Chronic meningoencephalitis

• Cause-• M .TB• Treponema pallidum• Borrelia

• Chronic bacterial meningoencephalitis• Tuberculosis• Gross-• Sub aracnoid space fibrinoid exudate .• Discrete white granules scattered over leptomeninges.• Tuberculoma- well circumscribed intraparenchymal mass.• M/E-• Central core of casseous necrosis surrounded by• tuberculous granulomatous reaction.• Long standing case-

• Fibrous adhesive arachnoiditis.In Mycobacterium avium intracellulare complex- Confluent sheets of macrophage filled with organism with little /no granuloma.

• Neurosyphilis• Tertiary stage of neurosyphilis• Occurs in 10% of patient with untreated patient.• Pattern-1) Meningovascular neurosyphilis-• Chronic meningitis with numerous plasma cell• Associated with oblitereted endarteritis2) Paretic neurosyphilis- • Inflammation• Parenchymal damage--• Loss of neuron• Proliferation of microglia (rod cell)• Gliosis• Iron deposition

3) Tabes dorsalis-• Loss of both axons & myelin in dorsal root• Atrophy of dorsal column of spinal cord.

• Viral meningoencephalitis• M/E-• Perivascular lymphocyte cuffing• Multiple foci of necrosis in GM & WM• Neuronphagia- single cell neuronal necrosis with phagocytosis of debris• Microglial nodules• Severe cases- necrotizing vasculitis with focal haemorrhage.

Herpes infection

• Gross- • Extensive destruction of inferior frontal & anterior temporal lobe.• M/E-• Necrotizing inflammation• Perivascular inflammatory infiltrate• Cowdry type-1 intranuclear inclusion viral inclusion in neuron & glial cell.

CMV infection

• Occurs- • Fetus• Immunosuppressed individual• Common- AIDS patient• M/E-Prominent cytomegalic cell with intranuclear & intracytoplasmic inclusion.

Rabies infection

• Gross- Intense edema• Vascular congestion• M/E-• Widespread neuronal degeneration most severe in brain stem• Inflammation• Negri body (Pathognomic)

HIV infection

• M/E-• Microglial nodule- near the small blood vessels• Multinucleated giant cell

Progressive multifocal encephalopathy

• Cause- JC polyoma Virus• Gross- Irregular poorly defined areas of demyelination• M/E- • Center- Scattered lipid laden macrophage• At the edge of the lesion- enlarge oligodendrocytic nuclei with glassy

amorphilic viral inclusion.• Within the lesion- bizzare giant astrocyte with irregular hyperchromatic nuclei

mixed with reactive astrocyte.

Sub acute Sclerosing Panencephalitis

• Cause- Measles virus• M/E-• Widespread gliosis & myelin degeneration• Viral inclusion within nuclei of oligodendrocyte & neuron• Inflammation of WM & GM & neurofibrillary tangles.

Fungal Meningoencephalitis

• Causative organism-• Candida• Mucor- most common with Diabetic ketoacidosis.• Aspergillus• Cryptococcus ( frequency in AIDS patient)• Endemic area-• Histoplasma• Coccidioides• Blastomyces

• Fungal infection- 3 main pattern-• Chronic meningitis• Vasculitis- frequently seen in mucormycoses & Aspergillous• Parenchymal invasion- commonly seen in Candida• Cryptococcus

• Candida – Multiple microabscess with/ without granuloma formation.

• Cryptococcus-• Gross- Multiple small cyst in basal ganglia• M/E- • Soap bubbles – Gelatinous material within subarachnoid space & small cyst in

parenchyma.

Others infection

• Protozoal infection-• Malaria• Toxoplasmosis• Amoebiasis• Trypanosomiasis

• Rickettsial infection-• Typus• Rocky mounted spotted fever

• Metazoal disease-• Cysticercosis• Echinococcosis

Toxoplasmosis

• Gross-• Cerebral abscess • M/E-• Central necrosis surrounded by acute & chronic inflammatory cell• Periphery of necrotic foci- Free tachyzoites & encysted bradyzoite.• Organism seen by –• H & E or Giemsa stain• Immunocytochemical stain